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[[The Johns Hopkins Medical Journal 30 (1919)]]
[[The Johns Hopkins Medical Journal 30 (1919)]]
http://www.archive.org/details/johnshopkinsmedi30john
THE JOHNS HOPKINS HOSPITAL BULLETIN
VOLUME XXX
BALTIMORE
THE JOHNS FK)PKINS PRESS
BALTIMORE, UD., U. 6. A.
Entered as Second-Class Mntter at the Baltimore, Maryland. PoatofDee
Acceptance for mailing at special rate of postace pn^viil.'d fnr in s.-rtinn llo.^. Art ..f Ortnht^r :i 1^17 Anthori^.^.i ..t, ,i.,k :i. ijjig.
Vol. XXX-No. 335]
BALTIMORE, JANUARY. 1919
Clinical Observations on Epidemic Influenza. (Illustratcil.)
By Abtiiub Bi.oomkield and George A. Hakrop. Jr.
Tlie Beliavior of tlio Blood Toward Oxygen in Inlliicnziil In
feetions. (Illiistratod.)
Bv (iEOBGK A. Harbop, Jr
==Contents==
Bacteriological Findings in Epideniie Inllneiiza. 1 By S. K. Howard, Jf. D 13
Ectopic Pregnancy. By H. M. X. Wynnk . . . l.O
1 Notes and News 25
10 I Notes on New Books 27
ECTOPIC PREGNANCY
By II. M. X
Hes'ideitl (li/necoloriisl. Thr
INCIDENCE
In the 2t years from 18!t0 to l!tl(i inclusive, there iiavc
Ijeen 303 patients with ectopic pregnancy in the tiynecological
Service of The .Johns Ho])kins Hospital who were operated
upon. There have been 22,fi88 patients admitted to the
Gj-necological Service during the S'i years, of which 303 had
extrauterine pregnancies, an incidence of l.:W.
Table Showino the Nimbeb ok Patients with ExTRAi'n':Ri.NE
PREOXANCIE.S Each Year
^ *
1990
2
18«!
6
1902
8
1908
23
1014
14
1891
3
18(t7
1
1003
15
190U
23
1915
13
1892
4
1 898
8
1!X)4
23
IftlO
13
1010
13
isns
8
18it!t
7
HI05
23
I91I
16
I8»4
7
lOOO
10
1900
13
1912
11
1895
'
1901
10
1907
10
1913
11
Total
.103
Race— Negroes, 101; white, 202. Total, 303.
Of the.s(. 22.688 patients. i:.H2 were wliit.- and .">2:(i wer.'
negroes. There were 202 eases of extrauterine pregnancy
among the whites (1.16:^) and 101 among the negro»
(l.'.il^).
Wynne.
Johns Ilopkins IlosjiHa]
AGE
(»f this .series of cases the age was rccnnlcil :>()() tunes. The
youngest patient was a 1 ."i-ycar-old white girl, married .seven
months previously to admission and never pregnant Ix'fore.
.\n unruptured left tubal |)rcgi»Hncy was removed at operation. The oldest jjaticnt was a l.")-year-old ncgress, who had
given birth to three full-term chihircn. .\t operation a fullterm litiiopedion. which iiad been in thf aiidomcn for four
years was removed ( Kcjiorted by .1. (i. Clark, The .lohns Hopkins Hospital Bulletin. l«!i:. Vlll. and in Kelly's Operative
Gynecology, Vol. 11). Of this series 182 (GH) occurred in
the decade 24 to .5.3 years inclusive. Seven patietits were
under 20 years and ten were over 10 years of age.
TAni.K Showixo Aokh ok 300 Patik.nth
MARITAL HISTORY
In a series of 284 there were 14 unmarried, two widows
and nine twice married.
Table Showing Time of Admission Aftee
Marriage
Time
Number
of
patients
Time
Number
of
patients
Time
Number
of
patients
Time
Number
of
patients
married
married
married
married
yrs.
yrs.
yrs.
2 wks . . .
1
9
9
8
18
9
4 wks...
2
22
10
14
19
3
6 wks...
3
18
11
9
20
7
2 mo8. . .
4
13
12
17
21
6
4 mos. . .
5
I.i
13
11
22
2
5 mos. . .
6
12
14
8
23
3
7 mos . . .
7
21
1.5
9
20
1
8 mos . . .
8
13
16
6
27
1
17
8
Total
268
PREVIOUS PREGNANCIES
In the histories of 375 patients, the number of pregnancies
prior to the ectopic pregnancy was recorded. In 57 (31^)
there had been no previous pregnancy and of the 218 (79^)
who had been pregnant before, 307 (95;?;), 75^ of the whole
series, had given birth to full-term babies and 11 (5^), 4^ of
the whole series, had had only miscarriages. Instrimiental deliveries had been performed on 19 patients (9;^ of those who
had had full-term pregnancies). Histories of prolonged puerperia associated with chills, fever and abdominal pain were obtained from 38 patients (17.5^ of all patients previously
pregnant) .
Table Showing Number of Previous Pregnancies
Number
Number
of
Number
of
Number
of
Total
Number
of
carriages
patients
children
patients
patients
1
65
1
77
57
2
25
2
32
1
67
3
8
3
27
2
42
4
5
4
21
3
22
5
2
5
17
4
22
6
2
6
14
o
16
7
8
6
16
Tola
1 107
8
2
7
13
9 .
2
8
8
10
3
9
11
1
10
3
12
11
1
13
1
12
1
14
2
13
14
1
1
Tota
1 207
15
16
1
Total 275
The interval between the last pregnancy and admission to
the hospital for an ectopic pregnancy was noted in the his
Table Showing the Interval Between the Last Pregnancy and
Admission to the Hospital for Ectopic Pregnancy
"oS
•5Z
- »i
• a
»- n
aj S
fc. g
t- g
tM C
b. a
1
ft
1
i
It
1
it
1
B
z
B
z
B
S5
B
§.
E
Iz
mos.
mo:.
yrs.
yrs.
yrs.
3
9
5
3
23
9
5
15
3
4
10
1
4
22
10
8
16
1
5
11
2
5
13
11
4
17
1
6
12
20
6
20
12
6
18
1
7
18
15
7
19
13
1
19
2
8
2
36
8
5
14
1
Total
226
tories of 226 patients, the shortest interval being three months
and the longest 19 years. The interval was between one and
seven years iu 168 patients (74^).
PREVIOUS OPERATIONS
Forty-five patients had had operations prior to admission
for ectopic pregnancy.
Dilatation and curettage had been performed on 15 patients
for bleeding caused by the ectopic pregnancy; two of these
operations were done in this hospital. One patient was
curetted twice before admission for bleeding caused by the
ectopic pregnancy.
Curettage was performed on 13 patients, from one to five
years before their admission and simple dilatation of the
cervix twice for sterility.
Incision of Bartholin gland abscess, five years before; one
patient.
Pelvic puncture for inflammatory disease; three patients.
E.rplorafori/ laparotomy five years before; one patient.
Multiple myomectomy five years before; one patient.
Ovarian tumor removed; one patient.
Tu.nior removed and appendectomy; six years before; one
patient.
Parovariancystectomy, right; suspension of uterus; appendectomy; two years before (Gyn. No. 16,409).
Suspension of tderus and appendectomy ; 18 months before
(Gyn. No. 15,751).
Salpingo-oopliorectomy, left, and appendectomy; one and
two years ago, for chronic pelvic inflammatory disease; two
patients.
Salpingo-odphorectomy, right, and appendectomy ; one
patient.
Appendectomy (only) ; three patients.
Appendectomy and nephropexy were done in another city
on one patient for the symptoms caused by a right tubal
pregnancy about six and eight weeks prior to admission to
this hospital.
Five patients have been operated upon twice in this hospital
for ectopic pregnancy.
Pelvic puncture, once.
Salpingectomy (alone), twice.
Salpingo-odphorectomy, twice.
COMPLAINT
The symptoms that patients complained of on admission
were as follows :
Bleeding 93
Pain, general abdominal or not specified 99
Pain in lower abdomen 69
Pain in riglit lower quadrant of abdomen 33
Pain in left lower quadrant of abdomen 33
Pain in back 20
Pain designated as "bearing-down," 4 times: and as "cramplike," 4 times.
Tumor in abdomen 17
Tumor in right lower quadrant of abdomen 1
Tumor in left lower quadrant of abdomen 4
Swelling of abdomen 3
Tenderness of abdomen 4
January, 1919]
17
Pregnancy 2
.Miscarriage I
Amenorrhea 1
Dysmenorrhoea 2
Vomiting 9
Nausea 6
Diarrhoea 1
Pain on defecation 1
Dysuria 2
PoUakiuria 1
Fainting 1
From the foregoing list we see that the most i-oiumon
causes for which these patients seek medical attention are
pain, complained of by 254 (84;^) bleeding, complained of
by 93 (31j^) and tumor, complained of by 28 patients (7^).
SYMPTOMS
Onset (1) Acute without prodromal symptoms other
than bleeding or a missed period 14(> (48%)
(2) Acute with prodromal symptoms 72 (247c)
(3) Gradual without acute attacks 84 (28%)
Irregular bleeding 229 (76%)
Nausea 146 (48%,)
Vomiting 126 (42% )
Tumor 45 (15%)
Fainting 38 (137c)
Fever 29 (IO70)
Chills 12 (47c)
Weakness 87 (29% )
Defecation painful 28 (9% )
Urinary frequency 40 ( 13% )
Burning on voiding 27 (9% )
Pain on voiding 87 (29%)
Loss of weight 6 (2% )
Bad taste In mouth 3 ( 17c )
Patients believing themselves to be pregnant 11
Patients not suspecting pregnancy 3
Patients suspecting an abortion 1
Patients who had felt life 1
Patients having a sensation of fluid in the abdomen. ... 1
Patients who had passed complete casts of the uterus. . 2
Patients complaining of pain in the abdomen not otherwise qualified 131 (437o)
Pain, general abdominal 21 (7%)
Pain, limited to the lower abdomen 28 (9%)
Pain, limited to the lower left quadrant 43 (14% )
Pain, limited to the lower right quadrant 41 (137o)
Abdominal pain over pelvis, with pain in the epigastrium 2
Abdominal pain over pelvis, with pain In the umbilical
region 1
Abdominal pain over pelvis, with pain in the bladder. . . 1
Abdominal pain over pelvis, with pain in the rectum. ... 2
Abdominal pain over pelvis, with pain in the flanks. ... 2
Abdominal pain over pelvis, with pain In the thighs. ... 1
Abdominal pain over pelvis, with pain In the legs 2
Abdominal pain over pelvis, with pain in the right
shoulder 2
.\bdominal pain over pelvis, with pain in the chest 1
Patients complaining of backache 19
Patients complaining of headache 2
fowl. — The symptoms that a patient considers as sufliriently unusual to cause her to seek medical attention an'
produced in the vast majority of cases by intraperitoneal
bleeding. A history of abdominal pain was procured from
300 patients (yiW), the other three patients stated positively
that there had been no abdominal pain or discomfort and
they came to the clinic on account of irregular bleeding. In
each of these three patients an unruptured tubal pregnancy
was found at operation, but no evidence of any clot or free
blood in the jicritoneal cavity.
The onset of the symptoms may be acute without other
prodromal symptoms, although there is usually a history of
a missed period or of irregular bleeding. In a second type
there is an acute attack following prodromal symptoms, which
the patient sometimes ascribes to her pregnancy. A third
type of patient gives a history of gradual onset without an
acute attack.
Recurring attacks of pain occurred in 102 cases (34^) ;
seventeen patients complained especially of soreness and
tenderness, ratlier than of definite pains. In several instances the pain was of several years' duration, generally with
a recent exacerbation, but in each instance at operation some
other condition, usually chronic pelvic inflammatorj- disease,
was also present.
The pains seem rarely to radiate. Tlie character of the
pain was described as violent, agonizing or severe in 90 cases,
cramping in 41, colicky in four, bearing down in 14, laborlike in nine, shooting, cutting or sticking in si.\ and as dull
or aching in 29.
Pain or irritation in the rectum and l)ladder occur after
intraperitoneal hemorrliage, most often when clots have collected in the pelvis and adhesions have formed. Pain and
vaginal bleeding often occur about the same time. Myssey
(St. Paul Med. Jour.. ]!)14, XVI, 588) states that pain on
defecation is almost pathognomonic of the condition, but in
our experience, this symptom is also frequently present in
cases of pelvic inflammatory disease.
MENSTRUAL HISTORY
One hundred and three patients (34'ii) stated definitely
that they had missed one or more periods; and 31 (10;^) said
that their last period had been overdue for from one to five
weeks, while 52 (IT"^) had noticed that the last period was
abnormal in some other respect.
Number
Number
Number
of periods
ol
o( period!
ol
mined
patienta
mined
patients
1
42
7
1
2
14
8
2
:<
14
9
4
2
lU
3
5
4
11
1
(t
U
Total
. .1U3 patients.
Increased frequency of menstruation 14
Constant bleeding since last period 60
No irregular bleeding 49
No irregular bleeding and no periods missed 18
Periods normally regular 210
Periods normally irregular 30
18
[No. 333
Last menstrual period :
Overdue 1 week 11
Overdue 2 weeks 1 1"
Overdue 3 weeks 2
Overdue 4 weeks 1
Overdue 5 weeks 1
Ahead of regular time 12
Shorter than usual 5
Longer than usual 2ii
Flow decreased 1^
Flow increased 9
Color abnormal 5
Xausea and vomiting occurred in a few cases, as in normally pregnant women and the patients with these symptoni>
considered themselves pregnant. In the great majority, however, there was a history pointing to intraperitoneal hemorrhage before nausea or vomiting had occurred.
Abdominal masses were noticed by the patients in cases of
advanced pregnancy and wliere a walled-otf hematocele was
present.
Fainting occurred in some cases wliere there was profuse
intraperitoneal hemorrhage.
Chills and fever were unusual .symptoms and always suggested the gravest complications.
Weakness is generally present in the more anaemic.
Loss of weight was noticed only in advanced tubal pregnancy, as also was the complaint of a bad taste in the mouth.
The notes in our histories as to whether the patient considered herself pregnant are very incomplete, and no conclusions
can be drawn from them except that not all believed that they
were pregnant.
SIGNS
In the following tabulation of physical signs, it is notable
that many of the presumptive signs of intrauterine pregnancy are not present in the majority of this series of ectopic
pregnancies. In the larger percentage of the cases in which
the table gives " a softened and enlarged cervix or fundus "
the notes Avere " slightly softened " or " slightly enlarged "
and often there was a difference of opinion in those cases examined by two men. We believe that most cases of tubal
pregnancy show no very definite gross changes in the cervix
and uterine body, unless the foetus is living. In no case was
a positive Hegar's sign recorded. Vaginal cyanosis was not
marked in any case.
The usual aksence of definite muscle spasm or rigidity is
in accordance with the signs of most pelvic diseases and,
where present, there was invariably blood in the peritoneal
cavity, not confined to the pelvis. Voluntary resistance to
deep pressure was a very common sign.
Abdominal tenderness was frequently alj.sent in cases of
pelvic hematocele ; in unruptured tubal pregnancy and in
advanced cases, but in patients who had had a recent severe
hemorrhage, the abdomen was generally exquisitely tender.
The figures recorded on pelvic tenderness are undoubtedly
too low. Certainly in those patients that have been under my
ob.servation, there is usually marked tenderness, and. especially when the pelvis is filled with recent clots, tliere is an
even greater degree of tenderness than is found in cases of
pelvic abscess. I have seen two eases of unruptured tubal
pregnancy in which firm bimanual compression of the mass
elicited no tomplaint or discomfort, but they are very unusual.
Signs ox Physical Examination
Shock (extreme) 15
Breasts:
Lactating 7
Colostrum present 46 (15%)
Abdomen:
Distention 90 (30%)
Free fluid 33 (10%)
Mass 72 (24%)
Tenderness, general 21 (7%)
Tenderness, limited to lower abdomen 71 (23%)
Tenderness, limited to lower right quadrant 52 (17%)
Tenderness, limited to lower left quadrant 39 (13%)
Muscle spasm 11 (4%)
Rigidity 17 (6%)
Pelvis:
Vaginal cyanosis 6 (2%)
Bloody discharge from vagina 85 (25%)
Cervix softened 85 (25%)
Cervix enlarged 48 (16%)
Fundus softened 15 (5%)
Fundus enlarged 86 (25%)
Mass, boggy 83 (24%)
Mass, firm 38 (12%)
Mass, cystic 40 (13%)
Blood clot crepitus 21 (7%)
Tenderness 146 (48%)
HEMOGLOBIN AND LEUCOCYTE COUNT
Unfortunately, hemoglobin determinations and leucocyte
counts were not done in many of the cases. It is to be remembered that the lowest point of the hemoglobin curve is
not obtained until from 48 to 72 hours after an acute hemorrhage (Dunn & AVynne, John Hopkixs Hospital Bulletin,
XXIX, No. 323, January, 1918). On this account, the degree
of ananiiia caused by the acute hemorrhage is not determined
as a rule before operation. A high leucocyte count is usually
found shortly after acute intrajieritoneal hemorrhage and cannot by itself be considered an indication of infection. In our
small series of leucocyte counts, there were between 20,000 and
30,000 leucocytes in 8 cases (10^) and between 10,000 and
20,000 in 39 cases (-17.5^). Tliis observation agrees with
those reported by other authors.
Hemoglobin
Before Operation
Per cent
of
hemoglobin
Number
of
patients
Per cent
of
hemoglobin
Number
of
patients
15
20-30
30-40
40-.')0
50-60
1
3
13
7
19
60-70
70-80
80-90
90-100
18
20
16
9
Total number of patients on whose blood hemoglobin determinations were done prior to operation, 106.
.I.\NIUHY, 1919]
19
LEfcocvTE Count Before Opebatio.n
W. B. c.
No. of
patienta
\v. B. r.
No. of
patienta
\V. B. C.
No. of
patients
3.000
5,000-6,000
6,000-7 ,00t)
7,00ft-8.0OO
8,000-9,000
9,000-10.000
1
2
6
.;
10.000-11.000
11,000-12.000
12.00(UI3.00()
13.0<K»-14,00«1
14.000-l.i.llOO
15,000-16,000
12
I
8
4
t>
Ifi. 000-17. 000
W.OOO-IS.IMHI
IS.OOO-lO.tKMt
20,000-21.000
22.000-23,000
30.000
3
1
1
5
2
Total number of patients on whom leucocyte counts were made
before operation, 82.
TEMPERATURE AND PULSE
The temperature on ailnii^t^ion to tlie hospital was less tliaii
101° F. ill 164 (9H) of a series of 180 eonsci-utive adiiiissions for ectopic jrestiition and the pulse was loss tlian I'iO
jH?r minute in the same number of patients. The majority
sliowed .some increase in both ]iulse rate and temperature.
Temperatire axi> Pfi-.sK ON Akmissiox to the Hospital of 180
Co.NSEClTIVE PaTIE.NTS
Teraperalure
No. of
patienta
Temperature
No. of
patienta
Temperature
No. of
patients
Did not
reginter. . .
97.0-98.0
98.0-98.5
98. .5-99.0
99.0-99.5
1
.10
26
41
99.5-100
100.0-100.5
100.5-101
101.0-101.5
101.5-102
2!)
30
8
5
3
102.0-102.5 5
102.5-103
103.0-103.5 i 1
103.5-104 2
Pulae
No. of
patienta
Pulie
No. of
patienta
Pulae
No. of
patients
60-70
70-80
80-90
90-100
100-110
4
9
46
110-120
120-130
130-140
140-l.iO
16
21
7
5
150-160
160-170 2
170-180 1
Could not be 1
counted
pre-operative diagnosis
The pre-operativc diagnosis wa.s recorded on the history in
212 cases. The correct diagnosis was made on admission in
!)8 cases (4G<) and confirmed on examination after the patients had l)een anu'sthetized for oi)erntion. Twelve additional ca.«es were diagnosed correctly oidy after the patients
were under ana-sthesia, while a probable diagnosis of extrauterine pregnancy was made in five other ca.ses, one of whicii
had a jwsterior vaginal coeliotomy performed before the
laparotomy for confirmation of the diagnosis. In 28 othc
i-ases the condition was suspected but not definitely diagnosc(l
until some operative procedure had been performed. In <>!•
ca.^es (•iS'i) the extrauterine pregnancy was not diagnosed,
although in a number of these cases some other pathologiciil
condition pre.«ent was diagnosed correctly. The diagnfiscs
recorded were made by some member of the resident staff in
the large majority of the ca.«es.
Table of Diaonosfs Before Opkratiox
Extraulprinp pregnancy (on admission examination I . . . . 98 cases
Extrauterine pregnancy (on examination under aniesthesis 12 cases
Extrauterine pregnancy (probable diagnosis)
Extrauterine pregnancy (after exploratory puncture) ....
Retained membranes of extrauterine pregnancy
Pelvic abscess or extrauterine pregnancy
Chronic pelvic inflammatory disease or extrauterine pregnancy
Appendix abscess or extrauterine pregnancy
Chronic appendicitis or extrauterine pregnancy
Cystoma of ovary or extrauterine pregnancy
Myoma uteri or extrauterine pregnancy
Calcified myoma or lithopedion
Flbro-cystoma
Ovarian cyst with twisted pedicle
Multilocular cystic ovary
Ovarian tumor
Ovarian tumor ( malignant )
Papillomatous cyst of ovary
Parovarian cyst
Myomata uteri
Myomata uteri with pregnancy
Myomata uteri, cystic, or sarcoma of uterus
Myomata uteri, cystic, or angioma of uterus
Myomata uteri with adherent dermoid cyst
Pelvic abscess
Pelvic abscess with general peritonitis
Pelvic abscess or appendix abscess
Chronic pelvic inflammatory disease
Subacute pelvic inflammatory disease
Acute pelvic inflammatory disease
Chronic appendicitis
General peritonitis
Retained membranes
Abortion, infected
Miscarriage due to retroposition of the uterus
Pregnancy
Retroposition of the uterus
Chronic pelvic inflammatory disease..
Tubo-ovarian abscess
Ovarian cyst
Submucous myoma, cystic
Ovarian tumor
Extrauterine pregnancy
Chronic pelvic inflammatory disease. .
Papillocystoma of ovaries "
Tuberculous pelvic inflammatory disease
Pelvic inflammatory disease with ovarian cyst. .
" No diagnosis made "
4 cases
1 case
11 cases
6 cases
<! cases
1 case
1 case
1 case
1 case
1 case
1 case
1 case
1 case
1 case
1 case
1 case
1 case
5 cases
2 cases
1 case
1 case
1 case
11 cases
1 case
1 case
20 cases
2 cases
1 case
2 cases
1 case
2 cases
1 case
1 case
1 case
2 cases
1 case
1 case
:! cases
We do not believe that the Hat-footed diagnosis of extrauterine pregnancy is as simple as many writers consider it.
Ill making an estimate of the percentage of faulty dingiio.^es,
we should al.<o include those cases diagno.'Jed as extrauterine
pregnancy which, at operation, prove to be another condition.
Ill this clinic the latter class of cases is nunierous. In jirivate jiractice among more intelligent patients, there sliould
be a higher percentage of correct diagnoses made than in a
free clinic. The classical case of an acute ruptured ectopic
pregnancy is usually clear if a .satisfactory history can be olitained, but there are a great many cases in which the history
points equally well to jielvic inflammatory disea.se. The latter
ili.sease also gives .symptoms that not infrequently strongly
suggest extrauterine pregnancy. Cases with unilateral intlammatory di.-^ea.se are .«een in this clinic fully as often as
extrauterine pregnancies and may be very puzzling. Thi'
differential diagnosis in this class of cases is often difficult
even when a careful history has been taken.
Very often there are other conditions present that make a
positive diagnosis practically impossible. Another stumblingblock is encountered occasionally in patients who have had an
early abortion with retained membranes and have a cystic
ovary on one side. We have seen three cases of this cliaracter
which were correctly diagnosed by one or more members of
the staff, but which were considered to be unruptured extrauterine pregnancies by other members who examined the
patients under equally favorable circumstances.
There are occasional cases in which the diagnosis is in
doubt even after operation has been performed, as in the
following :
Gyn. No. 22180. The patient was a white woman, age 33 ;
she was admitted to the hospital May 16, 191G, complaining
of "bowel trouble."
Married 18 years; three children, youngest six years of
age. No miscarriages. Labors normal. Fever for two
weeks beginning in the fourth week following the first labor ;
otherwise the puerperia were normal.
Last menstrual period February. 1916; last preceding
October, 1915. Miscarriage on January 1, 1916, after slight
vaginal bleeding for the preceding week. A curettage was
done by her family physician January 2 and the patient
was told that " the afterbirth was perfect." No foetus was
seen. A period normal, except slightly prolonged, began
on February 7 and lasted seven days. On February 21 an
appendectomy and a curettage were performed. The surgeon
who operated said that the uterus, tubes and ovaries were
normal at that time. No pain followed the operation until
April 6, when she had a gradually increasing pain in the
lower abdomen and back. This became quite severe, but
lasted only one day. The abdomen felt sore for the following
three days. She had no further abdominal pain until May
13 at 6 p. m., when she began to have pain in the left lower
quadrant of the abdomen, similar to the previous attack.
There had been slight vaginal bleeding for three days prior
to this attack, during which the bleeding increased considerably. This attack of pain lasted 36 hours.
P. .E.— Pulse 100. Temperature 99.6°, May 15, 1916.
W. B. C, 19,000. Hbg. 95;?;.
Abdominal tenderness marked in the left lower quadrant
and less marked in the right lower quadrant. ^Moderate
rigidity below the umbilicus. A firm, smooth mass can be
felt about half way between the umbilicus and pubis.
Pelvic Examination. — A bloody vaginal discharge is present. Cervix slightly softened and slightly enlarged. The
tumor described above seems to be the uterus. A moderately firm mass, which is tender, can be felt in the left fornix.
Blood clot crepitus in the cul-de-sac.
Diagnosis. — Extrauterine pregnancy, left, probablv witli
beginning tubal abortion.
February 17, 1916. — Operation. A pelvic puncture was
performed and about three ounces of old black blood was
evacuated from the pelvis. The patient was immediatelv
prepared for laparotomy. There was a considerable amount
of old blood in the abdomen. The tubes were found densely
adherent in the cul-de-sac, the fimbriated ends were open,
both tubes were considerably enlarged and oedematous. No
foetal or placental tissue could be found, nor was there any
visible site of an ectopic pregnancy in either tube. The tubes
were released from adhesions and a cigarette drain placed
through the cul-de-sac. There was a good deal of fresh
bleeding during the operation. The patient was discharged
June 16 after a rather prolonged convalescence. At the time
of discharge the uterus was still enlarged, but there were no
pelvic masses or tenderness.
TREATMENT
The treatment of our cases has been operative, either by
the abdominal or vaginal routes. In several cases posterior
vaginal coeliotomy has been performed for diagnosis. Pelvic
puncture has been employed for pelvic hematocele in a number of cases, although in 60^ of these cases a laparotomy was
performed immediately afterwards.
Table of Operatioxs
Vaginal (only ) 24 cases (S%)
Pelvic puncture (only) 16 cases
Pelvic puncture with laparotomy (for hemorrhage
following puncture, 4 ) 24 cases
Pelvic puncture with dilatation and curettage. ... 3 cases
Dilatation and curettage with laparotomy 5 cases
Vaginal salpingectomy 1 case
Exploratory above Poupart's ligament into sac ... 3 cases
Laparotomy 279 cases (92%)
Abdominal incision of sac with drainage 5 cases
Removal of fcetus and placenta 6 cases
Salpingectomy (unilateral) 180 cases
Salpingectomy (bilateral ) 56 cases
Resection of one tube 1 case
Puncture of hematosalpinx 2 cases
Total extirpation of sac and CONTENTSs. 12 cases
Partial extirpation of sac 1 case
Oophorectomy (unilateral) 108 cases
Oophorectomy (bilateral) 24 cases
Resection of one ovary 11 cases
Ovarian cyst tapped 1 case
Hysterectomy 30 cases
Resection of uterine cornu 7 cases
Myomectomy 5 cases
Excision of accessory tube 1 case
Ligation of remaining tube 1 case
Excision of abscess sac 1 case
Suspension of uterus 10 cases
Excision of mesenteric cyst 1 case
Excision of umbilical hernia 1 case
Resection of omentum 1 case
Release of intestinal adhesions 5 cases
Suture of rectum 3 cases
Suture of sigmoid 1 case
Resection of ileum 3 cases
Lateral anastomosis 3 cases
Additional: Perineal repair G cases
Additional: Perineal repair with suture of rectal sphincter 2 cases
Laparotomy by tlie abdoniiual rout4j has beeu preferred in
all cases except those in which there was a pelvic hematocele
with symptoms and signs indicating infection. In such
cases, pelvic puncture and drainage is usually a safer procedure, althougii a secondary laparotomy may be necessarj'
later for continued pain.
The majority of our patients have entered the hospital
after examination in the Out-Patient Department and have
l)een operated upon on the day following admission, unless
they were in serious condition at the time of admission, when
immediate operation has been performed, with very satisfactory results. One patient whose case has been previously reported by Richardson ( JoHxs Hopkins Hospital Bulletin )
was in very extreme shock when admitted to the hospital and
was treated expectantly. However, three days later, operation
became imperative on account of marked abdominal distention and she died on the third day after the operation.
Richardson thought this patient could have been operated
upon the day following admission, when she had recovered
somewhat from the primary shock and before serious distention had set in.
Whenever other pathological conditions demanding operation were present, they were included in the operative treatment, when the patient's condition justified a prolongation
of the procedure.
Peritoneal Toilet. — In the majority of our cases the
peritoneal cavity had been cleaned of blood and clot as well
as possible. In 259 cases the peritoneal cavity was cleaned
of blood and clot, and in eight cases no attempt was made to
evacuate blood. We believe that the convalescence is more
satisfactory when the blood is carefully removed.
Irrigation. — The peritoneal cavity was irrigated in 3^
cases, sterile normal salt solution being used in 35 ca.ses and
sterile water in two cases. In recent years this practice has
been discontinued.
The sac ha.s been irrigated following pelvic puncture in
nine cases, but this procedure has been abandoned on
account of the danger of breaking through the wall and filling the peritoneal cavity with the fluid, as occurred in one
case and resulted in a general peritonitis. This patient recovered after a secondary operation for drainage of the
abdomen.
Drainage. — Primary drainage has been used in 150 ca.«t
glass tubes were employed twice and in the remainder gaui /
usually in the form of a cigarette drain. The drains arc
l)referably placed through the cul-de-sac into the vagina,
rather than through the abdominal wall (38 cases were
drained through the abdominal incision). At the present
time drains are not employed unless there is .some evidence
iif infection in the pelvis or a general ooze following the
release of adhesions.
Stimulant.^. — Salt solution administered subcutancously \y
depended upon for stimulation during operation and halieen employed in 5fi cases. Salt solution by rectum has been
used in 13 cases and with equal parts of coffee in four rase.-.
The peritoneal cavity was filled with salt solution In'fore
(losing the abdomen in 34 cases, but this procedure has been
discontinued, as it seems to favor post-operative distention and
generally increases the patient's discomfort, as well as spreading infection over the entire abdomen, if any should be present.
In the case of one patient with very serious shock, an infusion
of normal .^alt .solution was administered through the radial
artery and resulted in gangrene of the hand. In a few cases
drug stimulants have been used hypodemiically, strychnine
in 16 cases, digitalis in three cases and brandy and ether in
one case.
Transfusion of blood has not been used in any case included
in this series. Very satisfactory results, however, have been
reported by others who have used both direct and indirect
transfusion, but sometimes there is no time to match the
bloods of donor and recipient and a severe reaction following
the transfusion may be fatal. The majority of these acutely
ruptured cases can be stimulated sufliciently with subcutaneous infusions of large quantities of salt solution to tide them
over the immediate shock. As all the.se patients are of ages
most favorable for operative risk and as a rule have been in
good health prior to the acute onset, they usually will recover
if stimulated with salt solution for the first few hours.
Lichtenstein (Muench. Med. Wchnschr., 1915. LXII,
1597) reports eight cases treated by reinjection of the blood
found in the patient's abdomen after defibrination and dilution with salt solution 3:2, a procedure open to criticism.
The intravenous injection of 7^ acacia in distilled water,
filtered and sterilized by boiling, will probably prove to be
of great value in those cases in which there is severe shock due
to great loss of blood volume (Rous-Wilson, Jour. Am. Med.
Assn., January 26, 1918). We have used this preparation in
one case in which there was an abundant hemorrhage at operation and severe shock, with gratifying results.
There are, of course, patients in such serious shock when
first seen that operation is contra-indicated. In these cases
shock must be combated by some of the methods mentioned
above, but as soon as the patient is in condition to stand operation, it should not be delayed.
The time consumed in operating is shown in the table for
255 cases.
Table Siiowixo the Dr
RATION ay
OrERATIONS
Number
Number
Timt
of
Time
ol
Time
ol
cues
C*Mt
cue*
mi».
An. Mill.
krf. ndi.
S
3
45
22
1 25
4
10
6
60
23
1 30
4
16
4
55
14
1 40
2
20
10
21
1 45
4
26
14
1 6
11
1 SO
2
30
21
1 10
17
1 65
2
35
29
1 16
2
2
40
23
1 20
8
2 10
2 26
2
1
Total, 256 operations.
All operations consuming less than 20 minutes were pelvic
punctures only.
22
[No. 33.
Thirty operators performed 267 operations.
One operator performed 44 operations
One operator performed 35 operations
One operator performed 27 operations
One operator performed 21 operations
One operator performed 15 operations
Two operators performed 14 operations (each)
One operator performed 12 operations
One operator performed 11 operations
One operator performed 10 operations
One operator performed 9 operations
One operator performed 8 operations
Two operators performed 6 operations (eacli)
One operator performed 5 operations
Four operators performed 4 operations ( each )
One operator performed 3 operations
Six operators performed 2 operations (each)
Four operators performed 1 operation ( eacli )
Ancesthesia. — Iii the large majority of these cases, nitrous
oxide followed by ether, administered by tiie open drop
method, lias been used. Some patients have been given chloroform or ether only, and a few chloroform and ether.
Diagnosis at Operation
Ruptured with free blood in peritoneal cavity 100 -, .„^ .
Ruptured with encapsulated blood in peritoneal cavity 66 r
Tubal abortion with free blood in peritoneal cavity ... 381
Tubal abortion with encapsulated blood in peritoneal I (19%)
cavity 13 J
Unruptured , 55 (20%)
Total 272
Interstitial pregnancy, right 2 '
Tubal pregnancy, right 135
Tubal pregnancy, left 131
Ovarian pregnancy, right 2 '
Total 270
' Wynne, J. H. H. Bull. XXIX, No. 324, February. 1918.
- CuUen & McAll. Surg., Gyn. & Obst.. 1912; M.ver & Wynne, to be
reported.
Advanced Extrauterine Pregnancy
In one case the pregnant tube was ruptured during the
examination under ether. Active hemorrhage at time of operation occurred in 20 cases.
The peritoneum was noted as blood stained before bcinu
opened in 43 cases.
The blood in the peritoneal cavity was designated as fluid
in 66, clotted in 24 (infected, three) ; there were fluid and
clots in 55 cases.
The opposite tube was noted to be normal in 15 cases.
The opposite ovary was noted to be normal in 12 case.s.
The appendix was described as normal in 31 cases.
The appendix was involved in the sac in 11 cases.
The appendix was adherent to a myoma in one case.
A CASE OF PREGNANCY IN A RUDIMENTARY HORN
Gyn. No. 16T27. The patient was a white woman, age 30,
admitted to the hospital June 9, 1910, complaining of vaginal
l)leeding and pain the left .side of the abdomen. Married five
vears; one child two years old. One miscarriage at two
months, one year ago. Labor and puerperia normal. Last
menstrual period January, 1910.
P. I. — The patient considered herself pregnant, but noticed
that the uterus had not enlarged as rapidly as during her
former pregnancy and that the enlargement was more on the
left side than on the right. For a month she has noticed
tenderness over the left side of the abdomen. At 6 a. m. on
the morning of admission, she was awakened by pains in the
pelvis, similar to labor pains and shortly after, passed blood
and bits of tissue resembling placenta. There was slight
bleeding afterwards, but the pain subsided. She was nauseated this morning.
Phi/gical Examination Under Ether. — On abdominal examination, a mass can be felt in the lower abdomen, which
is rather soft and boggy and about the size of a large orange.
The mass is movable and seems to be attached to the uterus.
Gyn. No.
Race
Age of
patient
Date
Fre-operative
diagnosis
Operation
Placenta
Result
Feetus
Years 114
B.
29
1890
Fibrocystoma.
Laparotomy.
Removed.
Died. Shock.
Dead. Male. Length 53 cm.
101
B.
28
1890
Abdominal pregnavicy
(several mos. past term) .
Lai "•^'tomv
Removed.
Recovery.
Wt. 2800 grms. Male. Dead.
Fully developed. Crown
rump 30 cm.
1,705
W.
42
1893
Ectopic, two months past
term.
Lapatpitomy.
Removed.
Died. General
peritonitis.
Dead. Length. 42 cm.: wt.,
4 lbs.
4,564
B.
45
1896
Calcified myoma or litliopedion four years past
term.
Laparotomy.
(Reported by
Removed.
J. G.Clark).
Recovery.
Lithopedion. Weight, 43 lbs.
7,182
W.
34
1899
M u 1 1 i 1 c u 1 a r cystoma
ovarii.
Ruptured tubal pregnancy,
Laparotomy.
Removed.
Recovery.
Dead. Length, 25 cm.
12.207
W.
41
1905
Laparotomy.
Removed.
Recovery.
Macerated. Weight, 12.')0
two months past term.
grms. Dead.
13.272
B.
28
1906
Laparotomy.
Laparotomv.
Recovery.
Recovery,
Full term, female. Living.
Six months. 33 cm. long.
13,546
W.
35
1907
Extrauterine pregnancy.
Removed.
ruptured.
13.673
B.
30
1907
Laparotomy.
Laparotomy.
Recovery.
Recovery.
13,806
B.
33
1907
Abdominal pregnancy.
Removed.
Macerated remains of foetus.
(Reported by CuUen,
Surg., Gvn. cS:
b.st., 1915, X
X, 261.)
17,056
W.
35
1911
Laparotomy.
Removed.
Recovery.
Dead. Intraligamentary, rt.
Weight, 6A lbs.
19,092
B.
22
1913
Extrauterine pregnancy,
infected.
Laparotomy.
Removed.
Died. General
peritonitis.
Macerated. Femur, 5.2 cm.
Humerus, 4.8 cm.
21,494
B.
29
1915
Ovarian tumor, right.
Laparotomy.
Removed.
Recovery.
Dead. Weight, 1911 grms.
44.5 cm.
Januabt, 1919]
23
Pelvic Examination. — The vagina and cervix are normal.
The fundus of the uterus is soft and boggy and, attached to
it by a pedicle, is the mass described above.
Pre-Operative Diagnosis. — Extrauterine pregnancy or
pregnancy in a rudimentary liorn.
Operation. — The mass was found to be a pregnancy in thi;
rudimeutarj' left horn of a bicornat* uterus and was attached
to the right side of the uterus by a small pedicle. The left
tube was stretched over the pregnant horn and togetlier with
the left ovary was so intimately associated with it as to necessitate their removal. The left horn was amputated close to
the right side and there remained a practically normal uterus.
The patient was discharged on the 13th day after an uncomplicated convalescence.
Diagnosis. — Pregnancy in a rudimentary horn, left.
Pathological Xo. 15,150. — The specimen has been opened
anteriorly in the operating-room and measures 7x8x5 centimeters. The walls measure 1.5 centimeter in thickness.
Foetus of 4 to 5 months in unruptured membranes.
Patholooicai, Retobts
The tissues removed at operation have been studied histologically and the diagnosis has been verified. We are unable
at the present time to give a thorough report on this interesting side of the disease.
The routine preparations, where the endometrium was examined, have been reported as follows:
Normal endometrium 13
Gland hypertrophy of the endometrium 5
Endometritis, chronic 5
Endometritis, acute 1
Decidual reaction of the endometrium 7
Cast of uterine cavity with decidual reaction 2
In addition to ectopic pregnancy the following diagnoses
were made at or before operation :
Atrophy of the opposite tube 1
Hematosalpinx of the opposite tube 3
Hydrosalpinx of the opposite tube 16
Chronic salpingitis of the opposite tube 8
Pyosalplnx of the opposite tube 6
Tuboovarian abscess of opposite tube 1
Ovarian abscess •. 3
Chronic pelvic inflammatory disease 92
Cystic ovaries 13
Ovarian cyst, follicular 9
Ovarian cyst, corpus luteum 3
Parovarian cyst 1
Retroposition of the uterus 6
.Myomata uteri 17
.Membranous dysmenorrhoea 1
Mesenteric cyst 1
General peritonitis 1
Pre-operative rupture of abscess Into rectum 1
Post-operative adhesions 1
Bladder adhesions 1
Omental adhesions 14
Intestinal adhesions 19
Meckel's diverticulum 1
Umbilical hernia
2
Appendicitis, chronic
52
Appendicitis, sub-acute
5
Appendicitis, acute
2
Periappendicitis
7
Complications before operation :
Pulmonary tuberculosis
2
Diabetes i
Insanity i
Arthritis deformans i
Chronic nephritis i
Ascaris lumbricoides i
Uncinaria Americana l
Post-operative Compucatioxs
The complications following operations have been as follows:
Acute bronchitis 2 cases with recovery.
Bronchopneumonia 2 cases with recovery.
Lobar pneumonia 2 cases with 1 death.
Fecal fistula, abdominal 2 cases with 1 death ")
Fecal fistula, vaginal 1 case with death. . . ll patient.
Urinary fistula, abdominal 1 case with death. . . J
Atonic ileus 1 case with recovery.
Peritonitis, general G cases with 5 deaths.
Infected drainage cavity with
collection of pus 3 cases with recovery.
Cystitis 2 cases.
Phlebitis (of left leg) 3 cases.
Tetanus 1 case with recovery.
(Reported by Casler at Southern Medical Association meeting
in 1917.)
Gangrene of the hand following
intraarterial (radial) salt infusion 1 case.
Mastitis, right 1 case.
Acute follicular tonsillitis 1 case.
Influenza 1 case.
Erysipelas (facial) 1 case.
Shock and antcmia have been omitted from this list, as
accurate data for all cases are not available.
SuBSEQfE.XT Operations for Co.mplicatio.vs Abisino erom the
Prim.\by Operatiom
Gyn. No. 2,612. Abdominal drainage for peritonitis following
rupture of sac by Irrigation after pelvic puncture. Symptoms of peritonitis 11 days after
operation. Recovery.
Gyn. No. 7,901. Exploratory laparotomy for localized poritonitta
36 hours after left salpingo-oophorectomy and
vaginal drainage. Death on the sixth day from
lobar pneumonia.
Gyn. No. 11,473. Pelvic puncture for drainage, 23 days after salpingo-oophorectomy. Recovery.
Gyn. No. 11,491. Dilatation of drainage tract and evacuation of
pus 10 days after pelvic puncture. Recovery.
Gyn. No. 12,380. Rupture of abdominal incision 22 days after laparotomy. Recovery.
Gyn. No. 15,529. Right salpingo-oophorectomy and release of adhesions 1.J days after pelvic puncture and
drainage of infected hematocele. Recovery.
34
[No. 335
Gyn.No. 17,251.
January 16, 1911, at the first operation, during
hysterectomy, left salpingo-oophorectomy and
release of adhesions, the rectum was torn.
Abdominal fecal fistulae resulted.
April 29, 1911. Excision of- fistulous tracts, suture of rectum and bladder. Appendectomy.
Failure.
September 18, 1911. The patient was readmitted
to the hospital (Gyn. No. 17,804) for abdominal fecal fistula and a recto-vaginal fistula following her first operation.
September 30, 1911. Excision of abdominal fistula, resection of sigmoid, end-to-end anastomosis, suture of bladder. Shock.
October 5, 1911. Enterostomy for ileus.
October 6, 1911. Enterostomy for ileus. Death
on the table.
CAUSE OP DEATH
There have been 13 deaths in our scries of 303 cases and
autopsies were performed on six of these.
Gyn.No. 114. (Autopsy No. 72.) Shock 12 hours after operation. This patient was in a very critical con
dition when operated upon. No anatomical
cause of death was found at autopsy.
Gyn.No. 521. (Autopsy No. 181.) Died 24 hours after operation. The anatomical diagnosis at autopsy
was: Acute general peritonitis (pure culture
B. coli from bloody peritoneal fluid), perforation of appendix with circumscribed abscess.
Gyn.No. 1,795. (Autopsy No. 38S.) Died 10 days after operation. At autopsy an acute fibro-purulent
peritonitis, chronic diffuse nephritis and gallstones were found.
Gyn.No. 7,901. (Autopsy No. 1562.) Death 6 days after operation, of lobar pneumonia.
Gyn. No. 10,678. (No autopsy.) Death 3 days after operation.
On admission the hemoglobin was 15 per cent
and on the day of death 10 per cent.
Gyn. No. 12,042. (No autopsy.) Death 9 hours after operation.
This patient was operated on by the vaginal
route and a large amount of clot and fiuid
blood evacuated, followed by a gush of bright
red blood. Laparotomy was immediately performed. Shock.
Table Showing Pbegnancies Since Operation
Character of operatit
No. of years
since operation
of ciiildren and miscarriages since operation
1,636
1,710
2,805
4,120
6,482
8,441
9,740
9,746
10,258
10,544
11,215
11,244
11,592
11,830
11,834
12,236
12,268
12,398
14,167
15,309
15,644
15,955
17,428
18,744
19,781
20,777
21,017
21,082
21,483
22,303
22,445
Incision of sac with drainage
Enucleation of sac
Right salpingo-oophorectomy
Pelvic puncture with drainage
Right salpingectomy
Right salpingo-oophorectomy
Left salpingectomy
Right salpingo-oophorectomy
Left salpingectomy
Left salpingectomy with resection of right ovary
Right salpingo-oophorectomy
Pelvic puncture and exploratory laparotomy
Right salpingectomy
Pelvic puncture •
Left salpingo-oophorectomy
Right salpingo-oophorectomy
Right salpingectomy
Right salpingo-oophorectomy
Left salpingo-oophorectomy and resection of right ovary. .
Left salpingo-oophorectomy
Right salpingo-oophorectomy
Left salpingo-oophorectomy
Right salpingectomy
Right salpingectomy
Right salpingectomy
Resection of right cornu
Right salpingectomy, resection of right ovary, myomectomy
Right salpingectomy
Right salpingectomy
Right oophorectomy
Left salpingo-oophorectomy
23 months
20 months
15 months
16 months
5 full-term children.
2 full-term children.
1 full-term child.
2 full-term children.
1 miscarriage at 2% months 4 years after operation.
2 full-term children, 1 miscarriage.
1 miscarriage.
5 miscarriages, the first 2 years after operation.
1 full-term child.
2 full-term children.
2 full-term children.
1 full-term child.
6 full-term children.
1 tubal pregnancy 8 years after operation.
1 full-term child.
2 miscarriages 10 and 8 years ago at 3 months;
1 full-term child 6 years ago.
1 miscarriage.
2 miscarriages.
1 full-term child.
1 full-term child 2 years after operation; 1 miscarriage 6 years after operation.
1 miscarriage and 1 full-term child 3 years after
operation.
1 full-term child.
1 full-term child.
1 full-term child 14 months after operation; 1 fullterm child 32 months after operation.
8 months pregnant when heard from.
1 full-term child 1% years after operation.
1 full-term child 1 year after operation.
1 miscarriage (induced) 6 months after operation.
3 weeks from term when heard from.
1 full-term child IS months after operation.
1 full-term child 11 months after operation.
F^VE Patients Opekated on fob Second Ectopic Pregnancy in This Clinic
Second operation
4,147
9,781
13,776
15,771
16,230
Pelvic puncture in 1896
Right salpingo-oophorectomy in 1902
Left salpingectomy in 1907
Right salpingectomy in May, 1909
Right salpingo-oophorectomy in November, 1909
Right salpingectomy in 1904
Left salpingo-oophorectomy in 1905
Right salpingectomy in 1908
Left salpingectomy in November, 1909
Hysterectomy; left salpingo-oophorectomy in January, 1911
11,590
12,290
14,895
16,188
17,251
January, 1919]
25
These six fatalities were reported in Kelly's Operative
Gynecology, Vol. II.
Gyn. No. 12,830%. (No autopsy.) Death 4 hours after operation.
The patient was in serious shock when operated upon. About 2 liters of free blood were
evacuated from the abdomen.
Gyn. No. 15,314. (No autopsy.) Death 3 days after operation
from shock. (Reported by E. H. Richardson.)
Gyn. No. 17,119. (No autopsy.) Death 2\i hours after operation.
The patient was in good condition after the
operation until 3 minutes before death. Probably embolus.
Gyn. No. 17,211. (.\utopsy No. 3489.) Death 8 days after operation. Anatomical diagnosis at autopsy:
Acute general peritonitis.
Gyn. No. 17,251. (No autopsy.) Death S days after secondary
operation tor fistula following primary operation. General peritonitis.
Gyn. No. 18,731. (No autop.sy.) Death 2Vi hours after operation.
Shock. This patient had diabetes.
Gyn. No. 19.092. (Autopsy No. 38S4.) Death 12 days after operation. .\t autopsy acute general peritonitis and
embolic pneumonia were found. At operation
the sac containing foetal bones and infected
material was ruptured.
Immediate Resvlts
Well 271 (89.4%)
Improved 19 (6.3%)
Died 13 (4.3%)
Ultijiate Results
Letters were sent to the 290 patients who recovered from
the operations for ectopic pregnancy. Answers to the fol
low-up letters were obtained from 118 patients and nine, who
did not answer the letter, were later readmitted to this hospital. Of 120 patients, 100 have been well since operation,
five have had poor health since operation, .seven report fair
health and two no change in general health since operation.
Four had good health for several months or years, and afterwards died, one of pulmonary tubenulosis, one of acute intestinal obstruction, one of post-operative pneumonia. In one
ease the cause of death was not stated.
Of the series of 127 cases, there was no possiltility of future
pregnancy in 33. Of the remaining 9G in whom there wa.s
a possibility of future pregnancy 36 (38°) have since become
pregnant one or more times; 61 pregnancies have resulted in
•?7 full-term children ; two patients were pregnant almost at
term when heard from. In 16 cases the pregnancy ended in
miscarriages and six patients had a second extrauterine
pregnane}'.
Opeuatioxs Subsequent to Operation fob Ectopic Pbeonaxct
Post-operative ventral hernia has occurred in eight cases;
four have been repaired in this hospital and one in another
hospital, and three patients have not been submitted to another operation. One patient was operated upon for intestinal
obstruction and one had a vaginal panhysterectomy performed in this hospital for carcinoma of the cervix.
In all 14.5 patients have been followed on this point.
I wish to thank Dr. Howard A. Kelly for permission to
publish this report.
NOTES AND NEWS
Dr. George Blumer is Chairman of the Medical Advisory Board,
Yale University, New Haven, Conn.
Dr. Montague Boyd is Associate Professor of Surgery (Genitourinary), Emory University: Andrologist, Wesley Memorial Hospital and Visiting Genitourinary Surgeon, Grady Hospital, Atlanta, Ga. Government service: Captain. M. R. C, on duty in
France.
Dr. Walter V. Brem is .Major .M. C, and Chief of the .Medical
Service, U. S. Army Base Hospital, Camp Fremont, Cal.
Dr. Helen Smith Brown is Lecturer In Social Hygiene for the
Commission on Training Camp .Activities, Washington. D. C.
Dr. S. W. Clausen is Instructor in Pediatrics, Washington University Medical School and Assistant Physician to the St. Louis
Children's Hospital. He Is First Lieutenant, M. R. C, and is in
active service.
Dr. Malvern B. Clopton is Major, M. R. C. He is a member
of Washington University Hospital Unit No. 21, and is stationpd
with General Hospital No. 12, B. E. F., Rouen, France.
Dr. Stanley Cobb is First Lieutenant. M. C, Division of Brain
Surgery.
Dr. Sydney M. Cone Is Captain, M. R. C, and is stationed at the
Alder Hey English Military Orthopedic Hospital. England.
Dr. Henry Wireman Cook is Associate Director of the Bureau of
Medical Service, American Red Cross, Washington, D. C.
Dr. W. L. Cousins Is Surgeon-in-Chlcf of St. Barnabas Hospital,
Portland, Me. Government service: Major, M. R. C, and Chief
of the Surgical Staff U. S. Army Base Hospital, Camp Gordon, Ga.
Dr. J. Stalge Davis is Captain, M. C, U. S. Army, and is on active
duty in Baltimore.
Dr. Ernest C. Dickson Is Associate Professor of Medicine, Iceland
Stanford University School of Medicine. Government service:
Captain, C. A. M. C, stationed In Basingstoke, England.
Dr. Richard N. Duffy Is Surgeon to the New Bern General Hospital, New Bern, N. C.
Dr. C. B. Dunn Is Chief of Staff, Southeastern Hospital for the
Insane, Madison, Ind., and on the teaching staff King's Daughters
Hospital, Madison, Ind.
Dr. Arthur B. Emmons Is Captain. M. R. C, and Is stationed In
Evacuation Hospital No. 2, A. E. F., France.
Dr. W. L. Estes, Jr., la Director of St. Luke's Hospital, South
Bethlehem, Pa. Government service: Captain, M. R. C, attached
to Mobile Operating Unit No. 1. Section No. 1, A. E. F., France.
Dr. William W. Farr Is Captain, .Medical Corps, U. S. A., stationed
at U. S. Base Hospital. Camp Shelby, Hattlesburg, Miss., with title
of Chief of Subsection of Otolaryngology.
Dr. A. L. Fisher is Captain, M. C, and is In charge of the Surgical Service, U. S. Base Hospital No. 30, A. E. F.
26
[No. 335
Dr. J. M. T. Finney is Brigadier General, M. C, U. S. Army, and is
Surgical Consultant, A. E. F., France.
Dr. Simon Flexner is Lieutenant Colonel, Medical Corps, U. S. A.
He is on duty at the Rockefeller War Demonstration Hospital,
New York City.
Dr. James R. Garber is Instructor in Obstetrics South Highlands
Infirmary Training School for Nurses, Visiting Obstetrician to the
Hillman Hospital, Attending Obstetrician to the Salvation Army
Home, Birmingham, Ala., and Acting Secretary of the Southern
Medical Association.
Dr. S. McPheeters Glasgow is Captain, M. C, and is stationed
at Camp Zachary Taylor, Ky.
Dr. L. W. Gorham is Captain, M. R. C, and is stationed with
I\ S. Base Hospital No. 33, Portsmouth, England.
Dr. F. F. Gundrum is Vice-President, California State Board of
Health, and Consulting Physician, Sacramento County Hospital.
Government service: Chairman Medical Advisory Board No. 7,
Sacramento, Cal.
Dr. Louis Hamman is Acting Physician-in-Chief to The Johns
Hopkins Hospital and Acting Professor of Medicine, Johns Hopkins University.
Dr. F. M. Hanes is connected with Base Hospital No. 65, A. E. F.,
France.
Dr. Henry Harris is Instructor in Medicine, University of California. Government service: Member of Medical Advisory Board,
District No. 5, California.
Dr. R. F. Hegeman is Captain, M. R. C, and Is Assistant Chief of
Base Hospital'No. 96.
Dr. Campbell P. Howard is Professor of Theory and Practice of
Medicine and Clinical Medicine, State University of Iowa, and
Physician to the University Hospital.
Dr. Henry T. Hutchins is Major, M. C, and is Surgeon-in-Chief,
Evacuation Hospital No. 49, A. E. F.
Dr. J. Edwards Kerney is Visiting Urologist, Memorial Hospital,
Pawtucket, R. I.; Visiting Urologist to Rhode Island State institutions; Associate Visiting Urologist to St. Joseph's Hospital,
Providence, R. I.: and Surgeon in Urology to Rhode Island Hospital, O. P. D., Providence, R. I.
Dr. Clarence F. M. Leidy Is Captain, M. C, 62d Pioneer Infantry,
Camp Wadsworth, S. C.
Dr. Hans Lisser is Instructor in Medicine, University of California Medical School, and Assistant Visiting Physician, University of California Hospital. Government service: Chief Examining Physician, Local Draft Board No. 4, Oakland, Cal.
Dr. Herbert M. Little has taken up again his work as Assistant
Professor of Obstetrics and Lecturer in Gynecology, McGill University, after two years' duty overseas with the Canadian Army
Medical Corps. He is also Assistant Attending Obstetrician, Montreal Maternity, and Assistant Attending Gynecologist, Montreal
General Hospital.
Dr. David Russell Lyman is Medical Superintendent, Gaylord
Farm Sanitarium, and Clinical Lecturer on Tuberculosis, Yale
Medical School. He was for six months with the Rockefeller Commission for the Prevention of Tuberculosis in France, and with
the Tuberculosis Bureau of the American Red Cross.
Dr. W. G. JlacCallum is Contract Surgeon, U. S. Army.
Dr. J. D. Madison is Captain, M. C, and is stationed in Milwaukee, Wis., as President of the Examining Board for Medical
Officers' Training Camp, etc.
Dr. W. McK. Marriott is Professor of Pediatrics, Washington
University Medical School, Physician-in-Chief to the St. Louis
Children's Hospital, and Consulting Physician to the St. Louis City
Hospital and the St. Louis Isolation Hospital.
Dr. Robert T. Miller is Lieutenant Colonel, M. C, Director U. S.
Base Hospital No. 27, and Chief of Surgical Staff Mobile Hospital
No. 1.
Dr. Ralph G. Mills, Assistant Resident Pathologist Johns Hopkins Hospital, is Professor and Head of Department of Pathology, '
Peking Union Medical College, Peking, China (absent on leave).
Dr. George R. Minot, Jr., is Assistant Professor of Medicine,
Harvard Medical School; Associate in Medicine, Massachusetts
General Hospital, and Assistant Consulting Physician to Collis P.
Huntington Memorial Hospital of the Harvard Cancer Commission.
Dr. Roger S. Morris is Forchheimer Professor of Medicine, Medical Department University of Cincinnati; Director of the Medical
Division Cincinnati General Hospital, and Director of the Outdoor
Dispensary. Government service: Major, M. C, on duty abroad.
Dr. W. Bean Moulton is Captain, M. R. C, and is stationed at
Camp Greenleaf, Chickamauga Park, Ga.
Dr. C. D. Parfitt is Lecturer on Medicine, University of Toronto,
and Advisor to the Tuberculosis Clinic, General Hospital, Toronto.
Dr. Francis W. Peabody is Assistant Professor of Medicine, Harvard Medical School; Physician to the Peter Bent Brigham Hospital, and Consulting Physician to the Collis P. Huntington Memorial Hospital. Government service: Major, M. C, on active
duty in France.
Dr. Louise Pearce is Associate in Pathology at the Rockefeller
Institute for Medical Research, New York City.
Dr. Clement A. Penrose is Major, M. R. C, at present on inactive
duty.
Dr. H. W. Plaggemeyer is Captain, M. C, and is on active duty
in France.
Dr. Alexander Randall is Captain, M. R. C, and is stationed with
the 6th Army Corps, France.
Dr. George K. Rhodes is First Lieutenant, Medical Corps, U. S. A.,
on duty at U. S. Base Hospital, Camp Meade, Md.
Dr. Hunter Robb is Major, M. R. C. He is stationed in the Medical Officers' Training Camp at Camp Greenleaf, Ga.
Dr. Peyton Rous is Associate Member, Rockefeller Institute for
Medical Research, New York City, and Vice-Chairman, Division
of Medicine and Related Sciences, National Research Council,
Washington, D. C.
Dr. W. G. Sexton is First Lieutenant, M. C. He is on duty with
U. S. Base Hospital No. 158, Camp Greenleaf, Ga.
Dr. W. F. Shallenberger is Associate Professor of Gynecology,
Emory University; Visiting Gynecologist, Wesley Memorial Hospital; Visiting Gynecologist, Georgia Baptist Hospital, and Assistant Visiting Gynecologist, Grady Hospital, Atlanta, Ga.
Dr. Frank J. Sladen is Captain, M. C, and is Assistant Chief of
Medical Service, U. S. Base Hospital, Camp Sherman, Ohio.
Dr. J. Morris Siemens is Major, M. R. C, and is Chief of the
Surgical Service, U. S. Base Hospital No. 92, Cape Greene, N. C.
Dr. F. Janney Smith is Captain, M. C. He is Chairman, Cardiovascular Examining Board, and President, Certificate of Disability
Board, 155th Depot Brigade, Camp Lee, Va.
Dr. Winford Smith is Colonel, Medical Department, U. S. A., and
Chief of Bureau of Administration, Hospital Division, Surgeon
General's Office, Washington. D. C.
Dr. Richard P. Strong is Major, M. C, and is stationed in France.
Dr. Solomon Strouse is Assistant Professor of Medicine, Northwestern University; Attending Physician, Michael Reese Hospital;
Director, Department of Medicine, Michael Reese Hospital Dispensary. Government service: Secretary and Member of Medical Advisory Board 3 J, Michael Reese Hospital.
Dr. Adrian Taylor, Assistant Resident Surgeon, The Johns Hopkins Hospital, is Professor of Surgery and Head of Department of
Surgery, Union Medical College, Peking, China.
Dr. W. S. Thayer is Physician-in-Chief to The Johns Hopkins
Hospital and Professor of Medicine, Johns Hopkins University.
Government service: Brigadier General, M. C, U. S. Army, and
Chief Medical Consultant, A. E. F., France.
Dr. Charles B. Thompson is Executive Secretary, Meulal Hygiene
Society of Maryland: Psychiatrist at the Hebrew Hospital Dispensary, and Lecturer on Psychiatry to the Training School of the
L'nion Protestant Infirmary.
Dr. Douglas Vanderhoof is Professor of Medicine in the Medical
College of Virginia, Physician-in-Chief to the Virginia Hospital,
Senior Attending Physician to the Memorial Hospital, and consulting Physician to the Johnston-Willis Sanatorium. Government
service; Secretary Medical .-\dvisory Board No. 2. Richmond, Va.
Dr. Cecil \V. Vest is Captain. .M. C. and is stationed at Camp
Meade, Md.
Dr. Carl \V. Waldron is Captain. C. A. M. C. O. C. The Canadian
Unit. He is stationed at The Queen's Hospital, Frognel. Sidcup.
Kent, England (for facial and jaw restorations).
Dr. Louis .M. Warfield is Major. M. C. and is Chief of the Medical
Service, Jefferson Barracks. Mo.
Dr. S. Shelton Watkins is Lieutenant, M. C. U. S. Navy.
Dr. Ernest M. Watson is Instructor in I'rology. .Medical Department, University of Buffalo; Attending Urologist to Buffalo City
Hospital, Municipal and Ernest Wende Hospital: Assistant Attending Urologist to Erie County Hospital, and Assistant in Clinical
Urology, Buffalo General Hospital.
Dr. Charles W. Webb is Chief Surgeon to the Clifton Springs
Sanitarium and Hospital. Clifton Springs, N. Y.
Dr. Harry 1. Wiel is Assistant in Medicine, University of California, and .Assisting Visiting Physician, San Francisco Hospital,
San Francisco, Cal.
Dr. Gordon Wilson has taken up again his work in Baltimore
after serving as Major, M. R. C. having been assigned to Camp
.Meade as Tul>erculosis Specialist.
NOTES ON NEW BOOKS
The liuntgcn Diagnosis of Diseases of the Alimenlary Canal. By
Ri'sstax D. C.vKMAN, M. D., and Auiebt Miixeb, M. D. (Philadel/ihia: W. B. Saunders Company. 1917.)
It Is quite refreshing to read such a splendid description of the
various methods and means of diagnosis as are put forth by Carman and Miller.
After a description of apparatus, technic and interpretation they
take up the different organs and the various manifestations of
disease as evidenced by rcpntgon examination.
Of especial value is the liescription of the normal findings before
each chapter on the various organs, thus giving the student a much
clearer conception of the pathologic states as outlined later. The
idea of giving classified lists of roentgenologic signs in various
diseases is noteworthy and a splendid idea.
Among other things which make the book graphic and impressive is the fact that practically all cases shown have been
verified by operation and noted in the text— also the references at
the end of each chapter prove to be another great asset.
Altogether the book is of great value — easy to read and understand because of the clearness of the text — the various points are
graphically portrayed by splendid illustrations, and every subject
receives thorough consideration from all points of view. It is a
book which should be read by every rrentgenologlst as well as all
practitioners interested in the roentgenologic diagnosis of gastrointestinal conditions, as It Is undoubtedly by far the foremost
publication on the subject to-day. E. H. G.
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==Contents==
Fluoroscopy of the Cerebral Ventricles. (Illustrated. t A Pliarmacological Appreciation of a BIhliral Reference to
By WAi.TtB E. Dandv J'J Mass Poisoning, 11 Kings IV, 3S-41. (Illustrated.)
Stereoroentgenogranis of tlie Injected Lung as an Aid to the B.v Uavid I. Maciit. A. B.. LL. B., M. D., F. S. .!.A. . 38
Study of the Lung Architecture. (Illustrated.)
By William Snow Miller 34 Titles of Papers Appearing Uurini; the Year. Elsewhere than in
An Electromyographic Study of Chorea. (Illustrated.) the Bulletin, by Present and Former Members of the Hos
By Stanlet Cobb, M.D 35 pital and Medical School Staff 42
TITLES OF PAPERS APPEARING DURING THE YEAR. ELSEWHERE
THAN IN THE BULLETIN, BY PRESENT AND FORMER MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF
Abel, J. J., and Pincoffs, M. C.
On the presence of albumoses in extracts of the posterior lobe of the
hypophysis cerebri. — Utiid. Kockejeller Inst. M. Research, N. Y., 1918,
x'xyiii, 193-203.
Atchley, D. W.
A study of eight cases of acute nephritis. — Arch. Int. ilcd.. Chicago,
1918, xxii. 370-408.
Renal action in acute nephritis. — Proc. Soc. Exper. Biol. A lied., X. Y.,
- 1917-18, XV, 85-88.
AUEB, J.
Generalized analgesia in cats after exposure to a war gas (CH3);S0,. —
Proc. Exper. Biol, d Med., N. Y., 1918, xv, 104-106.
Localized pulmonary edema in cats after the inhalation of \yar gas
I CH,)2S0,.— Ibid., 106-107.
AuEE, J., and Gates, F. L.
Experiments on the causation and amelioration of adrenalin in pulmonary edema. — Stud. Rocketeller Inst. M. Research, N. Y.. 1918,
xxviii, 131-150.
AuER, J., and Kleixee, Isabel S.
Morphine hyperglycemia in dogs with experimental paucreatic deficiency. — J. Exper. M., Bait., 1918. xxvii, 49-03.
AuER, J., and Meltzer, S. J.
Lantern slide demonstration of the effect of magnesium sulphate upon
tetanus. — Proc. Soc. Exper. Biol, d Med., N. Y., 191T-1S. xy. 36-37.
The administration of epinephrin by intraspinal injections in acute or
subchronic cases accompanied by a low blood pressure. — J. Am. M. .\ss.,
Chicago, 1918, Ixx, 70-71.
Baer, W. S.
Arthroplasty with the aid of animal membrane. — Am. J. Orthop. Surg.,
Host., 1918, xvi. 1-29: 94-115; 171-199.
Primary and delayed primary suture in the treatment of war fractures.
— Am. J. Orthop. Surg., Bost., 1918, xvi, 513-519.
Also: J. Am, M. Ass., Chicago, 1918, Ixx, 1530-1533.
Baetjer, F. H.
Differential diagnosis of bone tumors. — Am. J. Roentgenol., X. Y.,
1918, y, 261-264.
Baetjer, W. A., and Miller, S. R.
Bence-Jones proteinuria : some observations on its occurrence, with
particular reference to nephritis and hypertension. — J. Am. M. Ass.,
Chicago, 1918. Ixx, 137-139.
PoIIinosis or hay-fever : its specific treatment. — South. M. J. Birmingham, Ala., 1918, xi, 341-345.
Baetjer, W., Strong, R. P. let ah].
Report on progress of trench fever investigations. Trench Fever Commission of Medical Research Committee, American Reti Cross. — J. Am.
M. Ass., Chicago, 1918. Ixx, 1597-1598.
Barker, L. F.
Heart murmurs. — Canada Lancet. Toronto, 1918, 11, 545-551.
Endocrine functions and the digestive apparatus. — Med. d Surg.,
St. Louis, 1918, ii, 655-678.
The general diagnostic study by the internist. — -V. York M. J. [etc.],
1918, cvii. 489-493; 538-542; 577-582. Also: Med. Rec, N. Y., 1918,
Nervous and mental symptoms in exophthalmic goiter. — J. Am. it. Ass.,
Chicago, 1918, Ixxi, 327-329.
The value of the classics as a part of the studies preparatory to
medicine. — South. M. J., Birmingham. Ala., 1918. xi. 391-394.
Address in Medicine. On the significance of " heart murmurs " that
may be found on examination of candidates for military service. —
Canad. M. Ass. J., Toronto. 1918, viii, 577-585.
Oral sepsis and the digestive apparatus. — South. M. J., Birmingham,
-Ala., 1918. xi, 481-484.
The first ten years of the National Committee for Mental Hygiene, with
some comments on its future. — Ment. Hyg., Concord, N. H., 1918, ii.
557-581.
Barker, L. F., and Miller, S. R.
Perforating ulcer of the hard palate resembling tertiary syphilis. —
J. Am. M. Ass., Chicago, 1918, Ixxi, 793-797.
Barker, L. P., and Rowntbee, L. G.
A report of a case of myrtol poisoning with comments upon the toxicity
of eucalyptus oil and myrtoi in human beings and in animals. — Tr. Ass.
Am. Physicians, Phila., 1918, sxsiii.
Beall, K. H.
The diagnosis of nephritis. — Texas State J. M., Fort Worth. 1918, xiii.
349-351.
Berey, J. M.
Action of the gluteus maximus
strain. — AZftonj/ if. Ann., 1918,
Blackfan, K. D.
Lead poisoning in children.
-Midland M. J., Birmingham. 191S, xvii.
Blackfan, K. D., and Maxcy, K. F.
The intraperitoneal injection of saline solution. — Am. J. Dis. Cliild.,
Chicago, 1918, xy, 19-28.
Block, E. B.
The relation of oral sepsis to the nervous system. — South. If. ./.,
Birmingham, Ala., 1918, xi, 606-609.
Bloodgood, J. C.
Some hernias that disqualify for military service, whether operated
on or not. — J. Am. M. Ass., Chicago, 1918. Ixx. 515.
A warning against operations for varicocele on applicants for enlistment, registrants for the selective draft and soldiers. — J. Am. M. Ass..
Chicago, 1918, Ixx, 409.
Medical preparedness and medical and surgical problems in this war. —
Penn. M. J.. Athens, Pa., 1918. xxi. 389-394.
Medical preparedness in the great drive for democracy. — South. M. J.,
Birmingham, Alabama, 1918, xi, 51-56.
Aluo: Muruland M. J.. Unit.. T.HS. Ul. 1-0.
.ll»o; J. Florida it. Ast., St. Augustlue & .IiKksonvlllc, 1918. Iv, 2.-5
How the iniliisirliil surgodii <'iin host co-operate with the GoTornniPut
ilurlog the war.--NoM/fc. M. ./., BlrmlnKhain, Ala.. 1918. xl. 45:t-4ri4.
The liiiportiince of recocnlzlng the weakness or the obllteralinn of the
ronjolneil temlon In operations for Infrulnal hernia. — South. H. ./..
BlrmlDKhnm, Alabama. 191S. il. 3e«S(i9.
AKo: ">»f. il. Kr<-.. Omaha. Neb.. 1918. xilll. SOl-.W".
Soldiers illsableil In the war. (Letter). — South, il. J., BirinlDgham.
Alabama. 1918. xl. r,-2i;X , „ ,
Some principles Involvlne the treatment of Infeeteil wounds. — ./. J/.rf.
At: Georgia. Augusta. 1918. vlll, 9-i:i.
Bloomfield, a.
Typhoid bacterlemla during the course of miliary tuberculosis. — .liii.
Kei: Tuberc, Bait.. 191S. 11. 28-35.
Brem. W. v.. Rolling. G. E. and Caspee. E. J.
Pandemic Influenza and seiondarj- pneumonia at Camp Fremont. Calif.
—J. Am. il. .!»».. Chicago, 191S. Ixxl. 21.38-2144.
Bribgman, E. W., and Hibose, K.
The effect of diuretics on the general blood pressure in animals with
constriction of the renal arteries. — Arch. Int. Ued., Chicago, 1918. xxi.
3.-1-.3.J3.
Brooks. B.. and Allison, N.
Arthroplasty: exp<TimentaI and clinical methods. — Am. ./. ()ilhiii>.
Surg.. Boston. 1918, xvi, 83-93.
Brooks. B.. ScmMAciiER. H. W., and Wattenbero, J. E.
Intestinal obstruction: an experimental study. — Anil. Surg., I'hilii..
1918. IXTll. 210-214.
Bbowx, T. R.
studies on some unusual tvpes of diarrhea. — ilcd. d Surg., St. I^ouis.
1918. II. 640-«4.".
BiSTixG. C. H., Martin. H. G.. and Loeveniiabt. A. S.
The mori'hologlcal changes In the tissues of the rabbit as a result of
reduced oxidation.—^, i'j-pcr. J/., Bait., 1918. xxvii, 399-412.
BlBNS, J. E.
The diagnosis and treatment of urlnarr Ilthlasls. — llVst Virg. it. J.,
Huntington. 191s. xli. 280-291.
BfBNs, J. E.. and Hopkins, P. B.
A comparative study of the effects of thorium and other substances on
the renal parenchyma when retained.— >/. Vrol., Bait.. 1918. 11. 145-1.')9.
BiBBOws. M. T.
A note on the mechanism of heart muscle contractions. — J. ilisaouri
if. Atf.. St. liOUis. 1918. XT, 13S.
Why should autopsies be held? The argument to be used with relatives
and friends. — Interstate it. J., Chicago, 1918. xxv. 700-763.
Burrows, M. T., and Neyjiann, C. A.
Studies on the metiiboilsm of cells In vitro. The toxicity of ilipeptiils
for embryonic chicken cells. — i'ror. .S'oc. ICrpcr. Hiol. it iled., .N. Y.,
1918. XV. 1.38139.
Camac, C. N. B.
Clinical report upon cases of lobar pneumonia treated with nnti
Sieumococcus serum as observed at general hospital no. 6. Fort
cFherson. Georgia. October. 1917. to May, 1918.— .4m.. J. M. Sc,
Phila.. 1918. civi. 887-893.
Cameron. D. F.
Aqueous solutions of potassium and sodium iodlds as opaque mediums
in roentgenography. Preliminary re|)ort. — /. .l»i. il. Asa., Chicago.
1918. Ixx. 754-7.—I.
Camebon, D. F.. and Gbandy. C. C.
Sodium ami potassium Iodlds In roentgenographv.--./. .4m. .1/. Ana.,
Chicago. 1918, Ixx. 1,'.I0-1.J17.
Campbei.l, C. M.
The r<^le of Instinct, emotion and personalllv in disorders of the heart.
With suggi-sllons for a clinical record. — ./. Am. il. .4»«., Chicago, 1918.
Ixil. 1021 1020.
A city school district and its subnormal children: with a discussion
of some soilal pmlilems lnv(dved and suggestions for constructive
work. — ilrnl. Iliig.. Concorii. .\. II.. 1918. li. 232-244.
A case of chlldhond conflicts with prominent reference to the urinary
system: with 8<ime general considerations on urinary symptoms In the
psyrhonru roses and psychoses. — I'fuchoanalut. Her., Wash., 1918. v.
269 290.
Carter, E. P.
F^irther observations on the aberrant electrocardiogram associated with
sclerosis of the atrioventricular buniile branches and their tenninal
arborizations, rilnical and histologic report of a case in which such
aberrant complexes were obtained. — Arch. Int. iled.. Chicago. 1918.
xxil. 331 3.'-,3.
Carter, E. P. and Wedd. A. M.
Report of a case of paroxysmal taehycarilia characterized by unusual
control of the fost rhythm. — Arch. Int. iled., Chicago, 1918, xxil, 571!)80.
Casler. DeW. B.
Tetanus fnllnwlng laparotomy for ectopic pregnancy. Treatment hr
subarachnoid injections of magnesium sulphate and anll-tetonlc
serum — recovery —.Voiil A. il. ./,. Birmingham. Alo.. 1918, il, .-,12 .''.n;.
ider.- /ii; Hod. frol. (Cabot), 8°, Phila. Jt .V. Y.
St. Uiuls
Cailk. J. R.
Infectious of the bla
1918. 11. 80-131.
The treatment of undescended testicle. — Interstate il.
1918. xxv. 2S.'.-2S0.
The diagnosis of diseases of the central nervous system by means
of the cystctscopic appearance of the bladder. — Interstate il. J.,
St. lyouis. 1918, xxv. 102-104.
Remarks on kidney surgery. — South, il. ./., Birmingham. .Ma.. 1918.
xi. 299-305.
Caclk, J. R., and Greoitzer, H. C.
Occluded renal tuberculosis, nutune])hrectomy. — iled. d Sun/., St. Louis.
1918. ii. 4:.3-450.
Cecil, A. B.
An unique type of urethral obstrucllou.384.
^/. t rol. Bait.. 1918. 11. 379
Eiper. il.. Bait..
Chesxey. a. II.. and CtLij^N, G. E.
A note on the production of acid l)y pneuiiuic
1918. .\xvlil, 289-29i;.
Chesxey, A. M., and Moore, H. P.
A further study of cthylhvdrocui>rein toptochini In the treatment of
acute lobar pneumonia. — Arch. Int. iled., Chicago, 1918, xxi, 059-081.
Churchman, J. W.
Melanosnrcoma of the rectum, with the report of a case. — .4m. J. il. Sc.,
Phila.. 1918. dr. 039-044.
Treatment of acute infections of the joint bv lavage and direct meditation.—./. .4m. .U. .4«».. Chicago. 1!>I8. Ixx. 1047-10.')0.
Fibroma of the tongue with consiileratlon of other tumors of the
tongue an<I certain technical points in tongue resections. — iled. d
Surg.. St. I>ouis, 1918. ii. 173-177.
A new incision for exposure of the lower abdomen and pelvis. — .liin.
Surg., Phila., 1918, Ixvil, 180-182.
Clakk. a. H.. and Feltox, L. D.
A flltrable toxic product of the hemolytic streptococcus. — J. .4m. il.
Ass., Chicago. 1918. Ixxl. 1048-1049.
Clark, J. G.
Medical teaching and research nftiT tli<
1918. Ixxvlii. 220-2.30.
The therapeutic use of radium in gyncci
Chicago. 1918. xxvi, 019-024.
Clarke, T. W.
The baby that •
war.— tm. J. Obtt., S. Y..
ilogy. — Surg. Oynec. d Obst.,
ininot take milk.— trcd. Pcdint., X. Y.. 1918, xxxv, 193
Clausen. S. W.
a method for the estimation of potassium in blood. — .1. Biol. Chem..
Bait., 191.S. xxxvi. 479-484.
The effect of injections of pituitary solution on (he urinary output in
a case of diabi'tes Insipidus.- .4 m. ./. Dis. Child., Chicago. 1918. xvi.
195-204.
Clausen. S. W.. and Mo.senthal, H. O.
The malntinance diet In diabetes meliitus as determined by the
nitrogen equilibrium.— .Irc/i. Int. iled.. Chicago. 1918. xxl. 269-281.
Clausen, S. W., Mosentiial, H. O., and Hii.i.eb, Alma.
The effect of diet on blood sugar in eliabetis meliitus. — Arrh. Int. ilrd..
Chicago, 1918, xxl, 93-108.
Cobb, S.
A note on the supposed relation of the sympathetic nerves to dccere
hrate rigidllv. muscle tone, and tendon reflexes. — .Im. J. Physiol. Bait..
1918, xlvl, 478-482.
Cole, R.
I'revenllon of pneumonia. — J. Am. il. Ass., Chicago. 1918. Ixxl. (',3.-i
0.39.
Pneumonia as a public health problem. — Kentucky il. J., 1918. xvi.
563-505.
Cole. R., and MacCallum, W. G.
Pneumonia ut a base hospital.
1140-1 l.'.O.
CoxE, S. M.
a methoil
42-43.
if studying nerv<
(^hlcago. 1918, ixx.
Im. ./. Orlhnp. Surg., Bost., 1918. xvi.
Some of the results of work on the pathology of peripheral nerve
Injuries- Im. ./. Orthop. Surg., UnDt.. 1918. xvi. 319.322.
Surgliiil pathology of the peripheral nerves. -Ilrit. .1. Surg . Bristol.
-mal nervi's and war injured nerves
rath, d llaclcrlol, xxil, 1051 II.
1917 IV,
lllstolnglcal observations on
with the neurokeratin slain.
Corner. G. W.. and Ht bni. F. H.
The non effect of corpus iuleum preparations on the ovulation cycle of
the rat.— .4m. ./. I'hysiol., Bait., 1918. xlvl. 48.3486.
Cusiiiso, H.
A study of a series of wounds Involving the brain and Its enveloping
structures.- /Ir(». -1. Surg., Bristol. 1917-18, v. 5.1«.«84.
Notes on penetrating wounds of the brain. — Brit. il. J., Ixinil.. 1918. I.
221-220.
Dandy, W. E.
Extiniallon of the choroid plexus of the lateral ventricles In eommunl.nilng h^dnM ephalu". -.Inn. Surg.. Phila.. 1918. Ixvili. .-,09 .'.79.
Ventriculogrnpbv folbiwlng the injection of air Into the cerebral
ventricles— . I nil". Surg., Phila.. 1918. Ixvlii. 5-11.
Davis, E. G.
Duodeno urptei-al fistiilii of spcmtanpoiis oriRin : report of a case. —
J. Am. M. Ass.. Chicago. lOls. Ixx. ;;7(! ::7s.
Urinary antisepsis: a stiul.v of tlie antisi'ptic properties and the renal
excretion of compounds related to phenolsulphonephthalein : preliminary report.— .7. Am. M. A.1S., Chicago, lOlS. lx.\, 581-585.
Davis, E. G., and Hain, R. F.
Urinary antisepsis. The antiseptic properties of normal dog urine. —
J. Viol. Bait., 1918. ii, ;'.0S)-320.
Davis, E. G., and Harrell, B. E.
.Acriflavine in the treatment of gonorrhoea — an experimental and clinical study. — J. Urol., Bait.. 1918, ii, 257-27G.
Davis, E. G., and White, E. C.
Urinary antisepsis, further studies of the antiseptic properties and the
renal excretion of compounds related to phenolsulphonphthalein. —
J. Urol, Bait., 1918, ii. 107-127.
Urinary antisepsis. The secretion of antiseptic urine following the
Intravenous administration of acriflavine and proflavine ; preliminary
report. — J. Urol, Bait.. 1918. ii. 299-^07.
Davis, E. G., White, E. C, and Rosex, R.
Urinary antisepsis. The secretion of antiseptic urine following the
intravenous administration of an organo-mercury phthalein derivative.—,/. Urol, Bait.. 1918. ii. 277-297.
Davis, E. G., and Young, H. H.
The surgery of the douhle kidney. Report of a case of resection of
upper segment for calculous pyonephrosis. — Surg., Giincc. d Obst.,
Chicago, 1918, xxvii. 1-l.S.
Davis, J. S.
The use of the pedunculated flap in reconstructive surgery. — .liiii.
Surg., Phila., 1918. Ixviii, 221-230.
Davison, W. C.
The superiority of inoculations with mixed triple vaccine (B. typhosus.
B. paratyphosus A. and B. paratyphosus B. ) over successive inoculations with the single vaccines, as shown by agglutinin curves in
men and rabbits. — Arch. Int. Med., Chicago. 1918, xxi. 437-509.
Dawson, P. M.
I'nlversity ideals
Pa.. 1918. n. s..
Sci€7ice, y. Y. and Lancaster.
-,r. Am. If. .Iss.. Chicago,
ilf. Ass.. Chicago. 1918. Ixxi. 63S-G39.
Dick, Gladys H., and Murray, Eleanor.
The morphology of the inlluenza bacillus
1918, Ixxi, 1568.
Dickson, E. C.
Botulism ; a further report of cases occurring In the Pacific Coast
States. — Arch. Int. lied., Chicago. 1918. xxii. 483-495.
Botulism. A clinical and experimental study. — Monogr. Rockefeller
Inst. it. Research, X. Y.. 1918. no. 8.
Botulism.— Bh//. Canadian Army M. Corps. 1918. i. 85-87.
Al.w: Canad. M. .4.i.s-. ,/., 1918, vill, 903-909.
Dickson, E. C, and Burke, G. E.
Botulism : a method of isolating Bacillus Botullnus from infected
materials. — J. Am. M. Ass., Chicago, 1918, Ixxi. 518-521.
Felton, L. D., and Clark, A. H.
A Bltrable toxic product of the hemolytic streptococcus. — •/. .Im. J/.
Ass., Chicago, 1918, Ixxi, 1048-1049.
Flexner, S.
Control of meningitis. — .7.
Dr. p-ranklln P. Mall ; an appreciation. — Science. N. Y. & Lancaster,
Pa.. 1918, n. s., xlvli. 249-2.54.
Flexner, S., and Awoss, H. L.
The passage of neutralizing substance from the blood into the cerelirospinal fluid in actively immunized monkeys. — J. Exper. M.. Bait..
1918, xxvlii. 11-17.
FLEXNER, S., Amoss, H. L., and Eberson, F.
Physiological stimulation of the choroid plexus and experimeutal poliomyelitis. — J. Exper. M., Bait., 1918, xxvii. 679-687.
Flournoy, H.
Notes sur 4 cas d'obsessions et impulsions a debut instantan^. —
( Coinmunication a la Soci^te Medicate de Gen&ve), Geneve, 1918.
Kiludig. 24 pp. 8°.
l.'alcoi.iismt' et les enfants anormaux. — Extrait du xiii rapport de la
Soriet*^ g^uevoise de patronage des Alleu^s. 1918, 16 pp. 8"^.
Ford, W. W.
I'tirther observations on the bacteria of the intestinal tract. — Tr. Ass.
Am. Physicians, Phila.. 1918, xxxlli.
Fowler, H. A.
Anatomy, anomalies and injuries of the penis. — In: Mod. Urol
(Cabot), 8°, Phila. & N. Y., 1918, I. 193-222.
FroNTZ, W. A.
Presentation of device facilitating the introduction of the cystoscope
in certain difficult cases. — J. Urol, Bait.. 1918. ii. 39-41.
Froxtz, W. a., and Geraghty, J. T.
A study of primary hydronephrosis. — .7. Urol. Bait.. 1918. ii. 161-209.
Futcher, T. B.
Chronic hypertrophic pulmonary osteo-arthropathy following bronchiectasis. — Bull. Canad. Army Med. Corps. 1918, i. 38-40.
Career, J. R.
.\ iilea for prenatal care and the end-results of the h.vgiene of pregnancy.— Am. J. Obst., N. Y., 1918, Ixxviii. 506-575.
-.7. Indiana M.
Mod. Urol (Cabot). 8°, Phila. & X. Y..
Mod. Urol (Cabot). 8". Phila. & X. Y..
Radium. Pittsburgh. Pa.,
Phila.. 1917-lS.
ngham, Ala.. 1918. xi.
locytic leukemia.
Gatch, W. D.
Some observations on the surgerV of the thyroid gland. Ass., Fort Wayne. 1918, xi, 13-17.
Geraghty, J. T.
Tumors of the bladder.
1918. ii. 187-244.
Tests of renal function
1918, Ii. 337-376.
The results of treatment of bladder tumor
1918. X, 77-85.
Geraghty, J. T., and Fbontz, W. A.
A study of primary hydronephrosis. — J. Urol, Bait.. 1918. ii. 101-209.
GiBBES, J. H.
Ilodgkin's disease; primary involvement of mediastinal glands with
presentation of tumor mass over sternum. Blood-picture characteristic
of well-advanced disease. Differential diagnosis. Etiology. Pathologic
anatomy. I'rognosis. Treatment. — Med. Clin *'
i. 1587-1594.
Oral sepsis an<l arthritis. — Sonth. M. ./.. Bii
489-492.
GiFFIN, H. Z.
Splenectomy following radium treatment fo
Med. Rec, X. Y.. 1918, xciv, 1020-1023.
GiFFiN, H. Z., Sanford, a. H., and Szlapka, T. L.
Estimation of urobilin and urobilinogeu in the duodenal +++++
CONTENTSs. —
Am. J, M. Sc. I'hila.. 1918, civ. 562-579.
GOETSCH, E.
-Vewer methods in the diagnosis of thyroid disorders : pathological and
clinical. — .V. York State J. M., N. Y.. 1918, xvili. 239-207. Also:
Clifton Med. Bull, Clifton Springs, 1918. 1-12.
GOLDBAOH, L. J.
Nasopharyngeal tibro-myxoma. undergoing sarcomatous changes. —
Laryngoscope, St. Louis. 1918, xxyiii. 106-108.
GOODPASTURE, E. W.
An anatomical study of senescence iu dogs, with especial reference to
the relation of cellular changes of age to tumors. — J. Med. Research,
Bost., 1918. xxxviil. 127-190.
Observations on mitochondria of tumors. — Ibid., 213-224.
Goodpa.sture, E. W., and Jacobson, V. C.
Occlusion of the entire inferior vena cava by hypernephronm. with
thrombosis of the hepatic vein and its branches. — Arch. Int. M..
Chicago, 1918. xxii. 86-95.
GORHAM, L. W.
Xote on the diagnostic use of the X-ray in pneumonia, with especial
reference to the position of the diaphragm. — .ilhany M. Ann., 1918.
xxxix. 58-65.
.7. Physiol.
ulogy. — South. M. -/.. Birmingham.
eluding bands. —
Grey, E. G.
Observations on the postural activity of the sto
Bait., 1918, xlv, 272-285.
Griffith, F. W.
Some of the common errors in gyne
Ala.. 1918, xi. 40-42.
Gundrum, F. F.
Rat bite fever with report of two cases. — Calif. State J. M., San Fran..
1918, xvi, 16-18.
Nitro-benzol poisoning. — Calif. State J. M., San Fran.. 1918. xvi, 2o2
253.
Hain, R. F., and Davis, E. G.
Urinary antisepsis. The antiseptic properties of normal dog urine. —
,J. Urol. Bait.. 1918. ii. 309-320.
Halsted, W. S.
Dilation of the great arteries distal to partial
Proc. Nat. Acad. Si:. Bait.. 1918, iv, 204-210.
Cylindrical dilation of the common carotid artery following partial
occlusion of the innominate and ligation of the subclavian. — Tr. .im.
Surg. Ass.. Phila.. I'.US, xxxyi.
Ijetter to Dr. Keen. Communication on the subject of the Carrel
Dakin treatment of wounds. In: Keen, \V. W. The treatment of war
wounds, Phila.. 2. ed.. 1918, 252-259.
Harrell, B. E., and Davis. E. G.
Acriflavine in the treatment of gonorrhoea — an experimeutal and
clinical study. — •/. Urol Bait., 1918. ii. 257-276.
Harrop, G. a., and Mosexthal. H. 0.
The comparativi- food yalue of protein, fat and alcohol in diabetes
mellitus as measur. d bv the nitro.cen equilibrium. — Arch. Int. .Med.,
Chicago. Iill8. xxii. 7.50-75S.
Hazex, H. H.
Syphilis and the war. — .4»i. ./. Syph., St. Louis. 191s
A more intensive form of arsphenamine therapy.
St. Louis. 1918, ii. 778-779.
More contract surgeons (Letter). — J. .\ni. M. Ass.
Ixx. 1184. „^„
Duties of the dermatologist. — J. Am. M. Ass.. Chicago. 1918. Ixx. 1989
1990.
Dermatology and the war. — Med. if- Surg., St. Louis, 1918. ii. 145-l,.l.
Hiller, Alma, Mosenthal, H. O., and Clausen, S. W.
The effect of diet on blood sugar in diabetes mellitus. —
Chicago, 1918, xxi, 93-108.
. 144 135.
im. ./. Syph..
Chicago. 1918.
Arch. Int. Med..
Februabt, 1919]
45
Chi.ni:.!. 1!US. Ixxl.
Hl.NMAN, F.
Thi" nianagpiiicnt of siirKlcal risk: n review of 100 klilney iinil prostate
0[H>rations. auil 50 eases of enlnr^d prostate Dot operated iipou. —
Call/. Stole J. M.. San Fran.. 1!>1S. xvl. 2tl-::i."i.
A niodlfleatlon of CltzmaDH's syringe for iMSterlor urethral Insilllatlons.^. Am. .U. .!»«.. Chicago. lOlS. \x\. l:;!>i.
His.MAN, F.. and Lissek H.
Srpbllls of the epliUil.rmls without Involvement of the testicle : Itcporl
of cage.— .Im. .;. S„i>h.. St. Louis. 1018, II. 4»i.'>-471.
HlBSCIIFELDEB, A. D.
The leaching ni pharmacology. — ,/. Am Jl
tiU'.l-tilL'.
HiRscHFELDER. A. D., and Caxtwei.i,, W.
KITiMts of sonic aminii acl.ls upon the e.\clse<l segments of Intestine. —
J. Pharmntol. d f.'j-pcr. Thcrap.. Bait.. 1018. xl. ITS.
HrrzBOT, J. M.
The effect of spleneetomv on the normal Imllvhliial and In certain
pathological eoDilltlons.—' .4nn. Hurg.. I'hlla.. 11118. Ixvll. .i4()-."in.
Myeloma of the clavicle.— -Inn. b'urg., Thlla.. 1018. IxvUl. ICIM.
HoL.MES, J. B.
Keccnt work In anatomy, physiology and pathology of childhooil.- Am. ./. l>iH. Ihil.. ('hlcuga, IftlS. xv. L'78-308.
Hooker, D. R.
The veno-pre.
mechanism. — .liii. ./. I'hijHiol.. Bait.. lOlS. xlvl.
Hooker, D. R.. and Maciit. D. I.
Coueerning the action of the lodlile. bromide and nltnite Ions on the
respiratory center. — ./. I'hnrmncol. A Expcr. Thcr<ii>.. 1018. xl. 113-G7.
HoPKixs, J. G., and Parker, Jilia T.
The effect of Injections of hemolytic streptococci on susceptible nnd
insusceptible animals.—./. Exprr. J/.. Bait.. 1018. xxvU. 1-20.
Howard, C. P.
.Some of the medical lessons of the present war. — /. loira Sliitc U. .S'oc.
Clinton. 1018. vlU. :t.-2.
Howard, C. P.. and I.ngvali>.sen-, T.
The mlm-ral metabolism of experimental s<urvy i<( thi- monkey. — L'vif.
Iowa UonogrnphM, Studies In Med.. 1018. 1. 111).
Howard, C. P., and Steve.ns. F. A.
The Iron metabolism of hemochromatosis. — fiiir. loicii ilriHognipln-.
Studies In Med.. 1018. 1. 1 IT.
Howell. W. H.
The coagulation of blood.— //nrrci; Lict.. lOli; IT. I'hila. & I,ond.. I'.Hs.
JT2-:t2:t.
HowLAXD. J., and Marriott. W. M.
Ad.losls.— /'rnn. .1/. !.. Athens. I'a.. 101,8. xxl. 4i;0-4:!l!.
The Influence of a< Id phosphate on the elimination of ammonia hi I he
urini'.-.l rcA. Int. .Mrd.. Chicago. 1018. xxll. 4T7-48-.>.
Dbservatbms upon the calcium +++++
CONTENTS of the hlood In Infantile tetany
anil upon the effeil of treatment by calcium. — Quart. ./. .Med.. Oxford.
1018, xl. 280-tlO.
Hf.NXEB, G. L.
Anatomy, abnormalities. Injuries and diseases of the ureter. — In: .Mud.
I rol. (Cabotl. 8°. Phlla. & N. V., 1018. II. 24."i-:tll.
A rare type of bladder ulcer. Further notes, with a report of eighlicMi
cases. — /. .On. .1/. !»».. Chicago. 1018. \xx. 2();t 212.
Kluslve ulcer of the bladder. Further notes on a rare type of bladder
ulcer, with a reiiort of twenty-live cases. — Am. ./. Obxf., N. Y.. 101s.
ixxviii. :it4-:hi.-..
The etlologv of ureteral lalculus. — .S'lirtf. (Ifinrr. .{ olml.. Chicago. I'.ils.
xxvll. 2.'>2-2Tn.
HtRWITZ, S. H.
The value of renal functional studies In the prognosis and Ireiiliinnt
if nephritis.- f'liUf. State ./. U.. San Fran.. 1018, xvl. 28T-20:i.
HtRWITZ, S. H.. and Falconer, E. H.
The %nlue of Unehtgen rays and benxene In the treatment of poly
cythemla vera. — /. Am. .M. Afn., Chicago. 1018. Ixx. 114:!lU.-i.
HtRwiT7, S. H.. Meyer, K. F.. and Tacssio, L.
Studies on the Mooil proteins. III. Alliumln-globulln rallo In anillnxli
Immunity. — /. Infrrl. /ii«.. Chicago. I'.ils. xxll. 1-2T.
.Iack, W. D., and Balleiil, L. C.
The use of fascial transplants in war surgery. — -.Inii. Sinu . I'bll.i .
1018, IxvlU. 14.
Jaxe>vay, T. C. Richardson, H. B., and Park, E. A.
Kiperlmenis on the vasoconstrictor action of blood serum. — In/i fi;(.
-Ved.. Chicago, 1018. xxl. .-.tl.'i-l!o:<.
Keidel, A.
rorasltologv anil serologv of syphilis. — .tin. ./. Suph.. St. I.<iuls. IOI>.
II. 2Tii.2.sT. I No; South. .1/. ./., Birmingham. Ala.. 1018. xl. 2117 2T1.
Keidel, A., and Zim.mermann, E. L.
Tattooing and syphilis.— .tm. J. Spph.. St. Louis. 1018. I. 8.1. 00.
Keith, N. M.. and Thomson, W. W. D.
War nephritis, a clinical, functional, and pathological study. — (jiinri
t. Sled., Oxford. 1018. xl. 220-200.
Kelly, H. A.
Fibroid tumors of the uterus treated with radium. — Charlotte |.V. f'.j
.U. ./.. 1018. Ixxvll. l.'i.-il.'lT.
Fibroid tumors and radium. — Virginia J/. Slonth.. Kichmouil. Va..
lOLs. xlv. IT,
Two hundn-d and ten fibroid tumors treated by radium. — 7'r. Am.
Olinrr. Soe.. rhila.. 1018. x||||.
The.Hlore Caldwell Janewav. 18T2-101T. — lloiton \l. Jt S. J.. 1018.
clxxlx. .-.'.iT-.-iO'l,
.loseph Trice. 18.-.:t-inil.— «o«foii, if. rf S. J.. 1018. dxxlx. 081-084.
.lohn llerr Miisser. 18.'i0-1012.— «osf. U. <t S. ./., 1018. clxxlx. 7T2.
lir. Kec nieillcal research. — Nciciicc. X. Y. & l.<incaster. Ta.. 1018.
n. s.. xlvli. 41!i.
Kempf, E. J.
Social and sexual behavior of monkeys with some comparable facts in
human sexual behavior. — lAbstr.) Am. J. I rol.. .\. Y., 1018. xlv, 82-80.
Kino, J. T.
.\uscultation of pnlmonary apices in young men. — Mil. Surg.. Wash.,
lois. xlll. ou r,.-.
Knox, J. H. M.
.Vjnericas debt In Iranci. -.1 m. ./. /»i«. Child.. Chicago. 1018. xvl, 212
Kracse, a. K.
Itest.— .Im. Iter. Tuhrrc. Halt.. 1018. I. 080-082.
Klenientarv concepts of tuberculosis.— .4m. Urr. Tuberc.. Ball.. 1018.
il. o:t-Ti.
I'redlsposllliin. < IMltorial.l— Im. Rer. Tubere.. Bait.. 1018, II. 43-48.
Tobacco smoke and pulmonarv tuberculosis. (Kdltorlal.) — .4in. Ker.
Tnlnre.. Hall.. 1018. II. OO-lO.-i.
Autlliiberculosls measures.— .4m. Her. Tubere.. Bait.. 1018, II. 037-0.":;.
Fssays on tuberculosis :
1. Before the tiitiercle bacillus.
2. Before Itobert Koch.
:(. Hubert Koch.
4. The tubercle bacillus.
.'•. Infection: Introdiulory considerations.
0. Sources of infection : Cornels theory of dust Infection.
T. Infeclioii by inhalation : Fliigge's theory of droplet Infection.
8. Infection by Ingestion: part one.
!i. Infection by ingeslion : part two: the lirst experiments.
10. Infection by Ingestion: I'urt three: The occurrence of iMVlne
bacilli in man.
11. Infection: special characteristics of tuberculous infection.
— /. Outdoor l.i/e. N. Y.. 1018. xv. 1-0: 30-41: fl.->-73 : 80; 101
100: 120: 1201.17: 1031CO: 100.204.
— ./. Outdoor Lite. X. Y.. 1018. xv. 22ij-2:{0 : 24fl-2.'>0 : 20n-27.'i :
20."i-3OO.
^/. Oufrfooi- Life. X. Y.. 1018. xv, .{27-320: 342-344: :i03-:!fl7 :
374.
Lange, Linda B.
The complement Hxatlon test for tuberculosis.— Iwi. Iter. Tubere..
Bait.. 1018. II. .-.41 ..4.".
Lawrence. J. S.
.\ studv of the aerobic bacteria found In wounds received on the batllellelil o^ the Somme.— i/iJ. Surgeon, Wash.. 1018. xlll, 140-1.13.
Levy. R. L.
The effect of thvrold secretion on the excitability of the endings of the
cardiac vagus. — .4rr)i. Int. Ued.. Chicago. 1018, xxl. 203-208.
Levy. R. L., and Alexander, H. L.
The predisposition of streptococcus carriers to the compllcatlonH of
measles. Uesults of separation of carriers from non-carriers at a hniie
hospital.^/. .Im. .1/. Axu., Chicago. 1018. Ixx. IN2T I8:io,
Lis.'iER. H.
Svphllls of Ibe lung.— Im. ./. il.'Se.. I'hila.. liils. civ. :i.-.0-380.
The prevention of congenital svphllls by aullluellc prenatal Iberapy.
Cnli). state .1 . M.. .San Fran.. 1018. xvl, 384:t88,
A not 1 the use of corpus luteum to prevent the palurul breasts
of menstruation. — F,ndoerinolog)i . (llendale. Cal.. lois. II. 12 l.^i.
L18SER, H., and Hin.max, F.
Svphllls of ihc cpl.lldvmls without Involvement of the lesllde: Keport
of case.— Im. ./. s,iph.. SI. Louis. 1018. II. 40.% 4T1.
LoEVEXHART, A. S., BiNTiNo, C. H., and Martin. H. O.
The morphological changes In the tissues of the rabbll as a result of
reduced oxidation.- ./. Kxper. J/.. Bull., 1018. xxvll. 3011 412.
Lyman, D. R.
The control of the careless consumptive.— Ira. Iter. Tubere.. Bait..
1018. II. 30-42.
Following up the discharged sanatorium palleiit.- Im Her. fulirre..
Ball.. 1018. 11. 01.-, (121.
MacCalli M, W. G.
I'albologv of the epidemic Hireptococcnl bronchopneumonia In lb.' army
camps.—:/. Im. M. Am.. Chicago, 1018, Ixxl. 704-707.
MacCalli M, W. G., and Cole. R.
I'neumonia at a base hospital.-^/. .Im. M An,.. Chicago. 1018. In,
1140.I1.-.0.
McCli RE, W. B., and Sai er. L. W.
Observations regarding Ihi' loss of water vapor through the skin In
Infants.- Irr/i. Int. Sled . Chicago. 1018. xxl. 428-430.
MiCrae, T.
Tuberculosis am
iddler. — .Im. He
Ball.. lOIM. II. 372
46
[No. 336
Macht, D. I.
Jewish food problems. — Jenish Forum, 1918, Nosi, l-U.
A case of aspirin habit.— J/ed. Hec N. \. 1918. xciv, 't"- ,„,„.,„.,,
On the absorption of apomorphm and morphin through "uiji"-"
channels.— Fcoc. 8oe. Exper. Biol. <C Med N Y., 191 --18, ^,y-,-^-- '  ,,
On the comparative absorptive power for drugs of the bbuUler and
urethra (male). — Proc. Soc. Exper. Biol. <C Med., N. \., lUli-lb. xv,
On the relation of the chemical structure of the opium alkaloids to
their effect on smooth muscle and on the discoveiy of a new thHrapeutic
a°ent as a consequence thereof. — Proc. Soc. Exper. Btol. d Med., >. 1..
1§18. XV. 63-66. , ^ r ..t • 11 i,;,u
On the relation between the chemical structure of the opium alkalouis.
and their physiological action on smooth muscle with a pharm.iiological and therapeutic study of some benzyl esters : I. On the relation
of the chemical structure of the opium alkaloids to their action on
smooth muscle. II. A pharmacological and therapeutic study of some
benzyl esters. — J. Pharmacol, d Eiper. Tlierap., Bait., 1918, xi, 389417 ' 419-446 .
On the absorption of drugs and poisons from the bladder and the
urethra : I. Absorption of apomorphin and morphin. II. Absorption
of various alkaloids, antiseptics, local anesthetics and salts. — J. L rol..
Bait, 1918, 11, 43-49 ; 211-226. ,, ., „ x- v ims
On parotitis as a complication of influenza. — Mca. Hec, .^. i.. iJis,
xciv, 1117.
Macht, D. I., and Hooker, D. R.
Concerning the action of the iodide, bromide and nitrate ions on the
respiratory center. — J. Pharmacol, d- Exper. Thernp.. Bait., l.ilS, si,
63-67.
Macht, D. I., Isaacs, S., and Gbeexberg, J. P.
On the influence of some opiates and antipyretics on the field of
vision —Proc. Soc. Exper. Biol, d Med., N. Y.. 1917-18, xv. 4b-4S.
On the influence of some antipyretics on the neuromuscular coordination test of •' tapping." — Proc. Soc. Exper. Biol, d Med., N. \., 191(18,
XV, 61-62.
OS M. Soc, Topeka, 1918,
Gynec. <f Obst., Chicago.
the presence of the meningococcus in the blood,
birago, 1918, xxiii. 470-474.
Major, R. H.
Importance of focal infection in diseases of obi
Herald, St. .Toseph. 1918, xxxvii, 159-163.
Uremic ulceration of the intestine. — J. Kai
xvlii, 136.
A study of the Krukenberg tumor. — Surg
1918, xxvii, 193-204.
Major, R. H., and Black, D. R.
A huge hemangioma of the liver associated with heniangiomata of the
skull and bilateral cystic adrenals. — .Iwi. J. M. Sc. Thila., 1918, clvi,
469-483.
Marriott, W. M., and Howland, J.
The influence of acid phosphate on the elimin.ntion of ammonia in the
urine. — Arch. Int. Med., Chicago, 1918, xxii, 477-482.
Acidosis. — Penn. M. J., Athens, Pa., 1918, xxi, 429-436.
Observations upon the calcium +++++
CONTENTS of the blood in infantile tetany
and upon the effect of treatment by calcium. — Quart. J. Med., Oxford,
1918, xi. 289-319.
Marriott, W. M., and Sissos, W. R.
Variations in the lipoid ("tat") +++++
CONTENTS of the blood of infants under
certain nutritional conditions. — ^iii. J. Dis. Child., Chicago, 1918, xvi,
75-82.
Marshall, H. W.
Structural deformities versus functional efficiencies as objects of treatments —BosfoH M. & 8. J., 1918, clxxviii, 708-712.
Revised ideas concerning toot defects and orthopedic footwear. —
Boston M. d S. J., 1918, clxxviii, 428-432.
Maxcy, K. F.
Observations
J. Infect. Di.
Maxcy, K. P., and Blackfax, K. D.
The intraperitoneal injection of salin
Chicago, 1918, xv, 19-28.
Mendenhall, Dorothy R.
Milk, the indispensable food for children. — T". S. Dept. I,abor. Children's Bureau. Care of Children Ser. No. 4, Bureau I'ubl., No. 3.i,
Wash., Gov't I'rintlng Off., 1918.
Meyer, A.
Modern views and propositions on enforced treatment of mental
diseases. — Maryland Psychiat. Q., Bait., 1918. vii.
The mental hygiene movement.632-634.
Meter, A. W.
To Franklin Paine Mall. Ave Magister ! — Johns Hopkins Alumni May..
Bait., 1918, vi. 140.
Some observations on megacytes in lymphatic tissues. — Am. J. Anat.,
Bait.. 1918, xxiv, 91-104.
Studies on hemal nodes : VIII. The absence of hemal nodes in the
domestic pig. — Am. ./. Anat., Bait., 1918, xxiv, 109-120.
Miller, S. R., and Baetjeb, W. A.
Pollinosis or hay-fever: its specific treatment. — South. M. J., Biimiughani. Ala.. 1918. xi. 341-345.
Bence-.Tones proteinuria ; some observations on its occurrence, with
particular reference to nephritis and hypertension. — J. .im. M. Ass..
Chicago, 1918, Ixx, 137-139.
Miller, S. R., and Barker, L. F.
Perforating ulcer of the hard palate resembling tertiary syphilis. —
J. Am. M. Ass., Chicago, 1918, Ixxi, 793-707.
Miller, W. S.
A study of the nerves and ganglia of the lung in a case of pulmonary
tuberculosis.— Am. Rev. Tuberc, Bait.. 1917-18, i, 123-139.
solution. — Am.
Vhild.,
-banad. M. Ass. J., Toronto, 1918, vlil.
Mills, C. W., and Hendersox, J. T.
The effect of pulmonary tuberculosis on renal function. — -4m. Aei;.
Tuberc, Bait.. 1917-18, i, 573-597.
Mllls, C. W., and Forster, A. M.
The treatment of laryngeal tuberculosis by reflected condensed sunlight.— -Vat. Ass. Study d Prev. Tuberc, Tr., 1918, xiv.
Mills, R. G. . ,. , u h,
.lapanese medical literature. Review of current Pf^^'o^'cals by the
staff of the research department. Severance t nion Medical College.
Seoul. Korea.— Chino M. J., Shanghai, 1918, xxxu, 49-6o , 2o6--bi .
An'^unSsuarcaseof double carcinoma with extreme resistance to one
and death from the effects of the other.— C7mia M. J., Shanghai, 1918.
xxxii.
Mills, R. G., Ludlow, A. I., and Vax Biskirk, J. D.
A simple method of water purification tor itinerant missions
other travellers.— CftiJiO M. J., Shanghai. 1918, xxxu,, 13.-14o.
'^Pathologic hemorrhage. A group of cases illustrating this condition
with a note on the early diagnosis of pernicious anemia.— Metf. tlni.
X. Am., Phila., 1918, i, 1102-1124.
MixoT, G. R., and Loeb, R. F. „ , ,/ .
An attempt to prevent influenza at Harvard College.— Boston if. cCS. J., 1918, clxxix, 665-669.
ries and
-Surg.
' ""p^^mature separation of the .norm.allv implanted placenta.
Oynec. Ob.it., Chicago, 1918, xxvi. 133-138.
Morris, R. S., and Friedlaxder, A. . ,. - i,- ,„
The significance of presystolic thrill in the examination of soldieis.—
J. Am. M. Ass., Chicago, 1918, Ixxi, 3.o-3(i.
^"'RenaTJ'unf.^io^- as measured by the elimination of,^fl"^;^|- /"J^ ?nd
nitrogen, and the specific gravity of the tivine. H- !«« ejie" -if, inS
low and normal diets.— .Ircft. Int. Med. (^^^'^"SO. l^H-J^"- '-O^SO^,War nephritis, by P Ameiiille ..Transl. from the French by H. t.
Mosenthal.— J^. Urol., Bait., 1918, ii, d1-106.
Mosexthal, H. O., and Clausex, S. W. • , k h, „»,„
The maintenance diet in diabetes mellitus as determined by the nltiogen eQuilihrium.— .liTji. Int. Med., Chicago, 1918. xxi, 269--S1.
MO.SEXTHAL, H. O., ClAUSEX, S. W and HiLLER ALMA
The effect of diet on blood sugar in diabetes mellitus.— lif/i. /»' Mca..
Chicago, 1918, xxi, 93-108.
MOSEXTHAL, H. 0., and Harrop, G. A. , , ^,. ,:,,„.„- „,pi
The comparative food value of protein, f«^-XV'^» ™h" ' 'l'-'"';**''' f"^'"
litus as measured by the nitrogen equilibrium.— .liOi. Int. ilea.,
Chicago, 1918, xxii, 750-758.
Neymaxx, C. a., and Burrows, M. T. . . ^ ,- . ,
studies on the metabolism of cells i""''", ,, The toxicity of dipept.d,
for embryonic chicken cells.— Proc. Soc. Lxpc. Biol, d ilea., -n. i.,
1918, XV, 138-139.
-Ann. Surg.. Phila.. 191S. Ixvii,
Nrsox, P. I.
Inflammatory tumors of the abdoinen.306-311.
Infantilism and other hypoplastic conditions of the uterus.—/. Am. M.
Ass., Chicago, 1918, Ixxi. 1101-1107.
^'rhe^ pathological effects of Phthirus pubis.— Porasitoioffi/, London.
1918. X. 375-379. .^ , , j i oi c ., -ja^ jn".
The biology of Phthirus pubis.— Pai-asi<o7off!/, Lond., 1918, x, 3S3-4Uo.
NuTTixG, M. Adelaide. „„„,.,„„ vi„<,c*
War-time problems of the nursing profession. — lohns Hopkins .\uises
Alumna: Mag., Bait., 1918, xvii, 93-100.
Opie. E. L., Baetjer, W. [et all. . ^. ,^ . „ ^^^
Report on progress of trench fever investigations. Trench lever
Commission of Medical Research Committee, American Red Cross.—
J. Am. M. Ass., Chicago, 1918. Ixx. 159i-lo98.
Opie, E. L., and Wobus, R. E.
Elephantiasis : report of a case.9S7.
OsLER, Sir W. ,„,„ • -^i -..
Typhoid spine.— B"». Canadian Army M. lorps l^l;^- i- 'S.;-'Graduated exercise in prognosis. — Lancet, ixinii., i.iis. i, -oi.
The rimary examination for the F R. C. S. Eng. ; an appeal to the
President of the Royal College of Surgeons.— Lancet, Lond.. 191S, i.
Medicine in America (Speech to University Extension Stiidents,
summer meeting at Cambridge).- The Hospital, Lond., 1918, Ixiv, 43o.
The utility of artificial pneumothorax in the treatment of phthisis. —
Canada Lancet, Toronto, 1918-19, Hi, 64- 1 2.
P\rk, E. a., Jaxeway, T. C, and Richabdsox, H. B.
Experiments on the vasoconstrictor action of blood serum.— 4rc/i. Int.
Med.. Chicago, 1918, xxi, 565-603.
Patox, S. ,.,.,,,
Effects of low oxygen pressure on the personality ot the aviator.
J Am. M. Ass., Chicago, 1918, Ixxi, 1399-1400.
Am. M. Ass.. Chicago. 1918. Ixx.
Februakt, 1919]
47
Peabody, F. W.
Ciinliuc ilfspnea.— Jm. J. J/. iV., Phlln.. 1918. civ. 100117.
Cardiac dyspnea. — Harvey Led., 1910-17. Phlla. 4 lA>nd.. lOlS, 24S
•J71.
Peabody, F. W., Clovgu, H. A., Stubgis, C. C. {ft al.\
Effects of tbo Injection of eplnepbrln In soldiers with " irritable heart."
rrelimlnary report. — J. Am. J/. Aat., Chicago, 1918, Ixxl, 1912-1913.
Peabce, Louise, and Bbowx, W. H.
Kxporiiiioutnl ir.vp;iutiiioiiii:isis : its application in chemotberapeiitkInvestlgations. — J. Exper. 11., Bait., 1918, IxviU, 109-147.
Pesbose, C. a.
Plaooemeyeb, H. W.
Kadicnl treatment for veslco-vaginal flstuln. — Grate Hasp. Bull..
Detroit. 191718. 11. 17-19.
QUINBY. W. C.
Anatomy and pbTsiolog; of the cidney. — In: Hod. fro/. (Cabot), 8°.
r-bila. & N. Y.. lins. 11. 312-3.-16.
Anutumv and phvslologv of the prost;ite and seminal vesicles. — In:
Mod. Int. (CalMiti. S . Phlla. Jt N. Y.. 1918. 1, 541-552.
The treatment of genital tuberculosis in the male. — J. Am. if. Ass..
Chicago. 1918. Ixxl. 1790-179G.
Richaedsox, E. H.
Note on saphenous varljt simulating a femoral hernia. — Ann. Surg.,
Phlla.. 1918. Iivll. 471-472.
Interpretation of lumbo-SJicral backache in women. — South, if. J.,
Birmlngliam. Ala.. 1918. xi. 139-144.
The effect of hysterectomy upon ovarian function. — Tr. Am. Oynec.
Soc, I'hila.. 1918. xliii.
Richardson, H. B., Jaxeway, T. C, and Pabk, E. A.
Experiments on the vasoconstrictor action of blood serum. — Arch. Int.
Hcd., Chicago. 1918. xil. 565-003.
Roses, R., Davis, E. G., and White, E. C.
Urinary antisepsis. The secretion of antiseptic urine following the
intravenous administration of an organo-mercury phthaleln derivative.
— J. Crol., Bait.. 1918. II, 277-307.
Rocs, P.
Method for Intravenous Injection of guinea pigs. — ./. Exper. it.. Bait .
191, <(, xivll. 4.->9-462.
I'rinary slilcmsls. Hemosiderin granules In the urine as an aid In
the diagnosis, of pernicious anemia, hemochromatosis, and other dis
eases causing slilerosis of the kidney. — J. Exper. if.. Bait., 1918. xxvlil.
645-659.
Rovs, P.. and Olheb, J.
Experimental hemochromatosis
644.
Exper. if., Bait.. 1918, xxvlil, 02;
Rois, P.. and Robebtso.n, O. H.
Free antigen and antibody circulating together in large amounts
(hemagglutinin and agglutinogen In the blood of transfused rabbits). —
J. Exper. .1/.. Halt., r.iis. xxvli. 509-517.
Autobemagglutluutlun experimentally Induced by the repeated withdrawal of blood— J. Exper. J/., Ball., 1918. xxvll. 563-508.
Roi s. P., and Wilson, G. W.
hiuld substitutes for transfusion after hemorrhage; first communica
tion. — J. Am. it. Aat., Chicago, 1918, Ixx, 219-222.
Rowxtree, L. G.
Syphilis in its medical its general, and its sociological aspects —
Therap. Qai., Detroit, 15»1S, n. s., xxxTiti, 222-225.
Row-ntbee, L. G., and Bakker. L. F.
a report of a case of myrtol poisoning with comments upon the toxlcltv
of eucalyptus oil and myrtol In human beings and In animals. — Tr.
Alt. Am. Phyticiant, I'hila., 1918, xxxlli.
Rl'SIIMORE, S.
Progress In gynecology. — Boston if. <f S. J., 1918, clxxviil, 633-539.
Sabix, Fi.OBExrE R.
Franklin Paine Stall: a review of bis scientific achievement. — Science,
N. Y. & Lancaster, Pa., 1918. n. s., xivll, 254-261.
Sampson. J. A.
The escape of foreign material from the uterine cavity into the nl.Tlii.veins.— .tm. J. Obst., N. Y., 1918, Ixxvlii, 161-175.
SeM-ards, a. W.
Viii. Ill- .lis. nrery and associated conditions. — ifed. Clin, X. Am.. Phlln..
1141.
• if tropical sunlight with special reference to phot"
: — J. Hcd. Research, Bost.. 1918. xxxvlll, 293-334.
•n of dilute sodium hydroxld on certain races of the
pri, ,11,,,,, .„ , ,i.._v. .4m. .If. Ass.. Chicago. 1918. Ixxl. 1301-1.303.
The treatment of amcrblc dysenterv with chaparro amargosa casli'ln
nicholsonl. — J. Pharmacol, rf Exper. Therap., Bait, 1918. xl, 331.
Sellabds. a. W.. Spooseb, L. H., and Wyman. J. H.
Serum treatment of type I pneumonia. — J. Am. if. Ass., Chicago. 19I.K
Ixxl. 1310 IMll.
Sharpe. W.
Diagnosis and treatment of brain Injuries with or without fracture of
the skull.— .4m. ./. Surg., X. Y.. inis. ixxll. 109-114.
The operativ., treatment of trifacial neuralgia. — Ann. Surg., Phlla..
19IS. Iivill. .".71-.T7S.
Kecent advances In neurological surgery and especially in the diagnos!"
and treatment of brain Injuries— CJiorfoMc (.V. CI If. J., Ixxvll. 2.T1
erlpheral facial
the time of labor. — Am. J. Obst..
Operative treatment In selected cases of chronic perl
paralysis. — J. Am. it. Ans., Chicago. 1918. Ixx. 13541357.
Recent advances In the surgery of the brain and spinal cord.— ./ourriar.
I.ancct. .Minneapolis. 1918. xxxvlll, 313-318.
Fractures of the skull : the resulting intracranial pathology and the
treatment.— .»/cd. rf Surg.. St. Ixiuis. Mo., 1918, 11. 319-333
Observations regarding neurological surgerv. and especially the diagnosis and treatjnent of brain injuries. — J. Tenn. if. Ass., .Nashville.
Observations regarding the iliagnosis and treatment of brain Injuries
with or without a fracture of the skull. .l/iiiiir»«f<i I/.. I'MS. I. ;;n,-,
SlMON, C. E.
A manual of clinical diagnosis by means of laboratory methods. —
9. ed.. Phlla. & Lond.. 1918. Lea & Feblger. 851. p. 80.
The probable association of amino-aciduria with Bence- Jones |iroteinurla. — J. Am. it. Ass., Chicago, 1918, Ixx, 224.
SiSSOX, W. R.
A critical review of intestinal bacteriology in relation to certain
diarrheas of infants.- f<o»(on if. rf ,S. J., 1918. clxxviil. 492-408.
Sissox, W. R., and Mabriott, W. M.
Variations in the lipoid ("fat") +++++
CONTENTS of the blood of Infants under
certain nutritional conditions. — .4m. J. Dtt. Child.. Chicago, 1918 xvl
75-82.
Sladex, F. J., and Friedlandeb, A. [et al].
The epidemic of Influeniia at Camp Sherman, Ohio. — J. Am. i/. .4<r»..
Chicago. 1918. Ixxl. 1052-1650.
Slemons, J. M.
The significance of fever
1918. Ixxvlii. 321-328.
Analysis of the blood In
06sf.. N. Y.. 1918. Ixxvll.
S.MITII. W. H.
How nurses are meeting the present needs. — Im. ,/. Surging. Uorhester.
N. Y.. 1917-1918, xvlll. 979-989.
The civil hospital ami its duties in war time. lAbstr.l. — Trained
Xurse [etc.), N. Y.. 1918. Ix. 1315.
Medical aspects of the war. — Johns Hopkins Alumni Hag., Bait., 191S
vl, 348-307.
Some ospects of the nrognim of the medical department of the armv
and their effect on civil hospitals. — ifod. Hasp., St. Louis. 1918 xl
334-330.
Si'EBBY, J. A.
Results following operative treatment of pelvic inflammatory tilsea«e
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Stevens, A. R.. and Petebs, J. P., Jb.
A study lu war nephritis; a new condition associated with henior
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Stboxo, R. p.
Etiidogy and method of tninsmlssion of trench fever. — Bull Arad dc
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Stboxo, R. P.. Swift, H. F. fef at].
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Strovse, S.
.Juvenile diabetes in twins, (he Karell treatment of edema. The Importance of details In the treatment of angina pectoris. — .Ifrd. VUn. X.
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Stbouse. S., and Bi.ocii, L.
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Tiieoiiai.d. S.
Chief function of oblique tnuscles of the
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VoKGTLix, C, and Mvkiis. C. N.
Phosphorus as an lnc|lcator of the vitamin
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CONTENTS of corn and
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Wabfield, L. M.
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Chronic emiocardltis '
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The eti..li>gy of nrlerlo
III. 115<11i.
I.<ictosurla : case pn-f
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Studies on Irritable heart; preliminary report.
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wl.. 191 s
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Urinary antisepsis. The secretion of antiseptic urine following the,
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Williams, J. W.
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WOLFSOHN, J. M.
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The treatment of hysteria ; successful results of a rapid re-education
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WOOIXEY, P. G.
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Convulsions. ( Editorial, i—-/. Lab. .£ Clin. M., St. Louis, 1917-18, iii,
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Surgical methods in the treatment of malign affections of superficial
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Young, H. H.
Cancer of the prostate. —
1918. i, 657-719.
Sarcoma of the prostate.
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A new operation for epispadias. — ./. Urol.. Bait.. 1918. ii, 237-251.
Recent progress in the treatment of cancer of the prostate, seminal
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Changes in trigone due to tuberculosis of kidney, ureter, and bladder.
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1918, xxvi, 608-615.
Young, H. H., and Davis, E. G.
The surgery of the double kidney. Report of a case of resection of
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Zimmerman, E. L., and Keidel, A.
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2Iod. Urol. (Cabot), 8°, Phila. and N. Y.
i; Mod. Urol. (Cabot), 8°, Phila. & N. Y.,
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==Contents==
Antituberculosis Measures. By Allen K. Kraisi: 49
Insusceptibility of Monkeys to Inoculation With HlooJ From Measll•^ Patients. (Illu>tiiitcd.> By Andrew Watson Sellards ami John A. Wentwortii S"
The Production of Tetany by the Intravenous Infusion of Sodium liicarbonate. Report of an Adult Case.
By George A. Harrop, Jr 6
Changes in the Blood Immediately Following Transfusion.
By John G. Huck, M. D. 03
Elizabeth Fry — Quaker Reformer. (Illustrated.!
Bv Henry M. Thomas 72
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62
[No. 337
Sixteen days after this injection, this animal was reinoculated with measles blood taken from a patient (C) wirhin
from four to six hours after the rash had appeared. The
blood was mixed with an equal part of 2 per cent sodimn
citrate in physiological saline. Of this mixture 15 c. c. were
injected intraperitoneally. On the following day, 24 hours
later, another injection was made with blood taken from a
patient (D) 12 hours after the appearance of the rash. This
specimen of blood was diluted with an equal part of physiological saline and dcfibrinated ; 20 c. c. of this defibrinated mixture were injected intraperitoneally. After another interval of
24 hours a final injection was made with the blood of Patient
E, taken not later than 12 hours after the rash had appeared.
One part of blood was mixed with two parts of physiological
saline and 20 c. c. of the defibrinated mixture were injected
intraperitoneally. The efPect of these injections is given in
Chart I. The temperature charts of these patients are also
given. (Chart IV.)
Monkey II was kept under observation for 10 days. Blood
for injection was taken from Patient B within from 6 to
12 hours after the first appearance of the rash. The specimen
was mixed with an equal part of physiological saline and
20 c. c. of the defibrinated mixture were injected intraperitoneally. The white blood counts and temperature of this
animal are given in Chart II. The temperature of the patient
is recorded in Chart IV. Before injection this animal had
a marked erythema o\ er the face and eyebrows ; a few macules
were also present. This ra.sli faded during the first week of
the incubation period, but increased somewhat 10 days after
inoculation, mough its intensity was not so great as during
the period before injection. Since this time it has fluctuated
considerably. At present, two months after the last injection, it is more marked than at any time during the incubation periods. Twelve days after the first injection of blood
this monkey received injections of measles blood on three
successive days ; these injections were exact duplicates of those
just recorded for Monkey I, the same specimens of blood being
used.
Monkey III. This animal, a young adult, was given a
series of three injections simultaneously with Monkeys I and
II. The same specimens of blood were employed though
the details were different. The injection on the first day
consisted of 8 c. c. of the mixture of citrated blood injected
into the heart and 12 c. c. intraperitoneally. On the second
and third days 30 c. c. of the defibrinated mixtures were
given intraperitoneally. Tlie results in this monkey are
recorded in Chart III.
REFERENCES
1. Hektoen: Jour. Infect. Dis., 1905, II, 238.
2. Anderson and Goldberger: Public Health Reports, 1911.
XXVI, 847 and 887; Jour. Am. Med. Assn., 1911, LVII, 113, 476
and 971.
3. NicoUe and Conseil: Compt. Rend. Acad. Scien., 1911, CLIII,
1522.
4. Hektoen and Eggers: Jour. Am. Med. Assn., 1911, LVII, 1833.
5. Tunnicliff: Jour. Infect. Dis., 1912, XI, 474.
6. Lucas and Prizer: Jour. Med. Research, 1912, XXVI, 181.
7. Ricketts and Wilder; Jour. Am. Med. Assn., 1910, LIV, 463.
8. Tunnicliff: Jour. Infect. Dis., 1918, XXII, 462.
9. Plotz: Jour. Infect. Dis., 1915, XVII, 1.
THE PRODUCTION OF TETANY BY THE INTRAVENOUS INFUSION
OF SODIUM BICARBONATE
REPORT or A'm ADULT CASE
By George A. Hakrop, Jr.
(From the Medical Clinic of The Johns Hoiiki>is Hospital)
Many drugs and chemicals have been mentioned as causing
tetany in adults. Following Frankl-Hochwart,' it has been
customary to classify all these conditions in one group, as due
to toxins or poisons. The clinical history of a patient with
tetany which was produced, or at least precipitated, liy intravenous infusions of sodium bicarbonate follows :
L. H. Medical No. 39293. Colored. Aged 22. Domestic. Admitted, March 8, 1918. Died, March 18, 1918.
The family and past history were unimportant, except that the
patient remembered no previous attacks which in any way suggested tetany, and the members of her family corroborated her
statement.
Present Illness. — At 7.30 a. m. on the day of admission, before
she had taken any food, she swallowed two 7%-grain tablets of
bichloride of mercury, dissolved in a glass of water. Shortly
afterward she vomited, and within an hour commenced to vomit
' Frankl-Hochwart: Die Tetanic der Erwachsenen, Leipzig, 1907.
blood. She was admitted to the hospital about noon. At this
time she was vomiting dark colored material, and was very dull
and drowsy.
Physical Examination. — Nothing abnormal was made out aside
from tenderness and slight muscle spasm in the upper abdomen.
The throat was red, but otherwise it showed nothing. All of the
deep reflexes were normally active. No stigmata of rachitis could
be found. Weight, 130 pounds. Mercury was recovered from the
urine, feces, and vomitus.
Blood Examination. —W. B. C, 19,000. R. B. C. 5,624,000.
Hemoglobin (Sahli), 90 per cent. Differential blood count normal.
The Wassermann test was negative.
Course in the Hospital. — From the time of her admission the
patient passed blood in her urine and stools. The usual energetic
measures were taken to secure a large fluid intake and to eliminate the mercury.
On March 9 she became totally anuric and continued so until
her death. On this day the plasma bicarbonate capacity (Van
Slyke) was 45 volumes per cent, and the carbon dioxide tension
of the alveolar air (Marriott) was 28 mm. of mercury. She was
March, 1919J
63
given 500 c.c. of a 5 per cent sodium bicarbonate solution intravenously.' No untoward effect was noted and she said that she
felt more comfortable afterwards.
Twenty-four hours later (March 10). another intravenous infusion was given of 700 c.c. of a 5 per cent sodium bicarbonate
solution, prepared as before. This made in all 60 grams of sodium
bicarbonate given intravenously. A small amount given by mouth
on March 9 had not been retained. About five minutes after this
last infusion, which had been given slowly and had been apparently well taken, the patient's face suddenly grew pale, she
commenced to have great inspiratory difficulty, and became very
apprehensive. She complained of numbness and tingling of tlio
fingers, and begged to have them rubbed. The hands assumed
the typical obstetrical position, there was pedal spasm, and a
first degree facial phenomenon (Chvostek's sign) was obtained.
The pulse was accelerated to about 130, and the extremities became cold. There was no elevation of the blood-pressure. The
acute attack lasted for about 15 minutes, after which the breathing became easier and she was less apprehensive. The main
d'accouc/icur position was maintained for about two hours.
On March 11 a blood sample was taken for the calcium and
phosphate determinations recorded below, and at the same time
for a determination of the plasma bicarbonate capacity (Van
Slyke), which was found to be 80 volumes per cent. This sample
was taken about 20 hours after the original attack. On this day
a second degree Chvostek's sign was obtained and Trousseau's
phenomenon was easily elicited.
The further history of the case has no bearing on the present
discussion, except that Trousseau's phenomenon was present
until March 15, and Chvostek's sign was obtained the night before
her death. March 18. Commencing on March 12 there was pitting
edema of the lower legs, and on March 15 evidence of the accumulation of a moderate ascites. She became very anemic from the
continued bleeding from the bowel, the hemoglobin (Sahli) on
March 17 being only 20 per cent.
'This was prepared by boiling a sodium bicarbonate solution
made up with freshly distilled water, and then reconverting the
carbonate so formed back into the bicarbonate by passing a stream
of carbon dioxide through the solution until it was no longer
colored by a few drops of phenolphthalein.
The writer has been unable to find any clinical reports of
tetany ocourring in adults followin-; the administration of
sodium biiarbonato. Among the nuiny accidents following
its use in the treatment of diabetic coma, the occurrence of
convulsions, especially clonic in type, is frequently mentioned.'
These convulsions have usually knl to a rapidly fatal termination, often in a few hours. Tetany, however, lias not
been mentioned or identified as such, Ilowland and ilarrioic
have observed tetany in young children following the therapeutic administration of sodium bicarbonate for acidosis and cite
three cases.* During the period of tetany their patients showed
a low calcium +++++
CONTENTS of the blood serum, a condition which
they have shown to be pre.<ent during the active period of
infantile tetany, particularly during or shortly after the occurrence of convulsions. The amount is usually tiien less than
7.0 mg. per 100 c. c. In the present case of adult tetany,
analysis of the calcium +++++
CONTENTS of a blood serum samjile taken
20 hours after the original attack showed a value higher than
9.0 mg. per lOO c. c., iience about normal, and there was no
marked accumulation of pliosphates (the phosphate +++++
CONTENTS
of the blood serum was less than 6.0 mg. per 100 c. c.).* It
shoidd be noted, however, that in this case there had been no
actual convulsions. It seems clear that the condition here was
associatetl with, if not directly precipit^ttod by, the suddenly
increased alkalinity of the blood due to the sodium bicarbonate
infusions.
In conclusion, it is desired to call attention to a danger, not
too remote, attendant upon the intravenous u.se of sodium
bicarbonate in conditions in which the renal excretory function
is markedly impaired, and particularly when extreme oliguria
or anuria is present.
'L. Blum: Ergeb. der inn. Med. u. Kinderh. 1913, XI, 480.
" SjTuptomatologie und Therapie des Coma diabeticuni."
•Quart. Jour. Med., 1918, XL. 289.
'The calcium and phosphate determinations were kindly made
by Dr. Howland and Dr. Marriott
CHANGES IN THE BLOOD IMMEDIATELY FOLLOWING TRANSFUSION
]?y John- G. Hick. M. D., Baltimore
(From the Cliniral Laboratory of the Medical Department, The Johns Hopkins Univcrsilj/ and Hospital)
The ever-increasing use of transfusion as a therapeutic
measure has stimulated interest to seek a clear explanation
for the various changes that follow the introduction into one
individual of the blood of another. Nevertheless, some of the
simplest questions raised by this procedure remain still unanswered. For instance, although it is generally knowTi that
after a transfusion the hemoglobin and the red corpuscle values
are increased, the exact way in which the increase occurs is
not understood. ^lany have assumed that the immediate
effect is entirely mechanical, that is, that the blfjod of the
recipient- is altered in direct proportion to the quantity of
the blood introduced, just as though the two had been mixed
in a vessel outside of the body; that, later, reactions on the
part of the blood-forming organs come into play, and these
then take a part in detennining the succeeding changes. No
doubt the mechanical and reactive effects are both important,
but the relative importance of each is not clearly defined,
and the decision has practical value, because the outcome
may influence us to use either small transfusions frequently
repeated or larger transfusions at longer interv'als.
Certain observations already at hand cast consideraiilc iloubt
upon the view that the immediate effects of transfusion are
purely mechanical and lead us at once to anticipate that
these effects will be neither constant nor quantitative. T>am8on ' has shown how quickly and markedly the number of
red cells in the circulation may be altered by the injection
64
[Xo. 337
of adrenalin. He is convinced by his experiments that the
liver acts as a reservoir from which large numbers of red
cells are poured into the circulation. No doubt other influences may act in the same prompt way upon this reservoir.
Sellards and Baetjer,* from their experiments and a review
of the entire subject, conclude that there is no constant nor
quantitative response to the injection of foreign abnonnal
elements into the blood. The object of the present study is
to obtain detailed and exact infomiation upon the changes
that occur in the blood elements immediately after transfusion.
METHODS
Transfusion was performed in each instance by a modification of the citrate method of Lewisohn, as described by Sydenstricker, Eivers and Mason." The details of the technique
need not be repeated here. Especial care was taken in testing
the donors to be'certain that the bloods were compatible. The
amounts of blood given in different cases varied from 250 c. c.
to 1250 c. c. Studies of the blood were made immediately
before the injection, immediately after the injection, two
hours, five hours and aboiit twenty-four hours later. These
time intervals were followed rather closely in practically all
of the cases. Each examination consisted of counts of the
red cells and of the white cells, with a difEerential count of
300 white cells. Platelets were estimated in the smears and
the hemoglobin was determined. Notes were also made on
the moipliology of the blood cells. Counts were always made
with the same instrmnents and by the same observer, with
the same reagents ; and care was taken to draw the blood from
the same part of the body, with uniform punctures.
The effect of transfusion was studied in seven cases of
pernicious anemia, two cases of idiopathic purpura, four of
benzol poisoning, five of secondary anemia and two of Banti's
disease.
RESULTS
Eesponses to transfusion were so variable that it seems
desirable to append the detailed protocols. A few of the niaiu
points only will be summarized here.
Red Blood Cells. — In general, following the injection of
blood, there was an immediate increase in the red cell count,
the striking point being the marked increase in many cases
apparently out of proportion to the quantity of blood introduced. Thus, in Case 2, the red coimt rose from 880,000 to
1,488,000 immediately after the injection of 500 c. c. ; and
in Case 5, from 480,000 to 1,300,000, following the injection
of 650 c. c. Such remarkable changes indicate apparently
a rapid redistribution of blood following an injection. In
some cases the initial increase continued for several hours,
usually falling, so that at the end of 24 hours the count had
fallen to approximately where it was before transfusion. In
other cases, however, there was a marked increase at the end
of 24 hours. In several instances, after injection of blood,
the count fell for a few hours and then rose slightly.
Hemoglobin. — The hemoglobin in most cases showed a uniform rise following transfusion, usually reaching its maximum at the end of 24 hours. In some cases the hemoglobin
fell slightly after the initial rise. Changes in hemoglobin
did not run parallel with changes in the red count, as may
be seen best from the variations in the color indexes.
Leucocytes. — In practically every case following transfusion there was some increase in leucocytes. In several instances, however, they remained practically stationary or even
fell. These relations do not seem to be constant in any
particular type of case. The most striking change in the differential count is the increase in the polymorphonuclear neutrophiles, which was striking even in some cases where there was
little change in the total leucocyte count. Occasionally a
neutrophilic myelocyte was seen following transfusion, but
they were not constant. In these cases no outpouring of nucleated red cells occurred, although in four instances a few
were seen following transfusion, but not before. The numbers
are so small, however, that this may have been accidental.
DISCUSSION
A general review of the immediate effect of transfusion
upon the blood count in twenty cases does not reveal any constant changes following this procedure. The point of practical interest and importance seems to be that no exact mechanical effect can be demonstrated following the introduction of
definite quantities of blood. Whereas, in a general way, it
may be said that the introduction of blood raises the count,
the effect is essentially a biological one involving the redistribution of blood in the body and its exact nature is not at
present understood.
REFERENCES
1. Lamson: Jour. Pharmacol, and Exp. Therap.. 1915, VII, 169.
2. Sellards and Baetjer: Bull. Johns Hopkins Hosp.. 1918,
XXIX, 135.
3. Sydenstricker, Mason and Rivers: Jour. A. M A., 1916,
117, 719.
M.VRCH, 1919J
65
BLOOD CHART— CASE 1
Patie-nts Name, Bbant; Wabd F; Age, 47; Medical No., 124 S33: Diagnosis, Per.nicious Anemia; Transfusion, 1250 c. c.
5-S1-I8
Before Transfusion
4.00 p. m.
P. M. N 143 47.e^<
P. M. E 4 l.SSri
P. M. a
L. Lrm I 0.33%
S. Ljrm 146 48.e9<>
L. Mono 7 2.33%
Tnaa. 4 1.33%
K. Myelocytes
E. Myelocjtes
B. Myelocjtes
Mreloblasis I O.SS%
Smudtres 14 4.66%
Platelets Markedly decreased.
Nucleated R. B. C 2— Intermediate, 1
Normoblast. 1
Moderate anisocytosis.
Moderate poikilocytoeis.
Basophilia Slightly diffused anc
punctate.
No. Cells Counted and %. 300 99.91
lib 80%
R. B. C I 2.2SI.O00
W. B. C 3.200
C. 1 1.3
Condition of Patient No chill: no fever.
Blood Obtained Little fin^r left hand.
5-31-18
:.31-18
5-31-18
8-1-18
After Transfusion
5.00 p. ni.
T.wt p. m.
10.00 p. m.
4.00 p. m.
n
ni
IV
^
lOfi 55.3%
141 47.095,
180 60.0%
227 75.6%
5 1.68%
5 1.60%
II
II
1 0.33%
4 1.33%
2 0.66%
113 37.8%
97 32.3%
S» SS.0%
40 1.13%
6 2.0%
8 2.66%
fl 3.09'r
3 1.0%
0.66%
4 1.33%
1 0.33%
II
8 2.60%
6 2.0%
6 2.0%
43 15.0%
5 1.68%
17 5.68%
Markedly decreased.
Markedly decreased.
Markedly dccreaflcd.
1-Megaloblast, 1
T) — Normoblasts, 5
Moderate anisocytosis.
Moderate anisocvtoeis.
Moderate anisocytosis.
Moderate poikilocytoeis.
Moderate poikiloc>'tosis.
Moderate poikilocytosis.
Moderate poikiloc.vtosis.
Slightly diffused and
Slightly diffused and
Slightly diffused and Slightly diffused and
punctate.
punctate.
punctate.
300 99.96
300 99.98
300 99.98
65%
65%
70%
70%
3,424,000
3,a12.000
2,960.000
2,688,000
4,200
3,340
S,W0
4.440
1.0
1.2
1.3
No chill: no fever.
Slight fever.
Slight fever.
Slight fever.
Third finger left hand.
Little flngcr left hand.
Third finger left hand.
Little finger left hand.
BLOOD CH.\RT— CASE 2
Patient's Name, Pa vuK ; Ward G; Age, 30; Medical No., 123834; Diagnosis, Pernicious Anemia; Transfusion, 500 c. c. 2d Transfusion
Date
Time
3-26-18
Before Transfusion.
3.55 p. ni.
3-26-18
.\fter Transfusion
4.15 p. m.
3-26-18
6.15 p. m.
3-26-18
).30 p. m.
3-2718
1.55 p. m.
P. M. N 1 187 62.3%
P. M. E 9 3.0%
P. M. B 1 0.33%
I. Lvm ! 8 2.66%
8. Lvm 68 22.8%
L. Mono 4 1.33%
Trans, 7 2.33%
N. Myrlocvtes 2.0%
E. MvelocVles
B. Mvclocvtes
MveloblasU 3 1.0%
Smudges 7 2.33%
Platelets Practically absent.
Nucleated R. B. C 1— Normoblast, 1
Marked anisocytosis.
Marked poikiloc^'tosis.
Bsjiophilia Slightly diffused.
N'o. CelU Counted and %. 300 99.98
Hb. 19%
R. B. C. 880.000
W. B. C. 3,800
C. 1 1.1
Condition of Patient .... No chill; no fever.
Blood Obtained Little Anger right hand.
16 5.33%
4 1.33%
3
L0%
10 3.33%
57 19.0%
^r, 5.0%
30
10.0%
45 15.0%
8 2.66%
10 3.33%
7
2.33%
2.0%
10 s.ssr/c
11 3.66%
1 0.33%
6
IS 5.0%
II
D
1 n.S3% 8 2.60%
2 0.60%
8
2.68%
2 0.68%
Moderatcl.y diminished.
Markedly diminished.
Moderately diminished.
Moderately diminished.
1 — Normoblast. 1
l-Normoblast, 1
.J-N
irmoblasts. 3
Marked anisocytosis.
Slight anisocytosis.
Marked
anisocvtosis.
Moderate anisocvtosis.
!l(oderate poikilocytosis.
Slight poikilocytosis.
Moderate
poikilocytosis.
Moderate poikiloc}'loai9.
Slightly diffused and
Slightly diffused.
Slightly
diffused.
Slightly diffused.
punctate.
300 99.94
300 99.95
300
99.99
300 99.92
25%
30%
30%
32%
1,488.000
1.512.000
1.410.1"!
1,688.000
4.300
8,700
5.4.^11
3,700
0.89
1.0
1.0
1.0
No chill; no fever.
Slight fever.
Fever.
No chill; no ferer.
Third Bngrcr right hand.
Little flngcr right hand.
Third finger right hand.
Little finger right hand
These cells are very
I large in si7.e, the
I majority with many
lobed nuclei.
Patient's Name, Pavck; Ward G; Age, 30;
BLOOD rH.\RT— CASE 3
Medical No., 1L'S834; Diagnosis, Pebsiciocs Anemia; Transfusion, 500 c. c.
3-12-18
Before Transfusion
11.00 a. m.
312-18
After Transfusio
12.25 p. m.
3-12-18
.2.') p. ro.
3-1218
6.25 p. m.
3-13-18
11.00 a. n
P. M. X 194 54.6%
P. M. K n
P. M. B 1 0..'«%
I.. Lym » 1.68%
S. Lvm 80 26.8%
I.. Mono S 2.68%
Transitional 8 2.68%
N. MvelocTtes I n
K. Mvclocvtes ,
B. Myelocytes
Mvrlohlasts ; 2 0.68%
Smudges 2 0.80%
Platelets Moderately decreaaed.
Nucleated R, B. C. 6— Sormohlast, 4
I Intermediate, 1
I MegalohlasI, 1
Basophilia Moderately diffused am
punctate.
Marked aniwocvtosis.
Marked poikilocytosis.
No. Cells Counted and %. 300 99.83
lib 10%
R. B. C 824.000
W. B. C 1,877
C. I I 0,83
Condition of Patient No chill; no fever.
Blood ObUined Little finger left hand.
10.0%
1.60%
1,60%
0.38%
2.0%
atcly decreased.
Marked aninocytosls.
Marked poikilocytosis.
Slightly diffused and
punctate.
O.XVfr
7.33%
0,80%
0.60%
30n 99.93
l.V^o
920,000
.1,040
0.83
No chill; no fever.
Third finger left hand.
M,rl:.-I nniaocTtosIs,
Mark. I fiikllocytosis.
I :<!•' 99.98
10%
I (ca.noo
3,160
1.0
M;,rkc d animcytosls.
MarkiMl poikilocvlosls.
:ir«i 99.81
l.C.WI
I "
Krver.
Tliird finger left hand.
2.0%
14.0%
.3.0%
2.33%
1.60%
Practicall.r abflent.
ThrMe seen larger in size'
and liirarre in shape. I
l-lnlcnne<liatc, 1
Slightly diffused and
punctate.
Marked anisocytosis.
Markcfl poikilocytosis.
.mo 99.96
15%
1,096,000
1.800
0.75
No rhill; no fever. I
Little finger left hand.
66
[No. 337
BLOOD CHART— CASE 4
Patient's Name, Alexander; Ward F; Age, 33; Medical No., 125655; Diagnosis, Pernicious Anemla; Transfusion, 750 c. c.
2d Transfusion
Date
Time
6-29-18
Before Transfusion
11.00 a. m.
P. M. N
P. M. E
P. M. B
h. Lvm
S. L.vm
L. Mono
Transitional
N. Myelocytes
E. Myelocytes
B. Myelocytes
Myeloblasts
Smud,?es
Platelets
Nucleated R. B. C. . .
Basophilia
No. Cells Counted and %.
Hb
R. B. C
W. B. O
C. I
Condition of Patient
Blood Obtained
3 1.0%
Markedly diminished.
Marked anisocytosis.
Marked poikilocvtosis.
Slightly diffused and
punctate.
300 99.92
44951
2,080,000
2,600
6-30-18
11.00 a. m
0.33%
43.0%
1.0%,
o.e
Markedly diminished.
1 — Normoblast, 1
Marked anisocytosis.
Marked poikilocytosis.
Slightly diffused and
punctate.
300 99.95
73.0%
2.66%
0.33%
20.6%
1.0%
0.66%
1 0.33%
i 1.33%
Markedly diminished.
Moderate anisocytosis.
Moderate poikilocytosis.
Slightly diffused.
Markedly diminished.
Moderate anisocytosis.
Moderate poikilocytosis.
Slightly diffused.
2,706.000
3,040
67.3%
1.66%
0.66%
0.33%
19.0%
4.0%
0.66%
2.33%
0.33%
11 3.66%
Practically absent.
4 — Megaloblast, 4
Marked anisocytosis.
Slight poikilocytosis.
Slightly diffused.
30O 99.93
No chill; no fever.
Little finger right hand. Ft. transfused slowly
in left arm.
A few pathol. lymphocytes seen in I,
II, III.
Patient's Name, Bailet, Irwin;
BLOOD CHART— CASE 5
Ward M; Age, 30; Medical No., 121999; Diagnosis, Pernicious Anemia; Transfusion 650 c. c;
2d (1st Transfusion 12-15-17, 500 c. c; Washed Cells)
Date
Time
P. M. N
P. M. E
P. M. B
L. Lym
S. Lym
L. Mono
Transitional
N. Myelocytes
E. Myelocytes
B. Myelocytes
Myeloblasts
Smudges
Platelets
Nucleated R. B. C.
12-18-17
.\fter Transfusion
3.45 p. m.
12-18-17
12-18-17
8.45 p. m.
No. Cells Counted and %,
Hb
R. B. C
W. B.
C. I
Condition of Patient
Blood Obtained
— Megaloblasts, 2
Normoblasts, 3
Microcytes and macro
cytes. Megalocytes.
Slightly diffused and an
occasional punctate.
.\nIsocytosis.
Poikilocytosis.
300 99.91
Estimated (Sahli).
3%
480,000
6,080
0.37
No chill; no fever.
Little finger right hand.
Greatly decreased, large
in size.
3 — Normoblast, 3
Microcytes and ' macro
cytes. Megalocytes.
Slightly diffused.
300 99.98
12%
1,360,000
5,640
0.47
No chill; slight fever.
Third finger right hand.
12.3%
0.33%
Microcytes and macro
cytes. Megalocytes.
Slightly diffused.
0.71
Slight fever.
Little finger right hand.
Microcytes and macro
cytes. Megalocytes.
Slightly diffused.
300
23%
1,324,000
6,000
0.84
Slight fever.
Third finger right hand.
12-19-17
2.30 p. m.
89.0%
0.66%
0.33%
1.0%
8.0%
3 1.0%
Markedly decreased, not
large in size.
Microcytes and macrocytes. Megalocytes.
Slightly diffused and
punctate.
Marked anisocytosis.
Marked poikilocvtosis.
300 99.99
0.88
Slight fever.
Little finger right hand.
Blood transfused in
left arm slowly.
BLOOD CHART— CASE 6
Patient's Name, Ceockett; Ward G; Age, 65; Medical No., 120650; Diagnosis, Pernicious Anemia; Transfusion, 500 c. c.
10-22-17
Before Transfusion
11.45 a. m.
I
10-22-17
After Transfusion
12.40 p. m.
n
10-22-17
2.40 p. m.
m
10-22-17
5.40 p. m.
rv
10-23-17
11.45 a. m.
V
Remarks
P. M. N
108 36.0%
3 1.0%
1 0.33%
75 25.0%
79 26.3%
4 1.33%
4 1.33%
2 0.66%
24 8.6%
Normal; large in size.
8— Mieroblasts, 3
Normoblasts, 5
Many microcytes and
macrocytes.
Markedly diffused and
punctate.
Marked anisocytosis.
Marked poikilocytosis.
300 99.95
20%
1,176,000
5,000
0.90
No chill; no fever.
Little finger left hand.
98 32.6%
1 0,33%!
60 20.0%
100 33.3%
1 0.33%,
3 1.0%
2 0.66%
35 ll'.6%
Normal; large in size.
18— Mieroblasts, 4
Normoblasts, 14
Many microcytes and
macrocytes.
Markedly diffused and
punctate.
Marked anisocytosis.
Marked poikilocytosis.
300 98.72
35%
1,432,000
6,320
1.2
No chill; no fever.
Third finger left hand.
212 70.6%
2 0.66%
15 5.0%
53 17.6%
1 0.33%
3 1.0%
ii 4.66%
Increased; large in size.
13— Mieroblasts, 3
Normoblasts, 9
Intermediate, 1
Few microcytes and macrocytes.
Markedly diffused and
pimctate.
Sliirht anisocytosis.
Slight poikilocytosis.
300 99.85
34%
1.. '592,000
7,800
1.1
No rhill; no fever.
Little finger left hand.
238 79.3%
ft
14 4.66%
32 10.6%
ft
3 1.0%
13 4.33%
Increased; large in size.
5 — Mieroblasts, 1
Normoblasts, 3
Intermediate. 1
Few microcytes .-uid macrocytes.
Markedly diffused and
punctate.
Slight anisocytosis.
Slight poikilocytosis.
300 99.89
32%
1,856,000
7,840
0.88
No chill; no fever.
Third finger left hand.
108 36.0%
3 1.0%
4 1.33%
46 16.3%
77 25.6%
1 0.33%,
5 1.66%
1 0.33%
55 18.3%
Normal; large in size.
6— Mieroblasts. S
Normoblasts, 1
Intermediate, 2
Diffused and punctate.
Slight anisocj-tosis.
Slight poikilocytosis.
300 99.85
31%,
1,368.000
8,200
1.1
No chill; no fever.
Little finger left hand.
P. M. B
S. Lym
Nucleated R. B. C.
No. Cells Counted and %.
R. B. C
W. B. C
C. I
Condition of Patient
right arm, slowly,
then rapidly.
March, 1919]
G7
Patiest's Name, White; Ward F; Age, 50;
BLOOD CHART— CASE 7
Medical No., 1226 IH, Diagnosis, Pebmcioi-s A.nemia; 2d Tbaxsfisiox, 600 c. c.
(1st Transhsion. 2-3-18)
2-17.18
Before Transfusion
217-18
After Transfusion
2-1718
217 18
2-1818
Remark*
Time
10.45 «. m.
I
12.20 a. m.
n
2.20 p. m.
in
S.25 p. m.
IV
10.4S a. in.
V
140 46.9%
161 SS.OT'r
.>»
74.0%
246 82.0^0
21» 73.0%
3 1.0%
1)
1
0.38%
.< I.O^c
1 n.ss^'c
6 2.0%
; '1 1:!!&
8 2.«8rt
84 28.0%
11 3.68%
I
6
O.SS%
16.8%
2.0%
4 \.3S%
27 O.IKT,
8 2.00%
2 0.66%
.11 17.0%
4 1.3;i%
U Mono
! 8 2.as9e>
11 3.66%
4 1.33%
9
8
S.0%
2.68%
1 0.337e
i.6e7<>
.1 1.6870
N. MrelocytM
E. Mjeloc.vtes
"
1
1 0.33%
II 12 4.0%
17 5.68%
3
1.0%
5 1.88%
10 3.33%
Platelrts
Decreased slightly; some
verj- large.
Norma
; some Urge in
Markedly decreased.
Some large in size.
Normal; some Urge In
2— NormobUsts.
5— Normoblast, 4
27—
Normoblast, 21
2— Nonnoblast. 1
8— Normoblast. 7
Intermediate, 1
Intermediate, 6
Intermediate, 1
Megaloblast. 1
SliKhtly diffused.
Diffused and punctate.
Slightl
V diffused and
Slightly diffused and Slightly diffused and
Slicht anisocvtosis.
Slight anisocvtosis.
punc
ate.
punctate.
punctate.
Slight poikilocj-tosis.
Slight poikilocjtosis.
Slight
anisoc.vtogis.
Moderate aniso^-tosis.
Moderate anisocvtosis.
Slight
poikiloc>'t06i9.
Moderate poikilocvtosis.
.M.Klt-ratc poikilocvtosis.
300 98.92
300 99.70
3(XI
99.92
300 99.97
300 99.97
Hb
S5%
1,288.000
44%
2,184.000
4870
2,64(1,000
48%
2.748.000
48%
2.448.000
W. B. C
3.720
2,760
2.400
3,560
1.4
1.0
No chill: no fever.
Severe
(I.S8
chill ; fever.
0.85
Fever.
1.0
No chill; no fever.
Blood ubuined
Little finger right hund.
Third finger right hand.
Little
finger right hand.
Third finger right hand.
Little finger right liand.
Blood transfused
slowly in left arm.
BLOOD CHART— CASE 8
Patient's Name, Hopkins; Ward M; Age, 52; Medical No., 121133; Diagnosis, Banti's Disease; Transfusion, 400 c.
(I.ST Transfusion, 500 c. c.) (Same Donor as 1st)
ll-*'-17
11-22-17
After Transfusion
11.43 a. m.
II
11-22-17
1.4.1 p. m.
Ill
11-22-17
5.45 p. m.
IV
11-2S-17
10.40 a. m.
' V
Before Transfusion
10.40a.m.
Remarks
I 1
P. M. F,.
P. M. B.
Lym.
S. Lvm
U Mono
Transitional . . .
N. Myelocyte*
E. Myelocvtes .
B. Myelocvtea .
MyeloblaaU ...
Smudge*
PUteleU
Nucleated R. B.
Basophilia
i.S%
1.66%
2.33%
2.33%!
6.33%
2.68%
4.33%
0.33%
38 12.8%
Increased; large in size.
99.87
Diffused.
Marked anisocvtosis.
Marked poikilocytosis.
300 99.88
Diffused.
.\nisocytosis.
Poikilocvtosis.
300
81%
3,488,000 3,384.000
i 11,560 I 11,380
0.45 I 0.57
'Good; no fever; no chill. .No chill; no fever.
Little finger right hand. Third finger right hand.
72.3%
5.0%
2.66%
1.68%
4.0%
1.66%
6.0%
20 6.69%
Increased ; markedly en
Urged in size.
Diffused.
Marked anisocytosis.
Marked poikilocytoeis.
300 99.94
40%
3,552,000
ll>,380
0.57
Slight fever.
Little finger right hand.
83.0%
3.0%
2.sa%
1.33%
4.0%
0.66%
4.33%,
86.0%
2.3.1%
3.0%
1.0%
0.3.1%
4.60%
Greatlv increased.
Diffused.
Ani8oc>.t08is.
Poikilocytosis.
SOU
98.65
3.496.000
10.600
0.57
Slight fever.
Third finger right hand.
300 99.98
38%
4.352,000
10,049
0.44
No chill; no fever.
Little finger right hand.
Blood transfused In
left arm, rapidly.
BLOOD CHART^CASE 9
Patibnt'8 Name, Thomas Hopkins; Ward M; Age, 52; Medical No., 121133; Diagnosis, Banti's Disease (?); Transfusion, 500 c. c.
Dale
Time
11-917
rnre Transfusion
11.20 a. m.
11-9.17
ter Transfusion
1.35 p. m.
P. M. r.
P. M. B
L. Lym
S. l^
U Mono
Transltlnnal ...
K. Myelocytes
K. Myelocytes .
B. Mvelocvtes .
HyelohlasU ...
Smudges
Platelets
Nucleated R. B. C.
No. CelU Counted and %.
78,6%
3.0%
l.SS%
2.33%
8.86%
0.69%
Increased markedly.
Large in size.
2 — Normoblasts, 2
Macroc)-tcs aitd microeytes.
Diffused.
Marked anisocvtosis.
Marked poikilocytosis.
»nO 99.81
19%
2,890,000
9.940
.«
73.3%
2.99%
2,0%
2,99%
.1,99%
2,69%
14 469%
InfTcased markcdl.v.
Large in size.
4— Normoblasts, 2
Microblasts, 2
Macrocytcs and micro
cytei
Diffused.
Markeil anisocvtosis.
Marked priikilocytosis.
300 99,gS
23%
2.68fl.flfl0
7,000
,44
Good; DO fever; no chill. iNo chill; no fever.
81,8%
2.88%
1.98%
1.38%
1,69%
5,0%
1.0%
17 S.<S%
Increased markedly.
Large in <ize.
4— Normoblast*, 4
Macnvytes and microcytes.
Diffa«c<l,
Markcl anlaocytaria.
Marked puikilocjtaris.
300 W.M
2»%
2,880.000
7,000
.41
Slight fever.
Rlood ObUined LiUle finger right hand. Little finger right hand. Little finger richt hand.
76.0%
1.60%
2.3.1%
3.00%
.1.60%
1.3.1%
3.0%
Increased greatlv. Li
in size.
3— Normoblasts.
MacTocytes and mlcro
cyte*.
Diffused.
Marke<l anisocytosis.
Marked poikilocytosis.
800 99.98
24%
8,416,000
8.120
.15
Slight fever.
,rhird finger right hand.
59.3%
a 69%
0.60%
2.38%
890%
1.69%
7.69%
11.0%
Large In size.
Diffused.
Marked anisocytosis.
Marked poikiloc>.tosls
3110 99.
22%
2.840.000
9,000
..19
No chill; no fever.
Little finger right hand.
del.
cytcs.
These cells were seen
in slide n,
Clamifled under
Trans.
Seen in slide IV.
Classified under
Trans,
jPt, hsd no reaction
after transfusion
except fever of
lflO°,
Blood transfused In
I left srm, rapidly.
G8
[No. 337
BLOOD CHART— CASE 10
Patient's Name, Petee Skafidos; Wakd F; Age, 24; Medical No., 120S04; Diagnosis, Echinococcus Cyst of Right Lung;
Transfusion, 500 c. c.
10-25-17
Before Transfusion
2.45 p. m.
I
10-25-17
After Transfusion
3.15 p. m.
n
10-25-17
5.30 p. m.
in
10-25-17
Before Operation
8.15 p. m.
IV
10-26-17
After Operation (18 hrs.)
3.30 p. m.
V
Remarks
p. M. N
P. M. E
P. M. B
228 7G.0%
5 1.66%
2 0.66%
8 2.66%
27 9.0%
5 1.66%
17 6.66%
's 2.66%
Normal.
Diffused very little.
300 99.96
25%,
1,856,000
10.560
.69
Small hemoptysis and
blood-streaked sputum.
Little finger right hand.
227 75.6%,
1 0.33%
2 0.66%,
14 4.66%
16 5.33%,
3 1.0%
17 6.66%
!! '.'.
20 6.66%,
Normal.
Diffused very little.
300 99.90
35%
2,184,000
12,640
.83
Small hemoptysis and
blood-streaked sputum.
Third finger right hand.
248  82.0%
1 0.33%,
1 0.33%,
10 3.33%,
18 6.0%,
6 2.0%
9 3.0%;
'9 3.6%
Increased.
Diffused very little.
300 99.99
35%,
2,496,000
13,080
.73
Small hemoptysis and
blood-streaked sputum.
Little finger right hand.
247 82.3%,
3 1.0%
5 1.66%o
19 6.33%,
6 2.0%
14 4.66%,
'6 2.6%
Increased slightly.
Diffused very little.
300 99.95
33%,
2,160,000
14,800
.78
Small hemoptysis and
blood-streaked sputum.
Third finger right hand.
251 83.6%,
. 2 0.66%,
5 1.66%
9 3.0%
6 2.0%,
10 6.33%
ii 3.66%,
Increased slightly.
2 — Normoblasts, 2
Diffused very little.
300 99.91
32%,
2,776,000
20,120
.59
Fever. Some *' old "
blood-streaked sputum.
Little finger right hand.
Pt. died from hemorrhage on 10-31-17.
S. Lvm
L Mono
Cell seen in slide UI
classified here.
Nucleated R. B. C
No. Cells Ckjunted and %.
Hb
R. B. C
W. B. C
C. I
Condition of Patient
left arm, somewhat
rapidl.v.
BLOOD CHART— CASE 11
Patient's Name, Stlvia McMillian; Wabd O; Age, 26; Gyn. No., 122424; Diagnosis, Post-Operative; Transfusion, 300 c. c.
1-13-18
Before Transfusion
10.00 a. m.
I
1-13-18
After Transfusion
1.00 p. m.
n
1-13-18
3.00 p. m.
m
IV
V
Remarks
227 75.6%
1 0.33%
29 9.66%,
2 0.68%
12 4.0%
6 2.0%
1 0.33%
22 7.33%,
Practically absent.
144— Normoblast, 144
Markedly diffuse; slightly
punctate.
Moderate anisocytosis.
Moderate poikilocytosis.
300 99.91
5%,
1,112,000
37,700
0.22
Fever.
Little finger left hand.
126 42.0%,
3 1.0%
84 28.0%
6 2.0%
15 5.0%
42 14.0%
3 1.0%
21 7.0%
Practically absent.
1329-Normoblasts, 1000
Intermediate, 329
Markedly diffuse; slightly punctate.
Moderate anisocytosis.
Jloderate poikilocj'tosis.
300 100.0
22%
1.216.000
26,360
0.91
Fever.
Third finger left hand.
210 70.0%
3 1.0%
42 14.0%
3 1.0%,
6 2.0%
30 10.0%
3 1.0%
3 1.0%
Moderately diminished.
849— Normoblasts, 809
Intermediates, 40
Markedly diffused; slight
punctate.
Moderate anisocytosis.
Moderate poikilocvtosis.
300 100.
19%
2.480,000
24,500
0.39
Fever.
Little finger left hand.
To give transfusion
rt. arm was used
and had to cut
p. M. E
P. M. B
S. Lvm
p. m.
Nucleated R. B. C
No. Cells Counted and %.
Hb
R. B. C
W. B. C
C. I
Condition of Patient
BLOOD CJHART— CASE 12
Patient's Name, Charles Thomas; Ward D; Age, 43; Surgical No., 121146; Diagnosis, Sinus Tract in Old Wound; Transfusion, 500 c. c.
Date
Time
11-25-17
Before Ti'ansfusion
12.00 m.
11-2517
(er Transfusion
2.00 p. ni.
11-25-17
4.00 p. m
11-25-17
7.00 p. m.
11-26-17
12.15 p. m.
P. M. N
P. M. E
P. M. B
L. Lvm
S. Lym
L. Mono
Transitional
N. Myelocytes
E. Myelocytes
B. Myelocytes
M.veloblasts
Smudges
Platelets
Nucleated R. B. C. ..
Basophilia
No. Cells Counted and
Hb
R, B. C
W. B.
C. I
Condition of Patient .
Blood Obtained
14 4.66%,
Normal.
Slight anisocytosis.
Slight poikilocytosis.
300
42%
3,144,000
17,280
0.67
M chill; no fever.
.ittle finger right hand.
0.33%,
3.33%,
0.33%,
1.33%,
31 10.3%
Slightly increased.
Slight anisocytosis.
Slight poikilocytosis.
63%
3,296,000
14.640
0.82
Slight chill.
Third finger right hand.
30 10.0%
Slightly increased.
Slight anisocytosis.
Slight poikilocytosis.
Diffused.
300 99.95
62%
3,696,000
12,160
0.72
\o rhill; no fever.
Little finger right hand.
Greatly increased.
Slight anisocytosis.
Slight poikilocvtosis.
300
99.95
53%
3,656,000
14,5(X)
0.73
No chill; no fever.
Third finger right hand.
0.33%
2.33%,
3.0%
Greatly increased.
Slight anisocytosis.
Slight poikilocytosis.
300 99.91
52%,
4,288,000
11,620
0.61
No chill; no fever.
Little finger right hand.
Pt. was operated on
Sept. 20. 1917, for
gastric ulcer. 50
c. c. blood injected
when needle became clogged; interval of half hour
before continuing.
Seen in slide I.
Classified under
Trans.
Pt. was operated on
again on Nov. 28,
1917. Found tubercles throughout
abdominal cavity.
Pt. died on Nov.
29, 1917.
March, 1919]
69
BLOOD CHART— CASE 13
Patient's N.\me, M. STRrzYKOwsKi; W.\rd G; Age. 14; Medical Xo., 120599; Diao.nosis, Typhoid Fe\'eb; Tbaxsfcsiox, 300 c. o.
(10-8-17 1st TR.\NSFnsioN, 400 c. c.)
10-11-17
After Transfusion
1.50 p. m.
n
Date 101117
Before Transfusion
Time 12 m.
I I
P. M. X 138 46.0%
P. M. E 4 1.33%
P. M. B P
L. Lvm S6 18.6%
S. Lvm 70 23.3%
U Jiono 3 0.66%
Transitional : 17 5.66%
N. Myelocytes
E. Myelocytes |
B. Myelocytes ,
Myeloblasts '
Smudges 13 4.83%
Platelets Decreased slightly; large Normal; large.
in size.
Nucleated R. B. C.
Basophilia Diffused.
.\nisocytosi8.
Poikilocrtosis.
N'o. Cells Counted and %. 300 99.S8
Hb 33%
B. B. C 1,872,000
W. B. C 2,320
C. 1 0.91
Condition of Patient Slight fever.
Blood UbUineU Little finger left hand.
1011.17
3.15 p. m.
1011-17
5.15 p. m.
10-121
11.15 p.
65.0%
10.3%
21.6%
1.66%
2.33%
11.3%
is.e%
2.33%
2.83%
8 2.66%
Decreased; large in size. Large in size.
7.SS%
2.5.3%
2.33%
3.33%)
Diffused.
Slight anisooytosis.
Slight poikilocvtoeis,
3i<0 99.82
Slight fever.
Third Bngcr left hand.
Diffused.
Slight anisoc}-toei&
Slight poikilocytosis.
300 99.88
39%
2,168.000
5,200
0.93
Slight fever.
Third finger left hand.
Diffused.
Slight anisoc.^iosis.
Slight poikilocytosis.
300 99.87
40%
2,376,000
3,640
0.87
Fever.
Second finger left hand.
Decreased; large in size.
Diffused.
Slight anisoc.vtoeis.
Slight poikiloc^-tosis.
3U0 99.32
42%
2,352,000
3,240
0.91
Slight fever.
Tliird finger left hand.
Blood transfused
left arm, v<
1 slowly.
BLOOD CHART— CASE 14
Patiext's Name, Marie Zahbodka; Ward G; Age, 29; Medical No., 120464; Diagxosis, Ttphoid Feveb; Transfusion, 250 c. c.
10-10-17
.\fter Transfusion
12.05 p. m.
Dale 1010-17
Before Transfusion
Time 11.00 a. m.
' I
P. M. N 9S 32.6%
P. M. E 2 0.6%
P. M. B
L. L»-m 46 15.3%
S. L.vm. 122 4a6%
U Mono 6 1.6%
Transitional 15 6.0%
N. Mrelorytes
E. Myeloc}-tes
B. Mvelocvtcs |
Mveloblaats
Smudges 12 4.0%
Platelets I..arge in size; decreased. Large in size
Nucleated R. B. C. None. None.
' Slight anisocytosis.
Slight Doikilocytosis.
Bcaophilia Diffused and punctate. Diffused.
Many cells seen.
No. Cells Counted and %. 300 99.7
Hb. 30%
R. B. C I 2,128.000
W. B. C. 6,360
C. L 0.71
CondiUon o( Patient ....! Slight chill.
Blood Obuined 'Liule finger right band
10-1017
5.30 p. m.
10-lM
11.30 a.
13.3%
22.09<.
0.66%
9.6%
I Many cells seen.
38%
1.768,(100
7,440
99.89
51.3%
0.33%
20.6%
12.0%
1.0%
9.6%
I*arge
None.
Slight nnNoc.\-tosis.
Slight poikilocytosis.
Diffused; very few.
99.83
23.6%
10.0%
0.66%
7.0%
38.3%
10.3%
2.8%
9.8%
6.0% 14 4.6% 2 0.66%
size; decreased. r<arge in size; decreased. Slightly increased.
None. None.
Slight anisoc.vtosis. Slight anisoc.vtoeis.
Slight poikilocytosis. Slight poikilocytosis.
Diffused and punctate; Diffused; few.
few.
800 99.86 800 99.86
40% 39%
1,648,000 1,872,000
5,120 6,660
Chill. ' Fo
Third finger right hand. Third flngo
1.2
Fever.
1.0
38%
2,384,000
6,380
0.82
Slight feve
right hand. { Little finger right hand. : Little finger right hand.
Blood transfused in
left arm— rapidly.
BLOOD CHART— CASE 15
Patient's Name. Baceb; Ward G; Age, 28; Medical No., 125383; Diagnosis, Benzol Poisoning; Transfusion, 600 c.
Date
Time
520-18
Before Transfusion
3.15 p. m.
I
5-2018
After Transfusion
4.10 p. m.
II
520-18
6.10 p. m.
m
5.2018
9.10 p. m.
IV
5-21-18
3.16 p. m.
V
Remsrks
P. M. N
P. M. E
P. M. B
60 16.6%
2 0.66%
230 76'.^°
5 1.0%
6 l-etfH,
1 0.13%
2 0.68%
3 1.0%
PrartirallT absent.
Slight anUocTtosis.
Slight poikilocj-toris.
2— Normoblast, 1
Megaloblast, 1
Slightly diffused and
punctate.
300 99.94
38%
l.9R4.nno
1.160
1.0
No chill: no ferer.
Little finger left hand.
62 20.6%
8 2.66%
192 64.0%
20 6.66%
10 3.33%
2 0.66%
6 2.0%
Practically absent.
Slight ani«ooto»is.
Slight poikilocytosis.
Slightly diffused and
puncute
300 99.91
4.1%
1.768,000
2,640
1.2
No chill; no ferer.
Third finger left hand.
ft-. 81.6%
2 0.66%
n
n
1S7 62.3%
in 3.83%
n
2 0.66%
4 1.83%
Practically absent
Slight aniwcylods.
Slight poikilocytosis.
Slighily diiruacd and
punctate.
300 t».«e
47%
2,240,000
1.38)
1.0
Slight fever.
Utile finger left band.
62 2n.69i
5 1.66%
220 73..1%
4 1.83%
4 1.83%
(1
3 1.0%
2 0.66%
Prarticallv absent.
Slight ani.oK-vtnsis.
Slight iK.ikil<<-yto<iis.
2— Normoblasts.
Slightly diffused s n d
puncUte.
300 99.98
45%
2,796,000
1,280
0.83
Slight fevor.
Tliiril finger left hand.
47 l.'>.6%
3 1.0%
7 2.33%
218 72.6%
10 3.33%
8.0%
2 0.66%
1 0.33%
3 L0%
Pnireically absent.
Slight snisocylosis.
Slight iKiikilocytosli.
Slightly diffused s n d
puncUle.
ant 99.96
4.1%
2,.176,n00
2,000
0.96
No chill ; no fever.
Little finger left hsnd.
h. Mono.
V. Mrelorytes
r.. Mvplocytes
n. Mxlocrtes
MielnhlijU
Smudgm
rialelels
Nucleated R. B. C.
Buophilia
No. Oils Counted and %.
Hh
R. B. C.
W. B. C
C. I
Tondition of Pittent
Blood Obuined
Pt. transfused slowly
in right arm.
70
[No. 331
BLOOD CHART— CASE 16
Patient's Name, Chas. Webek; Waed F; Age, 17; Medical No., 122256; Diagnosis, Benzol Poisoning; Transfusion, 275 c. c.
p. M. N
p. M. E
p. M. B
L. Lym
S. Lj-rn
L. Mono
Transitional . . .
N. Myelocytes
E. Myelocytes .
B. Myelocytes .
Myeloblasts . . .
Smudges
Platelets
Nucleated R. B,
Basophilia
Ifo. Cells Counted and *
Hb
R. B. C
W. B. C
1-11-18
Before Transfusion
10.00 a. m.
1-1-18
After Transfusion
11.30 a. ni.
1-1-18
4.30 p. m
20.0%
22.6%
1.07o
10.3%
Practically absent.
Slightly diffused.
Slight anisocytosis.
Slight poikilocytosis.
300 99.86
54%
2.648,000
2,400
Practically absent.
Practicallj' absent.
Slightly diffused.
Slightly diffused.
Slight anisocytosis.
Slight anisocytosis.
Slight poikilocytosis.
Slight poikilocytosis.
300 99.79
3WI 99.88
59%
57%
2,272.000
2,512,000
3,160
1,880
1.3
1.9
No chill ; no fever.
Slight fever.
Third finger right hand.
Little finger right hand.
Practically absent.
"
Slightly diffused.
.flight anisocytosis.
Slight poikilocytosis.
300 99.92
67%
3,216,000
1,800
0.89
Slight fever.
Third finger right hand.
Practically' absent.
300 99.84
Slightly diffused.
Slight anisocytosis.
Slight poikilocytosis.
54%
2,368,000
1,720
Blood transfused in
left arm slowly.
BLOOD CHART— CASE 17
Patient's Name, Chas. Weber; Ward F; Age, 17; Medical No., 122256; Diagnosis, Benzol Poisoning; Third Transfusion, 300 c. c.
1-9-18
Before Transfusion
2.00 p. m.
I
1-9-18
After Ti'.insfiision
4.00 p. m.
n
1-9-18
6.00 p. m.
m
1-9-18
9.00 p. m.
IV
1-10-18
2.00 p. m.
V
Remarks
p. M. N
P. M. E
P. M. B
96 32.0%
1 0.33%
32 10,6%
115 . 38.3%
16 5.33%
28 9.33%
1 0.33%
II n
11 3.66%
Practically absent; those
seen large in size.
110 36.6%
1 0.33%
18 6.0%
129 43.0%
7 2.33%
28 9.33%,
1 0.33%
6 2.0%
Practically absent; those
seen large in size.
Moderately diffused.
Slight anisocytosis.
Slight poikilocytosis.
300 99.92
42%
2,704,000
2,680
0.77
No chill; no fever.
Third finger right hand.
111 37.0%
1 0.33%,
11 3.66%
127 42.3%
U 3.66%
23 7.66%,
5 L66%
U 3.66%
Practically absent; those
seen large in size.
Moderately diffused.
Slight anisocytosis.
Slight poikilocytosis.
300 99.93
43%
2,752,000
2,080
0.79
Slight chill; slight fever.
Little finger right hand.
90 30.0%
1 0.33%,
13 4.33%
162 54.0%
8 2.66%
18 6.0%
1 0.33%
1 0.33%
6 2.0%
Practically absent.
Moderately diffused.
Slight anisocytosis.
Slight poikilocytosis.
300 99.98
40%
2,120,000
1,880
0.90
Slight fever.
Third finger right hand.
90 30.0%,
3 1.0%
1 0.33%
17 5.66%,
130 43.3%
14 4.66%,
37 12.3%,
1 0.33%
7 2.33%,
Practically absent.
1 — Normoblast.
Moderately diffused.
Slight anisocytosis.
Slight poikilocrtosis.
300 ' 99.91
41%
2,296,000
1,840
0.93
No chill; no fever.
Little finger right hand.
Many patho. lym. in
S. Lym
I, n, V.
Nucleated R. B. C
No. Cells Counted and %.
Slight anisocj-tosis.
Slight poikilocytosis.
300 " 99.88
39%
2,232,000
1,920
0.88
No chill; no fever.
Little finger right hand.
R. B. C
W. B. C.
C. I
Condition of Patient
left arm slowly.
BLOOD CHART— CASE 18
Patient's Name, Ellen Foppino; Ward G; Age, 36; Medical No., 125109; Diagnosis, Benzol Poisoning; Transfusion, 750 c. c.
5-11-18
Before Transfusion
2.0O p. m.
I
5-11-18
.\fter Transfusion
3.45 p. m.
n
5-11-18
5.46 p. m.
m
5-11-18
8.45 p. m.
IV
5-12-18
2.00 p. m.
V
Time
Remarks
P. M. N
P. M. E
P. M. B
L. Lym
S. Lym
L. Mono
Transitional . .
N. Myelocytes
E. Myelocytes
B. Myelocytes
MyelobLists . .
Smudges
Platelets
Nucleated R. B. C.
Basophilia
No. Cells Counted and %.
Hb
R. B. C
W. B. C
C. I
Condition of Patient . , . ,
Blood Obtained
36.0%
56.3%
4.0%
Practically absent.
Moderate anisocytosis.
Moderate poikilocytosis.
Slightly diffused.
300 99.96
Occasional ; those se&n
large in size, bizarre in
shape.
Moderate anisocytosis.
Moderate poikilocytosis.
Slightly diffused.
300 99.94
46%
2,856,000
640
Little finger left hand. Third finger left hand
Practically absent.
Moderate anisocytosis.
Moderate poikilocytosis
Slightly diffused.
Little finger left hand.
'ractically absent.
1 — Megaloblast.
Moderate anisocytosis.
Moderate poikilocytosis.
Slightly diffused.
300 99.99
45%
2,464,000
800
Third finger left hand.
Practically absent.
Moderate anisocytosis.
Moderate poikilocytosis.
Slightly diffused.
Little finger left hand.
PL transfused slowly
in right arnu
March, 1919]
71
Patient's Name, Stbombebger; Ward G;
BLOOD CHART— CASE 19
Age, 19; Medical No., 126431; Diagnosis, Idiopathic Purpura;
Transfusion, 700 c. c.
Date
Time
5-12
IS
512
s
Before Triuisfusion
.\ft
er Transfusion
2.00 p
m.
3.10 p
m.
I
n
247
82.3%
233
77.6%
6
2.0%
6
2.0%
1
0.3S7c
2
0.66%
2
0.66%
SO
10.0%
SO
10.0^,^
4
1.33%
13
4.33%
8
2.68%
6
2.0%
1
O.SS%,
1
n.3S%
S
1.0%
8
2.66%
5
1218
8.M
p. in.
n'
230
7a 6%
7
2.33%
2
0.66%
SO
10.0%
14
4.66%
12
4.0%
1
0.33%
4
1.33%
Practically
absent.
Slight anisocytosis.
No poikilocytogis.
SISIS
i.OO p. m.
P. M. E.
P. M. B.
S. Lym
L. Mono
Transitional ....
X. Myeloc>-tcs .
E. Myelocytes ..
B. Myelocytes . .
Myeloblasts
Smudges
Platelets
Nucleated R. B.
78.0%
1.33%
0.66%
Prnrt ically absent.
I.^lifrht anisoc>'to6)S.
No poikilocytosis.
, ... 99.95
7S%
1 5.014.000
I 8.200
' 0.73
No chill; no fe\*er.
Little finger right hand.
Practically absent.
81%
5,120,(X»
12,r>(K)
Practically absent.
Slight anisocytods.
No poikilocytosis.
.i.lK.OOO
12.600
('.S3
Slight fever.
Little finger right hand.
79.0%
1.33%
0.33%
13.6%
3.0%
1.66%
Practically absent.
Slight anisocytosis.
No poikilocytosis.
81%
5.474.000
14,200
300 !
84%
5,616.I»K)
13,400
0.75
Slight fever. No chill: no fever.
Third finger right hand. Little finger right hand. Pt. transfused slowly
' in left arm.
BLOOD CHART— CASE 20
Patient's Name, Mary Stromuergeb; Ward G; Age, 19; Medical No., 126431; Diagnosis, Idiopathic Purpura;
1st Transfusion, 600 c. c.
Date
Time
P M. X
P. M. E
P. M. B
L. Lvm
L &.:::::
Transtitional ..
N. Mvelocyles
E. Mvelocvtes
B. Mvrlocvtes
Myeloblasu ..
Smudges
Platelets
4-29.18
Before Transfusion
12.30 p. m.
4.29-18
After Transfusion
1.55 p. ni.
4-29.18
>.5S p. m.
4-30-18
12.30 p. m.
65.3%
1.33%
22.0%
3.0%
4.0%
65.6%
0.66%
0.66%
2.33%
15.0%
2.66%
5.667e
2 7.33%
Practically absent; those Markedly diminished;
seen large in size. those seen large in size
I and bizarre in shape.
Nucleated B. B. C. !»— Normoblast, 3 I
Marked ani!<ocytosis. |
Marke<l poikilocytosis. I
Basophilia Moderatelv diffused. Moderately diffused.
No, Cells Counted and %. ' 300 "300
lib I 40% 46%
R. B. C 3.492,000 3,9(10.000
W. B. C I 7.600 8,100
C. I I 0.66 0,58
Condition of Patient ....|No chill; no fever. No chill: no fever.
Blood Obuined iLittle finger left band. Tliird finger left hand.
Markcdlv
Tliose 5C(
size and
shape.
85.0%
0.33%
0.33%
0.66%
4.66%
diminished ;
n large in
bizarre in
.Slightly diffused.
300
49%
3,904.000
11.200
0.02
Severe chill.
Little finger left hand.
0.33%
8.33%
4.33%
8.0%
3 1.0%
Practic-ally absent; those'
seen lar^c in size and
bizarre in shape.
Slightly diffused.
sno
49%
3.912,000
11,680
0.62
Fever 103°.
Third finger left hand.
).66%
r.0%
1.33%
>.6e7o
Practically absent;
seen large in size.
33%
33%
those
Marked anisoc.vtosis.
NLirkcd poikilocvtosis.
Sliglitly diffused.
0.«f
No chill: no fever.
Little finger left hand.
Path. Lym. (Reider)
Tu-o seen in I, one
seen in V.
BLOOD CHART— CASE 21
Patient's Name, William Meyer; Ward F; Age, 52; Medical No., 121243; Diagnosis, Hypertension with Myocardial iNsumciENCY;
Control; No Transfusion
Date
Time
11-30-17
Before Transfusion
2.20 p. m.
11.3017
r»cr Transfusion
4.30 p. m.
11-30.17
&30 p. m.
12-1-17
2.30 p. m.
P. M. B
U Lvm
S. Lvm
U llono
Transitions) ...
N. Myelocytes
E. Myelocyte* .
B. Myelocyte* .
M.velohlasts ...
Smudges
Platelets
Nucleated R. B. C
Basophilia
No. Cells Counted and %.
3.33%
17.0%
1.60%
3.60%
10 3.33%
Norma t
Vc anisocytosis.
No poikilccyt'.sjs.
1 — Normoblast,
300 9».n
73%
4,384,000
7,300
0.84
No chill; no fever.
Little Anger right hand.
S.0%
17.8%
2.83%
3.60%
; Normal.
1 No anisocytosis.
j No poikilocytosis.
74%
4.376.000
7,.1B0
0.86
Vo chill; no fercr.
Third finger right hand.
6.3S%
ie.0%
3.0%
2.00%
Xormal.
No anisocytosis.
No poikilocytosU.
No chill; no fercr.
Little finger right hand.
).0%
).66%
)..'«%
5.66%
r.0%
J..33%
1.0%
Xormal.
No snisocytosis.
No poikilocytosis.
300 »B.»1
74%
4,392.000
7,240
0.86
No chill: no fever.
Third finger right hand.
73
[Xo. 33:
ELIZABETH FRY-QUAKER REFORMER'
By Henhy M. Thomas
111 speaking of Elizabeth Frj- to my friends I am struck
with how little is kllo^vn about her, and yet one hundred years
ago she was beginning in London a career that made her
the most influential woman of her time, certainly in philanthropy and, I believe, in general.
To understand Elizabeth Fry and her struggles it is necessary to know something about Quakers, or the Society of
Friends, to which sect she belonged.
Most of you know that the Society of Friends was founded
by George Fox in 1647-48 as a protest against the formality
and abuses which he believed had affected the Church at
that time. He taught that true religion is a direct personal
experience, and that there is in every man's soul something
that responds to the truth as revealed in the Bible, which,
when properly regarded and attended to, is a safe guide for
conduct. This view led to a personal interpretation of the
Bible and did away with creeds and the authority of priests
or ministers. He and his followers " bore testimony," as they
would say, against many customs and beliefs that they disapproved of. They took many of the injunctions of the Bible
literally and felt it wrong to call any man master and to show
more respect to one than to another, and they therefore refused to take off their hats before the great and keep them
on before the lowly, said " thee " and " thou " to their equals
and superiors as well as to those usually called inferiors,
adopted a manner of dress which they did not change with
the fashions, refused to take legal oaths, and many other
such things. From the first they acknowledged the complete
equality of women and gave them equal influence in the conduct of the Society.
George Fox was a powerful, persuasive preacher, and influenced many people particularly among the lowly, but not
a few among the well-to-do and learned. Among these latter
were William Penn, Eobert Barclay and John Gurney. John'
Gurney, the ancestor of Elizabeth Fry, was put into prison
with other Friends and remained there for three years because
he would not take the oath of allegiance, his testimony being
against taking any oath. All the Gurneys appear to have
been prosperous, and were interested in woolen weaving and
in banking.
John Gurney, Elizabeth Fry"s father, married Catherine
Bell, the great granddaughter of Robert Barclay, the Quaker
apologist, and so the Gurneys of Earlham could trace their
ancestry on both sides through an unbroken line of influential
Quakers to founders of the Society.
John Gurney had inherited quite a large property and had
himself prospered. In 1786 he leased from Edward Bacon
the estate of EarUiam in Norfolk near Norwich, and it is
^ Read before The Johns Hopkins Historical Society, Pel)nuiry
12, 1917.
from this estate which stayed in the Gurney family for nearly
100 years that the Gurneys of Earlham took their name.
Augustus Hare's book (The Gurneys of Earlham) is by far
the most attractive account of this remarkable family. John
Gurney and his wife had 13 children, 11 of whom grew up.
Of these 11 there were seven daughters and four sons. Mrs.
Gurney died when her youngest child was only a little over
a year old, and tlie eldest, Catherine, who from that time
took charge of the family, was only 17. Mr. Gurney and his
wife were not strict Quakers, and although they conformed in
some respects to the customs of the Society, they were very
liberal in their manner of life and I have no doubt were the
objects of deep concern to their plainer relatives and other
members of the Society.
At the time of Mrs. Gurney's death, Elizabeth, the third
daughter, was just 12, having been born on the 31st of May,
1780. There was one sister between Catherine and herseK
and next to her came a boy, John, then four girls bom in
three years, and three boys ending the flock. These 11
children, deprived of their mother, were drawn closely together and developed themselves and each other into a wonderfully united family. Catherine, who when still very young,
was known as Mrs. Catherine Gurney, felt the chief responsibility of their bringing up, and with the help of the older
girls guided them as l^est she could. The father interfered
but little, requiring only that they go to Meeting on First
Day at least once and sometimes twice. Even this slight
conformity was resented by the young people and many are
the disparaging remarks recorded in the journals of the children, for keeping of journals appeared to be one of the methods
of education in this family, and, indeed, in general at that
period. In " The Gurneys of Earlham " we find interesting abstracts from these journals and I wish that I might
read you some of them. Indeed, I must read one note written
by Louisa Gurney when 11 years' old, particularly as it refers
to the subject of our study and gives us a glimpse of one
phase of the family.
Aug. 14 (1796). Betsy is so ill, I look forward with the most
gloomy ideas concerning her A great many Friends came
to tea. I did all I could to please tliem. How charming it
is to feel one is giving pleasure: though I can never say how
stupid they were to me After tea Kitty chose we should
work again; this was rather a tug to me, but I bore it pretty
well, only Kitty did provoke me by making me give up something
to Chenda, merely because she was the eldest; there is nothing
I hate so much as this sort of partiality; it does provoke me so.
We read a little Sacred History; I like the Old Testament
amazingly.
The house at Earlham was very large and the Gurneys
entertained freely, and as the girls grew older it must have
been a most attractive place to visit. The seven girls dressed
as gaily as possible, and were often seen in a band riding
THE JOHNS HOPKINS HOSPITAL BULLETIN, MARCH, 1919
msjs^
ELIZABETH, MRS, FRY.
After the Portrait by George Richn
Makch, 1919]
73
over the country on their ponies, wearing scarlet ridinj;
habits. The literary- and scientific youufr men of the neighborhood came to the house and tlicre was much discussion on
the subjects of the day. particularly in relation to the philosophy of Rousseau, Voltaire and other free-thinking autliors
of tliose times. Among this group there were only two young
men who took a serious view of life — one the Baptist minister,
the other a Roman Catholic chemist named Pitchford, and
strangely enough it was this latter who was the one steadying
influence to this flock of Quakers. Among this band Elizabeth was probably the gayest and in many ways the most
attractive. She sang sweetly, danced beautifully, and was
a remarkably independent character. From a very early age
slie appears to have been delicate and to have suffered from
marked nervous symptoms. She was dreadfully afraid of
many things, particularly of the dark and of the water. She
also kept a diarj-, but, unfortunately, when she read it over
towards the end of her life she felt it wise to destroy all the
early years. Judging from what she wrote later, it would
have been a most valuable accomit of the feelings and experiences of a nervous child. She herself when 48 recorded her
impressions of herself at an early age :
Dagenham. Eighth Month, 23d, 182S. My earliest recollections
are. I should think, soon after I was two years old; my father at
that time had two houses, one in Norwich, and one at Branierton.
a sweet country place, situated on a Common, near a pretty
village; here. I believe, many of my early tastes were formed,
though we left it to reside at Earlham, when I was about five
years. The impressions then received remain lively on my recollection; the delight in the beauty and wild scenery in parts of the
Common, the trees, the flowers, and the little rills, that abounded
on It, the farm houses, the village school, and the different poor
people and their cottages: particularly a poor woman with one
arm, whom we called one-armed Betsy; anotlier neighbor, Greengrass, and her strawberry beds around a little pond; our gardener,
who lived near a large piece of water, and used to bring fish from
it; here, I think, my love for the country, the beauties of nature,
and attention to the poor, began. My mother was most dear to
me, and the walks she took with me in the old-fashioned garden,
are as fresh with me, as if only just passed; and her telling mo
about Adam and Eve being driven out of Paradise; I always
considered it must be just like our garden at Bramerton. I
remember that my spirits were not strong; that I frequently
cried if looked at, and used to say that my eyes were weak; but
I remember much pleasure and little suffering, or particular
tendency to naughtiness, up to this period. Fear about this time
began to show itself, of people and things: I remember being
so much afraid of a gun. that I gave up an expedition of pleasure
with my father and mother, because there was a gun in the carriage. I was also exceedingly afraid of the dark, and suffered
so acutely from being left alone without a light after I went to
bed, that I believe my nervous system was injured in consequenre
of it: also, I had so great a dread of bathing (to which I was at
times obliged to submit) that at the first sight of the soa, when
we were as a family going to stay by it, it would make me cry;
indeed, fear wa.s so strong a principle in my mind, as greatly to
mar the natural pleasure of childhood. I am now of opinion,
that it would have been much more subdued, and great suffering
spared, by its having been still more yielded to; by having a light
left in my room; not being long left alone; and never forced to
bathe; for I do not at all doubt that it partly arose from that
nervous susceptible constitution, that has at times, throughout
my life, caused me such real and deep suffering. I know not
what would have been the consequence, had I had any other
than a most careful and wise mother, and judicious nurses, or
had I been alarmed, as too many children are, by false threats of
what might happen.
Even though treated so carefully by otliers her vivid imagination tormented her, and her early diaries must have
contained many outpourings of her spirit. These are lost and
we can only guess their character by her later struggles and
the records of her sisters and friends.
John Pitchford records ' that she told him of being so
impressed as a child by the story of Abraham and Isaac that
she was afraid to go to fleeting for fear that her parents
would be required to sacrifice her.
The state of her health secured her many privileges. She
was allowed to sleep later than the other children and was
usually excused from going to Meeting on Sundays — a much
prized privilege. The meeting house in Xorwich was reached
through Goat's Lane and the children always spoke of the meeting as " Goat's," and recorded in their journals their feelings
with such remarks as " I stayed at home from Goat's which I
was most glad of," "A long, dis(di.<gusting) meeting at
Goat's," etc. (Louisa. 11 years.)
Mr. Gurney was "labored with" about liis indulgence of
Elizabeth, and when she was older he required her to attend
Meeting more regularly. There were no paid ministers among
the Quakers and they depended for the " spoken word " upon
certain of their members feeling called; that is, having a
sense that they must either pray or preach. Certain members who spoke frequently and acceptably were acknowledged
Ity the fleeting and designated as ministers, and certain of
them traveled from Meeting to Meeting and were called
Public Friends or Visiting Friends. It was to hear one of
these that Elizabeth Gurney went when slie was 17 years old.
Her diary, which has been presened from about this time,
reads :
Sunday, Feb. 4th, 1798. This morning I went to Meeting,
though but poorly, because I wished to hear an American Friend,
named William Savory. Much passed there of a very interesting
nature. I have had a faint light spread over my mind, at least I
believe it is something of that kind, owing to having been mucii
with, and heard much excellence from, one who appears to me
a true Christian. It has caused me to feel a little religion. My
imagination has been worked upon, and I fear all that I have
felt will go off. I fear it now; though at first 1 was frightened,
that a plain Quaker should have made so deep an Impression upon
me; but how truly prejudiced in me to think that, because good
came from a Quaker, I should be led away by enthusiasm and
folly. But I hope I am now free from such fears. I wish the state
of enthudiasm may last, for to-day I have felt that there Is a God;
I have been devotional, and my mind has been led away from the
follies that it is mostly wrapped up In. We have had much
serious conversation; In short, what he said and what I felt, was
like a refreshing shower, falling upon earth, that has been dried
up for ages. It has not made me unhappy: I have felt ever since
Augustus Hare: Gurneys of Earlham. Vol. I, p. 47.
74
[Xo. 337
humble. I have longed for virtue. I hope to be truly virtuous;
to let sophistry ily from my mind; not to he enthusiastic and
foolish; but only to be so far religious as will lead to virtue.
There seems nothing so little understood as religion.
A most interesting struggle had begun of which I can only
give the bare outlines. She records two days following, on
the 6th:
My mind has by degrees flown from religion. I rode to Norwich,
and had a very serious ride there; but meeting, and being looked
at, with apparent admiration, by some oflicers. brought on vanity;
and I came home as full of the world, as I went to town full of
heaven.
However defective the education of the Gurney children
may have been; it had at least led to a remarkable independence of thought. Of all of them Elizabeth seems to have
been the most independent, and she then and all through her
life showed a ver}' clear insight into her thoughts and feelings. She records on Sunday, the 11th:
It is very different to this day week (a day never to be forgotten
whilst memory lasts). I have been to Meeting tnis morning
To-day I have all my old irreligious feelings: my object shall
be to search, try to do right, and if I am mistaken, it is not my
fault; but the state I am now in makes it difl5cult to act. What
little religion I have felt has been owing to my giving way quietly
and humbly to my feelings: but the more I reason upon it, the
more I get into a labyrinth of uncertainty, and my mind is so
much inclined to both scepticism and enthusiasm, that if I argue
and doubt, I shall be a total sceptic; if. on the contrary, I give
way to it. and as it were, wait for religion. I may be led away.
But I hope that will not be the case; at all events, religion, true
and uncorrupted, is of all comforts the greatest; it is the first
stimulus to virtue; it is a support under every afiiiction. I am
sure it is better to be so in an enthusiastic degree, than not to be
so at all, for it is a delightful enthusiasm.
There are many other records of the struggle. She was
so determined not to be carried away by her emotions that she
got her father's consent to send her to London so that she
might see for herself the attractions of the world and decide
whetlier she could be +++++
CONTENTS in their enjoyment. Wliile in
London she took music and dancing lessons, went to the plays
and to the opera, and saw as much of gay society as her opportunities allowed. Her diarj' for March 26, 1798, reads :
This morning I went to Amelia Opie's and had a pleasant time.
1 called on Mrs. Siddons, who was not at home: then on Dr.
Batty; then on Mrs. Twiss, who gave me some paint for the
evening. I was painted a little, 1 had my hair dressed, and did
look pretty for me. Mr. Opie, Amelia, and I, went to the Opera
concert. I own, I do love grand company. The Prince of Wales
was there: and I must say, I felt more pleasure in looking at
him, than in seeing the rest of the company, or hearing the music.
I did nothing but admire his Royal Highness; but I had a very
pleasant evening indeed.
On the other side, William Saverj- was also in London and
she went to Meeting to hear him preach and had some conversation with him, and when she returned after two months
she began to feel pretty sure that she was going to turn into
a plain Quaker. She regarded the change with great interest,
but with not a little apprehension, as she knew what a trial
it would be to her father as well as to the rest of the children.
In May, to distract her mind, her father proposed another
visit to London, and she writes in her journal on the 24th :
I wrote to my father this morning. I must be most careful
not to be led by others, for I know at this time I have so great a
liking for plain Friends, that my affection being so much engaged,
my mind may be also by them. I hope as I now find myself in
so wavering a state, that I may judge without prejudice of Barclay's Apology.
It was about this time, when she was just 18, that she
began her first independent philanthropic venture — the establishment of her school at Earlham for poor children. She
had always fotmd it easy to do for others, and even before
her religious awakening she had been her father^s instrument
for the distribution of his charities. She took such a delight
in doing for people and giving help that she recognized very
clearly that she deserved no great praise for so doing.
Her development into a plain Quaker progressed deliberately and she took no step in that direction without much
thought and travail of spirit, but she adopted one peculiarity
after another in spite of the open opposition of her immediate
family and often against what seemed to her the dictates of
reason. She gave up dancing — a pleasure she delighted in —
and singing, gradually changed the manner of her dress, and
used thee and thou, the so-called singular form.
To counteract all this Mr. Gurney took her with some of
the other children on trips, and she seems to have enjoyed
what she saw, but the Quakers whom they met at various
places interested her more. She on her part was the object
of the deepest interest to the Friends, as indeed was natural.
At one time, when 19, she was appointed on a committee
to in\-estigate the Ackworth School, and afterwards, wb.en the
young people were encouraged to speak and nothing was said,
she spoke. Of this she writes: "As it appeared to me it
was delaying the meeting I took courage (as I thought it
was more right than wrong to speak) : and said what I
thought of the grammar and ciphering; I felt glad I had
done it though i trembled at doing it not a little." She was
then asked  her opinion of other matters about the school.
This seems to have been her first service on a committee of
investigation.
During this visit she records on July 4, 1799 : " This
morning we walked to York and saw its wonders. We .*aw
the Friends' Retreat for crazy people which my father thought
extravagantly kept." This institution had been founded in
1792 by Friends, under the guidance of William Tuke, and
was the first place in England where the humane treatment
of the insane was attempted. I have fotmd no other references
to her having visited it again, but she was doubtless quite
familiar with the ideas and methods carried out there, as
the proper care of the insane was a common subject of discussion in the Society.
In America the Friends had long been interested in the
subject. In 1709 the Philadelphia Monthly fleeting took
steps towards the establishment of a hospital for the sick and
the insane, but it was not until 1751 that the Pennsylvania
Mabch, 1919]
75
hospital wiis founded. This institution among other sick
cared for patients "distempered in mind and deprived of
their mental faculties." In 1813 the Philadelpliia Friends,
stimulated by the success of the York Retreat, founded at
Frankford a Friends' Asylum.
Upon returninjT to Earlliani, Elizabeth befjan to take a more
active part in the ileetin<r, and in the fall of 1709 was appointed a representative. Her Sunday school for cliildren
increased rapidly, and here she began to show her remarkable power over audiences. She paid great attention to the
manner of reading (for she objected to the way the Bible was
usually read), and it must have been here that she be^an lo
develop the very remarkable style that was so effective throughout her life.
She was married when just 20 to Joseph ¥r\, the son of
another prominent Quaker family. The Frys were also wellto-do and were in business in London. Unlike the Gurneys,
they were the strict-est of plain Friends. You well imagine
that this important step was not taken without due deliberation. Elizabeth felt that she had a distinct work, and like
so many young women of to-day she was loath to give it up.
The sisters helped in the decision by filling their diaries with
hopes and prayers that Betsy might make no mistake. Joseph
Frv''s first proposal was refused, but thinking from the tone
of a note that he might receive a different answer, he went
back to Earlham. Augustus Hare, from whom I quote, gives
a most amusing account of the outcome. Joseph Fry did
not dare risk a second proposal so " he bought a very handsome gold watch and chain and laid them ujmu a white seat.
.... * If Betsy take up that watch,' he said, ' it is a sign tiiat
she accepts me, but if she does not take it up by a particular
hour, it will show that I mu.«t leave Earlham.' The si.\ sisters
concealed themselves in si.x laurel hushes, in different parts ol"
the grounds, to watch." When Betsy first discovered the
watch she retreated to the house, but the sisters kept up
their vigil from the laurel bu.'shes. Just where Joseph Fry
was tile account does not state, but continues: " Once again
did the an.xious sisters see Bct«y emerge from the house, with
more faltering steps this time, but still inwardly praying.
and slowly, tremblingly, they saw her take up the watch, and
the deed was done."
Upon going to London Elizabeth Frv' was thrown into quite
new surroundings, and it is amusing to find that, altliDUgli
she was considered austere and plain among the Gurneys,
among the Frys she was looked upon as far too gay and too
much given to worldly customs. Her children came rapidly,
and by a most unusual circumstance in exactly the numlier
and order as to se.x as her mother's, and as each one came it
was given the name of the corresponding Gurney child. Her
health was not good, and these first years were largely taken
up in adapting her^lf to her new surroundings. She was
always helping those in want when they came to her attention, but took no special part in public charities.
An interesting incident occurred shortly after her first child
was born, and we find in her journal (A Memoir of the life
of Elizabeth Fry, 1847, Vol. I. p. 108) the following:
Mildred's Court, Eleventh Month. 25th (1801). My cough has
been so poorly that my husband called in Dr. Slmnis. I asked
his advice about our little one being inoculated; he strongly
recommended the cow-pox, and said that he would undertake the
care of her if we liked: I think higlily of his judgment, and I
believe it to be our duty to avoid evil, both bodily and mentally.
So trifling a complaint as tlie cow-pox, being likely to prevent so
dreadful a disease as the small-pox, at least it appears justifiable
to try it; although the idea is not pleasant, it almost looks like
taking too much on ourselves to give a child a disease. But 1
altogether was easy to do it. I felt a good deal about the operation, which was very little and easily performed. What a wonderful discovery it is if it really prevents the small-pox.
You may remember that the first vaccination with cow-pox
was done by Jenner in 179G, just six years before this incident.
She became an ardent advocate of vaccination, and when,
after the death of her father-in-law, in 1811, she moved to
the large country place at Plashet, in the parish of East Ham,
she herself vaccinated the cliildren of the parish, having been
taught the method by Dr. Willan, an early and earnest exponent of the practice. She inspected the children from time
to time to see that none were left unvaccinated. In these
villages small-pox became practically extinct.
Elizabeth Frv- .^oon became the philanthropic Lady Bountiful of the parish, and there was nothing for the good of the
people that she was not busy about. She saw that the sick
and injured were visited, estiiblishcd a depot for the distribution of clothing, and in winter she had soup prepared at
her house in such quantities as to supply hundreds. With
the help of the clergyman and his wife she established a
school in which 70 girls were taught.
From the first, after moving to London, Elizabeth Fry was
iictive in the Society of Friends. She spoke more and more
frequently in Meeting, and in 1811 her gift was formally
acknowledged by the Meeting and she liecame a recommended
minister.
The Frys ciitcrtainiMl Friends constantly, and it was not
often that they did not have one of Elizaiictii Fry's brothers
or sisters from Earlham staying with them. After moving
to Pla.<het the hou-sehold became still more complicated, and
there are many notes in her journal telling of the thought
that she gave to her household, particularly to the proper
treatment of servants.
Her first 10 children were liorn in K! years, and the last
child six years aftenvards, Novemljer 1, 1822.
In 1813 she paid her first visit to Newgate Prison where
she was much impressed by the misery of the women. There
is nothing in her journal, however, that suggests that at that
time she felt prison reform to be her great work, and it was
not until three years later that she made her second visit,
this time at the instigation of two of her brothers-in-law.
The condition of this prison was most lamentable and some
of the descriptions are hard lo briieve. Years before John
[No. 337
Howard had called attention to the prisons in England and
had had laws passed by Parliament for their betterment, but
these laws seem to have been at this time almost completely
disregarded. The part of Newgate in which the women were
confined was the worst part, and the conditions were those
of utter squalor, misery and vice ; indeed, they were so terrible
that the governor himself went there as rarely as possible,
and it had for one of its titles " Hell above ground." All
the women were herded together without any attempt at
classification. There were many children among them, filthy
and half-naked. It was in these discouraging surroundings
that Elizabeth Fry and her companion requested to be left
alone with the women. I doubt whether upon going there
she had any plan formed in her mind, biit with her quick
instinct she made the one appeal that was most likely to be
effective. She spoke to the women of their children and
showed them how their behavior was affecting them, and she
suggested that, if they would co-operate with her, she would
form a class to instruct the children, but that this must be
with tlieir cO-operation and that they themselves were to
select one of their number to be the teacher. The women
immediately grasped at the plan and by the next visit they
had chosen Mary Connor, a young prostitute convicted for
stealing a watch, to be the school-mistress.
It was in these discouraging circumstances that the work
began. The prison authorities were entirely skeptical as to
the outcome, but allowed Elizabeth Fry and her associates
to try it. The plan succeeded from the first and it was not
long before numbers of the older women were clamoring to
be allowed to attend the classes. Other ladies joined Elizabeth Fry and visited tlie prison daily, and it then became
possible to extend the work to the older women. The women
were divided into different groups, a monitor from among
their number was chosen for each group, and occupation was
provided for them as well as daily Bible readings and other
instruction. A matron over the women prisoners was also
introduced.
To do all this required a considerable sum of money which
was provided by the committee, especially by Elizabeth Fry
and her brothers. The visiting committee of ladies became
later the British Ladies' Society for Promoting the Eeformation of Female Prisoners, with many branches throughout
the kingdom.
The changes that followed these reforms on the women's
side at Newgate were so marked and occurred so quickly that
they attracted widespread attention, and two years after their
inception, in 1818, Elizabeth Fry and her brother, Joseph
John Gurney, visited many of the prisons in Scotland and
the north of England. The notes (Notes on a Visit Made to
Some of the Prisons in Scotland and the North of England in
Company with Elizabeth Fry, etc., London, 1819) of this visit
were published by ]\Ir. Gurney. The state of each prison they
visited is recorded and at the end of the book he has brought
together their ideas as to prison management. Later, Eliza
beth Fry published her views on this subject (Observations on
the Visiting, Superintendence, and Government of Female
Prisoners, London, 1827), and they can also be learned from
the reports of various Parliamentary Commissions before
which she gave testimony. In brief, she believed it essential
that the women prisoners should be entirely separate from the
men prisoners, that they should be under the direct care of
only women, and should be visited by the men officers only
in the presence of women; that the women prisoners should
be classified, the tried from the untried, the more hardened
ofllenders from those less so, etc. ; that they should be properly
clothed, fed and warmed; that the uniform of each class
should be difl'erent, and that prisoners should be graded according to behavior. She insisted upon the importance of
instruction, particularly religious, and urged that the Bible
be read to them daily and that it should always be within easy
access. Useful occupation she regarded as of first importance,
the occupation being so planned as to bring them some remuneration while in prison and to help them to earn their living
when they were released. She did not feel that the lot of the
prisoners should be made too easy, but she insisted that the
first idea must be that of reformation. Solitary confinement
she believed to be open to grave dangers, although she advocated strongly that each prisoner be alone at night. She
earnestly opposed capital punishment in general, and especially when it was administered for trifling offences as it was
at that time.
The importance of the supervision of prisoners upon their
release was also insisted upon, and the ladies of the committee
gave special attention to those women who were to be transported to the penal colonies in Australia. The condition of
these women had been most deplorable and their residence in
the colony a scandal. The committee was instrumental in
providing work for the women to do during the voyage,
matrons to have charge of them and proper methods for their
recej)tion and care upon arrival.
Elizabeth Fry had the great satisfaction of seeing practically all of her suggestions adopted, and it was not long after
she had begim her work for the prisoners that to her consternation she found herself famous. Few distinguished
people visited London without accompanying her to her claSvS
at Newgate. Her advice was asked by very many people; she
appeared before committees of Parliament and many Societies. Her influence was little short of marvellous. Correspondence was established with philanthropic persons in various
countries in Europe. She gave advice as to the niana,gement
of prisons and the care of the insane. She had long correspondence with the philanthropic Venning brothers, John
and Walter, who were living in St. Petersburg. It was through
them that she sent advice as to the improvement of the lunatic
asylum at St. Petersburg, in which the Dowager Empress had
become interested and which she had taken under her special
care. Elizabeth Fiy recommended east-iron window frames
instead of the clumsy iron bars which had been used in the
old institution. She also recommended that all except the
Mabch, 1919]
violent lunatics dine together at a table covered with a cloth
and furnished with plates and spoons. Here, as cvenwhere,
she felt the importance of the Bible, and the Xew Testament
was introduced into this institution.
To show how closely Elizabeth Fn-'s suggestions were followed, I shall quote portions of a letter from Mr. Venning
written after her death (Memoir, Vol. 1, p. 387) :
When I received a letter from your mother I always wrote It
out in French and presented it in that language to the Empress,
and when she had read it, it was very encouraging to see with
what alacrity she ordered one of her secretaries to translate it
into Russian, and then deliver it to me to be conveyed to the
asylum, and entered into the journal there for immediate adoption.
I remember, on one occasion, taking a list of rules, at least
14 in number, and the same day they were confirmed by the
Empress; and these rules introduced the following important
arrangements, viz.: The treating the inmates, as far as possible,
as sane persons, both in conversation and manners towards them
— to allow them as much liberty as possible — to engage ihem
daily to take exercise in the open air — to allow them to wear
their own clothes, and no uniform prison dress — also to breat up
the inhuman system of permitting the promiscuous idle curiosity
of the public, so that no one was allowed to see them without
permission ; a room on entering the asylum was prepared for
one at a time, on certain days to see their relations. The old
cruel system drew forth many angry expressions from the poor
lunatics, " Are we wild beasts to be gazed at? " . . . . Another
important rule of your mother's was, most strictly to fulfil
whatever you promise to any of the inmates, and above all, to
exercise patience, gentleness, kindness and love towards them;
therefor, to be exceedingly careful as to the character of the
keepers you appoint. These are some of the pleasing results of
your mother's work. The Dowager Empress on one occasion,
conversing about your mother, said, " How much I should like
to see that excellent woman, Madame Fry, in Russia."
Her health was never ver}- strong, but even when ill she
could not restrain herself from trying to put right what she
thought was wrong. On one occasion, in 1824, when resting
at Brighton, she noticed the great number of beggars and how
the charity was given indiscriminately, and seemed to be
doing more harm than good. To meet this she organized the
charitably disposed among the different religious denominations into the " Brighton District Society," which was, in
effect, a charity organization society, and, so far as I know,
the first one ever formed. After this slie was instrumental in
establishing similar ones in many other places.
It was during this stay at Brighton, while she was suffering
from frequent attacks of faintness at night, for the relief of
which she was often taken to the window of lier room overlooking the sea. tliat her s_\-mpathy was aroused by the constant sight of tlie blockade man, or coast-guard, pacing the
beach. She thought how lonely and isolated his life was and
wondered how she could help him. She took the first opportunity of speaking to one of these men, but discovered that it
was against orders for the men to speak to any stranger, as
their duty was to prevent smuggling. To protect the man
she gave him her card with the request that he give it to his
superior oflHcer. Some days later she was much pleased to
receive a visit from the naval lieutenant in charge of the sta
tion and he explained to her the nature of the service. Mrs.
Frj' with her clear insight at once thought of a plan, probably
the best, that might alleviate the hard lot of the coast-guards —
.<lie established libraries containing tiie Bible and other books.
The libraries became very popular and were distributed
throughout England. Another national society was formed
to look after tlie interest of this work. Official sanction was
given and certain grants allowed. The report of tho committee in 1836 shows the magnitude to which the work had
grown. This report ends as follows (Memoir, Vol. II, p. 229) :
The means thus so liberally afforded, have enabled the committee to provide and forw^ard to the coast,
198 libraries for the stations on shore, containing. .25,890 vols.
74 libraries for the districts on shore, containing. 12,880
48 libraries for the cruisers, containing 1,867
School books for the children of the crews of
stations 6,464
Pamphlets, tracts, etc 5,357 in No.
Making a total of 52,464 vols.
and thereby to afford a body of deserving and useful men and
their wives and families (amounting to upwards of 21.000 persons) with the means of moral and religious instruction, as well
as profitable amusement, most of whom, from their station in
life, liave not the means of procuring such benefits from their
own resources, and who. in many instances, are so far removed
from places of public worship and schools, as to prevent the
possibility of themselves or their families deriving advantage
from either.
Mrs. Fry's interest in public institutions spread over the
whole of England, Scotland and Ireland, and many branches
of the British Ladies' Societj' were started in all of these
countries. In 1835 she extended her influence to the Channel
Islands and visited them again in the following year. The
acts of Parliament pertaining to prisons did not apply to
tliese islands, and their prisons were in a lamentable state.
As usual, she was able to suggest many improvements in their
management that could be and were carried out. Many of
lier correspondents urged her to visit the Continent and give
them the aid of her experience and personality. She felt it
lier duty to comply with this call, and in 1838 she began her
'' Visits of Gospel Love " to Europe. Siie made five such
visits, and, as Friends would say, the way was wonderfully
opened for her. Tliose in authority were nearly all more than
anxious to have her visit their institutions to suggest improvements. Tlie various royal families received her most cordially
:ind appeared to delight in her society. She must have made
a picturesque figure in such surroundings, dres.scd as she was
in the simple elegance of the plain Friend whicii harmonized
-o perfectly with her erect carriage, her dignified l)caring an<l
lier earnest, sympathetic face. Her principles did not allow
her to do many of the things that were considered neces.«ary
in court, but this seems to have made no difference. Royalty
in general seemed more pleased that she advi.sed them and
prayed with them than if she had ki.«sed their hands. She
^uggested many things about the conduct of their prisons,
asylums and hospitals, told them of her views as to the
[No. 337
religious state of their kingdoms, and when there was religious
persecution — as was frequently the case — she pleaded for religious freedom. All this she was able to do with such wisdom and tact that her counsel was accepted in the spirit in
which it was given and very frequently was acted upon.
She visited the Prussian Court twice, in 18-10, where she
was received with peculiar consideration, and when the King
of Prussia, Frederick William IV, visited England in 1843,
to stand sponsor for the Prince of Wales (the late King
Edward VII), he insisted, somewhat to the consternation of
those who had charge of his entertainment, in spending much
of his time with Elizabeth Fry. He requested that she dine
with him at the Mansion House, went with her to visit Newgate Prison, and then took dinner with her and her family.
He was heard to say, " She is the best friend I have in the
world."
Little did Betsy Gurney think when, she renounced the
pomps and follies of the world and adopted the customs of
plain Quakers, that the path she had chosen was to lead her
so often to the seats of the mighty !
Although Elizabeth Fry saw many things to criticize in her
journeys to Europe, she also found things to commend and
she met with many earnest workers for the amelioration of
the distressed. It was during her first visit to Germany that
she visited Pastor Fliedner's establishment at Kaiserwerth — •
an establishment for the training of nurses, the first secular
one that had ever been established. Fliedner had corresponded
with Mrs. Fry, had visited her on two occasions and seems to
have been much influenced by her example. Mrs. Fry, on her
part, upon returning to England followed his example and established the first band of professional nurses in Great Britain.
She herself could not take a very active part in it, but her
sister, Mrs. Samuel Gurney, and some other ladies took the
management of it. When not engaged in nursing, the " Nursing Sisters " resided at " The Home," in the city. They wore
a plain but inconspicuous dress and were maintained and paid
by the institution, but were not permitted to receive any
money or gifts under any circumstances for their attendance
in illness. The funds of the Society were small and were
derived partly from subscriptions and partly from the liberality of those who were benefited.
The intimacy between Elizabeth Fry and the other members of the Earlham family never waned and she paid frequent visits to Norfolk. Her sisters for the most part difl'ered
from her in religious matters, but this difference was never
allowed to cause any break between them. Whenever there
was illness, Elizabeth Fry, when possible, nursed the suft'erer
in a peculiarly sympathetic, skillful manner. However strict
she may have been with herself, she was more than lenient
with everyone else and had a never-failing sympathy. This
to some extent must have been due to the fact that she herself suffered frequently from bodily ills, particularly those
most troublesome ones of a nervous nature, and she had a
most unusual insight into such troubles.
In the Memoir " her daughters have included in the extracts
from her Journal a number of notes which bear on her bodily
state. These give some idea how, in her case, a peculiarly
nervous, sensitive nature was controlled and directed and
made most wonderfully effective by a firm religious belief.
These extracts are probably only a few of many similar ones
to be found in the original journal, but they are, I am afraid,
too many to be included in this paper, and so I have been
forced to select some which seem most interesting. I have
already read you her own recollection of her childhood in
which she speaks of her childish fears and nervousness. When
she was 18, during her religious awakening, she shows in the
following extract how she was struggling against her morbid
fears :
Jan. 4, 1799. A plan, at least a duty, that I have felt for some
time, I will now mention. I have been trying to overcome fear;
my method has been to stay in the dark, and at night to go into
those rooms not generally inhabited; there is a strange propensity in the human mind to fear in the dark, there Is a sort
of dread of something supernatural: I tried to overcome that, by
considering as far as I believed in ghosts, so far I must believe
in a state after death, and it must confirm my belief in the Spirit
of God; therefore if I try to act right, I have no need to fear the
directions of Infinite Wisdom; I do not turn away such things
as some do. I believe nothing impossible to God, and He may
have used spirits as agents for purposes beyond our conceptions;
I know they can only come when He pleases, therefore we need
not fear them. But my most predominant fear is that of thieves;
and I find that still more difficult to overcome, but faith would
cure that also, for God can equally protect us from man as from
spirit.
Before and after the birth of each child she usually suffered
a period of depression, accompanied by great bodily weakness
and a terrifying apprehension of death. After the birth of
her second child, when 23, she writes :
Plashet, Fifth Month, 21st, 1803. I have long been prevented
writing in my journal, by a severe attack of indisposition. It
is difficult exactly to express what I have gone through, but it
has been now and then a time of close trial; my feelings being
such at times as to be doubtful as to whether life or death would
be my portion. One night I was, I believe, very seriously ill; I
never remember feeling so forcibly how hard a trial it was in
prospect to part with life. Much as my mind, as well as body,
was then tried in this emergency, still I felt forcibly an inward
support, and it reminded me of that text of Scripture, " Can a
woman forget her sucking child, yea they may forget; yet will
I not forget thee." And then I told those around me, that I was
so ill, I could almost forget my child, but I felt the existence of
a power that could never forget. I have gone through much
since, in various ways, from real bodily weakness, and also the
trials of a nervous imagination: no one knows but those who
have felt them, how hard they are to bear, for they lead the mind
to look for trouble, and it requires much exertion not to be led
away by them; nothing I believe allays them so much as the
quieting influence of religion, and that leads us to endeavor
after quietness under them, not looking beyond the present. But
they are a regular bodily disorder, that I believe no mental
'Memoir of the Life of Elizabeth Fry. Edited by two of her
daughters. London, 1847.
March, 1919]
79
exertion can cure or overcome, but we must endeavor not to
give way to them.
Again six years later she records:
Seventli Month. 27th, 1S09. I am much better than I was, but
I have believed, in these trying complaints to which I am liable,
that the less I look outwardly for help the better; as I do not
believe any doctor can do much for me. I feel the best satisfied
when I simply endeavor to bear them patiently; I think I know
myself, wliat is the best to take for them: they appear to be
principally nervous, which I consider to be beyond the power of
man either to understand or cure; but how often have I experienced true spiritual support and help, when I have endeavored
patiently to wait on the source of good: and the mind being so
nearly connected with the body, whatever tends to tranquillize
it, really helps the complaint.
She often was pursued by the tlioujiht that possibly lier
nervous depression might be due to a lack of faith, and an
evidence that she was in some way untrue to her religious
standards, although her intelligence told her that the condition was largely a physical one as is sliowTi by the following
extract :
Plashet, Fourth Month, 30th, 1S14. None know but those who
suffer from them the deep humiliations such disorders create,
as those I have lately had; I mean great bodily weakness, accompanied by nervous lowness of spirits, and mucli mental fear. In
the first place, how deeply do they try us, being in their own
nature so painful: in the next, from the difficulty in doing strictly
right in them, how far to endeavor to divert by cheerful amusement, or by taking such things as may soonest relieve them; and
added to these, I think many are apt falsely to accuse themselves,
and to mistake the painful restlessness and fear occasioned by
them, for impatience and mistrust; I have sometimes a hope
that this is not my case, thougli at others great fear arises, lest
I should in any degree let go my hold, or be impatient after having so abundantly known the goodness, the loving-kindness of
the Almighty. Oh, saith my soul, may He once more revive the
spirit of His poor unworthy one. and breathe upon these dead
bones, that they may live.
The neurotic disposition seems to have been an inherited
tendency in this remarkable family, and Elizabeth Fry, when
53, wrote to one of her daughters, who was evidently suffering, the following helpful and encouraging letter:
(1833.) I feel in the first place, earnestly desirous that thou
shouldst think as little as possible of thy nervous feelings. I
luiow how extremely painful they are, but experience' has taught
me. the less I think of them the better. It is most important to
look upon them as much as possible like the toothache — that it
must be endured while it lasts, but it is not dangerous in its
nature. As for the discolored view, the imagination may at
times give to things, nothing is more important than to set it
down as a clear and fixed thing in the mind, that whilst this
nervousness lasts it is not sound, and must not be believed or
taken heed to. I would not have thee discouraged at this return
of it. I believe I never had death brought home very closely.
without being brought into a low nervous state, it is after all so
awful: though I increasingly see. that this is real weakness, and
that those who are believers In the Lord Jesus, however unworthy,
need not fear it, as through Him its plague and sting will be
done away. But it is folly in one sense to look ahead, we have
enough to do to seek for help and grace for the present time to
do our present day's work. When the day comes that we have
to give up "this mortal life." we may and ought humbly to trust.
that through the unmerited mercy and love of our Lord, His
grace will be found suflicient for us. I observe, for my great
encouragement, that what we call nervousness often proves no
common blessing, if made a right use of, and not given way to.
It so wonderfully humbles, prevents the creature glorying, and
makes willing to do anything to come to that peace, which quiets
every storm. Thy uncles and aunts have nearly all been striking
instances of this: and I believe, hard, very hard as it is to bear,
it is a baptism to fit for a fulness of joy and glory rarely partaken of; but it in no common degree calls for patience. I always
think both David and Paul largely partook of this sort of humbling experience. Therefore my dear .... if tried this way,
possess thy soul in patience, and look upon it as a suitable, though
bitter, medicine prescribed by the Physician of value to promote
thy health and cure.
She always, wJiile engaged in her various philanthropic activities expended her strength most lavishly, and afterwards
she usually had periods, often long ones, of great .suffering.
Together with the physical weakness, the accompanying menXaI depression was often combined with the fear tliat she had
received far too mucli personal adulation, and that she had
])erhaps put herself forward unduly. She was glad to use the
power of her reputation and position in the furtherance of her
]irojects, but was very fearful that she might take to her.self —
the instrument — the credit that was due to her Lord, and
she at times looked upon her illnesses as corrective agencies.
As she was returning from her second visit to Germany,
when 61, she WTites, in a letter to her husband and children,
the following:
Cassel. Ninth Month. 26th. 1841. I have continued very far
from well, with latterly a considerable stiffness in my limbs, so
that I am obliged to be assisted to walk upstairs, and helped into
the carriage, sometimes by one or two men. I might have had
the same attack at home; but one thing is certain, we may fully
trust in our Heavenly Father, who is constantly protecting us
under the wing of His love, and who knows what is best for us,
I have sometimes thought that after being so helped on my way,
from the palace to the prison, it was likely that the poor instruments should need a little further refining and purifying, for our
works are to be tried as by fire. I have very earnestly desired
not to repine, or to be unwilling to drink the cup that may be
given me to drink. We travel witli six horses to make the greatest
speed home. I have a board in the carriage, tliat when your uncle
and Anna are outside. I can quite rest and make a real sofa of It,
when I need it, which I do for one or two stages In the day. Mary
and Francois are very attentive and kind; indeed how differently
am I cared for to many poor missionaries. I wish you to feel for
me, but not to be too anxious about me; •ommil mo entirely to
Him wuo only knows what is best for me. Ynur aunt lOlizabeih's
Iflter wi.n very seasonable and acceptable. I wis!) her and all my
children to know how it is with me. for I need their sympathy
and prayers, at the same time that I feel the best help to be near,
and the Power that says to the waves " So far shall ye go and no
further." Often In my wakeful and at times distressing nights,
a sweet peace comes over me to calm my troubled spirit. We
hear from newspapers, that the poor Baptists In Copenhagen are
to be released from prison, a small sum being paid by way of fine.
What a comfort! and the poor Lutherans In Prussia say they are
now so well off, that they do not wish us to ask for any more
liberty for them from the King.
After this visit Mrs. Frj's health improved but slowly and,
although far from well, she felt it her duty to go again to
80
[No. 337
Fraufe in ]S43. Upon returning from this visit her health
failed rapidly and she was practically an invalid from then
until her death, although she was able to continue her correspondence and at times to take part in the various national
societies she had founded.
Among the number of interesting references in the Memoir
to this time I can only include the following :
One afternoon, when one or two members of her family were
reading to her, she was unable to attend to a very interesting
religious biography, saying, it was too touching to her — too aftecting. She added, after a pause, "How I feel for the poor when
very ill, in a state like my own, for instance, when ' good ' ladies
go to see them. ' Religious truths so strongly brought forward,
often injudiciously.' "
As she became weaker her fear of death decreased and to
one of the " Nursing Sisters " she thus expressed herself, " I
am of the same mind as Paul, I can say, 'to me to live is
Christ, but to die is gain.'"
Shortly before her death her daughters record a marked
change in her dominant disposition:
There was another wonderful change. Her powerful understanding and great capacity had given her the habit of control —
she was accustomed to power. During her long illness, this continued more or less to show Itself, and it was not always easy to
distinguish how far her opinions about her own treatment and
capabilities were well founded or not. This feature of her
character had disappeared. The will seemed wholly broken, the
inclination to resist, or even strongly to desire anything, passed
away; and she was +++++
CONTENTS to leave little things and great to
the direction of others. It was inexpressibly affecting to see
her look of meek submission, to hear her plaintive answer, " Just
as you like," to those about her.
These extracts that I have read show clearly how much
Elizabeth Fry suffered throughout her life from her peculiar
nervous organization. For two years before her death in 1845
she was an invalid, confined practically to her bed or chair.
Exactly what organic trouble she had, I have been unable to
determine, for her daughters speak only in very general terms
of the symptoms. She became less and less able to take any
active part in the various movements she had been instrumental in starting. She, however, attended Meeting whenever possible, often when she was too feeble to leave her wheelchair, and it is said that her mind remained remarkably clear
in regard to her ministry, even when she found it very diflBcult to concentrate her attention on other subjects.
During the last months of her life she appears to have suffered intensely, and her strong will seems to have become
passive, but her condition did not become acutely alarming
until three days before her death when, I think, she must have
had a thrombosis of the cerebral blood vessels. Slie gradually
became unconscious and died October 12, 1845.
Elizabeth Fry's religious faith never wavered, nor did she
ever regret having become a plain Quaker. She suffered
much for her principles, particularly from the fact that many
of her sisters and brothers could not see as she did and that
most of her children separated themselves from the Society.
Her eldest son renounced his membership and others were
disowned for marrjing out of Meeting. She believed most
strongly that young people should be left free in their choice
in marriage and encouraged her children in this by her svTnpathy and love. She felt as a minister of the Society of
Friends that she could not go to their weddings, but she did
attend the Meetings in which their names were taken from
the list of members.
She was thrown much with earnest people of all denominations and had no trouble in uniting with them all. Her attitude to others was one of love and helpfulness, but of herself
she was a severe critic. Although she felt it right for herself
to confonn rigidly to the customs of Friends, she regarded it
as a personal matter, and saw clearly that such conformity
might be a stimibling block to others, particularly to the
young. She had little patience with the empty forms of
piety, whether in plain Quaker or in the most ritualistic of
priests. Her religion was one of service and she truly followed George Fox's injunction, " That which Friends doe
speake they must live in."
Augustus Hare (Gurneys of Earlham, Vol. II, p. 201)
writes of her wonderful tenderness:
Mrs. Fry used pathetically to say at this time that she had
been " undermined by excessive love," an expression touchingly
significant of the secret spell of Elizabeth Pry — the spell which
unlocked the hearts of kings to her, and caused the prisoners'
chains to fall off at her approach. She had been no professional
philanthropist, too much absorbed in humanity at large to care
for the human item, but the public work had been, as it were,
only the overflow of her woman's heart, the expression of the fulness that remained after children, grandchildren, brothers,
friends, had been loved with an intensity which to her eyes
seemed " excessive," almost sinful. This marvellous tenderness
it was. thrilling in the tones of a voice whose natural music would
have been almost sufficient to melt and convince, which had been
the key to her influence and power — this, and her sweet humility
of soul, her child-like, single-eyed devotedness.
This certainly accounts for the charm and appeal of her
personality, but her effectiveness was due, I think, to the fact
that she had a most remarkable faculty of grasping a situation and knowing, seemingly intuitively, what under the circumstances should be done to meet it. This is genius, and
when genius is activated by Christian love what may it not do
and who of us would not gladly follow ?
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Vol. XXX— No. 338]
==Contents==
DcKi'tieration tJranulcs and Vacuoles in the V'ibroblasts of Clii<U
Enihryos Cultivated in 1 ifro. (Illustrated.)
By \Varri;n H. Lewi.s
Some Axpeet.s of Ovarian Pivgnaniy. With Keport of a Case.
lllliuitratod.)
By A. \V. Mevkb and II. M. N. W YNNK
Granville Sharp Pattison. (IHustrateil.)
By William Snow Millkr
Comments on the Pathology and Bact«'riology of Fatal In
lluenra Ca.ses. as Observed at Camp Devens, Mass. ( I litistrati'd.l
By S. BrnT Wolba( ii
l'roi'eedin(;s of Socictii'?.,
The Johns l!oiikinsH..>|>ital .M.Mli.al Society
Clinical Dliscivaf ions on Epideniie InlUiriiza [1)1!. .\. I..
Bloo.mkiki.h and Dr. (;. A. Harrop] ;— Comments on the
Pathology and Bacteriology of Fatal Inlliienza Cases, as
Observcil at Camp Devens. Massaclmsetts [Dr. S. B.
WoLUAi ii] ; — .-\ Kiinctioiial lie-education Clinic: Organi/.ation and Methods (Dr. W. (i. Tho.mp.so\) ; — Malaria in
the Federated .Malay States. A Coriection | Dr. W. (J.
MacCallusi j.
DEGENERATION GRANULES AM)
OF CHICK EMBRYOS C
VACUOLES IN THE Fir,HOBLASTS
TILTIVATEI) IN VITRO
By Wahukx
(From the llfpnrtmrnt of Anatomti.
l.NTKODrCTIO.N
Tlu' riirniiititiii ul' ;rriiiiuii'.s am! nT tluid vacuoli's within lin'
lil>ri)l)la.tt.>< of ti.ssut'-fulturi'.s is of fn-qui'iit owurrcncc in
|il)i.<iiia iinti in IxK-kcV .solutinn, witli or without tho ailditiun
i>f othtT siihstaiiws. TIrtc arc other t\in'.>; of licfjciu'ratidii.
Thi.>i vat-iioli/.utioii of the fytophLsni i.s one of the more coinnnin
iiUMles of cell (lefieneratioii unil (K-iitli in tissiie-<-iilture.«. It
liiis, however, reeeived very little eoiisiilenition, partly hecaiisi>
the vacuoles have often lieeii eonfu.seil with fat ilr<i|is ami
])artly heeause iiivesti;:ators have heeii reaihinj; out in other
tlireetion.*!.
I.icwis and Ix'wi.s ('!.")) eon.sidereil .somewhat hrietly tin
fn"aniiles and vacuole.s H|i|)earin;; in the eell.s of eiiltiires.
especially the ^rranule.** which .«tain with neutral red, Nile lilii.
B extra, and lirilliant eresyl hlue 'ih. In the normal cell tli«'
;;raiiule.s were few in number, hut were plentiful in cells with
many vacuole,*. It wa.* al.«o noted that they accumulate ahout
tho central liody (centrosphere) and are similar to the ;rraiiulcwithin the vacuoles. Xo relation.ship was founil between these
in-anules and mitochondria.
H. Lewis
The Johns Hopkitm Mcdiral S' hool)
'J'he aulliors al.sii (Icalt sipmcwii.it brictly witii the vacuoles
found in the cytoplasm, recoj^niziiifj that they were si^nis of
ilegeneration of the cylo))lasni and that there was a prof,Tt'i'-'*ive
accimiulation in some types of defreneration until most of the
cyto])lasm was useil up and only a framewurk remained. At
first it was .sdiiicwhat dillicult to distin<;uish the vacuoles from
tho fat ^.'lobule s|)aces in li.xi'd and staineil |)reparatioiis, but in
the living cells no such ililliculty was encountereil. Small
ihincinj,' oranules, varyinj,' in numiier from one to many, were
seen within the vacuole; sometimes the ^franules were motionle.>Js and adherent to the wall of the vacuole. It was al.so ftuind
that at times th(\v were colored jiale jfreeii with janus jfreen.
With Nile blue B extra anil brilliiint cresyl blue 'ih the +++++
CONTENTSs of the vacuoles stained ])ink', and the jrrannles blue or
purple. ('han;:es in the shape of the vacuoles and the formation of very unstable, thread-like processes exteiidin;: out from
them were also ob.served. We were unable to trace any relation
liotwoen mitochondria and vacuoles, although it wan often
noted that the niitochondria chanfred from threads and rods
to {.Tannics and vesicles, jiarallid with the increase in tin
82
[No. 338
number of granules and vauuoles, and that in extreme vacuolization the mitochondria were lodged in the eytoplasmic framework between the vacuoles.
Maximo w ('IG) noted in plasma cultures of subcutaneous
tissue of the adult rabbit, fixed with Zenker-formol, embedded
in celloidin, cut into histological sections, and stained with
cosin-azur, that the fibroblasts contain singular gi-anules which
stain bright pink — i. e., are slightly acidophilic. At first these
are minute and irregularly scattered in the cell body in small
groups. The number of gi-anules varies, but increases with
the age of the culture. " In old cultures vrithout cell proliferation all fibroblasts are often crowded full, up to the very
end of their outgrowth, with large, round, closely packed
granules Besides the above granules the protoplasma
of many fibroblasts of the same preparation contains small and
large vacuoles." In some vacuoles a large or small acidophilic
granule of the same character was occasionally detected.
ilaximow states that the impression produced is that the
granules dissolve from the outside inward and form the
vacuoles, and that the granules become permanent constituents which are transmitted to subsequent cell generations.
He further finds that " the whole cell-body and its processes
are then crowded full of spherical, occasionally very large,
granules, so that but little is seen of the protoplasm itself."
He regards this as an adaptation for life outside the organism.
The vacuoles usually present are either scattered singly or
joined in groups. " In the fibroblasts embedded in the masses
of the old fibrin the majority of the large granules are substituted by vacuoles and the structure of the cell-body appears
therefore coarsely foamy." These granules and vacuoles fomid
by Maximow in the fixed and stained cultures of the subcutaneous tissue of the adult rabbit correspond to the granules
and vacuoles previoush' described by Lewis and Lewis, and
are probably similar to the ones considered more in detail in
the present paper.
JIaximow concludes, from cultures fixed in Zenker-formol
and stained ^vith iron hematoxylin after sectioning, that the
above-described acidophilic granules represent the product
of the direct transformation of the chondriosomes. He bases
this view upon the very distinct pictures secured by the above
method. He says : " The black chondrioconts change into
round granules — the mitochondria, which increasing in size
seem to transform themselves into the acidophilic granules."
This theory regarding the derivation of the above-considered
granules and vacuoles from mitochondria is probably cjuite
incorrect. The two types of cytoplasmic inclusions have
nothing to do with each other. Maximow's conchtsions are
such as might be expected from the methods employed by him.
He introduces the article under consideration by the statement
that heretofore tissue-culture has lacked exact, authentic,
systematic researches of a histological character, and that
" we lack till now precise information concerning their
microscopic structure, their correlation, and, above all, their
origin from determined, well-knowTi elements of normal
tissue." After this introduction he proceeds to show how
cultures should be studied. What could bo more absurd than
to base practically all conclusions upon observations made on
tissue-cultures that have not only been cut into sections, but
have also been fixed in the same old mixtures that have so often
led observers astray in normal tissues. The very thing we are
trying not to do in tisstie-cultures is what ^Maximow seeks to
introduce with his histological technique. The absurdity of
depending ahuost entirely upon histological teclmique, section
cutting, etc., ^\-ill, I think, be obvious to most American
observers familiar with cultures. The greatest value of the
tissue-culture method lies in the fact that it admits of a study
of the living cell, and affords an opportunity actually to watch
some of the changes which take place therein, both under the
usual conditions of the culture and under various experimental
conditions through the introduction of knowTi factors, such as
vital stains, various chemical substances, drugs, poisons and
other alterations of the mediimi. Maximow gives little or no
attention to observations on the living cell, at least as far as
one can judge from liis article. This is partly due, no doubt,
to the fact that living cells are not so easily observed in plasma
as in fluid media. I do not wish to undervalue the use of
fixed and stained material, especially total mounts (we use
them extensively) ; but the pictm-es found in fixed and stained
material should be interpreted and controlled from extensive
observations upon the living cells. The emphasis, in fact,
should be laid on the study of the living cells, and this we have
constantly done. It is, of course, more easily accomplished
when fluid media are used and the culture grows out on the
under surface of the cover-slip, than with the use of plasma.
The fixed specimens are of great help in the construction uf
illustrations, and some structures are more clearly revealed
than in the living; but tmless they are to be seen also in the
latter, their existence in the living cell, as seen in the fixed
specimen, must always be open to question.
Maximow criticizes our methods very severely : "' In view
of the imperfection of their methods (the preparations were
made by vapors of osmie acid and examined in ioto, without
making sections) their results are of but little importance."
In the first place, osmic acid vapor, wdth the virtues of which
Maximow is apparently not familiar, is a most excellent
fixative for cultures in fluid media, far better than any of
those employed by him — we have tested them all. It may not
answer as well for plasma ctiltures, but with that we are not
concerned. In the second place, there is little point in making
sections of cells that are already flattened out on the coverslip, unless one wishes to trace their origin from the old piece ;
for that purpose we have, of course, occasionally made sections.
Maximow also criticizes, as have others, the tise of Locke's
solution. We have never claimed that this solution alone contained all the necessary food-stufEs, but with the addition of
dextrose and bouillon or egg-yolk the need can be partially
met. Just how complete a supply of food can be given in this
manner has not yet been determined. Cultures have been
kept alive for a month by washing and changing the medium
every day or two, and possibly they might be carried on much
lono-er. The cultures in plasma degenerate somewhat more
slowlv, as a rule, than those in our solutions, but here also
April. liMOl
83
replantation is necessary for long continued growth. Burrows
and Xeymann ('IT) believe that food materials for the growing cell^. in both i.-iotonic .<alt solutions and jilasma, come
directly from tissue fragments in the explanted piece through
disintegration caused by unfavorable environment. \Ve have
long thought tliat some of tlie food elements might be sup])lied
in this manner. The conditions, of course, are not normal
either in ])lasnni or in Locke's solutiou, but tlu' first fibroblasts
that grow out into the media show no al)normal cytologic
chaugi^s. The conditions in these embryonic chick filirohlasts
undoubtedly ditTer somewinit from those found in the aduh
mammalian fibrol)lasts studied l)y Maximow.
Burrows and Xeynninn find that the cells in rilro " come to
rest after a short ])eriod aiul .«how evidences of deterioration
through vacuolization and failure to stain deeply." These
authors evidently recognize that vacuolization is a sign of
degeneration. We have not found that the process interferes
with the staining of the c-ells unless they are ilead before fixation. A cell may be almost completely filled with vacuoles ami
yet stain brilliantly with iron hematoxylin and a counter stain.
Luna ('IT) found small vesicles or vacuoles aj)pearing in
the pigment cells of the retina, cultivated in ritro, and as their
number seemed to increase with a corresponding decrease in
the mitnchiuidria, he thought it probable that they were
derived from the latter. Vesicles such as he pictures in his
Fig. 7 correspond to the mitochondrial vesicles already figured
and described by us in degenerating cells (1915). They do
not correspond to the degeneration vacuoles described in the
present paper.
M.\TERI.\I> A.NI) METHODS
Most of the observations were nnule on small explants from
the leg& of G-, T-, and S-day chick embryos cidtivated in the
usual manner in Ix)cke's solution plus 0.5 per cent dextrose.
Such cultures show fibroblasts, clasmatocytes, and often ectodermal membranes and muscle-buds. The cultures of this
special series usually rc^iched the maxinnim growth in about
48 hours. Some of them showed more or less degeneration at
T2 hours, and at 0(! hours most of the cells were ccmipletelv
degenerated an<l dead.
I wish to emi)hasi/.e liere tiiat the particular series of cultures (several hundred) used for these observations were
made by an inexperienced a.ssistant and that the number of
cultures showing granular and vacuolar degeneration was far
in excess of that shown in any of our other series where such
a mode of degeneration is not by any means the rule. Not
only did most of the cultures show such degeneration, but the
growth was usually below the average and sometimes there
was no growth. I have not been able to analyze the factors
responsible for this excessive amount of granular and vacuolar
degeneration. The process is, however, essentially the same
as that ob.served in other series except that in the latter case
the cultures lived longer with normal appearing cells before
degeneration liegan and that this particular type of degeneration was not so common.
The cessation of growth, of mitotic division, and degenerative changes, may depend luit so much on the exhaustion of
the food supjdy as upon the accumulation of waste jjroducts
in the medium. There was very little Huid in the small drops
used in these cultures, and it is possible that it did not take
very long for the accumulated waste |)roducts to exert injurious
effects upon the cells.
Mitotic figures were found in some of lhe.<e cultures, often
many in the same culture at the same time. Such dividing
cells are found in the 24-, 48-, and T2-hour cultures. On the
other hand, some cultures do not contain a single mitotic
figure, and these are usually the ones which show degeneration
changes, some even as early as the second day. We are still
])uzzled by the great differeiurs in the vitality of the cultures,
ilue, perhaps, to unknown factors during the manipulations.
This is more especially true when the method is used by an
inexperienced worker. The rate and extent of growth are
often equal to that seen in ])lasnui.
The living fibroblasts were observi'd over varying lengths of
time in cultures of various ages, both with and without the
use of vital stains and various other substances. The vital
stains most frequently employed were neutral reil and janus
black Xo. 2. The combination of these two stains proved the
most satisfactory of all. We have, in the past, frequently used
the combination of tun \ il;d stains, more especially neutral red
and janus green. Tiie latter combination has been u.sed also
liy Coghill ('15) on fresh amphibian material, and by Mrs.
Lewis ('IT) on certain eggs and embryos. The neutral red
is rapidly taken up by the vacuoles and certain granules of
the fibroblasts, while the janus black No. 2 stains only the
mitochondria a deej) blue-i)lack. Neutral red was used in
strengths varying from 1-5000 to 1-800,000 in Locke's solution. For most of the observations I use 1-20,000 or 25,000.
The janus black No. 2 was usually of the strength of 1 j)art
of janus black No. 2 to 10,000 or 20,000 part,s of Locke's
solution. Brilliant cresyl blue 2b and methylene blue (Ehrlich rect. or Ilarmer Lab.) were also used. These stain the
same granules and vacuoles that take up the neutral re<l.
Until recently we contiinied to use osmic acid vapor as a
fixative with excellent results. l.ately, however, the osmic
acid in the market has not given satisfaction, and we therefore
substituted Zenker's solution without the glacial acetic acid
(2.5 per cent bichromic acid solution plus 5 per cent corrosive
sublimate plus 1 per cent sulphate of sodium). This has
given most excellent pre])arations when followed, as were the
osmic acid specimens, with the iron hennitoxylin stain. The
trover-slip with the attached growth is innnersed in the bichromate corrosive sublinnite mixture from i to 12 hours, washed
and carried through the alcohols with a little TiUgol's solution.
It must be borne in mind that fhe |)rocedure here used is
suitable for cultures grown in Tiocke's .solution and not necessarily for jdasma cultures where the clot aits as a buffer
through which the fixatives must penetrate. In cultures in
Ijocke's soluiton the naked cells are exposed to the action of
the fixative and the process is correspondingly rapid, reducing
post-mortem changes to a minimnm. Comparatively few
84
[No. 338
cultures were fixed, as we relied upon living material for our
(onelusions. With the iron hematoxylin stain it was often
impossible to disting-uish between small granular mitochondria
and the degeneration granules, as both are stained black. The
study of the living culture aids in the interpretation of the
fixed material and vice versa. Some jioints would undoubtodlv liave been missed if only one method had been cniploycil.
DEGENERATION GRANULES AND VACUOLES
Degeneration graniiles may be characterized brietiy as
follows :
(1) They are rare or non-existent in tlic more normal,
vigorous fibroblasts of the verj' young cultures.
(2) They vary in size from the ultramicroscopic grannies
to ones larger than mitochondrial gi-anules.
(3) They increase in number with the age of the culture.
(4) Tliey tend to accumulate about the centriole or centrosphere.
(5) They are often moved about actively (by cytoplasmic
currents), usually in paths from the periphery to the centriole
or centrosphere, or vice versa.
(6) They take the neutral red stain with great avidity, also
brilliant cresyl blue 2b and methylene blue (Ehrlich).
(T) They are not stained by jan\xs black Xo. 2 which stains
the mitochondria.
(8) In fixed specimens stained witli iron hematoxylin many
of these granttles are not distinguishable from mitochondria.
(9) They do not arise from the mitochondria.
(10) The degeneration vacuoles develop al)out tln'ni.
(11) Tliey are probably waste products.
(12) They accumulate under certain conditions in degenerating fibroblasts, and hence might be called degeneration
granules.
The degeneration vacuoles show the following characteristics :
( 1 ) They are not found in tlie normal, vigorous fibroblasts
of the cidtures.
(2) They are first apparent after there lias lieen a considerable accumulation of granules.
(3) They always seem to form about the granules and
almost always contain one or more granules.
(4) "When first recognizable the vacuoles arc small and
contain a relatively very large granule.
(5) They vary much in size.
(6) They tend to accumulate about the centriole or centrosphere.
(7) They often move in paths from the ju^ripbery to the
centriole or centrosphere, or vice versa.
(8) They stain avidly with neutral red. l>ut not as deeplv
as the granules; they also stain witli mctliylenc Idue and
brilliant cresyl blue 2b.
(!>) They are not stained liy janns black Xo. 2.
(10) They often change shape in the living cell, all gradations from spheres to long thread-like channels being seen.
(11) They do not arise from the mitochondria.
(12) They are probably waste products.
(13) They accumulate under certain conditions in degenerating fibroblasts until the latter are often crowded full of
them, and then as the cell dies they disappear and the dead
cell has a moth-eaten appearance.
The granules and vacuoles especially considered here are
most readily singled out from other cytoplasmic inclusions by
their property of rapidly absorbing the neutral red dye. It is
well known that neutral red stains certain granules in various
types of cells in other animals, and the fact that they absorl>
neutral red does not necessarily indicate that the granules are
identical in composition : very likely they are not. We do not
know whether the union of the dye with the granule is a
physical or a chemical one. Such grantiles, however, probably
have certain characters in common.
The determination of the presence of such granules in the
normal, living embryo or animal is most easily aecomplisheil
in small, more or less transparent forms that live in an aqueous
environment. In embryos, such as the chick, it is more difiiciilt to ascertain with certainty if such granules are normal in
any particular type of cell, such as the fibroblast. The mere
act of isolating the fibroblast by separating it from the
organism in teased preparations, in spreads, or in cultures,
immediately alters the environment. Changes in the normal
metabolic activity probably follow immediately, and the formation Qf such granules may result from the changed environment through alterations in the normal supply of gases, salts,
carbohydrates, protein products or through the inadequate
elimination of waste products from the immediate environment of the cell.
For the present, at least, we are micertain whether such
granules actually exist in the fibroblasts under the normal
conditions of the embryo. Occasionally one finds here and
there, in cultures less than 24 hours old, fibroblasts entirely
free from granules that take the neutral red stain. If these
granules do exist normally they are probably small and few in
number. Such filiroblasts exhibit a marked contrast to those
found in many of the older cultures.
fiRAXULES IX THE TOUSG FIBROBLASTS
Tlu' liealthy vigorous fibroblasts of the young cultures are
free from vacuoles and contain very few scattered granules
that stain red with the neutral red. In the ordinary cultures
there are usually to be fotmd, at the end of 24 hours — in the
fibroblasts that have migrated from the explant, or other
fibroblasts that have arisen from these by mitosis — scattered,
clear, refractive g-rannles. They vary in number, often quite
markedly, in difl'erent cultures and also in cells of the same
culture. After 24 hours none of the fibroblasts are entirely
free from such granules and many of them also contain small
vacuoles with relatively large granules.
niSTRIBt'TIOX OF GE.VXILES IX THE HEALTHY FIBROBLAST.S
The comparatively few grantdes seen in the fibroblasts of
the very young cultures are scattered through the cytoplasm
without any definite arrangement, so far as I have been able to
determine. Those in the body of the cell, however, a]iproacb
April. 1919]
85
to within varying distances of the edge of the much flattened
cells. (Jriuiules are not uncommon in the lari;i'r iiroi-csscs,
and here sometimes, since they may be nearly as larjje as tlic
diameter of the i)rocess, they come close to tlie surface. It is
not surprisinji that the granules are irregidarly and apiJarently
indiscriminately scattered through the cytoplasm, as under
the best conditions tlicy often move about, usually in a patJi
from the periphery to the nucleus, or riVe cersu, and are tliu;!
constantly changiutt ])osition. As we shall .^ee later, in tlu'
fibroblasts of older cultures the granules and vacuoles come
to have a very definite relation to the ccntriole, and their
paths of movement are between the ccntriole and the ]icripliery,
rather than between the nucleus and the periphery. The position of the ccntriole is dillicult to determine until there has
been a considerable acciunulation of granules, but T think if it
could be located in the younger, healthy tihrohlast.s wc should
find that the granules were moving in jiaths between it and tlic
j)eriphery. rather than between the nucleus and the ])eri|ilicry.
Its close proximity to the nucleus makes it a])]>ear as thougii
it were the nucleus that was the center for such activity.
IXCRKASK IN rilK XI .MBER .VXD SIZK OF THE GRAXfl.ES .\NI)
VACUOLES
As the cultures get older there is a gradual increase in the
number and size of the granules and vacuoles. In spite of
great variations in the rate of accimiulation and the ultimate
size of the granules and vacuoles in ditferent cultures, an
accurate picture can be given of the more usual process found
in the majority of cultures that undergo vacuolar degeneration.
As the granules increase in number it soon becomes noticeable that |)art of them accumulate at one side or at one end of
the nucleus. In fixed material and in later stages this accumulation at the side of the nucleus is clearly seen to take ])lacc
about the ccntriole or centrosphcre. It is rarely possible to
recognize in the living cell, during the early stages of the
accumulation of the granules, the ccntriole or centrioles at or
near the center of the granular mass. Since, however, it is
possible to do so in fixed material, and at later stages also in
the living cell, I have not the slightest doubt but that this
accimiulation of granules at one side or at one end of the
nucleus always takes place about the ccntriole. This is a very
interesting and im|)ortant ])oint. It is the centricde, then, ami
not the nucleus that is most directly concerned in the accumulation or location of degeneration granules and vacuoles.
The ccntriole or the ap|iaratus surrounding it is the determining factor that in name manner governs, by its ju'culiar
metabolic activity, the accnnndation of the granules and
vacuoles about it. I shall speak of an accumulation of graindes
about the ccntriole in these earlier stages, even though in the
great majority of instances the centrifde was not positively
recognized in the living material.
As the granules and small vacuoles increa.«e in nHnd)er, then,
they accunndate nmre and more about the ccntriole. The nniss
is den-^er at the center than at the iieriphery, and there arc
always a few granules scattered through the cytoplasm. With
the increase in number of the grannies the presence of snndl
vacuoles about many of them becomes more ajiparent. The
granules also show more variation in size, in that nniny of
them are larger than before. As the jjrocess goes on. the
number and size of the vacuoles grailually increase, so tlial
they form an ever-widening hah) about the centriule and
centrosphcre. Most of the granules iieconie enclosed in vacuoles or show more and more distinctly their va<-uolar envelope.
Vacuolization may continue until tiie entire cytoplasm i>
crowded lull ol vacuoles except for the enlarging centrosphcre
and a narrow peripheral nuirgin which usually renunns more
or less clear. The cytoplasm in such highly vacuidized cells is
reduced to a thin framework between the vacuoles, and to a
dear, well-defined centrosphcre about the ccntriole tliat is
entirely or almost entirely free of granules or vacuoles. I.,ong
s])indle-shapcd fibroblasts, with the nucleus exten<ling nearly
the full width of the cell, often have the ccntriole at one end
of the nucieus, and the cytoplasm between the nucleus and that
end of the cell may become ])acked with vacuoles lielore any
appear in the other einl of the cell.
The rate of increase in the nundier of granules and vacuoles
varies greatly in different cultures, ami also somewhat among
the cells of a single culture. There is. however, usually more
variation between different cultures than among the cells of
the same culture. No two fibroblasts are ever exactly alike,
even in the same culture: yet in sjiitc of this <lissimilarity
among the individual cells tliere exists enough uniformity t^i
give a peculiar character to each cidture. Since the rate of
accumulation of tlie vncmiles :ni(l granules varies in different
cultures, often quite niarkedly. one finds occasioindly in a
"i-i-hour culture an accunnilation of vacuoles and granules as
extensive as in the average 48- or even T2-hour culture. On
the other liand, it sometimes hajipens that a 48- or a 7"<?-hour
culture presents no greater accumulation of grainiles than the
average 24-hour culture.
There are many other variations in the minilicr. size,
inequality of size, etc., of the granules and vacuoles. It is the
control ami production at will by enviroimiental alterations
of such variations that will enable us to analyze more fully
the processes that arc taking ]ilace. It <loes not seem beyond
the realms of po,<sibility that some day we may be alile to
jiroduce at will any desired variation.
The above conclusions in reganl to the increase in the number and size of the vacuoles and granules were not drawn from
the continued observations of imiividual cells over long periods
of time, but from shorter observations on thousands of cells
in hundreds of cidtures. It would i)roiiably be possible so to
rcgidate the comlitions of ob.servation that one conlil follow
in a single cell this accumulation of granules and vacmdes
from the condition foumi in the healthy fibroblasts, with few
scattered graindes. to tin- completely viiciiolized cell, and r-vcn
to the death of the cell.
Often during the observations, through the manipulation of
the culture and the apfdication of neutral red and janns black
Xo. 2, the c(dls were found to live hut an hour or so after the
observations were begun. Such cells do not exhibit (hiring
that hour or two anv niarkeil increase in the nnndicr of
86
[Xo. 338
granules or vacuoles. Their death may ensue at any stage
in the granular and vacuolar formation. Death may also take
place at any stage in the cultures that are not thus manipulated. Several factors imdoubtedly contribute to the death of
the cell, and sometimes one and sometimes another may predominate. In the highly vacuolated cells stained with neutral
red the final death process is often quite rapid. The behavior
of the colored vacuoles is quite striking; one after another, in
rapid succession, they suddenly lose their color and flash out
of siglit. When the process is complete, the cell has a peculiar,
clear, unstained, moth-eaten appearance. Changes in the
mitochondria and in the nucleus are also to be seen.
SIZE AXD SHAPE OF THE GRANULES
The granules vary iu size in the same cell. Some are barely
visible with the highest powers, even with the neutral red
stain; others are of considerable size and maj' measure onequarter or one-half the diameter of the nucleolus. The
extreme minuteness of some of the granules indicates that
other still smaller, ultramicroscopic ones are probably scattered
tlirough the cytoplasm. Within certain limits it can be safely
stated that the more healthy the cell the fewer and smaller are
the granules. The granules undoubtedly increase iu size.
One cannot actually see this increase, since the process is
probably slow and the difficulty of following the same graiuile
through any considerable length of time is too great.
Most of the granules are somewhat angular in outline, suggesting a crystalline formation. There is but a suggestion of
this, however, since they are usually irregularly angiilar. I
suppose an irregular angular mass might result from crystallization or from the accumulation of ultramicrosco[)ic
particles. Such granules are difficult to distinguish, by their
shape alone, in unstained cells, from the small gra:udar
mitochondria (when the latter are present). In most healthv
cells, however, the mitochondria are in the form of rods and
threads which can be easily distinguished from the degeneration granules. In fixed specimens stained with iron hematoxylin it is likewise difficult or impossible to distinguish
between granular mitochondria and degeneration granules.
There is a method, however, by which the two types of granules
can be distinguished in the living cell; i. e., the combination of
neutral red and janus black No. 2, by which the granules are
stained bright red and tlie mitochondria blue-black. Some of
the special mitochondrial stains also enable one to distinguish
the two types of granules in the fixed specimens ; on the other
hand, certain fixatives, especially those containing acetic acid,
destroy the mitochondria, but leave the granules miaffected.
Maximow noted that the griinules described by him were at
first minute and irregularly scattered in the cytoplasm. This
extreme minuteness of some of the granules is an important
point, especially in relation to their possible origin from mitochondria, as alleged by some authors; for it would be logical
to assume, if tliey do arise from mitochondria, that the latter
first become reduced iu size to a minuteness which renders
them invisible, and that this is followed by a change in constitution and a gradual increase in size. Mitochondria are
sometimes minute to the limits of visibility and yet retain
the characteristic staining reaction with janus black No. 2.
The most minute degeneration granules, on the otlier hand,
exhibit the same characteristic coloring with neutral red seen
in the larger granules. It is perhaps importtmt to note in this
connection that those minute mitochondria are not always or
usually found in fibroblasts that are just beginning to show
the minute neutral red granules. It is only in the later stages
of degeneration that the normal mitochondrial threads and
rods tend to break up into granules.
THE RELATION OF GRANULE AND VACUOLE
It is not always possible to distinguish the granule from the
small vacuole, as the granule may occupy practically all of
the vacuole with only a thin rim of fluid. It may be that all
the granules we are considering are included in vacuoles. The
fact that granules are often irregular in outline would not
nullify such a +++++
CONTENTSion, since vacuoles themselves are sometimes irregular. It is conceivable that even the smallest
granule may be surroimded by a rim of fluid too thin for
detection. In our present state of knowledge concerning these
bodies it is of no particular consequence whether all granules
lie within vacuoles or all vacuoles contain granules. Practically all vacuoles do contain granules, one or several, and it
is vmcertain whether vacuoles exist that are entirely free from
granules. We do not know why the vacuole should develop
around the granule. It may be that minute vacuoles appear
first and granules develop within them, or the granule may
appear first and the vacuole develop about it. Since we arc
not certain of the exact relations when the granules have
attained visible sizje, the idtramicroscopic condition must
necessarily be still more uncertain. The impression one gets
from the study of uiunerous specimens is that many of the
granules in the healthy cell are free from vacuoles, and that
the latter subsequently develop about them. The granules in
the smaller vacuoles often appear to be larger than those in
the large ones. The larger vacuoles, however, usually contain
several granules, with perhaps an aggregate of material equal
to the larger granules of the smaller vacuoles.
In vacuoles of the same diameter containing solitiiry
granules, the latter often vary in size. The amoimt of fluid
in the larger vacuoles is much greater in proportion to the
size of the gTanules than that in the smaller vacuoles.
Multij)le granules within vacuoles can be conceived of as
arising in at least four ways: (1) By the coalescence of
smaller vacuoles each with a single granule, the number of
granules in the larger vacuole depending upon the number of
smaller vacuoles which coalesce; (2) large granules may split
up into small granules; (3) new granules may develop in
vacuoles, by a process of crystallization, for example ; (4)
granules free in the cytoplasm might be taken info the vacuole
as it enlarges.
THE rOSITioX OF ORIGIN OF THE GRANULES AND VACUOLES
We have not been able to determine the position of origin
of the granules and vacuoles. In the earlj' stages tliey are
APBIL, I'JIOJ
87
scattered, but as tlicy become more numerous, most of tlieiii
are located in the immediate rejrion of the centriolc. Since
they move about freely in the cytoplasm, either towards the
centriole or away from it, one mifrht conclude tluit they form
in the more i>eriplieral rej^ons of the cytoplasm and arc
carried towards the centriole where they tend to accumulate,
or that they arise near the centriole and arc carried outwards
into the more peripheral rejiions of tiie cytoplasm. The ditliculties of the problem are increased by the fact that the
smallest firanules are on the boundary of visibility, and from
that one must conclude that they begin their existence in tlic
cells as dustdikc jrraiiules invisible even with the hijflicst
powers. Such •rranules in cyto])lasm would be unlikely to lie
found in their position of orijrin when they attain the size of
visibility. The fact that they accumulate about the centriole
may indicate only that they are carried tiiere, as they form, l)y
cyto])lasmic currents, if such currcntjj exist; and that tlie.^e
currents tend, during degeneration, to flow more towards tlic
centriole than away from it. Such a view receives some sujiport from tiie changes which oci-ur al)out the centriole. W'p
have noted elsewhere that the centrosome increases in size
during degeneration, and that about it a centrosphere develojis
which gradually increases in size until it may become as large
as the nucleus. The enlarging centrosphere is usually free or
nearly free from granules and vacuoles, the latter surrounding
it in a zone of varying thickness.
In cells with many vacuoles and a large centrospbcre, the
latter is sometimes tilled with enormous numbers of the finest,
du.«t-Iike granules which stain red with neutral red. What
relation the.<e l)ear to the granules under discussion is not
known, but very likely they represent a similar degeneration
]>ro<!uct. We have seen that the ordinary degeneration
granules begin to form before the centrosphere apjiears; tlms
they may arise independently of it.
TIIK MOVEiLEXTS OF TIIE ORAXILES .WD VACKH.ES
The granules and vacuoles exhibit a considerable amount of
movement, ditfercnt from an<l more extended than the ordinary mit(H-hondrial movements. It is irregxdar, sometimes
rapid and jerky, sonu-times slow and of varying speed. The
distances traveled differ greatly; in general, the direction is
from the region of the centriole or centrosphere to tiir
|)eri[>hery, or lire \erxii. The amount of activity varies in
ilifferent cultures and in cells of tiie same culture, and is
apparently easily affectcfl liy environmental factors. Under
certain conditions no movements r)f the granules are to l)c
seen. Thes«' movements are probably not de|(cndi'nt upon the
activity of the granules themselves, but upon either cytoplasmic currents in which the pa.ssive gramdes are carried or
metabolic changes. It has not l)cen possible to .see cytoplasmiicurrents.
As statcfl aitovi', the movements of the granules are somewhat dilTerent in character from the mitochomlrial movements ; the amplitude is often greater and they are more
lively. The movements are best followed in cells where the
granules are stained red with neutral red and the mitochondria
blue with janus black No. 2. .\ red granule is sometimes seen
passing along close to a blue-black mitocbondrium, .sometimes
extending beyond the extremity of the mitocbondrium. Again
the granules may pass back and fortli in paths that are some
little distance from a mitocbondrium, and nniy cro.ss at varying angles above or below a mitocbondrium. Sometimes
granules are detiected by the initocliondria as the latter are
bent, or a])pear to l)e bent, i)y the tlowing granules. These
appearances are such as to suggest that the granules arc
located in a more fluid, streaming jiart of the cytoplasm, while
the mitochondria arc in a less Huid part, tiie movements of
which would be of a different ciiaracter, thus giving to tlic
mitocbondrium and to the granule eacii its own peculiar tyjie
of motion. On tiie otiicr iiand, tiie different types of motion
may ijc due entirely to tile differences in I'cmijiosition of the
mitochondria and of tiie granules, witii a resulting dill'ereiicc
in tile inter-action tictween tlicin and tlie enclosing cyto|dasm.
niAMJKS IN IllK IDlfM OK THE VACUOLES
The viicuolfs Miry not only in size and jiosition. liut ai.so in
sliape. In some ceils tiiey are constantly altering tlieir form
such changes often occurring coincidently witii ciiange of
position. Frequently many or almost every cell in a culture
will show vacuoles tiiat are constantly ciianging iiotii form and
position. -Vgaiii, viTy few if .uiy of tlic ceiis wiii siiow sucii
changes.
The variations in siiajie wiiiili tiie vacuoles may assume arc
quite remarkable. The usual form is spherical. Tiiis is the
most staiiie condition and such vacuoles may remain unciianged for a long time. In contrast to this may iie found a
complicated, tliread-like network of channels, very unstaliii'
and constantly changing. Between tiiese two extremes a
multiiilicity of forms occur in different ceils. The most
common change is the sending outward from a \acuole of a
long tiiread-like channel or process. Tiiis apparently cont^iins
fluid similar to t.liat within tlie vacuole. These processes arc
likewise constantly changing tiieir ])osition and length. The
entire vacuole may iie converted into such a channel, wiiicii
in rare instances may brancii and anastomose with other
similar ciianneis to form a more or less comjdex network witii
granules .scattered here and tliere witiiin the ciianneis. In
such sjiecimcns the granules fre<|ucntly are larger than the
diameter of tiie ciianncl and produce a distinct i»ulge in its
wall. Tile granules are often oijscrved to sliift along tiie
channel.
These vacuolar ciianneis are vi-ry unstaiiie and ciiange niucli
more rapidly tiian tiie mitochondria. Many of tiiein are aiiout
llie same size and siiape as tiie mitochondria, and at first may
prove to be somewiiat confusing; but witii tlie use of neutral
red and other vital dyes (methylene blue and brilliHul cre.syi
lilue) tiicy can lie sliarply an<l clearly .separated from tiie
mitochondria. Their ttehavior, too, is so difTerent tliat one
soon comes to recognize that tiiey are entirely different. The
vacuolar channels may change back into splitrical or oval
vacuoles.
88
[Xo. 338
I should suppose that these various changes iu the form, and
]ierha]is also in the position of the vacuoles, are dependent
upon the metabolic activities, or upon the interchang-e of substances between the exterior and interior of the cell. The longprocesses and networks also suggest that there may be some
relationship between vacuoles and the canalicular ai)]iaratus
found in some other types of cells.
MITOCHONDRIA AND MITOCHONDRIAL VESICLES
Iu the vigorous, healthy fibroblast the mitochondria are
usually scattered throughout the cell as long threads or rods,
often branching or anastomosing and running in lines more or
less parallel to the long axis of the cell; in others, radiating
somewhat from the nucleus and centriole towards the periphery. As the granules and vacuoles increase in number
the radial arrangement of the mitochondria about the centriole becomes more and more marked. In the earlier stages
the mitochondria extend beyond the granular and vacuolar
area into the clear cytoplasm. In some of the cultures the
mitochondria come to lie in the cytoplasmic net between the
vacuoles, and also partly in the clear peripheral regions at the
ends of the cells. In such cells, even though the entire
cytoplasm becomes packed with vacuoles and granules, the
mitochondria may remain as short threads or rods until the
cell is about to die.
Otlier cultures show fibroblasts in which the mitochondria
midergo much more change. As the vacuoles and granules
increase in number the mitochondria show more of a tendency
to break u]) into short rods and granides, and these in turn may
swell u]) into spherical bodies or vesicles of various sizes. The
granules form very minute vesicles and the longer rods may
form \esicles as largo as the neutral red vacuoles.
These changes apparently begin first in the mitochomlria
lying immediately about the centrosphere and gTadually extend toward the periphery. They are usually preceded by
changes in the mitochondria which give them an irregular
appearance, and the longer threads seem to he broken up into
short rods. The irreg-ularities of the mitochondria gradually
become more marked and arc chiefly characterized by differences in the diameters of the various tlireads and of the
different i)arts of the same thread or rod. These clianges are
also accompanied by irregularities in the staining; that is, the
mitochondria exhibit lighter and darker areas, especially w ith
such stains as janus black Xo. 2. Under ordinary conditions
of the culture, these changes in the mitochondria indicate
degenerative changes in the cell. Similar changes can be
brougiit about in a relatively short time in the long thread-like
mitocliondria of Iiealthy fibroblasts by the use of potassium
jiermanganatc. Witli a 1-20,000, 1-40,000, or 1-80,000 solution
there takes place with varying degrees of rapidity, depending
upon the strength of tho sohition, changes in the mitochondria
similar to those observed in the more slowly degenerating cells
of the cultures.
During these cliaiigcs both the thread and rod-like mitochondria and tile niitochoiulrial vesicles stain bluish witli
janus l)l;ick Xo. 2. and ncxcr at any time do they take up tlie
neutral red. In fact, there is always a sharp distinction
between the staining of the ntitochondria and the mitochondrial vesicles with janus black Xo. 2 and the staining ol'
the degeneration vacuoles, the granules, and the processes of
the vacuoles with neutral red. There are undoubtedly at
times certain similarities between the two types of vacuoles
when unstained, and in our earlier observations we were uncertain as to the relationship existing. For example, one often
sees a small vacuole with a long mitoehondrium-like process
that is continually changing in shape, size and position. Xow
both the mitochondria and the neutral red vacuolar processes
I are subject to constant changes in form, size, and position.
I As mitochondria form vesicles the vesicular enlargement often
takes place first at one end of the mitochondrium; the length
of the unchanged narrow portion would vary, of course, with
the length of the original mitochondrium and the size of the
vesicle at the time of the observation. In unstained living
cultures it might be impossible for the untrained eye to distinguish between such a changing mitochondrium and a neutral
red vesicle with a mitochondrium-like process. With the
application of a 1-10,000 solution of janus black No. 3 the
mitochondria and the mitochondrial vesicles are stained bluish,
whereas the neutral red vacuoles and granules remain unstained. If this stain is folloAved by a 1-25,000 solution ol'
brilliant cresjd blue, it will be seen in a few minutes that the
color in the mitochondria rapidly disappears, while the previously ixnstained vacuoles and granides take up the brilliant
cresyl blue and appear bluish or violet in color. If, however,
the janus black Xo. 2 is followed by neutral red ( 1-20,000 or
1-25,000), the blue color of the mitochondria and the mitochondrial vesicles is often increased in depth, while the previously imstained vacuoles and gi-anules take up varying
amoimts of the neutral red dye. Then, too, the differences in
the behavior of the two types of vacuoles when stained and
followed with the application of potassium permanganate oichloroform indicate that we are dealing with two quite
different things.
In some cells with almost complete vacuolization the mito- I
chondria may show very little sign of degeneration or change,
but apj)ear as rods and short threads in the cytoplasmic network between the vacuoles. In some of the long spindle cells
\acuolization may be complete at one end of the cell and the
mitochondria be more or less broken up into rods and granides ;
while at the other end, the nucleus lying between the two parts,
there may be almost complete absence of vacuoles and granules,
and very little change in the long thread-like mitochondria.
The degenerating end of such a cell seems to be always the end
containing the centriole.
CHANGES IN THE REGION OF THE CENTRIOLE
As the cultures get older there is a gradual increase in the
number and size of the granules and vacuoles. Parallel witii
tliis increase very important changes take place in the region
of the centriole. As the granules increase in number, they
tend to accumulate about the centriole, which is located near
one side or one end of the nucleus. This gradual accumulation
APKIL, lUlUj
8!)
of the granules, and later of the viuuolcs, about the eentriole
gives a very characteristic picture, especially when tlic
granules and vacuoles are stained with neutral red. One is
often unable to recognize the centriole in the earlier stages in
the living cell. In lixed material the centriole can usually l)c
seen at the center of the mass of granules and vacuoles. Later,
as these accumulate, the centriole becomes surrounded by a
more or less dear area (the centrosphere) near the center of
the mass of granules and vacuoles, and near one side or one
end of the nucleus, with which it is more or less in contact.
As the granules increase in number, the centrosphere increases
in size, and at its center can usuallv be detected the double
centriole. The centrosphere is usually entirely free from
neutral red granules and vacuoles. It gradually increases and
may eventually attain a diameter equal to, or even greater
than, that of tiie nucleus. With its enlargement tiie granules
and vacuoles api>ear to be pushed farther and fartb.cr away
from tile centriole. The centrosphere usually presents a clear
medullary zone immediately about the centriole or centrioks,
and a much wider cortical zone, which often shows radiations.
Occasionally one or two small neutral red granules appear td
lie within the centrosphere. In some cultures which have been
stained with neutral red the centrosphere .shows many very
line, red, dust-like granules. Since this seems to occur only in
c-ells that show somewhat advanced vacuolar degeneration, it
may be that it is indicative of the beginning degeneration of
the centrosphere.
We have already considered the radial arrangement of the
mitochondria about the centriole and centrosphere; the
i^ranules and vacuoles, lying between the mitochondria, also
at times assume a more or less radial arrangement. We have
considered also the movements of the granules and vacuoles
which take place more or less in paths between the centriole
or centrosphere and the perii)iiery. The accunudation of
granules, vacuoles, and mitochondria about the centriole, and
the accumulation or building up of an increased amount of
what .«(H'ms to be a special type of cytoplasm about the centriole, would indicate that its activities are in some nninncr
increased during the degeneration of the cells.
DISCUSSION
I venture to suggest that in due course of time it will lie
found that the living part of the cell cannot be stained by any
of the so-called vital dyes, since the combination of the dye
with the living protoplasm would so upset the delicate molecidar constitution of the latter as to kill it : and because living
]>roto}>lasm is so eonstituteil that it cannot combiiu', either
jihysically or chemically, with any other substances exce[)f
such as are synthetically built up into itself. The corollary
will be that till' so-raIle<l vital dyes stain only the non-living
cytopla-smir inclusions, such as granules, vacuoles, secretion
granules, food-glol»ules, mitochondria, etc.
One might well hesitate to ela.«s the mitochondria witli nonliving c.\-toplasmic inclusions, in view of the many claims tluii
have been set forth as to tiie r«"ile of mitochondria in the transmission of hereditari- qualities, and above all as to their part
in the formation of various cell structures during histogenesis.
They are supposed to form the coUagenic libers (Meves).
myolibrils (Benda, Meves, Duesberg, Hoven and others),
epidermal fibers (Firket and Uuesbcrg), neurofibrils (Uoven,
Meves and G. Arnold), and .secretion granules (Grj-nfeltt,
Bobeau, Kegaud and Marvis, Nicolas. Kegaud and Favre,
Hoven and others) — a formidable list of authors imbued with
the idea that the mitochondria po.s.scss magic qualities.
I'owdry, in his recent excellent contribution, " The Mitochondrial Constituents of Protoplasm," states that " the
radical claims concerning their role in histogenesis have forced
the reinvestigation of the entire field." He is inclined to
believe that the mitochondria are concerned, either directly
or indirectly, witli nu>tabolism or with proto|)lasmic respiration. The mitochondria may well play an important role in the
general metabolism of the cell, more especially in that particular part of the metabolism which is common to all cells,
such as respiration, perhaps, as has been suggested by several
authors (Kingsbury, Mayer, Kathery and Schaetler). The
mitochondria niight jilay such a role in the general metabolism
of the cell and still not be considered as a part of the living
cytoplasm, any more than are the stored-up yolk-granules
found in many eggs.
t'oghill suggests that during the i)rocess of digestion and
assimilation of yolk in amphibian embryos certain end-products of the process segregate into what he calls alpha bodies
and beta bodies, and that the former, proltably undergoing
some chemical change, become free as mitochondria in the
process of assimilation into protoplasm. AVlietluT this be true
or not, more interesting still is the suggestion that the more
toxic action of janus green (whicii st-siins the mitochondria),
as compared with that of neutral red (which stains the bctn
bodies), is due to the fact that tiie proces.«es leading up to tiie
construction of protoplasm arc oi)structed i)y the reaction of
tiiis stain ; whereas, only the residue, so to speak, of these
processes is attacked liy tiie neutral red. If the mitochondria
are concerned in tiie respiration of the cell, the action of jaiiu.green on the niitociiondria. for which it has a special alliiiity.
might obstruct the rcs])iration to such an extent as to kill tiic
cell. Coghill's suggestion as to the less toxic action of neutral
red would apply to our conception tiiat neutral red stains only
llie non-living matter, such as accumulated waste products or
stored-up food-stuffs, or .some partially digested food-stuffs
that are not iminediateiy essential to tiie ceil.
(Jranules witli a special affinity for neutral red iiavc been
described in many iliffercnt types of cell in many different
species of animals, and it will be interesting in tiiis connection
to consider a few of the more striking cases. Fischel ('01)
found in the living ectodermal cells of ampiiiiiian larva; many
such granules. He considered tliem as living elenient.s, in conformity, perhajis, with the views of .\ltmann prevalent at that
time. We know that tlie ectodermal cells of various vertelirates deposit witiiin themselves substances which are usually
<-onsidered as non-living elements, and which in many ca.ses
ultimately accumulate to such an extent as to finally transform the cell into a non-living scale. The fact that such
90
[Xo. 33S
deposits may serve a useful purpose in the organism does not
invalidate the view that they are non-living inclusions.
The Clarks have described in the lymphatic endothelial
cells of the tadpole's tail numerous gi-anules which take up the
neutral red in the living. E. R. Clark has shown that the
lymphatic endothelium is actively phagocytic, and since these
cells possess the power of taking up particulate matter it may
well be that they also take in ultra-microscopic particles and
segregate them into granules that take up the neutral red.
Whether these granules are of this nature, or whether they
consist of waste products, is of course impossible to determine
at present. Other phagocytic cells, such as the clasmatocytes
and leucocytes, are especially rich in vacuoles and granules
that have a great affinity for neutral red. The clasmatocytes
are especially interesting in this connection, as they are abundant in most of our cultures. Certainly the vacuoles, and
[irobably all the granules which stain so avidly with neutral
red, are non-living inclusions, the granules for the most i)art
being derived from cellular debris taken up by the cells.
It is well known that the partially digested dead +++++
CONTENTSs of
the food vacuoles of protozoa stain with neutral red (Plato,
Stole) and that disintegrating bacteria and cell debris in leucocytes stain in a similar manner (Plato, Arnold). Many
eggs contain nmnerous granules and globules, probably foodstuffs, and perhaps accumulated waste products also, that
stain with neutral red. The eggs of Cerebratulus, of the sanddollar, and of Lojthius piscatorius (M. R. Lewis), as also the
amphibian egg (Coghill), have recently been studied with the
aid of neutral red, and all were foimd to contain numerous
neutral red-staining granules probably of the nature of storedup food-stuffs.
There are reasons for believing then that the granules and
vacuoles considered here are non-living cytor()lasmic inclusions.
Since the granules and vacuoles accumulate without noticeable enlargement of the cells, they must be formed in greater
part from the cytojilasm rather than by the diffusion into the
cell of substances and fluid from the outside ; moreover, thev
are formed from the cytoplasm, ])resuniably as jiroducts of the
metabolism of the living cell. Tliese products of metabolism
may be divided into two classes — food products and waste or
secretion products. The former are found most abundantly
in egg and embryonic cells, and we should scarcely expect to
iind cells cultivated in Ijocke's solution storing up food-stuff's.
We are led, therefore, to accept the alternative theory, i. e., that
the granules and vacuoles are accumulated waste products and
that they are formed in part, at least, hy the breaking down of
the cytoplasm. This process may be looked upon as a degeneration j)henomenon. since it ultimately leads to the death of
the cell.
The altereil environmejit of the fibroblasts in the cultures
pr<ibably sooner or later interferes in many ways with their
normal metabolism, either from the absence of oxvgen, salts, or
food-stuffs, or through the accumulation in the culture medium
of waste products in suificient amount to prevent their normal
elimination from the cells by osmosis. This altered environment M'itli its lack of certain essential salts, food-stutfs, and
perhaps of oxygen, would favor the breaking down of the cell
protoplasm through starvation, and the accumulation of waste
products. We have no method of determining whether the
+++++
CONTENTSs of the vacuoles and granules are identical with the
normal waste products excreted from the cell. An alteration
in the composition of the waste products, however, might he
expected to accompany the starvation of the cell.
Since the cells do not appear to increase in size as vacuolization spreads, we are more or less forced to conclude that part of
the cytoplasm is broken down into granules and vacuoles. This
process maj' use up most of the cytoplasm, leaving only a
slender framework between the vacuoles. The enlarged centrnsphere usually remains intact and does not become vacuolated.
The cytoplasmic framework is continuous with the centrosphere, radiating out from it in all directions.
The relationship of the gTanuoles and vacuoles, and likewise
of the mitochondria, to the centriole and to the gradually
enlarging centrosphere is not at all dear, if we attempt to
explain it in physiological terms. The anatomic picture is
plain enough, but why the granules and vacuoles should surround the centriole and centrosphere is miknown.
The centriole and its centrosphere have long been considered
by many authors as the dynamic center of the cell, the focal
point of the more active archoplasm of Boveri, the kinoplasni
of Strasburger, the spongioplasm of Leydig, etc. This peculiar
cytoplasm, which accumulates about the centriole during
degeneration and which I have also seen much augmented in
amount in giaait cells in certain cultures, seems to be different
from the ordinary cytoplasm that occupies the bulk of the
cell. Whetlier there is an actual increase in the amount of the
stuff" forming the centrosphere or merely a concentration of
already existing material about the centriole, is difficult to
determine. There appears, however, to be an actual increase.
Conklin speaks of the spongioplasm of the egg of Crepidula
as " the interalveolar or continuous substance within which
are found enchylemnni, microsomes, mitochondria, as well as
yolk, oil, and other inclusions." He finds that " large inclusions such as yolk spheres are forced out of regions where the
spongioplasm concentrates." A somewhat similar phenomenon seems to take place about the enlarging centrosphere.
where the vacuoles and granules are forced away hy the concentration or increase in the archoplasm or spongioplasm about
the centriole in the degenerating fibroblasts. The framework
of cytoplasm, which extends from the centrosphere to tlie
peripheral layer in these highly vaciiolized fibroblasts, corresponds, perhaps, to the spongioplasmic framework in Crejiidula that remains throughout the entire cell and connects the
nucleus and centrosphere of the resting stages to the peripheral
layer after the centrifugal force has displaced the more fluid
part of the cytoplasm, tiie yolk, and the other cytoplasmie
inclusions. It is the spongioplasm that seems to be the living
part of the cytoplasm, the ])art which determines the polaritx
of the cell. In the normal fibroblast the cytoplasm, except for
the mitochondria and a few granules, appears homogeneous.
Does this a|)parent homogeneous cyto])lasm consist of two ])arts.
THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL. 1919
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91
a sponorioi)la.«mic framework ami a more fluid enchvlemma y
Or is it all H|)(iiijri(i|>la.-;mii- material. cxeeiJt for tlie iiKJusioiis
above iiotinl 'i
The eauses of. or faetors eoiicemed in, the firadual enlar<,'emeiit of the eentrosphere are not known. It is well reeojjnized
that in many ejijrs where food aceiimulations are eonsiderahlc
tile attraction sphere is larjre. It is also larger in cells that
are about ready to divide tluui in the restin<r cell. There is
undoubtedly a relationship between the accumulation of foodstuffs in the eg-r and the size of the attraction sphere; and
again, between the growth in size of cells which are destini'd
to divide and the increase in the size of the attraction sphere.
Is the accumulation of granules and vacuoles about the
centriole the factor that causes the enlargement of the eentrosphere?' Such an accumulation of granules and vacuoles
would naturally alter the usual relation.ship of the centriole
to the periphery of the cell, ujjsetting the metabolic balance
in such a manner as to eaiise. perhaps, the building iip of the
enlarged eentrosphere, since the metabolic activities which
are centered in the centriole probai)ly de|)end upon a constant
interchange of materials i>etween the centriole and periphery.
The accimiulating waste products about the centriole in the
form of granules and vacuoles would certainly tend to alter
this.
BIBLIOGRAPHY
Burrows. M. T.. and C. .-V. Xey'raann: 1917. Studies on the
metabolism of cells in vitro. Jour. Exp. Med., XXV.
Clark. E. L.. and E. R. Clark: 1919. On the reaction of certain
colls in the tadpole's tail toward vital dyes. Anat. Rec.. XV.
Coghill. Ct. E. : 1915. Preliminary studies on the intercellular
digestion and assimilation in amphibian embryos. Science. N. S.,
XLIII, 347.
Conklin. E. G.: 1917. Effects of centrifugal force on the structure and development of the eggs of Crepidula. Jour. Exp. Zool..
XXII.
Cowdry, E. V.: 1918. The mitochondrial constituents of protoplasm. Contributions to Embryology, VIII. Carnegie Institution
of Washington, Pub. No. 271.
Fischel. A.: 1901. Untersuchungen liber vitale Farbung. Anat.
Hefte, Bd. XVI. 417.
L^wis. .\I. K.: 1917. The effect of certain vital stains upon the
development of the egg of Cerebratulus lacteus. Echinorachniu.s
parma, and I..ophius piscatorius. Anat. Rec, XIII.
Lewis. .\l. R.. and \V. H. Lewis: 1915. Mitochondria and other
cytoplasmic structures in tissue cultures. Am. Jour. Anat., XVII.
Luna, E. : 1917. Note citologlsche sull" epltello pigmentato
della retina coltlvato " In vitro." Arch. Ital. di Anat. e dl Embr .
XV.
.Maximow. Alexander: 1916. The cultivation of connective
tissue of adult mammals in vitro. Russian .Archiv of Anat., Hist.
and Embryology. I.
Plato, J.: 1900. feber die " vitale " Karbarkeit der Phagocyten
des Menschen und einigen Saugethiere mit Neutralroth. Arch. f.
mikr. Anat . LVI. 868.
Stole, A.: 1902. L'eber das Verhalten des Neutralrots ini
lebendigen Protoplasma. Zeit. f. allg. Phys.. I. 209.
EXPLANATION OF FIGCRES
The figures are all drawn free hand from living cells stained
with neutral red. and many of them with janus black No. 2 in
addition. The original drawings gave only vague outlines for the
cells, as the author's attention was concentrated on the relations
of granules, vacuoles, mitochondria, centriole. eentrosphere, and
nucleus. Since then the borders of similar cells, both in living
and fixed material, have been examined, and appropriate outlines
added to the original cell drawings. Thus the greater number of
the figures are composites. The edges of most of the fibroblasts
present a peculiar scalloped condition, with slender processes of
varying lengths extending from the points, much longer, as a rule,
than those shown in the figures.
Figs. I, 2. 3, 4. and 5 are from 78-hour-old cultures; explants
from the legs of 8-day chick embryos. Figs. 2 and 3 are from
the same culture, the others are each from a different culture.
Fig. 1.— Healthy fibroblast with few granules. Figs. 2. 3, 4,
and 5 show the gradual accumulation of granules about the
centriole and the increasing radial arrangement of the mitochondria. In Fig. 5 are also seen many small vacuoles. Fig. 4
and 5 show small centrospheres.
Fig. 6. — A 74-hour-oId culture; explant from leg of 9-day chick,
showing' increased number of vacuoles and granules about an
enlarged eentrosphere. Mitochondria broken up into short rods.
Figs. 7 and S. — 54-hour-old cultures: explants from leg of 8-day
chick. In Fig. 7 the centrospliere is at the side of the nucleus and
the granules, vacuoles and mitochondria are arranged more or
less symmetrically and radially about it. In Fig. 8 the eentrosphere is at one end of the nucleus. Very few granules or vacuoles
are seen in the opposite end of the cell.
Figs. 9 and 10. — 7S-hour-ol(l cultures: explants from leg of 8-day
chick. The eentrosphere either has not developed or is obscured
by the crowded granules and vacuoles. The centriole was not
seen, but its position in both cells is undoubtedly at the side of
the nucleus.
Fig. 11. — A 78-hour-old culture; explant from leg of 8-day
chick. Large eentrosphere surrounded by granules, vacuoles, and
mitochondria. Wide cortical zone of eentrosphere shows radiations. The vacuoles in this cell were constantly sending out
long processes.
Fig. 12. — A 4S-hour-old culture: explant from the leg of a 7-day
chick. Cell crowded full of large vacuoles, except at the thin
edge. Mitochondria broken up Into short rods which seem to lie
in the cytoplasmic framework — eentrosphere obscure.
Fig. 13. — A 48-hour-old culture; explant from leg of 7-day chick.
Very large eentrosphere surrounded by many large vacuoles.
Radially arranged mitochondria, rather long rods and threads.
No vacuoles or granules in the opposite end of the cell.
Fio. 14.— A 2-day-old culture: explant from leg of 7-day chick.
Large eentrosphere: entire cell crowded with large vacuoles;
mitochondria in form of short rods.
Fig. 15.— A 3-day-old culture: explant from leg of 7-day chick.
The vacuoles showed much motion and were constantly sending
out long processes or changing into channels, which are seen
to anastomose at one end of the cell.
Fig. 16.— a 24-hour-old culture from the leg of a 7-day chick.
The vacuoles and gianules showed considerable motion, and the
vacuoles were constantly sending out processes and changing In
form.
Fig. 17.— a 3-day-old culture from intestine of a 7-day chick.
The mitochondria have all changed Into vesicles. Degeneration
has progressed to such an extent that the vacuoles have begun to
disappear.
Fic8. 18, 19, and 20.— 2-day-old cultures; explants from the
legs of 7- and 8-day chicks; showing variations In the vacuoles,
eentrosphere, etc. eentrosphere full of dust-like granules.
Fio. 21— A 3-day-old culture; explant from leg of 9-day chick.
Mitochondria arc changing into vesicles.
92
[No. 338
SOME ASPECTS OF 0\ ARIAN PREGNANCY. WITH REPORT OF A CASE
By A. W. Meyer and H. M. X. AVyxxe
From the Department of Gyneeology of The Johns Hopkins Medical School, the Department of Embryology of the Carnegie Institiition.
and the Department of Anatomy of Stanford University
Although the first case of ovarian pregnancy under that
heading in the Index Medicus is that of Kouwer ('97) (van
Tnssenbroek, '99), careful scrutiny of the titles listed for the
last decade reveals the fact that 5 cases of ovarian pregnancy
were reported in 1908, 4 each in 1909 and 1910, 7 in 1911.
13 in 1912, 9 in 1913, 7 in 1914, 3 in 1915, 1 in 191G, and 5 in
1917. This makes a total of 58 cases apparently reported
\vithin this decade. Since the reports on some of the cases
were published in three different Journals, these were, of
course, counted merely as one, and although the authenticity
of four of the cases must be questioned on the basis of the
titles alone, the series, nevertheless, is a large one in spite of
these facts and of a marked decline in the number reported
during the war. Since Norris ('09) stated that only 19 certain cases, a])proximately only one-third as many as all cases
Usted in the last decade, were reported in the decade between
1899 and 1909, it would seem that ovarian pregnancy not only
is receiving increasing attention, but that a change in attitude
probably is in progress. Tliis conclusion would seem to be
justified even though a careful examination of the descriptions
of the cases reported in the decade between 1908 and 1917
would reduce somewhat the number listed.
Loekyer ('17) accepted as authentic only 22 cases of those
reported between 1910 and 1917, but his review is only
a partial one. Even so, it shows that there is a decided
increase in the number of cases which have been regarded as
genuine from decade to decade. The marked increase in the
number of genuine cases re])orted in recent decades becomes
still more evident if one recalls that Williams ('10) found
only 13 positive cases up to 1906, whereas Norris found 19
positive cases in the single decade between 1899 and 1909.
That is, ISTorris foimd more positive cases reported in this
decade than had been reported in all previous medical history
up to 1906. This surely is a significant fact.
The opinion that many, even if not all, cases of so-called
hematocele, hematoma, apoplexy, blood cysts, and rupture of
the ovaries, probably are nothing but cases of ovarian pregnancy in disguise, has been held by various investigators for
some time. Hence, if hematocele of the ovaries repeats the
history of hematosalpinx, it is not tmlikely that the near
future will see a marked increase in the reported frequency
of " a fact so curioiis and important in itself," as Granville
aptly put it a century ago. This would seem to be true in
spite of the fact reported by Norris and Mitchell ('08), that
only a single case of ovarian pregnancy was found among
44 extra-uterine specimens and 58 hemorrhagic cysts contained in the collection of 1700 gynecological specimens at the
hospital of the University of Pennsylvania. At any rate, a
careful microscopic examination of all such eases would seem
to be indicated in the future in order to determine, if possible,
which cases are, and which are not, conceptual in origin.
To-day it is no longer true, as stated by Freund and Thome
('06) and by Sencert and Arom as late as 1914, that authentic
cases of ovarian pregnancy belong to the great rarities. Yet
the fact that many of our states, as well as many large clinics,
have not a single case on their records seems to suggest that
the condition still is seldom recognized, a century after Granville observed his first case. Moreover, a nimaber of continental gynecologists and obstetricians, for a quarter of a
century, have regarded the oceiu-rence of ovarian pregnancy
as undoubted. Anderson ('17) stated that German writers
began to report eases of ovarian pregnancy with some frequency after 1901, and Gilford ('01) also called attention to
the fact that continental opinion long had accepted ovarian
implantation not only as possible, but as proven. Gilfonl
further referred to the often quoted opinion of Tait that
ovarian pregnancy is as rare as " A blue lion or a swan with
two necks," and in his article in 1899 also called attention to
the opinion of Bland-Sutton, that ovarian pregnancy not only
has no existence, but that it is impossible. These opinions are
particularly interesting in view of the carefitl reports made
by Granville (1830 and 1834), in connection with the two
cases which he then and which others since have regarded a.<
cases of undoubted ovarian pregnancy, in spite of the absence
of microscopic examination. In view of this lack it is particularly fortunate that both of these reports of Granville are
accompanied by splendid illustrations by Bauer, which also
won his praise and admiration and which greatly strengthened
his cases. It may be recalled in this connection that Werth
('01) accepted Granville's case recorded in 1820, but said
nothing about his second more convincing instance reported
in 1834.
Although there is as yet no agreement as to what constitutes
an authentic case, a re\'iew of the literature justifies the growing and apparently well-founded belief that in the past too
much emphasis has been laid on certain criteria wliich later
experience has shown to be partly inapplicable. It is becoming clear that some cases, formerly excluded for reasons regarded as sufficient, with our present knowledge could no
longer be rejected. Moreover, it does not seem at all improl>able that some cases listed as tubal really were orarian in
origin. Xor must it be forgotten that not even the entire
absence of remnants of the conceptus can positively exclude a
case from the category of true ovarian pregnancy. In a number of cases in the literature, and also in the present case, the
clinical history and gross anatomic findings suggest the conclusion drawn by Scott ('01) on a priori grounds alone, that
the conceptus may be completely resorbed. It may, of course,
also be aborted and disintegrate completely. That such an
April. l!il!t|
i:s8umptiuii is justified is indicated by the lysis of tlie emljiv"
or fetus in a large number t)f eases of ovarian jtrejrnancy, and
also by the very degenerated condition of some of the vesieles
and of the surrounding ovarian stroma. The |)ossil)ility ol'
such an occurrence is estal)lislied also by similar events in tlic
uterine and tubal jiregnancies discussed elsewhere (Meyer.
'19), and ])robal)ly is illustrated by such cases as those of
Anning and Littlewood {'01 ). in which no mention is made (if
an embryonic disc in a translucent conccptus the size of m
*' pea." Then, to be sure, there are the cases of unruiiturcil
ovarian ])regiinncies containing villi only, as well as the rare
case, probaltly of double ovarian pregnancy, of Holland ('11 ).
Although one cannot be certain that embryonic tissue was
removed from the left ovary with the blood-clot which was
forcibly c.\]ielled at the time of operation, it is not at all
improbable that the small jdasmodial masses found in the Icli
ovary were the only remnants of the concejitus. 1 realize fully
that the conclusion that young concejjtuscs may be wholly dissolved is fraught with great uncertainty, but I am quite sure
that it is justified by the facts, and that it therefore is in the
direction of truth. It could oidy fail to be so if every ovum
that beconu's implanted within the ovaries were al)orted or
were removed by operation before lysis was possible.
One cannot rightly refuse to recognize the i)<)ssil)ility of tlie
spontaneous disap])earance of an ovarian pregnancy. Sinee
implantation in the ovary occurs under such al)normal conditions, it would .seem that for this reason alone the gn^at
majority of .such implantations inevitably must succumb.
This would .>;eem probable wholly aside from considerations
regarding the development of the corpus luteum, although
lack of, or interference with, the development of the latter
also woulil .'ieem to condition early death of the conceptus if
the results of the long series of experiments on rabbits by
Frankel ('0.3-'10) are indicative of the role iilaycd by the
••orpus luteum in early imidantations in nian also. It surely
is didicult. if not impo.ssible, to see liow implantation witbii:
the (Jraalian follicle, and esj)ecially the later development ol
the conceptus, can fail to interfere with the development of ii
normal corpus luteum. Ca.^es in the literature, and also in tlie
present case, did not reveal the presence of any well-pre.'<er\eil
or even true luteal cells at the time the pregnancy was terminated. Although this fact does not presu|)pose an entire lack
of developnu'ut of these cells in the earliest stages of tlu'
implantations, it undoubtedly does im|)ly a defective development, which in it.*elf nniy have become responsible for tbi>
death of the conceptus. \or should the jiossiide toxic eti'ect
upon the conceptus of luteal lells be forgotten in this
i-onnection.
I do not assnnu'. to j)e svire. that the eliiiieal symptoms mikI
signs alone should suflice finally to group a s|)ecinien as truly
ovarian, but when these arc indicative of the pre.«ence of an
ectopic gestation, and when undouiitcd intra-uterine decidual
changes are present, in the absence of abdominal pregmincy or
tubal involvement and a normal corpus luteum. and the
presence of a blood-dot within the ovary, there would seem
to he little reason for doubting the authenticity of the ovarian
implantation even in the absence of cnd)ryonic remmint.-.
Siiu-e i-hanges suggesting decidual reaction in the ii\ary ha\e
l)eeu reported so seldom it is doubtful whether nnich emphasi^
can be laid on them. One seems justified in saying this in
spite of the fact that the presence of decidua in the ovary
formed the only anatomic evidence U])on which Kantorowic/
('04) confidently classed his two rather atlvanced cases of
ectopic pregnancy anumg the authentic. Moreover, if it be
true, as stated by Webster ('04 ) that changes which cannot be
distinguished from true decidual changes not infrequently
occur in the ovary in connection with normal uterine pregnancies, then the ])rescnce of islands of decidual cells in an
ovary surely cannot be regarded as indicative of ovarian
pregnancy. 1 wonder, however, whether it woidd not be
po.ssible to distinguish genuine decidual cells by modern histnchemical methods. In making this observation, 1 am fully
aware that various criteria have been advanced from time to
time by means of which to judge ovarian pregnancies, and
that many of these have met with objection and have hence
been nu>dified. Such modifications would seem to be inevitable as long as there is progress in the sulutinii nf mm unsettli'd
question.
The absence of tlie iCtus in inanv of the recorded cases
in itself demonstrates tlie entire inapplicability of the criterion addeil by .lacobsoii ('(I.S). .Moreover,' the histologiiappearance of the ovarian tissue around certain jiortions of
the blood-clot in the present, ami also in some of the ca.ses in tinliterature, would seem to suggest that it may be very diflicull
to find remnants of ovarian tissue at several points in a casi'
of pregnancy which has ailvanced far. Hence, this criterion
of Spiegelbcrg ('7S) cannot be regarded as necessarily crui-ial.
Whenever the implantation is developed at the outer instead
of at the inner margin of a follicle, as in the ca.^e of Banks
('12), early destruction, even if not early rupture, of the
overlying ovarian stroma and cajisule would seem to be
inevitable. Indeed, whenever the layer of ovarian stroma
overlying the pliuiiita is thin, very early death of the fetus
would seem to lie inevitalde from defective nutrition alone.
On the other hand, when jdaccntal development occurs in the
region of the follicle directed toward the body of the ovary,
great destruction of the ovarian stroma woulil seem to be
unavoidable, even if something akin to normal decidual formation actually took ]dace. In the case of Kngelking ('lU), f<ir
exani])le, not a trace of an ovary was found in an ovarian
pregnancy which had become interstitial. Kven without
assuming the complete aidhenticity of this rather ecpiivocal
case, it W(uild seem highly probable that the presence of
ovarian tissue later in the pri'gnaiiey probably is determined
very largely by the location of the fertilized follicle within, or
by the e.\act location of the im|ilanta1ion upon the ovary.
Werth ('8T) is said to have collected 12 ca.srs. among which
he regarded only that of Leopold ('S2) as authentic. Ix-opolil
('1)9) reported 14. (Jilford ('01), in a splendid succinct
review of tlu' literature gave 28 cases. Hi of whi<h he regarded
as nndoubteil and 12 as ]>robalile. Koclie {'02) accepted only
12 ca.<es. Filth {'02) accepted 21. Kantorowicz {'04), using
the criteria of I.,eopold {'99), together with a microscopic
examination as a basis, groujied the cases in the literature a
94
[No. 338
certain, probable, and uncertain. He considered 17 as certain,
10 as probable, and 13 as uncertain. And to the 17 cases
regarded as certain by him, Kantorowicz then added two of his
own, basing his decision, however, mainly upon the presence
of deeidua in the ovaries, thus making 19 cases regarded as
authentic by him. Freund and Thome ('06) regarded 23 of
all the cases reported up to that time as certain. Norris ami
Jlitchell ('08) considered 16 as positive, 15 as probable and !)
as fairly probable. Warbanoff ('09) collected 3-t cases and
iSTorris ('09) regarded 19 of those contained in the literature
of the previous decade as positive; but Williams ('10), from
a critical review of the literature up to 1906, and upon tlic
l)asis of the criteria of Spiegelberg, regarded only 13 as positive, 17 as highly probable, and 5 as probable. Mapes ('14)
collected 30 cases, but wholly from secondary sources, and
Lockyer ('17) 42, from the years 1910 to 1917. Of these eases
Lockyer accepted 22 as authentic and 20 as questionable ami
undecided from the evidence available to him.
This short summary suffices to show that there is as yet
no consensus of opinion as to what constitutes an ovarian pregnancy. Although this fact finds its explanation partly in our
lack of sufficient knowledge, it is due also to the meagerness of
some of the reports. Besides, if complete disintegration and
lysis of intraovilrian conceptusps can occur, then it must always
remain a. question of opinion in the future wliether some of
the cases so rejiorted really were or were not true ovarian
jiregnancies. This must remain true no matter how thorouuh
the microscopic examination, unless the clinical history or
changes in the maternal organism can afford us crucial tests in
such cases.
Anyone who reads far into the literature of ovarian pregnancy also nnist become aware of the fact that even very
recently skepticism has been carried too far. Jacobson ('08),
for example, placed the case of Ivouwer-van Tussenbroek (a
ease which finally convinced Bland-Sutton) and that of
Webster ('01) in the doubtful class! Furthermore, .Tacobson
also insisted upon the presence of an cndiryo or fetus as absolutely essential.
It must be emphasized, however, that even a liberal attitude
on the part of a reviewer would not justify him in accepting
all cases reported as genuine upon the basis of the reports
themselves, for they — especially the older ones — often are too
meager to enable one to form a reliable opinion. This is
illustrated also by such recent reports as those of (iarrard
('16), Martin ('17), Sweeney ('17), and of Mills ('17).
Although it must he remembered that from the very nature of
tilings it sometimes is impossible to make a report which in
itself carries conviction, it is regrettable that in a niunber of
relatively recent cases in which such a report apparently could
have been made, this was not done. ^lills' case seems to have
been an instance of ovarian implantation in a region other
than the Graafian follicle, and hence recalls the first ease of
Granville and the cases of Franz ('02), Norris ('09), Paucot
et Debeyre ('13)?, and perhaps also that of Kouwer ('97)
(van Tussenbroek, '99).
From evideiu'e contained in the literature, it is clear that
further re|)orts of single cases are not needed for the purpose
of emphasizing the occurrence of ovarian pregnancy, yet such
reports nevertheless may help in the determination of the
relative frequency of this novel and sinister condition, and
also throw further light upon its genesis and the finer relations of the implantations, as well as upon other matters.
Moreover, since the cases which are accompanied by a careful
histologic examination and wliich for this reason alone are
wholly unequivocal from an anatomic standpoint still are
relatively few, the report of an additional case would seem to
be justified. The present specimen (Carnegie Collection, No.
1322) was donated by Wynne to the Department of Embryology of the Carnegie Institution of Washington, and the
following clinical report furnished by him :
CLINICAL HISTORY
Gy.n. No. 22303. — The patient, an Italian woman of 37 years, was
admitted to, the Gynecological Service of The .Johns Hopkins Hospital July 12. 1916, complaining of pain in the lower abdomen,
nausea and vomiting.
Famil)/ History. — Negative.
Past History. — General health good. She has never had any
serious illness. For the past five years following a labor she has
had recurring mild attacks of pain in the abdomen without nausea
or vomiting.
Menstrual History. — Always regular every month except when
pregnant or lactating. Duration four to five days; painless, moderate flow. Last period ,Iune 25, 1916. Last preceding period
March 16, 1916. No intermenstrual bleeding before present illness.
Marital. — Married IS years; seven children, oldest 16, youngest
born IVa years ago (died. 1915). Has had three miscarriages.
History of labors and puerperia vague.
Present Illness. — Began five days ago (July 7, 1916) with sudden pain in lower abdomen, nausea and vomiting. She has had
marked dysuria and painful defecation. For 12 hours after onset
there was rather profuse bleeding from the vagina and there has
been a bloody vaginal discharge since.
(The patient does not understand English and her husband
acted as interpreter. )
Physical Examination.— T. 101.6° F. P. 96. R. 20. W. B. C.
8400. Hbg. 46 per cent.
The patient lies in bed grunting with pain. The skin is pale.
The lips and raucous membranes are quite pale. There is a systolic
blow heard at the apex and increasing toward the base, being
loudest over the pulmonic area.
A drop of clear fluid was expressed from the right breast.
The abdominal respiratory movements are limited, although she
does not complain of pain on deep inspiration. The flanks bulge
somewhat. There is no demonstrable movable dulness. There is
tenderness all over the abdomen, most marked over the lower left
quadrant. There is increased resistance over the lower abdomen,
but no muscle spasm. No masses can be made out.
There is a profuse bloody vaginal discharge. The cervix is
pushed up behind the symphysis by a soft, exquisitely tender mass,
filling the cul-de-sac. No crepitus is made out. Rectal examination confirms the vaginal. The fundus of the uterus is not felt.
July 13. Ifiia. — Ether examination.
There is a dark, bloody discharge from the vagina. There is no
vaginal cyanosis. The cervix is lacerated, firm, and normal in
size. The fundus of the uterus is about normal in size and is in
anteposition. A boggy mass fills the cul-de-sac and to the right of
the uterus a fairly firm mass, the size of a small orange, which is
somewhat movable, can be felt. Definite blood-clot crepitus can be
felt on rectal examination.
Pre-Operative Diagnosis. — Extra-uterine pregnancy, ruptured.
Operation (Dr. W. R. Holmes, Resident Gynecologist). — A free
midline Incision was made below the umbilicus. The peritoneum
Al-KIL. I'.IUtJ
95
was blood-stained. The abdomen contained 200 to 300 c. c. of
dark fluid blood and clots, and a large clot filled the cul-de-sac.
Active bleeding had ceased. The left tube and ovary were normal
and free of adhesions. The ri,i;ht tube, which was quite normal in
appearance, lay over a mass which had replaced the right ovary.
This mass was roughly spherical. 5 to 6 cm. in diameter and semisolid in consistency. Over the surface there were six or eight
nodular projections, about 1 cm. in diameter, .^t the top of one
of these projections there was a very small opening, from which
bloody fluid could be squeezed. The surface of this mass was
white with spots of bluish-black discoloration.
The appendi.x was normal except at the lip. where it was adherent to a blood-clot.
The tumor was removed by clamping, tying, and cutting into
the^ right iiifundibulo-pelvic ligament and the right utero-ovarian
ligament. The right tube was not removed. The appendix was
also removed and all blood and clots were cleaned out of the
abdomen. The incision was closed without drainage. At the close
of the operation, the uterus was curetted. The uterine cavity
measured 7.5 cm. in length.
A subcutaneous salt solution infusion was started on the table
and continued on the ward until 2000 c. c. had been absorbed.
The patient was in good condition at the end of the operation
and made an uneventful recovery.
The urinr on admission contained red blood cells, white blood
cells, no casts, acetone, a trace of albumin and no sugar. Several
days after the operation it was negative, except for a faint trace
of albumin.
August J, V.Hi't. — Discharged in good condition.
Oyn. Path.. \o. i^.?}'i". — Normal endometrium from curettage.
A letter from the patient dated February 12. 191S. said that she
had remained in good health since the operation and had given
birth to a full-term child January 29. 1918.
Several features in this cliuit-al history ikviTvo coninu'iit.
First amoii<^ these is the menstrual a<;e as eoni|)ared witli the
size of the chorionie vesiele. Since the eross-seetions of t!u'
latter measure 15 x 18 mm. and since it and the amnion are
degenerateil and devoid of an enihryo, it is evident that the
latter must have <lied a jjood while before the time of o|)eriition. Hence, the menstrual period rei«)rted for June 25, l!)l(i.
very evidently wa.s not the lii.it period before prejrnancy supervened, but the lirst jteriod which recurred after the death of
the coiHej)tus. Consequently, tiiis prejrnmuy undoul)tedly
dates from near April 13, the time of the first omitted period.
Moreover, the conceptus must have died long enough before
Jtine 25 to have niatie iidiiltition of the succeeding period impossible. It shoidd lie noted, however, that the original
menstrual cycle n f) pure nil i/ was broken, for with the customary inter-menstruar period of 28 days, menstnuition normally would have fallen due on June 7 instead of .June 'i'>.
Hence, the mainteimnce of the original cycle woidd have
brought rufiture of this ovarian pregnancy, as indicated liy the
symptoms, on July 7. in direct relation with the on.*et oi
menstruation. Nor does it seem unlikely that the hyperemiii
accompanying the return of menstruation on June 25, if sudi
it really was, may have been jiartly responsii)le for the on.<el
of a sufficiently large and persistent hemorrhage to cause tiie
slight rujiture indicated by the symjitoms on July 7. It must
also be rcmembere<l in this connection that cases of ovarian
()regiiancy have been reported in which menstruation was
uninterrupted. But in the ca.«o of Chiene ('13), fi>r example,
the death of the conceptus may have occurred .«o early that tli''
succeeding period was not inhibited, and the same thing may
be true of the case of Lea ('10).
Since the material from the curettage, done al ihc time of
operation, showed the presence of a normal endometrium, the
uterine deeidua as.sociated with this ])rcgnancy nnist have been
shed some time jireviously. Such a conclusion also woulil
seem justified iiy the condition of the conceptus. which apparently was unai)le to |)revent a return to the normal. Tinabsence of deeidua at the time of operation al.^o suggests thai
what was re|)orted as a return of imrmal menstruation on
June 25 may have iiecii licniorrhage accompanying the expulsion of the deeidua.
Since, in the present ca.-:c, the .iKiriunic vesicle was so
degenerated and .<o completely isolated in a large clot, and
especially since no well-iin|)lanted villi were found in the
.sections and gross jiortions examined, it is not at all jirobahle
that the hemorrhage that caused the rupture \va.< due to a
contemporaneous invasion of the ve.-ssels by the fetal trophoblast, such as occurs in uterine and tubal im|ilantations, and
as has been actually described also in ovarian implantations
by Franz ('02) and by others. In the present, and in similar
cases in the literature, it would strm that hemorrhage was
made jiossihle also by degenerative changes in the highly
va.«cular stroma of the ovary which ha<l been greatly com|ircssed and stretched by the proportituiately large blooddot, the organization of whieli would seem U> iiare been precluded by its size alone.
The fact that relatively few unruplured ovarian pregnancies
are recorded suggests that the old tenet that rupture is le.>is
likely the more advanced the jiregnancy becomi-s. probably is
open to .serious doubt, as suggested by Hanks ('12), who
bclievetl that the lubes can accommoilatc themselves more
readily than the ovary. Hanks stated that in the majority of
cases of ovarian jiregnancy rupture occurred in the lirst two
or three weeks, and Caturani ('11) also cxjinwed doubts
regarding the dictum that rupture of the ovary is lc.«s likely
the more advanced the pregnancy. .No one will di'ny, 1 prc.sume, that the .symiitoms of rupture nniy have been totally
absent, as rejiortcd in the ca.^es of .N'nrris ('OK) ami (Jrimsdale
('13), but this does not imjily that the ovarian stroma or the
germinal cjiithcliuni still surrounded the lull-term i-onceptus.
Such an occurrence would be possible only if tlu' ovarian
stronni and the overlying germinal c|iithcliinn undi-rwent an
astonishing hyperplasia. Although such a thing is conceivable
it is decidedly significant that no one has reported any such
finding or observed the presence of mitotic figures.
Insteail of undergoing hyperplasia the ovarian .stroma in
this ca,«e is found invaded, stretched, compre.<.-<cd, anil degenerate, and the germinal epithelium is entirely absent. The
fact that several observers have seen what they took for the
fibrin layer of Xitabuch also shows that degenerative changes
in the ovarian impbinlations may be extensive. Heur-e, it
would seem to follow that the absence of symptoms of rupture
merely nniy mean that the ovarian stroma and epithelium
which ha|ipcned to overlie the fetal membranes gradually
have died and degenerated before being forced apart by the
expanding conceptus or the increasing hetnorrhage. That such
96
[No. 338
a sequence of events is possible would seem to be undoubted,
and merely distension of the ovarian stroma until it com])letely
surrounded a full-term pregnancy ' is hardly conceivable ;
whereas, the absence of pain upon the yielding of an exceedingly thin degenerate layer of ovarian stroma is quite
conceivable.
That rupture may occur very early is exemplified also by the
cases of Chiene ('13), Seedorff ('15), and especially by that of
Aiming and Littlewood ('01) and of Holland ('11). In such
curious instances as that of Grimsdale ('13) one can hardly
assume that the ovarian tissue was preserved about the entire
.•onceptus, and it is not at all unlikely that full-term ovarian
]iregnancies, which, according to WarbanofE, supplied a sur])risingly large percentage of all cases collected by him, will
form a far smaller percentage in the statistics of the near
future. Indeed, they already form a far smaller percentage
of those reported up to the present, and the advances in diagnosis alone make it very imlikely that in the future many
cases of ovarian pregnancy will advance far before being
detected.
The present specimen, which had been hardened and cut
before it came to my attention, is a firm, nodular, dark-colored
mass, 26 X 16 X 11 cm., shown in Fig. 1. In the gross, it
especially recalls the specimens of Freund and Thome, Giles
('14-'15), Jaschke ('15), and Lockyer's ('17) second case.
The exterior is smooth though bosselated and formed by a
rather injected layer which is extremely thin, showing tlie
blood-clot beneath, aroimd the greater extent of the specimen.
The surface layer is eroded over several small elevated areas
in which the blood-clot imderneath is exposed. Hence, the
capsule may have been ruptured in several or only in one ol'
the areas as noted at the time of the operation. Xear the
region of amjjutation through the mesovarium shown to the
right in the figure and marked by the corrugations of the
hemostat, the tissue overlying the clot becomes more opaque,
thicker, and also more yellowish. Here it is studded with
small cysts, the character of which in itself suggests ovarian
tissue. The color of the area to the right also is suggestive,
and the cysts later were foimd to contain a clear viscid fluid,
so characteristic of cysts of the ovary. The location of the
main portion of the ovarian stroma shows that implantation
occurred near the mid-point of the free convex or posterior
border of the ovary, and that the stroma forming the sides
gradually was forced apart, not by the growing conceptus,
except perhaps at the lieginning, but mainly by the liemorrhage itself.
The major ]iortion of the surface of the divided specimen
shown in Fig. 2 is composed of blood-clot, the presence of
which confirms the " blood-clot crepitus " spoken of in the
history. This clot contains an empty vesicle, the wall of
which is formed for the greater part of its extent by a thin
fibrous layer, except near the proximal or lower portion in the
figure, where a thicker portion of ovarian tissue hoods the
clot. Approximately only about one-third of the ovarian
stroma seems to be preserved.
Xear the exterior of the thicker portions of the latter, a
small cvst with clear +++++
CONTENTS is fomid directlv beneath the
surface, as indicated in Fig. 4. The distal or upper portion
in the figure shows the clot to contain an empty, smoothwalled, degenerate chorionic vesicle, such as is frequently
seen in tubal clots.
Examination of the cut surface with the binocular microscope shows the presence of only a few isolated, degenerated,
and some hydropic villi scattered through the clot. Examination of the chorionic vesicle shows the presence of only a few
attached villi and that the amnion is fused to the chorion.
Since the entire sjjecimen obtained at operation is still covered
by a layer of ovarian tissue which is unbroken save in a few
very small areas, it is e^ddent that we are dealing with a very
good example of an undoubted ovarian pregnancy in spite of
the absence of an embryo. The latter undoubtedly did not
escape through the small rupture in the capsule, for the
chorionic vesicle seems entirely intact. Although the absence
of a corpus luteum in the opposite or left ovary was not
especially mentioned, lack of comment would seem to suggest
that none was present, for the ovary very evidently was
examined. Hence, this implantation probably took place
within the Graafian follicle itself, and not in some other area
of the ovary.
Celloidin sections of the excised portion show that the bloodclot contains no fibrin and that it is composed of relatively
fresh and fairly well-preserved blood in the region near the
main body of the ovarian stroma. The latter is quite normal
although decidedly vascular, and contains ova. The layer of
the ovarian stroma which surrounds the clot becomes thinner
and thinner the nearer the free border is approached. It also
becomes more trabeculated, hemorrhagic and degenerate. No
overlying layer of smooth muscle, as mentioned by Yoimg
and Rhea ('11) and also by Kantorowicz, was seen. Some
infiltration with pohauorphonuclear leucocytes is noticeable.
Degenerate villi are scattered about in the blood and a few
others are apparently still attached to the equally degenerate
ovarian stroma. Trophoblast is absent on these, although
some of the villi that lie isolated in the clot possess a very e\\dent epithelium and also are associated \\'ith a few small
masses of very degenerate syncytium. Only a few degenerate
nonvascular vilU are still seen on the chorion. Very little
evidence of epithelial proliferation is present on these, despite
the fact that the blood in which the vesicle is eml^edded is not
very degenerate. This seems to suggest that the hemorrhage
wliich caused the rupture of the ovary was comparatively
recent, although the conceptus had been dead for some time.
Some of the villi scattered about in the blood-clot are outlined
by degenerate syncytium only, and nothing but small degenerate masses of the latter are seen on the chorionic membrane
or lying about isolated in the degenerate blood foimd in other
places. Nevertheless, the epithelium of the chorionic vesicle
is thickened at several points. The amnion is fused -nith the
chorion and both membranes are very degenerate and destroyed
almost completely in several places. The surroimding ovarian
tissue, which is markedly vascidar and degenerate, shows
infiltration in jdaces, especially where it is stretched over the
large clot. No fibrous layer bounds the implantation cavity,
as in the case re]>orted by Seedorff. The ovarian stroma merely
THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL, 1919
Fn;. 1. — External appearance of the reconstituted gross specimen (Carnegie Collection,
No. 152'^). Natural size.
Fiu. 2. — Appearance of cross-section of specimen shown in Fig. 1. X 1.
Fin. 3. — Photograph of a section from a part of the specimen
showing the clot largely surrounded by ovarian stroma and containing the empty vesicle. The arrow points to the portion near
which degenerate masses of what may have been lutein cells
aro found. X 2.
I"i(.. 4 l'liotopra|)h of a section t;il<in from the
thick portion of the ovarian stroma near the mesovarlum, showing a well-developed Graafian follicle.
X 3.
April, 1919]
97
is slightly i-ondenscil here ami thero. and in places contains
areas of hyaline ilegeneratioii, tlie exact origin of which conld
not be definitely determined. A few of these are found near
tile thin bounding layer of the ovarian stroma, hut no lutein
layer or even luteal cells could i)e recognized. Tiie only objects
seen which might be regarded as ])ossibly luteal in origin arc
two microscopic rhoniboidai areas which lie near a small
depression upon tiie surface, indicated in Fig. 3. The.se areas,
which were covered by a very thin layer of ovarian stroma
only, were made up of parallel, ilegenerate, slightly separated
cords consisting of a syncytium containing numerous rather
pycnotic unequal-sized nuclei. No pigment was seen in these
areas, and were it not for the arrangement of the syncytia!
cords, one would not be reminded even remotely of a ])ossil)le
luteal origin. Although the germinal epithelium was wholly
absent in the areas examined, these questionable areas nevertheless may have had such an origin. In the absence of lutein
cells the present ca.se corresponds to that of Freund and
Thome luid others, and stands in marked contrast to the ca.se
• if van Tussenbroek, Franz, Anning and Littlewood ('01 ) and
Thompson ('0^). As in the tase of Seedorff, no decidua was
jircsent and nothing suggestive of an attempt at decidual
formation, as rejwrtcd by Franz, Webster ('04 and '07), and
by Caturani and Kantomwicz, was seen in the jiortioiis
examined.
In describing his ca.se, .Sccdorif declared that in some places
"f c-ontact between the fetal and maternal tissues he could
not discriminate between trophoblast and connective-ti.ssue
cells which looked like decidual cells and lutein cells. It is
interesting that Sudortf al.«o spoke of villi which were almost
Idled with Langhans' cells, an observation which naturallv
makes one wonder whether by any possibility these cmdd not
have been Ilofbauer's cells.
The pre-served ovarian tissue which was found near the
amputation stumji contained hemorrhagic follicles, as observed
al.so by Mall and fuUen ('13). A Graafian follicle 3 mm. in
section, shown in Fig. 4, protruded above the rest of the
.-troma ajid was quite mature. The presence of this follicle
might be taken as an evidence of the occurrence of ovulation
during pregnancy, were it not for the fact that the pre'sence of
so degenerate a conceptus shows that as far as any effect u|)oii
the maternal organism was conc-erned, the pregnancy virtually
had been terminated long before. That both ovulation and
menstruation can and do return after the death of an ovarian
conceptus, but before its removal from the ovary, is illustrated
also by ca.ses in the literature, especially by that of Xorri^
('09). One must assume, however, that few, if any, surviving
fetal element.* can be present under these circumstances. This
concliLsion also would seem to lie confirmed by the remarkable
case of Sencert and .\ron ('14). These authors reported a
case of ovarian pregnancy in which nothing but a portion of an
umbilical cord ."> mm. long containing Wharton's jelly, two
arteries and a vein, and what was regarded as a placenta,
remained. The latter was said to be composed of a narrow
layer of plasmodiuni and a much thicker layer of trabeculat..!
syncytial trophoblast containing blood between the trabecula-.
Because of the singidar structure of this placenta and also
because of the failure to find villi or any remnant of the
membranes, the authors concluded that the chorionic vesicle
therefore could not ha\e reached the villous sUige. How such
a supposition can be reconciled with the survival of a portion
of an umbilical cord entirely nornnd in structure, it is dilHcult
to see. The ovary concerned was brown, of the size of a " large
fresh walnut," and contained a tumor, apparently the socalled placenta, which was 2 cm. in diameter. Although these
fetal remnants had brought about not only almost complete
amenorrhea for two years and also atrophy of the ovary and
uterus, ablation of the affected ovary was followed not onlv
by a return of the menses, but by a normal pregnancy within
.seven months.
A sec-ond instance of ovarian pregnancy of sjiecial interest
was that of Giles. Xo fetus was found, although the jtregnancy was unrujitured, and Giles estimati'd that the conceptus
had died in the third or fourth week. The operation was not
done until five months after the onset of the pregnancy. What
is particularly interesting in this case is that Giles s])eaks of
the mucoid degeneration of the connective tissue of the villi.
The latter were found to be large, much branched, and had
ramified in the clot. Since Giles also spoke of one of the
illustrations as showing a vascular state of some of the villi,
it seems possible that this was a case of hydatiform degeneration, even though there were no signs of activity of the syncvtium. Since the fetal membranes were isolated in a bloodclot very much degenerated and the villi without a Langhans'
layer, one scarcely could exi)cct to find much evidence of
epithelial jiroliferation .so common (but not essential) in
hydatiform degeneration. Giles estimated that four months
had elapsed since death of the conccptu-s, and if this specimen
really was a hydatiform degeneration, it is the first one
observed in ovarian ])reginincy and hence of particular interest
for this reason alone.
REFERENCES
Anderson, S.: 1917 Primary ovarian sestation. Intern. Clin.,
XXVII, ser. 2.
Anning, G. P.. and Harry Littlewood: 1901. Primary ovarian
pregnancy willi rupture 14 days after last menstruation. Trans.
Lond. Obst. Soc, XLIII: and Lancet. 1901. I.
Banks, A. G.: 1912. A case of ovarian prcRnancy. .Tour. Obst.
and Gyn. Brit. Emp.. XXI.
Caturani. M.: 1914. Ovarian pregnancy with report of a case.
Am. Jour. Ob.st.. XLI.X.
Chiene, G.: 191:!. A case of raptured very early primary
ovarian pregnancy. Edin. .Med. Jour., N. S.. X.
Engelking, Ernst: 19i;{. Intraligamentar entwickelte Eierstockschwangerschafl. Eln Beitrag zur anatomlschen Dlagnoatlk
vorgeschrlttener Falle. .Monatschr. f. Gcb. u. Gyn.. XXXVII.
Franz, K.: 1902. Teber Einbottung und Wachstum des Eies Im
Elerstock. Beitr. z. Geb. u. (Jyn.. VI.
Fraenkel, L. : 1903. Die Function des Corpus luteum. Arch. f.
Gyn., LXVIII.
Idem: 191ii. Noue experlmente zur Function des Corpus
luteum. Arch. f. Gyn., XC.
Fiith. H.: 1902. Ueber Ovarialschwangcrscbaft. Beitr. z. Geb.
u. Gyn., VI.
98
[No. 338
Freund. H. W., u. R. Thome; 1906. Eierstockschwangerschat't.
Arch. f. path. Anat., CLXXXIII.
Garrard, J. I.: 1916-17. A probable case of ovarian pregnancy.
,Tour. Med. Assn. Ga., VI.
Giles. A. E., and C. Lockyer: 1914-15. Case of ovarian pregnancy. Proc. Roy. Soc. Med. Lend.. VIII; Obst. and Gyn.,
Sect. 2-10.
Gilford, Hastings: 1901. Ovarian pregnancy. Brit. Med.
Jour., II.
Idem: 1S99. Two further instances of extra-uterine (one tubal
and one ovarian) gestation in which rupture occurred before the
first month; operation. Lancet, I.
Granville, A. B.: 1820. A case of a human fetus found in th.^
ovarium of the size it usually acquires at the end of the fourth
month. Philos. Trans. Roy. Soc. Lond., Ft. 1.
Idem: 1834. Graphic illustrations of abortion. J. Churchill.
Lond.
Grimsdale, T. B.: 1913. Case of ovarian pregnancy with fulltime fetus. Jour. Obst. and Gyn. Brit. Emp., XXIII.
Holland. E.; 1911. A case of ovarian pregnancy; probably
bilateral. Jour. Obst. and Gyn. Brit. Emp., XX.
Jaschke, R. T. ; 1915. Ovarialgraviditat mit wohlerhaltenem
Embryo. Ztschr. f. Gebh. u. Gyn., LXXVIII.
Jacobson, S. D.: 1908. True primary ovarian pregnancy ; operation; recovery. Contributions to the Science of Medicine and
Surgery, N. Y. Post-Grad. Med. Sch. and Hosp.
Kantorowicz, Ludwig: 1904. Eierstocksschwangerschaft.
Samml. klin. Vortr.. Volkmann, N. F., Nr. 370, Gyn. 136, Leipzig.
Kouwer, B. J.: 1897. Ein geval van ovarlalzwangerschap
(zwangerschap in ein Graafschen follikel ) Nederl. Tijdschr. v.
Verlosk en Gynaec. Haarlem, VIII.
Lea, S. W. W. : 1910. A case of ovarian pregnancy with diffuse
intraperitoneal hemorrhage. Jour. Obst. and Gyn. Brit. Emp.,
XVIII.
Leopold. G. : 1882. Ovarialschwangerschaft mit Lithopadionbildung von 35-jahriger Dauer. Arch. f. Gyn., XIX.
Idem: 1899. Beitrag zur Graviditas extrauterina. Arch. f.
Gyn., LVIII.
Lockyer, C. : 1916-17. Two cases of primary ovarian pregnancy,
with a review of the literature 1910-1917. Proc. Roy. Soc. Med.
Lond., X; Sec. Obst. and Gyn.
Mall, F. P., and E. Cullen: 1913. An ovarian pregnancy located
in the Graafian follicle. Surg., Gyn. and Obst., XVII.
Mapes, Chas. C: 1914. Ovarian gestation — being principally a
review of the literature. Amer, Jour. Surg., XXVIII.
Martin, R. S.; 1917-18. Three interesting cases. Va. Med. SemiMonthly, XXII.
Mills, H. M.; 1917. Probable ovarian pregnancy. Am. Jour.
Obst., LXXVI.
Meyer, A. W. : 1919. Uterine lysis, tubal and ovarian, and
resorption of conceptuses. Biol. Bull., XXXIII.
Norris, C. C: 1909. Primary ovarian pregnancy and the report
of a case combined with intra-uterine pregnancy. Surg., Gyn.
and Obst., IX.
Norris, C. C, and C. B. Mitchell: 1908. Primary ovarian pregnancy with report of a case. Surg., Gyn. and Obst, VI.
Paucot, H., et A. Debeyre: 1913. Etude sur les grossesses
ovarlennes jeune. Ann. de Gynec. et d'obst. 2s, t. 10.
Roche, J.: 1902. De la grossesse ovarienne. These de Lyon.
Scott, N. S. : 1901. Ovarian pregnancy; is it an explanation of
ovarian hematomas? Am. Med.. II.
Seedorff, M.: 1915. Ein Fall von geborstener Ovarialgraviditat.
Monatschr. f. Geb. u. Gyn., XLII.
Sencert, L., et M. Aron: 1914. De Tindependance qui existe
entre le development du placenta et celui de I'embryon (t propos
d' un cas de grossesse ovarienne.) Bibliog. anat., t. 24.
Spiegelberg, Otto: 1878. Zur Kasuistik der Ovarialschwangerschaft. Arch. f. Gyn., XIII.
Sweeney, Thompson: 1917. Ovarian pregnancy. Med. Rec,
XCII; Am. Jour. Obst., LXXVI.
Tussenbroek, van, Catherine: 1899. Un cas de grossesse
ovarienne (Grossesse dans un follicule de Graaf). Ann. de gyn.
et d'obst., t. 52.
Thr same: 1899. Ovarialschwangerschaft (ein Fall von
Schwangerschaft in einem Graafschen Follikel). Intern. Gynak.
Kong. zu. Amsterdam; Centralbl. f. Gyn., XXIII.
Thompson, J. F. : 1902. Ovarian pregnancy, with report of a
case. Trans. Am. Gyn. Soc, XXVII.
Warbanoff. Peter: 1909. Ein Beitrag zur Graviditas ovarica.
Inaug. Dissert.. Miinchen.
Webster, J. C: 1904. Study of a specimen of ovarian pregnancy.
Am. Jour. Obst., L.
Webster, J. C: 1907. A second specimen of ovarian pregnancy.
Trans. Amer. Gyn. Soc, XXII.
Werth, R.: 1887. Beitrage zur Anatomie und operativen
Behandlung der Extrauterinen Schwangerschaft. Stuttgart.
Werth. R.: 1901. Ovarialschwangerschaft. Handb. der Geb..
von Winckel, Bd. II. Th. 2, Wiesbaden.
Williams, J. W. : 1910. Ovarian pregnancy. Gynecology and
abdominal surgery, Kelly-Noble, Phil, and Lond.
Idem: 1917. Obstetrics; A text-book for the use of students
and practitioners, N. Y. and Lond.
Young. E. B., and L. J. Rhea: 1911'. Ovarian pregnancy. Report
of a case. Bost. Med. and Surg. Jour.. CLXIV.
GRANVILLE SHARP PATTISON
By AVii.Li.VM .Sxdw iliLLEE, University of AViscoiisin
Gro.ss, in his biojiraplucal sketch uf Pattison, say,< :
It is no exaggeration to say that no anatomical teacher of his
day, either in Europe or in this country, enjoyed a higher reputation; his forte as a teacher consisted in his knowledge of visceral
and surgical anatomy, and in the application of this knowledge to
the diagnosis and treatment of diseases and of accidents, and to
operations.
Being a man ui' iiitunsc feeliiii;' and .-^tvoni; pn-juiHces he did
not easily brook oppositimi. Because of tlic^e characteri.sties
'Read before The Johns Hopkins Hospital Historical Club. December 2, 1918.
tlie early years of his career were stuvniy and his reputation as
a teacher was fully acquired only after many bitter controversies, one of which was so acrimonious that it was fought out
on " the field of honor."
The year of Pattison's birth is usually given as IT!)], Imt he
says in his " Refutation," addressed to Dr. Nathaniel Chajinian, of Philadelphia, under date of November 28, 1820, " 1
shall soon enter on the 28th year of my age " ; this ap]>areutly
makes 1793 tlie more correct date. He died November 12.
18.52, after a short illness, of nlistrtictiim of the ductus eonimunis choledochus.
THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL. 1919
GRANVILLE SHARP PATTISON.
Courtesy of Dr. J. M. H. Rowland.
THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL, 1919
PLATE VIII
7i V
NATHAMEL CHAPMAN.
Courtesy of Dr. Howard A. Kelly.
April, 1919]
99
Granville Sharp Pattison was the youiijjest sou of John
Pattisoii, of Kelvin Grove, Glasgow. Of iiis early eilueatioii
we know nothing eseept the statement tiiat he was probaliiy
edueated at the I'niversity of Glasgow. That he was a hanlworking student is shown by his being, when hut 18 years old.
assistant to Allen Burns, and on the death of Burns, in 181:!.
l)ec<)niing his suecessor to the Chair of Anatomy, I'hvsiology
and Surgery in the Andersonian Institution, a recently organized medical school in Gla.'Jgow. Here he made quite a reputation as a lecturer, and had it not been for his naturally
indolent nature and love of ea.se, would, no doubt, have attained
in his later years preeminent re]iutation as an anatomist.
In Novend)er, 181S, charges were brought against him liy
Dr. Ure. one of his colleagues, of having committed adultery
with his wife, and a divorce was obtained by Dr. I' re on that
ground. The divorce laws of Scotland were at that time
iwpuliar; all divorce |)roeedures were brought in the consi.story
court, which was an ecclesiastical organization. It was not
newsisary that the parties charged with adultery liad ever seen
each other ami the reputed paramour might not have ever
existed. In any event, the accu.«ed ])aramour could not appear
and defend himself. If the husbaiul obtained a divorce from
his wife on the ground of improper conduct, he could immediately bring a .<econd action for damages and the accused
party could then appear in court and endeavor t" disprn\r
the charge.
This second action was never instituted by Dr. I'rc. .Vftcr
the arrival of Pattison in this country. Dr. Ure attemjitcd \<y
publish an octavo volume dealing with the case. One of liis
witne.s.ses, however, having confessed that her declaration was
false and that she had been induced to make her statements
by means of threats and i)ribcs. Dr. Ure suppre.s.sed the volume,
for he could not sustain his charges, and had he attempt^'d
under the.<e circumstances to circulate the publication he
would have subjected himself to criminal prosecution. This
epi.sode was unfortunate for Pattison and it j)layed an im|)ortant role in the turbulent years which f(dlowed : for,
although generally known to be luifounded, many venrs
cla])sed before it ceased to be recalled.
In Glasgow the charge was generally discredited, for Dr. L r.
did not poss<'ss an enviable reputation ; in fact, a statement is
made that he barely escaped transportation to Botany Bay
" for fraudulently stealing and destroying his father's will."
In spite of this accu.<ation Dr. Ure retained his position in the
.Vndersonian Institution. Pattison explains the situation in
the following statement :
The Andersonian Institutinn of which Dr. I're is a member is
an establishment of late date. The funcis which were ol)tain>(l
for the erection of its buildings were procured by sul)scrlptioii :
and as Dr. fre was very active, at the time when the niom-y was
raised, in obtaining it. an(i gra<ite<l to the subscriber of t20 :i
perpetual ticlcet of admission to one of the courses of his lectures,
it has become a question, wliether the money was bestowed on
him as an Individual, he granting personally an equivalent, or to
the Corporation of the Institution.
When Dr. Cre. about six years asio. fraudulently stole his father s
will for the purpose of defrauding his family, an attempt was niadi
to expell him from the institution: but as the Trustees, upon taking advice, learnt that his expulsion would involve them in a
tedious liti!;ation. a litigation which would require to be carried
on by money advanced by them as individuals, the attempt was
abandoned.
IJejdying tu tliis. Dr. t'liapman shows that the institution
was incorpordtctl on June !t, Kyti; when the buildings were
ready for occu])ation he does not state, but he docs infer that
Pattison was guilty of a misstatement in that he considered an
in.stitution 21 years old as an " fstabli.shment of late date."
The founder of this Institution was .lohu Anderson, a Scottish
naturalist, who in his will provided I'or its establi.shment; he
died January 13, 17!)6, and the incorixtration on .lune 9, 1790.
was undoubtedly the first step in carrying out tiie iirovisions
of the will. The mcclical dc|)artnicnt gave its (irst courses in
1799.
Dr. Chapman attempts to offset the stateinciit in regard to
the will of Dr. Fre's father by saying:
.\'ot long before he came to this country. .Mr. Pattison was tried
for a felony, in stealing a body from the grave Mr. Pattison
merely escaped from want of evidence that he had taken the
clothes of the deceased: the part of the offence most penal under
the Scotch law.
In this instance Patti.son was in the lii>i nf cinnpany. for
.Tohii Hunter. Sir .\stley Cooper and nearly every teacher of
amitomy up ti> the ])as.<age of the "Anatomy Act" in ]S.i2.
might with more or less justice be termed an " acquitted
fellon."
The occasion of Pattison's coming to Pliiladclpbia was the
e.xpectation of occtijiying the Chair of .\mitomy in the Medical
Departnu'iit of the I'niversity of Peinisylvauia. nuide vacant
by the death of Profes.sor Dorsey and temporarily lilled i)y
Prof. Philip Syng Physick. That he was given to understand
before leaving England tiiat the position was ojicn to him is
certain, but that this was unofficial is also certain.
On Deceml)er 24. 1818, I'attison received a letter from his
In-other, .lohu Pattison, who at that tiiue resided in Philadelphia, in which he .states that his legal adviser. Mr. Chauncy.
agreed with him that there was an opportunity for a man of
talent lo be appointed to the |)osition left vacant by the death
of Dr. Dorsey. The fact that he was a foreigner was certainly
against him. but he was " inclined to think tiiat the trustees
will be more guidecl iiy talent, than l)y any otlier consideration." He advised that letters be obtained from Astley Cooper
and others and " you had better say the extent of your museum.
etc.. wiiich I know Mr. Bnrns considered invaluable."
liider date of April 20. 181!l. Dr. Dcwees. of Philadelphia,
wrote Pattison a letter which eonlained the following statement :
I have, contrary to any right, taken the liberty to advise upon
the subject. As far then as a firm belief that you would succeed
(and that belief founded on pretty certain data) will offer an
inducement lo pay us a visit, I have no hesitation to declare, that
no question remains In my mind, that were you on the spot, your
election would he certain. It Is unquestionably the opinion of two
of the most intlucntial and best informed men here. Your visit
should be as prompt as possible, that you might have the necessary
time for the preparatory arrangements here. .My opportunities
100
[iS'o. 338
to judge of the sentiments of those, who have this gift in their
power, will be best explained by your brother.
Acting on thi.s advice Pattison arranged his affairs as
qiiickly as possible and sailed from Liver])ool for New York,
where he landed Jnlv 6, and on the evening of Jnly 7. 181 '.i,
reached Philadeljihia.
The two " most infiueutial and best-informed men " referred to above were Drs. Chapman and Physiok. Each of
these denied having authorized the use of his name. ('ha])maii
.states :
The trustees, after postponing the appointment for six months
.... had publicly advertised that they would receive applications
from any quarter. But we soon discovered our mistake — for at
their first meeting which took place not many days afterwards,
when all the testimonials of Mr. Pattison were submitted to them,
so far from a favorable impression being made, these recommendations were treated contemptuously, as extravagant and
hyperbolical — it being quite manifest, that no individual with
halt the merit which they set forth, would sacrifice his actual possessions, to embark in so adventurous a scheme!
Chapman evidently forgot that Philadelphia and the country
in general was peopled with those who had left the old countrv
and settled in this country because they thought that tlu'\
had here an opportunity to improve their condition — that they
were adventurers.
Shortly before sailing, while he was in London, Pattison
Avas made a member of the Medicq-Chirurgieal Society of
London and a Fellow of the Eoyal College of Surgeons. Had
there been the stain on his character which was charged
against him, it seems doubtful if these honors would have
been bestowed on him. The " testimonials " were written by
Prof. John Barclay and Dr. Thompson, of Edinburgh :
Francis Jeffrey, editor of the Edinbvrgh Revieu' : James
Wardrop and Astley Cooper, of London; the Eev. Dr. Love,
of Glasgow, a celebrated clergj-man of the Kirk of Scotland :
Sir James McGregor : Sir William Adams ; and others.
Just at this time there was a good deal of intrigue taking
place in the faculty of the University of Pennsylvania, and
in 1819 Philip Syng Physick,
Yielding up his own better judgment to the schemes of others,
for perhaps the first time in his life, allowed himself to be
transferred — for the act was not of his own choice — from the
chair of Surgery, to that of Anatomy, from the place where he
was emphatically at home, to one in which he was comparatively
a stranger.
Pattison did not accept any appointment in tlie L'uiversity.
though one was offered to him : he also declined a professorsliip in the Transylvania L^niversity at Lexington, Ky. Cha])man makes Pattison's declination of the call to Lexington
appear in a false light and says :
The College, were, moreover, as I am told, justly indignant at
the disrespectful manner in which they were treated, considering
the only motive of Mr. Pattison, in procuring the appointment,
was to have it published as an early recognition of his consequence in this country.
He also states that Dr. Caldwell was furnished witli all of
Pattison's documents, and had a distinct miderstanding with
Pattison that if lie were elected he would accept. If such
«ere the case, Dv. Caldwell would not fail to make mention
of it in his " Autobiography," for such episodes as this are
favorite themes in his narrative. A careful reading of Peter's
" History of the Medical Department of Transylvania University " also fails to reveal a single reference to this incident.
In 1820 Pattison was elected Professor of Surgery in the
University of ilaryland, and he looked forward to leaving
behind him all the intrigue and malevolence he had encountered at Philadelphia, fostered in a large degree by
Dr. Xathaniel Chapman. This did not materialize, for
One of the faculty, a Professor in the University of Pennsylvania!
came to Baltimore immediately after my settlement in that City,
apparently for the purpose of shutting me out from the hospitality
of the citizens, by the most foul, the most malignant, the most
false asperations against my character.
The animosity existing between Pattison and Dr. Chai)man.
who seems to have been the moving spirit in the campaign
against Pattison, soon reached an acute stage and Pattison
issued a challenge to Dr. Chapman, which he did not accept.
This led Pattison to go to Philadelphia, and on October 23.
1850, he put up in two jntblic places the following post:
To THE Pviu.ic
Whereas Nathaniel Chapman, M. D., Professor of the Theory and
Practice of Medicine in the University of Pennsylvania, etc. etc.
has propagated scandalous and unfounded reports against my
character; and Whereas when properly applied to. he has refused
to give any explanation of his conduct, or the satisfaction which
every gentleman has a right to demand, and which no one having
any claim to that character can refuse, I am therefore compelled
to the only step left me, and Post the said Dr. Nathaniel Chapman,
as a liar, a coward and a scoundrel.
Granville Sh^vbp Pattison.
Following tlie European custom Pattison resolved to stay
two days in Philadelphia ; but, he says :
My stay, however, was not long. left to my option I was
arrested at 11 o'clock A. M. of the day on which I had put up the
post. Dr. Chapman denies all agency in the matter, be it so.
When the case came before the grand jury, all the correspondence in the case was furnished by Chapman, and Pattison says :
Perhaps he did this that I might be convicted, in order that an
opportunity might be furnished him of displaying his (lenerosity
and magnanimity, by applying " instantly in person to the Executive " for my " pardon."
In his letter refitsiug to meet Pattison, Chapman gives as
his reason, " tlie character and conduct of Mr. Pattison, as
well in relation to the causes which compelled him to leave
Scotland, as to events which have subsequently happened."
Xot satisfied with this, in Xovember, 1820, Chapman issued
a pamjihlet in which he attempts to Justfy his conduct. To
this Pattison replied in a like manner November 28, 1820.
Pattison " had the good fortune and address to enlist the
sympathy of his colleagues and a large part of the community
in Baltimore in his behalf, and presenting his side of the case
to a committee of prominent citizens, he was exonerated from
all blame."
April. 1919]
101
This was iu)t Chapmiiirs first "affair"; hi- had soim- ycar^:
ln't'oro i-halleii<.''0(l Dr. Dewecs. In rogaril to this alTair ( liii|iiiiau says :
It happened fifteen or sixteen years ago: and if my conduct was
reprehensible. I hope I have since atoned for it, by a friendship
warm, cordial and sincere. What, however, will be thought of tln'
nialiBnity of a man. who thus endeavors to disturb the hnpplnes>
of families, by references of this nature! ! I
Patti.soii r('|ilyili;r to tliis does not |mt (liainnaii in :ni
"•nviahle lijrlit :
I have not a " numerous family," I admit, and here I allow there
is ii distinction. But did Dr. Chapman before he had a family,
when he challenged Dr. Dewees. who had a numerous one. think
this excused him?
The quarrel lietwoon Chapman anil I'attison was finally
taken up hy General Thonuis Cadwalailer, Dr. t'haiimanV
hrother-in-law, and four years after Pattison's arrival in thi>
<Miuntry (IS'iS?) they met somewhere in Delaware. Cailwalader received the ball from Pattison's pistol in his " pistol
iirm " which was disabled thereby durini; the remainder of lii>
life. Pattison was uninjured, " but a ball i)assed tlu-oiii:]i the
skirt of his coat near the waist."
In 1820 Pattison resigned his professorship at Baltimore
and returned to England. Why he resigned a position whiib
with liis professional services he states was bringing him
^10,000 a year is not clear; for, as a teacher, he had a successful record while in Baltimore, and the University ot
Maryland enjoyed its greatest prosperity. On the one liand.
is tile statement that he " led a very gay life " in Baltimore
jind that his health was thereby impaired and that after he
left it was doubtful whether he recovered; on the other hand.
there is Pattison's flat denial and 'Hi additional years of activr
life.
In July, 1827, Pattison was ap]>ointeil Professor of AnatoniN
in the newly organized University of London. Before long Inbecame involved in difficulties, different from those at Philadelphia, but equally disastrous. Pattison was a Scotchman
and had taught in Scotland and "America"; he had iiifroduced as a te.\t-bo(»k Fyfe's anatomy, written by a Scotchman :
he had for his demonstrator a Mr. Bennett, an Englishman.
who had conducted a school of anatomy in Paris which had.
very properly, been refused credit at an English institution :
he had iiicurrecl the displeasure of Wakley, editor of tlu'
f.iincet, who supjjorted Bennett; hut chief of all he was a
Scotchman. If any one doubts the attitude of London at thitime towards Scotchmen let him read Pichot's " Life ami
Labors of Sir Charles Bell " and the " Lett^'rs of Sir Cbiirli Bell " by his brother Tieorgc.
Wakley began his attjick on Pattison by a sharp criticism
of Fyfe's anatomy ; it must be acknowledged, however, that tln'
criticism was justified. Wakley was a friend of the mclii jl
students an<l supported them in most of their comjilaints ami.
|)0ssibly, promptetl .<ome of them. That he was responsible fm
many reforms in medical in.struction and medical i)racticcs ito his credit, and he deserves all the credit accorded to him.
but he sometimes overshf>t bis mark; take, for e.\amj)le, bi
altitude towards Sir Charles Bell, Marsiiall Hall, and .itlu is
who have left an honored name and life work.
On .luly 23, 1831, Pattison was dismissed from Hie Chair
of Anatomy at the I'niversity of London. The events preceding and following his dismissal are full of interest. Clarke,
in his " Autobiographical Recollections of the Medical Pr<ifession," says :
No matter what a mans talents and acquirements might be. he
had little or no chance of advancement at a Hospital, except
through family or money influence. .•\11 the prizes in the Profession were monopolized by those who could pay for them, or who
were fortunate enough to have friends at Court. The apprentice of
the Hospital Surgeon paid a very large premium for his inden
tures, and. as a rule, it was understood, that he was to be placed on
the Hospital staff as part return for his money outlay. This gave
rise to a system of nepotism of the most objectionable character:
Hospital Surgeons were selected, not from the ma.ss of the
Profession, but from the private pupils and relations of the
" staff," ....
To add to the dis+++++
CONTENTS prevailing, there had been (1S27) an
unseemly quarrel at the great Hospital of St. Uartholomew's. in
which .Mr. .-Vbernethy did not bear an enviable part At this
time, too, the establishment of what was then called the " University of London " attracted increased attention to the system
of nepotism The announcement of the names of Professors
of this Institution startled the Profession by the fact that most,
if not all but one of them, were "outsiders"; were not. in fact,
connected with any of the large endowed Hospitals, but were all
of high and deserved distinction.
The first iiaiiie on tlic list given by Clarke is that of
Pattison.
In the is.suc of the Lancet for March .">, 1831, tiiere is a
communication signed " A Senior Student of the London
University" in which an attempt is made to show that Patfison is unworthy of his professorship and that Bennett shotdd
have the position. Much of " Senior Student's " compl.-iint
and most of the student dissatisfaction is based on the fa<t
that Pattison attcmpte<l to enforce discijdine in his cla.ssroom. That Wakley had jirevious knowledge of wlnit was
taking place in Patti.son's lecture room is shown by the following quotation from the above-mentioned communicafioii :
You are already, Sir, aware of the proceedings which were Instituted during the last session by a part of the medical students
against one ot the lecturers upon anatomy, Mr. Pattison.
This communication was replied to by another student, who
signs himself " Veritas," under date of March 7, 1831, and
throws considerable light on the case. One of the charges
brought against Patti.son in the original complaint was "that
the defect in his articulation rendered him unfit for the chair."
This charge was afterwards erased. It is interesting to note
that this is identically the same charge brought by Wakley
against Sir Charles Bell. " Veritas " says " a more inikind
and unfeeling imputation could not have been made." Toward
the clo.«c of his reply " Veritas " says:
Picture to yourself. Sir, an assembly of mere youths, many of
whom have Just commenced their studies, met together to decide
upon the ability or inability of a professor who was engaged in
teaching anatomy before many of them had an existence. The
very idea is preposterous.
103
[No. 33b'
He goes ou to say that he has attended two sessions of
Pattison's lectures and has always found them instructive and
any one who pays attention to his lectures "cannot fail of
reaping abundant store of anatomical knowledge."
As stated above, Pattison was dismissed July 23, 1831. Tlie
resolutions passed by the Council show that they finally yielded
to the student clamor ; but
In taking this step the Council feel it due to Professor Pattison to
state, that nothing which has come to their knowledge, with
respect to his conduct, has in any way tended to impeach either his
general character, or professional skill and knowledge.
One member of the Cotmcil protested vigorously, but vainly,
against Pattison's dismissal and enumerates eight reasons
why he should not have been dismissed. In the seventh item
the statement is made that the other professors testified to tlie
excellency of Pattison's qualifications and that " many of them
liad expressed their firm conviction to the Council, that the
dissensions in the medical school did not ari.se out of any
defect or misconduct of Professor Pattison." They evidently
had in mind outside influences.
From this time mitil the end of the controversy in the
Lancet the discussion was confined mainly to Wakley and
Pattison, with now and then short communications from some
of Wakley's friends. The final shot was fired by Pattison and
his closing paragraph is exceedingly interesting reading:
In the letters of Drs. Turner and Thompson, and in your " strictures " on my Statement, the fact of my having been a successful
teacher in the United States is treated with great contempt. " It
does not follow " observes Dr. Turner, " that he could succeed in
London because he was successful in America." The Americans,
forsooth, are easily satisfied. It is very well for John Bull to say
so. I should, however, have expected that you were too well informed as to the state of medical science in the United States, to
have given currency to such a vulgar and unfounded prejudice.
The Americans, I assert, are as far advanced and as enlightened
in their medical opinions as any country in Europe: and I would
further assert, without the fear of contradiction, that there may
be numbered amongst the medical profession of that country,
gentlemen who, tor extent and profundity of knowledge, and for
capacity of conveying instruction, have no reason to fear comparison with the most eminent teachers in Europe. Let the improvements in medical and chirurgical science be reviewed for
the last thirty years, and it will be found that America has
furnished her full quota.
This defence of American medicine and American nuHJical
men by one who had good reason for resentment shows Pattison to have been a man of more character than is generally
acknowledged.
Shortly before Pattison was dismissed from the Chair of
Anatomy Bennett died and the Committee of Education cif
the University of Loudon looked about for a new jjrofesscir.
They were fortunate in their selection, for they recummendcil
Mr. Jonas Quain lur the |)rofessorshi|i and his In-nthei'.
Mr. Eichard Quain. inr (lenioustrator, and ]ieace reigned fur
the time being.
Pattison was not long withottt a professorship, for in lcS3v!
he took up his duties as Professor of Anatomy in the Jefl'erson
Medical College, in Philadelphia, where he met with innnediate success. He held advanced ideas as to the best wav in
which anatomy should be studied, as the following abstract
from the annual announcement of the Jefferson ^ledieal College for the year 1832 shows :
Anatomy, the basis of all medical reasoning, can only be studied
practicoUy during the term of the student's attendance on lectures.
Should he neglect his opportunities for acquiring a complete
knowledge of the science during the term passed by him at college,
he must be +++++
CONTENTS to continue forever afterwards a mere driveller
in his profession. Now, anatomy is not to be learnt by an
attendance on lectures. Dissection, and dissection alone, can make
a man an anatomist. The Professor of Anatomy, it is true, may,
by animated and masterly demonstrations, do much to guide and
assist the anatomical student in true prosecution of his studies,
but it is in the dissecting room, with the dead body before him. by
patient and assiduous dissections, that the student can alone
acquire a knowledge of anatomy.
Pattison remained in Philadelphia tmtil 1841, when he
joined in founding the iledical Department of the University
of New York. Here he held for the remainder of his life the
Professorship of General Descriptive and Surgical Anatomy.
With his return to this country, the strife and turmoil of his
life very largely disappeared. He married a Scotch lady by
the name of Sharp, who was possessed of some fortune. I
have been ttnable to ascertain the date of their marriage, but it
proved to be a very happy one, for Gross gives a pleasing
pirtnre of their domestic life. He was social, ever ready to
do a kind act, a lover of the beautiful in nature and art. He
took an active interest in establishing the Grand Opera House
in New York. He also was an enthusiastic disciple of Izaak
"Walton.
Pattison was the atithor of " The Register and Library of
iledical and Chirurgical Science." He edited with notes
Burns' Surgical Anatomy of the Arteries of the Head and
Neck, !Masse's Anatomical Atlas, and Cruveilhier's Anatomy :
he \\'as one of the editors of the American Medical Recorder, a
journal which contains many of his contributions to medical
literature.
NOTES
Pattison's Exoneration. — All the facts concerning the divorce
obtained by Dr. Ure were laid before the managers of the Andersonian Institution by James Burn. " Writer of the Signet." and
Pattison was completely exonerated by them.
Pattison's Museum. — Cordell states that this " was extensively
advertised in the medical journals and newspapers of the country."
After he went to the University of Maryland he exerted a considerable influence in the councils of the University and he
eventually induced the University to purchase it for $8000, and in
1S21 a new building (Practice Hall) was erected for its accommodation. It consisted " of upwards of 1000 selected morbid and
healthy specimens, and in variety, excellence and number was far
superior to any other in America." For some time it constituted
the chief attraction for visitors to the University. Many of the
preparations are still extant, but in a somewhat neglected condition.
Dr. Phj/sick's Transfer to Aiiatonu/. — Chapman made the statement to Pattison that he thought by transferring Dr. Physick to
the Chair of Anatomy and by bringing Dr. Gibson from Baltimore
to occupy the Chair of Surgery the changes " would operate
beneficially in two ways. It would strengthen the University of
Pennsylvania, and at the same time weaken that of Maryland."
This was before Pattison received his call to Baltimore.
Apkil. 1!M!)J
io;i
Position Offered at the University of Pennsylvania. — The position offered Pattison at thr University of Pennsylvania was to bo
shared with another, and he did not care to accept such an
arrangement. He therefore besan to sive independent lectures
on anatomy and surgery and he says that he had " a class of above
one hundred and ninety students. " The hour of Pattison's lecture
was fixed after consultation with Chapman and was one which
Chapman assured Pattison would not conflict with any of the professors. When, however, ("liapnian learned that Pattison's lectures
were popular with the students he changed the hour of his own
lecture to that used by Pattison and thus prevented the students
from attending Pattison's lecture.
Gibson-Putt ison Controversy. — Apparently no one in Philadelphia knew of the particular structure demonstrated by Pattison. Gibson, however, found in CoUes' Surgical Anatomy ' an
unusually full and well-written account of those very parts, which
Mr. Pattison had claimed as a discovery of his own." Like many
another worker Pattison thought he had found something new.
but as soon as he found he had been anticipated he withdrew all
claims of discovery, only claiming that certain post-operative
results were best explained by the presence of this structure
(Colles' fascia).
Gibson's Chnnirteri.'itics. — " He was very vain in his personal
appearance, and more so of his reputation as a surgeon and teacher
of surgery. His style of lecturing was easy, agreeable, and instructive, but he never omitted an opportunity to set forth his
own merits and to depreciate the ability of surgeons whom he
disliked. He was especially vindictive against his leading rival
in Philadelphia." In 1847 Cibson was in Europe and returned
late in the fall with a wardrobe of broadly striped waistcoats and
trousers to match. These he displayed to his class until the lot
was exhausted, causing much merriment in the class-room and
prolonged rounds of applause which he received as evidence of his
personal popularity (Busey. l". P.. 1848). Dr. S. D. Gross says.
"Gibson was not an amiable man. His ill temper often betrayed
him Into unkind expressions, even in the lecture room."
During his last illness Gibson sent for Gross. " .\ly acquaintance
with him was slight, and I was therefore not a little surprised
when I received a message to visit him at his country residence.
.\n old friend, to whom I mentioned the fact, exclaimed, ' Don't
you know that lie has no friends in the medical profession of
Philadelphia. "
Pattison's Hroiiue. — " What added interest to the speaker was
a slight lisp and a Scotch accent, which never entirely forsook
him. despite his efforts to overcome them in early life " (Gross).
Chnitmiin us n Teathrr. — " A cleft palate, with its consequent
indistinct utterance, robbed him of every charm as a teacher, for
which his vast experience, great learning, and qualities of heart
and mind so well fitted him. The most careful attention, near and
in front of him was necessary to catch the words as they were
spoken, except by those who by long experience had become
accustomed to his unfortunate and defective enunciation " (Busey.
V. P.. 1848).
He (Chapman) "has seen several cases of hydrocephalus in
girls about the age of puberty, caused by metastasis of action from
the uterus to the brain."
Chapman believes " many cases that have a decided character of
angina pectoris afterwards terminated in well-marked gout cases.
-A gentleman long afflicted with this affection had gout induced
In his extremities by the use of sinapisms, and the former affection
was relieved: but. Improperly removing the sinapisms, the disease
suddenly returned to Its place and Immediately killed him."
Epilepsy. " usually assigned to a certain state of the nervous
system — a peculiar sensibility or irritability — It Is the temperament of genius and intellect — Julius Cspsar, Mahomet, Napoleon,
etc." (From bound volume of MS. notes taken by .lames C. Hall
(U. P., 1827 » of Chapman's lectures delivered In 1826.)
Pattison's Resignation from the University of .UuriiUind. — Pattison. in his " Statement of Facts in his connection with the I'niversity of London, " says that it was his intention to return to the
States and deliver another course of lectures: instead of doing
this he spent some time in Germany. I have tried to ascertain the
date of nis resignation, but have been unsuccessful. This mlgtil
help by showing that he resigned from the I'niversity of .Maryland
to accept the position in the I'niversity of London.
Putti-ioii's iKtsiiniutioii Jrum the I'nirrr.iilii u) London. — The
only medical man who was a member of the Council of the University ol London (Dr. Birkheck) supported Pattison and opposed
.Mr. Bennett and the way in which Bennett was appointed. I do
not think that Pattison. at the time he wrote his " Statement of
Facts." realized the extent of Wakley's opposition and influence.
Later he understood it better and gave it proper consideration.
Defense of Amrricuu .Mrdirim-. — Medicine in the I'nited States
1800 to 1830. Pattison, in the closing paragraph of his final communication made the statement that if the advances In medicine
and surgery " be reviewed for the last thirty years, it will be found
that America has furnished her full quota." 1 have had the
curiosity to look up American medicine during this period and
find abundant material to substantiate his aflirmation.
In Boston, there was .lohn Warren and J. C. Warren, eminent
as anatomists and surgeons — the latter founder of the Massachusetts General Hospital: James Jackson in internal medicine
and Jacob Bigelow. who published in 1820 his " American .Medical
Botany " — his essay " On Self-Limited Diseases " did not appear
until 1835. In New York, Wright Post and Valentine .Motl were
doing pioneer work in surgery. In Philadelphia, there was Casper
Wistar and W. E. Horner in anatomy: Philip Syng Physick in
surgery; John C. Otto in clinical medicine (he was the first to describe hemophilia): J. K. .Mitchell in neurology: W. P. Dewees in
obstetrics: Nathaniel Chapman in the theory and practice of medl
cine. In Connecticut. Elisha North was introducing vaccination,
recommending the use of the thermometer in fevers and in 1S17
established the first eye infirmary in the United States.
Nathan Smith was establishing medical schools in New England
and furnishing the entire faculty: he was a pioneer operator for
ovariotomy and. in 1824. published his essay on " Typhus Fever."
now a medical classic.
In the West there were four men who have made a name in
American medicine. Ephraim McDowell, B. W. Dudley, Wllllani
Beaumont and Daniel Drake. .McDowell Is known the world over
as the father of ovariotomy (Nathan Smith did not know of his
operation when he operated in 1821). Dudley was famous in his
day for his success in lithotomy. Beaumont, in 182.';, began those
studies on digestion which he gave to the world in 1833. Drake
was estal)lishin,< medical schools and publishing essays on niedlcal
education in the Wrslrm .loiirnul of the .Urdirnl und Phii.siiul
Sciences: at the same time he was preparing for his great work.
" Diseases of the Interior Valley of North America."
Other names could be added to this list, but it is unnecessary.
I consider the point raised by Pattison well proven.
Has the lurotid (Uund Ihrr liec, h:.rtiri)uled.'— The Professor
of Surgery at the University of Pennsylvania (Dr. t;ibson) In a
cUnic at the Philadelphia Alms House, open to students of the
Jefferson and the University, referred slightingly to the claim
of the Professor of Surgery at Jefferson (Dr. McClellan) that he
had performed the operation (under a general attack on Sir
Charles Bell who had made the same claim). He refers to Bell
as a Cunvu.ihuik </i(' t more worthy of his gun than the Dipper
(Dr. McClellan).
Pattison took up the challenge and made a reply which was
brilliant for Its wit and sentiment and convincing with its weight
of learning. In the same publication Pattison ridicules the story
that he was so Ignorant of the subject that he mistook the omo
hyofd muscle for the carotid artery and was about to llgate it
104
[Xo. 33S
when one of his students called his attention to the mistake and,
being set right by his pupil, found the artery and tied It.
I have tried unsuccessfully to ascertain what were the relations
between Chapman and Pattison after his return to Philadelphia
as Professor of Anatomy at Jefferson. Dr. J. W. Holland, of Philadelphia, made Inquiries for me of a distant relative of Dr. Chapman
and reported that " he does not know a living soul who could state
what were Cliapman's relations to Pattison in later years." As
nothing further appears in print, the animosities of earlier years
seem to have died out and disappeared.
BIBLIOGRAPHY
Bell, John: Philip Syng Physick. Philadelphia, 1S61.
Busey, Samuel C: Personal reminiscences and recollections.
Washington. 1895.
Chapman, Nathaniel: Correspondence between Mr. Granville
Sharp Pattison and Dr. N. Chapman. Philadelphia, 1S20.
Idem : Case of divorce of Andrew Lire. M. D., vs. Catherine L're
Philadelphia. 1S21.
Idejn : Correspondence between ilr. Granville Sharp Pattison
and Dr. N. Chapman. 2d edition, with explanatory remarks. Philadelphia. 1821.
Clark. J. F. : Autobiographical recollections of the medical profession. London, 1874.
Cordell, E. F.: Historical sketch of the University of Maryland
School of Medicine. Baltimore, 1891.
Gibson. William: Strictures on Mr. Pattlson's reply to certain
oral and written' criticisms. Philadelphia, 1820.
Gross, Samuel D.: Autobiography, 2 vols. Philadelphia, 1887.
Henry, F. P.: History of medicine In Philadelphia. Philadelphia.
1897.
Lancet, The: London, 1830-31, 1831-32.
Pattison. G. S.: Experimental observations on the operation of
lithotomy, with the description of a fascia of the prostate gland,
which appears to explain anatomically the cause of urinal infiltrations and consequent death. Am. Med. Recorder, 1820, III.
Idem: An answer to a pamphlet entitled "Strictures on
Mr. Pattlson's reply to certain oral and written criticisms, by
W. Gibson. M. D." Philadelphia. 1820.
Idem: A refutation of certain Calumnies published in a pamphlet, entitled Correspondence between Mi. Granville Sharp Pattison
and Dr. Nathaniel Chapman. Baltimore, 1820.
Idem : Final reply to the numerous slanders circulated by
Nathaniel Chapman, M. D., Professor of the Institutes and Practice
of Medicine in the University of Pennsylvania. Baltimore, 1821.
Idem : Professor Pattlson's statement of the facts of his connection with the University of London. London. 1831.
Idem: A lecture delivered in Jefferson Medical College, Philadelphia, on the evening of Tuesday, the 22d of January, 1833, on
the question " Has the parotid gland ever been extirpated? " Published by the students of Jefferson Medical College. Philadelphia.
1833.
COMMENTS ON THE PATHOLOGY AND BACTERIOLOGY OF FATAL
INFLUENZA CASES, AS OBSERVED AT CAMP DEVENS, MASS.
Bv S. BuKr WOLBACH, Bo.stou
Death from influenza means death from Imig eomi)lieiitions — pneumonia in some form. The pathological picture ol'
the Itmgs as seen in a series of postmortems is a kaleidoscopic
one. At first it was most difficult to correlate the various gross
findings, and it also has been difficult to correlate the microscopic findings, and this part of the work is not yet completed.
I have had the advantage of comparing my observations with
those of Dr. Goodpasture at the Xaval Hospital at Chelsea,
Mass., and again with a study of the series of cases we have had
at the Peter Bent Brigham Hospital in Boston, and it now is
possible to give a fair account of tlie probalile sequence of
events and to explain tlie apparent great diiferences in the
])athology.
In a series sucli as is presented here two types of lungs staml
out as strikingly characteristic findings in this disease. The
first is encountered in those cases in which death has occurred
within a few days after the onset of pulmonary signs. These
cases yield lungs which are partially collap.sed, dark red, la.\.
but meaty in consistency. Tlie pleural surfaces are often
partly covered with a dusky red mottling, due to small
extravasations of blood beneath the serous coat. There mav
be a thin layer of dusky red fibrinous exudate u])on the pleural
surfaces, particularly over the posterior borders. On sectimi
these lungs are dark red and wet. They are dripping wet, and
the fluid from some portions is a blood-tinged serous liquid and
from others dark red and bloody. On close inspection the cut
surfaces are usually found to be thickly sprinkled with air
vesicles of considerable size. The lung tissue as a whole, after
the liquid has drained from it, is brownish-red in color, and
somewhat translucent and friable. The mucosa of the bronchi
is usually very dark red in color, and the bronc'hial lymph nodc^
are enlarged and deep red in color.
The other type of lung, which is found in patients that ha\ e
lived for 10 days or more after the onset of the disease, whilr
showing traces of the type of lesion just described, is characterized by a very extensive bronchitis, n'ith bronclio-pneumonia, discrete or confluent, and peri-bronchitis. These hmgs
are more voluminous than the preceding, but they do not fill
the chest cavity at postmortem. They are nodular, and the
]deural surfaces occasionally show a striking tracery, due ti>
the injection of the stib-pleural lymphatics. Portions of the
surfaces of the lungs may be covered with a thin layer of
fibrinous exudate. On section the most prominent feature is
the extensive injection of the bronchi, particularly the smaller
imes, with a fibrino-purulent exudate. The injection of the
lu'onchi may be so extensive and uniform as to produce geometrical patterns, which are very striking when the condition
is accomijanied, as it usually is, by a marked infiltration of the
inter-lobular septa. A casual inspection suffices to show that
the smaller bronchi are distended, nsuallj' markedly dilated,
and in eases of two weeks' duration spherical and cylindrical
bruncliiectases are very common. The gross appearances of
this type of lung are very much like those described by Dr. MacCallum in pneumonias after measles. The condition in fact
Ai-KiL. 1919]
105
is one of pan-bronchitis; peri-bronchitis with extensive infiltration of thf interlobular sopta : and organization in alvi-oli
and bronchioles.
These two preduniinatiiig types on first consideration seem
to represent ditTerent processes. 1 hope to show convincinglv
that they simply represent difTeri'ut stages of the same process.
Before I undertook tlie study of the Camp Devens cases I had
.some experience with influenza pneumonias at the Peter Bent
Brigham Hospital, and I have since quickly surveyed tlie
material obtained there during the time I was at Camp Devens.
The Brigham Hospital cases, on the whole, have been t|nit('
diflferent in their gross appearances. On the other hand, the
cases at the Naval Hospital in Chelsea have been very similar
to those at Camp Devens, and I think a cross-section of the
study of one series of cases is very much like that of the other —
to which Dr. Good|)asture agrees. There are many other
interesting features of the i)athology of the lungs, such as tlic
rapidity with which bronchiectasis occurs and the large number of case.s which develop interstitial emphysema, and of
course the consequences of both of these conditions ; bronchieitatic abscesses and gangrene of lungs from the first, emjiiiysenia of the mediastinum and subcutaneous emphysema fnmi
the second. Of this series of 2S postmortems, done between the
2d and 32d day of the disease, there were six that showed sulicutaneous emphysema: eleven showed emphysema of tlic
mediastinum.
In comparing notes with other pathologists one is struck by
the dillerenees in gross appearances of the lungs in dilferent
localities. The .same is true in regard to the bacteriology.
The table which accompanies this report shows the very higii
percentage of pure liarillus injUienza: jmeumonias at Camp
Devens : again, a similarity with the series at the Chelsea Na\;il
Hos|)ital as reporteil i)y Keegan. However, in the Camj) Dcveii>
series there were a few cases in which the hemolytic strejitocoecus and the pneumococcus were found, and the.se hnigs
presented different gross apj)earances. In a cursory analysis
of the Brigham Hospital cases auto])sied (about 30), I find a
predominance of hemolytic streptococcus and pneumoco((ii>
lungs. Without going into corroborative details at this time,
I nniy say that in the gro.ss appearance of the lungs I have laid
tniphasis ujion, li. iujiuenzte was the only organism wliirli
could be cultivated and I iniliesitatingly associate these distinctive conditions with tiiat organism. In lungs .showing
other types of solidification, other organisms were responsililc
for the exudation characttrizing the pneumonias. The iicniulytic streptococcus, the staj)hylococcus and the pncumncoccn~.
each produces its distinctive picture, the last often that i>\
lobar jtneunionia.
While the bacteriological evidence, based u|irin the assumption that B. iiiflttetizie is the cause of influenza, is very
good in support of the stand that there is a distinctive lung
lesion in these influenza [>neumonias, the histological sttiily
has afforded very definite proof. Early in this study of tlic
Camp Devens ca.ses. I recognized the fact, as have others, that
a striking type of reaction was present, a condition of acute
idveolar emphysema with the deposit of a hyaline fibrinoumaterial on the alveolar walls. The intervening alveoli af
compressed and filled with exudate, which in the early cases is
largely serous or bloody, containing but little fibrin. It is this
acute alveolar emphy.<ema, with the .-icrous and hemorrhagic
exudate, that gives the characteristic gross appearance to the
lungs in the early stage of the disease. In order to determine
how eounnon this lesion is, I have gone over all of the Brigham
Hospital autopsies on influenza cases, and find it to be constant. It may be nuisked by a jjueumococcus or streptococciis
exudation or bv extensive hemorrhage, but its presence can
always be determineil by the finding of the hyaline fibrin outlining greatly distended air spaces in the lungs. It is the one
di,stinctive feature in the ]iathology of influenza i)neumonias.
and its constant occurrence is indicative of the entity of the
initial lung infection. The interjn-etation of this lesion was
not ca.sy. The hyaline fibrin, because of its prominence and
the jiixta])osition of cellular exudate, often simulates the outlines of alveoli. As a matter of fact, it outlines cavities filled
with air, which may or may not completely fill groups of
alveoli. Although alveolar walls in contact with tliis fibrin
may be necrotic, tissue elements ])lay no part in its formation.
.\ similar hyaline fil)rin was found in two cases of emphysema
of the mediastinum where the mediastinal areolar tissues weninfected by ])neumococcus, secondary to ])neumococcus peri<arditis. The jihysical characteristics of this fibrin are determined by its contact with air, and an imiiortant factor is
probably the mechanical com|)ression of strands of fibrin i)y
air. What is the source of the exudation in the alveoli in these
early jmeumonias!'' The exudation may be ])re.sent in alveoli
^vith intact walls, or walls showing very slight reaction, mainly
evidenced by activity of the resjiiratory e])itheliuni. In all
cases severe lesions were found in the finest bronchioles, and
in the alveolar ducts. The latter show an exudation eompo.-icd
mainly of polymorphonuclear leucocytes and small (pnintities
of fibrin. The walls are filled with leucocytes, and are often
necrotic in places. The intralobular bronchioh's show severe
lesions of the mucosa, and it is often po.ssible to demonstrate
the source of hemorrhages from cajiillaries. The obvious
explanation, and indeed the only possible one from the material
at hand, is tliat the major injury is to the bronchial system.
and nniinly in the finest bronchioles and alveolar ducts. To
secure the degree of cniphysenni ])re,sent it is necessary to
assume a valve action of the exudate in the bronchi. Tbe
character of the hyaline fibrin de])osit annmd air vesicles and
upon the alveolar walls suggests a jiouring of exudation into
the alveoli from the bronchioles and alveolar ducts, at a time
when air is able to pass. Thus the patient is virtually blowing
bubbles in his own lungs, into a medium of exudation relatively
poor in fibrin.
The meibanism of interstitial eniiiby.senni formation is
easily seen, where tbe greatly distended alveoli are in contact
with the pleura of interlobular septa. In tlie.s' locations it is
liossiblc to demonstrate ru])turc of the alveolar walls and the
direct continuity of fibrinous strand.s, partially filling cleft*
dis.sected by the air from alveoli to pleural or interlobular connective tissue. A series of gross .sections and microscopic sections from lungs with interstitial emphysema shows that the
air finds the easiest route of exit from the lung in the con
106
[No. 338
iieetive tissue surrounding blood-vessels. It dissects altnig
blood-vessels to the hylus of the luug and from there along the
great vessels and bronchi into the mediastiuuni, over the
j)ericardium into the anterior mediastinum, and upwards along
tlie trachea into the tissues of the neck, whence it escapes into
the subcutaneous tissues. This subcutaneous emphysema may
appear very early, as will be seen by the accompanying chart.
The earliest case was seven days from the first symptom,
which means, of course, a shorter duration of the lung involvement. The majority of the cases were noted on or after the
10th day from the initial symptoms of the disease.
It must be l)orne in mind in considering the i)atliology of
these lungs, that the lesions are not imiformly distributed, and
therefore very extensive injury in portions of one or several
lobes are compatible with life for a considerable period of time.
The bronchial lesions apparently progress, and may extend
throughout tlie whole of one or both lungs, producing the
anatomical picture of the more chronic cases, that of a panbronchitis with bronchiectases and peri-bronchitis. During
this period of extension in bronchi, a number of things may
happen to the portions of the lungs first involved. They may
become secondarily infected with pneumococcus or stre])tiicoecus, or the Gram-negative diplococcus called by English
workers "Diplococcus mucosus." In rare instances Staphylococcus and Friedlander's bacillus have been encountered. Tlie
fate of the tissue depends on the nature of the infectingorganism; as, for example, fibrinous exudation with the pneumococcus and abscess formation with the staphylococcus. In
a number of instances these portions of the lungs, severely
damaged at the onset, did not become secondarily infected ;
at least, these lungs have shown only the influenza bacillus at
the autopsy, and have undergone extensive organization resulting in cicatrices of large sizes. If we take a series of lungs
which have shown only the influenza bacillus in cultures and
in sections, we may still have all the stages described exclusive
of those with secondary infection, and accordingly we must
conclude that the reaction to the influenza bacillus is less
intense in the later stages of lung involvement than in the
earlier. This is shown best in comparing two lungs from the
same ease, where in one lung, iisually the right, we find the
severe damage of the early lesion with bronchiectasis ami
peri-bronchitis, and in the other kuig a much less intense
bronchial reaction, with much less marked peri-bronchitis, or
none at all. The involvement of the pleura in lungs infectetl
solely with tlie influenza bacillus is very slight. There are
hemorrhages into the pleura and perhaps a thin layer of fibrin
upon the surface. The amount of fluid in the ])leural cavities
was always small, though blood-tinged. Empyema was found
in cases secondarily infected with the streptococcus or pneumococcus. The involvement of the pleura may result from the
extension of the inflammatory process along the interlobular
septa and lymphatics, or, and this I believe is more commonly
the case, from bronchiectatic cavities situated close to the
pleural surface.
Gangrene of the lung was noted in one of the Camp Devens
series in a case showing very extensive bronchiectases, witli
bronchiectatic abscesses. Extensive necrosis of the hum- lias
been observed in a number of eases in this same series and at
the Brigham Hospital — necrosis due to organisms other than
the influenza bacillus.
Organization in the jiure B. infliienzce cases was a common
end result. The organization of the exudate begins early, certainly before the 10th day of the disease, and a prominent
factor in liringing about this result is, I believe, the plugging
of the bronchi with exudation. In patients who had survived
three weeks or more there Avere very complicated gross appearances, due to extensive cicatrization of large portions of the
lung. The contraction of interlobular septa, due to the
avascular organization of exudate, causes marked distortion
of the lobules of the lung, and peculiar lines of retraction on
the pleural surfaces.
It is not the purpose of the present report to include the
whole pathology of influenza. There are a few interesting
features in other organs which are worthy of emphasis, howover. Eight of the Camp Devens series showed waxy degeneration of the rectus muscles, and subsequent experience at the
Brigham Hospital indicates that it was probably overlooked
in some of the earlier postmortems done at Camp Devens. A
number of these cases showed rupture and extensive hemorrhage into the rectus muscle. This lesion has been noted in
other muscles ; for instance, the transversalis, the internal and
external oblique muscles, the latissimus dorsi, the pectoralis
major and the intercostal muscles. The testes occasionallv
showed minute petechia, but on the whole no striking gross
change was observed. Microscopically very striking changes
were encountered in nearly every case, nameh', the cessation
of activity in the seminiferous tubules; actual degenerative
changes were frequently noted, and in late cases beginning
fibrous tissue replacement of the degenerated tubules. This
lesion of the testes seems to be wholly a toxic one, as there is
very little cellular reaction. It is difficult to imderstand why
such severe toxic lesions of the muscle and testes should occur,
in the absence of effects attributable to toxins in other organs.
For instance, the reaction of the spleen is very slight, the heart
muscle rarely has shown any gross or microscopic lesion, and
in general seems to escape entirely the toxic effect of the disease. Lesions of the adrenal, when extensive, such as hemorrhage, can be attributed to secondary infection, usually tlie
hemolytic streptococcus. Minor acute lesions are constantly
found in the cortex in influenza cases, but these lesions are
similar to those found in manj^ infectious diseases — the disappearance of lipoid +++++
CONTENTS, and focal necrosis with mononuclear phagocytic cell reaction. The head was opened in
20 of these cases. Infection of the middle ears was found
in 13. Infection of the sphenoidal sinus in 20, frontal sinus
in seven, and of the ethmoidal cells in eight cases. The
bacteriology of the sinuses is given in tlie chart. Three cases
showed punctate hemorrhages in the cereliral cortex.
BACTERIOLOGY
I do not intend to discuss at length the bacteriology of the
epidemic. The table is a true account of the findings, and I
prefer to have individuals draw their own conclusions. The
opportunities for bacteriological work were particularly good.
THE JOHNS HOPKINS HOSPITAL REPORTS
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Thf Maliirial Fevers of Baltimore. l'..v \V. S. Tii.\vi:n. M. 1
.T. Hewetson. M. D.
A Study of some Ifatal Cases of Malaria. By Leweli.y
Studies in Typhoid Fever.
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Simon Flexnkh. JI. 1>.. W.vi.tek Keed, M. D.. and II. C. 1'ak.sc -
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Studies in Genito-Urinary Surgery.
The Treatment of Trostatic Hypertrophy by Conservative Perineal I'rostatectomv. An analysis of cases and results based on a detailed
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Recto T'ri'thril I'i-Jtiil-e 1 le^crintiivn "f New Procedures for their Trevnilinn iihI iiiir I'.v 111 .;ll II ^n^^,;. M. D.
The I'lih hi rn.i-i~ ,i!mI K;Hli.,il I'nir "f iicr.inoma of the Prostate. biMu;:
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fwi-lve p,ipii-i on pneiuiuini.i. By liK.s. Cir.iT.tRD. Fabyan. Emeksox.
Mvi:sii\i,i. :MrCiiAE. STEiNER. IlbwAun and Hanes.
V sfiii'ly of Uinrrhiea in Children. J. II. Mason Knox. Jr.. M.I)., and
El. WIN II. SCH.iItER. M. 11.
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C.ii.lili.iii ..r tb.' |.Me» alliT .-lli'li
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S(alpln._- A.ci.leiits. I'.v .limx Staige Davis. M. D.
Db-itnii tion of the Inf.'rior Vena Cava with a Report of Eighteen Cases.
Bv .1. IlAl.I. I'LLASANrs. M. D. . .
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Primarv Cariinoma of the Mvit. Bv Milton C. Winternitz. M. D.
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Mil IS'lJ-lllll. By FllKl.KKl.K I,. II..,1MAN. LU D., F. g S.
The iirii.'iii ami I ii-\ .•loi.iii.nt "1 tli.' I.ympbatic System. By Florence It.
Th.- N'u.ri'i Tnbiris I.aterab-s ami the So-called GanRlion Dpticum Basale.
Bv la.wMili F. MA1...M:. M. D.
Venous Tln-aiibosis 1 luring My. .cardial Insufficiency. P.y I.'rank .T. Si.aden.
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Fasciculus I.
.\ Stndv of a Toxic Substance of the Pancreas. By E. W.
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Old Aire ill Belation to Cell-oversrnwth ami Cai
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The Eff.-cl i'.r l!..lll..val of til.. S|ile,-n fpon Metabolism in Doss; Pn
limiiiarv lieport. Bv .1. II. King. M. D.
The FfFcct I'.f Kemoval of the Spleen I'pon Blood Transfusion. By .1. II.
King M II B M. Bernheim. M. D.. and A. T. .Tones. M. D.
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llAURV C.
By E. W. GooD
Spontaneous and Experimental Leuksemia in the Fowl. Bv 11. C.
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Studies on the Relation of Fowl Typhoid to Leuksemia of the Fowl. By
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Hyaline De,i:eiierati..n ..f tbi- Islands of Langerhans in Pancreatic Diabetes.
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Generalizeil .Miliary riibir.ub.sis Resulting from I5xtension of a Tubercular
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Acute Suripurativr llypi.pbysitis as a Complication of Purulent Sphenoidal
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.M.D.. and M. C. Pincoffs. M. fl.
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Knox. M. D.. II. R. Waul. .M. D.. and H. C. Schmelsser, il. D.
A Fatal Case of Multiple I'rimary Carcinomata. By E. D. Plass. M. D.
Congenital Obliteration of the Bile-ducts. By James B. Holmes. M. D.
Multiple Abscesses of the Brain in Infancy. By James B. Holmes, M. D.
Gastric Carcinoma in a Woman of Twenty-six Years. Bv R. G. HussEY,
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Subdiaphragmatic Abscess with Rupture Into the Peritoneal Cavity Following Iniliiii'd Pneumothorax for Pulmonary Hsemorrhage. By' R. G.
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Heart Block Caused by Gumma of the Septum. Bv E. W. Bridge.man.
-M. D.. and H. C. Schmeisser. M. D.
Analysis of Autopsy Records.
A. The .Johns Hopkins Hospital. I Table Showing Percentage of
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Fasciculus II.
The ROIe of the Autopsy in the Medicine of To-day. Bv M. C. Winternitz.
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Exp.riin.-nt.il N.'i.liii.pathy in the Dog. Lesions I'rodnced by Injection
..I /;, Ijiniiiliisi plii'iin into the Renal Artery. By M. C. Winternitz.
-MI... ,111.1 WllllAM c. (JriNBY. M. D.
Mesaitiritis ,.r lb.. Pnliminary Artery. By M. C. Winternitz, M. D., and
II. C. Schmeisser. M. D.
A Clinical and Pathological Study of Two Cases of Miliary Tuberculosis of
the Choroid. By Robert L. Randolph. M. D., and H. C. Schmeisser.
M. D.
The l!bi..il-vess.-Is of the Heart Valves. Bv Siamioff I', v \ m. .Ii.nes. M. D.
Equilibria in Pir.ipitin Keaitions. Bv Stanii.hi 1'.a\\i .I..\fs, M. D.
Car.iii..ma ..f 111.' I'leura with ITvpertrophic ( ki . ,,;i 1 1 In ..jij 1 h v. Report of
a Case with a Des.ription of the IIist..l..::v ..1 th.- I'.oii.. Lesion. By
STANH..1.F P.AVNE-J.INFS. M. II.
The InteiT.lation of the Siiiviving Heart and Pancreas of the Dog in Sugar
Metabolism. P.y ADM..\r II. Clark. M. D.
Congenital .\tri'sia of the I'^sopbagus with Tracheo-Esophageal Fistula
Associated with Fused Kidney. A Case Report and A Summary of the
Literature on Congenital Anomalies of the Esophagus. By E. D.
Plass. M. D.
Ectopia Cordis, with a Report of a Case in a Fifteen-Month-Old Infant.
Bv Jami:s p.. Holmes. .M. D.
Studies in th.' M.^ihanism of Absorption from the Colon. By Sami-el
Golds. iiMiLi-. Mil., anil A. B. Dayton. M. D.
Report of Two Fatal Cases Following Percy's Low Heat Treatment of
Carcinoma of the Uterus. Bv V. X. Leonard, M. D., and A. B. Davton.
JI. D.
The Relationship in Typhoid Between Splenic Infarcts and Peritonitis
T'nassociated with Intestinal Perforation. By A. B. Dayton. M. D.
Left Duodenal Hernia. Bv A. II Davl.n, M. D.
Hist..l..gi.:rl a^ K.l.i t .'.l t.. I 'In si..li .L-i. ii I an. I Chemical Differences in Certain -Mils, l.s ..f the Cat. Pv II IIA^s Billard. M. D.
A Method of cb.arins Fr.iz.'n s.,li.ln^. I'.v H. Hays Billard. M. D.
On the Occurrence ami Signiti.am-.' of Fat in the JIuscIe Fibers of the
Atrio-Ventri.'ular Svstem. P.y H. Hays Billarii. :M. D.
Studies on the .M.^talmlism ..f C'lls in ritrn. 1. The Toxiiaty of a-Amino
Acids for Einbyonii- Chiikeii Cells. By .Montrose T. Burrows. M. D..
and Clarence A. Xeymann. M. D.
The Significance of the Lunula of the Nail. By Montrose T. Burrows.
.M. D.
The Oxvgen I'ressure Necessary for Tissue Activity. By Montrose T.
BiRROws. M. D.
The Fiincti. iial Relation of Intercellular Substances in the Body to Certain Stru.tures in the Egg Cell and Unicellular Organisms. By
Montr. >si: T. ItcRKOws. M. D.
Studies on th.' Gr.iwth of Cells iji ritro. The Cultivation of Bladder an. I
Proslat.. Tumors iiuisi.l,- the Bo.lv. Bv Montrose T. Bfrrows. M. D..
J. EnwAia. Ill iiNs. .M. Ii., ami Y..S111.1 SrziKL. M. D.
The Stndv of a Small Dutl.reak ..f P.. Ii.. my. litis in an Apartment House,
Occurring in lb.' Coiirs.' of an Fi.i.l.iiii. ill a Large City. By Montrose
T Bliiiiows. M. D.. an. I I:i.»m:i.^ .\, I'akk. M. D.
Papilloma of tbi. I.aivnx. i;rii..ii ..1 a Ca-.e Treated with Radium with
Resultant Chronic Diftiisi' I by n.i.lii is. By William C. Duffy. M. D.
Analysis of Autopsy Records.
Autopsy Statistics.
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The Effect of Diet on the Healing of Wounds. (Illustrated.) The Effect of Different Bloods on the Growth of //. Inftucn^n.
By Admoxt H. Clark. M. D 117 (Illustrated.)
Bv T. M. KivERS. M.D.. Haltimor.-. Md 129
The Relation of Spontaneous Nephritis of Rahbits to Experi- ".
^ , , ,1, » i J Observations on the Clinical Pharmacolofjv of DiKitalis. (Illus
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' By Alfred M. \\ EDO, M. D., Pittsburgh, I'a l.U
A Sketch of Dr. Lyman Spalding. N'otes on New Books 1;16
By Henry M. Hurd, M. U 123 Books Received 139
THE EFFECT OF DIET ON THE HEALING OF WOUNDS
By Admoxt
(From the Pathological Laboratory of
The work uf lluojur and Whipple' on blood regeneration
after anseniia .-jIiow.* that .;pecifie diets produce a very markcil
effect. The rate of blood regeneration on a meat diet is very
rapid, a matter of ilays or a few weeks ; whereas, on a diet rich
in carbohydrate it is very slow, months being .sometimes required for coni])lete regeneration. Tliese results suggested the
possibility that specific diets mi;,'ht influence the rate of wound
healing and the following experiment.-; were accordingly
underUikcn.
Carrel '• ' has studied the process of wound healing in both
men and animals and has found that the curve representing
thediminution in size of an aseptic wound while it is cicatrizing
is regular and geometric. From Carrel's curves Du Xoiiy "
has derived mathematical formula?, by means of which the
area of a wound at any given date can be predicted. Ilis
formula; arc :
S-S'
(1)
(VI
• The experiments reporte<l in this paper were carried out b.v
Dr. Clark during the spring of 1918. Owing to Dr. Clark's death
the results which they show are of a preliminary nature and represent incomplete work. I thought tliem. however, of sufficient
interest to publish, hoping that they might suggest further work
along the same line. — Janet Howell Cl,\rk.
II. Clark. M. D.
Thr Johns Hopkins i'niversitj/. Baltimore)
S represents the original area of the wouml.
S' — area i days later.
T = time from first observation and — I'm ( 1 ).
<' = time from .S" to S" .
i=constant coefficient which is ciiaracteristic of the womid
and which varies with the size of the wound and the
age of the jiatient.
After calculating i from (1) S" can lie jiredicted with a
remarkable degree of accuracy, any deviation from the calculated curve showing the |)resence of an infection.
In his e.\i>erinicntal work on animals'-' (dogs, guinea-pigs
and cats), where the wounds were kept as sterile as possible.
Carrel found the process of cicatrization ta be divided into
four part.s:
(1) Quiescent I'l-riml. — During this period tlicrc is no contraction and the main characteristic of tiie period is its variable length, I-.") days.
(2) Period of Granulotis Contraction. — During this jieriod
the wound contracts at a rate wiiich is jiroportional to tiie size
of the wouiul.
(3) Period of ICiiidermizalinn. — Tiie epithelium iicgins to
form and the process of healing may now continue by epidermization alone or by epidcrmization and contraction
together.
(4) Cicatricial Piriml. — .\<Ut thr wound is healed the scar
enlarges.
118
[Xo. 339
No previous work on the effect of specific diets on wound
healiug has been reported.
EXPERIMENTAL METHOD
Twelve dogs as nearlj' the same age, size and general condition as possible were cliosen and three were put on each of
the following diets :
(1) Mixed Diet. — 41 gm. of fat (lard or butter) and
107 gm. of lean meat (beef or liver) were boiled together, then
mixed with 354 gm. of bread and run through a meat chopper.
This was divided among three dogs.
(8) Carbohydrate Diet. — 500 gm. of bread moistened with
water were divided among three dogs.
(3) Protein Diet. — 500 gm. of lean meat, either round of
beef or liver, were boiled and divided among three dogs.
(4) Fat Diet.— 300 gm. of fat (equal parts of butter and
lard) were boiled and groimd with 100 gm. of bread.
The dogs were fed on these diets for three days before the
wouuds were made. Throughout the experiments the dogs
were weighed and the weight was found to remain practicallv
constant.
Preliminary experiments with various types of dressings
showed that the wounds healed better and showed less tendency
to infection when left entirely open with no dressing of anv'
kind. The dogs were given ether anaesthesia, the backs were
shaved and two circular skin flaps (one large and one small)
were removed from each side of the back. The wounds were
placed where the dog could not lick them and were left open.
As soon as they were made, the size of the wounds was traced
on a piece of transparent celluloid with a wax pencil and
similar tracings were made at intervals of three or four days
throughout the experiment. These areas were copied on heavy
tracing paper and measured in square centimeters by means
of an Amsler polar planimeter. If a wound showed marked
infection the results were discarded.
A second set of wounds was made after the first had healed
and finally a third set in which the dogs were interchanged in
diets.
I. Effect of Diet on }Yound Healing. — The results for Sets 1
and II are averaged in Fig. 1. The large and small wounds
are averaged together; the area given being the total wouml
area on one dog (i. e., the area of two large and two small
wounds). As there were three dogs on each diet in each set,
each curve shows the average result on six dogs. Tlie diet
seems to aiiect the length of the quiescent period. The \m>tein-fed dogs have no quiescent period, the contraction beginning at once. The carbohydrate dogs have a quiescent period
of three days, those on the mixed diet, of four days, and the
fat-fed dogs, of six days. After the sixth day the curves run
parallel and the dates of final healing differ by the same amount
as the lengths of the respective quiescent periods.
The diet, therefore, is a factor in determining the date of
the beginning of Period II, the period of granulous contraction.
In Set III, four dogs which had been on a fat diet in Sets I
and II were put on a protein diet. The results sho^^n in Fig. 2
c
V
r
10
"X
\
«
\ \
\\J
^
M t
\
\!^
r
\^
^
<
u
n 5
\
!^
^^^^^^
HAYS
3
t
q
la
p
15
«
Fig. 1.— Effect of Diet on Wound Healing.
Average results of Sets I and II.
C = carbohydrate diet.
P = protein diet.
M = mixed diet.
F = fat diet.
Abscissae = time in days; ordlnates :
wound area In sq. cm.
give the same result as Curve I, though not so markedly as
might be washed. I believe that there should have been an
T
P
\~
S
\
\ '' t
1
1 tj
\ 1
0
\
\
*
\
\,
\
^^->- T
SAYS
o
3
t
1
1%
1*
l«
3(
Fig. 2.— Effect of Change in Diet.
Curve F gives results for fat- fed dogs in Sets I and II.
Curve P gives results for same dogs fed on protein diet in Set III.
Abscissae = time in days: ordinates = wound area in sq. cm.
interval between the two sets of experiments during which tli''
dogs could be fed on the new diet. In this experiment Set 1 1 i
Mav, 1919]
119
was begun as soon as Set II was finished and the change in diet
was simultaneous with tlie making of new wounds.
c
^
AHEA
Anr»
AMD
WOUND
MOUND
St»K
X
c
\ ^
\
fc
\\v
^~.
r
H U
v
^
"~"-~
-.^
xn
a, ?
K
\
S
^^^
->
<
\
\J
>^
HAYS
e
3
c
<?
f^
ir
Mi: T
IT
a/
Fig. 3. — Curve Showing Formation of Epithelium.
area of wound and scar.
area of wound.
Abscisss — time in da.vs: ordinates = wound area in sq. cm.
Ill Fig. 3, the pmgri-s.s of Period III. the period of epidermization, is shown, the dotted line indicating the area of
the wound and the scar, the heavy line the wound area.
It is evident that the formation of the epithelium starts on
the same day, irrespective of the diet and the size of the wound.
%
*n
p. V..O
Ik VtOUH
i
\
T^ *
1
X \
VL
XT
r.
1
V X
/
.-ATo;;
\
"
/
:
S
S
\ »A^a
-♦
"
lo
IT
Fio. 4. — Average Curve for Sets I ami II (all Diets).
area of wound and scar.
area of wound.
Abscissa- = lime in days: ordinates = wound area In sq. cm.
Contraction continues throughout Period III and tlie closing
of the wound is due to a combination of the two factors, contraction and epidermization. The dotted curves giving tinarea of wound and .<car are parallel, showing that diet has no
effect on either the date of beginning of Period III or the
course of epidermization. The difference between the two
curves gives the area of the epithelium.
In Fig. 4 an average curve is given for all four diets (Sets
I and II), showing the course of all four periods of wound
healing. It shows that contraction continues all through the
period of epidermization and even for live days after the
wound is completely healed. At this point the formation of
jiigment begins at the outside edge of the scar and as the
pigmentation moves inward the scar rapidly enlarges until
the pigmentation is complete, when it reaches a stationary
state.
It would be interesting to compare this fourth period in
animals with different degrees of pigmentation and determine
the exact relationship l)etween the formation of pigment and
the scar area. Carrel ' says that the expansion of the cicatrix
after the wound is healed is less marked in man than in the
^
N \
n
\
^
F
\
.V
C"
\
^s^
^
p
N^
Q
r.
\
r
^1
nJ
\
v.
•
<
1
s^,
"^
<o
DATS
Ir
1-^
It
l>
°
10
i;. 5. — Results of Sets I and II Averaged Separately for Large
and Small Wounds.
Curve if = mixed diet.
Curve C = carbohydrate diet.
Curve P — protein diet.
Curve F = fat diet
Abscissa* = time in day.s; ordinates = wound area In sq. cm.
(log. If the expansion is conditioned by the formation of the
])igment this would naturally result.
II. Effect of Size of Wounds on Ckatriznlion. — Carrel'
has already shown that tlie rate of contraction is proportional to the size of tlie wound, but tliat tbe rate decreases
le.ss rapidly than the area, .«o that large and small wounds
tend to become equal. Fig. 5 shows the results in Sets I
and II averaged for large and small wounds separately for
all four diets. In every case the curves siiow tiiat the rate
of healing in large wounds is greater, so that tbe wounds heal
in the .same length of time. The rate of healing as measured
by the change in area per day is not, however, proportional to
the size of the wound on any one day. For example, take
120
[No. 339
Fig. 5 (C). The area of the small wound is 2 sq. cm. on the
fifth clay. At this time the rate of healing is .10 sq. cm. i)ev
day. The area of the large wound is 2 sq. cm. on the teutli day
when the rate of healing is .35 sq. cm. a day. However, if tlie
rates throughout each set of curves are compared it will lie
found that the ratio
rate of healing of large wounds
rate of healing of small wounds
on any given day is approximately equal to the ratio
original size of large wounds
original size of small wounds
if the quiescent period is neglected (see Table I). So that,
knowing the rate of healing of a wound of any given size, the
rate of healing of a womid of any other size can be calculated.
However, this probably would hold true only within certain
limits of the original size. In these experiments the wounds
are all relatively small.
TABLE I
Bo
Day
S, _ or
ginal size large wounds
Rate healing
Bi 1 ,
Rate healing ;i„x V='^i
large wounds ^=
Sj original size small wounds
in square cm.
per day
M
.3-6
1.7
.04
.11
.07
fi-9
.16
.30
.27
9-12
.20
•33
.34
12-15
.13
.23
.22
P
3-6
1.7
.08
.13
.14
6-9
.16
.23
.27
9-12
.20
.40
.34
12-1.')
.l.T
.23
.25
C
3-6
1.8
.07
.12
.12
6-9
.20
.30
.36
9-12
.17
.32
.31
12-1.5
.17
.23
.31
F
3-6
1.7
.08
6-9
.36
.52
.61
9-12
.26
.33
.44
12-15
.10
.17
.17
The results for F are poor, but for the others are fairly good.
If this fact has any general application and can be extended
to the interpretation of womids of any size it would mean that
the rate of contraction is governed by a variable factor depending on its age and a constant factor depending on the original
size.
In comparing the curves for different diets in Fig. 5 it is
seen that the effect of the diet on the length of the quiescent
period is greater in the small than in the large wounds.
Xejtlier the diet nor the size of wounds has any effect on the
time of beginning of Period III. The formation of the
epithelium starts about the ninth or tenth day in every case.
The amoimt of contraction subsequent to this depends on the
size of the wound when the epidermization begins. The contraction and epidermization complete the healing together.
The size of the sear when complete healing has taken jilace is
about ihe same in every case, and equals approximately onequarter the size of the original wound.
DISCUSSION
In connection with these results it is interesting to consider
the well-known fact that the ingestion of proteins produces a
much greater increase in body metabolism than that of any
other foodstuff's. In a recent monograph on the subject of
the stimulating effects of nutrients, Benedict and Carpenter "
have given a very complete report of this question. They find
that while carbohydrates give a maximum increment to the
metabolism of 25 per cent and fats 12 per cent, this increment
occurs within two hours and the metabolism then returns
rapidly to the base line. With proteins the increment reached
a maximum of 25 per cent to 45 per cent and persisted for as
long as 8 to 12 hours. This increase in metabolism, or excess
energy given off by the body as a result of the ingestion of
food, may be regarded as waste energy, but Benedict suggests
that we may consider the extra heat developed under these
conditions as a normal physiological stimulus to cellular
activity. Practical experience with heavy muscular work on
protein and carbohydrate diets points to this conclusion and
the results reported here would certainly support the idea that
proteins have a specific influence in stimulating the whole
cellular system to greater activity.
CONCLUSIONS
The length of the quiescent period of wound healing is
affected by the diet. It varies from zero in protein-fed dogs to
six days in the fat-fed animals. This variation in the quiescent
period is more marked in smaller wounds. As a consequence,
the date of final healing differs by about five days for the
protein- and fat-fed dogs.
When the second period, or period of contraction, has set in
the rate of contraction is not affected by the diet. It is governed by a variable factor depending on the age of the wound
and by a constant factor proportional to the original size —
^ = -^when Rj and /?„ = rates
if healing of large and small
wounds and S^ and .S\ = original areas of these wounds.
The beginning of Period III, the period of epidermization,
is independent of the size of the wound and the diet. It is
determined by the age of the wound. Contraction and epidermization continue together until the wovnid is entirely
healed.
After the wound is healed the scar continues to contract
until pigmentation sets in. During this latter process it
enlarges and reaches a stationary state after pigmentation is
complete.
REFERENCES
1. Hooper, C. W.. and G. H. Whipple; Amer. Jour. Physiol., 1918,
XLV, 573, 576.
2. Carrel, A.: Jour. A. M. A., 1910, LV, 214S.
3. Carrel, A., and A. Hartman: Jour. Exp. Med., 1916, XXIV,
429.
4. Du Noiiy. P. L.: Jour. Exp. Med., 1916. XXIV, 451: 1917,
XXV, 721.
5. Benedict, P. G., and T. M. Carpenter: Food Ingestion and
Energy Transformation. Carnegie Inst., Wash., 1918.
May. I'Jlii]
121
THE RELATION OF SPONTANEOUS NEPHRITIS OF RABBITS TO
EXPERIMENTAL LESIONS*
By AuTiiiu L. Bloomkield
{,From the Medical Clinic. The Johns Hopkins University and Hospital)
into the renal nrterv tliroujrh a fine needle. During the injection tlie kidney became mottled or blanched, but the normal
color ])roni|)tly returned. Bleeding from the punctured artery
was slight, and stopix-d when the kidney \va.< put back into the
abdominal cavity. The wounds were closed with catgut and
healed by first intention. In a few instances total or partial
infarction of the kidney resulted from an arterial thrombus,
but in most cases at autopsy the vessels were jiatent and there
were no gross signs of circulatory disturbance.
After, two weeks a series of intravenous injections was begun
with the organism previously used. The size of the dose and
the interval between injections varied with the animal's
reaction. The injections were regulated in such a way that
the animals lost weight and seemed ill. In diilerent experiments from 1 to 19 re-inoculations were made over periods
varying up to 15 months. Frequent urine examinations were
made throughout the experiment, and in a few cases 'thallein
tests were done.
Most of the animals died of cachexia and toxemia ; the
remainder were sacrificed. Gross specimens were preserved,
and blocks were fixed in formalin, embedded in paraffin, cut,
and stained with hematoxylin and eosin.
Si.x strains of strejitococci were used : strains Q and Y were
avirulent, long-chained green streptococci isolated from urine:
strains T and S were hemolytic varieties obtained from septic
infections and were highly virulent for rabbits; strains A and
R, isolated from tiie throats of scarlet fever patients, were
markedly hemolytic and virulent for rabbits. In the initial
injections into the renal artery from 0.5 to 1.0 c. c. of a thick
.saline suspension of organisms grown for 24 hours in meat
infusion broth and killed by heating for half an hour at
60 to 70° was used. The charat'ter of the emulsion was such
that most of the bacteria were filtered out by tiie kidney. This
was controlled by microscopic examination of a few kidneys
removed shortly after the injection. Living 24-hour cultures
were employed in the intravenous reinjections.
EXPERIMENTS
A single protocol of a typical experiment is givin m detail
I in Table I ; the remainder are summarized in Table II.
Taiii.k I. — DhrTAii.Ki) Photocol of a Complete Exi-kkimknt
No. 51. White male rabbit
March 1. 1916. Weight 1580 Km. Trine clear.
March 2. Left kidney exposed llirouKh lumbar Incision. It Is of
normal size an'l consistency, but there are many shallow depressions on the surface, varying In size up to 2 mm. In
diameter. Growth from 0.5 c. c. broth (24hour) of strain S
(killed) Injected into renal artery. During injection, yellowish blotches appeared over entire kidney, except the lower pole
and anterior surface.
During the past few years an extensive literature has accumulated, dealing with the experimental production of renal
lesions. A variety of injurious agents has been employed,
among which may be mentioneil cytotoxic sera,' cantliaridin,'
foreign proteins,' uranium nitrate,' bichloride of mercury,'
tartrates,' diphtheria toxin,' anesthetics," and a variety of
bacteria, such as streptococci,' staphylococci," colon bacilli,"
Friedliinder bacilli," and others. Although lesions of
various types have been obtained, many of them specific of the
particular poison employed, it has not been possible adequately to reproduce a condition corresponding clinically or
anatomically with advanced types of chronic nephritis in man.
The work of Faber," who was able to produce arthritis in
rabbits with great constancy by injecting streptococci intravenously .some time after a preliminary intra-articular sensitizing inoculation with the same organism, suggested the employment of a similar procedure in the attempt to produce experimental nephritis. It was thought that a preliminary injection
of bacteria in relatively high concentration directly into the
renal artery might sensitize the kidney in such a way that
subsequent small repeated intravenous injections might result
in renal lesions of a chronic type. Coulter and Pappenheimer" employed a somewhat similar method. Working
with rabbits, they gave a series of intravenous injections of an
extract of typhoid bacilli, and two weeks later injected the
same material directly into the renal artery. To avoid possible
confusion with " spontaneous lesions," attention was confined
to the acute lesions, and the animals were killed after 48 hours.
Scattered focal glomerular lesions, similar to tho.se described
in bacterial endocarditis, were found. In the unsensitizcd
animals these changes were either very slight or absent.
The following experiments are re|)orted because they represent an attempt to produce chronic renal disease by a method
different from those previously used, and because it was
possible accurately to control the significance of " spontaneous
lesions " by direct inspection of the kidney at the beginning of
the experiment, as well as by later examination at autopsy.
Healthy rabbits weighing from 1000 to 2500 gm. were used.
After a preliminary urine examination,! the animal was
anesthetized with ether and the left kiilney delivered through
a lumbar incision. The vessels were stripped free of fat and
connective ti.«suc and the bacterial suspension wa,< injected
• These experiments were carried out during the winter of 19151916, at the suggestion of and in collaboration w^lth Dr. Theodore
Janeway. Publication has been unavoidably delayed.
f The urine was obtained by massaging the abdomen over the
bladder.
122
[No. 339
March 3. Animal in good condition. Urine contains albumin,
granular casts and a few R. B. C.
March 4. Urine clear.
March 6. Urine clear. Weight 1550 gm.
March 16. Growth from 1/20 c. c. 24-hour broth culture strain S
(living) intravenously.
March 17. Urine clear. 1/20 c. c. (S) intravenously.
March 18. Looks sick. 1/10 c. c. (S) intravenously.
March 20. Urine clear. 1/10 c. c. (S) intravenously. 1490 gm,
March 22. Urine clear. 1/10 c. c. (S) intravenously. 1450 gm.
March 27. 1430 gm.
March 2S. 1/20 c. c. (S) intravenously.
March 30. 1350 gm.
April 5. Urine clear. 1390 gm.
April 8. Urine clear. 1/100 c. c. (S) intravenously. 1470 gm.
April 10. Urine clear. 1/100 c. c. (S) intravenously. 1490 gm.
April 11. 1450 gm.
April 12. 1/lOQ c. c. ( S ) intravenously.
April 17. 1/100 c. c. (S) intravenously.
April 19. 1400 gm.
April 22. 1/100 c. c. (S) intravenously.
April 24. 1350 gm.
April 25. 1/lOOc.c. (S) intravenously.
April 28. 1/lOOc.c. (S) intravenously. 1300 gm.
May 2. Urine clear. 1/100 c. c. (S) intravenously.
May 3. Urine clear.
May 6. 1/100 c. c. (S) intravenously. 1360 gm.
May 9. 1/100 e.c.(S) intravenously. 1320 gm.
May 11. 1/lOOc.c. (S) intravenously.
May 14. Urine clear. 1/100 c. c. (S) intravenously. 1300 gm.
May 15. Animal killed. Autopsy: General condition good. A
few parasitic cysts of omentum. Heart and lungs normal.
Left kidney: Weight 5.0 gm. It is loosely adherent to
region of scar without new formation of vessels. Capsule
moderately thickened (post-operative), but strips freely. Same
degree of surface pitting as seen at operation. Consistency
seems normal. Cortex of normal width, markings distinct.
Glomeruli appear as red dots. Intermediate zone separated
from cortex by an irregular, grayish-yellow line about 1 mm.
in thickness. Medulla rather pale. Microscopicallp: A good
many small scattered areas of round-cell infiltration are seen.
In some places there is a beginning fibrosis which causes the
cortical depressions. The lesions are focal and interstitial.
The glomeruli look normal. The vessels and tubules are
normal except where Involved in the scars.
Right kidney: Weight 5.0 gm. Gross and histological examination similar to that of left; same degree of scarring.
Renal vessels patent on both sides.
, RESULTS
Apart from the " spontaneous nephritis " described below,
no definite lesions were found. The glomerular, tubular,
vascular and interstitial structures differed in no way from
those of untreated controls. This result was unexpected in
view of the direct and intensive injury, the constitutional reaction of the animals and the e\idence of at least transient renal
irritation furnished by the appearance of albumin, casts or
blood in the urine after some of the injections. Pappenheimer,
Hyman and Zedman " studied rabbits' kidnej's removed at
short intervals after the injection of streptococci into the renal
artery. They found that the organisms were rapidly disposed
of by leucocytic and fixed cell phagocytosis, with return of the
glomerulus to normal. An overwhelming bacterial injury, on
the other hand, led to immediate partial or complete disorgani
zation of the glomerulus by thrombotic or suppurative processes. This is possibly the explanation of the difficulty of
producing experimentally a gradually progressive process such
as that seen in the subacute or chronic glomerulonephritis of
man. In our animals, despite repeated injections, the immediate injury was apparently promptly repaired without the
initiation of an advancing lesion.
SPONTANEOUS NEPHRITIS
In connection with attempts to produce experimental
nephritis, many writers refer to the difficulty of interpreting
lesions which occur spontaneously in the kidneys of various
animals, such as the rat," dog " and rabbit. Spontaneous
rabbit nephritis has been recently described by Le Count and
Jackson," who summarize the literature on the subject. Such
lesions were found in many of our animals and correspond
with those pictured in previous reports (Figs. 1-10).
Every grade of change from accumtilations of a few round
cells between the tubules to extensive scars was seen in one
or another of the specimens. On gross examination, the
earliest forms of lesion appear on section as streaks about
1 mm. wide, slightly more yellowish than the normal kidney
substance running from the base of the intermediate zone to
the surface. At this stage there is no corresponding depression on the cortical surface, but the lesion is shown by a
mottling of the kidney over it. With more advanced disease
there are very slight depressions, and in extreme cases a coarse
pitting which may affect the entire renal surface. These
depressions vary in size from minute dents up to pits 2 or
3 mm. in diameter.
Microscopically, the earliest lesions appear as collections of
a few round cells in the interstitial tissues between the tubules.
The latter show granular degenerations and the cell boundaries
and the nuclei become indistinct. Later the remains of the
tubules may be seen between dense collections of round cells.
The next stages show the presence of new connective tissue,
wMch finally may take the form of scars which contract and
distort the tissues. The tubules may be greatly dilated and
contain detritus or casts. The glomeruli, as a rule, show
relatively little apparent change, even when the intervening
tissue has been largely destroyed. In some eases there is
marked fibrosis about the capsule, htit the glomerular structure
shows no definite alteration. Finally, the glomeruli may also
disappear in the scar. The individual lesions may be large or
small, they may be abundant or widely scattered, and they are
located in cortex or in medulla. They are always distinctly
focal, however, with normal intervening tissue, and are never
diffuse, as in the contracted kidney of human nephritis. It
seems probable that the lesion is a reaction to an injury which
is not primarily interstitial.
In reviewing the reports on experimental rabbit nephritis,
it is striking that many of the lesions described correspond
in detail with these spontaneous lesions, thus raising the question of possible misinterpretation of the findings. An attempt
was made in these experiments to control the significance of
these lesions by careful inspection of the kidney for scars at
May, 1919]
123
the beginning of the experiment when the renal artery wa:injected, comparing its appearance with the later autopsy findings. It was also possible to compare the left kidney, which
was directly treated with a large dose of bacteria, with the
right, which was affected only by the smaller intravenous reinjections. These findings are summarized in Table III.
In all but four of the 16 animals the appearance of the
kidney at the end of tlic experiment was exactly like that seen
at the preliminary operation. In these four animals, periods
of 161, 25T, 352 and 4C0 days had elapsed since the beginning
of the experiment, so that it is probable that the sliglit focal
lesions which were similar to those seen in mitreated controls
had developed spontaneously. The duration of the other
12 experiments varied from 8 to 74 days. In all of these
animals in which tlic kidney had been smootli at the start no
lesions were found later at autops}-, and where the kidney had
TABLE II.— SUMMARY OF RESULTS OF EXPERIMENTS
Brown (emile..
Brown male.
Weight 251(
While mile.
Weight 1420
Black male.
Weight 1600
Brown hare.
Weight 1990
gm.
Brown hare.
Weight MM
gm.
Dec. 8, 1915. Injection
into left renal arter>'
of growth from 5 c. c.
of broth in 0.5 c. c.
salt sol. of strain Y
(killed).
Dec. 30, 1915-Mar. 13.
1917. Six intravenous
injections of strain Y
(living).
Dec. 13, 1915. Injection
into left renal artery
of growth from 5 c. c
broth in 0.5 c. c. salt
sol. of strain Y
(killed). •
Dec. 24. 1915-Feb. 8,
1916. Six intravenous
injections of strain Y
(living).
Occasional trace
of albumin in
urine after injections. Condition goud
except for lo^s
of weight
after injections.
.\ 1 b u m i n ir
urine at times
after the injections. Moderate loss of
weight.
into left renal artery
of growth from 1 c. c.
broth in 0.5 c. c. salt
sol. of strain Y
(killed).
Dec. 27, 1915-Jan, 28,
1916. Five intravenous injections of
strain Y (living)
Dec. 14. 1915. Injection
into left renal artery
of growth from 5 c. c.
broth in 0.5 c. c. salt
sol. of strain Y
(killed).
Dec. 27, 1915-.\ug. 29.
1916. Seven intravenous injections of
strain V (living).
Dec. 22. 1915. Injection
into left renal artery
of growth frt)in 3 c. c.
broth in 0.5 c. c. sail
sol. of strain T
(killed).
Jan. 5, 1916-Jan. 22
1916. Three intravcn
ous injections o
strain T (living).
Killed Mar. 13, 1917,
460 days from beginning of experiment.
Both kidneys look
normal except for few
slight surface depress i o n s. Microscopi
call]/: Glomeruli
normal; moderate
spontaneous lesions
iq. v.).
Killed Feb. 8. 1916, 61
days from beginning
of experiment. Right
kidney normal. Infarct of left except for
lower pole. Microscopically: No lesions
except the infarct.
Dec. 14. 1915. Injection [Steady loss of Died Jan. 20, 1916, 44
days from beginning
of experiment. Both
kidneya normal in
g' r o 8 8 and microscopically.
Loss of weight Killed .\ug. 29, 1916.
after each ii
jection. .\ftei
sixth injcc
tion, albumin
and R. B. C,
in urine (oi
two days.
Steady loss of
weight,
bumin and
casts in urine
for five days
after last injection.
Dec. 22. 1915. Injection
into left renal artery
of growth from 3 c. c.
broth in 0.5 c.c. salt
iol. of strain T
i (killed^
tJan. 5. 1919-Jan. 20.
I 1916. Four intravenous injections of
strain T (living).
lUar. 2, 1916. Injection
into left renal artery
of growth from 0.5
c. c. broth culture in
0.5 c. c. Halt ftol. of
Rtrain S (killed).
Mar. 16. 1916-May 14.
1916. 17 intravenouA
injections of strain S
(Hiring).
I
.Mar. 2. 1916. Injection
into left renal arterv
of .25 c. c. culture S
(killed) in 0.5 c. c.
•lalt sol.
lar. 16. 1916~May 14.
1916. 17 intravenous
intertions of strain S
(living).
Stead;r loss ofloied Jan. 23. 1916. 32
weight,
bumin after
first Injection. Albumin, casts and
R. B. C. for
one day after
fourth injection.
k-eight. Tran
sicnt albuminu r i a following some Injections.
days from begin
of experiment. IV-th
kidneys show markr<l
grade of sponlanpnu'
Interstitial lc<<{on<^.
Otherwise normal.
257 days from begi
ning of experiment.
Both kidneys normal
in gross and microscopically, except for
a very few lesions of
spontaneous nephritis.
Died Jan, 22. 1916. 31
days from beginning
of experiment. Both
kidneys normal in
days from beginning
of experiment. Both
kidneys show marked
h[Nintiineous interstitial lesions. Otherwise normal in grotis
and microscopically.
Killed .May 15. 1916.
days from beginni
of experiment. B*
kidneys show mo<l
ate grsde of upontji
ous inten«litinl
sions. Otherwise n
nial.
Steady Iom of Killed May 16. 1916. ~\
DescriptioD
Brown female. Mar. 20, 1916. Injection Steady loss of
Weight 1250 I into left renal artery weight,
gm. I of growth from .25
I c. c. broth in 0.5 c. c. [
, salt i^ol. of strain S
(killed).
Apr. 4, 1916-May 4,
1916. 13 intravenous
I injections of strain S
I (living).
Brown female. Mar. 20. 1916. Injection Steady loss
Weight 1020 into left renal artery weight,
gm. of growth from .""
c. c. broth in 0.5 c.
' salt sol. of strain
I (killed). I
I Apr. 4, 1916-Aug. 29,
1916. 15 intravenousj
iivjcctions of strain SJ
(living).
Brown female. Mar. 20, 1916. Injection Loss of weight
Weight 1260 into left renal arter>- after injecgrn. uf growth from .25
' c. c. broth in 0.6 c.c.
salt sol. of strain S
t (killed).
Apr. 4, 1916-Mar. 7,
I 1917. 16 intravenous
injections of strain S
(living).
JIale. Weight Mar. 25. 1916. Injection
1080 gm. into left renal artery
I of growth from 0.6
c. o. broth in 0.6 c. c.
salt sol. of strain R
(killed).
Apr. 8, 1916-June 15.
1916. 14 intravenous
' injections of strain R
(living).
Male. Weight Apr. 1, 1916. Injection
1090 gni. I into left renal artery
of growth from 0.6
c. c. broth in 0,5 c. c.
salt sol. of strain R
(killed).
Apr. 15. 1916-May 19.
1916. 10 intravenous
injections of strain H
(living).
Apr. 1. 1916. Injection
into left renal artery
of growth from 0.5
c. c. broth in 0.5 c. c.
salt sol. of strain R
(killed).
Apr. 15. 1916-.Iunc 1.
1916. 12 IntravenouH
injections of strain R
I (living).
Brown female. Dec. 9, 1916. Injection
Weight 1550 into left rcnnl artery
of growth from 6 c. c.
broth in 0.5 c. c. salt
sol. of strain (j
(killed).
Dec. 2*1. 1916. One intravenous injection of
train () (living).
Male. Weight Apr. 27. 1916. Injection
1270 gro. i Into left rma! artery
of \ an agar fiUnt of
I hronchxAtptiruM in 0.5
I c. c. Hit sol.
lions.
i t h
occasional albuminuria.
Steadv loss of
Steady loss of
weight Developed a r tliritis of left
hind leg.
Rapid emaeiatinn. Albumin and casta
'zr.
Killed May 15. 1916. 55
days from beginning
of experiment. Both
kidneys normal in
every way.
Died Aug. 24. 1916, 161
days from beginning
of experiment. Slight
spontaneous lesions
in both kidneys.
Died Mar. 7, 1917, 352
days fnmi beginning
of experiment. Minimal degree of spontaneous lesion. Kid*
neys otherwise normal
Died June 15, 1916, 71
days from beginning
of experiment. Kidneys normal in every
way.
Died May 19. 1916, 49
days from beginning
of " experiment. Kidneys normal in gross
and microscopically.
Died June 5. 1916, 66
days from beginning
of experiment. Kldnej-s normal except
for a few early spontaneous lewiuns.
Died Dec. 23. 1916. 14
days from beginning
of experiment. Both
kidneys normal in
gross and microscopically.
Died Mav 5, 1916. eight
days from beginning
of experiment.
Extreme spontaneous
Icitions.
124
[No. 339
been pitted at the start, focal interstitial lesions were found.
Furthermore, in spite of the intensive direct treatment of the
left kidney, in every case in which changes were present they
were of equal extent in the two kidneys. It seems impossible
to interpret these findings in any other way than that all these
lesions were spontaneous and independent of the experimental
procedure. The great frequency and variety of the changes,
their apparent independence of any constant factor in the
animal's condition, such as age, weight, etc., suggest that
possibly many of the chronic interstitial lesions ascribed in
the literature to experimental infection are really the effects
of spontaneous nephritis.
CONCLUSIONS
1. An attemjjt was made to produce chronic nephritis in
rabbits by intraveiaous injections of streptococci, following a
direct injection into the renal artery.
2. Failure to produce chronic glomerular lesions was
thought to be due to the means used by the kidney to dispose
of injected organisms, which resulted in complete healing if
the glomerulus survived the acute injury.
3. Chronic focal lesions were found in many animals.
4. Control examinations of the kidney at the beginning of
the experiment, and comparison of differently treated right
TABLE I IL— SPONTANEOUS LESIONS
COMPARISON OF APPEARANCE OF LEFT KIDNEY AT OPERATION WITH LESIONS FOUND LATER AT AUTOPSV
Description
Appearance of
left kidney
at beginning
of experiment
at operation
No.
days
to autopsy
Lesions at autopsy
No
Description
Appearance of
left kidney
at beginning
of experiment
at operation
No.
days
to autopsy
Lesions at autopsy
No
Right kidney
Left kidney
Right kidney
Left kidney
11
Normal size
460
Weight 8 gm. Looks
Weight 8 gm. Looks
63
White male.
Numerous mark
74
Weight 5 gm. Very
Weight 5 gm. Post
, ,
and appear
normal except for few
normal except f o r
Weight
edly depressed
many marked cortical
operative capsular
Weight
1560 gm.
ance ; surface
slight cortical depres
some thickening of
1450 gm.
scars over sur
depressions. Capsule
thickening. Similar
smooth.
sions. Capsule not
capsule (post-opera
face.
strips freely. Micro
lesions to those on
adherent. Micro
tive). Capsule strips
scopically: Man y
right and of same
scopically : Moderate
freely. A few slight
well-advanced lesions.
degree.
number of linear in
cortit-al depressions
with fibrosis, con
terstitial lesions, mod
(less than on right).
tracted scars, com
erately advanced. A
Microscopically:
pression and atrophy
few small, scatter
Same as right.
of glomeruli and tu
ed, round-cell infiltrations.
bules. Apart from
these focal interstitial lesions, kidney is
14
Brown
X r m a 1 size
61
Weight 8.5 gm. Looks
Total infarct of kidney
normal.
male.
and appear
perfectly normal.
except for lower pole.
56
Brown
Nonnal.
55
Weight 4 gm. Normal
Weight 4 gm. Like
Weight
ance; surface
Capsule not adherent.
Microscopic sections
female.
in gross and micro
right except for post
25 lU gm.
smooth.
Microscopically : No
of lower pole show
normal kidney.
W^eight
1250 gm.
scopically.
operative capsular
thickening.
15
White male.
Weight
1420 gm.
and appearance; surface
smooth.
44
Weight 4.-1- gm.. Looks
normal ; surface
smooth. Capsule not
adherent. Micro
Weight 4.-h gm. Some
post-operative thickening o f capsule;
strips freely. Micro
57
Brown
female.
Weight
1020 gm.
Surface perfectly- smooth.
161
Weight 5 gm. A very
few very slight depresions on surface.
Capsule strips freely.
Microscopically : A
few round-cell infil
Weight 5 gm. Same as
right except for postoperative capsular
thickening.
scopically: No lesions
scopically: No le
seen.
trations with beginning fibrosis.
16
Black male.
N o r m a 1 size
257
Weight 5.5 gm. Capsule
Weight 6.-r gm. Post
Weight
and appear
strips freelv. A verv
operative capsular
59
Brown
.Surface perfect
352
Weight 5 gm. A very
Weight 5 gm. Same as
1660 gm.
ance; surface
few small '"' pits " on
thickening; strips
female.
ly smooth.
few scattered slight
right except for post
smooth.
surface; in general, is
a smooth kidney. Microscopically: Two
small round-cell accumulations with be
freely. No " pits "
seen. Microscopically:
One lesion seen in entire section, similar
to right.
M" eight
1-360 gm.
beginning surface depressions. Microscopically : No abnor
sections.
operative capsular
thickening.
ginning fibrosis in entire section of the
63
Male.
Surface perfect
71
Weight 4.5 gm. Nor
Weight 5.5 gm. Like
cortex.
Weight
1030 gm.
ly smooth.
mal in gross and
microscopically.
right except for postoperative capsular adhesions.
17
Brown hare.
Normal size
31
Weight 5.0 gm. Capsule
Weight 5.5 gm. Post
Weight
and appear
strips freely. Surface
operative thickening
65
Male.
Surface perfect
49
Weight 5 gm. Normal
Weight 5.+ gm. Like
199U gm.
ance ; surface
smooth. Normal in
of capsule; strips free
Weight
ly smooth.
in gross and micro
right except for post
smooth.
gross and microscopically.
ly. Normal in gi-oss
and microscopically.
1090 gm.
scopically.
operative capsular ad
66
Male.
Surface perfect
66
Weight 5 gm. Surface
Weight 5 gm. Like
19
Srown hare.
Kidnev showa
32
Weight 6.5 gm. Multi
Weight 7.5 gm. Post
Weight
ly smootli.
smooth and normal.
right except for post
Weight
multiple de
ple small depressions
operative thickening
1100 gm.
Microscopically : A
operative capsular
1650 gm.
pressed areas
an surface. 1
to 1.6 mm. in
diameter.
on surface, but capsule strips freely. Microscopically : Abundant, well -advanced.
of capsule; strips freely. Similar lesions to
those on right and of
same degree.
very few small, scattered, roimd-cell infiltrations
thickening.
scattered interstitial
12
Brown
Surface perfect
14
Weight 4.5 gm. Normal
Weight 4.5 -i- gm. Like
lesions, both in cortex
female.
ly smooth.
in gross and mici-o
right except for post
and medulla, with ex
Weight
scopically.
operative capsular
tensive round-cell in
1550 gm.
thickening.
filtration, fibrosis, and
compression and atro
77
Male.
Extreme pitting
S
Weight 6.0 gm. Ex
Weight 4.5 gm. Same
phy of tubules.
Weight
1270 gm.
of kidney surface.
treme pitting of kidney surface, but capsule strips freely.
kind and degree of lesions as on right.
51
White male.
Weight
1580 gm.
Many small, depressed scars
over kidney
surface.
73
Weight 5 gm. Multiple small depressions
on surface, but capsule strips freely.
Microscopically : A
good many small accumulations of round
cells with beginning
fibrosis. Kidney otherwise normal.
Weight 5 gm. Postoperative tli.kening
of capsule; strips freely. Similar lesions to
those on right and of
same degree.
Microscopically : Tlie
sections are shot with
numerous contracted
scars which distort
the kidney structure.
Areas of compressed
o r dilated tubules
containing casts. The
most extreme grade
of spontaneous lesion.
THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919
V
^:^^<'*'^* '--•-•
^<|V^
Fig. 1. — Earliest typ<' oi l. sum Shows beginning accumulation
of round cells between the tubules.
Fig. 2. — Earliest type "l l. sum aii|» arini; :is ;i linear streak of
round-cell infiltration.
Fig. 3. — Portion of Fig. 2. Higii pun^r. Siiuws round-cell Infiltration with beginning tubular changes.
Fig. 4. — Moderately advanced lesion.
THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919
.1. ' '^ ,
— Portion of Fig. 4. Higli power. Beginning scar witli
slirunken and distorted tubules.
"t  .' -SJ^^"^^,;^:^
Fig. 6. — Multiple small areas of scarring with normal intervening
tissue. Well-advanced lesion.
.<?fiWH5«?^,
Fig. 7. — Same as Fig. 6. High power. Shows area of fibrosis with
atrophied dilated tubules and fibrosis around a glomerulus.
Fig. S. — Very advanced lesion showing a linear scar with destruction of normal elements.
THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919
PLATE XIII
FiQ. 9. — Low power. Most advanced type of lesion, resulting in
a scar.
m
Fio. 10.— Portion of KIg. 9. High power.
May, 1919]
135
and left kidneys sufr^est that all these lesions represented the
" spontaneous nephritis of rahhits."
REFERENCES
1. Pearce, Richard M., and Elsenbrey, A. B.: A physiological
study of experimental nephritis due to bacterial poisons and
cytotoxic sera. Jour. Exp. Med., 1911, XIV, 306.
2. Opie. E. L.: Lymph formation and edema of the liver with
experimental nephritis produced by cantharidin. Jour. Exp. Med.,
1912, XVI, 831.
3. Longcope, Warficld T.: The production, of experimental
nephritis by repeated proteld intoxication. Jour. Exp. Med., 1913,
XVIII, 678.
4. Oliver, Jean: The histogenesis of chronic uranium nephritis,
with especial reference to epithelial regeneration. Jour. Exp.
Med., 1915. XXI, 42.5.
5. MacN'ider, William de B.: A study of acute mercuric chlorid
intoxications in the dog, with especial reference to the kidney
injury. Jour. Exp. Med.. 1918, XXVII. 413.
6. Underbill, Frank P.. Wells, H. Gideon, and Goldschmidt,
Samuel: Tartrate nephritis. Jour. Exp. Med., 1913, XVIII, 322.
7. Frothinghani, Channing, Jr.: A glomerular and arterial
lesion produced in rabbits' kidneys by diphtheria toxin. Jour.
Med. Res.. 1914, XXX, 365.
8. MacNlder, Wm. de B.: A study of the naturally nephropathlc kidney of the dog rendered acutely nephropathic by uranium
or by an anesthetic. Part 2. Jour. Med. Res., 1916, XXXIV, 199.
9. Le Count, E. R., and Jackson, Leila: The renal changes in
rabbits inoculated with streptococci. Jour. Infec. Dis., 1914, XV.
389.
10. Major, Ralph H.: The production of kidney lesions with
staphylococcus aureus toxins. Jour. Med. Res.. 1917, XXXV. 349.
11. Bailey. C. H : Chronic nephritis in rabbits by repeated
intravenous injections of living colon bacilli. Jour. Exp. Med.,
1916. XXIII. 773.
12. Major, Ralph H.: The production of acute and chronic
kidney lesions with bacillus mucosus capsulatus. Jour. Med. Res.,
1917, XXXII, 125.
13. Faber, Harold K.: Experimental arthritis in the rabbit.
Jour. Exp. Med.. 1915, XXII, 615.
14. Coulter. C. B., and Pappenheimer, A. M.: Proc. New York
Path. Soc. 1916, XVI, 80.
15. Pappenheimer, A. M., H>Tiian, H. T., and Zedman. F. D.:
Proc. New York Path. Soc., 1916, XVI, 73.
16. Ophiils, W., and McCoy, George W.: Spontaneous nephritis
in wild rats. Jour. Med. Res., 1912, XXVI, 249.
17. Winternitz, M. C, and Quinby, Wm. C: Experimental
nephropathy in the dog. Jour. Urology, 1917, I, 139.
A SKpyrCH OF DR. LYMAN SPALDING '
By Henry M. IIukd, M. D.
Dr. Lyman Siial(lin<r wa.s iwrn at Cornish, X. 11., in 177").
His early education was ohtained at the Charlestown Academy,
and later he was a student in the office of Dr. Nathan Smith,
the eminent founder of medical schools, and the first of the
name of the Smiths who later hecame distinguished in New
England and Maryland. He afterwards visited the Harvard
Medical School in 1794 ami attended two courses of lectures
there, hut clid not receive his degree of M. D. until 1797. He
returned to Cornish, N. H., the residence of Dr. Smith, an<l
took charge of his jiractice during the hitter's ahsence in
Euro|)e. He suK-iequently tauglit chemistry and materia
medica witii Dr. Sniitli at the newly estahlished medical .school
at Dartmouth College. N. H. He also hecame demonstrator
of anatomy.
He soon removed to \Val|Mile, N. H., where he practised for
a few months also. His residence there is mainly interesting
hecauseof the fact that he purchased a set of Perkins Tractors,
then much u.^cil ami highly prai.^ed for the treatment of disea.xes. These tractors were sold for -$30,00, with the c.xclnsivc
right to u.«e them in |)ractice hoth in this country and in
Europe. It was one of the common medical frauds which arc
perpetrated on all nations ahout once in so often,
Dr, Spalding removed to Port.'^mouth, N. H., in 1797, and
there had a succe.<sful career. He hecame a contract army
surgeon, and had .«o much to do that ho relinquished his connection with Dartmouth College. He was a diligent student,
and active in all matters i-onnected with medical co-o|)erHtioii.
'Read before The Johns Hopkins Hospital Historical Clvib,
February 10. 1919.
He established a medical society, an anatomical museum, and
originated and distributed .'Jo-called " Bills of Mortality," giving the causes of death of persons who died in Portsmouth
from the years 1800-1 SI 3. He al.so essayed the growing of
opium and lettuce in his garden for medicinal purposes.
In the "Life of Dr. Lyman Spalding " several interesting
chapters are given on the introduction of vaccination into
this country. Dr. Spalding, who was living at Portsmouth,
wrote to Dr. Waterhouse, of Cambridge, who had received
the Kiiie Po.x from Jenner in England and seems to have had
the monopoly of the introduction of vaccination into this
country. Waterhou.se was undoubtedly a man of ability and
energy, but proi>ably lackwl money and felt the need of
•.\|)Ioiting the new discovery for his own benefit. He, accordingly, writes to Dr. Sj)alding, in reply to his letter, asking
for one-quarter of the amount received from Dr. Spalding's
va<'ciinitions during the succeeding 14 months, insists that
" the small sum of five dollars" be charged for each vaccimition, and ginirantees that the e.xclusive privilege will be granted
upon these terms. He also nnikes carefid mention of the fact
that he has .Tenner's matter direct from England. A long
i-orrespondence took |)lace between Spalding and Waterhouse.
Both parties seem to have been an.vious to make money from
the introduction of vaccination, but Waterhouse appears in the
most unfavorable light. After acceding to Spalding's proposition that he have e.xclusive control of vaccination in Portsmouth, ho shows great an.xiety that he, Spalding, should associate with him a Dr. Cutter and, later, Dr, Cutter's son, on the
ground that the activity of these men would increase the
number of vaccinations and thereby increase the profits to be
126
[No. 33"J
derived from the exclusive privilege of managing them. In
one letter Spalding asks for the privilege for 12 months, and
later suggests that he will pay 10 per cent of all the sinus
which he receives for vaccination until such time as vaccination becomes public property. All that he received from
Dr. Waterhouse seems to have been the exclusive privilege of
vaccinating persons within the limits of Portsmouth, and a
small piece of thread which had been dipped in the vaccine
lymph. Later it seems that Spalding was to pay $130.00 for
this piece of thread, and a certain proportion of the money
which he received for the vaccinations. Owing to the fact
that it soon became apparent that one patient could be vaccinated directly from the arm of another, the exclusive privilege
of using the vaccine lymph was soon broken up.
This destruction of the monopoly was undoubtedly much
hastened by the unsatisfactory character of the vaccination
when the thread impregnated with lymph was used, and the
great inferiority of this method to tlie method of vaccinating
from arm to arm. The physicians had many failures. It is
also interesting to note that Dr. Spalding, on two separate
occasions, made observations upon patients who had been
vaccinated and afterwards placed in smallpox hospitals, and
freely exposed to the disease for a number of days without
acquiring smallpox. Spalding also received a letter from
Edward Jenner, the discoverer of vaccination, and subsequently a specimen of vaccine lymph directly from him.
Spalding issued at Portsmouth during the following 12
years bills of mortality— so-called— beginning in the year
1801. Copies of these bills were sent to John Adams, then
President of the United States, and subsequently to Thomas
Jefferson, Benjamin Waterhouse and Benjamin Bush. Waterhouse, with his usual critical spirit, made reply in the following letter :
Cambridge, March 18, 1802. Dear Sir: Your letter of the 11th
mst. came duly to hand and I have endeavored to comply with
your request, so far as to send you some matter on the point of a
quill. As to the thread, it is full a month old, but was from a very
perfect case and has been kept in a proper degree of temperature
ever since. I am now so in the habit of taking the vaccine fluid
from arm to arm, that I am not so constant in preserving it on the
thread or otherwise. Considerable attention and patience are
required in the first use of an old thread. It ought always to be
moistened with the vapor of hot water.
You mention my not having answered your last letter. I have
received no letter from you since you wrote to me in answer to one
of mine. I received a printed bill of mortality, 5 or 6 weeks ago,
but no written line whatever with it and I have had no letter from'
you for 4, 5 or perhaps 6 months past.
I have just received "Observations on the Cow Pox" from
Dr. Lettsom. I shall probably publish a second pamphlet in a
month or so. being practical observations, etc. In the meantime I
sent a few to the Medical " Repository " for their next number.
I am glad to find that you attend to the occurrences of Mortality. Excuse me for making a few remarks on the one you were
so obliging to send to me. 1. Did APHTHAE kill the infant, or
was it a symptom of another disorder, or in other words: was it
sympathetic or IDIOPATHIC?
2dly. We very rarely see consumption in patients above 50
years of age, more rarely above sixty and very rarely indeed at 70.
There is a chronic cough and emaciation, and great expectoration
in old people, but it is not the true Phthisis Pulmonalis.
3dly. Is not DEBAUCHERY rather a VAGUE term for a general Head? Does it mean Drunkeness exclusively?
4thly. I never yet saw a very young child with Epilepsy. There
is a wide space indeed, between the convulsions of infants, and
that truly wonderful disease, EPILEPSY.
5thly. Mortification: Was it in the bowels or the feet? As they
are widely different in their cause. See Pott in the LATTER.
6thly. Death from SCROFULA is very uncommon. It predisposes to fatal diseases.
7thly. PAREGORIC: Does it mean that the Child was poisoned
by that composition? If so, had it not better been by Opium as
Paregoric means a Mitigator?
You will excuse these hasty observations that occurred on the
perusal. They have not originated from a disposition to criticise
but from a desire to have them free from every exception. Yours
Steadily, B. WATERHOUSE.
In 1802 Spalding invented a galvanic battery, which gave
rise to considerable corresjiondence, and which unquestionably
was used extensively among his brother physicians. He had
letters asking how to make similar batteries and also their
exact therapeutic itses. He further devised a process for
manufacturing oxygen for inhalation, and later invented a
soda water fountain, which seems to have been quite extensively used. As he neglected to protect his invention by
patents, as it appears in his biography some years later, patents
were secured by other persons, and he was forbidden to use it
without paying a royalty for his own invention. He was an
active writer, especially upon anatomical and surgical subjects.
His practice also extended in surgical line.s, and he performed
operations for hernia, extraction of cataract and removal of
necrosed bone. He continued his interest in vaccination, and
received a second letter from Jenner, who acknowledged the
reception of some interesting details concerning vaccination
and the bills of mortality, for which he thanked him. In
Jenner's letter an interesting detail is given concerning the
good effect of vaccination in controlling cases of smallpox in
Vienna. Prior to vaccination the annual average of such
cases was 800. Four years subsequent to the introduction of
vaccination, but two cases of smallpox occurred iii the city.
Dr. Spalding seems to have had a remarkable facility for
friendship, and made warm friends in many parts of the
country. One of his friends and subsequent correspondents
was Bishop Philander Chase, a boyhood acquaintance, who
subsequently became Bishop of Ohio, and later of Illinois and
founder of Kenyon and Jubilee Colleges. Dr. Luther Jewett
was another friend, a Vermont worthy who liad excelled in
the practice of medicine, the practice of law. the gospel
ministry and the editorship of an influential news])aper; four
distinct branches of effort, in each of which he achieved
marked success. He was also a warm friend of Dr. John C.
Warren, of Boston; Dr. Alexander Eamsay, the famous
anatomist from Scotland, and Dr. George Shattuck, of Boston.
He wrote letters to John Bell, the distinguished Edinburgh
surgeon, and also to Charles Bell, and as his thoughts turned
very much to medicine abroad, he made every effort to get an
opportunity to visit England and the continent to bettur fit
May. 1919J
12i
liimself to teach medicine. He sent a petition to the Secretary
of State of the United States Government, asking that he be
made a .«j)ec-ial messongcr to t-arry (li.<|mtehes to France, and
received a courteous message to the elTcct that the services of
no such messengers were nec(k'(l at that tinu'. He visited
PhihHh'l|)liia in order to lit liinisidf hotter for his profession,
and tlieri' saw tlie eminent Dr. I'liysick, and Drs. Wistar,
Hush, Slii|)|)fii and Harton. lie writes tliat the school in
Philadelphia had 3.")0 medical students and later, when in
Xew York, he contrasts the ])o|)uhirity of I'iiiladelphia and tlie
large nund)er of students witli tiie fact that New York had
only about 100 medical students.
There is an interesting chapter in Spalding's life wiiich has
been detailed at considerable length i)y his biograplier and
deserves mention. In 1809 he became connected with the
Fairfield .\cademy, located at Fairlield, aiwut 10 miles from
Little Falls, N. Y. Fairfield .\cademy was one of a chain of
academies whieli had been establisheil to promote edmation
in tile state under the charge of the Board of Regents. The
great demand for medical men to provide for the needs of an
ever increasing emigration to the west at tliis time gave rise to
many medical sdiools. In addition to the Xew England
.schools founded by Ur. Xathan .Smith, there were schools at
Pittsfield, Mass., and t'astleton, Vt., in addition to Harvard
anil the schools in Philadelphia and Xew York. He was
appointed lecturer at Fairfield .Academy in 1809, and lectured
there for several years. The journey to Fairfield from Hoston
wa.s a matter of three days and nights. He was made lecturer
on chemistry and surgery during his first appointment, while
Dr. George t". Shattuck, of Harvard, was made lecturer on
medicine. The courses .seem to have been not simultaneous,
but t-tindeni, as it were, Dr. Spalding lecturing on chemistry
and surgery for si.\ weeks, and being followed by Dr. Shattuck,
who lectured for tlie .same period on medicine, this making a
term of three months. The success of tlie school was so great
that it became nei-cssary to erect a new building, and ])ermi.ssion was aske<l of the legislature to establish a lottery to
raise $.")000. Ix)tteries, it may i)e remarked, were at this time
a popular method of raising money for educational and
religious purposes. The Washington Monument in Baltiniori'
was startetl ity a lottery, as also the University of Maryland,
the First Presbyterian Church and St. Paul's Church. JIany
<letails are given in the iiiography of S|ial<ling in reference to
the lottery plan, and new light is thrown upon it by the suggestion in one of the letters that, if the Icg^islature granted the
authority, the privilege of the lottery might lie disposed of to
.xonie other parties at a discount. The success of the .school at
Fairfield became .-io great as to e.xcite the cupidity of persons
who were interested in the development of Hamilton .\cademy.
at Clinton, X. Y.. into Hamilton ('(diege, and an effort to
establish a siinilar medical school at Hamilton. The agitation
finally brought an appropriation of $100,000 to Hamilton
-Academy, and it l)ecanie Hamilton College, wiiile Fairfield was
obliged to Im" satisfied with receiving $10,000 for the construction of a building and a <-harter giving the privilege to grant
ilegrees, and thus to become an established medical .<chool.
The following letter, sent by Dr. S))alding to Dr. George
Shattuck, of Boston, gives a very interesting idea of his conleption of the infiuencc of medical teaching, and its benefit to
I he medical teacher:
Dear Sir: I can only say that I regret exceedingly the opinion
of yourself and friends, that your avocations will not sulTer you
to Wsit Fairfield once more. I acknowledge that, at present, the
compensation is not adeqiiale lo the output and the loss of business, but. Sir. 1 do really believe that this school may be made
second to none but Philadelphia. If not. I will join with you in
resignation. What eflect has the Professorship already had on
you? It has compelled you to pay close attention to your profession, to pass the wliole of CuUeu's " Nosology " in review, before
you annually, and llureby qualifying yon for the practice of your
profession more than any other way in which you could have spent
your time. It is the high road to fame, and usefulness. I know
that my sacrifices have been great. I know that yours must be.
But, show mc the man who has risen to be a Prince of Physicians,
while slumbering on the couch of idleness.
Soon after I came to Portsmouth. I resigned my office of Professor of Chemistry in Dartmouth, no doubt from the same
motives that now influence you, with this addition, that my lectures there had to continue three months. I soon found myself
slumbering on my oars and relaxing my pursuits. In fact, so far
from Improving, I hardly kept pace with the others. A kind of
indifference for science pervaded nie: Indignant I aroused. I went
lo Hanover to see Ramsay, I went to Philadelphia, and I planned
a voyage to Europe. This change, Sir, I consider the most happy
circumstance in my wliole Professional career.
Admit tliat you resign your office. Man is an indolent animal.
What inducement have you then, to labor incessantly? None!
Your reputation is as liigh as that of your contemporaries. Then,
wrapped in the lap of affluence and ease, you will slumber and
sleep till old age creeps upon you. when you will find yourself outstripped in the race of usefulness and fame, your opinions so
antiquated as to be regarded not, and yourself a mere old Granny!
Look at the Priaces, or rather. Fathers of Physic. Who have
they been or who are they now? So far as my memory serves me;
Teachers of Physic. Boerhaave, CuUen, Desault. lx>ok at Hush,
Warren and Smitli. What has put them at the head of the profession? Notliing but their being compelled to labor, and annually
to review their profession, and incorporate with their old slock all
the new improvements. Show me a man in private practice who
does this, annually. He is not to be found. But. your friends say
that you can do this, yet stay at home. I acknowli'dge (his, but
tell me honorably. Will you do it? No, Sir, you have no inducement. For a man to be pre-eminently great, there must be a great
occasion. What made Washington Great? Opportunily. You are
now on the same high road lo reputation that every Prince of
Physicians has travelled. If you turn aside, you are lost forever.
These in conjunction with those in my last letter are the reasons
which ought lo inMuence you. You can have no doubt of my
wishes on the sul)jecl. The time for the commencement of the
lectures Is so near at hand, that no successor can be appointed in
season for the next course. I therefore beseech you, on my
account, if neither honor nor fame will move you, to deliver This
One Course, and I will consent to any arrangement that you may
then choose to make If nothing farther, as a mere matter of
policy. I wish you to withhold your resignation till the meeting
of the Trustees of tlie New Medical College and let us see what
they win do for us.
Dr. Mann I knew had be<'n appointed a Hospital Surgeon, but 1
did not know that he had been made Surgeon General. He must
be with the Army by this time, ami cannot be prepared for the
ensuing course. 1 have no objection to this man, but must for
want of room decline saying anything about your successor until
I hear from you again. Your friend, Lyman Spalding.
128
[No. 339
Sliattuck, after serving two terms as professor of medicine,
relinquished the position, but Spalding, in 1813, was made
president of the Fairfield College, and filled most of the chairs
in 1814-1815 and 1816. The number of students seems to have
varied between 50 and 70. Spalding seems to have done very
faithful, conscientious work, for which he received somewhat
irregular paj-, and often more pay in promises than in actual
money. The school remained in active operation until 1839,
when it went to pieces in consequence of squabbles among the
faculties as to the division of fees from medical students. The
fees seem to have been very small.
In 1814, Spalding went to New York to reside, and had an
office on Broadway, for which he was to pay about $200 per
year. His fees from his patients during the first year
amounted to a little more than $1000. At this time, Spalding
seems to have attempted to write a book entitled the " Institutes of Medicine " which, as far as I can learn, was never
published in book fomi, but was circulated in pamphlets,
each chapter furnishing a pamphlet. It was praised by
Shattuck and Waterhouse, and the reception of a sample
pamphlet was certainly acknowledged even by Dr. Caldwell,
but the book seems to have made little impression.
The following letter is from Governor Plunier, of New
Hampshire, a friend of Spalding's :
Epping, N. H., Oct. 24, 1818. Dear Sir: This weelc I received
your letter with your "Reflections on Fever," and Report of the
Trustees of the Free Schools, for which you will please accept my
grateful acknowledgments. I have read your pamphlet with
attention and pleasure, but it is on a subject with which I am not
sufiiciently acquainted to decide with precision. You know the
low state of the Faculty in New Hampshire. We have scarcely
any who write on the subject of medicine, and of the great body
of our country physicians but few who have any books to read.
and what is worse they have little inclination to purchase books,
to read those few that they have, or to investigate the complex and
intricate subjects of their profession. These facts have long
induced me to believe that, in many cases, the patient has more to
apprehend from the ignorance of the physician, than from the
disease, and that it is safer to trust to nature for a cure than to
rely on the prescriptions of those whose knowledge is limited to a
few hard technical terms. With us. the Gentlemen of the Faculty
have made less progress than those of law and divinity: the latter,
indeed, have much to do before they can attain real eminence.
In your profession I have long considered it a desideratum to
have an able but simple work, accurately describing the nature
and functions of the several parts of man in a state of health, the
effect or changes diseases produce on each of those parts and of
the remedies for those diseases.
I would purchase and read such a work with pleasure, and that
pleasure would be enhanced if it was simple, plain and free, so
far as the nature of the subject would admit, from abstruse
technical terms, and of attachment to existing theories. Mystery
is the enemy of improvement, and it is better suited to prolong
the reign of ignorance and of error than to promote that of truth
and science. And, the knowledge of things is vastly more important than that of words.
I really wish we had an accurate Journal kept in different sections of our Country of the actual state of the weather, the crops,
the general diet and regimen of our citizens, the diseases most
prevalent in each, their type, character and mode of treatment,
etc., so as to exhibit the means by which health was preserved and
lost and how far they depended on climate and modes of living.
Such a Society, I think, might be formed of Gentlemen living in
various parts of our Country, with little expense and from whose
reports much information could be obtained which would be useful
to all, and particularly to Medical Characters. I would freely
contribute to such an establishment.
But, I am wandering from the object of this letter, which was
to thank you for your Pamphlets and to say, that if you or the
Historical Society of N. Y., should need any of the few pamphlets
we publish here, it will afford me pleasure to procure and transmit them. I remain with much esteem and respect. Yours, etc.,
William Plumer.
About 1817 Spalding began to agitate the preparation of a
national pharmacopceia, notwithstanding the fact that several
local pharmacopoeias already existed, the most extensive and
authoritative one being that of Massachusetts. His motive in
urging a national pharmacopoeia was due to his desire to
secure uniformity, and also to discard local remedies which
seem to have been used in different parts of the United States
without any sufficient scientific authority. As an example of
such local favorites may be mentioned Scutellaria or skullca])
as a remedy for hydrophobia. It was shown by Spalding that
the authority for the use of this remedy was weUnigh universal. Numerous cures through its employment were reported, and in the literature its claims were overwhelming.
We now know that it is worthless, and its elimination from the
pharmacopceia was promptly made. The plan proposed by
Spalding for the preparation of the pharmacopoeia was an
excellent one, and has practically been followed for the last
100 years.
The pharmacopoeia was originated in a paper by Dr. Spalding, read before the medical society in the city of New York,
in wliich he pointed out the difficulties attendant upon the
present lack of uniformity in the preparation of drugs in the
different states. As a result of the discussion which followed
the reading of his paper, a committee was appointed, of which
Dr. Spalding was chairman, to suggest measures for the
preparation of a national pharmacopoeia. The country was
divided into four districts, known as the nortliern, middle,
southern and western. Through the medical societies of these
regions, delegates were cliosen to meet at some central jioint
in the district to discuss matters pertaining to the drugs to go
into the pharmacopoeia, and to elect two delegates, each to go
to Washington later to prepare the book for publication. The
only two district conventions were those of New England, at
Boston, and of the Middle States at Philadelphia, which met
on June 1, 1819. The meeting in Philadelphia, although
attended only by delegates from the middle district, had done
valuable work in the discussion of remedies aud methods. The
delegates chosen at the two district meetings met in a general
convention in Washington on January 1, 1830, Dr. Spaldiii'jbeing one of the delegates. The two rough drafts from tlic
district meetings were examined and discussed, and the prej):!ration of the pharmacopoeia was outliaied and plans made for
its completion and adoption. A Committee of Publication was
chosen, with Dr. Sjialding as chairman, which met in New
York in June, 1820. The pharmacopoeia wa.s printed in
English and Latin, and was immediately adopted as autlmritative throughout the covuitrv.
Mat, 1919]
129
About the same time Dr. Spalding also had, in addition to
the pharmacopceia, a jdan for the establishment of what he
ternieil a medical police to liave charge of all sanitary matters.
The latter scheme, however, seems to have faded from public
sight.
Dr. S])alding did not live long after the publication of the
pharmacopoeia. In 1821, while walking in the city of New
York, he was struck down by some building material whicli
fell upon his head, and rendered him unconscious. Although
he recovered apparently, he never enjoyed good health, and
gradually went into a state of physical and mental decline.
He gave up practice, sent his family to New England, and
later rejoined them there. He died on October 31, 1831, a few
days after he reached them.
It is evident that he was a man of unusual ability, being
industrious, efficient, and with large powers of initiative.
Imperfectly educated as he was, he had made himself an excellent physician, a remarkable surgeon and anatomist, an
interesting and ins])iring medical teacher, and a member of
the profession full of enthusiasm for its advancement and perfection. He wa.s denied the great desire of his life, the
privilege of studying aiiroad, and doubtless liad lie been able
to do so, and had returned to .\merica with tlie new ideas, his
subsequent lal)ors might iiave resulted in great additions to
the medical knowledge and resources of the country. The
story of his life is a most inspiring one.
N(>T>:. — Since the above sketch was written and presented to the
Historical Club, Dr. Kelly has placed in my hands a copy of tlie
first edition of the Pharmacopoeia of the United States of America.
It bears the following title page:
The
PH.\R.MACOPOEIA
of the
rXlTEn STATES OF AMERICA.
1820.
By the
Authority of tlie Medical Societies and Colleges.
Printed by Wells and Lilly.
For Charles Ewer. No. 51, Cornhill.
Dec. 1820.
It is bound in leather and is in excellent state of preservation.
The name on the fly leaf cannot be deciphered definitely. It is
in pencil and is dim in places. The inscription seems to be James
Burbeck. 1827. It has undoubtedly belonged to a druggist or
apothecary as it contains many recipes neatly interleaved In
various portions of the book. There are also prescriptions for
various diseases. The book contains an interesting Historical
introduction explaining the object of the preparation of the
National Pharmacopeia. There is also a Preface which gives full
details as to the movements which led up to the preparation of the
work. In the list of delegates orisinally selected to attend district conventions to prepare lists of medicines and to select local
committees are to be found names eminent in the profession one
hundred years ago, many of whom figured in medical literature.
A good many of tlicm also were meiubers of the linal committee
which prepared tlie National I'liarmacopeia.
From New York there were; llavid Ilosack, Samuel L. Mitchell.
T. Romeyn 13eck. Lyman Spalding, John W. Francis and Valentine
Mott. From Massachusetts; Jolin C. Warren. Jacob Uigelow,
James Thaclier and George C. Sliattuck. From New Haven;
Eli Ives and Nathan Smith. From Philadelphia; T. T. Hewson
and Joseph Parrish. From Maryland; Nathaniel Potter, Elisha
DeButts, Samuel Baker and Ennals Martin.
THE EFFECT OF DIFFERENT BLOODS ON THE GROWTH OF
B. INFLUENZAL'
P.y T. M. liivos. M.I)., Ballimorc :Md.
The growth of B. infiwnzx has been described as small dewdrop colonies invisible by direct light, but becoming larger
when near colonies of other bacteria, as staphylococci, pneumocoeci and streptococci, this latter phenomenon being called
obligate symbiosis. This is a correct description of the colonies
as they appear on human blood agar.
In making routine throat cultures it was noticed that on
certain days the colonies of B. influenzcB were large and easy to
isolate, whereas on other days they were very small and often
overlooked. The results from day to day differed so much tluit
an explanation was sought. It was found that on tiie ilays
when the colonies were large either cat or rabbit blood luid
been used and human blood when thev were small or over
' From the Departments of Pediatrics and Patholog>', Johns
Hopkins I'niversity.
looked. Tiiis led to the comparison of the effects of different
bloods and sera on the growth of B. influenza:.
In three petri dishes respectively was placed 0.5 c. c. human.
0.5 c. c. cat and 0.5 c. c. rabbit blood. Then 10 c. c. of meat infusion agar were added at 40° C. from the same llask to each
of the dislies. After liic agar had solidified, each plate was
streaked with a broth siuspension of two strains of B. influenzcE. The growth on the raiiliit blood (Fig. 1) and cat blood
agar was lu.vuriant. The colonies which were well separated
became very large and slightly opaque, and when they were
48 hours old some were umbilicatod or checker-sluiiied. The
growth on the human blood agar (Fig. 2) appeared very
slowly and at the end of 48 hours was still seen with difTiculty.
Three other plates were made lus above and streaked wilii
a broth suspension of B. influcnzw. In the center of ea<li
plate there was also streaked a broth suspension of piicunio
130
[No. 339
cocci. On the rabbit blood and the cat blood agar the colonies
of B. influenza grew best at the edges where they were well
separated. There was no tendency to be large.'it near colonies
of pneumocoeci (Fig. 3). On the human blood agar the
colonies of B. inftuenzm were just visible at the edges but
grew large near pneumococcus colonies (Fig. 4). This has
been repeated with six lots of meat infusion agar and each
time the difference has been observe<;l.
B. influenzcE grows well on rabbit blood agar, cat blood agar
and Averj' medium when 1 per cent of washed cells is added
to the agar at 95° C. There is also no difficulty in growing
the bacillus on " chocolate blood agar " even when human blood
is used. If the " chocolate agar " is good there is no obligate
symbiosis, but at times, when the medium is improperly made,
this occurs. Very rarely does the symbiotic relationship appear
on rabbit or cat blood agar.
It would seem that fresh human blood either has an inhibitory effect on the growth of B. inflii^nzce which pneumocoeci
or other bacteria remove by their growth, or else it lacks something which is supplied in the neighborhood of other bacteria
by the products of their metabolism. The fact that it grows
well on Avery medium and on " chocolate human blood agar "
makes it seem most likely that there is an inhibitory factor
which is removed by heating or by the growth of other bacteria.
Two tubes each containing 0.5 c. c. of defibrinated human
blood were inoculated respectively with api)roximately 100,000
influenza bacilli and "pneumocoeci. Two tubes of 0.5 c. c.
defibrinated rabbit blood were likewise inoculated. A loopful
from each was streaked on a separate rabbit blood agar plate
20 minutes later. There was a heavy growth (400-500
colonies) on all the plates except the one streaked from human
blood and influenza bacilli which had only several colonies.
After four hours' incubation a good growth was obtained from
all except hiunan blood and influenza bacilli which was sterile.
To be certain it was sterile an extra plate was streaked with
one-tenth of the +++++
CONTENTSs of the tube. Still no growth was
olitained. This precaution was taken because it had been
observed that influenza bacilli' occur in chains and clmnps in
liuman blood and serum whereas in smears from rabbit blood
and serum they are found diffusely scattered. Clumping could
account for a marked difl'erence in the number of colonies from
a loopful, but not for a sterile plate from one-tenth the +++++
CONTENTSs
of a tube.''
Approximately 100,000 influenza bacilli were added to
0.5 c. c. meat infusion broth, 0.5 c. c. normal human serum,
and 0.5 e. c. rabbit serum. The broth was used as a control.
The tubes were incubated for two hours and a loopful from
each was streaked on a blood agar plate. A heavy growth was
obtained from the broth, less from the rabbit serum, and only
a few colonies from the human serum. After 18 hours' incubation, the human serum was sterile while there was a heavy
growth from the rabbit serum (Figs. 5, 6, 7, 8, 9).
- Uniformity of growth has been sought by using rabbit blood
agar for plating and for each experiment the plates were all poured
at the same time from one large flask of meat infusion agar.
Sera from four adults and one infant, some of whom had
had influenza, others not, have been tried with several strains
of influenza bacilli and all have shown a bactericidal effect.
Sterile plates cease to be obtained at different points in the
dilutions of the various sera when a constant number of bacilli
are used for an inoculation. The same is true when one serum
is used and the number of bacilli inoculated is varied. Normal
human serum kills influenza bacilli rapidly, in many instances
causing the death of thousands of bacteria in 20 minutes at
room temperature. This bactericidal property is lost very
rapidly upon dilution. Rabbit serum, also, is slightly bactericidal and, if a light inoculation is used, the midiluted normal
serum may yield a sterile plate. There is no comparison, however, between the two sera. Guine'a-pig serum, too, is not very
bactericidal for B. inflxienzce.
Inactivating himian serum at 54° C. for one-half hour
markedly decreases its bactericidal properties for B. influenza.
Normal rabbit and guinea-pig sera were tested at the same
time with normal and inactivated human serum. Rabbit
serum decreased the number of colonies at first, but this effect
soon disappeared and at the end of 18 hours a heavy growth
was obtained from the rabbit and guinea-pig sera. Even
inactivated human serum kills in 12 to 18 hours.
Experiment Showing the Difference Between Normal and Inactivated Human Serum. The Count.s are Reported in Round
Numbers for Convenience
Dilutions of normal
and inactivated
Approximate
inoculation
of each tube
with B. in
fiuenza:
Number of colonies obtained at different times by
streaking a loopful from each tube
on a blood agar plate
liuman aerum
20 minutes
4 hours
18 hours
Serum
Locke's
Solution
Normal
Inactivated
Normal
Inactivated
Normal
Inactivated
1.00 c.c.
0.75 c. c.
0.50 c.c.
0.25 c. c.
0.00 c. c.
0.25 c. c.
0.50 c.c.
0.75 c. c.
100,000
100,000
100,000
100,000
35
20
40
150
300
300
200
250
300
300
300
300
10
200
400
Attempts have been made to reactivate the inactivated
human serum with rabbit and guinea-pig serum as they do not
inhibit the growth of influenza bacilli to any great extent.
This has been accomplished a number of times. It has been
accomplished also with normal human serum. An objection
might be raised to the use of normal human serum because
it is in itself bactericidal. The experiment as shown in the
table on page 131 .seems to show that it can be done.
During the epidemic of influenza last fall thousands of antemortem and post-mortem blood cultures were taken and very
few positive results were reported for B. influenza, de.spite the
fact that at autopsy they were as numerous in many of the
lungs as pneumocoeci and hemolytic streptococci which were
easily obtained in a large percentage of the post-mortem blood
cultures. Positive blood cultures are at times obtained from
patients with influenza endocarditis and from children with
PLATE XIV
F|... :.. -i.r.,.,;i, r.«.,ii,i,K ;. .u. .li.akinlfa
rabbit blood Hg^r pUK »illi • loofiful of meat
Infuaion broth which hxl been inoculateil with
ft .v»l-fr^--r n"-? nr''ihflf<»d 'wo hour".
THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919
•/ v.- • .#• V '.:•.•* . •
Fin. 8.— Growth obtniniil aa in KiK. R i-xccpt
that incubation was for eJKhtccn houra iiiatcail
oltwo.
Kiii.li.-firowth obialniMl iia in hit. 7 i-xep|.t
that incubation una (or <'l([litcen houra inatcad
of two (plate iaatiTik-).
May, 1919]
131
influenza meningitis, but these are the exception when compared with the patients who died during the epidemic and had
influenza bacilli in the lungs at autopsy. B. infiuenza eitlu-r
does not invade the blood stream, is promptly killed when it
does, or, if alive, is not recovered by the present cultunil
EXfBRI.MK.NT Til SilOW Rl--\rTIVATl<).N OF THE I.VAITIVATEU HlMA.N
SERf.M AMI Resix)RATION OK ITS Baotkkiciuai, Pkoperties. Thb
Counts ark Rkpokted in Rocnd Nimbers for Convkniencb
Number of colonies obtained in streaking blood
agar plates witli a loopful from each
tube at different times
Smin.
,hr.
2 bra.
4bri.
7 hrs. U brs.
0.5 c. c. normal 100,000
human serum.
0.5 c. c. inacti- 100,000
vated human
Derum.
0.4 c. c. inatti- lOO.OOO
vated human
serum +0.1
c. c. norma!
human serum.
0.4 c. c. Locke's 100,000
solution 4- 0.1
c. c. normal
human serum.
400
400
400
400
400
50
300
400
25
200
200
300
125
400
methods. As shown above, human serum and defibrinated
blood are very bactericidal for the influenza bacillus in vitro as
compared with other bloods used and also as compared with
the pneumococcus. This bactericidal property is lost rapidly
upon dilution, and laboratory strains have been grown in
100 c. c. of meat infusion broth with 10 c. c. human blood
added even when very light inoculations have been made (le.>;s
than 100 bacteria). Although conclusions cannot be drawn
concerning hai>i)cnings in vivo by what occurs in vitro, may it
not be possible that a combination of such factors accounts for
so many negative blood cultures for H. inftuciiztp when they arc
so abunilant in many lungs at autopsv?
CONCLUSIONS
1. B. infiuenzcE grows well and produces large, often o|)aquc,
colonies, upon the projjcr medium.
2. B. infiuemm grows better on rabbit blood and cat blood
agar than on human blood agar. Some of the discrepancies
between the findings of various laboratories during the i'\ndemic may be explained possibly by the difference in the media
used.
3. Obligate .symbiosis occurs more conmionly on liunum
blood agar than on rabbit or cat blood agar and in part, at
least, is due to the inhibitory effect of the blood which is
removed by heating or by the growth of other bacteria.
4. Defibrinated hmiian blood and normal hujuan serum arc
very bactericidal for the strains of influenza bacilli studied as
compared with defibrinated rabbit blood, normal rabbit .serum
and normal guinea-pig serum.
5. Inactivated human serum, although less bactericidal than
normal serum, also kills in from 12 to 24 hours.
6. There is evidence that the marked bactericidal properties can be restored to inactivated human serum by a quantity
of normal human serum which by itself is not bactericidal
in the same lengtli of time. Keactivation can be accomplished
by other normal sera.
OBSERVATIONS ON THE CLINICAL PHARMACOLOGY OF DIGITALIS
By Ai.FRKD M. Wedd,
{From the Medical Clinic nf the Clcvelniitl
Although introduced into therapeutics by Withering in
1T85, digitalis received but little consideration from medical
scientists until comparatively recent years, and the modem
clinical knowledge of the drug may be said to date from the
work of Jlackcnzie," reported in 1911.
The present communication is comjjiled from data on un.selected cardiac and caniiorenal patients admitted to the I'ity
Hospital during the past year to whom digitalis was given,
including 29 in who.se ca.ses electrocardiographic records were
taken every 24 hours, or more frequently, during the period of
administration of a standardized preparation of the drug.
I'rkparation and Dosaor
The preparation was the tincture, two different lots being
u.sed, each of which had been standardized by Prof. R. .\.
M. D., rittsburgh, Ta.
I'ity Hospital. Scrvi( e of Dr. K. P. Carter)
Hatcher, of ("ornell University. Digitalis dosage, referring
to the tincture, in clinical practice is subject to rather wide
variation; from a ihiily dose of 1 c. c. or less, used by some
practitioners, tlirough the dose of from 4 to 6 c. c. recommended by ilackenzie, up to the massive doses of 15 to 25 c. c.
in 2-1 hours (usually O.lKi c. c. \wt |)ound of body weight),
advocated by Kggleston ' and recently studied ami indorsed by
White and Morris.'
In this work it was desired to give enough of the drug to
bring the ])atient pmnijitly under its influence, but to avoid
such amounts as might by the early producti<in of toxic symptoms prevent us from following its jirogressive action. The
daily dose us«'d was from 8 to 12 c. c, usually 10 c. r\, and this
was continued until definite evidence of digitalis action was
'Mackenzie: Heart, 1911, XI, 273.
'Eggleston: Arch. Int. Med., 1915, XVI, 1.
' White and Morris: Arch. Int. Med., 1918, XXI, 740.
133
[No. 339
noted. The indications to discontinue the drug were alimentary disturbances, derangements of the cardiac mechanism
or slowing of the pulse rate to a level beyond which it was
deemed inadvisable to continue.
The cat unit of Tincture A was 1.11 c. c. and it was, acccjrdiiig to Professor Hatcher, a fairly good specimen. This ])re]iaration was given to five patients. The following are lirief
details of these cases:
No. 320. Diagnosis, clironic myocarditis. Age, 16 years: body
weiglit, 125 pounds. Total dose, 72 c. c. Rate wliile in bed slowed
to 60.
No. 299. Diagnosis, chronic myocarditis. Age, 44 years; body
weight, 140 pounds. Total dose, 115 c. c. No clinical effect.
No. 321. Diagnosis, chronic myocarditis and nephritis. Age,
48 years; body weight, 135 pounds. Total dose, 101 c. c. Rate,
when up, reduced from 120 to 110. No toxic symptoms appeared.
No. 323. Diagnosis, chronic myocarditis and nephritis. Age,
52 years; body weight, 140 pounds. Total dose, 137 c. c. Pulse
slowed from 120 to 60 after 119 c. c, then increased to 84 and
remained at that rate. No toxic symptoms.
No. 332. Diagnosis, chronic myocarditis with atrial fibrillation,
nephritis. Age, 45 years; body weight, 140 pounds. Total dose,
149 c. c. Fulse rate slowed to 56. No toxic symptoms.
These were the first cases studied and in tliree of them the
drug was discontinued because it was feared that some unex])ected result might occur, since the dosage then far exceeded
that usually given.
In the remaining work a second tincture was used, the cat
unit of which was 0.85 c. c. The total dosage with this
preparation showed considerable individual variation. In
No. 368 nausea and vomiting occurred after 20 c. c, while in
No. 374, 100 c. c. were given without the development of any
toxic symptoms. Because of an oversight No. 304, a case of
complete dissociation, received 280 c. c. during a period of
10 weeks without showing any clinical symptoms. In nine
cases toxic sym])toms were produced by 40 c. c. or less; in
seven lascs, by 40 to 60 c. c. ; six patients took from 95 td
100 c. c. The average total dose required for the production i>r
toxic symptoms in 22 patients was 52 c. c.
No. 321 entered the hospital a second time six months
after the first admission, with moderate decompensation, presenting a clinical picture similar to that when first seen.
Digitalis was again given and nausea and vomiting occurred
after 35 c. c. of the second tincture, whereas 100 c. c. of the
first produced no clinical effect. The inefficiency of the first
tincture was undoubtedly due to delayed absorption from tlic
alimentary tract, as will be shown when the effect of digitalis
on the T-wave is considered, but the cause of this is not known.
It is evident, however, that biological standardization showiim'
approximation to theoretical strength is no guarantee of the
clinical efficiency of a given preparation of the drug. Individual power of absorption for a given tincture appeared to Iw
quite uniform, so variation in toxic dosage is due to variatido
in individual tolerance for the drug.
No constant relation between the amount of digitalis that
could be given and the age or body weight of the patient or the
condition cil' the nivocardium could be discovered.
Effect on Edema, Dyspnea and Cyanosis
That digitalis has no specific diuretic effect is now generally
recognized. The decrease in edema depends on improvement
in the circulation, and rest in bed alone is an important factor
in bringing this about. In three purely cardiac cases the
edema had almost entirely disappeared before any digitalis
action was recorded. Its removal in cardio-renal cases was
much more slowly accomplished. The value of determining
the output of phenosulphonaphthalein before and after the
administration of digitalis may be pointed out as a means of
determining the relative cardiac and renal elements in the
original clinical picture.
The alleviation of dyspnea was also seen to be an indirect
digitalis effect, depending on improved pulmonary circulation,
the rest, morphin and venesection, when used, affording the
immediate relief, while more permanent removal of this distressing symptom came with improvement in the myocardium.
Cyanosis was a characteristic and persistent sign of myocardial involvement. In those cases in which true myocarditis
was believed to be present, and especially in those whose
electrocardiograms showed intraventricular or bundle branch
block, even though free from edema and dyspnea on moderate
exertion, the cyanosis was not influenced by any treatment.
The Effect on the Heart E.\te
It was formerly maintained that the function and the
prinpipal action of digitalis was to slow the pulse. However,
excessive slowing with the ordinary use of the drug usually
occurs only in atrial fibrillation, and according to Cohn *
reduction in rate is not constant, and to produce slowing is
not a function of digitalis in therapeutic doses. In five cases
of fibrillation the pulse rate was reduced to 55 or lower before
or without the onset of toxic symptoms ; in one case it fell
from 130 to 84 when nausea and vomiting occurred.
Eighteen cases with normal mechanism were studied ; in five
the rate fell to 60 or lower ; in three there was no change :
ill the remainder the reduction of the initial rate varied
between 8 jier cent and 33 per cent, the average fall being
about 20 per cent. Contrary to the statement of Sollman '
that fairly normal hearts are slowed by large doses, but that
this is due to blocking of impulses from the atrium, the rate
in six cases was reduced to 65 or lower before the onset of
tdxic symptoms with an increase in the P-R interval varj'ing
from 0.02 to 0.05 sec. as the only sign of block. In one case
the rate after 10 c. c. had increased from 89 to 96 and after
20 I', c. nausea and vomiting occurred, the rate remaining at
96. In a number of cases after reaching a low level the rate
increased as the point of toxicity was approached, c. g.. No.
323 ; rate after 119 c. c, 60, after 137 c. c, 84. This is comparable to the ex])erimental findings of Robinson and Wilson °
in which slowing continued until about three-fourths of the
*Cohn: Jour. Amer. Med. Assn., 1915, LXIV. 463.
'^Sollman: Manual of Pharmacology, 1917, Philadelphia.
"Robinson and Wilson; Jour. Pharni. and Exp. Therap., 191S,
X, 491.
May, 191!) J
133
U'thal dose had been injected when acceleration set in and
continued until fibrillation replaced the normal beat. Tiiis
acceleration is due, accordinj; to Cushny, to increased irritability of the heart muiide rather than to any nerve influence.
It d(x\< not seem jKissiblc to form any definite conclu.«i(in
alx)Ut the time factor in the slowinfr of the initial rate.
Usually there was a jrradual fall of from four to ten beat.^^
daily. Other ajjents than difritalis, the rest in bed and the
sedatives given, certainly contribute to the first sudilen lowering which occurs before there has been time for any specitic
digitalis action. Thus, in Xo. 329, a case of fibrillation, an
initial rate of HiS fell to 108 in 12 hours, during which 10 c. c.
of the tincture had been given. Comparing this with other
eases it does not seem reasonable to attribute this prompt
reduction of 60 beats solely to digitalis. In general, there
seemed to be a gradual ilecline in rate, which in the fil>rillation
cases nearly always progres.<ed to a much lower level.
In each of 13 csises of atrial fibrillation examined while
under the influence of digitalis, an increase in rate occurred
following the administration of atropin (the dose usually given
was 2 mg.). In all of these ca.<es in which the effect of atropin
was studied both before antl after digitalis, the ma.ximuni rate
after atropin in the digitalized heart was not equal to tiiat
obtained before any digitalis was given ; in five of six eases
this decrea.«e was exactly GO beats, and in one 72 beats.
Atroj)in was given to 13 ca.ses witli normal mechanism lieforc
and after the course of digitalis; in seven tliere was a decrease
in the maximum e.<cape ranging from 4 to 32 beats; in Hiree
there was an incrca.<e in the maximum of 3, 4 and 17 beats,
res|)ectively ; three cases showed no escape after digitalis.
TllK KfFE( T (IN THK Hl.iiOl) rHKSSlKK
.Altiiough the digitalis ixidies profluce a characteristic rise
of bifiod pressure in animals, the effect on the pressure in man
is very variaiile. The subject has been recently reviewed and
studied by Eggleston.' In 1(5 cases the blood pre.«sure was
carefully followed: in 10 there was no appreciable change;
in three the systolic increa.^ed without change in the diastolic:
in two casi-s with high pressure the .systolic fell 3.") mm. and
30 mm., respectively, with a corresponding reduction in the
diastolic of 10 mm. an<l 2.> mm.; in one the diastolic fell
2.J mm. while the systolic renniined unchanged. The conclusion is that the alteration in blood pressure is again an indirect
digitalis effect which depends on the improvement in thi'
circulation and is always in the direction of the optinuini
pressure for the individual.
ToxK Kkkkcts
The manifest-atir)ns regarded as evidences of digitalis
toxicity were all included in the alimentary disturbances nr
cardiac irregidarities. From 24 tf> 3(5 hours In-fore actual
nausea and vomiting <wcurred, many |)atients complained "f
general malaise, often headache or of some indefinite and
indescribable sensation of discomfort and usuallv refused food.
Eggleston: Jour. Amor. Med. Assn.. 1917. LXIX. 951.
Considering 20 cases, nausea occurred in 12 and vomiting in
six of these; diarrlnea was encountere<l five times. In nearly
all eases these disturbances disai)])eare(i promptly after discontinuance of the drug. In Xo. 355 miu.<ea aiul diarrhum
persisted for fo.ir days. This was the only instance of anything that might be regarded as evidence of the so-called
cumulative action if digitalis. The central origin of the
nausea and vomiting i>.-oduced by digitalis has been established
by the work of Ilatchar and Eggleston." In six cases it was
necessary to discontinuo the digitalis becau.se of the onset of
serious cardiac irregularities unaccompanied by alimentarv
symptoms.
DiGIT.VUS Irregil-vrities
Digitalis " coui)ling," a familiar sign of excessive digitalis
dosage, appeared twice in the series. The occurrence of premature beat^ at irregular int^-rvals was frequently seen, usually
at the time of otlier evidences of toxicity. These ])rcnniture
beats, an expression of heightened irritai)ility of the ventricular muscle, always disa|)peared after atropin.
Sinus arrhytlunia <lue to digitalis occurred in two cases.
In Xo. 334 (see Fig. ID) it disappeared |iromptIy after
atropin, but returned and persisted, though gradually decreasing, for 10 days. In Xo. 37.J the arrhytlunia was not removed
by atropin, although there was an escape of the pacennikcr
(Fig. oD).
Production of " jiuisus altcrnans," dcscrilicil by Mackenzie
and others was not encountered. In one ca.se in which that
condition was originally present the alternation disappcareii
under digitalis (Fig. 2). ."Similar results have been reported
by Wimlle.*
In Xo. 342 after 25 c. c. of digitalis atrial tachycardia with
irregular ventricular response and varying conduction time
was present. .N'ornuii nirchanism was rcstoreij bv atropin
(Fig. 3).
That com|)lcte atrioventricular dissociation may occur iluring the administration of digitalis is well known. Christian '"
has reviewed some of the literature and reported ca.ses. Hoi)inson and Wilson ' have shown that in cats with the vagi intact
complete dissociation constantly occurs when 7.") per cent of
the mininnim lethal ilose has liecn given ;.with the vagi cut. the
effect on conduction is not constant. In two cases transient
complete di.ssociation occurred, beside the case of atrial tachycardia with high-gradi- block previously mentioned. The production of dissociation by action on the iidiibitory mechanism
is illustrated in Fig. 4, which shows in sequence, prolongation
of the I'-R interval, dropped beats and dissociation. In these
cases of di.ssociation atrr>|iin restored the normal mechanisu)
and this persisted during the hour under examination in the
laboratory and was still present at examination 12 hours later.
That "e.sca[)e" from vagus a<'tion on the con<luction system
may occur is illustrated in Fig. 5; tlu- I'-H interval had
•Hatcher and Egglfston: Jour. I'harm. and Exp. Tlierap.. 1912.
IV. 113.
•Windle: Quart. Jour. Med., 1917, X. 274.
"Christian: Arch. Int. Med.. 1915. XVI. 341.
134
[No. 339
lengthened from 0.12 to 0.22 sec, dropped beats were present
and complete block was anticipated ; however, a record taken
eight hours later showed the mechanism to be normal and the
P-K interval 0.16 sec.
Changes in the Electrocabdijgram
Modification of the T-wave of the e^ jctrocardiogram by
digitalis has been carefully studied 'jy Cohn and his coworkers." The following changes in tlie T-wave were observed
in this study: Any degree of flattening of an upright or
inverted wave until the isoelectric line was reached ; inversion
of an upright wave ; reversion of an inverted wave ; the formation of a diphasic wave, either alone or in conjunction with
any other change. The change in the wave continues throughout the administration of the drug so that its conformation
varies from day to day with the amount given. Compare the
T-waves in Figs. 1 and 3. These changes are attributed by
Cohn to an alteration in the muscle balance, resulting in turn
in an alteration of the relation of apex to base negativity.
This action is for the most part on the myocardium itself.
That the true digitalis effect may be masked by vagus stimulation is seen in the changes that frequently occur after atropin.
The height or depth of a wave may be affected or reversal may
occur, as in Fig. 3. These changes disappear with the action
of atropin and the specific digitalis effect is again evident.
In every case the first definite digitalis effect was a change
in the T-wave. This was found by Cohn in his cases and
Robinson and Wilson ' in their experimental study observed
the first change to be a flattening or inversion of T, which
occurred with 25 per cent of the lethal dose.
A comparison of the T-wave changes produced by each of
the tinctures used is interesting and points clearly to slow
absorption of the first as the cause of its inefficiency. In
No. 320 lowering of T, was observed after 16 c. c, definite
inversion after 84: c. c. In the four remaining cases in which
the first tincture was used an average of 34 c. c. was given
before any definite change could be recognized. With the
second tincture definite changes were recorded in most cases
after 10 c. c. or less. In No. 371 Tj was lower after 5 c. c. ; in
No. 368 Tj was definitely inverted after 10 c. c. Eecords were
seldom taken between 10 and 20 c. c. and no attempt was made
to establish the minimum amount that would produce a change.
From this small series in which large doses were used so
that changes in more than one wave were recorded simultaneously it is not possible to say which T usually changed
first, but it did appear that T. is most frequently affected and
undergoes the greatest change.
The disappearance of the digitalis action may likewise be
followed by changes in the T-wave which begin soon after the
drug has been discontinued. The duration of the digitalis
effect, as might be estimated by these changes, was not determined.
The alteration in tlic P-wave seen in some of these cases
has been considered elsewhere." In nine cases, 30 per cent of
"Cohn, Fraser and Jamison: Jour. Exp. Med., 1915, XXI, 593.
"Carter and Wedd: Arch. Int. Med., 1919, XXIII, 1.
the series, the P-wave was affected; in eight of these the
change occurred only in the third lead, and in one in both the
second and third leads (Figs. 1 and 5). In five cases an
originally inverted P was rendered upright by digitalis and in
three of these the return to the original form was followed
after the drug was discontinued. In four of the cases of this
group a temporary reversion occurred after atropin. In four
cases an originally upright wave was inverted by digitalis and
in three of these the wave was reversed by atropin and remained upright, whereas in the fourth the inverted wave was
upright 12 hours after the discontinuance of digitalis. Satisfactory explanations for these observations are wanting. There
may be a rearrangement of atrial muscle fibers, but the
response to atropin in both groups indicates greater vagus
influence than in the case of the T-wave. Concerning the
limiting of the effect to the third lead, it may be noted that
this lead represents primarily the left side of the heart, and
all but two of these cases clinically showed marked enlargement to the left, and in six the electrocardiogram was of the
type characteristic of left ventricular preponderance.
The occurrence of tlie U-wave as a component of tlie ventricular complex in the normal electrocardiogram is recognized. According to Lewis," it is not uncommon and is related
to the early events of diastole. In the records of this laboratory it has seldom been seen. In one case (Fig. 6) a U
summit appeared after 30 c. c. of digitalis had been given and
continued throughout the remaining observations. It was not
due to the appearance of a latent wave with a slower rate, for
the rate when it was first seen was faster than the original, and
it did not seem to be influenced by atropin. As the patient
left the hospital, changes occurring after digitalis was discontinued could not be followed.
In his text Sollman states that, in man, a-v conduction
is constantly impaired and that this is an early and positive
sign of digitalis action, and Cohn and Fraser " found changes '
in 12 patients studied by them, including four who had no
heart lesion. According to AVhite and Sattler " " this impairment of conduction is practically entirely due to increased
vagus tone " and they report that in every instance after
digitalis in which delay in conduction amounted to more than
0.05 sec. atropin reduced the P-R interval to less than its
original value. In six of 21 cases in this series there was no
appreciable change in the P-R interval. Measurements were
made with calipers and a hand lens, but are believed to be
sufficiently accurate for clinical purposes. In not one of five
cases in which the conduction time was prolonged 0.05 sec. or
more did atropin restore the original, and in two cases in which
complete dissociation occurred the P-R interval in the normal
mechanism after atropin was longer than in the original
(Fig. 4). In the case with atrial tachycardia and high-grade
block the P-E interval after atropin was the same as the
original.
"Lewis: Clinical Electrocardiography, 1913, London.
"Cohn and Fraser: Jour. Pharm. and Exp. Therap., 1913-14, V.
512.
» White and Sattler: Jour. Exp. Med., 1916, XXIII, 613.
THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919
r
1
>»
1
t
I
R
f
[
[
[
I
i
;
>
Ui
V
f
THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919
PLATE XVII
Fiii. 2 (Case 321). — A. on admission; B,
after 102 c. c. of digitalis.
HBn^iji^^i*^iiP^N*jii^i'^i*iFVfci^*'*^wMi^^^
IKWl^lll
i:^ ^ -^  -a
^ ' ^ ' ^
mwii'liii mimitmiWjiMrmi] i owji^n "i
;:-- "f vv;-:::" / V - ^".f'--=
-f immm
- ' -H:5E-i
y^-mmAj'jm>^
Fig. 3 (Case 342). — A, on admission; B, after
12 c. c. of digitalis; C, after 25 c. c, atrial rate
216, ventricular rate 80; D. 30 min. after atropin;
E. 1 hr. after atropin; F. 12 hrs. later.
Fig. 4 (Case 351). Lead II.— A. on admission; B, after 24 c. c. of digitalis; C,
after 72 c. c. ; D, after 96 c. c. ; E, after
atropin.
THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY. 1919
PLATE XVIII
rAiN>/VvV^'^i'N*s^/
/9
U¥«'w*'^*'^'w**^' " '***^* ^ ^ ^ W' * *''**^ *» «>ii n »»»i^
'«M,^-''^\V-*-**/-- s,,^^
TC
:3> A. an.
HMMM V«y^MHMMM«<MMMM«
-rff
Fig. 5 (Case 375).— .4. on admission; /}. aft. r nn c c of diK'iialis;
C. 8 hrs. later: D. after 100 c. c. (a) ; after airopiu (b).
:2)o.
I I
^t^mmmi p^^^
^^^-^^-A.
S,0m^*m^-Si
I I
^^,^,i0^f/m^Jf^^0^^
Kic. 7 (Case 354). Lead II.— .1. on
admission: «, after 22 c. c. of digitalis:
C. 19 lirs. later, after 29 c. c. (a) ; after
atropin (b); /J. after 39 c. c. (a): after
atropin (b).
fl a.
tr
y'*S/*V Xy*-V S,,r^V H.V<-v
atropin.
di»!iUiM.> 1 .1 p . .111. I HI II. 1. 1
later.
I
May, 101!) I
JOHNS HOPKINS HOSPITAL lULLETIN
135
Direct action on the conducting; tissue may be illustrated
i)y Xo. 323: orijrinal P-R, 0.120; after digitalis, 0.213; altor
atro])in, 0.163, and there was no escape of the pacemaker. In
Xo. 27!) in which a lenirthening of 0.02 sec. occurred there
was no shortening of conduction and no sinus escape after
atropin. Also consider the I'-R intervals in Fig. 7. In otiior
cases there was partial or complete reduction of the conduction time. The data ohtaincd tend to show that impairment
of conduction by digitalis nuiy be due to either increased vagu-^
tone or to direct action on the conducting system, or to a
combination of both, which is the usual mechanism in cases of
pronounced action.
Definite ini|)airmcnt of conduction was certainly not an
early evidence of digitalis action, but a gradually progressive
one, and an appreciable change in it* time relation .seemed
comparable to the finding of Robinson and Wilson, that prolongation of conduction time occurred after 50 per cent of the
lethal dose had been given.
But few cases with an original conduction time of more
than 0.18 sec. were studied. In Xo. 364, a referred patient,
an original conduction time of 0.25 which had been increased
to 0.29 by 12 c. c. of digitalis was restored completely by
atropin. The possibility of escape from digitalis action on
the conduction system has been mentioned (Fig. 5). Xo
criterion was apparent by which a marked effect on conduction might be predicted and the conclusion reached is that of
Cohn.* that any effect on conduction is a specific effect of the
drug, a])art from any pre-e.xisting damage in the .system.
Action ix Fibrill.\tiox .vxd Flutter
There is sufficient satisfactory experimental evidence that
digitalis produces its characteristic effects by acting centrallv
in the medulla and locally on the heart muscle. The usual
test for differentiating central and local action is the behavior
after removal of vagus intluence, by section of the nerve or
the use of atropin. That the various digitalis effects may l)e
pro<luced in man through either mechanism alone or througli
both simultaneously has been jiointed out when considerin":
the specific digitalis actions.
In 1871 Traube showed that digitalis slowing was due to
(itimulation of the vagus center and this has been confirmed
by many experimenters since that time. Cushny " has demonstrated that in the perfused mannnalian heart, in certain rare
cases with normal mechanism in man and specially in atrial
fibrillation in man, digitalis may slow the pul.<e inde|)endently
of the inhibitory mechanism. Robinson and Draper" have
shown in atrial fibrillation in man that mechanical stimulation of the right vagus nerve usually cau.i^ed marke<l slowing or
stoppage of the ventricular rhythm and state that the ventricular pauses were apparently due to blocking of .stimuli
from the atria. Ilirshfelder" found that in dogs with artificially induced fibrillation the heart could be markedly slowed
"Cushny; Jour. Pharm. and Exp. Therap., 1918. XI, lO.S.
"Robinson and Draper: Jour. Exp. Med.. 1911, XIV, 217.
" Hirshfelder: Jour. Pharm. and Exp. Tlierap.. 1915, VI. 597
by digitalis and that tlie rapid arrhythmia promptly returned
after paralysis of the vagi with atropin, and also that further
.^lowing and com|)lete block could be i)roduced after the vagi
liad been paralyzed, although the fibrillation continued. Commenting on this work, Cushny says: "But this is not the
characteristic reaction in clinical fibrillation as he seems to
suppose; the slowing in these cases is independent of tiie
iidiibitory mechanism."
In all cases of fibrillation under the inllucnce of digitalis to
which atro|)in was given an increase in ventricular rate
occurred. Similar results have been reported by Cushny " and
by Mackenzie. The atria are seen to continue in fibrillation,
so there is no functioning pacemaker. Hence the increased
ventricular rate must result from an increase in the number
of impulses ])ermitted to pass through the conducting tissues,
and such an increase brought about by atropin implies a former
depression of conduction by vagus tone. Tinit digitalis produces more marked slowing by the direct action on the mu,«cle
of the fibri Hating heart no one would attempt to deny, but that
the vagus center in the medulla, the usual site of action of the
drug, should be ignored because of an altered condition of
the mycx-ardium which is less obvious. That the decrease in
the ma.ximum rate under atropin of the digitalized heart which
was observed in 100 per cent of the fibrillating hearts and in
76 per cent of those with normal mcchaiiisni nniy be tjiken as
a measure of the local action of the drug is seemingly a possible
interpretation.
From a compari.son of the reaction of the perfu.sed heart tfi
digitalis with that of clinical fibrillation, Cushny concludes
that the reaction so characteristic of fibrillation is due not to
the fibrillation itself but to a more fundamental factor, malnutrition. Furthermore, it is conceivai)le that i)ecau.«e of the
faulty circulation of the fibrillating heart an accumulation of
cellular metal)olites may result, by virtue of an increased
H-ion concentration in the jiroduction of a more highly glucosidolytic medium, and that because of increased destruction,
there may result an increa.sed capacity for digitalis bodies.
Similar action may jm.ssibly occur in other tissues also and
may constitute the mechanism by which many individuals
with .severe myocardial lesions can take large amounts nf
digitalis before toxic symptoms a])])ear.
The action of digitalis in atrial fiulter, a condition similar
to fibrillation, is both central and local (Figs. 7 and 8). In
four cases of flutter examined the administration of atropin
reduced the block to 2:1. Unfortunately atropin was not
given after the change to fibrillation, but in Xo. 354 the
normal mechanism jircsent after the last flutter record shows
sinus cscajK' and partial n'ductidn of the conduction time.
.SUMMAKY
Careful observations on the action of tincture of digitalis
have been made in many j)atients. It wa.s soon apparent that
successive tinctures supplied to the hospital wards showed
marked variation in their efficiency. Two biologically stand
" Cushny. Marrls and Silberg: Heart. 1912, IV, 33.
136
[No. 339
ardized tinctures of approximately theoretical strength were
studied and it appeared that the ineificiency of one was due to
failure of prompt absorption from the alimentary canal, as
was indicated by the larger amount necessary to produce a
change in the T-wave, the earliest demonstrable digitalis
effect.
Daily doses averaging 10 c. c. were given and continued imtil
alimentary disturbances or abnormalities in the cardiac mechanism appeared. In no case was there any ill effect attributable to digitalis and there were no evidences of the so-called
cumulative action. The toxic dosage showed marked individiial variation, from 20 c. c. to 100 c. c. The earliest signs
of toxicity were slight nausea and premature beats. It is
believed to be a perfectly safe procedure and one which will
promptly bring about the expected benefits of digitalis to begin
with an initial dose of 5 c. c. of tincture and to continue with
8 or 10 c. c. daily until signs of toxicity appear or until clinical
improvement warrants discontinuing the drug.
The various changes in the electrocardiogram have been
considered. Of these alteration in the T-wave was the earliest
and most constant. Modifications of the P-wave in the third
lead in about one-third of the cases is noteworthy. In one case
digitalis appeared to be responsible for the appearance of a
U summit. Definite prolongation of the P-E interval, indicating increased conduction time, was seen in 80 per cent of
the cases. In two cases complete dissociation occurred and in
one atrial tachycardia with high-grade block, and in all these
normal mechanism was promptly restored by atropin.
From a consideration of the effect of atropin on the pacemaker, the ventricular response and the conduction time, it is
believed that in all cases the action of digitalis is both central,
in the medulla, and local, in the myocardium, with relatively
greater local action in atrial fibrillation. Exception is taken
to the statement of Cushny that in fibrillation there is no
digitalis action through the inhibitory mechanism, and it is
suggested that the decrease of maximum rate after atropin of
the digitalized heart may be taken as a measure of the local
action of digitalis on the myocardium.
In the series studied were cases with all possible valvular
defects, all grades of decompensation, renal lesions of varying
degrees of soveritv', systolic blood pressures ranging from
90 mm. to 230 mm. and almost all of the recognized types of
myocardial involvement, including cases of intraventricular
block, bimdle branch block and complete dissociation, and
there was not found any clinical entity which might be said to
constitute a contraindication to the use of digitalis.
NOTES ON NEW BOOKS
The Principles of Acidosis and Clitiical Methods for Its Study.
By Andrew Watsox Sellards, Associate In Harvard Medical
School. {Harvard University Press. 1917.)
This work of some 111 pages exclusive of the bibliography deals
with acidosis with a terseness of style and elimination of unnecessary detail which make it very interesting as well as valuable
to the physician and student. There is careful consideration of
the various theories concerning acidosis and the evidence in favor
of each is thoroughly discussed.
The first three chapters are given to the consideration of the
chemistry of acids &nd bases, their metabolism in the human
body, and methods of diagnosing pathological alterations in the
mechanism. Particular attention is paid to the exact importance
of change in the alkalinity of the blood and the physiology of
the kidney in adjusting its excretion to these changes. In the
next chapter the reaction of the body to sodium bicarbonate in
health and disease is taken up. The value of observing this
reaction is brought out. In this chapter also a very valuable
test for the changes in the alkalinity of the blood is described in
full. .
Succeeding sections deal with the occurrence of acidosis and a
definition of the condition. The determination of a definition is
most timely, since there is considerable variance among writers
as to the exact meaning of the term " acidosis." The part dealing with therapy is very suggestive, although no definite working guide is given. Nevertheless, from a discussion of cases and
results sufficient data are given to enable the practitioner to make
immediate use of the method described by the author.
By no means the least important part of the work is that contained in the appendix, in which necessary laboratory methods are
described fully and clearly. Definite instructions for carrying
out the author's test for acidosis are given explicitly. There is
also a very helpful method described for determining the patient's
tolerance for sodium bicarbonate.
A very important feature of the book is the discussion of the
pathological processes in the acidosis of diabetes, nephritis, and
Asiatic cholera, with a differentiation of the steps in each. It
is perhaps to be regretted that the writer did not take up the
more intricate problems of protein, carbohydrate, and fat metabolism with the relation of each to acidosis, or that other acetonurias
were not considered in the same thorough manner. But what
the book may lack in tliis respect it gains in being concise, containing no confusing details, and being available for any one wltn
a rudimentary knowledge of biochemistry and physiology. It is
an important contribution both from the standpoint of information contained and also from the suggestions made concerning
other problems in tlie same field which offer rich opportunity
for study.
H. M. W.
Trench Fever: Report of Commission Medical Research Committee, American Red Cross. Prepared for publication by
Richard P. Strong. (Printed for the American Red Cross
Society at the Oxford University Press ty Frederick Hall,
Printer to the University, 191S.)
Members of Commission: Richard P. Strong, Major, M. R. C,
Assistant Director Division Laboratories and Infectious Diseases.
In charge Subdivision Infectious Diseases, A. E. F. Homer F.
Swift, Major, M. R. C, Senior Medical Officer, No. 1 United States
Army General Hospital. B. E. F. Eugene L. Opie, Major. M. R. C,
Pathologist, United States Army Base Hospital No. 21, B. E. F.
Ward J. Macneal, Captain, M. R. C. Head Department Bacteriology,
Central Medical Department Laboratory, A. E. F. Walter Baetjer,
Captain. M. R. C, in charge Clinical Laboratory, United States
Army Base Hospital No. 18, A. E. F. A. M. Pappenheimer. Captain, M. R. C, Pathologist, No. 1. United States Army General
Hospital. B. E. F. A. D. Peacock, Captain, R. A. M, C. (T.). 2d
London Sanitary Co. (Entomologist). (Subsequently attached.)
May, IDli)]
137
David Rapport, first Lieutenant, M. C, National Guard, A. E. F.
Major Richard P. Strong, M. R. C, In liis report on trench fever,
has given another proof of the brilliant work which the public
is now learning to expect from the army medical corps: and the
investigations he reports in regard to trench fever should rank
with their model, the classic studies of Reed and his colleagues
on the method of transmission of yellow fever. The fact that
during 1916 and 1917 no other infectious disease caused so much
sickness among the soldiers in France as did trench fever, and
its great prevalence at Salonica, in Italy and in Mesopotamia,
made it of primary importance. To ascertain the method of its
transmission would enable the authorities to take proper preventive measures, and thus much could be done to minimize an
enormous wastage among the fighting forces.
Accordingly. Dr. Strong, in October, 1917, was selected by the
Medical Research Committee of the American Red Cross to take
charge of the work ot a special Trench Fever Committee. From
that time the committee conferred with the British Army and
medical authorities, who were also studying the problem, with
the result that in February, 1918, experiments on a group of 82
selected volunteers from the United States Army were commence<i.
The work was carried on at a stationary hospital of the I3ritish
Expeditionary Force in France, sufficiently near to the front line
to insure the study of trench fever cases early in their course.
As the spring offensive was expected in two months' time, Uie
workers had only this short period to investigate the problem
before them. There resulted a marvel of coordinated research,
which required simultaneous experimentation along many closely
associated lines, each modifying the others as the work proceeded.
The clinical, bacteriological, serological, louse investigation, blood
inoculation and other studies all contributed their part in completing the work, which was reported as it developed to the
British Army medical officers, who were also at work on trench
fever.
In all a total of 103 different human experiments were carried
on in the study of trench fever and its cause, and in these the disease itself was produced experimentally 62 times in different ways.
Too much cannot be said in praise of the soldiers of the United
States Army who offered themselves so heroically in order to make
possible this splendid medical study. The results of this masterly piece of work are best summarized in Dr. Strong's own
words:
"The most Important facts which have been demonstrated by
our investigations are:
"1. That trench fever is a specific, infectious disease: that
it is not a modified form of typhoid or paratyphoid fever, and is
not related, from an etiological standpoint, to these diseases.
"2. That the organism causing the disease is a resistant, filterable virus.
" 3. That the virus causing trench fever is present particularly in the plasma of the blood of trench fever cases, and that
such plasma will produce the disease on inoculation Into healthy
individuals.
" 4. That the disease Is transmitted naturally by the louse
Prdivulus humanus. Linn., var. rorpohs. and that this Is the important and common means of transmission. That the louse may
transmit the dieease by its bite alone, the usual manner of infection, or the disease may be produced artificially by scarifying
the skin and rubbing in a small amount of the infected louse
excrement.
" 5. That a man may be entirely free from lice at the time he
develops trench fever, the louse that Infected him having left him
some time previously as his host, and that the louse neea only
remain upon the Individual for a short period of time In order to
infect him.
" 6. That the virus of trench fever is also sometimes present
in the urine of trench fever cases, and occasionally In the sputum.
and that the disease may be produced in man by the introduction
of the virus in the urine or sputum through the scarified or
otherwise abraded skin.
"7. That since the urine and sometimes the sputum of trench
lever patients are infective, these should be sterilized in order
to avoid the possibility of accidental infection from them.
" 8. That in order to prevent trench fever or limit its spread,
and thus save manpower for the armies, greater efforts must be
made to keep soldiers in general from infestation with lice.
"On account of the great importance of the matter, the following sanitary regulations are advised:
" Exceedingly great care should be taken to disinfect completely
all patients as soon as practicable, and particularly upon their
entering the hospital. Patients on entrance should be carefully bathed, and subsequently sponged with alcohol. Their clothing and blankets should be removed, and. whether or not lice or
ova are found upon them, should be carefully sterilized by moist
heat at a temperature not below 70° Centigrade for half an hour,
since it is possible for the virus to be still present on the clothing.
It should be borne in mind that a man with trench fever may be
entirely free from lice at the time that he develops symptoms of
the disease. Trench fever patients should at all times be carefully
protected from louse Infestation, and inspection of them for lice
should be made daily. They should be treated in separate wards.
As the urine contains the virus and is infective, It should be
sterilized durins the active stages of the disease. Sputum cups
should be provided for patients, and any expectorated sputum and
saliva from tliom sterilized. Officers should regard the systematic
destruction of lice as one of the most urgent of their duties, and
shotild exercise every effort to prevent louse infestation among
soldiers and to see that any of them Infested with lice are promptly
disinfected and their clothing sterilized."
He further discusses in some detail the nature of the experiments above referred to, with special reference to tlie transmission
of the disease, and points out that tlie incubation period of trench
fever, when studied experimentally, was shown to be from 14 to
38 days, depending on the dosage and other factors. No reliance,
however, can be placed on a study of the apparent incubation period
in uncontrolled cases, naturally produced anions the troops. The
practical value of these incubation period studies lies In the fact
that it may be from 10 to 23 days after the last bite by an
infected louse before a man will develop trench fever. A man
may be quite free from lice at the time of the outset of the symptoms of the disease, and. although a sufferer himself, he is of no
danger to others, unless he is in a louse-infected community, so
long as his urine and sputum are carefully sterilize<l.
The remainder of the book contains a careful and systematic
detail of the numerous experiments which were the foundation of
these conclusions. They enable the writer to examine the evidence
and to decide upon the justice of tfie conclusions formulated by the
commission. The work is most creditable to scientific medicine,
and is a fresh example of what can be done by the association of
a number of observers under the leadership of a competent and experienced head. Similar problems are existing throughout the
world, and the need of equally coordinated investigations Is
pressing.
G. H. W.
The Third Orrat Plague. By John H. Stokj^, M. D. Cloth $1.50.
(Philadelphia: W. II. Saunders Company, 1!>1~.)
Stokes' essay Is a most timely one. This book is Intended primarily to enlighten the lay mind on the ever-Important topic of
syphilis. It fulfills more than the author's purpose, for we believe
any individual with medical training can profit by a thorough
study of it.
The history, nature and course of syphilis; the blood test and
treatment; the cure, hereditary aspects, transmission and hygiene
338
[No. 339
of this ever-Increasing plague — so aptly termed — are sketched in
a lively, virile, and Intelligible style, and best of all In a most
understandable manner.
In the chapter on " Mental Attitudes in Their Relation to
Syphilis," the moral and personal prophylaxis and the public effort against syphilis are approached and handled with a fairminded conception of what they entail. A very brief and unprejudiced expose of the pros and cons of this ever-burning problem are
given with a circumspection and Judgment which entitle the
author to a most respectful hearing.
The book, therefore, is decidedly illuminating; it answers so
satisfactorily many of the every-day questions regarding the
handling of this, one of our greatest and most serious medical
liabilities. It is attractively presented; the style is easy and clear,
and the author's attitude on the various moral, social and economic aspects of syphilis are very sane and commendable.
I. R. P.
Syphilis and Public Health. By Edvvabd B. Veddab, M. D. Cloth
$2.25. (Philadelphia and New York: Lea and Febiger, lOlS.)
Following an introduction on the " Importance of Syphilis in
Relation to Public Health," together with statistics of mortality,
and after a discussion of syphilis as a sanitary problem, the book
is divided into four chapters:
1. Prevalence.
2. Sources of Infection and Method of Transmission.
3. Personal Prophylaxis.
4. Public Health Measures.
An appendix is included describing the technic of the Wassermann test of the blood serum; and. In addition, several sections,
including the " Control of Syphilis in the Army." " Methods Employed In Some Cities," etc.
This book is a real contribution to the literature of syphilis.
Statistics are frequently a " necessary evil " and always open to
criticism, but the value of figures in a book of this scope is essential, and therefore beyond the domain of a critical review.
Veddar's discussion of facts and of figures is supplemented by
a splendid bibliography, especially on the methods of transmission.
This latter chapter is worthy of careful reading. The presentation
of the pros and cons of prophylaxis, as well as the discussion on
the value of chemical methods of prevention, together with a
history of the use of calomel ointment, are splendid features. The
author's views on notification, treatment, and especially on the
sociological aspects, are rational and worthy of commendation.
This handy volume is well written and well typed. We would
recommend it most warmly to the notice of all individuals interested in the medical and (consequently) sociological field of
syphilology.
I. R. P.
Diseases of the Skin., By Mllton B. Haktzell, M. D. Cloth $7.00.
(Philadelphia: J. B. Lippincott Company, 1917.)
With the appearance of another text-book on dermatology, the
reviewer naturally looks, among other things, for something new
or for a different presentation of facts already known. Dr. Hartzell's book is, in this connection, both satisfying and disappointing.
The subject is handled by the author in the manner usually followed by the every-day text-book. Nothing new is suggested or
proposed. One finds the invariable divisions of anatomy, symptomatology, general etiology, etc., followed by the customary division of the dermatoses, according to anatomic characters,
hyperaemias, inflammations, hjemorrhages, new growths, neuroses, etc.
The size of the book is adequate, but it is neither a short resume
for the student nor an encyclopedic reference treatise tor the
specialist. Nevertheless, it should prove to be very profitable read
ing for the general practitioner who is not too deeply concerned
with the finer distinctions of diagnosis, pathology and treatment.
If considered in this light one finds the book sufficient, and
although it presents nothing startling or new in the consideration
of general etiology and treatment, it deserves credit for voicing
the author's personal views on many subjects. It is unfortunate
that the author, after attributing so much well-deserved credit
to X-ray therapy, has not incorporated a brief section on this
ever-increasing and important therapeutic agent, and also on
radium therapy.
With the exception of several worthless colored plates, the
photographs and plates are notably splendid; and the photomicrographs in particular — a genuine relief from the almost diagrammatic sketches in the older treatises — brook no criticism. The
remarks on etiology and pathology are eminently concise, rational
and clear; they are adequately stressed.
There are other outstanding features: the author has avoided
much needless discussion; in tact, his somewhat didactic method
of presentation is a real advantage; but it is questionable whether
the omission of at least a selected bibliography enhances the
value of the book. He has certainly done a service in clarifying
our knowledge of some dermatoses usually relegated to an obscure grouping. The other brief chapter on sarcoids is ample
proof.
It would lead too far to take up the various chapters in critical
review. Although the discussion of syphilis appears to be rather
scanty, and the pathology somewhat briefiy discussed, there are
excellent chapters on ringworm and on carcinoma.
The few typographical errors will surely be remedied, together
with correction of the spelling of some proper names. The book,
therefore, should appeal primarily to the general practitioner;
next, to the specialist for a brief review; and lastly, only to the
student who, without delving too far, wishes to read and to learn.
I. R. P.
Radio Diagnosis of Pleuro-Pulmonary Affections. By F. Baejon,
Medicin des Hopitaux de Lyon. Translated by James A.
HoNEij, M. D., Assistant Professor of Medicine in charge of
Radiography, Yale Medical School. (Yale University Press.)
This volume Is the second work published by the Yale University Press on the Williams Memorial Publication Fund — a gift
made to Yale University by George C. F. Williams, M. D., a member
of the class of 1S7S, Yale School of Medicine.
Although this translation is a little late in appearing, it arrives
at a time when it is most needed. Nothing concerning the X-ray
examination of the thorax as yet published has been so thorough as
this book. The fluoroscopic examination at the expense of the plate
method of study of lesions of the thorax might be mentioned as
one of its few weak points.
Frequent reference to other French Investigators exclusive of all
other nationalities is made and. although the book may have
been intended only tor use by our French colleagues, it nevertheless must create a little embarrassment to other notables who have
so earnestly tried — and, it may be added, not in vain — to elaborate
this valuable asset to clinical diagnosis.
The book is divided into five parts with many chapters subdividing each part:
Part I. The Fluoroscopic Appearance of the Normal Chest
Shadows when Viewed from All Different Angles.
Part II. The Study of the Pleur».
All the different pathological states of the pleurte are taken up
somewhat in detail. Especially interesting is the dissertation on
the influences in the production of the curve of Damoiseau. The
second chapter deals with circumscribed and encysted pleurisy
and is especially clear and well illustrated. The paragraphs dealing with pleurisy of the hilus region with case reports and illus
May, 1919]
139
trations is a genuine addition to tlie chapter. The pages devoted
to pneumothorax are well illustrated, interesting and instructive.
Part III. Foreign Bodies in the Bronchi.
The metallic foreign bodies and foodstuffs are discussed in detail
and the possibility of late and serious pulmonary complications
resulting from failure to diagnose them is worthy of mention.
The X-ray findings in acute and chronic bronchitis, bronchial
stenosis and bronchial dilatation are also instructive. Tracheobronchial adenopathy is next studied and a very acceptable and
descriptive explanation is given. The various groups of glands
are discussed and the best means for observing them on the screen
are pointed out. Emphasis is laid upon the fact that too litile
attention is paid to the study of adenopathy. Illustrations and
diaphragmatic drawings also help to complete this part of the
work.
Part IV. The Lungs.
The first chapter deals with the fluoroscopic appearances in
acute primary and secondary congestion, passive congestion and
oedemas. Infarction, its appearance and differentiation from other
pulmonary sliadows, is particularly clear.
The remaining chapters of Part IV, which are the longest of
any, are given over to the study of acute infectious pulmonary
processes, chronic pulmonary processes, pulmonary tuberculosis
and lung tumors.
Pulmonary tuberculosis is considered under three distinct
groups; (1. Pulmonary tuberculosis without clinical or stethoscopic signs. ( Latent forms. ) b. Pulmonary tuberculosis with
positive clinical but negative, doubtful or very limited stethoscopic
signs. (Early Forms. Period of incubation. Miliary.) c. Advanced pulmonary tuberculosis with evident clinical and stethoscopic signs. ( Chronic pulmonary tuberculosis with its many
forms. )
Nothing new in the way of diagnosis is offered, but the appearance, development of complications and their appearance fluoroscoplcally is well pointed out and the total absence of fanaticism
certainly adds materially to tliis greatly discussed topic, the X-ray
diagnosis of pulmonary tuberculosis.
Lung tumors complete this part of the book and, aside from
mentioning the good illustrations, little need be said.
Part V ends the l)ook and deals with the penetrating wounds of
the thorax by war projectiles. A brief clinical and radiologic
entity Is given which proves interesting, but certainly not comprehensive enough from a clinical standpoint to be of any material
aid to the surgeon or internist in determining the course of procedure in these grave cases. The points discussed in diagnosis
and complications are interesting and instructive, but the problems in the localization and extraction of these projectiles are
still unanswered. c. A. W.
liointgen Tahnic (Diaffiiostic). By Noknian C. Prime, M. D.
St. Louis: C. T. ilosby i( Co.. UU7.)
This book of 140 pages deals principally with the technic employed In making X-ray plates of different parts of the body.
The descriptive technic is mainly good, but one cannot help
feeling that some of the manufacturers of X-ray accessories have
used undue influence in advocating their particular products.
In view of the increasing popularity of technicians for the performance of technical duties in an X-ray laboratory the book
might have some usefulness in this phase of the work, but when
this has been said, no further need for it can be found.
C. A. W.
ll'or Neuroses. By John T. M.mCihkv, M. D. With a preface
by W. H. R. Ri\TERs, M. D. (Lond.). 132 pages. (Camhrirlgr:
At The Universit)/ Press. H'lS.)
This book consists of observations originally published in the
P.ii/chintrie BuUctiii of the New York State Hospitals, and records
the author's conclusions after a brief visit to Great Britain in
1917.
The point of view adopted, with the emphasis on the conflict
between the different instincts, that of self-preservation and that
of loyalty to the group, and on the adaptive role played by the
symptoms in the neuroses, is now so widely accepted as not to
require special elaboration. The different groups of neuroses,
those with predominance of anxiety symptoms, those with predominance of physical synii)toms, those where cardiac symptoms
are specially in evidence, etc., are discussed in a clear and interesting manner. In special chapters the questions of etiolog>' and
of treatment are succinctly dealt with.
C. M. C.
BOOKS RECEIVED
.Veir Jersey. Forty-First Annual Report of the Department of
Health of the State of New Jersey, 1917. 1918. 8'. 381 pages.
State Gazette Publishing Company. Printers. Trenton, N. J.
Persei-uiions of th'- <;riil;s in Turk-ii t<inrr the Beginning of the
European ^\^nr. Translated from official Greek documents by
Carroll N. Brown, Ph. D., and Theodore P. Ion. D. C. L. 1918.
%'. 72 pages. Published for the American Hellenic Society by
Oxford University Press, American Branch. New York City.
Miehigan State Board of Health. Forty-Fourth and Forty-Fifth
Annual Reports of the Secretary of the State Board of Health
of the State of Michigan for the years ending June 30, 1916.
and June 30, 1917. 1917. 8 . 243 pages. Wynkoop Hallenbeck Crawford Company, Lansing, Mich.
Amputation Slumps. Their Care and After Treatment. By G.
Martin Huggins, F. R. C. S. Oxford War Primers. 1918. 16 .
228 pages. Henry Frowde and Hodder & Stoughton, Oxford
University Press. London.
Bipp Treatment of War Wounds. By Rutherford Morison. Oxford War Primers. 1918. 16°. 72 pages. Henry Frowde and
Hodder & Stoughton, Oxford University Press, London.
Xursing Terhnir. By Mary C. Wheeler, R. N. 32 specially prepared illustrations under personal supervision of the author.
11918.] 16°. 265 pages. J. B. Lippincott Company, Philadelphia and London.
The Essentials of Materia Mediea and Therapeutiea for Xurses.
By John Foote, M. D. Third edition, revised, enlarged and
reset. Llppincotfs Nursing Manuals. 11918.] 8°. 310 pages.
J. B. Lippincott Company, Philadelphia and London.
I nited States. Department of Commcree, Bureau of the Census.
Sam L. Rogers Director. Deaf-mutes in the United States.
Analysis of the Census of 1910, with Summary of State Laws
Relative to the Deaf as of January 1, 1918. 4°. 221 pages.
Government Printing Office. Washington.
The Indian Opi ration of Couehing for Catarart. Incorporating
the Hunterian Lectures delivered l)efore the Royal College
of Surgeons of England on February 19 and 21, 1917. By
Robert Henry Elliot, M. D., B. S. (Lond.), Sc. D. (Edin.),
F. R. C. S. (Eng. ). etc.. Lieut. Colonel I. M. S. (retired).
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Diseases of the Male Urethra, Incluciing Impotence and Sterility.
By Irvin S. Koll, B. S., M. D., F. A. C. S. Illustrated. 1918.
8°. 151 pages. W. B. Saunders Company, Philadelphia and
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Clinical Diagnosis. A Manual of Laboratory Methods. By James
Campbell Todd, Ph. B., M. D. Illustrated. Fourth edition, revised and reset. 191S. 12°. 687 pages. W. B. Saunders Company, Philadelphia and London.
International Clinics. A Quarterly of Illustrated Clinical Lectures and Especiplly Prepared Original Articles. By leading
members of the medical profession throughout the world.
Edited by H. R. M. Landis, M. D. Volume II. Twenty-eighth
series, 1918. 8°. 286 pages. J. B. Lippincott Company, Philadelphia and London.
The Harvey Lectures. Delivered under the Auspices of the Harvey
Society of New York, 1916-1917. By Prof. J. S. Haldane, Dr.
F. M. Allen, Dr. Paul A. Lewis, Prof. H. H. Donaldson, Prof.
E. V. McCollum, Prof. J. W. Jobling, Prof. John R. Murlin,
Prof. F. W. Peabody, Prof. W. H. Howell. Series XII. 1918.
8°. 323 pages. J. B. Lippincott Company, Philadelphia and
London.
The Hodgen Wire Cradle Extension Suspension Splint. The Exemplification of this Splint with Other Helpful Appliances in
the Treatment of Fractures and Wounds of the Extremities
and Its Application in Both Civil and War practice. By Frank
G. Nifong, M. D., F. A. C. S. With an Introduction by Harvey
G. Mudd, M. D., F. A. C. S. With 124 illustrations. 1918. 8°.
162 pages. C. V. Mosby Company, St. Louis.
A Treatise on Cystoscopy and Urethroscopy. By Dr. Georges
Luys. Translated and edited with additions by Abr. L. Wolbarst, M. D. With 217 figures in the text and 24 chromotypographic plates outside the text, including 76 drawings from
original water colors. 1918. S°. 386 pages. C V. Mosby
Company, St. Louis.
A Manual of Otology. By Gorham Bacon, A. B., F. A. C. S., assisted by Truman Laurance Saunders, A. B., M. D. Seventh
edition, revised and enlarged. With 204 illustrations and two
plates. 1918. 12°. 583 pages. Lea & Febiger, New York and
Philadelphia.
Botulism. A clinical and Experimental Study. By Ernest C. Dickson, M. D. Monograph No. 8. 1918. 4°. 117 pages. Rockefeller Institute for Medical Research, New York.
University of Michigan. Transactions of the Clinical Society,
October, 1916-October, 1917. Volume VIII. Edited by the
Secretary-Treasurer. 1917. 8°. 146 pages. University Hospital, Ann Arbor, Michigan.
University of Michigan. Contributions from the Department of
Obstetrics and Gynecology. Volume IV, 1915-1918. 4°. Ann
Arbor, Michigan.
Neurological Clinics. Exercises in the Diagnosis of Diseases of
the Nervous System Given at the Neurological Institute, New
York, by the Staff of the First Division. Edited by Joseph
Collins, M. D. 1918. 8°. 271 pages. Paul-B. Hoeber, New
Y'ork.
Food Primer for the Home. Compiled by Lucy H. Glllett. 1918.
8°. 19 pages. Bureau of Food Supply, Association for Improving the Condition of the Poor, New York.
Clinical Disoj-ders of the Heart Beat. By Thomas Lewis. M. D.,
F. R. S., D. Sc, F. R. C. P. [Fourth edition.] 1918. 8\ 120
pages. Paul B. Hoeber, New York.
The Medical Clinics of Xorth America. Vol. 1. No. 6. May. 1918.
8°. W. B. Saunders Company, Philadelphia and London.
The Action of Muscles. Including Muscle Rest and Muscle Reeducation. By William Colin Mackenzie M. D., F. R. C. S.,
P. R. S. (Edin.). With 99 illustrations. 1918. S\ 267 pages.
Paul B. Hoeber, New York.
Symptoms and Their Interpretation. By James Mackenzie, M. D.,
LL. D. [Aber. and Edin.] Third edition. 1918. 8°. 318
pages. Paul B. Hoeber, New York.
Naval Hygiene. By James Chambers Pryor, A. M., M. D. Published with approval of the Surgeon General, United States
Navy and by permission of the Navy Department. With 153
illustrations. 1918. 12°. 507 pages. P. Blakiston's Son & Co.,
Philadelphia.
The Wassermann Test. By Charles F. Craig, A. M. (Hon.), M. D.
(Yale). Published with authority of the Surgeon General,
United States Army. Illustrated with colored plates, halftone plates, and 57 tables. 1918. 8°. 239 pages. C. V. Mosby
Company, St. Louis.
Essentials of Dietetics. A Text-Book for Nurses. By Maude A.
Perry, B. S. 1918. 12°. 159 pages. C. V. Mosby Company,
St. Louis.
Concerning Some Headaches and Eye Disorders of Nasal Origin.
By Greenfield Sluder, M. D. With 115 illustrations. 1918. 8°.
272 pages. C. V. Mosby Company, St. Louis.
War Surgery of the Abdomen. By Cuthbert Wallace, C. M. G.,
F. R. C. S. (Eng.), M. B., B. S. (Lond.). With 26 illustrations.
1918. 8°. 152 pages. P. Blakiston's Son & Co., Philadelphia.
La Suspension dans le Traitement des Fractures. Par P. Desfosses et Charles Robert. Preface de M. Pierre Duval. 1918.
12°. 172 pages. Masson et Cie, Paris.
Surgical Applied Anatomy. By Sir Frederick Treves, Bart., G. C.
V. O., C. B., LL. D., F. R. C. S. (Eng.). Seventh edition, revised by Arthur Keith, M. D., LL. D. (Aber.), F. R. C. S.
(Eng.), F. R. S., and W. Colin Mackenzie, M. D. (Melb.),
F. R. C. S. (Edin.), F. R. S. E. Illustrated with 153 figures,
including 74 in color. [1917.] 16°. 702 pages. Lea & Febiger.
Philadelphia and New York.
A Text-Book of Physiology For Nurses. By William Gay Christian,
M. D., and Charles C. Haskell, M. D. Illustrated. 1918. 12°.
168 pages. C. V. Mosby Company, St. Louis.
Surgical and War Nursing. By A. H. Barkley, M. D. (Hon.), M. C,
P. A. C. S. With 79 illustrations. 1918. 12°. 208 pages.
C. V. Mosby Company, St. Louis.
Hygiene for Nurses. By Nolie Mumey, M. D. With 75 illustrations. 1918. 12°. 160 pages. C. V. Mosby Company, St. Louis.
Nursing in Diseases of Children. By Carl G. Leo-Wolf. M. D.
With 72 illustrations. 1918. 12°. 314 pages. C. V. Mosby
Company, St. Louis.
Gymnastic Treatment for Joint and Muscle Disabilities. By Brevet Col. H. E. Deane, R. A. M. C. With preface by Temp.
Colonel A. Carless, Army Medical Service, and by Brevet
Lieut. Col. F. W. Mott, P. R. A. M. (T.). 1918. 12°. 146
pages. Henry Frowde and Hodder & Stoughton, London.
(Oxford University Press, American Branch, New Y'ork.)
Contribution to the Pharmacology of Opium. 1915-1918. By Dr.
David I Macht, Baltimore, 1918.
Metropolitan Asylums Board. Annual Report for the Y'ear 1917.
(20th year of issue.) 1918. 8°. 57 pages. London.
Hygiene of the Eye. By Wm. Campbell Posey, A. B., M. D. 120
illustrations. 1918. 8°. 344 pages. J. B. Lippincott Company, Philadelphia and London.
May. 1919]
141
Neuropsychiatry and the War. A Bibliography with Abstracts,
Prepared by Mabel Webster Brown, Edited by Frankwood E.
Williams. M. D. 1918. S". 292 pages. War Work Conmiittee,
The National Committee for Mental Hygiene, Inc., New York
City.
The Medical Association of the Isthmian Canal Zone. Proceedings of the Medical Association of the Isthmian Canal Zone.
Vol. X, Part I, January to June. 1917. 1918, 8'. 149 pages.
Published by the Health Department, The Panama Canal.
Panama Canal Press, Mount Hope, C. Z.
Public Health Reports. Issued weekly by the United States Public Health Service, containing information of the current prevalence of disease, the occurrence of epidemics, sanitary legislation, and related subjects. Vol. 32, Part I, January-June,
1917. 1918. S'. 1074 pages. Government Printing Office,
Washington.
The Surgery of Oral Diseases and ilalformations. Their Diagnosis and Treatment. By George Van Ingen Brown, D. D. S.,
M. D., C. M.. F. A. C. S. Third edition, with 570 engravings
and 20 plates, and a selected list of examination questions.
1918. 8°. 734 pages. Lea & Febiger, Philadelphia- and New
York.
Anatomy of the Human Body. By Henry Gray. F. R. S. Twentieth edition, thoroughly revised and re-edited by Warren H.
Lewis, B. S., M. D. Illustrated with 1247 engravings. 1918.
4°. 1396 pages. Lea & Febiger, Philadelphia and New York.
Oenilo-Urinary Diseases and Syphilis. By Henry H. Morton, M. D..
P. A. C. S. Fourth edition, revised and enlarged, with 330
illustrations and 36 full-page colored plates. 1918. 8'. S07
pages. C. V. Mosby Company, St. Louis.
Ah Introduction to the Mammalian Dentition. By T. Wingate
Todd, M. B., Ch. B. (Mane), F. R. C. S. (Eng.), Captain,
Canadian Army Medical Corps. With 100 illustrations. 191S.
8°. 290 pages. C. V. Mosby Company, St. Louis.
Radio-Diagnosis of Pleuro-Pulmonary .Iffertions. By F. Barjon.
Translated by Jam&s A. Honeij, M. D. 1918. 8°. 183 paws.
Yale University Press, New Haven; Humphrey Milford. London.
Dispensaries. Their Management and Development. A book for
Administrators, Public Health Workers, and All Interested
In Better Medical Service for the People. By Michael M.
Davis, Jr., Ph. D., and Andrew R. Warner, M. D. 1918. 8'.
438 pages. Macmillan Company. New York.
The Diseases of Infaney and Childhood. Designed for the use of
Students and Practitioners of Medicine. By Henry Koplik.
M. D. Fourth edition, revised and enlarged, Illustrated with
239 engravings and 2.t plates in color and monochrome. 1918.
8'. 928 pages. Loa & Febiger, Philadelphia and New York.
Roentgen Diagnosis of Diseases of the Head. By Dr. Arthur
Schiiller. Authorized translation by Fred F. Stocking, M. D.,
M. R. C. With a foreword by Ernest Sachs, M. D. Approved
for publication by the Surgeon General of the United States
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The Human Skeleton. An Interpretation. By Herbert Eugene
Walter. With 175 Illustrations. 1918. 12'. 214 pages. Mac
millan Company, New York.
Abstracts of War Surgery. An Abstract of the War Literature of
General Surgery that has been Published since the Declaration of War in 1914. Prepared by the Division of Surgery.
Surgeon General'.s Office. 1918. 8'. 434 pages, c V .Mn.-^hy
Company, St. Louis.
Engliah, French, Italian. Medical Vocabulary. By Joseph Marie.
1918. 24." 112 pages. P. Blakiston's Son & Co., Philadelphia.
Text-Book of .Anatomy and Physiology for Nurses. By Diana
Clifford Kimber and Carolyn E. Gray, B. So. (Columbia
University), U. N. Fifth edition, revised. 1918. 8°. 527
pages. Macmillan Company, New York.
Vaccines and Sera, Their Clinical Value in Military and Civilian
Practice. By A. Geoffrey Shera, B. A., M. D., B. C. (Cantab.).
With an introduction by Sir Clifford Allbutt, K. C. B., M. D.,
F. R. S. 1918. 16'. 226 pages. Henry Frowde and Hodder
& Stoughton, London.
Tumours. Innocent and Malignant. Their Clinical Characters
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D., F. R. C. S. With 383 illustrations. Sixth edition. [1917.]
8'. 790 pages. Paul B. Hoeber, New York.
Stanford University. Medical Bulletin No. 5, 1917-1918.
The Newer Knowledge of Nutrition. The Use of Food for the
Preservation of Vitality and Health. By E. V. McCoUum.
Illustrated. 1918. 12'. 199 pages. Macmillan Company,
New York.
College of Physicians. Transactions of the College of Physicians
of Philadelphia. Third series. Volume the Thirty-Ninth.
1917. S°. 518 pages. Philadelphia.
War Neuroses. By John T. MacCurdy, M. D. With a preface
by W. H. R. Rivers, M. D. (London.) 1918. 8°. 132 pages.
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lioyal College of Surgeons of England. Calendar of the Royal
College of Surgeons of England. August 1, 1918. 407 pages.
8'. Taylor and Francis. London, England.
The Effect of Diet on Endurance. By Irving Fisher. 1918. 12°.
, 55 pages. Yale University Press, New Haven; Humphrey
Milford, Oxford University Press, London.
.1 Text-Book of Home Nursing. Modern Scientific Methods for the
Care of the Sick. By Eveleen Harrison. Second edition, revised. 1918. 12°. 193 pages. Macmillan Company, New York.
Dietetics for Nurses. By Fairfax T. Proudflt. 1918. 8". 444
pages. Macmillan Company, New York.
Compendium of Histo-Pathologieal Teehnie. By Emma H. Adler.
1918. 12°. 92 pages. Paul B. Hoeber, New York.
Mental Diseases. A Handbook Dealing with Diagnosis and Classification. By Walter Vose Gulick, M. D. Illustrated. 1918.
8'. 142 pages. C. V. Mosby Company. St. Louis.
Equilibrium and Vertigo. By Isaac H. Jones, M. A., M. D. With
an Analysis of Pathological Cases. By Lewis Fisher, M. D.
Adopted as Standard for Medical Division, Signal Corps, Aviation Section, by Surgeon General and Chief Signal Ofllcer.
United States Army. With 130 Illustrations. 1918. 8°. 444
pages. J. B. Llppincott Company, Philadelphia and London.
Physiology and Rioehemistry i7i Modern Medicine. By J. B. Macleod, M. B. Assisted by Roy G. Pearce. B. A., M. D., and by
others. With 233 illustrations, including 11 plates In colors.
1918. 8'. 903 pages. C. V. Mosby Company, St. Louis.
The Rockefeller Foundation. International Health Board. Fourth
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Information for the Tuberculous. By F. W. WIttlch, A. M., M. D.
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Mortality Statistics, 1916. Seventeenth annual report. 1918.
4°. 543 pages. Government Printing Office, Washington.
142
[No. 339
THE JOHNS HOPKINS HOSPITAL REPORTS
VOLUME I. 423 pages, 99 plates.
VOLUME II. 570 pages, witli 28 plates and figures.
VOLUME III. "66 pages, with 69 plates and figures.
VOLUME IV. 604 pages, 33 charts and illustrations.
VOLUME V. 480 pages, with 32 charts and illustrations.
The Mal.nri.ll Fevers ot B.iltimore. By W. S. Thayer, M. D.. and
J. Hewetson. Jl. D.
A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.
Studies in Typhoid Fever.
. D.. with additional papers
D.. Walter Keed, .M. IL. ai
VOLUME VI. 414 pages, with 79 plates and figures.
VOLUME VII. 637 pages with illustrations.
VOLUME VIII. 552 pages with illustrations.
VOLUME IX. 1060 pages, 66 plates and 210 other illustrations.
Contributions to the Science of Medicine.
Dedicated by his Pupils to William Henky Welch, on the twenty fifth
anniversary ol his Doctorate. This volume contains 38 separate
papers.
VOLUME X. 616 pages, 12 plates and 25 charts.
VOLUME XI. 555 pages, with 38 charts and illustrations,
VOLUME XII. 548 pages. 12 plates and other illustrations.
VOLUME XIII. 605 pages, with 6 plates, 201 figures, and 1 colored chart.
VOLUME XIV. 632 pages, with 97 figures.
Studies in Genito-Urinary Surgery.
The Treatment of Prostatic Hypertrophy by Conservative Perineal Prostatectomy. An analysis of cases and results based on a detailed
report of 145 cases. By Hugh H. Young, M. D.
Recto-Urethral Fistula. Description of New Procedures for their Prevention and Cure. By Hugh H. Young. M. D.
The Early Diagnosis and Radical Cure of Carcinoma of the Prostate, being
a study of 40 c:ises and presentation of a radical operation which
was carried out in four cases. By Hugh H. Young, M. D.
VOLUME XV. 542 pages, with 87 illustrations.
Twelve papers on pneumonia By Drs. Chatard, Fabyan, Emefson,
Marshall, McCrae, Steiner, Howard and Hanes.
A Study of Diarrhoea in Children. J. H. Mason Knox, Jr., M. D., and
Edwin H. Schorek. M. D.
Skin Transplantation. By John Staige Davis. M. D.
Epidemic Cerebrospinal Meningitis and Serum Therapy at The Ji.hns
Hopkins Hospital. By Frank J. Sladen. M. D.
VOLUME XVI. 670 pages with 151 figures.
Studies in the Experimental Production of Tuberculosis in the GenitoVrinary Organs. By Ceorge Walker. M. D.
The Effect on Breeding of the Removal of the Prostate Gland or ot the
Vesicute Seminales. or of Both ; together with Observations on the
Condition of the Testes after such Operations on White Rats. By
George Walker. M. D.
Scalping Accidents. By John Staige Davis, M. D.
Obstruction of the Inferior Vena Cava with a Report of Eighteen Cases.
By J. Hall Pleasants. M. D.
Physiological and Pharmacological Studies on Cardiac Tonicity in Mammals. By Percival Douglas Cameron. M. D.
VOLUME XVII. 586 pages with 21 plates and 136 figures.
Free Thrombi and Ball Thrombi in the Heart. By Joseph H. Hewitt.
M. D.
Benzol as n Leucotoxin. By Lawrence Selling. M. D.
Primary Carcinoma of the Liver. By Milton C. Winternitz, M. D
The Statistical Experience Data of The Johns Hopkins Hospital, Baltimore,
Md.. 1802-1(111. By Frederick L. Hoffman. LL. D., F. S. S.
The Origin and Development of the Lymphatic System. By Floreni:e R.
Sarin. M. D.
The Nuclei Tuberis Laterales and the So-called Ganglion Opticum Hasale.
By Edward F. Malone. M. D.
Venous Thrombosis During Myocardial Insufficiency. By Frank J. Sladen.
M. D.. and Milton C. Winternitz. M. D.
Leuk.Tmia of the Fowl : Spontaneous and Experimental. By Harry C.
SCH5IEISSER. M. D.
VOLUME XVIII. 445 pages with 124 figures.
Fasciculus I.
A Studv of a Toxic Substance of the Pancreas. By E. W. Goodpasture,
M."D.. and George Clark. M. D.
Old Age in Relation to Cell-overgrowth and Cancer. By E. W. Goodpasture. M. D., and G. B. Wislocki. M. D.
The Effect of Removal of the Spleen Upon Metabolism in Dogs : Pre
liminarv Report. By J. H. King. M. D.
The Effect ot Removal of the Spleen Upon Blood Transfusion. By J. H.
King. M. D.. B. M. Bernheim. M. D.. and A. T. Jones. M. D.
Studies on Parathyroid Tetany. By D. Wright Wilson. M, D.. Thornton
Stearns, M. D., J. H. Jannet, Jr., M. D.. and Madge DeG. THCRrx)w,
M. D.
Some Observations on the Effect of Feeding Glands of Internal Secretion
to Chicks. By M. C. Winternitz, M. D.
Spontaneous and Experimental Leukemia in the Fowl. By H. C.
Schmeisser. M. D.
Studies on the Relation of Fowl Typhoid to Leukaemia of the Fowl. By
M. C. Winternitz. M. D.. and H. C. Schmeisser, M. D.
Hyaline Degeneration of the Islands of Langerhans in Pancreatic Diabetes.
By M. C. Winternitz. M. D.
Generalized Miliary Tuberculosis Resulting from Extension of a Tubercular
Pericarditis Into the Right Auricle. By M. C. Winternitz. M. D.
Acute Suppurative Hypophysitis as a Complication of Purulent Sphenoidal
Sinusitis. By T. R. Boggs. M. D.. and M. C. Winternitz. M. D.
A Case of Pulmonary Moniliasis in the United States. By T. R. BoGGS,
M. D.. and M. C. Pincoffs, M. D.
Gaucher's Disease (A Report of Two Cases in Infancy). By J. H. M.
Knox. M. D.. H. R. Wahl. M. D.. and H. C. Schmeisser. M. D.
A Fatal Case of Multiple Primary Carcinomata. By E. D. Plass. M. D.
Congenital Obliteration of the Bile-ducts. By .Iames B. Holmes. M. D.
Multiple Abscesses of the Brain in Infancy. By James B. Holmes. M. D.
Gastric Carcinoma in a Woman of Twenty-six Years. By R. G. Hussey,
M. D.
Subdiaphragmatic Abscess with Rupture Into the Peritoneal Cavity Following Induced Pneumothorax for Pulmonary Haemorrhage. By R. G.
Hussey. M. H.
Heart Block Caused by Gumma of the Septum. By E. W. Bridgeman,
M. D.. and H. C. Schmeisser, M. D.
Analysis of Autopsy Records.
A. The Johns Hopkins Hospital. (Table Showing Percentage of
Autopsies.)
B. The City Hospitals. Bay View. (Table Showing Percentage of
Autopsies. )
" The Monday Conferences."
Clinical Representatives on the Staff of the Department of Pathology.
Donation.
Fasciculus II.
The Role ot the Autopsy in the Medicine of To-day. By M. C. Winternitz.
M. D.
Experimental Nephropathy in the Dog. Lesions Produced by Injection
of B. bronchisepticus into the Renal Artery. By M. C. Winternitz,
M. D.. and William C. Quiney. M. D.
Mesarteritis of the Pulmonary Artery. By M. C. Winternitz, M. D.. and
H. C. Schmeisser, M. D.
A Clinical and Pathological Study of Two Cases of Miliary Tuberculosis of
the Choroid. By Robert L. Randolph, M. D., and H. C. Schmeisser,
M. D.
The Blood-vessels of the Heart Valves. By Stanhope Bayne-Jones. M. D.
Equilibria in Precipitin Reactions. By Stanhope Bayne-Jones. M. D.
Carcinoma of the Pleura with Hypertrophic Osteoarthropathy. Report of
a Case with a Description of the Histology of the Bone Lesion. By
Stanhope Batne-Jones. M. D. ,
The Interrelation ot the Surviving Heart and Pancreas of the Dog in Sugar
Metabolism. By .\dmont H. Clark. M. D.
Congenital Atresia of the Esophagus with Tracheo-Esophageal Fistula
Associated with Fused Kidney. A Case Report and A Summary of the
Literature on Congenital Anomalies of the Esophagus. By E. D.
Plass. M. D.
Ectopia Cordis, with a Report of a Case in a Fifteen-Month-Old Infant.
By James B. Holmes, M. D.
Studies in the Mechanism of Absorption from the Colon. By Samuel,
Goldschmidt. M. D., and A. B. Dayton. M. D.
Report of Two Fatal Cases Following Percy's Low Heat Treatment of
Carcinoma of the Utenis. Bv V. N. Leonard, M. D., and A. B. Dayton,
M. D.
The Relationship in Tvphoid Between Splenic Infarcts and Peritonitis
Unassociated with Intestinal Perforation. By A. B. Dayton. M. D.
Left Duodenal Hernia. By A. B. Dayton. M. D.
Histological as Related to Physiological and Chemical Differences in Certain Muscles of the Cat. By H. Hays Bullard, M. D.
A Method of Clearing Frozen Sections. By H. Hays Bullard. M. D.
On the Occurrence and Significance of Fat in the Muscle Fibers of the
Atrio-Ventricular System. By H. Hays Bullard. M. D.
Studies on the Metabolism of Cells in vitro. 1. The Toxicity of o-Amino
Acids for Embyonic Chicken Cells. By Montrose T. Burrows, M. p.,
and Clarence A. Neymann, M. D.
The Significance of the Lunula of the Nail. By Montrose T. Burrows.
M. D.
The Oxygen Pressure Necessary for Tissue Activity. By Montrose T.
Burrows. M. D.
The Functional Relation of Intercellular Substances in the Body to Certain Structures in the Egg Cell and Unicellular Organisms. By
Montrose T. Burrows. M. D.
Studies on the Growth of Cells in vitro. The Cultivation of Bladder and
Prostate Tumors Outside the Body. By Montrose T. Burrows. M. D..
J. Edward Burns. M. D.. and Yoshio Suzukl. M. D.
The Studv of a Small Outbreak of Poliomyelitis in an .\partment House,
Occurring in the Course of an Epidemic in a Large City. By Montrose
T. Burrows. M. D.. and Edwards A. Park. M. D.
Papilloma of the Larynx. Report of a Case Treated with Radium with
Resultant Chronic Diffuse Thyroiditis. By William C. Duffy. M. D.
Analysis of .Autopsy Records.
Auto'psv Statistics.
(n) Bay View.
(hi Johns Hopkins Hospital.
Report of the Photographic Department.
General Improvements.
==Contents==
The Occurrence of Gastric Mucosa in a Case of Meckel's Diver- Tlie Development of CroasStriations in the Heart Muscle of
ticulum Producing Intestinal Obstruction. (Illustrated.) the Chick Kinbryo. (Illustrated.)
By Emu. Goetsch 143 By Margabkt Reed Lewis 176
A Graphic .Application of the Principle of the Equilateral
Triangle for Determining the Direction of the Electrical Spina Bitida with Associated Disturbances in a Human
Axis of the Heart in the Human Electrocardiogram. Embryo 17 mm. Long. (Illustrated.)
(Illustrated.l p^. g j \Valli.s Ccll 181
By Edward Perkins Carter. Curt P. Richteb and
Carl H. Greexe I(!2
_, . . , . , i- .  ^1 f  . i T 1 The Manus Meditationis. (Illustrated.)
Phaeocytosis and Agglutination in the Serum in Acute Lulmr . „ „ ,_.
„ ' .If -c •. c Tu ij . J 41 By Charles Si.noer ... 184
Pneumonia: the Specificity of lhe.«e Reactions and the "
Regularity of Their Occurrence.
By Paul \V. Clough 107 , Books Received 183
THE OCCURRENCE OF GASTRIC MUCOSA IN A CASE OF Mi:CKEL'S
DIVERTICULUM PRODUCING INTESTINAL OBSTRUCTION
By K.Mii> (ioETScii
(From thi- Departments of ffurgrry of The Peter Bent Brigham Hospital and The Harvard and Johns Hopkins Mrdiial Sihooli)
The occurrence in the human liody of ahcrrant glandular
tissue, at times in place,* far removed from the motlier tis,«uo,
is a subject not only of general medical interest and of special
interest to the embrj-ologist, but also attract'* the attention of
the pathologist and surgeon, who frequently meet with alinormalities arising from such aberrant tissue. The purpose of
this report is to record such an in.«tance occurring in an interesting case of partial obstruction caused by Meckel's diverticulum in which, at operation, a striking variation was discovered
in the mucous membrane of the distal half of the diverticulum.
This area of mucous membrane at the tip of Meckel's diverticulum was differentiated strikingly from the pro.ximal mucosa
by a sharp line of demarcation and by a difference in color,
surface character and in thickness. On subsequent sectioning,
this area of muco.sa proved to be of the preci.«e character of
gastric (fundus) mucosa, containing the typical gastric glands
(foveol.T gastricaj) composed of the two distinctive types of
cells, the parietal and chief, each of which presented their characteristics of morphology and of staining reaction. It is desired further to explain the probable embryological origin of
tiiis ga.stric ti.ssue in Meckel's diverticulum with a view to
throwing further light upon the occurrence of aberrant glandular tissue at the umbilicus and in the renuiins of the omphalomesenteric duct, as reported in the literature.
The ca-fe, Hospital No. (123, is that of a well-developed,
single young man, lit years of age, and caterer by occupation.
lie was born in Ireland and came to America four years previous to bis entrance into the Peter Bent Brigham Hospital
on August 26, 191.3. He was admitted into the surgical clinic
of Prof. Harvey Gushing, to whom I am indebted for the privilege of reporting this case. The young man complained of
pain in the abdomen and vomiting. No information was obtained in regard to his family or past history which had any
licaring on his present trouble except for the fact that six
years previously, while he was in Ireland, he was operated
upon for what he called a stomach abscess. The details of the
condition for which he was operated upon he was unable to
give. At that time the abdomen was explored at a point just
below the umbilicus and drainage in.-^tituted. The abscess
healed in a few weeks and the patient made a complete recov
144
[No. 340
ery. Except for this experience he had enjoyed exceptionally
good health.
Without going into the details of his present illness suffice
it to say that his symptoms began with headache 48 hours
before admission to the hospital and were followed in about
36 hours by severe cramps in the abdomen, especially in the
lower half and toward the right side. The day before coming
to the hospital he suffered severely with vomiting and retching,
the vomitus containing large quantities of bile. These symptoms persisted up to the time he came into the hospital. His
appetite was poor during the two days of his illness, and his
bowels moved once on the day previous to admission. During
this same day the patient had a definite fever.
On admission to the hospital he appeared very ill. As a
consequence of his excessive vomiting and retching his mouth
was exceedingly dry, his tongue red and " beefy " and there
was some bleeding of the gums. His temperature was 101.2°,
pulse 92 to the minute and his leucocytes numbered 15,000
per c. mm. Examination of the abdomen showed no discernible
irregularities, nor were any peristaltic waves seen. There was
some fullness present, especially in the lower half. Eespiration was entirely costal in type. There was no marked general
muscular rigidity, although there was increased tension of the
abdominal muscles over the lower half of the abdomen. On
deep palpation over McBurney's point slight tenderness could
be elicited. Elsewhere there was no abnormal tenderness. On
percussion, dulness could be demonstrated in the right lower
abdomen and in the flanks. This dulness shifted with change
of position of tlie patient and gave a splashing sound when the
overlying abdominal wall was tapped while pressure was made
in the flanks. There was evidence, then, of free fluid in the
peritoneal cavity. The upper abdomen was markedly tympanitic. The evidence of former operation was present in an
irregular scar just below the umbilicus, measuring about 1.5
cm. in transverse and 2 cm. in vertical diameter. Rectal examination revealed nothing abnormal. Without entering into
further details of the examination it may be stated simply that
the diagnosis appeared to be either intestinal obstruction or
acute appendicitis with perforation. As the patient's general condition demanded immediate operation, abdominal exploration was advised and readily consented to.
The operation, done about one hour after the patient entered
the hospital, was carried out through a right rectus incision.
In the peritoneal cavity there was present a fairly large amount
of free, serous fluid. Several moderately distended reddishlooking loops of small bowel were seen and also some collapsed
grayish loops. Exploration was first made in the region of the
appendix. Numerous adhesions resulting from the former
abscess and operation had to be carefully separated. After
considerable difficulty the appendix, which was coiled back
on itself in U-shaped fashion and firmly adherent in the right
iliac fossa, was freed and brought into view. It was unusually
long, measuring 17-18 cm. in length, of uniform thickness and
of fibrous consistency. There was evidence of a moderate
chronic inflammation in this region ; the appendix, however,
was not acutely inflamed. Appendectomy was done. The
condition of the appendix, I felt, could not be held responsible
for the patient's present condition and furtlier exploration
was made. At once a collapsed small intestine was seen low
in the abdomen and pelvis, while numerous overlying, reddish,
distended loops of small bowel were seen coming from above.
After further seardi it was found that the division between
distended and collapsed bowel was sharply demarcated by a
thick, firm, pinkish-white cord, measuring 1.5 cm. in thickness
and 6-7 cm. in length, attached at the distal end to the abdominal wall by means of adherent omentum at a point just below
the imibilicus and connected at the proximal end with the
terminal ileum at a distance proximal to the ileocecal valve,
common for Meckel's diverticulum (cf. scliematic drawing.
Fig. 1). Over this cord the loops of small intestine were
draped like clothes on a line and had become obstructed. The
distal end or tip of the diverticulum was attached to the
abdominal wall at the site of the former abscess and operation. Without great difficulty, the distal end together with the
adherent omentum was dissected free from the abdominal
wall and the base of the diverticulum at its attachment to the
ileum amputated and treated in the manner of an appendectomy. Further rapid search revealed no other abnormal findings, such as infection or seriously damaged loops of small
intestine, whereupon closure of the abdominal wound was made
without drainage. There were no disturbing symptoms following tlie operation and the patient made a rapid, complete
recovery.
In view of the findings at operation it seems likely that the
abdominal abscess for which the patient was operated uj>ou
six years previously had its origin in a perforation at the tip
of Meckel's diverticulum and that simple drainage of the
abscess was done through a small incision just below the
umbilicus, following wliich the abscess healed. The possible
cause of the perforation will be considered later.
Upon further examination it was found that the diverticulum had a large lumen which at the point of attachment to
the ileum measured about three-fourths of a centimeter in
diameter. It did not have the appearance of acute inflammation. The diverticulum was then slit open in a longitudinal
direction, whereupon a striking appearance was presented by
the mucous membrane. The proximal three-fourths of the
mucosa had a rather smooth, rolling, slightly folded surface.
It was pale-pinkish in color and resembled in this respect the
mucosa of the terminal ileum or first portion of the large
bowel. The distal one-fourth of the mucosa was considerably
thicker and was elevated above the surface of the proximal
mucosa from which it was separated by a sharp line of transition. It had, furthermore, a sharp differentiation in color,
in that it was of a deep red, cherry hue and its surface was
thrown up into large folds, the surface of which again was
irregular and granular in appearance. {Cf. drawing, Fig. 2,
g. m.) There was a marked difference also in the thickness
of the diverticular wall which, in its proximal portion, was
of the thickness of the terminal ileum, while at the tip it
was three to four times as thick as the latter. The muscular
coat, on the whole, was rather thin, and externally there was a
THE JOHNS HOPKINS HOSPITAL BULLETIN, JUNE, 1919
PLATE XIX
Fill. 1- Meckel's <livrrti<'uluni, with
adherent oiiieiituni.* iittjchetl to the anterior alMliiniinal vtall at a point just
below the unibilii'us. ( Sehemal ir. )
The chn>ni<- Hbrous adhesions resulted
from old abs<^?>s (urniation and jjubsequent operation.
Ki<
-Meokel>
inc Ihe thinner pnixinial inuttis;! t i. n
appearance, and the thicker tlislal
jp|H?arinK Kastrif nuiros.1 [ff. m.). V
-harp line of transition (T.). At O
"riientuin. (Natural size.)
'.I {..neilndinallv :
) rt'scniblinu' iUun
lie of irntrnlar.
of adherent
- A
:f^^;^
-*V
tofirraph -.ho\v^ tho strikinic «li(It
left in the drawing (KifC. H.
fflands in (he gastric niiic<>«a a
•e in thi< knew. U-twe*-!! tli'
y a ^mall portion .*r the
alM shown.
ftf
^'A
^y
^jf'-^.^ak^miM
the TiKht and the pi
, . • M,, Im.I.- I,.. Ill
Mill in -lain I The J
mal iiitesliniil niiicnsa on the
lortuojily and depth of the
June, 1919]
145
serous peritoneal covering continuous with the serosa of the
small bowel itself. At the tip there was a mass of adherent,
corrugated-looking omentum which had probably become adherent tliere at the time of the former abscess and operation.
Further examination at the time revealed no perforation nor
evident defect in the mucosji at the tip of the diverticulum.
The whole specimen was j)laced in 10 per cent formalin for
subsequent study.
Frozen sections were made of the wall of tlie diverticulum
BO as to include the transition line (cf. photomicrograph,
Fig. 3) between the two types of mucous membrane and were
then stained in lia.'mato.xylin and eosin. The proximal, thinner,
mucosa (similar to that seen on the left in Fig. 3) resembled
in structure that of the duodenum, or in many respects also
tlie ascending and transverse colon ; whereas in the thicker.
more irrt>gular. distal mucosa (on the right in Fig. 3), at the
tip there were si^n deep glands which resembled in structure
the fundus glands of tlie stomach and which were composed of
two types of cells — the larger, less numerous, bright-red-staining eosinophilic parietal cells and the more numerous, smaller,
indifferent-staining chief cells. In order to study in greater
detail the two types of mucosa, paraffin sections were prepared.
Several additional staining methods were used, namely, cresylecht-violett, the iron-ha-matoxylin method, the acid fuchsiii
and the neutral gentian methods as recommended by Bensley
and the mucicarmine method for the demonstration of mucus
in the goblet cells and in the distal goblet zone in the surface
columnar cells of the gastric mucosa.
I. Stkvctlre of the MrcosA Proxim.\l to the Transition
Point (T) (cf. Fios. 2 and 3)
Sections were made at the line of demarcation or transition between the two adjoining types of mucosa. Fig. 3
represents a low-power photograph of an ordinary section
stained in hsematoxylin and eosin and magnified 24 diameters.
The photograph shows the sudden transition from the thinner
proximal mucosa, on the left in the piiotograph, to the thicker,
more irregular, distal mucosa on the right. The striking difference in the relative thickness of the two mucous membranes
is well shofrn. A section of the proximal mucosa on the left
when observed under the higher power and after staining in
cresylecht-violett is seen to consist of a propria containing
simple, unbranched, comparatively shallow tubular glands
(cf. drawing. Fig. 4, of a similar section after iron-hiematoxylin). The mucous membrane has an irregular surface
and forms papillar}- outgrowths between the openings or
crypts of the glands. The lining epithelium is almost uniformly of the tall columnar variety, containing numerous
goblet, mucous cells throughout the extent of the mucous
membrane. These goblet cells in the neck and depth of the
glands are so numerous as to form in places the majority of
the cells lining the tubules. Here and there between the swollen goblet cells are seen thin, tall, irregularly compressed,
columnar cells — probably discharged goblet cells. Their protoplasm is compact, non-granular and more deeply stained.
The cells on the surface are of a low columnar, in places almost
cubical, type, with fewer goblet mucous cells tlian elsewhere
in the glands. In sections doubly stained in iron-alum-hiematoxylin followed by mucicarmine (the strong stock solution
of Mayer), as recommended by Bensley,* the goblet cells contrast strikingly on accomit of tiie brigiit red stiiin which their
irregular, stringy or spongy +++++
CONTENTSs take, showing tlius tiie
mucous character of the secretion of these cells. Afte'r staining in cresylecht-violett the mucous takes on a faintly purple
tint as compared witii the remainder of the cell. Near the
center of the cell is a denser, more deeply bluish stained zone
of c}'toplasm separating the mucous section of the cell from
the basal protoplasmic portion. The nuclei are large, rounded
or oval, fairly clear and basally placed. They contain a moderate amount of chromatin and have each a densely stained
purple nucleolus. Many of the nuclei, however, are elongated
and flattened, due to pressure from adjoining cells; in tlie
smaller cells they are basally placed, while in the discharged
cells tliey have a more central location. The protoplasm of
those cells lying between the goblet cells does not contain
secretion granules.
Many of these appearances are seen as well in the sections
stained after the iron-alum-ha»matoxylin method. Thus in the
drawing (Fig. 4) the goblet cells appear unstained, being
represented as clear spaces. There are no true villi of the
small intestine type. In studying the section further in the oil
immersion we find that the cells on the surface have a kind of
striated cuticular Iwrder. The nuclei of the cells, which apparently rest upon a definite basement membrane, have the
same character as those just described in the preceding paragraph. The protoplasm of the UM columnar cells between the
goblet cells fails to show any granules which one would consider as the antecedents of fennent secretion.
The propria (Fig. 4) is a loose tissue, containing numerous
.small blood-vessels and lymphatics, lymphoid cells and connective-tissue cells. In it are also a few smooth muscle
fibers from the L. muscularis nuiscosce running upwards into
the mucous membrane prolongations. In one area there is a
definite aggregation of lymphoid ti-ssue with a germinating
center; in fact, a lymphoid follicle with an outer denser. zone
of small round cells in the center of which appears a clearer
zone with larger cells and richer reticulum. Lymphoid tissue
of this kind is seen also in the sections taken from this proximal portion of the mucosa.
The submuco.sa consists of a layer of loose connective tissue
which contains blood-vessels and above which lies the L. muscvlaris mucosa (Fig. 4). Externally to this again there
appears a thick tunica muscularis, consisting of a thick inner
circular and an outer longitudinal layer, between which there
lies a plexus of nerve tissue. A small portion only of this
muscle coat appears in the lower right-hand comer of the
drawing (Fig. 4).
Additional sections including both types of mucosa were
made of the transition zone (T, Fig. 2) and .stained in hapmatoxylin and eosin, cresylecht-violett, iron-aluni-ha-matoxylin
and in mucicarmine. In tlie mucosa just distal to the transition line (on the right in Fig. 3) the following changes
146
[No. 340
occur: The proximal duodenal or perhaps transverse-colon
type of mucosa rather suddenly changes into a kind of transitional surface epithelium, consisting of two or more irregular
cell rows and two different types of cells. The majority of
these cells are of a taller t}'pe than those lining the intestinal
mucosa, and the nuclei, which are irregularly oval or rounded,
are more centrally placed and stain in ha?matoxylin a diffuse
bluish-purple in which a darker pifrple centrosome is usually
evident. These cells are often flattened and compressed, cylindrical, fusiform or dumb-bell shaped. Each surface cell has a
marginal cuticular border and a distal clearer zone separated
from the more proximal protoplasmic portion of the cell by a
transverse denser cytoplasmic band. In the eresylecht-violett
stain the distal clearer zone just described has a rather homogeneous structure and stains a very pale blue, as distinct from
the denser blue proximal protoplasm. The nuclei stain a pale
violet. In the mueicarmine the distal zone in many instances
is stained bright red, showing the presence of mucus. In
neither the eresylecht-violett nor in the iron-alum-hsematoxylin stained sections are any secretion granules apparent in
these surface cells.
The cells of the second type in the surface mucosa are
usually more deeply situated. These cells are rounded or
hexagonal in shape and have a comparatively clear protoplasm.
The nuclei are irregularly rounded or oval and deeply stained.
The propria is rich in lymphoid cells, blood capillaries and
connective-tissue cells. Numerous mast-cells, so frequently
seen in the normal stomach mucosa, are seen here also, and in
their cytoplasm the characteristic large red granules, after
staining in eresylecht-violett, can be recognized.
Numerous crypts or tubular prolongations are seen dipping
down from the surface into the propria. These glands are
highly tortuous, especially in their depths, and are lined by
two kinds of cells. The majority of them, the chief cells, to
use the terminology as applied to the gastric fundus mucosa,
are low columnar or cuboidal in shape, with a darker-staining
basal zone of protoplasm which has a slightly granular appearance. The lumen border of each cell is relatively clearer and
the nucleus is rather large, irregularly rounded or oval, and
basally placed. These cells after staining in eresylechtviolett are pale blue, with violet nuclei and bluish nucleoli.
Secretion granules do not appear in this stain, but after the
iron-alum-hajmatoxylin method, great numbers of black-stained
zymogen secretion granules are seen, such as one finds typically
in the chief cells of the gastric mucous membrane. A more
detailed description of these cells is given later.
The cells of the second type found in these glands are considerably larger than the chief cell just mentioned. They
do not, as a rule, touch the lumen of the tubule, as they have
a parietal situation and f reqiiently lie between or upon the chief
cells just mentioned. In the hfematoxylin-eosin preparation
a cell of this type stains light red or pink in the eosin, as distinct from the chief cell. It has, further, a distinct cell definition and a round, usually centrally placed nucleus, rich in
chromatin. Uniformly distributed in its protoplasm can be
seen rather large, highly retractile, practically unstained
granules, suggesting in every way the appearance in the
typical parietal cell of the stomach. In the cresylechi^violett
these parietal cells contrast clearly with the chief cells by
staining a faint pinkish-blue, while the latter are darker
especially in their basal portions, which are dark blue. The
secretion granules in such a preparation are of a violet color.
The nuclei are well defined, large and vesicular, and contain
relatively little chromatin. Many of the parietal cells are seen
to communicate with the lumina of the tubules by a cleft between the neighboring chief cells. In the iron-alum-haematoxylin the parietal cells are clearly shown, and in their cytoplasm
the secretion granules are seen to be uniformly distributed and
stained black. Except for the columnar cells on or near the surface, the mueicarmine fails to show the presence of any mucussecreting cells in the neck, body or depths of the tubules. A
further description of tliese glands as they occur in a section
just beyond the transition line is given below (c/. Fig. 5). In
the neck and body of a gland tubule the parietal cells are
almost as numerous as the chief cells, while in the depths of
the glands the smaller chief cells become more abundant. The
appearance throughout in fact is that of gastric fundus mucosa, except perhaps for the greater tortuosity in the tubules
than in the glands of the gastric fundus region (c/. Fig. 5).
Just below the mucosa there is a well-developed L. muscularis mucosce, which at one point just beyond the transition
line runs upwards, as a papilla or indentation, into the mucous
membrane and thereby suggests, together with the thickening
in the outer muscle coat, the formation of a sphincter. Just
beyond this point, furthermore, the mucous membrane assumes
the exact appearance of the fundus mucous membrane and will
be described in greater detail later.
The submucosa consists of a loose connective-tissue framework containing blood-vessels in great abundance.
The outer muscle coat is thick, and composed of muscle
bundles, not in two definite layers as in the proximal intestinal portion of the section, but running in all directions and
intertwining with one another. Numerous nerve fibers can
be seen in the outer connective-tissue coat below the parietal
covering and also between the muscle bundles. Here also
scattered ganglion cells are seen.
II. Typical Gastric Fundus Mucosa From a Point Just
Distal to the Transition Line Described
Above (Fig. 5)
At a short distance beyond the transition line between the
two types of mucosa the glands of a typical gastric fundus
type just described for the transition zone are seen in great
numbers. A more detailed description may here be given of
the glands as revealed after staining with hematoxylin, eresylecht-violett, iron-aluni-h£ematoxylin, mu^picarmine, neutral
gentian and acid fuchsin-niethyl-green. The appearance as
revealed in the high-power magnification and in oil immersion
need only be given here. Many of the findings in repetition
of those described as occurring at the transition point are
either omitted or only briefly mentioned. The drawing (Fig.
THE JOHNS HOPKINS HOSPITAL BULLETIN, JUNE. 1919
A
:^®»,.
^l« — ItiMttiiiic lit intNJfnitelv inan
niA.-<l «lion ( • 7S) (5 niiira Ihirktma, ironlu-niatox.vllii nirlhiHl) taken
from the ilJMtjil niiKfKii iit ii point ju*t
l>ry<>nfl the lnin>.it>on iniic. X.ite the
tvpif-al fhiiniitrr. of ira>lri<' funilti'.
niwoia. the lull airfare ooliimnar relU
at (.4), an<l the too charnrterislir t>Te<
of rell». the . hief an<l parietal, in the
ne.-k III), Ik.Iv (f| and Iwse (11) of
the dee|> tortuou.i gland.
Km. Ii- Jlr;mnii[« "r m|Uuii'.I
aTOw (.4, //. C, /(. Kilt. .'.I afliT
hiKh.|>ower uil-innnerNion niaKniltnition, to Khiiw the rjiol.iKiiiil
.luirarlerK of the i-<'llt. .. .iiipri.ini:
the Klanil tnliiile. .V.>lr llie tall
irfai-e. i-olunuiar. non 7.>tniHt<-riir
-.•IIk. (.1) the larite r.lill ively i le:ir
purli'l4il cHIh i-oiiliilnhiK nioilerale
nuMilx'iv of liirve, Mark MalllinK.
iii-iil<iphili<' (granule., a(i<l the ntorr
nnlnenm.. 'nialhr. .lurkrr •hief
r-ellv coiitajiiiiiir Iitrt;e ininilierM of
hiai'k otaininK. /> iteiiir Kranulea
airtrr<ifate<l aloiiie the lumen bor.ler> lit the ..lU III. <. /').
(FiK. 2. n (:
• of llru
thi» nertion with the
simple tvi>e of
rellii. the lymph foil
de\eiope«l L, mu*rula
• diKMlenuni. .Note the
n. the nunterfiuo jfohlet
Kland., and the well
June, 1919]
147
5) illustrates the appearance of a tvpieal gland in moderate
maguifit-ation, after irou-alum-ha>matox_vlin staining. Four
areas squared in this lower power drawing (Fig. 5, A, B,C,D)
are represented as seen in high-power oil iuiniersiou magnitication (Fig. 6, A, B, C,D).
Surface Epithelium. — Numerous crypts or depressions
found in the mucous membrane resembling the typical gastric crypts represent the openings or communications through
which the more deeply situated glands discharge their secretion into the lumen of the diverticulum. These crypts are
lined by epithelium of the surface type, composed of tall,
cylindrical cells in a single row or layer (Figs. 5 and 6, .4).
The large nucleus of each cell witii a well-marked nucleolus is
round or oval in shape and is usually centrally placed, but often
is found above or below the center of the cell. It stains fairly
densely by all methods, due to a fair abundance of chromatin.
The protoplasm of these cells takes a pale blue stain in the
cresylecht-violett and a gray in the luvmatoxylin and has a
spongj" structure. Secretion fjranules are not seen in the protoplasm. In the distal one-fourth of many of the cells there is
a clearer zone, in places grossly granular in appearance, having
a cup shape and separated from the remainder of the cell protoplasm by a transverse cytoplasmic band. This is the mucuscontaining end or zone of the cell, which is not, however, a true
goblet cell. True types of the latter were not seen at all in
sections from this area. In the cresylecht-violett this mucus
stains a pale blue and after mucicarmine a few of the cells
on the surface showed this cup-shaped end, or theca, red
stained and cither grossly granular or string}- in structure.
Just below the surface in the cr}-pts the mucus-containing
cells are more numerous than on the surface where they are
very few in number. Many of the cells have, furthermore,
an outer cuticular border.
Glands of the Gastric Fundus Type. — (Figs. 5 and 6, B,
C, D.) Into the depths of the crypts empty the secreting
glands, one or two, occasionally more, tubules to each cr}7)t.
These glands are of the simple tubular variety and occasionally
branched. The necks of the glands arc quite straight, but in
the depths the glands are usually tortuous or convoluted, as
indicated by the numerous tubules seen in cross-section in the
deeper zone of the mucosa. The glands are in close contact
with one another, with almost no intervening tissue of any
kind. The propria forms the groundwork or supporting tissue for the glands, surrounds them evervTvhere and extends
upward to the surface epithelium. Under the surface epithelium the propria contains a great many lymphoid cells uniformly and ditTusely scattered and fairly abundant. These
lymphoid cells, together with numbers of mast-cells, a blood
capillar}' network and some slips from the L. mu-scularis mucosa are also seen extending from the level of the latter
upwards between the glands to the surface epithelium. A
typical gland may be divided into three portions: the neck
(Fig. 5, B), the body (Fig. 5, C) and the depth or base of the
gland (Fig. 5, D). The neck of the gland consists of a rather
straight tube with a ven- narrow lumen, lined by two types of
cells. The first tj-pe is smaller, low columnar or almost cubi
cal in shape and stains bluish in hsvmatoxylin, with a darker
basal zone and a clearer zone bordering on the lumen and containing numerous rather large, black-stiiining secretion
granules. After the neutral gentian technique (Fig. T) these
same cells are stained a violet, especially in the basal portion,
and the secretion granules along the lumen border of tlie cell
now stain a dark violet. In the acid fuchsin-methyl-green
method (Fig. 8) these granules are faintly green or unstained.
These are the characteristic chief cells as seen tyi)ically in
the gastric fundus mucosa.
The second type of cell is larger, is irregularly rounded or
oval, borders on the lumen or is slightly removed from it and
covered in part by the neighboring chief cells. This cell is
clearer, the protoplasm is stained uniformly pinkish in eosin,
pale blue in cresylecht-violett, grayish in iron-htematoxylin,
faintly orange in neutral gentian ( Fig. 7 ) and red in the acid
fuchsin-methyl-green method (Fig. 8). Scattered uniformly
through tlie protoplasm are definite, large, discrete secretion
granules, black in the iron-h»matoxylin (Fig. 6, B, C, D),
faintly orange in the neutral gentian (Fig. t) and red in the
acid fuchsin methods (Fig. 8). The nuclei are large and
vesicular, with relatively little chromatin, are centrally placed
and contain a well-marked nucleolus. The cell outlines are
sharp. These are the parietal cells, the second characteristic
cell of the fundus mucosa of the stomach. The neutral gentian
(a neutral combination of the acid orange G and the basic
gentian violet) and the acid fuchsin-methyl-green methods
were employed to demonstrate the specific staining affinities of
the cells and granules of these fundus glands, to add additional
evidence to that obtained from the iron-ha.'matoxylin method,
that we are dealing with specific secreting gland cells of the
true gastric fundus type. The zymogenic secretion granules
of the chief cells, having a peculiar affinity for the gentian
violet in the neutral gentian stain, are seen colored a dark
violet, while the acidophilic granules of the parietal cells have
a relatively slight iiftinity for the orange G and hence appear
faintly orange. In the acid fuchsin-methyl-green method,
the conditions are just reversed, for which rea.son this method
was employed. We now find that the acidophilic granules of
the parietal cells stain a brilliant red in the acid fuchsin,
whereas the zymogenic secretion granules of the chief cells are
faintly or not at all stained in the methyl-green. The absence
of mitochondria, so well demonstrateil after osmic-bichromate fixation of the tissue and staining after the acid fuchsinmethyl-green method, is doubtless exi)lainable by the fact
that the tissue in this case had remained for a long period of
time in 10 per cent fonnalin. It would have been interesting
to study the mitochondria in this tissue as well as the secretion
granules, had it been possible to fix some of the original fresh
tissue in some other fixing fluids, such as the well-known
acetic-osmic-bichromate mixture. The findings described
above are well illustrated in the beautiful drawings in color
(Figs. 7 and 8) by Miss E. Norris.
Body aiul Depth of the Gland. — As one observes the gland
tubules at greater depths one finds that the same two types of
cells are found as described in the neck of the gland tubule.
148
[No. 340
Here, however, the larger or parietal cell has a truly parietal
situation, that it lies removed from the lumen at the periphery of the tubules and communicates with the lumen of the
tubules by a cleft between the chief cells. It also occurs
oftener. The chief cells show the same characteristics described above. At the base of the cells and forming a kind of
basement membrane, the membrana propria is evident. Secretion canaliculi in the parietal cells were not definitely seen,
due probably to faulty fixation. We have here, then, a type of
mucous membrane resembling in every particular, both as to
structure and staining affinities, the characteristics of the
fundus mucous membrane of the stomach.
A well-developed L. muscxdaris mucosce is seen, which here
and there sends off small, thin prolongations into the overlying
propria and between the glands. The submucosa has the usual
structure of this layer in the intestinal tract.
The tunica muscuJaris is thick and composed of smooth
muscle fibers intertwining with one another in various directions and not definitely demarcated into an outer and inner
layer of longitudinal and circular direction. No definite nerve
plexuses were recognized.
III. Section Taken From Proximal Part of Meckel's
Diverticulum
The structure of the mucous membrane and wall of the
diverticulum near to its intestinal attachment does not differ
in any important detail from that described above as occurring
just proximal to the line of transition (Fig. 4). It was
thought that possibly the principal type of mucous membrane,
that resembling transverse colon in structure, would assume
at the proximal end of the diverticulum the character of ileal
mucosa. This is not the case however, for the mucous membrane still resembles that of the transverse colon as described
above. There is this difference, however: the mucous membrane is slightly thinner, the folds or plicae are lower and there
is less IjTiiphoid tissue, both diffuse and in the form of follicles. There are more nerve fibers occurring in the submucosa, the tunica muscularis is thicker and more sharply
demarcated into an inner circular and an outer longitudinal
muscle coat, between which there are more nerve fibers recognizable. Inasmuch as the other findings are similar to those
occurring more distally (Fig. 4), a further description need
not be given here.
Thus, positive evidence has been advanced by the methods
of finer cytological study, that the zone of aberrant glandular
tissue in the tip of Meckel's diverticulum is identical in every
respect with gastric fundus mucosa. It was thouglit desirable
to make this detailed study of the histological character of this
anomalous Meckel's diverticulum for three reasons: In the
first place, to establish definitely the fact that we are dealing
with a zone of aberrant, but typical, gastric mucosa. This
was necessary in view of several reported cases of a somewhat
similar nature in which the anomalous or aberrant tissue
occurred at the umbilicus and was said to give the appearance
of pyloric or simply gastric mucosa, although no histological
examination is reported. For purposes of argument in the explanation of these anomalies it was first of all necessary to
advance definite proof that we were dealing with real gastric
mucosa. This having been done I feel I have advanced good
reasons for believing that the anomalous and aberrant glandular tissues occurring at the umbilicus, in obliterated vitelline
cords, and, as in my own case, in Meckel's diverticulum, have a
common origin, namely, from the remains of the omphalomesenteric duct. Cases in which pancreatic acini and Lieberkiihn's
and Brunner's glands have occurred in Meckel's diverticulum
have been reported and are given below. Undoubted cases of
gastric mucosa, of pancreas and of Lieberkiihn's and Brunner's
glandular tissue, occurring at the umbilicus in the form of
polyps, depressions or fistulas, have been reported. Several
cases are reviewed below in which such aberrant glandular
tissue occurred in instances of umbilical fistulse which were
connected with Meckel's diverticulum by a strand or cord.
In one or two instances a patent Meckel's diverticulum connected with the umbilicus at which such glandular tissue was
found. If we are forced to believe that certain fistulaj at the
umbilicus, fibrous cords connecting with Meckel's diverticulum, and the latter itself represent the remains of the vitelline or omphalomesenteric duct, then it would naturally follow
that all these anomalous glandular tissues have a common
origin. With the discovery of gastric mucosa in Meckel's
diverticulum, the chain of evidence of the common origin of
these tissues is complete. Additional evidence is then afforded
for believing that the umbilical anomalies arise from the
omphalomesenteric duct, inasmuch as we know that Meckel's
diverticuhmi represents the remains of the latter structure.
A plausible explanation of the embryonic origin of these umbilical anomalies is thus afforded, a fact which is highly
desirable in view of the many conflicting explanations with
regard to the latter which have been advanced by authors
writing on this subject. In the second place, it is interesting
to speculate upon the manner in which true gastric mucosa
comes to lie in Meckel's diverticulum, so far removed from the
mother organ ; and in the third place, inflammations, ulcerations, and certain pathological new growths occurring at the
umbilicus and in Meckel's diverticulum receive a rational
explanation on an embryological basis.
In reviewing the literature in search for accounts of the
occurrence of gastric mucosa elsewhere than in its normal
location, I have found Chapter VII, pp. 144-158, of Dr. T. S.
Cullen's ' excellent book on " The Umbilicus and Its Diseases "
most helpful. A complete review is given in this chapter of the
reported cases of gastric mucosa occurring at the umbilicus.*
In the brief accoimt here to be given I have dra'mi f reelv from
* The occurrence of intestinal mucosa at the umbilicus, in the
form of polypoid growths, with or without depressions or fistulfe,
is relatively common as compared with the frequency with which
gastric mucosa has been found in the same region. For a good
review of the cases of umbilical polyps composed of intestinal
mucosa the reader is referred to Cullen: "The Umbilicus and Its
Diseases," Chapter VI, pp. 120-143. A complete bibliography on
this subject is also given at the end of the chapter.
THE JOHNS HOPKINS HOSPITAL BULLETIN, JUNE. 1919
,5
r1
>.•' ^
t - V ^ *  »
-V
I*;,
\T
_»^A
Fiii. 7. — DrawinfT of a Klaii'l tuhule (.'i niicra, neutral
Ci'iitijii ttiiiii. uil iMiiiHToioiit fr.iiii ihc lip "f Mrckel's
div<*rtit-itliim. rfim-spondink: tn tin- :iii>a ri*)ires<-n(i>(] in
Kiff**. 5 aiKl fi. r anj D, I" wIm.w ihe rompItU' similarity
in ttnirtntt' i)n<l Mainjni; atflnilv with the appi-annces
tvpirally s*-«n in ffantrit- fumltiH iinuovi. Noti- (1) the
rhiff o'IIh with ilicir zvni<>t.'i'ni< "M-rrclifn trriinnli's iili.nff
thi- Iniiipn hor<)(-r «f tlif r^-IK ^.tainiil in the vi^lot: ;in<l
(2) Ih.' pari.'tal (ills, Y.-.thvt and (l.artr and with larne.
fjinily oranKP-fltained ffraniilf» MiitiercHl difTiiscly thn>iiKliout Ihe cyl'^plasm.
^%t -^^ *^  ^ 3^?''
^4^  • ^.0^
»Gv .•j>'' ;y:- f-'^r'sJ'
I
Fin. 8. — Prawine of \hv Kliind lubiilcs in cross-wrtion
(formalin, h niicra thickness, acid-fuclliln-niethvl-ifreen
sliiiii. oil iinnursiolil from Ihe B-iini- ar.M as r.|)ri«,nliil
in V\s. 7. The .hiif (ills iirc now scfii slain..! a taint
Ki-c.'ii nnd the /.iiloKeni.- s.'.Ti'tion (rniniilfs ar.- Iiar.ll.v
visible. The l.arietal .ells. liow. v.r, show their trial
afflnilv for Ihe aii.1 fiichsin. and the laru-e irranules which
the.v eonlain ar.> slain.sl a l.lilliani red. Note al-o an
occii-si.iiial inast-eell in the inter-tubiilar conne.'tive tisnue.
JrxE. 1919]
149
this review. Cullen (p. 145) classifies the lunbilical abnormalities in wliifh gastric mucosa was found into three tvpes,
thus, for example :
I. An umbilical polyp attached to the umliilical depression
by a short pedicle.
II. An umbilical polyp with a cystic cavity opening on the
surface of the polyp.
III. An umbilical listula with or without a small projection.
Fig. 9 will serve to illustrate the second type.
I. A most interesting example of the first type was described
by Tillmanns" in 1882. In a boy, 13 years of age, there was
found at the umbilicus a pedunculated tumor, the size of a
walnut, bright red in color, without a central opening and
covered with mucosa. After a meal had been eaten, the tumor
would swell perceptibly, while the mucosa became redder and
thicker. The secretion on the surface of the polyp had a
tenacious mucoid character. Whenever the tumor was irritated the flow of secretion was increased so that at such times
Flo. 9. — A long umbilical polyp with a central fistulous opening,
a remnant of the omptulomesenteric duct, (Schematic, after Cullen, p. 156.) This is an unusual t>-pe. the pol>-p being shorter and
more KMile. A feu- instances are reported in which the lining
mucofta was shown to be of gastric character. There is no connection
between the umbilical polyp and the email inte.stine in this t^-pe of
polyp.
2 to 3 c. c. of fluid could be collected in 15 minutes. The
secretion was acid in reaction, digested albumen, and upon
chemical examination was found to reseml)le normal gastric
juice. Upon microscopic examination by Weigert the mucosa
was found to have a structure similar to that of the pyloric
region of the stomach. On account of its digestive action the
secretion of the tumor had caused a maceration of the skin in
the vicinity of the umbilicus. Histological examination of
the mucosa of the tumor showed this to be similar in structure
to pyloric mucous membrane. Tillmanns then explains the
condition by showing schematically how a diverticulum of
the stomach may be included in the umbilical cord as a prolapse of stomach wall through the umbilicus just as the ileum
may do. This explanation will be considered again. No connection with the stomach or other organs was found.
Although the literature upon this subject is scanty, a few
subsequent reports of ga.«tric mucosa occurring at the umbilicus were found. Thus, umbilical polypi with a covering of
gastric mucosa have been desc-ribed by van Heukelom "
(1888), Keichard" (1898), Strada " (1903), and Minelli"
(1905).
In van Ileukolom's case, a child two and one-half years of
age, a tumor the size of a hickory-nut was found in the umbilical depression. It was red in color and had a granular.
moist surface and was attached by a thin pedicle. The latter
was divided and the tumor removed. On microscopic examination the tumor was seen to consist of an inner portion composed of muscle, connective tissue and vessels, luid an outer
portion or cortex 2 mm. in thickness and consisting of a
mucous membrane with long gland tubules, some interstitial
connective tissue and some lymphoid tissue at the base of tlie
glands. The latter resembled intestinal glands of tlie Lieberkiihn type. (Van Heukclom's explanation for tliis finding is
given below.) Van Heukelom refers to 12 cases of this kind
reported in the literature, his own being the 13th case. He
feels that there doubtless are many more which have been
reported under the diagnosis of " umbilical granuloma " and
have not been examined further. Most of tliese granulomata
when examined have been found to contain epithelium and
glands of intestinal type. In these cases there is no mention
made of gastric mucosa.
In a further study of the occurrence of gastric mucosa at
the umbilicus and with particular reference to Tillmanns' case
and his explanation of it, namely, that the gastric mucosa
is derived from a gastric diverticulum, van Heukelom examined a number of human fetuses with this point in view.
In one of his fetus cases he foimd a nodule of mucous membrane
at the tip of Meckel's diverticulum constricted otf from the
lumen of the latter. On microscopic examination this nodule
was found to resemble the pyloric mucous menibriuic of
this same fetus. The epithelium was very regular, composed
of long cylindrical cells with refractile protoplasm and basally
situated nuclei. There were no goblet cells. The mucous
membrane of the diverticulum, on the other hand, and of the
ileum itself was of an entirely different character, namely,
intestinal in type. Van Heukelom att^Mupts to explain the
origin of this heterotopic mucous membrane, a matter which
we shall again consider. It is to be emphasized here that this
piece of gastric mucosa was constricted off from the cavity of
the diverticulum and in no way communicated with it.
Eeichard reports the case of a boy five years old who presented a tumor, the size of a hickory-nut, in the umbilical
region, which had a small fistulous opening and from which a
clear fluid escaped. There had been a " weeping navel " since
birth. At operation the umbilicus was circum.scribed, the
jjeritoneum was opened and a cystic, bluish, demarcated tumor
was seen, from which a thin stalk ran upwards into the abdominal cavity. The stalk, which was very delicate and could not
be followed, was divided. The tumor with the surrounding
area of macerated skin was excised. Closure was made of the
peritoBcum and abdominal wall and the patient made a good
recovery.
The cavity of the tumor was lined with a mucous membrane which, when microscopically examined, was seen to
resemble the gastric type. No further histological description
18 given and no statement is made as to whether it was clearly
of pyloric or fundus character. Reichard is reminded of the
case of Tillmanns, except that in his own case the condition
had not gone on to evagination and prolapse of the tumor.
He was inclined to believe in the theory of Tillmanns, namely.
150
[No. 340
that this mucous ruembrane is derived from a diverticulum
of the stomach, and that due to the rotation and further
development of the stomach there is a twisting and later
obliteration of the cord of communication with the stomach.
Siegenbeek van Heukelom, as we shall see, is opposed to this
view.
Strada reports the case of a young woman of 20 who had a
tumor at the umbilicus covered with mucosa. On microscopic
examination this mucosa was seen to consist of cylindrical
epithelium and glands of the pyloric type.
Minelli describes an adenoma occurring at the umbilicus
presenting a picture of gastric adenoma.
II. A case of the second type, namely, an umbilical polyp
with a cystic cavity opening on the surface of the polyp, ha.s
been described by Eoser" (1887) in a boy one and one-half
years old. A bright red swelling was found at the umbilicus.
Opening on the surface of this swelling, which, as stated, belongs to the second type, was a cystic cavity 1 cm. in diameter.
The case was very much like that reported by Tillmanns. The
secretion from the umbilicus digested the surrounding skin
area, was acid in reaction and was responsible for a considerable induration and a red granulation-formation around the
opening. The walls and mucous membrane of this cavity were
excised. A secondary cauterization had to be done three weeks
later on account of incomplete removal. A detailed description of the structure of the mucosa is not given, mention
being simply made that the closely aggregated tubular glands,
between which there was a good deal of muscle tissue, resembled in every way gastric mucosa. There is no mention made
of a serosa nor as to whether the glands were of the fundus or
the pyloric type. Eoser was inclined to accept the explanation
of Tillmanns for this occurrence, namely, that a portion of
gastric mucosa had been constricted off from the pyloric region
at a time when the stomach had a vertical position and the
pylorus was supposed to be nearer the umbilicus. It is hardly
necessary to state, as will be explained in further detail below,
that this assumption does not suffice, for it is well known that
the pylorus in infants and very young children is in no such
proximity to the umbilicus, inasmuch as the large liver sepalates the pylorus and the stomach from the anterior abdominal
wall.
III. Fistulous tracts occurring at the umbilicus and containing gastric mucosa have been described by von Eosthorn "
(1889), Weber'' (1898), Lindner"" (1898), Lexer" (1899)
and Denuce' (1908). These belong to the third type of cases
mentioned above.
Von Eosthorn reports the case of a boy seven years old who
had an umbilical fistula. Its presence was first recognized
when the cord dropped off. After this a red papule formed
which secreted watery fluid and into which a sound could be
introduced for a distance of 2 cm. There was a continuous
flow of this secretion which amounted to 5 c. c. in 24 hours.
It was acid in reaction, slowly digested albumen and did not
positively contain free hydrochloric acid. The fistula was
excised and the patient was wall in 10 days.
On microscopic examination of the tissues from the depths
of the tmnor, gland lobules were found which reminded one
of parotid gland, whereas the branched tubules resembled
pyloric glands of the stomach. Von Eosthorn assumed that the
acid reaction of the secretion was due to zymotic external
influence which had altered the original alkaline reaction.
Lieberkiilm's glands were also found in the fistula, von Eosthorn ofliers and accepts the explanation of Siegenbeek van
Heukelom for the occurrence of his findings.
In Weber's case there was found in a boy three years old
a small red tumor at the umbilicus from which a fistula
led downwards for a short distance. From this fistula flowed
a watery secretion which contained mucous shreds, but never
intestinal or gastric +++++
CONTENTSs. The secretion amounted to
half a wineglassful in 24 hours. At meal times the secretion
was increased and then often accompanied by a colicky pain.
A digestion ulcer had formed around the fistulous opening at
the umbilicus which was one-half of a centimeter in diameter.
This secretion was alkaline to litmus. Weber felt that the
secretion of the tumor was increased during digestion probably by a reflex action through its nerve supply which he
thought was doubtless the same as for the normal stomach,
for, as we shall see, he felt that the tumor was derived from
the stomach by a process of diverticulum-formation. This is
iu keeping with Tillmanns' view.
The fistulous tract with the surrounding macerated skin
was excised. After the peritoneum was opened a thin cord was
found leading from the inner end of the tract to the under
surface of the liver, but without attachment to either stomacii
or intestine. A cystic bluish tumor was found at the umbilicus. The stalk was divided, the tumor extirpated as mentioned and closure was made, followed by recovery of the
patient.
The cavity of the tumor was lined with a thick mucosa
which was of the pyloric type. The columnar surface epithelium was seen to dip down to form glands which were
made up of only one kind of cells. There were no chief
and parietal cells as in the fundus region and no goblet cells,
no villi and no glands or follicles of the Lieberkiihn type.
There was an L. niuscularis mucosce and outside of this a longitudinal and circular muscle coat and a thick serosa. Weber
felt that from the gross and microscopic appearances it was
safe to assume that he was dealing with normal stomach
mucosa from the pyloric region. He felt, also, that the cord
passing to the under surface of the liver represented the remains of the umbilical vein. Weber was inclined to the view
of Tillmanns, that this fistula and tumor represented a portion
of the diverticular stalk from the pyloric region and had
become constricted off at the umbilicus.
Lindner, iu the discussion of a case of extirpation of a persistent ductus omphalomesentericus reported by Korte in
1898, reports a ca.se of his own in which there was a small,
reddish papule at the umbilicus in a boy three years old. For
some weeks or even months there was a secretion from this fistula and around it there was a large area of digestion of the
abdominal wall. A sound could be introduced into this fistula
JiXE. 1919]
IT) I
for a short distance. At operation a tumor was found, the size
of a walnut, behind the umbilicus, wliich connected in no way
witii tlie intestine. From the upper pole of the tumor there
was a fine connective-tissue strand running to the under surface of the liver in the re>;ion of the incisura. There were no
vessels palpable in tliis cord, which seemed to have no importance whatever. The tumor was excised and was found
to be lined by mucous membrane of the pyloric type. Lindner
states that ca.ses of this kind are extremely rare and dillicult
of explanation. He refers to the cases reported by Tillmanns,
but does not ajrree with Tillmanns' explanation of their occurrence. He states that there was no evidence in his case that
the tumor had any connection with a diverticulum or former
prolapse of the .<tomach. Lindner did not attempt to explain
the oc-currence further.
Lexer's patient was a child one year old with a congenital
umbilical fistula around which the skin was macerated. The
fluid secreted bv the fistula was clear, tenacious and iicid in
Flo. 10. Persist*nre of the out«r end of the omphalomesenteric
duct in the form of an umbilical flKtula attached to the small bowel
by a (Ibroun cord. (Schematic, after CuUen, p. l.'>6.) This is the
tj-pe of remnant of the omphalomesenteric duct described by Lexer.
In the latter's rase, however, there was a blind fistula at the umbilicus leadinir downwanls a short distance and also a fistulous tract
leadinf? from the small intestine through the fibrous cord or obliterated Meckel's diverticulum. The two fistulous tracts, however, did
not communicate. The outer umbilical fistula was lineal by (gastric
mucosa and the inner or proximal fistula by intestinal mucos;i.
reaction and chemically resemliled gastric juice, in that it
readily digested egg albumen and fibrin. At operation the fistulous tract was found to have a cord of attachment, as thick as
a lead pencil, to the convexity of the small bowel. The cord
was amputated from the intestine and the fistulous tract
excised. The child made a rapid recovery. The proximal or
inner end of the cord, which was attached to the intestine, evidently represented Meckel's diverticulum (Fig. 10).
The extirpated fistulous tract had a rather wide opening at
the umbilicus and al.so at the intestinal end, although it was
not completely patent throughout it.« whole extent. The external fistula was one and one-half centimeters in depth. The
specimen was thus divided into two i)art.«. The proximal
larger section, which communicat<'d freely with the bowel,
had a mucous membrane very similar to that of the intestine
and of the type generally found in Meckel's diverticulum.
Lieberkiihn's glands with numerous goblet cells and individual
lymph follicles characterized this mucosa. In the original, a
plate of a low-power drawing is shown of the histological appearance which resembles my own case, the mucous membrane
appearing very much like transverse colon in many respects.
The appearance, as shown by section, of the external or umbili
cal portion of tliis fistula was very different. The mucous
membrane was of tJie pyloric type, as similarly described by
von Kosthorn and Lindner. The epithelium was tall and cylindrical and the protoplasm highly refractile. The nuclei were
basally situated and there were no goblet cells. In the deptli
there was to be seen a riclily developed zone of tubular glimds
connected by numerous crypts with the lumen of the fistula.
In general, then, the wliole structure of the mucous membrane
resembled that of the pyloric region of the stomach. This
structure was not as regular, however, as in the normal structure. In the original, a second plate is showi to illustrate
this mucosa. External to the mucous membrane there are
the usual muscular layers. For a short disUmce the luniina
of the two segments overlapped one another, so that in a single
section taken at this point one could see both types of mucous
membrane: the intestinal, belonging to the proximal fistula
or cavity, and the pyloric type, corresponding to the external
or distal fistula. In the deptli there was only an imperfect
cellular connection between these two types of mucous membrane. At this point tliere was a mixture of the two types of
mucous membraJie and Ix'.xer believed that the outer fistula
was formed originally, by a constricting process, from the
original diverticulum of Meckel. The findiiig.s, as a whole,
Lexer believes, allow of no other explanation than that there
is a complete persistence of the ductus ompluilome.sentericus,
whose outer portion, probably as a result of very early separation, is subjected to a different evolution of its mucous membrane than that portion of the fistulous tract which connected
with the intestine, namely, Jlcckel's diverticulum.
In explanation of the similarity of the secretion from the
outer portion with that of gjistric juice. Lexer was unable to
give any satisfactory facts and referred to the rather unsatisfactory attempts at explanation by van Hcukelom and von
Rosthorn. Lexer was more inclined to believe tliat tlu^se formations arose from rest* of the original omphalomesenteric
duct and Meckel's diverticulum rather than from gastric
diverticula, even though there was lacking the anatomical
connection between the umbilicus and Meckel's diverticulum.
In order to feel that the gastric mucosa at the umbilicus was
derived from the same mucosa or from the same structure*
from which Meckel's diverticulum develops. Lexer said he
would like to see a case in which there was a preservation of
the connection between the gastric mucous memiirane at the
umbilicus and a Meckel's diverticulum. My own case shows
that even without such an anatx)niical connection gastric mucosa is found in Meckel's diverticulum and thus affords additional proof that the cases of gastric mucosa at the umbilicus
have an origin similar to that of Meckel's diverticulum.
Denuce described in a boy 21 months old a congenital fistula
at the umi)ilicus from which there was an abundant flow of
secretion which was ordinarily colorless, sometimes slightly
hemorrhagic, and which gave an acid reaction and upon chemical examination was found to be practically identical with
gastric juice. There was digestive action on the skin around
the umbilicus. The microscopic examination of the fluid
revealed nothing of imjiortancc. Free hydrochloric acid was
152
[No. 340
present. By means of a sterile pipette 3 c. c. of secretion were
collected and examined chemically. The principal findings
included demonstration of the presence of albumen, peptone
and free hydrochloric acid. The fluid digested coagulated
albumen. He concluded, then, that the secretion must be considered a kind of gastric juice. At the operation the fistulous
tract was removed without necessitating the opening of the
peritoneal cavity. The peritoneum was transparent and it
was possible to see, a little to the left of the deeper attachments
of the fistula, a cylindrical cord which, at its proximal or inner
extremity, was connected with one of the intestinal loops
(Fig. 11). It was at once recognized that this cord represented Meckel's diverticulum and connected at its distal
extremity with the umbilicus. The diverticulum was then
exposed and amputated at its base. The child made a good
recovery.
Fig. 11. — An umbilical polj-p connected with Meckel's diverticulum by a fibrous cord. (Schematic, after Cullen, p. 121.) This
is the type of remnant of the omphalomesenteric duct which was
described in IJenuce's case. In the latter, however, the umbilical
polyp had a central fistula which was lined by mucosa of the fundus
tj-p'e. Remnants of practically the whole of the omphalomesenteric
duct are present here. The outer end is represented by the umbilical
polyp, the centrai portion by a fibrous cord and the inner end by
Meckel's diverticulum. The latter had the usual intestinal type of
mucosa.
The tissue removed was preserved in formalin. The specimen consisted of two parts : the outer fistulous part attached
to the external surface of the peritoneum and the inner part
or segment consisting of Meckel's diverticulum attached at
its distal extremity to the inner peritoneal surface. A section from the outer fistulous part showed the mucous membrane to liave the characteristic structure of gastric mucosa
of the fundus type. The surface cells were tall, cylindrical in
type, and filled with mucus. In the connective tissue there
were some fibroblasts, mast-cells and eosinophilic cells. The
superficial tubules were continuous below with the true peptic glands. The latter were lined with clear cells containing zjaiiogen granules and a second type of cell, the parietal
cells. These were very numerous in the depth of the culde-sacs, but less abundant in the deeper portions of the gland
tubules. The eosinophilic cells and the mast-cells were also
found in the deeper portions of the glandular zone. In the
corium true lymphoid nodules with germinating centers were
present. The muscular layer on the outside was very thick.
In brief, then, Denuce felt that he was deahng with a gastric
heterotopy in the form of an isolated small cul-de-sac or fistula
at the umbilicus, plainly and fully functioning. Before discussing further his own case he then refers to some previous
observations on the development of our understanding of the
peculiar histology of congenital umbilical fistula of the socalled pseudo-pyloric type, which is extremely rare.
Finally, it may be well to refer briefly to the case described by Salzer "' (1904) of a patent diverticulum (Fig. 12),
which in the free abdominal portion showed normal characters
of the intestinal mucosa. In the prolapsed portion at the
umbilicus, however, there were found glands resembling in
structure the cardiac glands of the stomach. In the histological description of these glands he says the cells of the gland
tubules are clear, finely granular, polygonal in shape and have
a basal nucleus and some affinity for eosin.
In explanation thereof he suggests that, in the closure of the
abdominal cavity, for some reason or other, there is a partial
or complete cessation in the evolution of the vitelline duct
and that thereby the entoderm is irritated or stimulated to
Fig. 12. — .\ patent omphalomesenteric duct with a polj-poid formation at the umbilicus. (.Schematic, after Cullen. p. 190.) This
represents the type of case described by Salzer. The lumen is continuous through the umbilical polyp, through the persistent omphalomesenteric duct, and communicates with the small intestine.
a variable difl'erentiation, so that there is a development at one
time of intestinal mucosa, at another time of gastric; again,
there may be produced parotid gland or even pancreas. He
says, furthermore, that these pathological pictures are always to be found at the distal end of the remnants of the
\'itelline duct, in fact, just at that point where the incomplete
involution of the vitelline duct is so apt to be found. There
have been many different views in explanation of the origin
of these aberrant tissues at the umbilicus, with particular
reference to the occurrence of gastric mucosa. Before entering
upon these, however, it will be helpful to review briefly the
embryological evolution of the omphalomesenteric duct. In
this way a clear conception can be had of the probable origin of
a large number of anomalous conditions which one finds at
times at the umbilicus and in its neighborhood.
The vitelline or omphalomesenteric duct represents in
fetal life the communication between the intestine (ileum)
and the yolk sac. The yolk sac in time develops into the
umbilical vesicle. Ordinarily, at about the seventh week
to the tenth week the yolk stalk, which connects between
the ileum and the umbilical vesicle, separates from the intestine. The latter, which at first lies in part in the
umbilical cord, retracts into the abdominal cavity and thereafter there is no further indication of the original connection between the intestine and the yolk sac. If the separation of the intestine from the yolk stalk is delayed or fails to
June, 1919]
153
occur at all, then various resultiug anomalies are found in the
region of the umbilicus at the time of birth or even later in life.
The slightest persistence of the vitelline duct is represented by
a thin connective-tissue strand extending from the umbilicus
to the ileum. This strand is of little interest aside from the
fact that occasionally intestinal obstruction may be produced
by it. The fullest degree of persistence of this structure is
represented by complete patency of the duct, thus establishing
a free communication between the umbilicus and the intestine.
From a condition of this kind there develops the well-known
type of congenital umbilical fecal listula, numerous cases of
which liave been reported. Through such a listula a portion of
the bowel wall or even a loop or more of small bowel may prolapse. Between these two extremes there are all possible
transitions. The most common partial persistence of the
vitelline duct is that of the well-known finger-like diverticulum of Meckel, which is usually entirely separated but may
be connected with the umbilicus by a few fine strands of connective tissue. Such cases are also numerous. A diverticulum
thus attached to the umbilicus may cause various types of
fetal strangulations, torsions and obstruction. At other times,
this duct connecting between the umbilicus and the intestine
becomes obliterated at both the umbilical and the intestinal
extremities with an intervening lumen lined by a cylindrical
epithelium and containing more or less secretion. From a
remnant of this kind arise the well-known cysts or entcrocystomata. Again, the duct may remain open at the umbilicus
and become obliterated within the abdominal cavity. This
type of persistence gives rise to umbilical fistulas, tumors and
cysts. These may be opened externally at the time of the ligature of the umbilical cord or through umbilical inflammation.
Again, there may be a nodule of mucous membrane with or
without a lumen and constricted off from the tip of Meckel's
diverticulum with which it thus has no communication. Both
structures, however, evidently arise from a partial persistence
of the original vitelline duct.
We might consider now the theories and views which liave
been advanced to explain the occurrence of aberrant glandular
tissue at the umbilicus and which concern particularly those
cases of gastric mucosa reported above.
The first view was that of Tillmanns (1882), namely, that
in the cases exhibiting gastric mucosa at the umbilicus in
the form of a tumor or fistula we are dealing with remnants
of gastric diverticula which have been preserved at the umbilicus, but which have severed their former connections with the
motlier organ. This view was accepted by Reichard, Roser
and Weber. The last, particularly, was a firm believer in
this probable origin of the aberrant gastric tissue, and in his
report in 1898 explains in detail the mechanism of this formation. As it was impossible for me to get Tillmanns' original
article I have quoted largely from Weber's article which follows
in general the views of Tillmanns. According to this view, then,
there occurred in early fetal life a herniation of the stomach
at the umbilicus, which herniation was still connected with the
stomach by a kind of diverticulum and that this diverticulum
was opened at the time of birth. The question which Weber
now puts to himself is this : How does a gastric diverticulum
or herniation come to lie in the first portion of the umbilical
cord? His explanation is as follows: In the youngest human
embryos which had been examined up to his time, and which
were from 14 to 18 days old, the intestine has not yet become
a more or less closed tube, but communicates by a rather wide
stalk with the yolk sac. Gradually the yolk sac develops into
the umbilical vesicle, which is connected by means of the vitelline duct with the sub.sequent tubular intestine. The vitelline
duct becomes a portion of the umbilical cord and later obliterates. The bowel retracts into the abdominal cavity and all
connection with the umbilical cord disappears. Up to this
point the presence of a portion of the intestine in the beginning of the umbilical cord is a physiological occurrence. If
separation of the vitelline duct from the intestine is delayed,
then traction within the umbilical cord is exerted upon the
intestinal tract and the intestine remains as a normal +++++
CONTENTS
of the first portion of the cord, thus producing an umbilical
herniation with small intestine as its +++++
CONTENTSs. If this herniation remains it can be readily overlooked by the physician
or the midwife, and at the time of ligature of the cord it may
be opened so that a fistula may rise from which the child
generally dies as a result of complicating peritonitis. On the
other hand, such a hernia may be only a temporary occurrence
and subsequently, after separation of the vitelline duct, the
bowel may retract into the abdominal cavity. In a case of this
kind a dilated ring persists at the umbilical opening and thus
predisposes to a potential hernia. In this manner a diverticulum of the stomach might enter the umbilical opening, or
even without assuming a delayed separation of the vitelline
duct such a herniation is conceivable if one imagines the
stomach held in application against the umbilical opening by
the presence of adhesions.
The second question which Weber asks himself is this:
Why is it that there is no tract or strand connecting with the
stomach ; in other words, why is it that the prolapsed piece
of mucous membrane appears as an anlage entirely separated
from its point of origin ? He believes that there are processes
of con.striction during the period of development which play a
role if Tillmanns' theory is at all correct. Thus, if we assume that in an early developmental period there is an attachment between the first portion of the umbilical cord and the
stomach, then, as a result of this, traction is exerted upon
the stomach as against the traction of the mesentery. The
stomach is drawn out into a diverticulum and the connection
between the adherent portion and the stonuich proper is narrowed down to a very small duct. In addition to this, there
are the subsequent changes of position to which the intestinal tract and the stomach are subjected in their further
embryological development. Originally the stomach is formed
as a fusiform dilatation of the otherwise uniform intestinal
tract and has a vertical position. Its long axis becomes transverse and the pyloru.s comes to lie high on the right and the
cardia moves to the left. The portion to the left then develops
as the fundus. In addition there is also a torsion of the long
axis, so that the left surface becomes anterior and the right
154
[No. 340
posterior. The mesentery also makes these twists and must
therefore alter its length and form, thus creating the bursa
omentalis. If we now assume that abnormal adhesions have
held tlie stomach wall in apposition with the region of the
umbilicus, then this change in position can readily cause a
narrowing of the duct-like connection between the umbilical
herniation and the stomach, resulting in the formation of a
twisted cord which in time obliterates and finally disappears
entirely. Assuming these facts as a plausible hypothesis,
Tillmanns and his adherents endeavor to explain the occurrence of gastric mucosa at the umbilicus as a form of ectopia
ventriculi. Against this view van Heukelom takes a decided
stand.
Van Heukelom, whose view was accepted by von Eosthorn,
believes that these aberrant growths at the umbilicus represent remains of the vitelline duct and arise in a manner which
he explains as follows : In the second month of fetal life the
intestine still forms a loop which is to be found in the umbilical cord. The tip of this loop represents the point from
which the ductus omphalomesentericus is constricted off. In
the third month this intestinal loop retracts and then the intestine lies free in the abdominal cavity. If we now assume
that this diverticulum or loop, for some reason or other, does
not retract at its proper time on account of the tension of an
unobliterated vitelhne duet, then the portion of the diverticuhim connecting with the intestine may be pulled away, and
being thus entirely separated from the latter comes to lie
isolated at the umbilicus. In this manner we have the beginning of our ectopia. If now this mucous membrane and
musculature of the open diverticulum at the umbilicus continue
to grow while the surrounding umbilical structures retract,
then the former will evaginate and in this fashion, in time,
a tumor forms, which is covered with mucous membrane.
Van Heukelom refers to 12 cases of this kind which he has
collected and gives reference to them, his own being the 13th.
There are probably many more which have escaped notice because they are classified under umbilical granulomata without
further report as to their histology. Many of these aberrant
tumors at the umbilicus have been shown to contain intestinal
glands and epithelium. In these 13 cases there is no mention
made of gastric mucosa.
As already mentioned, van Heukelom described a case of
his own of gastric mucosa occurring at the tip of Meckel's
diverticulum and feels that there is a uniform origin for all
the various aberrant tissues found at the umbilicus. There is
a general consensus of opinion that these tissues are derived
from the tractus intestinalis, but as to what part of the tract
represents the mother organ there is a great difference of
opinion. Van Heukelom, in the first place, answers what he
considers the erroneous explanation of Tillmanns and Roser,
namely, that umbilical gastric mucosa represents a portion
constricted off from the early fetal stomach at a time when the
stomach is supposed to lie in the vertical position, in close
proximity to the umbilicus. Van Heukelom examined a series
of fetuses with the purpose of determining the probability of
such an occurrence. He concludes that it is impossible to
believe that gastric diverticula can thus be formed, for the
reasons that the enormous liver occupies the space between the
imibilicus and the deeper lying pylorus and relatively takes
up more and more room, the younger the embryo. There is
no connection between the pylorus and the umbilicus, but on
the contrary there is always a wide separation between them.
On the basis of his findings in one of his fetus cases, namely, of
a portion of gastric mucous membrane at the tip of Meckel's
diverticulum and separated from it, and the finding in Meckel's
diverticulum itself of the usual intestinal epithelium, he constructs his theory for the explanation of these variations in
histological differentiation.
Two questions, he says, now arise : Firstly, how can one explain the great difference between the epithelium of the distal
portion separated from the diverticulum and that of the proximal portion of Meckel's diverticulum? And secondly, is it
possible upon the basis of this observation to explain the origin
of aberrant gastric ectopia at the umbilicus without resorting
to the dangerous assumptions, such as those of Tillmanns and
Roser ? In answer to the first question there are the f ollo%ving
facts which are helpful : In very young embrj'os the intestinal
tract is lined by a single layer of entodermal epithelium which
is everywhere of uniform character. Later differentiation
into gastric and intestinal epithelium appears and at the
same time one recognizes folds and crypts which later become
glands. Van Heukelom states further that the difference between stomach and intestinal epithelium occurs first at the
time when the meconium or better when bile-stained material
is found in the intestinal tube. Then for the first time one
can differentiate the tall, regular epithelium from the intestinal epithelium, which is granular, low, shows a different kind
of nuclei and contains many goblet cells. If we now remember
that the portion of mucous membrane constricted off from
Meckel's diverticulum was not in connection with the cavity
of the diverticulum and therefore not in contact with the
+++++
CONTENTSs of the intestinal tract and that this separated portion
of mucous membrane corresponded in histological structure
to that of the stomach, the thought arises that this differentiation in the types of mucous membrane is brought about by the
influence of the intestinal +++++
CONTENTSs. It was van Heukelom's
opinion that it is the influence of the bile which causes the
differentiation into intestinal epithelium, and that the gastric
mucosa and also this portion of mucosa separated from the
diverticulum of Meckel, which do not come into contact with it,
take on a different course of histological evolution. This
explanation of van Heukelom can at once be considered as
quite erroneous, for in the first place it is well known that the
fetus swallows certain materials which must contain intestinal
+++++
CONTENTSs and therefore bile. Van Heukelom assumes, however,
that this swallowed portion is without the agent, which he feels
acts upon the intestine differently than upon the stomach.
In the second place, in my own case, the area of gastric mucosa
occupied the distal third or fourth of Meckel's diverticulum,
had a perfectly free communication with it and therefore the
intestine and hence was subjected to the same influences as the
intestinal mucosa. There could be no doubt about this point.
JUNB, 1919]
155
One, therefore, need not assume, as van Heukelom did, that it
was tlie total separation from the intestinal tract which caused
this peculiar development of gastric mucosa.
Now as to the second question van Heukelom asks : Can the
facts thus derived give a reasonable explanation for the ori^'in
of aberrant tumors of gastric mucosa, such as Tillnianns,
Roser and van Heukelom himself described? The latter felt
that tliey could. He felt that Meckel's diverticulum might of
course give origin to ectopia at the navel. The difficulty in
the cases of Tillmaniis, Koser and van Heukelom lay in the fact
that, whereas previous observers had derived the inti'stinal
epithelium from Lieberkiilin's crypts, in the latter three cases
the epithelium showed the character of pylorus. Van Heukelom e-xplains this variation by assuming that the ectopia
at the umbilicus originated from the intestinal tract, inasmuch
as in his own case the gastric mucous membrane was still attached to Meckel's diverticulum, which, as everyone grants,
arises from intestine. The reason, then, for the variations in
the initial ditferentiation into gastric and intestinal types of
mucous membrane he explains by assuming that if the nmcous
membrane preserved its communication with the intestinal
tract up to and beyond the period of bile formation and was
thus subjected to the influences of the latter, then intestinal
epithelium developed; if, however, this aberrant epithelium
became separated off from the intestinal tract before the secretion of bile appeared, it developed into gastric mucosa, and thus
became morphologically identical with pyloric epithelium.
Van Heukelom prefers this view to accepting the hypothesis of
Tillmanns and Koser as to the origin of these tissues from
gastric diverticula, which view has no anatomical basis and
which a priori is doubtful. Here again my findings refute
this view, for in my own case the gastric mucosa was developed in full connection and communication with Meckel's
diverticulum and therefore in the presence of bile and its
influences. Van Heukelom thus derives the intestinal ectopia
at the navel from portions separated off from a true Meckel's
diverticulum and as a consequence divides this umbilical ectopia into two groups: the first group which separated by constriction and became isolated very early, that is, before bile
formation, and thus developed into gastric mucosa ; and the
second group which became separated off at a later time. The
former will thus contain pseudo-pyloric epithelium and later
secrete an acid juice, the latter will show Lieberkiihn's crypts
with goblet cells and secrete an alkaline fluid.
The third explanation for the origin of this aberrant tissue
is that of Salzer (1901) and Kirnii.sson. According to this
view, the following a.ssumption is made: At the time of the
closure of the abdominal cavity, for some reason or other, there
is a partial or complete cessation in evolution of the vitelline
duct. As a result, the entoderm at the umbilicus is stimulated
to manifold differentiation and, consequently, at one time we
find a diverticulum of intestinal epithelium and at another
time of gastric epithelium, and then again we may have the
formation of parotid gland or pancreatic tissue. These pathological formations, according to Salzer, are always to be foum!
at the distal end of the vitelline duct, at that point particularly
where the predisposing cause of the incomplete involution of
the vitelline duct seems to be located. This cause may be in
part local irritation or inflammation. In favor of the irritation or inflammatory view, these men pointed to the presence of lymphocytes, mast-cells and eosinophile cells in the
mucosa. One need merely state, however, in refutation of this
assumption that the finding of such cells is very common in
the normal mucosa of the stomach and intestinal tract. There
is the statement further that aberrant tissues are always to be
found at the distal end of the vitelline duct, never at the
proximal. With this assumption it would not be possible in
my own case to explain the occurrence of gastric mucosa in
Meckel's diverticulum, in a position certainly not subjected
to irritative influences such as are supposed to be present at
the umbilicus.
The fourth theory was that advanced by Albrecht and Fischl.
According to this view these aberrant tissues arose from fetal
inclusions or rests occurring at the time of the closure of the
abdominal wall. This view is similar to that offered for the
explanation of the occurrence of atypical tissues in various
parts of the body. The misplaced rests from the junction
points of the blastodermic layers are assumed to be the points
of origin of these new tissues. It is thus assumed that these
misplaced cells may retain their original powers of differentiation. This is the old teratological view for the origin of tumors
and aberrant new growths. Here again one need not assume
this view, for, in van Ileukelom's case in the fetus and in my
own, the aberrant tissue was found in the former attached to
Meckel's and in the latter within Jleckel's diverticulum, and
thus probably was not the result of misplaced tissues at the umbilicus. In fact, in my own case the gastric mucosa was in
direct continuity with the intestinal mucosa of the diverticulum. Salzer, however, admitted that in many cases in the
closure of the umbilical ring there was a complete or partial
persistence of the omphalomesenteric duct. Fischl felt that
his theory explained more satisfactorily the fact that the abnormal formations of gastric, duodenal and pancreatic tissues are
most often to be found in the distal extremity of the diverticulum than did those of Tillmanns and Salzer.
The fifth explanation offered by Lexer (18'.)9) and Denuce
(1908), whose view is doubtless most nearly the correct one,
assumes that these umbilical abnormalities represent the
remains of the omphalomesenteric or vitelline duct. Lexer
gives no real explanation for his peculiar finding of pseudopyloric glands in the case of the umbilical fistula which was
attached to but did not communicate with .Me<'kcl's diverticulum ; but he leans toward the views of van Heukelom, that these
tissues represent rests of Meckel's diverticulum rather than of
gastric diverticula even in tiiose cases in which we find a
mucous membrane with gastric structure and secretion, and
in which there is no anatomical connection between the umbilicus and Meckel's diverticulum. He would like to see a specimen in which there is a connection between the umbilical
gastric mucosa and Meckel's diverticulum in order to afford
anatomical proof for his belief. Such a case is that described
by Denuce, in which case the fistula at the umbilicus did not
156
[No. 340
communicate with but was attached to Meckel's diverticulum.
My own case completes the evidence, for in this case gastric
mucosa is found at the tip of Meckel's diverticulum. Denuce,
in spite of this latter view, cites the following facts : Originally the intestinal tract is lined throughout by a simple
uniform entoderm. The differentiation into gastric and intestinal types is a later development. The cause of this differentiation in the epithelium is not clear. He suggests that
isolation and occlusion of segments of a diverticulum from the
intestinal tract are essential to the formation of gastric epithelium, and that there might be very early displacement in the
original vitelline duct which gives rise to variations in subsequent differentiation. He is inclined to agree with van
Heukelom that the occlusion of the segment is the initial cause
for this variable differentiation, but he does not accept
van Heukelom's view that the differentiation depends at all
upon the action of the bile. He says this leads us into the
domain of pure hypothesis. In other words, Denuce and Lexer
lean to the view that these tissues arise from remains of the
omphalomesenteric duct, namely, the intestinal tract, but
offer no further explanation for the variations in subsequent
differentiation. Denuce thinks that while occlusion and separation are probably responsible, the action of bile is not a
factor. He gives no further explanation. Here again tliis
view can be answered in a word, namely, that occlusion and
separation are not necessary, for they surely were not present
and could not be responsible for the variation in my own case.
In a review of the cases reported in the literature of aberrant
glandular tissue occurring in Meckel's diverticulum itself, I
have been unable to find mention of the occurrence of gastric
mucosa. In the search it became apparent, however, how often,
relatively, pancreatic tissue has been found in the intestinal
tract; in fact, cases were found in which pancreatic nodules
occurred in the stomach, duodenum, jejunum, ileum and even
in Meckel's diverticulum. There were no cases found in which
pancreas was discovered below Meckel's diverticulum, a fact
which will be considered again. Because of the relative frequency with which aberrant pancreas has been found in the
intestinal tract, a brief review is given of these cases and
finally a few others are also reported in which Lieberkiihn's*
and Brunner s glands and pancreatic tissue were found in
Meckel's diverticulum. There is one case also reported in
which pancreas was found at the umbilicus. These cases are
reviewed with the hope that they may throw some light upon
our own case and in general upon the occurrence of gastric
mucosa at the umbilicus and in Meckel's diverticulum. The
case reports are reviewed in groups according to the location
of the aberrant pancreatic tissue ; the first cases being those in
which pancreatic tissue occurred in the stomach wall, then in
the duodeum, jejunum, ileum, Meckel's diverticulum and at
the umbilicus. In only a few instances are the histological
descriptions complete and in many instances not really convincing enough to make one feel that the author was really
dealing with true pancreatic tissue. On the whole, the explanations offered for these abnormal findings are rather unsatisfactory. Eeference, however, will be made to them in order to
complete our review of tlie theories which have been offered
to explain these occurrences.
Klob " (1859) found a flat, circular swelling, of glandular
appearance, inserted between the peritoneal and muscle coats,
in the middle of the greater curvature of the stomach. Upon
microscopic examination this glandular mass showed pancreatic structure throughout. No further description or
measurements are given. Klob called this tissue " pancreas
accessorium." In substantiation of the belief that he was
dealing with an accessory pancreas, he refers to Leydig," who
claims that in the land salamander in the wall of the jejunum
and in pelobates in the wall of the stomach one can find isolated portions of the pancreas with excretory ducts.
Gegenbauer " (1863) similarly described an accessory pancreas occurring in the wall of the stomach, 2 cm. from the
pyloric sphincter and near the lesser curvature. It consisted
of a rounded, somewhat elevated, tumor mass 14 mm. in
width and 6 mm. in thickness and covered everywhere by
stomach mucous membrane. Upon microscopical examination the mass was found to he an acinous gland, resembling
pancreas in structure. No further description is given. He
found a small duct opening upon the surface.
Merkel " (1905) described two cases of pancreatic rests
occurring in the submucosa of the stomach.
Wagner" (1863) described two cases of aberrant tissue
occurring elsewhere than in the normal location. In one of
these cases, which was very similar to Gegenbauer's case described above, the pancreatic tissue occurred in the wall of the
stomach.
Hyrtl " (1860) mentions a rare occurrence of accessory pancreatic tissue behind the arteria and vena mesenterica superior
and surrounding these vessels at their roots.
Bernard" (1858) described a second, smaller, pancreatic
duct communicating with the main duct, oftentimes, however,
emptying independently just below the main duct, in man,
dog, cat and rabbit. Bernard has also described tubuloacinous glands in the wall of the duodenum, which are supposed to have the same physiological properties as the pancreas.
Klob" (1859), in a second case similar to the one he described above, found a mass in the posterior wall of the first
portion of the jejunum, 4 cm. beyond the duodeno-jejunal turn.
No duct was found. Upon microscopical examination the
mass was found to consist of pancreatic tissue.
Merkl" (1905) described a pancreatic rest in the subserosa
of the jejunum.
Zenker °' (1861) described a frequent variation called the
"pancreas minus," a lobe of pancreatic tissue possessing a
kind of attachment to the caput pancreatis and emptying
usually into the ductus wirsungiajius:, often, however, 1 cm.1.5 cm. below the normal duct. Zenker records five eases, in
three of which the accessory pancreas occurred in the wall of
the small intestine. In the fourth case there were two accessory pancreases, one 16 cm. the other 48 cm. below the duodenum. The most curious was the fifth case : in this one there
occurred, 54 cm. above the cecal valve, a finger-like, true diverticulum 5.5 cm. long, with a narrow, fatty mesentery, in the fat
JlNE, 1919]
157
of which the accessory pancreas was found situated near tlic
tip of the diverticulum. In a foot-note Zenker says:
Vielleicht bezleht sich eine alte von Meckel (Patholog. Anat. I
Bd. S., 590) citirte Beobachtung von Schulze auf elnen gleichen
Fall. Dieser (Acta, natur. curios. Tom. T. Obs. 226, p. 504, Ao.
1727) fand bei elneni Neugebornen an der Spitze eines wahren
Darmdivertikels "cine driisenahnliche Warze." (Im oriprinal
beisst es, cuius apicem glandulosa papilla quaedam quasi roronabat. ) Da dieselbe nicht welter beschrieben ist. lasst sich freilich
dariiber nicht entscheiden. Vielleicht ist damit auch nur eine
jener Ausstiilpungen gemeint, die sich bisweilen an der Spitze
des Divertikels finden.
The location of the accessory pancreas in the bowel wall
varies. It may be in the submucosa or between the serosa and
muscularis. Zenker gives a general histological description,
makes no mention of the zymogen granules or islands of
Langerhans and states simply that the general structure was
that of true pancreas. He was able to find a duct in all
his cases. The largest accessory pancreas of this series had a
diameter of 3.5 cm. The true pancreas in all cases was normal.
He regards the occurrence of accessory pancreas as a developmental anomaly originating in the earliest anlage of the
pancreas.
Zenker thinks these anomalies can be explained as follows:
The usual pancreatic evagination is single, sometimes double.
occasionally triple for the first anlage. These evaginations
when multiple then develop into separate glandular bodies.
In the further course of development, one becomes the main.
true pancreas ; the remaining evagination, either above or below
the pancreatic duct, is carried upwards or downwards by the
further growth and elongation of the original straight intestine. If above, it comes to lie in the wall of the stomach; if
below, it may occur either in the duodenum, jejunum, small
intestine or even in Meckel's diverticulum. The last would
be the lowest possibility, as Meckel's diverticulum lies at the
transition line between the upper and the lower intestine. It
is difficult to understand how the gastric anlage in our case
could get below the embryologically possible position of the
pancreas or how gastric mucosa normally above could get below
the level of the pancreatic duct according to this explanation.
Zenker could find no evidence of an effect of the accessory
pancreas upon the digestion in these individuals.
Several cases are reported further of the occurrence of pancreatic rests in Meckel's diverticulum. Thus ilerkel (1905)
demonstrated a pancreatic rest or anlage in the tip of Meckel's
diverticulum.
Neumann" (18T0) found, in a child 10 months of age. a
swelling the size of a ."mall bean attached to the tip of Meckel's
diverticulum by a short pedicle. In its center was a lumen
connected by a kind of duct with the lumen of the diverticulum. Upon histological examination, this body was said by
Neumann to have gland alveoli resembling in appearance those
of the pancreas. No further description is given. This case
in many respects resembles the one of the hiunan fetus reported by van Heukelom. except that in this instance the
nodule was completely con.stricted off from Meckel's diverticulum at its tip, .separated entirely from the lumen and Wii<
composed of gastric nmcosa. It is interesting to have two
cases in many respects simulating one another, one case composed of pancreatic tissue, the other of gastric tissue.
Regarding this anomaly as a Meckel's diverticulum, and
this in turn as coming from the ductus omphalomcsentericus,
Neumann finds it difficult to see an association between tlie
presence of the diverticulum and the occurrence of pancreas.
Neumann suggests that the former may not have been a true
Meckel's diverticulum, but rather a secondary formation due
to mechanical pull of the evaginating glandular mass on the
bowel wall. The location of the diverticulum and the subsequent report of a number of similar findings in true Meckel's
diverticula would indicate th.it this evagination was probably
also a true Meckel's diverticulum.
A good description, together with illustrations of a case in
which an accessory pancreas was found at the tip of a Meckel's
diverticulum, was given by Bize ' in 1904.
Albrecht' (1901) foiuid in the tip of Meckel's diverticulum a yellowish nodule, about the size of a pea, which resembled microscopically typical pancreatic tissue. In this case,
contrary to many other cases described, the author fakes pains
really to identify the new tissue formation. He mentions the
occurrence of abundant zymogen granules in the cells, centroacinous cells, islands of Langerhans, ducts emptying into the
lumen of the intestine, nerves and blood-vessels occurring in
normal fashion. Five, possibly six, ca.«es of similar nature
are reported in the literature, but without further discussion
or description.
In regard to the origin and development of the.fe structures
this author suggests that they are possibly :
1. Aberrant Pancreas. — He thinks this pos,<ibi]ify cannot be
denied, for on the basis of comparative anatomy it has been
shown by v. Kupffer that in the sturgeon pancreatic tissue
has been found in the ductus cholcdochus. Others have demonstrated the occurrence of pancreas in the pajiilla minor. These
probably represent isolated portions of the original anlage.
It is questionable, however, according to this author, whether
such rests would lie found as low down as the umbilicus. Furthermore, this conception does not explain why these rests,
when found in the region of the lower ileum, occur regularly in
the tip of Meckel's diverticulum.
2. Hestx of Glandular Formations Orii/itiatint/ from the
Yolk Stalh- or Sac. — That such an origin might be possible is
perhaps indicated by the findings of Graf Spec, who described
in the yolk sac in the case of the human embryo numerous
tubular glands with prismatic epithelium. Opposed to this
view, however, is the fact that an analogy of the normal pancreas is impcssible, and furthermore that one would have to
imagine that a comple metaplasia of an embryonic organ had
taken place.
3. The Alaii.stic Formation. — There is no evidence for this
view.
4. " Cdrro(ieneti^." — By exchwion, f.liis conception seems
to be more probable as compared with those just mentioned.
Whichever view one prefers, a number of interesting thoughts
arise. In the first place, the same general developmental fac
158
[No. 340
tors or influences must have been present which determined
the formation of the normal pancreas, except for the causes of
tlie greater growth and the topographical relationship of the
normal pancreas. Thus at once we are forced to dismiss the
belief that pancreas develops as a result of factors which are
present only in the region of the duodenum, such as certain
mechanical combinations or strictly localized hormones or
similar tissue-stimulating substances. It would seem that,
according to this author, the influences which can give rise to
these aberrant pancreatic formations are not specific for the
duodenum. In fact, the specific reasons for the occurrence
of this aberrant pancreas must be sought for in the potentiality
for pancreatic formation in the whole small intestinal portion
of the original intestinal anlage, namely, the entoderm, certainly in that portion extending from the normal pancreas
anlage down to the ductus omphalomesentericus. Perhaps the
frequent location of the heterotopic pancreas in the tip of
Meckel's diverticulum is consequent upon causative factors
similar to those responsible for the formation of pancreas in
both instances and sharply localized in the immediately contiguous bowel. These factors may be of a mechanical character.
In conclusion this author speculates upon the possible benefit this type of pancreas can have for its possessor. Since, at
least in this present instance, the aberrant pancreas was
capable of active normal secretion, it would seem to all appearances that there was a lessening of the danger to the patient
of stagnation of the intestinal +++++
CONTENTSs with its consequent
possible mechanical and infectious complications, Meckel's
diverticulum in this instance being 25 cm. long.
Brunner,' as cited by Tschiknawerow, found in a case of invagination, in a child four and a half years old, a Meckel's
diverticulum, 37 cm. above the ileocecal valve, which had at
its blind tip a tumor measuring, in its various dimensions,
25 X 22 X 19 mm. Microscopic examination of the tumor
showed it to be composed of two parts : one consisting of adipose tissue; the other composed of gland lobules, ducts and
lymphoid nodules and resembling pancreas in structure.
Hedinger " (1906) demonstrated in the body of a 30-yearold man, dead of cardiac disease, a Meckel's diverticulum 5 cm.
in length. In the wall at the tip of the diverticulum a granular, light yellow nodule of tissue was found measuring 2.5 cm.
in length and .5 cm. in width. Microscopical examination
showed this nodule to consist of typical pancreatic tissue with
an occasional duct and with a second lobule resembling Brunner's glands in structure. He adds a review of the literature
bearing upon similar findings and discusses the significance of
them.
Nazari " (1909) reports the occurrence of aberrant pancreas
in the tip of Meckel's diverticulum.
Tschiknawerow " described three cases of Meckel's diverticulum in which pathological tissue formation was found.
In Case I he described a spindle-celled sarcoma occurring
in the diverticulum.
Case II was that of a man 25 years of age who had died of
pneumonia. At the tip of and extending into the lumen of the
diverticulum, which was 3 cm. long, there was found a small
body, 1 cm. in length. Near the surface of this enlargement
glands of the Lieberkiihn type were found, while those in the
depths resembled Brunner's glands both as to structure and as
to position. The remaining mucosa of the diverticulum had
the structure of intestine. The villi were well marked, lymph
follicles occurred in areas, and everywhere typical Lieberkiihn's
glands were present.
Case III was that of a woman of 55 years of age. At the tip
of Meckel's diverticulum, which measured 7 cm. in length,
there occurred a rather hard swelling which was found to consist of atypical Lieberkiihn's glands and to resemble pancreas
to a certain extent.
Lecene " described an adenoma developing at the level of the
free end of a Meckel's diverticulum.
A number of additional instances are reported of aberrant
pancreas occurring in intestinal diverticula other than in the
true diverticulum of Meckel. The aberrant tissue in the bowel
wall is supposed by many to be the primary factor in the subsequent formation of these diverticula, which then enlarge by
a secondary evagination of the bowel wall due to pressure
within its lumen at a point probably weakened by the glandular mass. Whether this conception is correct or not remains
an open question.
Nauwerk ™ ( 1893) reports the occurrence of a diverticulum
9 cm. in length, occurring 2-3 mm. above the ileocecal valve
in which an accessory pancreas was found, covered on the outside by serosa and having an excretory duct. He explains the
formation of the diverticulum by the mechanical pull of the
accessory pancreas on the bowel wall. In addition to pancreatic acini a hyperplastic overgrowth of Lieberkiihn's glands
was also found, and the impression was gained that numerous
transitions occurred between these overgrown Lieberkiihn's
glands and the true pancreatic lobules. Besides this diverticulum a true Meckel's diverticulum was also found, measuring
3 cm. in length and situated 80 cm. above the ileocecal valve.
Further examples of this condition are reported by Thompson,'" Hulst " and Albrecht and Arzt.''
A case of pancreas occurring at the umbilicus was described
by Wright." In a girl 12 years of age there was found a congenital umbilical fistula which, after breaking down twice
following operation, healed as a result of complete extirpation
of the fistulous tract in which a pancreas nodule was found.
Franchomme* (1893) has described in greater detail the
anomalies which are apt to occur in the remains of the vitelline
canal.
Discussion
It is seen, then, that the occurrence of aberrant glandular
tissue, particularly gastric and pancreatic, may occur in the
stomach, intestine, Meckel's diverticulum, in the obliterated
cord connecting the latter with the umbilicus and at the
umbilicus itself. These aberrant tissues have a great interest
for embryologists in view of their possible explanation and to
pathologists for this reason also, and furthermore for the
reason that new growths and other pathological processes may
rise from these aberrant tissues. To the surgeon, furthermore,
June, 1919]
159
because they may be the seat of inflammation, perforation, abscess formation and even subsequently of intestinal obstrui'tion. In jreneral. very few complete histological studies with
the idea of absolutely determining the nature of these tissues
under consideration have been reported. As a consequence,
there has been considerable confusion in the past in certain
instances as to the exact type of glandular tissue witii which
one was dealing. The case reported in this present ])ublication
offered, therefore, a good opportunity for positively identifying
in the tip of Meckel's diverticulum an area of gastric mucosa
of the fundus type. This was done beyond question, and therefore the facts can he used in clearing up or in refuting a number of theories wiiich have been offered in the past to explain
the origin of these aberrant tissues and to furnish certain facts
for a more probable theory as to tiieir origin.
Speaking in the first place of aberrant mucosa it may be
recalled that several cases of gastric mucosa occurring at the
umbilicus, in the form of polyps, depressions or fistulae, were
reported by Tillmanns, Reichard, Roser, Weber, Lexer, Denuw
and a few others. In one or two instances such a fistula was
blind and was attached at its inner extremity to a librous
cord or to Meckel's diverticulum itself. The latter in these
instances had the structure of intestinal epitliclium. In one
instance, namely, that of van Ileukelom, there was found in
a human fetus a small nodule of gastric mucosa at tiie tip of
Meckel's diverticulum which had become com})letely constricted off and separated from tiie lumen of the divertiiuluni,
but was still attached to the latter.
In many of these cases the reports, in which histological
examination was more or less incomplete or not made at all,
are rather unsatisfactory. In only one instance, I may say, was
there a very careful histological examination made, namely,
by Denuce, who reported mucosa of the gastric fundus type
occurring at the umbilicus. Aside from this there were no
other cases in which gastric fundus mucosa was found or
described. My own ca.<e, then, represents the only one in the
literature in wliich a consideral)le area of mucosa at the tip of
Meckel's diverticulum, communicating freely with it and in
continuity with tiie remaining muco.sa of the diverticulum,
was found to be of the gastric fundus type or even gastric at
all.
In this manner, then, the link in the chain of evidence which
goes to show that this aberrant gastric tissue arises from
remnants of the omphalomesenteric duct is complete.
Several of the theories which have been advanced to explain
the origin of this tissue are thus effectively answered in the
negative. Thus. Tillmanns' theory, which had few adherents
and which supposed that gastric mucosa occurring at the
umbilicus is derived from gastric diverticula, becomes quite
improbable. Van Heukelom had already quite effectivelv
answered this theory.
The second theory is that of Siegenlieck van Heukelom, who
believes that these aberrant growths at the umbilicus and at the
tip of Meckel's diverticulum represent tiie remains of the
vitelline duct. He, however, felt that the differentiation into
gastric or intestinal epithelium depended upon whether or
not the mucosa in early fetal life had become differentiated
before or after the influence of bile had become effective. This
view is doubtless in part correct, but not altogether, for again
my findings show that gastric mucosa may differentiate from
the intestinal epithelium even under the same influences so far
as concerns the action of the intestinal +++++
CONTENTSs. In other
words, isolation of the mucosa very early in fetal life is not
essential for the development of gastric mucosa.
The third explanation, namely, that of Salzer, that misplaced entoderm at the umbilicus is stimulated to a variable
differentiation by irritation or inflammation and consequently
may give rise to gastric, intestinal, or even pancreatic tissue,
similarly does not fully explain, for again, as my case shows,
gastric mucosa may develop in the absence of such irritative
or inflammatory conditions.
The fourth theory, tiiat of Albrecht and Fischl, that these
aberrant tissues arise from fetal inclusions or rests occurring
at the umbilicus at the time of the closure of the abdominal
wall, similarly does not suffice, for the occurrence of these
tissues in the tip of Meckel's diverticulum can certainly occur
without these factors being present.
The fifth explanation, which is doubtle-^s the most nearly
correct, was practically accepted by Lexer and by Denuce.
These authors assumed that these umbilical aijuormalities
represent the remains of the omphalomesenteric or vitelline
duct, although no very detailed facts have been offered to support this view. My own case would complete the evidence so
far as gastric mucosa is concerned, for it shows in the first
place that gastric mucosa can and does arise from the remains
of the vitelline duct if one assumes, which is doubtless correct,
that Meckel's diverticulum itself is the representative of
such remains. One need assume no further factors nor circumstances, such as improi)able constrictions in tiie stomach or
misplacements and irritations affcK-ting the entoderm, which
are thus caused to undergo this peculiar differentiation. It
becomes evident then how important this finding has been,
because it has allowed us to answer effectively the previous
views and to furnish indisputable evidence that the gastric
mucosa as reported in previous cases occurring at the umliilicus has doubtless arisen from the omphalomesenteric duct.
.\s to the ultimate influences which iiave caused this differentiation one cannot state definitely in the present condition
of our knowledge concerning these processes.
The sixth and last explanation, practically that of Albrecht,
is, so far as present evidence goes, the most nearly correct, and
this holds for pancreatic tissue or gastric or in fact any of the
glandular tissues of the intestinal tract, such as Brunner'a
glands. According to this view the original entodemial lining
of the intestinal tube and omphalomesenteric duct pos.sesse8
potentialities of development into any of the glandular structures in the adult intestine or of its acces-sory glands, and
under the influence of certain circumstances, which we do not
understand, groups of cells may retain one or the other potentiality and develop into a glandular tissue or organ very
different from the surrounding glandular tissue and rescm
160
[No. 340
bling the adult organ, such as stomach or pancreas, which may
be far removed.
In view of his findings of aberrant pancreatic tissue at
various points in the intestinal tract, Zenker felt that these
anomalies represented pancreatic anlages, which in the further
course of development were carried upwards or downwards
by the further growth and elongation of the original straight
intestine and which might come to lie hence in the stomach
or in any part of the intestinal tract down to and including
Meckel's diverticulum. If this assumption is made in the
case of the pancreas, then one should assume the same, I think,
in the case of the stomach, in which instance it seems quite
impossible to believe that a gastric anlage could by such
mechanism become displaced so far as to lie below the possible
embryological position of the pancreas. One certainly could
not apply this view to the occurrence of gastric mucosa at tlie
umbilicus or in Meckel's diverticulum.
Finally, Albrecht's view as stated above is probably tlie
correct one. If we accept this view of the imiform potentiality of the entoderm to develop into any of these glandular
tissues, we can readily understand how cases of aberrant
stomach, pancreas, Lieberkiihn's glands and Brunner's glands
can occur anywhere in the intestinal tract as far down as
Meckel's diverticulum. The intestine below Meckel's diverticulum which represents the hindgut doubtless has not these
potentialities, as a consequence of which these aberrant structures have never been found below the level of Meckel's diverticulum.
To summarize then, I have reported a case of a young man,
19 years of age, who presented before operation symptoms and
signs suggestive either of acute appendicitis or partial intestinal obstruction. On examination, among other things there
was found just below the umbilicus a scar which had been
produced by a former operation for an abscess. The nature of
the abscess was not determinable. Upon subsequent operation
it was found that the small bowel had become strangulated
over a thick, fleshy cord consisting of Meckel's diverticulum
and some adherent omentum which fastened the former to a
point on the anterior abdominal wall just below the umbilicus.
Excision of Meckel's diverticulum with the adherent omentum
was done and the patient made an uneventful recovery.
Upon examination of the open diverticulum there was found
in the distal third or fourth of the diverticulum an area of
thickened, irregular, granular, dark red mucosa which was
demarcated sharply from the proximal pale finer mucosa,
which in turn was of intestinal character. Furthermore, upon
careful histological examination this distal segment was found
to consist of a mucosa definitely resembling in every particular
that of the gastric fundus region. The glands were precisely
of the fundus type and showed the characteristic zymogen
granules of the chief cells and the eosinophilic granules of the
parietal cells as characteristic in the glands of the stomach.
Upon a careful search of the literature it is found that a
number of cases have been reported of the occurrence of gastric
mucosa at the umbilicus in the form of polyps or fistula?.
Other aberrant tissues, such as pancreas, have been described
along the intestinal tract and even in one instance in a nodule
at the tip of Meckel's diverticulum and connected with its
lumen. Another interesting case reported is that of van Heukelom in which a nodule of mucosa was foimd at the tip of
Meckel's diverticulum, constricted off from it, not connected
with the lumen, but attached by a fibrous cord. This mucosa
proved to be of pyloric nature. My own case is the only one
of which I am aware of gastric mucosa occurring in the wall
of Meckel's diverticulum and in free communication with its
lumen. Careful histological examination was made necessary
because of the rather uncertain findings reported by previous
authors and of the various theories which have been constructed to explain the occurrence of these aberrant tissues at
the umbilicus.
The finding in my own case of gastric mucosa in Meckel's
diverticulum, which it is agreed quite generally is a definite
remains or persistence of the vitelline or omphalomesenteric
duet, makes it appear certain that these al>errant tissues
occurring at the umbilicus, in fibrous cords and in Meckel's
diverticulum, have a uniform origin, namely, from the entoderm of the original intestinal tube or yolk stalk. It was very
important to complete the evidence that these aberrant tissues
may arise anywhere along the tract of the original omphalomesenteric duct in order to answer the various hypotheses
which were previously advanced.
After a review of these hypotheses and in view of the
evidence that I have brought forward, the best explanation for
the occurrence of these structures is, that the original entodermal lining of the intestinal tube and omphalomesenteric
duet possesses potentialities of development into any of the
glandular structures of the adult intestinal tract or of its
accessory glands, and under the influence of certain circumstances, which we do not understand, groups of cells may
retain one or the other potentiality and develop into a
glandular tissue very different from the surrounding glandular
tissues and resembling the adult organ, such as stomach or
pancreas, which may be far removed. The finding in my case
of gastric mucosa in Meckel's diverticulum effectively answers
the various theories that the gastric growths at the umbilicus
may have arisen by constriction or separation from gastric
diverticula in the early fetus, or that a differentiation in the
mucosa or in these aberrant tissues is brought about by the
presence or non-presence of the bile, or that irritations, inflammations or fetal inclusions at the point of union of the blastodermic layers are necessary. In fact, there is good evidence
now, with the findings in my own case, for believing that these
aberrant tissues arise from remains of the omphalomesenteric
duct ; but as to the ultimate factors which cause this differentiation we cannot state in the present condition of our
knowledge.
The finding of this gastric mucosa explains well the reasons
for the finding of acid secretion with digestion at the umbilicus, in cases of umbilical polyps and fistula as reported in
the literature, although cases in which gastric mucosa oc
June, 1919]
161
curred at the umbilicus had been reported before. Again, we
have a good embryological basis for understanding certain
adenomatous tumors and growths of an intestinal glandular
nature occurring at the umbilicus, in oblitenxted intraabdominal umbilical cords and in Mecicers diverticulimi. In
fact, in the caj?e reported it is interesting to speculate as to the
condition for which the patient had been operated upon several
years previously. It seems probable that there was at that
time a perforation at the tip of Meckel's diverticulum, though
none was found at the operation. As a consequence of this an
abdominal abscess formed which was simply drained and whicli
healed with the formation of adhesions between the tip of
Meckel's diverticulum and the anterior abdominal wall. It is
interesting to think also that this perforation at the tip of
Meckel's diverticulum might well have been a perforative gastric ulcer, for so far as the structure of the mucosa went we
were certainly dealing with the fundus type of mucous membrane. This perforation evidently healed subsequently. The
case further illustrates the desirability of examining carefully
all cases of Meckel's diverticulum for the possibility of occurrence of aberrant glandular tissues in the mucosa, both
for embryological reasons imd also because of the importance of these structures in pathology and certain surgical
conditions.
In conclusion, I wish to acknowledge my indebtedness to
Mr. H. F. Aitken for the drawings in black and white, to Miss
Ethel Norris for the two figures in colors, and to Dr. T. S.
CuUen for the use of the drawings of the umbilical anomalies
as illustrated by Mr. Max Brocdcl.
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Hellk., Leipzig, 1870, XI, 200.
23. Reichard, V. M.: Demonstratlonen zur Magen-Darmchirurgle. Zentralbl. f. Chir., 1898, XXV, 587-588.
24. Roser, W.: Zur Lehre von der umbilikalen Magencystenfistel. Zentralbl. f. Chir., 1887, XIV, 260.
24'. Salzer, H.: Ueber das offene Meckelsche Dlvertikel. WIen.
klin. Wchnschr.. 1904. XVII. 614-617.
25. Strada, F. ; Adenoma congenlto ombelicale a tlpo gastrlco
(Contributo alio studio dei tumor! congenitl dell 'ombelico).
Sperimentale Archlv. dl Biol., 1903, LVII, 637-658, I pi.
26. Thomson, A.: Diverticula of the alimentary tract, with particular reference to those met with In the ileum resulting from an
accessory pancreas and from tuberculosis. Tr. Med.-Chlr. Soc.
Edinburgh, 1908, n. s. XXVII, 118-129, 2 pi.
27. TlUmanns, H.: Ueber angeborenen Prolaps von Magenschleimhaut durch don Nabelring (Ectopia ventricull) und iiber
sonstige Geschwiilste und P'isleln des Nabels. Deutsche Ztschr. f.
Chir., Leipzig, 1882-3, XVIII, 161-202.
28. Tschlknawerow, L.: Zur Kenntnis dor pathologlschen Gewebsbildungen In Meckel'schen Dlvertikel. Berl. kiln. Wchnschr.,
1911. XLVIII, 1676-1679.
29. van Heukelom, S.: Die Genese der Ectopia ventricull am
Nabel. Vlrchow's Arch., 1888, CXI, 475.
30. von Rosthorn, A.: Ein Beitrag zur Kenntnis der angeborenen
Nabelflsteln, Wlen. kiln. Wchnschr., 1S89, II, 125; 154.
31. Wagner, E.; Accessorrlsches Pankreas In dor Magenwand.
Arch. d. Hellk.. Leipzig, 1862, III, 283.
32. Weber, W.: Zur Kaaulstik der Ectopia Ventricull. Beltrftge
z. klin. Chir.. 1898, XXII. 371-385.
33. Wright. J. H.: Aberrant pancreas in the region of the umbilicus. J. Boston Soc. Med. Sc, 1900-1, V, 497-498. 1 pi.
34. Zenker, F. A.: Nebenpancreas In der Darmwand. Arch. t.
path. Anat. (etc.), Berlin, 1861, XXI, 369-376.
163
[No. 340
A GRAPHIC APPLICATION OF THE PRINCIPLE OF THE EQUILATERAL TRIANGLE FOR DETERMINING THE DIRECTION OF
THE ELECTRICAL AXIS OF THE HEART IN THE
HUMAN ELECTROCARDIOGRAM
By Edward Perkins Carter, Cdrt P. Eichter and Carl H. Greene
(From the Cardiographic Department of The Johns Hopkins Hospital and University)
In 1908 Einthoven ' first called attention to the fact that a
definite relationship exists between the amplitude of the deflections of the electrocardiogram obtained from the three leads —
right arm, left arm and left leg — and that when the amplitude
of any two such derivations is known the third can be determined ; formulating his law, based upon this relationship, that
A year later, in a joint paper with Fahr and De Waart,'
he expanded more fully the principle of the equilateral triangle and published tables, based upon trigonometrical formulae, which made it possible to determine, within a negligible
factor of error, the direction of the electrical axis of the heart,
the relative preponderance of either the right or the left ven
L.R.
Fig. 1. — After Einthoven. Illustrating the fundamental principle of the equilateral triangle. P^Q - E, p, — g, = c„ p, — 9, = e„ P, — a, = e« e, = c, + e,. The angle
= + 55°.
under like conditions of electrical resistance and tension Lead
III must equal Lead II minus Lead I.
In 1912, in an address before the Chelsea Clinical Society
of London,' he furtlier developed his fundamental conception
of the course of the excitation wave in the heart, based upon
the analogy of the three leads employed to the sides of an
equilateral triangle in which the direction of the axial current bears a definite and determinable relationship to the
parallel plane of Lead I (E. A. and L. A.).
tricle and the shifting alteration of tlie axis of potential difference in the more bizarre forms of electrocardiograms so
frequently met with.
The fundamental principles involved are briefly as follows:
Assuming that the tliree leads usually employed — the right
arm, the left arm and the left leg — represent the three sides of
an equilateral triangle (see Fig. 1), we draw a line parallel
to the line uniting the two ann leads at a level corresponding
to the center of a circle enclosing tlie triangle, the right-hand
JvxE, 1919]
163
end representing 0° and the left-hand ond 180°. At the
center of this line is placed the point // representin<r the
heart, the electrical axis of which is diagTanimatically illustrated by the arrow p-q. Rotation, then, counter-clockwise
of the axis above this horizontal line represents a negative
angle, whereajs rotation clockwise below tlie horizontal represents a positive anjrle. The normal electrical axis is illustrated by the direction of the arrow in the figure in which the
angle a, tlie angle of deflection between the arrow p-q and the
horizontal line corresponding to the plane of Lead I, measures
in our figure +55°.
If upon this arrow indicating the direction of the axial
current we mark off two points p and q, Einthoven has shown
that the distjince between lines projected from these points:
at right angles to any one of the three sides of the triangle,
which correspond to the three leads, will represent the amplitude of the deflections for that lead, and that under all normal
conditions the amplitude of i?,-f i?3 = 7?j. Furthermore,
from the amplitude of these deflections we may determine the
direction of the axis of potential difference in the heart and
may calculate the angle a, thus determining in degrees the
rotation of the electrical axis in the sagittiil plane and the
accurate measurement of the angle formed in relation with the
horizontal plane representing Lead I (R. A.-L. A.).
It should be clearly understood that the amplitude of any
given deflection represents the difference in potential in the
electrical axis existing in the heart at a given instant of time
in relation to the lead employed, and that this amplitude will
vary as the electrical axis alters its position in relation to this
lead. Hence, it is evident that the amplitude of any given
deflection may not represent the greatest difference of potential possible in that lead, and Einthoven insists that we must
distinguish between what we may call the recorded difference
of potential and the maximal possible deflection, which he
designates as the " manifest potential difference " or the
" manifest value.'"
This manifest value depends upon the maximal distance
separating the two points between which the potential difference is developed and is only met with when the electrical axis
and the lead employed lie in parallel planes. It can be calculated from the height of the recorded curves and can be
expressed in absolute measure in millivolts by multiplying
the deflection measured in millimeters by lO"* when the galvanometer string ha,s been standardized for the usual deflection. In determining the angle a, however, for all clinical
purposes we may disregard this manifest value, though a tat)le
giving the various determinations of this potential differeni c
is incorporated in the last paper referred to above.
Einthoven's formulae are as follows: If we let p-q = E,
representing the manifest value, Pi — 7i = ^i, Pz — <Ii'=^i
e, =f^eo6a. (1)
f5 = £cos (a-60). (2)
«', = i?cos (120-O). (3)
e, = e,-e,. (4)
It is evident that under these conditions the potential
difference present between the angles of the triangle must
bear the following relationship e, : f, : e,. From these data
when the angle a is unknown it can be determined from the
relationship of any two of these potential differences from the
following formula? :
ie —e
Losing r, and c. /fl. a = ' ^'•
Using c, and e., tg. a =
Using Co and e, tg. a =
(5)
(6)
(7)
2e^ + c^
f,V3
We have stated above that under normal conditions this law
that 62 = 6,-1-63 holds true. That clinically, however, we constantly meet with apparent exceptions to this statement
is a matter of common observation. It must be kci)t in mind
that while we are dealing theoretically with a fiat i)lanc we
have actually to do with a very complicated muscle mass and
it is the more remarkable that this seeming exception to this
fundamcntjil law is apparent rather than real, and that it is
due, as Einthoven has shown, to the phasic variation between
similar peaks of the electrocardiogram.
In order to determine exactly the proportional amplitude of
a given deflection in the three leads, especially in all instances
showing conspicuous pliasic variation, we must know the exact
time relationship of the deflection to the cardiac cycle in each
of the three leads, ilanifestly, this can only be determined
by simultaneous records of the heart sounds and the electrocardiogram, such as have been made by Falir,* or by the use
of two galvanometers as employed by Williams.' Fortunately,
this apparent exception to the simplicity of the fundamental
principle involved does not invalidate the application of the
formulae given above in all normal instances and may be corrected for as Einthoven has shown in the more obscure forms.
Using two galvanometers Williams (I. r.) has shown by the
projection of vectors determined from the manifest value e,
in conformity with the different leads, the essential nature of
this phasic variation in homonymous peaks of the electrocardiogram, and has further demonstrated that the bizarre
curves met with are due entirely to the manner in which the
direction of potential difference is shifting within the heart,
and that, although the peaks arc absolutely in phase in only
a few instances, such absolute accuracy in the calculated values
is not essential for. the majority of clinical records.
Based upon the principle of the equilateral triangle Pardee'
has published a graphic method by which the negativity of the
initial ventricular deflections determines within the limits of
60° the direction of tlie axis of potential difference. This i.s
accomplished by dividing tlie circumference of the circle into
six quadrants, into any one of which it can be shown, by the
positivity or negativity of the recorded deflections, that the
axis of potential difference must fall.
It is interesting to note how closely the angle, determined
by means of the tables published by Einthoven, Fahr and
De Waart, coincides with the results calculated bv the use of
164
[No. 340
their formulas 5, 6 and 7 given above. These observers have
further demonstrated that the angle varies with inspiration
and expiration in different individuals from 12° to 36°, being
always greater in inspiration than in expiration, the normal
angle falling between +40° and + 90°.
In a true left ventricular preponderance the angle a has
a value approaching —20°, falling between 0° and —40°,
while with a right ventricular preponderance it has a value
approximating +120°, falling between +90° and +150°. If
we assimie that the electrical axis in these cases originally had
a normal value, we must postulate a rotation of the direction
of potential difference through an arc of from 70° to 140°.
That this, however, implies a rotation of the anatomical axis
of the heart throughout anything like the same extent is manifestly absurd, and the explanation for the rotation of the axis
of potential difference must be sought in the shifting balance
of the muscle mass and the ensuing relationship of the plane
of the electrical axis to the Derivations I and III.
Figs. 2, 3 and 4 may serve to make this point clear. Fig. 2
illustrates the normal direction of the axis of potential difference. In this figure the excitation wave passes from base to
apex within the heart and from apex to basal structures
through the galvanometer, the deflections being upright in all
three leads. In Fig. 3, the deflections are upright in Leads I
and II, though the predominant deflection may be do'miward
in Lead II, and downward in Lead III ; while in Fig. 4, the
deflections are downward in Lead I, and upright in Leads II
and III. The direction of the course of the difference in potential is indicated in each instance by the direction df the arrow.
In a paper upon the localization of the origin of the excitation wave in the human heart, Fahr and Weber ' have demonstrated the soundness of the principle involved in the use of
the geometric figure and the facility with which one can
graphically determine the measurement of the angle a and
the direction of the axis of potential difference by plotting
upon an angle of 60° the values, in tenths of a millivolt, of
the two leads and projection from these values of right angle
lines.
In the graphic method of plotting the angle a, illustrated
by Fig. 5, we have made use of the principle of the equilateral
triangle inscribed wdthin the circumference of a circle upon
which are marked the degrees from 0° at the right to ± 180°
at the left-hand end of the axis of the circle. Following Einthoven's original description rotation of the angle downwards
and to the left, clockwise, constitutes a plus angle, whereas
rotation upwards and to the left, counter-clockwise, constitutes
a negative angle.*
The point marked by the intersection of the ordinate from
the middle of the line representing Lead I and the horizontal
axis of the circle represents the heart, and may further be
regarded as the point p of the axis of potential difference,
as illustrated in Ficr. 1.
* This method of reading a positive or negative angle is at
variance with the accepted custom in vogue as given by Wentworth
and Smith, " Plane Trigonometry," Chap. V, p. 77, 1914.
If from each side of our equilateral triangle we project
ordinates, at a distance of 1 mm. apart, assigning to those on
either side of the center of each base line, corresponding to the
Leads I, II and III, their proper positive or negative sign
determined by the projection of our arrow p-q, then the point
of intersection of any two of these ordinates, representing the
value of «!, e^ and e^ under their proper sign, must coincide
with the point q in our diagram Fig. 1. A line from the center H to this point of intersection corresponds to the manifest
potential difference E, and will give us the direction of- the
axis of potential difference. By projection of this line to
the circumference of the circle the angle a may be read off
in degrees with its corresponding positive or negative value.
Utilizing the measurements of all three derivations in the
terms of e^, e„ and e^, tmder their proper sign, we shall find
that with the physiological electrocardiogram our point of
intersection for all three leads coincides very closely, and that
in those instances with a conspicuous phasic difference the
point of intersection will vary slightly, depending upon the
ordinates employed, thus suggesting in a graphic way the
extent of this phasic variation.
In the instances suggesting a ventricular preponderance,
the values e^ and e^ should be used, and whenever the initial
ventricular deflections are definitely diphasic in character,
their corrected value should be determined by deducting the
lesser amplitude from the greater.
Figs. 6, 7 and 8 may serve to illustrate the method of application of the principles stated above for determining the axis
of potential difference in the heart.
In Fig. 6, which represents a physiological electrocardiogram, i?i measures 9 mm., R^ 16 mm. and ^3 7 mm. in height.
We may express these values in the terms of e, as e^=-\-9,
e«=+16, and 63= +7, then ej^ej + fij. If we follow the
ordinate +9 from the side corresponding to Lead I to the
point where it meets the ordinate +16 from the side representing Lead II, we shall find that the ordinate +7 representing Lead III intersects this point (see the small circle in
Fig. 5 in the lower right-hand quadrant) and a line from the
center H projected through this point of intersection to the
circumference of the circle gives the direction of the axis of
potential difference and the value of the angle a as + 55° and
approximately 30'. Determining the value of a for this electrocardiogram by Einthoven's formula 5 we get a value of
+ 55° and 53'.
In Fig. 7, the initial ventricular deflections have the following values: i?i=15 mm., jSi=— 1.5 mm., i?, = 4 mm.,
jSj = — 9 mm., i?3 = 1 mm., Sj = — 16 mm. We may ignore the
values of S-^ and R^ as they approach each other so closely,
and utilizing i?i and S^ (e, and 63) we repeat the steps outlined above and follow the ordinate + 15 representing the
Lead I to the point intersected by the ordinate — 16 representing Lead III. A line from the center H through this point
of intersection and projected to the circumference of our
circle gives the value of the angle a as —34°. Determined
by formula 6 the value is found to be —33° and 12' — an
June, 1919]
165
•K.A
X.A
•U.A
X.V..
Flo. 2. — lllutitmtin? the normal physiological dirrction of the axis of potentui difference in the heart. The arrows indicate
the dirertiKii of the initial ventricular dellectlona in the three leads. See Fig. 6 and
description in text.
Fio. 3.— IIlustratiiiK the direction of the
axis of potential (Jiffercnce in left ventricular
preponderance. See Fig. 7 and description
in text.
Flo. 4. — IllustnitinK the direction of the
axis of potential difference in ri(fht ventricular preponderance. See Via. 8 and description in text. Fiffs. 2, 3 and 4, modified after
Pardee.
-i : : .
ii
m:
-L
1
• •!
r^'
1
! 1
1
electro. ar.liugrain. Tl.e iJ.Kli- a in..,..urM
+ .55" and approiimalel.r 30' bv plotting,
and + i.i* and SS' by formula i.'
punilcmiiL-e. I lir titiKJi- a iii««Burcii — AA
and i>nnie niinut>'< I'.t plotttlv, nd — 33'
and 12' by fomiiilu ti.
Ittr prepondrmnce. The nnKJe a meiuiure« approximulciv -» 1'20" bv pliittInK,
and exurllv -r I'JO by formula 0.
166
[No. 340
^^o_j:3o
Fig. 5.— Illustrating the graphic determination of the angle a by means of ordinatcs projected from each side, or base, of the triangle representing the
three leads. The ordinates are drawn to scale 1 mm. apart. The small circles in the figure represent the points of intersection of the e values determined
from Figs. 6, 7 and 8. The arrows projected to the circumference point to the plotted measurement of the angle a in degrees of these figures. Se3 description in text.
June, 1919]
167
angle known to be associated with left ventricular preponderance.
In a similar way we may plot the values of Fig. 8, which
after correction for tiie slightly dipliasic curves in Leads I
and III are found to be as follows in the terms of e: e,= — 5
mm., «j= + 10 mm. Projecting our line from the center 11
through tliis point of intcrs:ection (see point in lower left-hand
quadrant of Fig. 5) we find that the value of a falls between
+ 120° and +121°. Determined by formula 6 the value of
the angle a for this figure is exactly +120°, an angle known
to be associated with right ventricular preponderance.
The points of intersection of the ordinates as given above are
marked by the small circles in Fig. 5, and the arrows indicate
the projection of the axis p-q from the center H through these
points of intersection to the circumference of the circle giving
tlie direction of the axis of potential difference and the value
of the angle o in degrees.
In addition we may determine graphically the true manifest value of the potential dilTerence. As Einthoven has shown
{loc. cit., 1913), if the angle a = t)0° the manifest value E is
equal to the deflection in Lead II, for this lead is then parallel
to the electrical axis. If the angle a is equal to 0° or to ± 180°,
E = e^. If the angle a=+120° or -60°, E = e,. Referring
again to the examples given above, in Fig. 6, £=16.2. In
Fig. 7, J5:= i:.8. In Fig. 8, A'= 10.
It is then plain that this diagrammatic usage of the equilateral triangle is available for accurate det<>rminations of
the direction of the axis of })otential dilTerence, the angle a and
the manifest value H.
SU,M.\L\RY
We have emphasized the value of the fundamental principle of the equilateral triangle as applied in the interpretation of clinical electrocardiograms, and have illustrated
graphically a simple method of procedure by which the value
of the angle a may be quickly found.
BIBLIOGRAPHY
1. Einthoven, W.: Pflug. Arch. f. die ges. Phys., 1908, CXXII,
55S.
2. Mem .• The Lancet, London, 1912, March 30, 853.
3. Einthoven, W.. Fahr, G., and De Waart, A.: Pflug. Arch. f.
die ges. Phys., 1913, CL, 275.
4. Fahr, G.: Heart, 1912-13, IV, 147.
5. Williams, H. B.: Am. Jour. Phys., 1914, XXXV, 292.
6. Pardee, H. E. B.: Jour. Am. Med. Assoc., 1914, LXXII. No. 17,
1311.
7. Fahr. G., and Weber, A.: Deut Arch. f. klin. Med., 1915,
CXVII. 361.
PHAGOCYTOSIS AND AGGLUTINATION IN THE SERUM IN ACUTE
LOBAR PNEUMONIA: THE SPECIFICITY OF THESE REACTIONS
AND THE REGULARITY OF THEIR OCCURRENCE
By Paul W. Clovoh
(From the Medical Clinic of The Johns Hopkiyis Honpital)
In a previous article ' the writer reported the results of
some observations in a .small series of cases on the activity
of the serum developing, after crisis or lysis, in patients with
acute lobar pneumonia. In agreement with the results obtained by most previous observers, it was found that the serum
at this time usually developed a definite, though often feeble,
protective power for mice, provided the test was made with
the homologous strain of pneumococcus, isolated from the
patient whose .scrum was being tested. This activity was not
demonstrable in .«erum obtained during the active stage of
the disease, either from patients who subsequently recovered
or from those who died. It was further shown that, in a considerable percentage of the cases (six of 11 ca.ses), a definite
phagocytic activity could be demonstrated in the serum from
convalescent patients. It was especially emphasized that this
phagocytic activity has a significance quite different from that
of an increa.se in opsonic index, as determined by the Wright
method. In the latter, one uses heterologous stock strains
of pneumoi'wci of low virulence, which are at least moderately
phagocytable in fresh normal serum. The strains studied
by the writer, on the contrary, were (with one exception) of
high virulence, and absolutely resistant to phagocytosis in
fresh normal serum.
This phagocytic activity ran clo.«ely parallel with the protective power of the serum. It was entirely absent during
the acute stage of the di.sea.se, and appeared only at or near
crisis or lysis. It was not present in the serum of a fatal
case. Like protective power it was manifested (with one
exception) only toward the homologous strain of pneumococcus, and not toward those heterologous strains which were
tested. It wa-s further siiown that in the two cases ti-sted as to
this point, phagocytosis in riro ran ])arallcl to that in the testtube. In the peritoneal exudate of the protected mice, the
pneumococci were ingested and dissolved within the leucocytes; whereas in the control mice receiving normal serum
the organisms multiplied rapidly and remained exclusively
extra-cellular.
In view of these facts, and of tiie ]mrt that jibagocytosis has
been shown to play in the activity of jyotent immune serum,'
the writer felt justified in concluding that jihagocytosis probably plays an imirortant role in the immunity developed in
man at crisis.
The series of cases was too small, however, to demonstrate
the regularity with which phagocytic activity develops. Furthermore, the strict limitation of the activity of each serum
tested to the homologous strain of pneumococcus was sur
168
[No. 340
prising, in view of the findings of Cole and Dochez '' that most
strains can be classified in a small number of groups. It,
therefore, seemed desirable to extend these observations over
a larger series of cases, and to determine more definitely the
exact specificity of the reaction.
The results previously reported by the writer ' were shortly
confirmed by the independent observations of Lister ' in South
Africa. Using a similar method, he also demonstrated in most
of his cases definite phagocytic and agglutinative activity in
the serum after crisis, when tested with the homologous
organism. When these sera were tested with heterologous
strains, pliagocytosis and agglutination occurred in some
instances, but in others they did not. By trying crossed reactions with the cultures and (convalescent) serum obtained from
20 cases of pneumonia, he was able to classify the organisms
into five definite groups. The individual strains in each
group he found to be serologically identical; while strains in
different groups had no serological relationship to each other.
In a subsequent article," he reported further similar observations confirming the regularity and absolute specificity of
the reaction, and added several new groups to his classification.*
The development of agglutinins in the serum of patients
with lobar pneumonia has been noted by numerous observers.
Bensangon and Griffon,' in 1900, reported positive findings
in all but six of a series of 64 cases of pneumococcus infections
of various types, of which 39 were lobar pneumonia. They
obtained these results only by cultivation of the pneumococcus
in concentrated serum from the patients, and failed to demonstrate any agglutinating activity when the serum was added to
a broth culture of the organism. They found the activity most
marked at crisis, and more effective toward the homologous
strain than toward stock strains of pneumococci. Huber,"
using a similar method, obtained positive results in all of
10 cases of lobar pneumonia examined at or near crisis.
Neufeld,' in connection with a study of the agglutinating
action of immune serum, mentions the fact that in five out
of about 15 cases of lobar pneumonia examined, the serum
at crisis, when added to a culture of the pneumococcus,
caused marked agglutination of the organisms. This occurred
with serum dilutions of 1 in 4, or 1 in 8, but not in higher
dilutions. Gargano and Fattori," in a series of 63 cases, reported that the development of agglutinating activity in the
serum was " an almost constant phenomenon." The sera
were all active in a dilution of 1 in 2, but none in a dilution
over 1 in 10. They also found the homologous organism more
readily agglutinable than heterologous strains. Jehle " also
reported positive results in all of six cases examined. However, his findings differ radically from those of other observers,
in that he found the seriun active in relatively high dilutions
(1 in 20 to 1 in 80 and even 1 in 160) ; that the activity was
well marked as early as the second or third day of the disease ;
that it showed no tendency to increase as crisis approached ;
* As the earlier literature dealing with the subject of phagocytosis is summarized in my former article,' it will not be discussed
here.
and that it disappeared entirely within from two to four days
after crisis. More recently Chickering" has reported the
demonstration of agglutinins in a 1 to 2 dilution of serum in
73.8 per cent of a series of 40 cases of lobar pneumonia. Most
of the negative reactions were with serum from fatal cases.
He found that the agglutinative activity developed only at or
near crisis, and that it might be present only for a single
day, or persist {in vivo) for several weeks. The agglutinating
activity of the serum was strictly limited to organisms of the
same type as that with which the patient was infected, but
sometimes was more marked for the homologous strain than
for a heterologous strain of the same type.
The method used by the writer was described in detail in
the previous article,' hence only the essential points will be
repeated here.
The cultures used were, with a few exceptions, those isolated in the routine study of the cases in the medical bacteriological laboratory of The Johns Hopkins Hospital, which
have been reported by Mildred C. Clough," and by Sydenstricker and Sutton," and I am indebted to them for transfers
of most of the strains.
Through the courtesy of Dr. E. I. Cole of the the Eockefeller Hospital, New York, who kindly furnished us immune
serum for the purpose, it was possible to determine the type
of each of the organisms isolated. The phagocytic activity
of the Type I and Type II immune sera has been tested with
most of the organisms studied, and in some of the later cases
observations have also been made with Type III serum, and
with serum corresponding to Avery's Subgroups 2A and 2B."'
The leucocyte suspension was obtained by adding a few
cubic centimeters of normal human blood to 1,5 per cent
sodium citrate solution, washing three times in 0.85 per cent
• salt solution, and pipetting off the leucocytic cream after the
last washing.
The bacterial suspension was prepared by carefully emulsifying a loop of growth in one or two drops of physiological
salt solution. The suspension must be fairly dense to give the
most clear-cut results.
Fresh serum obtained from the patient by any convenient
method, usually venapuncture, was used in a majority of the
cases, though it was found that in nearly all cases the activity
of the serum persisted in vitro for several days at least. In
some cases inactivated serum was also used.
Equal volumes of undiluted serum, bacterial suspension and
leucocyte suspension were mixed and incubated in capillary
pipettes at 37° C. The actual concentration of serum in the
final mixture was, therefore, 1 in 3. The time of incubation
varied from 15 minutes to two hours, depending on the strain
of pneumococcus in question.
When a negative result was obtained, if possible, the test
was modified by making the culture suspension directly in
the serum to be tested, and by using defibrinated blood from
the patient instead of a salt solution suspension of washed
normal leucocytes. In this way the organisms were exposed
to concentrated serum, instead of to a 1 in 3 dilution of serum.
Corresponding control preparations were made, consisting of a
JlNE, 1919]
169
suspension of the organism in normal serum and defibrinated
normal blood. Five cases which gave negative reactions by the
first method were tested by this method; tliree gave positive
results.
Smears from the mi.vtures after incubation were made on
slides and stained with Hastings' stain (polychrome methylene blue). Suitably prepared films are free from sediment,
and both the bacteria and the protoplasm of the leucocytes are
clearly stained. As a rule, the margins of the capsules are
sharply outlined and the capsular material is diffusely stained
a bright pink, in contrast with the bluish-black color of the
organisms.
As in the previous work, counts of the ingested organisms
were not made. Only gross differences were regarded as significant. The degree of phagocytosis was recorded as (0) absent
(or not to exceed five pair in 50 cells) ; ( + ) definite (about
100 or more pair in 50 cells) ; ( + + ) strong ; and ( -F -f- -(- )
maximal. Degrees of phagocytosis less than ( -|- ) in the test
preparations were regarded as inconclusive.
In practically every case the tests were subsequently repeated, different specimens of normal serum and leucocytes
being used to guard against possible errors.
This metliod is very simple, but in order to obtain reliable
results certain precautions must be observed :
(1) The leucocyte suspension must be active. Tliis can
usually be determined by simple inspection of a fresh preparation under the high power. As pointed out by Xeufeld," if
the majority of the leucocytes show numerous filiform pseudopodia, one can be fairly sure that they are active. It is
advisable also to set up a preliminary test with a strain phagocytable in fresh normal serum (not one spontaneously phagocytable). If a very marked phagocytosis has occurred after
15 minutes' incubation, the leucocytes are suitable for use.
Attempts to compensate for an inactive leucocyte suspension
by prolonging the period of incut)ation give unreliable results.
The best results are obtained with fresh leucocytes. Phagocytosis is usually less active in older suspensions.
(2) The bacterial suspension should be fairly dense, and
must be homogeneous and free from clumps.
(3) In every case controls must he made with normal
serum, of the same age and condition as the serum under
investigation, and all tests without exception be discarded if
any appreciable degree of phagocytosis is present in the
controls.
(4) The time of incubation should, if necessari-, be adjusted for each individual strain, so that the test preparation
will show as marked a degree of phagocytosis as possible without permitting any phagocytosis in the controls. For organisms of Types I, II and III, one hour is usually the optimum,
though clear-cut positive results are often obtained after I'l
to 30 minutes. If the results are negative or inconclusive bfcause the degree of phagocytosis in the test preparations is
slight, convincingly positive results may sometimes be obtained
by prolonging the period of incubation to two hours. Rarely is
anything to be gained by a longer period of incubation.
For organisms of Type IV and .\typiral Type II. the period
of incubation should, as a rule, be shortened to 30 minutes,
and in some cases to 15 minutes. If the incubation is too
prolonged, there may be sufficient phagocytosis in the control
preparation with normal serum to obscure the difference between these and the test preparations, a difference which would
have been clear-cut after a shorter period of incubation. Too
prolonged incubation may also obscure results, because it gives
sufficient time for intracellular digestion of the ingested
organisms, and because prolonged contiict with the organisms
seems to injure the staining properties of the leucocytes.
(5) TJie films must be properly spread and stained. The
leucocytes and the larger bacterial clumps, if agglutination
has occurred, will be found along the margins of the film, at
and near the terminal portion. If the film is too thick, so that
the leucocytes are heaped up or not well flattened out, observations are difficult. The presence in a serum of isoagglutinins active on the red cells present in the leucocyte suspension
does not interfere with phagocytosis, but it makes it difficult
to secure even films.
Before considering the result« obtained with serum from
convalescent patients, the behavior of the organisms in normal
human scrum should be discussed. In no instance were
strains of Types I, II (typical) or III, on isolation, phagocytable in fresh normal human serum under the conditions
outlined above. They also rcmainwl rcsistjint to jthagocytosis
for at least several months while under cultivation on artificial media. The medium used was 5 to 10 per cent human
blood agar; transfers being made at intervals of a week or 10
days. One Type II strain became very slightly phagocytable
after two months' cultivation, and a second after cultivation for about a year. Type I strains seemed more resistant
Of three Type I strains followed for a long period, one became phagocytable in fresh nonnal scrum during tlie third
year of cultivation on artificial media ; a second, during the
fourth year; while a third, after four years' cultivation without
intervening animal passage, is still not phagocyt«l)lc.
The behavior of Atypical Type II and Type IV strains was
variable, but most of those observed were less resistant to
phagocytosis than were organisms of the fixed types. The
majority of the Atypical Type II strains, and some of the
Type IV strains, on isolation (from patient* with pneumonia).
were not phagocytable in fresh normal human scrum after an
incubation of half an hour, though after longer periods a
slight degree of phagocytosis was occasionally observed. This
resistance to phagocytosis was frequently reduced after one to
three weeks' cultivation, so that the organism became phagocytable in fresh normal serum. In some cases the original
resistance could be restored by animal pa.ssage. Such strains,
after Ix-coming phagocytable in frcsli normal serum, were not
phagocytable in normal scnim which had been inactivated
cither by heating or by preservation for several days in the ice
"best, and they usually retained this degree of resistance to
phagocytosis after many weeks, and several even after two
to three years of cultivation on artificial media.
Other strains, even immediately after isolation, were phagocytable in fresh normal serum, though resistant to phagocy
170
[No. 340
tosis in inactivated normal serum, even after considerable
periods of cultivation. It was found that the phagocytic
reaction of these organisms in inactivated homologous serum,
either from an immune animal or from a convalescent patient,
were nearly as clear-cut and just as specific as were those of the
more resistant strains when tested in active serum. Two
such cases (Nos. 40 and 41) are included in Table I. Such
strains may possess a moderate virulence for rabbits and mice,
and, as a rule, were not phagocytable in fresh normal rabbit
serum.
In examining (in inactivated serum) these strains which
are phagocytable in fresh normal human serum, it is, of course,
imperative that the leucocyte suspension be very thoroughly
washed in salt solution (at least three times) to remove as far
as possible all traces of fresh serum. Absolutely complete removal is probably not possible, and, as might be expected,
there was frequently a very slight degree of phagocytosis of
these strains in the control preparations. This must be allowed for in interpreting the final results of tests made with
these strains.
Finally, there is a group of Type IV organisms which are
spontaneously phagocytable, i. e., they are phagocytable in
inactivated normal serum or in salt solution. They are, of
course, entirely unsuitable for use in phagocytic tests, although, since some of them show no agglutination in normal
serum, the demonstration of agglutinative activity in the
homologous serum might be possible. In the course of this
work I have examined 13 such strains, all isolated from the
sputum or blood of patients with lobar pneumonia. In four
of the 13 strains, all isolated from sputum cultures, it was
definitely shown that the organism isolated from the sputum
was not the etiological agent in the disease, but was probably
an ordinary saprophytic inhabitant of the mouth, since the
serum of these patients in convalescence acquired the power of
causing phagocytosis and agglutination of stock strains of a
fixed type (in two cases typical Type II and in two cases
Atypical Type II strains). In one case a second attempt was
successful in isolating from the sputum the Atypical Type II
strain for which the serum had developed phagocytic activity.
Of the remaining nine, five were obtained only from the
sputum (four by culture, one by mouse inoculation). The
patients all recovered, and no further evidence was obtained
confirming or disproving the relationship of the organism in
question to the pneumonia.
In four cases, however, the strains were obtained by blood
culture from patients subsequently dying of the disease. In
three of the cases there were 2000 or more colonies per cubic
centimeter of blood. The pathogenicity of the organisms in
these cases can scarcely be questioned.
Although the primary object of this study was to determine
the phagocytic activity of the serum, note was also made as to
the occurrence of agglutination in the preparations, and a
rough estimate recorded of the degree of agglutination present.
With ordinary care in emulsifying the growth, it was easy to
obtain homogeneous suspensions entirely free from clumps,
with virulent organisms of the fixed types. In a large number
of tests no agglutination of these organisms was ever observed
in normal human serum even when undiluted. In the active
(convalescent) sera, however, clumping was usually a striking
feature of the preparations. The clumps varied in size from
groups of a dozen pair up to masses occupying a large part of
an oil-immersion field. Of course, no clumping was regarded
as significant unless the suspension was perfectly homogeneous,
and unless the control preparations with normal serum were
entirely free from clumps. The agglutinated masses of pneumococci, however, differed strikingly in appearance from the
masses occasionally met with in poorly prepared suspensions.
In the former, the individual organisms were more widely
separated, and presented an appearance such as might be produced if the capsular substance between the organisms had
been greatly swollen in the process of agglutination. This
appearance has been described by Neufeld,' Huber ' and others.
Equally clear-cut results were obtained with a majority of
the Atypical Type II and with many of the Type IV organisms
studied. With a number of cultures, however, which showed a
sparse dry growth on blood agar, and in which the capsules
either were small or were not demonstrable, it was difficult or
impossible to secure satisfactory suspensions free from clumps.
Some other strains acquired this characteristic after prolonged
cultivation on artificial media. Such strains also occasionally
showed some tendency to agglutinate non-specifically in normal or in heterologous serum, and they were, without exception, discarded. The majority of these organisms were spontaneously phagocytable, and probably were saprophytic inhabitants of the mouth.
The results of the tests made with the serum of patients with
acute lobar pneumonia are tabulated individually in Table I
and summarized in Table II. With a few exceptions noted
in the table, the homologous strain of pneumococcus was used
in the test : Of 33 cases in which serum obtained at or shortly
after crisis or lysis was tested with the homologous strain,
isolated from the same patient, 28, or 85 per cent, showed
definite phagocytic activity, while five, or 15 per cent, were
negative. Of these five negative cases, in three only a single
specimen of serum was examined, and only in a 1 to 3 dilution.
Tests in concentrated serimi (if tried) might have yielded postive results. Of five cases which gave a negative reaction on
the first test in a 1 to 3 dilution of serum, three gave positive
results when tried a second time in concentrated serum. To
these 28 positive cases may be added six others (included in
Table I) in which the infecting organism was not isolated,
but in which the serum after recovery caused phagocytosis
and agglutination of a stock strain of one of the fixed types
(Type I, two cases; Type II, three cases; Type Atypical IIA,
one case). Only three patients in the series (Nos. 13, 14 and
21) received serum treatment with Type I serum, and in the
two cases (Nos. 13 and 14) giving positive reactions there did
not seem to be any immediate association between the administration of the serum and the appearance of phagocytic activity
in the patient's serum.
Of the 33 eases tested with the homologous strain of pneumococcus, 26, or 79 per cent, gave definitely positive agglu
June, 1919]
171
tination reactions. The two sera which showed phagocytic
but no agglutinative activity were among the three relatively
feeble sera which were active only in full concentration. These
figures correspond quite closely with those reported by Chickering" and obtained by a different method.
This phagocytic and agglutinative activity appeared with
equal constancy after infection with pncumococci of Types I,
II and IV, and also in the only patient in the series with Type
III infection who recovered.*
Serum was also e.xamined from seven patients who later died
of the disease, and the result was negative in six. The one case
in which death occurred after serum activity developed will
be discussed later.
In 18 of the 34 patients whose serum in convalescence was
active in stimulating phagocytosis, tests were also made with
serum obtained during the active stage of the disease. All
were negative with three exceptions, and these three specimens were all obtained one day (or less) before the crisis.
Of nine cases (eventually positive) tested 2-1 hours or less
before the crisis, four were positive and five negative. Of
nine cases tested about 24: hours after the crisis all were
positive.
Very scanty data were obtained to indicate how long tlic
activity of the scrum persists in the body. In one case it disappeared within 11 days, but it was usually present on discharge, from 10 days to three weeks after the crisis. In one
case (No. 27) serum obtained two years later still showed
slight phagocytic activity and fairly marked agglutinative
activity for a stock Type II strain.
We may, therefore, conclude that the serum is inactive
during the acute stage of the disease, and that phagocytic and
agglutinative activity develop only at or near the crisis, occasionally appearing shortly before it, but often demonstrable
only after recovery has definitely set in.
The only instance met with which seems to constitute an
exception to this rule is No. 44, Table I. This patient was
a man aged 61, alcoholic, with arteriosclerosis and hypertension. He was admitted to the hospital on the fifth day
of the disease with signs of consolidation in the right upper
lobe. On admission (fifth day), a Type IV pneumococcus
was isolated from the sputum and also from the blood ( 1
colony per cubic centimenter of blood). On the 13th and 14th
days the temperature fell by lysis, and it seemed probable that
the patient would recover. However, the temperature did
not reach normal. On the 16th day it again became markedly
elevated, and a high remittent fever of the " septic " type
persisted till death on the 21st day. A Type IV pneumococcus was again cultivated from the blood on the 18th day
(2 colonies per cubic centimeter). All three strains were
found to be serologically identical. On the 19th day the
heart was found to be dilated, and a systolic murmur appeared
•The sera from two recent patients recovering rrom Type III
empyema, not included in this series, showed well-marked phagocytic activity, but no agglutinative activity. This activity was
present only In the fresh serum, and was limited to the homologous strain of pneumococcus.
at the apex. On this day the patient suffered a left hemiplegia. Nothing definite could be made out in the lungs
or pleurae to explain the recrudescence of fever. No autopsy
was obtained. While it was not certain tiiat the hemiplegia
was not the result of a coincident cerebral hemorrhage, it was
thought probable that a sepsis had developed, with an acute
bacterial mitral endocarditis and a cerebral embolism.
The pneumococcus isolated from this patient was slightly
phagocytable in fresh normal serum, but not in inactivated
serum. The inactivated serum of the patient obtained on the
fifth day caused no phagocytosis or agglutination of his organism, but a specimen obtained on the 13th day (during the
remission), both in the fresh state and after inactivation,
caused very marked phagocytosis and agglutination of this
organism. A third specimen of serum obtained on tiie 18th
day was equally active. This was two days after the recurrence
of fever, and was after the reappearance of the organisms in
the circulating blood. In this case, therefore, sepsis ai>parently
ensued, despite the presence of phagocytic and agglutinative
activity in the serum.
To determine the specificity of tlic reaction, a large number
of crossed tests were made with the active post-critical .-ierum
of each case, heterologous strains belonging to the same type
and also strains of different types being employed. Table
III shows results obtained with sera from patients recovering from Type I infections, and Table IV from infection
with other types. In general, these data may be summarized
as follows: A scrum which is active on the homologous
strain, will, as a rule, cause phagocytosis and agglutination of
any other strain of the same type, but is entirely inactive
toward strains of any other type. This differs from the tentative conclusions previously reported by the writer. In the
former series of cases, phagocytic activity, in the six sera in
which it was demonstrable, was strictly limited to the homologous strain of pneumococcus, with the single exception of
one serum, which was also active on one only of several lieterologous strains with which it wa.^ tested. In view of the findings
in this present series the ex])lanation for the previous results
probably is that only two of the organisms examined happened
to belong to the same type.
The serum from patients recovering from Tyjic II iiifictidn
showed no activity toward Atypical Type II strains (with the
exception, possibly, of Xo. 27: Los., S.; Table IV). Serum
from cases of Atypical Type II infwtions acted only on members of the corresponding suiigroup.
Case No. 14, Table I, illustrates well the sjjccificity of these
reactions. This patient was admitted with a lobar pneumonia
which was proven by si)utum and blood cultures to be due to
an Atypical IIA infection. The serum shortly before crisis
was inactive toward this organism, but shortly after crisis
caused active phagocytosis and agglutination of it. Four days
after crisis a second attack of pneumonia developed, a different
lobe being involved, and a Type 1 strain was isolated from both
blood and sputum. His serum at this time was inactive toward
the Type I strain, though active toward the IIA strain. He
had a second crisis on the eighth day, and after this crisis
172
[No. 340
phagocytic and agglutinative activity for the Type I strain
had also developed.
Serum from one of the three patients infected with a Type
IV pneumococcus was active only on the homologous strain.
That from a second case was equally active on the homologous strain and on one other Type IV strain from another
case of pneumonia, serum from whicli could not be obtained for
study. The third case also furnished a serum which was active
in promoting phagocytosis, not only of the homologous strain,
but also of one other Type IV strain, isolated from the spinal
fluid of a case of pneumococcus meningitis. The demonstration, among a comparatively small number of Type IV
strains examined, of two pair of serologically identical strains,
is in conformity with the recent findings of Olmstead,"
and indicates the probability that further study will reveal
new types among the pneumoeocci now included in Type IV.
The serum of this last case (No. 27; Los., S.; Table IV)
also caused phagocytosis of typical Type II strains and, less
actively, of several Atypical II strains as well. This patient's
serum four days before lysis was inactive toward the homologous Type IV strain, but was not tested at this time as to its
activity toward a Type II strain, as this anomalous behavior of the serum was not anticipated. This is the only instance
in the series in which a serum showed phagocytic activity
toward a strain of a type different from that which was isolated from the sputum (except for four cases in which spontaneously phagocytable mouth saprophytes were isolated from
plate cultures). This might be explained either on the assumption that the patient had a double infection with a Type
II and a Type IV organism, or that he had previously had a
Type II infection, with persistence of the antibodies for Type
II strains. The possibility of such a persistence of antibodies
for a long period is demonstrated by the fact that a specimen
of serum obtained from this patient two years later still
showed slight phagocytic and well-marked agglutinative activity for Type II strains. The activity of this specimen of
serum for the homologous Type IV strain could not be tested,
as the strain had been lost.
The agglutinative activity of this serum was less specific
than its phagocytic activity, in that it not only agglutinated
those strains which it caused to be phagocyted, but several
other Type IV strains as well. The agglutinative reactions
of the Type IV strains, and of some of the Atypical II strains,
as observed in these tests, were not as specific as were the
phagocytic reactions.
A special effort was made to detect any possible quantitative
serological differences between different strains belonging to
Type I. In two sera (Nos. 1, T. A., and 5, M. M., Tables I
and III), both of which were but feebly active, the homologous strain was somewhat more actively phagocyted than were
the heterologous strains tested.* This is in accordance with
the observations of Chickering " on agsrlutination in the serum
* In two recent patients recovering from Type III empyema,
not included in this series, tlie piiagocytic activity of the serum was
strictly limited to the homologous strain.
of convalescents. He reported that in several instances " the
first organism to be agglutinated was the homologous strain,
and only later was the stock strain agglutinated." Different
strains may differ considerably in their phagocytability in the
same serum. Thus, in one series of tests with stock Type I immune serum, strains S and R were phagocyted in 1 to 48 dilution ; strains V and B in 1 to 24 dilution ; while T and F were
phagocyted only in a 1 to 12 dilution. When an active human
serum was titrated in increasing dilutions with several different Type I strains, the highest titre was usually obtained with
those strains which were most readily phagocytable in any
Type I serum rather than with the homologous strain. Although such specific strain differences undoubtedly exist, they
must be relatively slight, and it is not always possible to
demonstrate them conclusively.
The activity of immune serum of the various types on most
of the strains studied was also observed, and some of the
results are recorded in Tables IV and V. The same complete
specificity is observed here, except in the agglutinative action
of Type II serimi on Atypical Type II strains. Type II
serum in a concentration of 1 in 3 and with an incubation
period of about 30 minutes caused agglutination of all the 25
Atj'pical II strains tested. However, Type II serum was much
more specific in its phagocytic reactions toward these strains.
With only two strains was any definite phagocytosis observed ;
and this was much less active than was the phagocytosis of
typical Type II strains.*
The Atypical Type II strains were actively phagocyted and
agglutinated by an immune serum corresponding to the particular subgroup to which they belong, but were not affected
by serum corresponding to the other subgroup or to any strain
not belonging to their subgroup.
This test, therefore, offers an additional simple method
for the differentiation of typical Type II and the various
Atypical II strains, and has proved to be of practical value in
the case of certain Atypical II strains, which were agglutinated
macroscopically in Type II serum in dilutions of 1 in 32,- and
even in 1 in 64, though somewhat more slowly that Tj-pical
II strains.
The existence of other undescribed subgroups among the
Atypical II strains is indicated by the fact that an immune
serum prepared with a strain from a case of empyema, which
did not fall into either Subgroup A or B, caused phagocytosis
and agglutination of one other Atypical II strain.
As to the properties of the active substance which stimulates
phagocytosis in these human sera, the observations previously
reported by the writer have been confirmed. They are in the
main thermostabile. In eight of nine cases tested, serum
inactivated for 20 to 30 minutes at 56° C. retained its activity.
When the lieating materially exceeded this, either in duration
• Several other Atypical II strains, after their resistance to phagocytosis had been lowered by cultivation on artificial media for
a considerable period, also acquired a slight degree of phagocytability in T>-pe II serum. With the two exceptions noted, however, all strains when tested shortly after isolation were not
phagocytable in Type II serum.
June, 1919]
173
TABLE I
PHAGOCYTIC AND AGGLUTINATIVE REACTIONS IN THE SERIM OF PATIENTS WITH LOBAR PNEUMONIA. TESTED WITH THE
HOMOLOGOUS STRAIN OF PNEUMOCOCCUS
Reault
Testa during meute itase
Tests during convalescence
Titre of
phagocytic
activity of
serum
No.
Name
Hospital
number
Source of
•train
Type
Ccri.18
L-lysis
D-deatb
Day of
disease
Result
Daya before crisis,
lyala.or
death
Reault
Days
after
crisis or
lysis
Remarks
Phag.
Agren.
Phag.
Aggn.
1
T.. A.
3SS80
Sputum
I
L
21 !1 ..
+
,
4
1-1. -I
f»
•
18
t
v.. J.
3S430
Sputum
I
C
16
+'
+'
1
+
1
8
1-3,-11-6,0
3
R., C.
35482
Sputum
I
L
13
7
4
1
19
1-6, -^
1-12.0
4
S., J.
35517
Sputum
I
C
9
D
3
+'
+'
2
4
11
l-12,-(
Serum had become inactive
11 days after lysis.
s
M.. M.
35828
Sputum
I
L
6
c
4
+'
1
1-1, -t1-3,0
«
P.. P.
35582
Sputum
I
C
6
1
+ '
+'
2
1-1. +
1-8,0
7
P., C.
35082
Sputum
I
L
11
8
+'
+*
1-3, -t1-6,0
8
li.,W.
35901
Sputum
I
L
10
8
+'
+»
4
1-3,-1
8
McK., C.
39702
Empyema
I
L
f
+*
-I-'
80(f)
1-3,+
10
R., J.
35902
Sputum
I
11
4
+
+•
1-3, -h
11
a., N.
35274
None obtained
(I)
C
6
+
+'
12
1-3,-1
Tested with stock Type I strain.
U
B..C.
35681
None obtained
(I)
L
12
6
+'
+*
1
1-3,-11-6,0
TestedwithstockTypel strain.
18
W., H.
37334
Blood, Sputum
I
C
7
+'
f»
10
l-S.-t
It
W., 0.
37&S0
Blood, Sputum
I
C
8
12
+'
+*
1-3, -h
1 1 A pneumonia. See No. S3.
<
IS
T.,C.
38870
Sputum
I
C
8
+
+'
1
1-3, -^
This (ollowcd 3 davs after a
Type 11 pneumonia.
Not tested till 11 days after
1«
B.,U.
35028
Sputum
I
L
6 11
1-1,0
16
Ivsis.
17
W., M.
35082
Sputum
I
L
7
2
2
1-1,0
Clinicallv broncho-pneumonia.
18
M., 8.
35594
Blood, Sputum
D
19
14
Pneumothorax following aspi
18
F., J.
35588
Blood
I
D
?
f
ration.
to
J. W.
35308
Sputum
I
D
9
B
21
J.
37409
Sputum
I
U
3
3
n
8.. F.
353 IS
Sputum
11
L
10
3
1
+'
+'
4
1-12,0
a
M.. T.
37419
Sputum
II
Lf
f
+'
+•
f
1-3,-1
u
D.,H.
39040
Ulood, Sputum
II
C
7
+'
-I-'
u
C, J.
35311
None obtained
(11)
C
9
+'
+'
11
1-3, -h
Tvpe IV from sputum 8 days
after crisis. Tested with
stock Tvpe [1.
M
T.. J.
35871
Sputum (IV)
(11)
L
9
+•
+'
1
1-3,-f
Phajfocvtiiole IV from sputum.
Tested with stock Type 11.
17
L..S.
35681
Sputum (IV)
(II)
L
18
+'
1
1-S,-I
Tvpe IV from sputum. Tested
with stock 11. See No. 41.
»
0.. E.
37279
Sputum
II
L
9
+
4
1-8,0
Not tested in concentrated
serum.
18
W.. H.
39103
Sputum
III
C
3
+'
+
1-3, -h
30
C.,C.
35596
Sputum
III
D
7
4
31
H.,0.
37200
Sputum
IIA
C
7
+'
-I-'
S
i^,+
32
B, W.
37328
Sputum
Blood, Sputum
IIA
C
7
+'
+'
33
W.. (;.
37556
IIA
C
7
+'
+'
6
See No. 14.
34
H., B.
37354
niood. Sputum
IIA
L
7
+*
+*
35
8..T.
37298
IIA
C
9
+'
+'
6
1-3,+
3«
McC.. 0.
37468
(See remarlia)
IIA
C
8
+*
+'
3
1-3,+
Phagocytahle IV from sputum.
Testeil with stock IIA.
37
J., H.
37074
Blood, Sputum
IIA
D
8
2
38
E.. R.
35806
Blood, Sputum
Atyp.II
C
10
7
1
+'
+'
6
1-6,0
88
D.. W.
37433
Sputum
Atyp.II
C
8 3
1-3,0
Not tested in concentrated
40
B..J.
35679
Sputum
IV
L
8
3
+'
-I-"
2
1-3,+
41
L.. 8.
35660
Sputum
IV
L
13
4
+'
-I-'
1
1-3,+
See No. 27.
41
W..H.
374U0
Sputum
IV
C
7
+'
+'
8
1-3,+
43
N.. A.
37810
Sputum
IV
L
8
+'
1
44
W.. J.
35627
Blood, Sputum
IV
D
21
18
8
1-3,+
4S
B.. W.
37335
Sputum
IV
L
8
+"
+»
3
6
1-3,0
Not tested in concentrated
4<
N.. H.
37285
Sputum
IV
D
8
'
"
TABLE II
SUMMARY OF PHAGOCYTIC REACTIONS IN THE
SERU
MOP
PATIENTS
WITH LOBAI
IPNE
UMONIA
Reacttona with serum from convalescent patients (lobar pneumonia).
Cases tested with the homologous strain
Additional
cases tested
with stock
strains
Total
positive
No.
Reactions of serum d
from patients whose
gave positive
ring acute stage,
serum eventually
reactions
Reactions of scrum from patients
who subsequently died
Ko.
Poaltire
Negative
Pofitive
No.
PoaitiTt
1 NegatlTO
No.
PoaitlTC
Nagitir*
Type 1 1 IS
Type II 4
13
8
1
6
«
2
2
i
IS
S
s
8
U
3
8
2
1 '^
4
t
1
4
Type III 1 1
Type IV 6
Type Atyp. II 7
28-88%
6-lS%
6
34
IS
•8-17%
1 16-83' .
^
1-124%
7-874%
* TheM thrM fpccfmena were obtsineU on the da/ before criiii.
174
[No. 340
or height of temperature, the activity was lessened or destroyed.
The serum usually remained active in vitro for several weeks,
though it gradually weakened in activity. In two cases, serum,
which in the fresh state was feebly active, lost its activity
after from two to four days. Nearly all the sera, however,
remained active throughout the period during which they were
under observation, which varied from a few days to four
months.
If the serum had become inactive or feeble as a result of
overheating, long preservation or dilution, the phagocytic
activity could not be restored or increased by the addition of
complement. The substance is, therefore, quite different from
the active substances (opsonins) of fresli normal serum, and
corresponds to the bacteriotropins as defined by Neufeld."
The active substance was present in the serum in relatively
small amount. In a majority of the sera tested as to this
point, no phagocytosis occurred if the concentration of serum
in the mixture was less than 1 in 3. In a few cases it was
active in a 1 in 6 dilution, and in one case in a 1 in 12
dilution.
These bacteriotropins, as well as the agglutinins, were
precipitated from immune serum with the euglobulin, on the
addition of 36 volumes per cent of saturated ammonium sulphate solution. The euglobulin fraction of the precipitate,
redissolved in salt solution and freed from an excess of ammonium sulphate by dialysis, caused marked phagocytosis and
agglutination. The pseudoglobulin fraction of the precipitate,
obtained by the further addition of saturated ammonium sulphate solution to give a concentration of 44 volumes per cent,
was likewise redissolved and diah'zed, and was found to be
inactive, as was the dialyzed supernatant serum from which
the globulins had been removed. In this respect, therefore,
the bacteriotropins resemble most other antibodies which
have been similarly studied.
These bacteriotropins are probably not identical with the
agglutinins. In two sera in which definite phagocytic activity
was demonstrable, no agglutination whatever occurred. As
a rule, however, the agglutinative activity of the serum was
more marked, was usually present in higher dilution, and
persisted longer in vitro than did the phagocytic activitj' of the
serum. In one case agglutinative activity was observed to
precede the development of phagocytic activity. However,
the observations with reference to this point were not sufficient to determine which type of activity is usually the first
to appear.
Of 33 cases of acute lobar pneumonia in which the phagocytic activity of the serum after crisis or lysis was tested
with the homologous strain of pneumococcus, 28, or 85 per
cent, gave definitely positive results. These results confirm
and extend those previously reported by the writer.
In 26, or 79 per cent, of these cases agglutinative activity
was also demonstrable.
In 18 cases in which definite phagocytic activity was demonstrable in the serum after recovery either for the homologous
strain or for a stock strain of known type, tests were also made
with serum obtained during the acute stage of the disease, and
negative results were obtained in 15. The three sera which
showed phagocytic activity were obtained 24 hours or less
before crisis.
Serum was also examined from seven patients who subsequently died of the disease, and negative reactions were obtained in six. A positive reaction was obtained in one patient,
who, after a short remission, died apparently of sepsis and
endocarditis.
This phagocytic and agglutinative activity of the serum
developed after the recovery from infection with pneumococci
of all the recognized types. It was strictly limited to organisms of the same type as that with which the patient was
infected, but, as a rule, was exerted equally well on the homologous strain and on heterologous strains of the same type.
It is, therefore, specific as to type, but not specific as to strain,
as the writer originally believed.
The agglutinative activity of the serum as observed in these
tests paralleled closely the phagocytic activity. In the case
TABLE III
PHAGOCYTIC AND AGGLUTINATIVE REACTIONS IN THE SERUM OF PATIENTS RECOVERING FROM TYPE I INFECTION,
TESTED WITH
HOMOLOGOUS AND HETEROLOGOUS
TYPE I STRAINS Strain of pneumococcus-Typc I
Serum
Type I
(stock)
Type II
(stock)
T., A.
v., J.
R., C.
S., J.
M., M.
p., p.
P., c.
M.,W.
McK.
R., J.
B.,H.
W.,M.
So.
Joh.
Fen.
McC.
Mt.
For.
Scrum, Type I (immune).
Serum, Type Iliimmune)
+' +'
+
+ ! +3
+' +>
+3 +>
+
+" +'
+» +=
+ +"
+» +'
U
+ S +3
+'
+= +'
+s +3
+3 +3
+ +=
+ +
+ 3 +3
+ 3 +3
+ 3 +3
+ 3 +3
+3 +3
+3 +3
+3 +3
+3 +3
+3 +3
u
+3 +3
+2 +3
±
+ +=
+» +'
+2 +3
+3 +3
±
+ +'
+2 +3
+2 +3
+
+ = +3
+= +»
+3 +3
+ S +3
+
+ 3 +3
+ ' +'
+' +'
+ 3 +3
Serum, V., J
+ 3 +3
+ 3 +3
+ 1 +3
+
43 +3
+S +3
+»
+:
+' +=
+' +'
+ 3 +3
+ ' + =
'+="6'
+»
+' +"
-r' +»
+ 11
+ 2 +3
+3 +3
+3 +3
+! +8
+3
+ +=
+ 3 +3
+ +'
+ 2 +3
+ 3 +3
+ 3 +3
+ 3 43
+ 3 +3
+=
+ 2 +3
+3 +3
+
+s
+ +'
+1 +3
+2
+ 2 +3
+ » +»
+ 2 +3
+3 +3
Serum, S., J
+> +'
+ 3 +3
+ 2 +3
+3 +3
+ 3 +3
+ 3 +3
+ 3 +3
+2 +2
+3 +3
+ +»
+1 +3
+3 +3
+ 3 +3
+ 3 +3
+ +»
+ +=
+ 2 +3
+ +'
+ +'
+ +'
+ +'
+ +»
+ +"
+ +=
+ +=
+ +'
+=
+»
+s +»
+2
+"
+'
ach column represents phagocytosis, ami the second a^'g^lutination.
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er
176
[No. 340
of Atypical II and of Type IV strains it was not so sharply
specific as was the phagocytic activity.
This phagocytic activity is entirely different from a possible
rise in opsonic index, in that it brings about active phagocytosis of a virulent pneuniococcus, not at all phagocytable in
normal human serum.
The active substances in the serum also differ from tlie
opsonins of normal serum in that they are usually thermostabile ; they usually remain active for several weeks in serum
preserved in vitro; and when their activity is lost, they cannot
be reactivated by fresh normal serum (complement). Tliey
are therefore qualitatively comparable with the bacteriotropins
of potent immune serum.
In view of the facts: (1) That this activity of the serum
develops in nearly all patients who recover, but only appears,
as a rule, at or near crisis; (2) that it is limited to organisms of the same type as that with which the patient is infected; (3) that, as previously reported, the "phagocytic
activity of the serum ran closely parallel with the protective
power for mice, both in incidence, in time of appearance and
in strict specificity as to the type of pneumococcus concerned"; and (4) that phagocytosis in the peritoneum of the
protected mouse closely paralleled phagocytosis in the testtube; it seems probable that this factor plays an important
part in bringing about recovery in man.
The part played by agglutination in immunity to the
pneumococcus in animals has been emphasized by Bull,'' and
in all probability it is also an important factor in human
immunity.
That other factors are also concerned is indicated by the
death of one patient from sepsis, despite the previous development of phagocytic and agglutinative activity in his serum ;
and by the fact that in several instances pneumococci, which
had been cultivated from the blood of patients dying of pneumonia, were phagocytable in normal serum or even spontaneously phagocytable in salt solution.
The clinical value of the test will not be great as a method
either of diagnosis or of prognosis, since the reaction develops
only when recovery sets in. In cases in which as a matter of
scientific interest it is desirable to determine the type of organism concerned in a recent infection, the development of a
positive reaction either with a stock pneumococcus of known
type or with an homologous isolation, would furnish practically conclusive evidence that this organism was the etiological
agent concerned in the disease.
REFERENCES
1. Clough, P. W. : The development of antibodies in the serum
of patients recovering from acute lobar pneumonia. Bull. Johns
Hopkins Hosp., Baltimore. 1913, XXIV, 295-306.
2. Neufeld, F., and Rimpau, W.: Weitere Mittheilungen iiber die
Immunitat gegen Streptokokken und Pneumokokken. Ztschr. f.
Hyg. u. Infectionskrankh., Leipzig, 1905, LI, 283-299.
3. Cole. R. I., and Dochez, A. R.: Report of studies on pneumonia. Trans. Assn. Am. Physicians, Philadelphia, 1913, XXVIII,
606-616.
4. Dochez, A. R., and Gillespie, L. J.: A biologic classification
of pneumococci by means of Immunity reactions. J. Am. M. Ass.,
Chicago, 1913, LXI, 727-732.
5. Lister, F. S.: Specific serological reactions with pneumococci
from different sources. Johannesb., 1914, W. E. Horter & Co.
S. African Inst. Med. Research., Pub. No. 2.
6. Lister, F. S.: An experimental study of prophylactic inoculations against pneumococcal infection in the rabbit and in man.
S. African Inst. Med. Research., Johannesb., 1916, No. 8, 1-57.
7. Bensangon, P., and Griffon, V.: Etude de la reaction agglutinante du serum dans les Infections exp^rimentales et humaines a
pneumocoques. Ann. de I'lnst. Pasteur, Par., 1900, XIV, 449.
8. Huber, F. 0.: Ueber Agglutination der Pneumokokken. Centralbl. f. innere Med., Leipzig, 1902, XXJII, 417-421.
9. Neufeld, F. : Ueber die Agglutination der Pneumokokken
und viber die Theorien der Agglutination. Ztschr. f. Hyg. u. Infectionskrankh., Leipzig, 1902, XL, 68.
10. Gargano, C. and Fattori, C: SuU' agglutinazione del dlplo
cocco; contributo di fatti e di osservazioni. Riv. crit. di clin. med
Firenze, 1903, IV, 177, 193, 209, 225.
11. Jehle, L. : Ueber Pneumokokken-Agglutination mit dem Blut
serum pneumoniekranker Kinder. Wlen. kiln. Wchnschr., 1903
XVI, 917-919.
12. Chickering, H. T. : Agglutination phenomena in lobar pneumonia. J. Exper. M., Lancaster, Pa., 1914, XX, 599-613.
13. Clough, M. C: A study of the incidence of the types of
pneumococci isolated from acute lobar pneumonia and other infections, and an analysis of the cases classified by types in regard to
mortality, complications, associated diseases, bacteriemla, and
leucocytosis. Bull. Johns Hopkins Hosp., Baltimore, 1917,
XXVIII, 306-311.
14. Sydenstricker, V. P., and Sutton, A. C: An epidemiological
study of lobar pneumonia. Bull. Johns Hopkins Hosp., Baltimore,
1917, XXVIII, 312-315.
15. Avery, O. T.: A further study of the biologic classification
of pneumococci. J. Exper. M., Lancaster, Pa., 1915, XXII, 804.
16. Neufeld, F.: Bakteriotropine und Opsonine. In Handb. d.
pathogen. Mikroorg. (Kolle and Wassermann), 2. Aufl., Jena,
1912, II. 401.
17. Olmstead (Miriam): A preliminary report on the classification of pneumococcus IV. Proc. Soc. Exper. Biol, and Med.,
New York, 1916, XIV, 29-31.
18. Bull, C. G.: The mechanism of the curative action of antipneumococcus serum. J. Exper. M., Lancaster, Pa., 1915, XXII,
457-464.
THE DEVELOPMENT OF CROSS-STRIATIONS IN THE HEART MUSCLE
OF THE CHICK EMBRYO
Bv Margaret Reed Lewis
The results obtained by different observers in regard to the
development of the cross-striations in muscle-fibers differ so
decidedly that one is forced to question whether any one of
the views presents the entire story. Even though the discus
sion be confined to the development of this structure in one
organ and to one form, as, for instance, the histogenesis of the
myofibrils in the heart muscle of the chick embryo, it is
found that, although the papers published are few in number.
JrxE. 1919]
177
they nevertheless differ fundamentally from each other. In an
effort to determine, if possible, the reason for these differences,
a careful cytological study of the development of the heart
of the chick embryo was undertaken. For this purpose preparations of embryos varyin<i in ape from 10 myotomes to four
days incubation were made by a number of different mctbixls.
The astonishing result of the study of these was that one
particular procedure always resulted in the presence of complete cross-st nations in the heart, whether in very young
embrv'os (10 to 15 myotomes — about 28 to 30 hours), or in
older ones (two to four days).
Heidenhain (1899), in his Fig. 13, showed that the heart of
a goose embryo of 3 days incubation contained many completely cross-striated myofibrils of different thicknesses, which
stained with varying depth of color with iron-hematoxylin.
Schlater (1907) contests this point, and although he finds
that a few cross-striated myofibrils are located in the heart
of chick embryos as early as 2i days incubation, the pattern of these cross-striations is not the same as that given by
Heidenhain. Even in embryos as old as seven days Schlater
failed to demonstrate the 2-band, although he presents figures
of many long myofibrils extending through several cells. He
is not the only obsener who was unable to find this band :
Rouget (1863), Wicman (1907), Mlodowska (1908), Kurkiewicz (1909), I^vi (1910) and Bruno (1918) show no trace
of it in any of their figures. Duesberg (1910), however,
observed the z-band in the heart muscle, as well as in the
skeletal muscle. He describes the development of the myofibrils only verj- briefly. He states that it takes place in the
heart of the embryo chick in the same manner as in the skeletal muscle, except that the myofibrils of the former are differentiated verj- much earlier than are those of the latter, as he
has observed completely cross-striated myofibrils in the heart
as early as tlie third day. In his Fig. 5 (Duesberg, 1910),
a section through a chick embryo of 11 to 12 somites, there are
no myofibrils shown.
Rouget (1863), Kurkiewicz (1909), Ixni (191(;). and
Bruno (1918) also distinguished the cross-striations at an
early stage, but each of these observers demonstrates the
same pattern as that presented by Schlater. The youngest embryo observed by Rouget was of 36 hours incubation.
In his figures the myofibrils found at this early age have
the same type of cross-striation as that represented for a
four-day embryo. In neither is the z-band shown. Kurkiewicz depicted cross-striated fibrils in his drawings of the
heart muscle of a 2.J-day embrAo. Levi (1916) described
the occurrence of fiiirils in fixed preparations of cells grown
out from pieces of the heart of a three- to four-day chick
embryo explanted in plasma. In his figures most of these
fibrils are smooth, others are varicose and a few are crossstriated. The z-band, however, is lacking in all. The latter
is also true for the obsenations of Bruno (1918) carried
on in the same laboratory. Bruno, however, found rather
long varicose fibrils in the heart of embrvos of 10 somites.
Although Meves (1908), previous to Duesberg, concluded
that the fibrils of the heart muscle are differentiated from
mitochondria, he nevertheless failed to indicate the presence
of cross-striated fibrils in the heart of young chick embryos.
Ferguson and Jordan (1916, Fig. 102, page 95), show a
group of myoblasts from the heart-muscle syncytium of a 48hour chick embryo. This figure contains no evidence of crossstriation, although at tliis age such structures are numerous.
Instead there are present in the cell various black granules
and long black or gray threads, stated to be " myochondria,
mitochondria and myofibrils."
Wieman (1907), apparently the first investigator to study
the histogenesis of the myofibrils in the heart muscle of the
chick embryo, obtained results quite different from any of
the above authors. By means of a special tcclinic, he found a
definite reticulum in the muscle-cell. This network (cytoreticulum) is largely concerned in the development of the crossstriations, and in order to accept Wieman's view in regard to
the formation of the cross-striations it is necessary to acknowledge his premise that such a network exists in the muscle-cell.
In the past few years it has come to be accepted by most cytologists as an established fact that such a reticulum is not
normal. This has been shown for fixed muscle material by
Duesberg, Luna, Meves and many others. Moreover, it has
been demonstrated by Lewis and Lewis (1917) that the living
muscle-cell is not reticular.
A consideration of Wieman's figures suggests a quite different conclusion than that arrived at by him. At 30 hours (a
period when tlie licart muscle can be shown to contain many
cross-striated fibrils) he depicts a somewhat round cell with
no trace of cross-striation, but instead, a network (cytoreticulum). At 126 hours, at the time when the cross-striated
fibrils are numerous, the cell is figured more elongated and
with the network arranged in longitudinal bands. From these
figures it is possible to conclude that the two cells represented
the effect of coagulation under different degrees of stretching.
However tliat may be, Wieman's paper is carefully worked out
and seems to exhaust the subject from this particular stjindpoint, especially so in view of the fact that more modern
studies of technic have determined that such a reticulum does
not exist in the living cell, but is the result of coagulation.
For this reason it is rather surprising to find that Congdon
(1918) has taken the subject up again from a somewliat similar point of view. Instead of a cytoreticulum, Tongdon
(p. 147) expresses this structure in terms of " three systems of
membranes each parallel among themselves which intersect
to form hexahedral compartments." At all intersections of the
three planes he claims to find small, uniform mitochondrial
granules. It is questionable whether these granules are mitochondria, since he misinterprets several types of granules supjiosed by other observers to contribute to the formation of the
fibrils. For instance, he claims that Godlewski (1902) found
the mitochondria to be concerned in the devcloimient of the
fibrila, when it seems evident from the fixatives employed by
that author (sublimate, sublimate acetic, acetic alcohol, etc.)
that all the mitochondria were probaidy destroyed.
Thus a review of the literature on the histogenesis of the
myofibrils, confined to the narrow field of the heart-muscle of
178
[No. 340
the chick embryo, brings to light a number of divergent views
upon this subject. The origin of the myofibril has been attributed to a row of granules (Kurkiewicz), to the differentiation of the mitochondria (Duesberg), to a network (Wieman) and to a system of hexahedral compartments (Congdon). Most of the observers failed to demonstrate the 2-band.
Heidenhain and Duesberg found completely cross-striated
myofibrils in the heart muscle as early as the third day. These
two writers differ, however, in their view as to the origin of
the fibril.
The experiments given below show that the complete crossstriations can be demonstrated to be present in the earliest
heart, i. e., about 10 myotomes or 28 to 30 hours' incubation.
In other words, cross-striations are already present at the age
when certain observers demonstrate the appearance of granules, the formation of a network, the elongation of mitochondria, etc., from which they claim that the cross-striated fibrils
are later derived.
METHOD
When the heart of a young embryo (up to 3 days) is fixed
under the microscope it can be seen that practically any
method of fixation will show the cross-striated fibrils at some
stage of the process. Many of the solutions, especially those
containing acetic acid or other coagulative reagents, rapidly
cause distortions which partially or entirely obscure the crossstriations. Zenker's solution without acid (potassium bichromate 2^ -I- sodium sulphate 1^ -f corrosive sublimate 5,^) with
the addition of a little osmic acid just before using was found
to be the most successful. However, the secret is not in selecting the proper solution, for any one of these may give poor
results if an added factor, the extension of the muscle, is
neglected. The heart may be extended in various ways — by
injection, etc. — but the simplest and most easily controlled
method is by means of the weight of the coverslip. The procedure for the chick embryo heart was as follows : The egg
was opened, the blastoderm cut around and lifted off into a
dish of Locke's solution. In this the vitelline membrane was
removed, the blastoderm shaken free from yolk and floated
yolk-side down upon a coverslip. If the preparation was to be
stained, or if very clear cells were desired, the membranes were
dissected away from around the heart. In the very young
embryos (10 myotomes), in which the heart is only a short
tube in the midventral line and it is impossible to determine
to which side it will extend when subjected to pressure, the
membranes on each side of the head were taken away, the
excess fluid was removed and the coverslip then inverted on
to a drop of fixative (Zenker without acid to which a little
osmic acid had just been added) on a slide. This fluid was
rapidly withdrawn by means of two pieces of filter paper until
the weight of the coverslip slightly flattened the heart. Care
was taken to avoid crushing the embryo. The preparation was
at once studied under the microscope with the oil-immersion
lens and No. 6 ocular. The cross-striated fibrils appeared
rapidly and could be observed more readily in this way than
when stained. Such preparations keep for days, provided the
coverslip is sealed with vaseline to prevent drying.
For studies upon the living muscle the method was the same,
except that a drop of Locke's solution was used in place of a
fixing solution. In such preparations contraction continued
for an hour or longer and no fibrils were formed.
When vital stains were used, these were added to Locke's
solution. The heart was first injected on the coverslip with
the solution containing the vital stain, and afterwards
mounted in a drop of the same solution. In these preparations,
also, the heart continued to contract and no fibrils were formed
during that period. None of the preparations were sectioned,
but were always observed in the total mounts, either living
or fixed.
OBSERVATIONS UPON FIXED PREPARATIONS
It was difficult to distinguish the heart-muscle cells before
the heart formed into a single tube (about 10 myotomes) and
no effort was made to do so. At this early age it was already
composed of an outer layer of flat cells, a middle layer of
muscle-cells and an inner layer of endothelial cells. In the
fixed preparations of the heart muscle, the cell boundaries
could seldom be determined. The muscle tissue of the heart
of the youngest embryo appeared to be more or less a syncytium. Certainly in the embryos of 12 myotomes and older
there was no doubt but that the fibrils passed across several
cells, and that the fixed tissue formed a syncytium.
MYOFIBRILS IN FIXED TISSUE
As the heart matures there is a gradual increase in the
number of the fibrils which appear upon fixation. In the heart
muscle of a chick embryo of 10 myotomes only a few fibrils
were formed; in those of from 15 to 18 myotomes a number of
such structures appeared ; in those of from 20 to 22 myotomes
the fibrils were numerous; while in older embryos the heart
became full of fibrils, passing in every direction. They were
of varying widths in all ages of heart-muscle tissue (Fig. 5).
Occasionally they were very thick, at times almost the width
of the cell ( Fig. 3 ) ; but usually they were narrower, sometimes
about the width of a mitochondrium. In the muscle of the
older embryos the fibrils formed were more uniformly narrow
threads, while in that of the young embryos there were great
divergences. None of the extremely narrow fibrils described
by Heidenhain were distinguished. That writer claimed that
a higher power of tlie microscope always demonstrated a still
more delicate fibril, until the magnification at his control was
exhausted. This may be shown by means of sections, but was
not evident in my preparations. The fibrils were most frequently straight or only slightly bent, but in certain places
they became curved with the outline of the cell. They were
never wavy or undulating, except in poorly fixed preparations.
They extended for long distances across a number of nuclei
and passed in various directions across each other. The fibrils
possessed depth when focussed and were not difiicult to observe ;
they were also found at different depths of the focus.
After many observations upon each of the embryonic ages
enumerated above, it became evident that there was a gradual
accumulation in the cell of some substance which appeared as
THE JOHNS HOPKINS HOSPITAL BULLETIN. JUNE, 1919
PLATE XXII
Fie. 2.— A phi>lnKi:i|>li "I H ' hi. K :mi.'i 48 lioiirs ini'iiliation. Tlii
embo'O had 22 iti.vuluiiio. The lieiirl iiiu.*.i-le wu?. full of 4-niv.-striiitoil llbrils.
•
i 1 1 » il
II
i\
J I
Km. S. — A niiiiiTu ilrauiiiK from Ihe heart of an eiiibivo in wliiili the tcneli M.mili' was just Kiii. fi.— Ciliiieni ilrawiliif "f a »nnill |.iirliim iif a few nliril« tn .hmv
i^Hii|ilFtr<l. The riuik-i mi-ii- lielow the kiirlarv uikI their pre~eri(e i. only ^liKhtl.v indicated. the different wiillh iif «liril» found in u given region •>! Ilie li.ad
Z.nker without aiili. uri.l pins a few ilr.ip, .,( i prr twit o»mic aiid. I'nstaiiied. Z^l^» No. S oc. nniM-le ..f a dii.k i-nil.ryo ..f 1.', wmiiU-s.
and 2 mm. lelu.
Kl... 4.- A laii.rra .|ra»init nf a (.« •! in. ii....
were more fibriU pro*«nt lliaii are Khown m the dr.
oc. and i mm. Ien>.
..i oi II,. M...,i .,1 the «mbr>o ..1 1 ..; J There
dliuji « 4ibove. MrtinefJ with lron-heniatuA>hu. jCciu No.
June, 1919]
179
fibrils upon fixation. Whether these fibrils became crossstriated, varicose, or smooth, or whether they were broad or
narrow, depended entirely upon the treatment to which they
had been subjected.
Stained preparations were much more ditticult to control.
Many of tlie stains ditfused across the cross-striation ; in other
eases, much of the substance of the cross-striation, but not of
the fibril, was dissolved out in the process of dehydrating and
staining. The unstained preparations were so satisfactory
that little experimenting was done with stains. Fig. 4, however, is drawn from a preparation successfully stained with
iron hematoxylin.
The embryo was occasionally mounted in a drop of Locke's
solution and the fixing solution permitted to penetrate under
the edge of the coverslip. By this means the formation of the
fibril eould be observed under the microscope. In this way it
was found possible to control the phenomenon and to produce
various types of fibrils at will, thus showing that the form
assumed is due to factors present during the fixation of
some substance in the muscle tissue.
From the above it may be seen that by tlie use of Zenker's
solution (without acid, and with the addition of a little osmic
acid) and fixing with the muscle slightly extended, completely cross-striated fibrils are formed in the heart of the chick
embryo at the early age of 10 myotomes. Many of the discrepancies of opinion shown by the above-mentioned writers
were evidently due entirely to the lack of extension of the
heart muscle, while others depended upon the fixing solution selected.
CROSS-STRIATIOXS
The simplest method of designating these cross-striations
seemed to be the dark band, the light band and the gray band.
When the wing muscle of the house fly was fixed side by side
with the embryo heart, there was a marked resemblance between
the pattern of the cross-striations of the two tissues. Text Fig. 1
Dark
LioKt
Dark
z
J
Q
Q
J
z
m KroLvjLsels (nemurcLn.e.
^= ^arcou-c, SubstQ.rv.ce.
tvijool irx.e_
Tkxt Fio. 1. — A diaj^ammjitir re|)re^entAtion o( the pattern of the crowi-iitriati«ii»
found In the heart mu«-le of the rhirk embrj'o of 10 domlten. The temis used to
indicate the different partjt of the rross-striationa are placed opposite the part.
shows the manner in which the various terms used by other
observers may be applied in these observations. The most pronounced part of the cross-striated pattern was the light band.
This band was lighter than the cytoplasm and probably was
composed of some substance which upon fixation did not
become as dense as that of other portions of the cell. The dark
band was much darker than any other structure of the cell and
was probably quite dense. The gray band was practically the
same as the cytoplasm. The dark band was never seen without
the adjoining light band on each side. In certain rather round
cells the fibrils could not be found, but the dark and light
bands wefe present and sometimes appeared to be scattered
dark granules of uniform size, surrounded by a light area.
From Congdou's figures it might be supposed that what was
present in his material were not hexahedral compartments,
but some such appearance as this. In his Fig. 2 the dark band,
or granule, and the adjoining light bands are so spaced as to
require little imagination to form them into such cross-striated
fibrils.
Occasionally the cross-striations extended entirely across a
cell without the presence of fibrils. These cross-striations were
meager in depth and difficult to focus. The gray band was not
noticeable as a special structure, but the regular space between
the two light bands indicated its presence. The dark and light
bands, however, were striking contrasts to other parts of the
cell. Their appearance remained practically the same wherever found. The whole cross-striated fibril retained its characteristic appearance, whether widely spread out or only a
narrow thread (Fig. 4).
The observations described above are based entirely upon
fixed material. They show that the completely cross-striated
fibrils can be demonstrated to be present at an age younger
than that found by any other observer and also that they are
already present at the time when these observers describe
the presence of certain granules, threads, etc., from which
tlie cross-striations are supposed to be derived later.
The presence of some substance which coagulates to form
fibrils has been shown by Lewis (1919) to be characteristic
of the smooth muscle, the heart muscle and the skeletal
muscle. The same phenomenon is exhibited by these young
embryos; t. e., fibrils form upon fixation in the smooth muscle
of the amnion, in the heart muscle and in the skeletal muscle.
In all probability the cross-striations are laid down in the
heart muscle-cell coiucidently with the diiferentiation of these
cells to form the muscle layer around the heart. This substance coagulates to form fibrils. It increases in amount in the
cells during the development of the heart, with the result that
the cross-striations become clearer and clearer, and the number
of fibrils which can be caused to fonu becomes greater. With
the increase in depth of tliis material along the surface of the
miscle-cell the pattern of the cross-striations becomes less
readily distorted upon the formation of the fibrils. Since it
can be demonstrated by one procedure that the fibrils are
completely cross-striated from their first appearance it is
logical to assume that other methods fail to preserve these
structures in their early form. For this reason, it is not necessary to discuss which theory so far advocated as to the origin
of these interesting bodies is correct.
LIVING HEART MUSCLE TISSUE
Needless to state, the various aspects presented by the heart
tissue as descril)ed above, including those observed by the several investigators mentioned, do not correspond to the appearance of the living tissue. This might readily be surmised
if for no other rea.son than that one is dead and the other
living. When preparations are made by the same method as
that specified herein, except that in place of a fixing solution
180
[No. 340
a drop of Locke's solution is used, very thin living hearts are
obtained and these continue to contract for an hour or longer.
The most noticeable feature of such tissue is the complete lack
of fibrils of any type.
The muscle-cells are not spread out into a flat layer as in
the fixed preparations, but remain rather round or spindleshaped, and because of this it is very difficult to determine
whether there are processes between the cells or not. Certainly,
the cells do not appear to form a marked syncytium.
In these observations on the living heart several embryos
with 11 myotomes were studied, and as many as six of each
of the different ages of older embryos (12, 15, 18, 20 and 22
myotomes). The muscular tissue of the hearts of embryos of
from 12 to 15 myotomes appeared to be essentially the same.
In that of older embryos trabeculse began to appear. The cell
walls were distinguishable in places. Sometimes only a single
cell in a given field showed contraction. Again, all the cells
of a given region took part in the same contraction. The
continued movement of the cells made it difficult to trace their
individual boundaries. The tissue of the heart of older embryos (from 15 to 22 myotomes) appears to be more syncytial
in nature. No preparation of a living heart was obtained in
which contraction did not occur. The movement of these
muscle-cells takes place so rapidly that it is almost impossible
to be certain of the actual occurrences during the phenomena.
In none of .the hearts observed (about 50) was there any
evidence of a slowing of the actual contraction. The rest
periods became longer and longer, the number of contractions
fewer and feebler, but the last contraction that took place was
as rapid as any of the previous ones and in every case relaxation occurred after each contraction, even the last one. Rigor
mortis was not observed.
MYOFIBRILS
No structure resembling the fibrils of the fixed preparation
was present in the living heart muscle at any of the ages
studied. In fact there were no long threads of any kind, not
excepting the mitochondria. The latter did not extend farther than past the region of the nucleus, and were never seen
to extend from one end of a cell to the other, or to pass from
one cell to an adjoining cell. Certain preparations of pieces
of the heart of four- to six-day embrj'os were used for comparison. No fibrils could be found even in this older heart
muscle.
MITOCHONDRIA
The mitochondria were very abundant in the heart-muscle
tissue of embryos of all stages up to four days' incubation.
They exhibited active movement, bending, twisting and traveling in the cytoplasm. The most frequent forms were those of
threads and rods. The longest filament, however, never extended the length of the cell. The long axis of a mitochondrium usually coincided with that of the cell. In round or
only slightly spindle-shaped cells, the mitochondria seemed
to lie in almost any direction. The outer cytoplasm of the cell
was not invaded by these bodies.
When the heart of a 30- to 48-hour chick embryo was injected with Locke's solution, to which janus green has been
added, and the preparation then mounted in a drop of the
same solution, the mitochondria in the muscle-cells became
stained. In such stained preparations the mitochondria appeared as bright blue threads, rods and granules. Certain portions of a mitochondrium occasionally stained more deeply
than the remainder. There were no elongated blue threads,
either smooth or varicose, extending the length of the cell.
NEUTRAL RED GRANULES
Preparations stained with neutral red in the same manner
as that described above for janus green contained few small,
red granules. When such a preparation was sealed with vaseline and kept under observation many red-stained bodies appeared in the cytoplasm. Similar bodies were observed in
a few unstained preparations which had been kept under
observation for a long time. The stained bodies were mostly
in the form of round vacuoles, with one or more deeply stained
granules; a few active pink filaments, with darker granules,
were sometimes observed. Owing to their accumulation in
such sealed preparations these neutral red vacuoles appear to
resemble the neutral red bodies supposed by W. H. Lewis
(1919) to represent waste products of the cell.
CROSS-STRIATIONS
The cross-striations are difficult to observe, either in the
hearts of young embryos (11 to 18 myotomes), or in those of
older ones (two days), without the most careful search. The
most active cells contain the cross-striations as parallel bands
of light and dark material. They extend only so far as the
surface of the cell is in the plane of focus, becoming lost as soon
as the vision penetrates below the surface. They may consist
of only five or six parallel bands, or of as many as 10 or 12,
again depending upon the plane of the surface. This is quite
different from the fixed material, in which the cross-striated
fibrils extend for long distances within the field of vision.
In a few regions, such as along the side of the trabeculaj, the
cross-striations can be readily distinguished. Here they are
arranged in the characteristic pattern, i. e., dark band, light
band, gray band, light band and dark band.
The cross-striations were most readily observed in the living heart by the aid of janus green. In such muscle tissue
they appear frequently as a blue band with an adjoining light
band. These were either close together or separated by a space
where the gray band was indicated. The blue band was undoubtedly the dark band stained with janus green. In preparations which had been stained for some time the material
between the two light bands (the gray band) also became
slightly blue. In no instances were the cross-striations of the
living material as marked as in the fixed preparations. This
was largely due to the fact that they were never drawn into
thicker bundles, i. e., fibrils, but remained spread out over
the surface of the cell.
Jl NE, 1919]
181
SUMMARY
Thus it is st-eii that in the liviii-r irll cross-striations an
|)rest'iit. hut not filirils. The cross-striations art- very tliin l)an<ls
on tlie surface of the cell. They extend across the cell and
are never in the narrow threads or lihrils. The fixation of
the cell causes the formation of the surface layer into fihrils
in which the cross-striations are drawn toj;ether into dee]ier
bundles and thus hei-oine evident as shar])ly marked structures.
In places where the pull on the surface of the cell is such that
the latter is not coajrulated into (ihrils, the cro.ss-striations
remain spread out as thin hands across the cell (Figs. 2 and 4).
The comjjlete cross-striations are present in the muscle of
the heart of very younjr emhryos (10 myotomes) much earlier
than was su|)posed hy other ob.servers.
The physifdojrists have endeavored without success to formulate a theory, based upon the myofibrils, to account for the contraction of the muscle-<'ells. It is not surprising that such
a theory has not proved satisfactory, at least in regard to the
heart muscle, since the structure u|)on which it was ba.sed is not
a part of the living heart-muscle cell, hut only of the dead cell.
In other words, a cell containing the structure upon which it
was attempted to huihl the theory is not capable of undergoing contraction.
LITERATI-RE
Bruno. G. : 1918. La struttura del miocardio dell 'embrione di
polio air inizio della sua funzione contrattile. Monitore Zool. Ital..
XXIX. 53.
Congdon, E. D.: 1918. The embryonic structure of avian heart
muscle with some considerations regarding its earliest contraction.
Anat. Rec. XV, 135.
Duesberg, J.: 1909. Ueber Chondriosomen und ihre Verwendung zu Myofibrillen beim Hiihnerembryo. Anat. Anz.. XXX IV.
123.
Idem: 1910. Les chondriosomes des cellules embryonnaires du
poulet, et leur role dans la gen^se des myoflbrilles. .Arch. f.
Zellforsch.. IV, 602.
Godlewski. E.: 1902. Die Entwickelung des Skelett- und Herzmuskelgewebes der Saugethiere. Arch. f. mikr. Anat.. LX, 111.
Heidenhain. M.: 1899. Beitriige zur .\ufklarung der wahren
Wesens der faserformigen Differenzirungcn. .\nat. .Anz., XVI, 97.
Jordan, H. E., and Ferguson. J. S.: 1916. Textbook of Histology. New York, p. 95.
Kurkiewicz, T.: 1909. Zur Kenntnis der Histogenese der Herzmuskels der Wirbelthiere. Bull, intern, de I'acad. des sciences de
Cracovie, p. 148.
Levi, G.: 1916. Migrazione di element! specifici dlfferenziati in
colture di miocardio e di muscoli scheletricl. Arch, per le Scienze
.Mediche. XL. 1.
Lewis. M. R.: 1919. .Muscular contraction in tissue cultures.
Contributions to Embryology 35. Pub. 272. Carnegie Instit. Wash
Lewis, \V. H., and Lewis. .M. R.: 1917. Behavior of cross
striated muscle in tissue cultures. .Amer. .lour, of Anat.. XXII. 169
Luna, E. : 1913. Sulla importanze dei condriosomi nella gene!-i
delle mioflbrille. Arch. Zellforsch.. IX. 458.
Meves, F.: 1908. Die Chondriosomen als Trager erblichcr Anlagen. Arch. mikr. Anat., LXXII, 816.
Mlodowska. J.: 1908. Zur Histogenese der Skelcltniuskcln.
Bull, intern, de I'acad. des sciences de Cracovie. p. 145.
Rouget. C. : 1863. .Memoire sur le d^veloppement embryonnaire des fibres musciilaires de la vie animale et du cii>ur. Jour, de
la Physiol, de Brown Sequard. t. 6, p. 459.
Schlater, G.: 1907. Die Myofibrillen des embryonalen Hiihnerherzens. Arch. f. mikr. Anat., LXIX. 100.
Wieraan, H. L.: 1907. The relation between the cytoreticulum
and the fibril bundles in the heart muscle of the chick. .Amer.
Jour. Anat., VI, 191.
SPINA HIl IDA WITH ASSOCIATI
EMBRYO 17
Hy S. T. W
TlieJoln,.^lIoi,l.-i
Human monsters at full term or in late fetal stages are .seen,
sooner or later, hy almost every i)hysician. Similar anomalies
in very young embryos, such as the one described herein, arc,
however, not so well known. Dr. Mall ' estimates the frequency
of full-tenu monsters as ."JO to every 5000 pregmmcics and
gives a resume of the ])rotocols of 7."> specimens showing localiw*! anomalies (which he regards as the forerunners of monstx'r
formation) found among 1000 specimens in the Carnegie
Colle<'tion of Human Kmbryos. This particular embryo (N'o.
1961, Carnegie Collection) is, however, of especial interest
in view of the fact that, although having a nu-nstrual age of
only 79 days, it pn-sents ahnornuilities of brain, spinal cord,
viscera and skeleton, generally suppo.sed to be characteristic
' Mall, F. P.: On the frequency of localized anomalies in human
embryos and Infants at birth. Amer. Jour. Anat.. 1917. XXII.
49-72.
:i) DISTruHANCES IN A HUMAN
MM. LONG
M.I.IS C'l 1,1,.
)/v Miilirnl Schoul
only of much oldir monsters. The cliiiiial history is hrielly
asf.dlows:
Parents white. Mother 42 years of age; has had five pregnancies,
two of which ended at term, one child living ( 14 years), the other
dying of "inanition." The third, fourth and fifth pregnancies
terminati'd In abortion, the last furnishing the specimen under
discussion. The last menstrual period began on August 19, 1917,
and lasted four days; abortion look place on Novemlier 6. As
both parents were very anxious for another child the possibility
of mechanical interference may be excluded. There Is no history
o[ venereal disease. The only clinical symptoms which the woman
presented were severe nausea and vomiting Immediately before
and during the abortion.
The gross appearance of the specimen is shown in the figure
on p. 182. reference to which will emibic the reader to under-tand better the following description. This is based upon
^1 i)reliminary c.vaniination with a binocular microscope, supple
182
[No. 340
iiieiiti'd by exaniiiiatiini under liiiiiuM- powers of serial sections
tlirougli the cinbryo.
As seen in the \eiitral view, the enihryo is normal above the
level of the eyes. The latter are synmietrieal, except that the
left eye is placed slightly higher than the right. Microscopically, the lens of each eye is found to be hollow, the retina
and choroid nuicb macerated, and pigment is scattin-ed
throughout the vitreous. The e.xternal nares are represented
by two pin-point depressions asymmetrically placed, and the
lateral nasal processes are but feebly evidenced. The mouth
is of normal width and in correct proportional position. It is
gaping, however, and an enlarged tongue can be seen. The
medial and lateral palatine processes are likewise visible. The
ears show a well-marked helix, with no evidence of the original
tubercles. There is a Tuint antitragus, and the primordium
of the crus helicis can lie distinctly made out. Microscopically,
the external auditory meatus and the Eustachian tube were
Spi.na Bii IDA wrrn A.s
!)CIATED DlSTUKHANCES I.X A HU.MAX EmiiKYO
17 .MM. Lo.NG.
traced in section, but nothing could be made of the labyrinth.
Taken as a whole, the face represents a development considerably in advance of that noted in the oldest of the human embryos described by Rabl in his " Entwicklung des Geschichtes,"
which measured 14 mm. vertex-ljreech. and was estimated to be
36 or 37 daj's old. The face aaid ears, in comparison with
other embryos in the Carnegie Collection, represent rather
closely a stage of development corresponding to that of a
normal embryo of the same length. Such embryos, according
to the Mall curve, are about seven weeks old. From the degree
of development of the head we may safely assume that 49 days
is the maximum develofimental age of this specimen. The
discrepancy between this and the menstrual age, namely, 30
days, undoubtedly represents the length of time the embryo
remained in the uterus after its death.
The arm buds .show the transverse lines of division, and the
contour lines of arm, forearm and hand. The hand pad .shows
the rays for five fingers, but progress toward digitation is not
marked. Except for this, the arms correspond to the normal.
The legs are disproportionately .short for the general stage of
development of the embryo, the foot pad showing practically
no indi(ation of beginning digitation. Study of the sections
shows that the cartilaginous sbouldcr and pelvic girdle are
normal, but there is some stunting of the tarsals, metatarsals
and phalanges of the foot pads.
There is a small genital tubercle behind which the clt^acal
membrane has disappeared, leaving the sinus patent. The tail
bud has been absorbed until only a blunt coccygeal eminence
remains. There is some slight indication of a urethral furrow,
whereas, according to the tables of Keibel atid Elze, this should
be *' fairly deep " in an embryo of 17 mm.
Practically the whole ventral wall of the abdomen has
undergone pathological changes, sloughed or been torn away,
leaving the abdominal +++++
CONTENTSs exposed. The viscera of thorax
and abdomen show extreme maceration and histolysis, but
their main outlines are well in evidence. In sections the
alimentary canal may l)e readily made out : the mouth,
pharynx, cesopliagus, stomach, duodenum and coils of gut
can he followed throughout their length. The larynx, trachea,
main bronchi and macerated portions of the lungs could also
be followed through the sections. The heart has suffered in
the general maceration, but one chamber for auricles and one
for ventricles can be clearly made out. The bulbus and first
part of the aorta were traced, iiut no vessel was found leading
from the latter. The liver was in a state of extreme maceration,
but masses of liver tissue could be traced in sections, and also
some vascular attachments connected with them.
The mesonephros is fairly well preserved, and there are
discrete masses of badly macerated tissue occupying the positions where the suprarenals should lie. No evidence of a
liladder or any of the urogenital ducts can i)e found. The same
is true of the spleen and pancreas. There is widespread destruction of . the vascular system; not even the main vessels
can be traced with any sort of continuity.
From the dorsal aspect the most striking feature is the apparent failure of the medullary plate to close, a fact whicli was
confirmed by microscopical examination. Caudad to the upper
cervical region, and extending throughout the thoracic,
luntbar and sacral regions, are two parallel rows of spinal
ganglia on either side of the mid-sagittal plane, with discrete,
scattered masses of nervous tissue between. Contrary to gross
appearances, none of this tissue is naked, but all of it is covered by loose cellular tissue, undifferentiated and of irregular
thickness. There is no trace of closure to form a cord. In the
cephalic region as far back as the level of the eyes, closure
seems to have taken place, and sections prove tliis to be the
case, as the macerated remains of two cerebral hemispheres
and a brain stem, covered with the same loose cellular tissue,
are to be made out. The whole region, however, presents an
irregular, bulging appearance indicative of an embryonic encephalocele. Meninges could not be found for the brain or
other tissue of the central nervous system. In the region of
the vertex there is a breach of continuity in tlie cranial vault,
giving rise to an opening into the cranial cavity. This o])ening, upon a study of the sections, ajipears to be traumalic or
the result of sloughing.
Twelve ribs and 30 verteVira' could be counted in sections,
the latter with ditlicnltv, owint;- to the fusion and twisting
June, 1919]
183
of various centra. As determined from the sections, the vertebral axis shows the following points of interest : In the upper
two-thirds of the back tliere is a deep cuneiform cavity, and
exactly corresponding to this region is a very pronounced
lordosis of the column. The middle of this region of lordosis
marks a pivot point about which the posterior half of the
vertebral column is twisted sharply to the right. In this way
the ribs on the right side and the spinal ganglia are crowded
together and appear in successive sections at the bottom of the
depression. They are covered with loose cellular tissue. Tiic
cavity is due to the lordosis. In the region of the sj-mmetrical
depressions there is likewise a lordosis, and between these and
the cavity the column is bent in the opposite sense — t. e., there
is a slight kyphosis. The vertebra? show little or no evidence
of neural processes, and of course no mcmbrana reuniens.
Technically speaking, therefore, we have an eml)ryonic rachischisis and partial aniyelia. Owing to the maceration and poor
staining, the details of the chondrocraniimi could not 1)C made
out.
If due allowance is made for the extensive maceration,
most of which probably occurred in xdero after the death of the
embryo, we arc perhaps justified in asserting that the chief
point of patliological attack lay in the axial skeleton and
central nervous system below the brain. At any rate, it is here
that we find its most important result*. There is some stunting of the arms and legs, but not sufficient to be of any great
significance, except that, had the viscera been early and
seriou.sly attacked, it is difTicuIt to see why greater nutritional
damage did not effect the extremities; for in spite of the fart
that its aliment is furnished by the mother, the embryo must
of necessity possess a correlated metabolism of its own. There
is nothing to indicate that the viscera did not develop in a
fairly normal way: at least the state of maceration docs not
suggest the contrary.
From the menstrual histories found among the records of
the Carnegie Collection of embryos, it is more than probable
that most of the pathological specimens are aborted witliin the
first half of pregnancy, and, Uierefore, particularly if very
young, their significance frequently escapes the notice of the
j)ractitioner. It follows that, in those cases in which the
pathological involvement is not sufficient to cause the death
and expulsion of the embrj'o, the latter will sur\ive until the
term or near term, and it is upon this limited group that tlie
popular idea of the frequency of monsters is based. In the
" Manual of Human Embryologj'," Dr. Mall has tabulated
the comparative frequency of various types of monster formation at term and in aborted material, and finds a close parallelism between the two. The percentage of frequency of spina
bifida is greater in the embr}o, however, than at birth, indicating that the mortality is greatest in this variety of monster.
A more careful examination of abortion material in the future
will probably reveal numerous specimens like the one here
reported.
That the cause of such conditions exists early in pregnancy
is splendidly shown in tlie specimen above described. As
pointed out by Dr. JIall, the popular conception that mechanical influences have an important bearing upon the formation
of monsters has been ovcrthrowni by recent chemical experiment*. The specific action of dilute salt solutions upon amphibian eggs, for instance, will produce spina bifida in a large
proportion of the embryos. The trouble would seem to lie,
therefore, not in the ovum iteelf. nor in the external mechanical influences acting upon it at a later date, such as amniotic
bands which compress the imibilical cord, but rather in the
impairment of nutrition associated with faulty implantation,
or in the toxic influences arising from a diseased uterus.
BOOKS RECEIVED
United Statrs Army Xray Manual. Authorized by the Surgeon
General of the Army. Prepared Under the Direction of the
DivlBlon of Roentgenolog>-. 219 Illustrations, 1918. 12°. 506
pages. Paul B. Hoeber, New York.
United Btatet. Department of Commerce. Bureau of the Census.
Financial Statistics of cities having a population of over 30,000. 1917. 4°. 373 pages. 1918. Government Printing
Office, Waahlngton.
United (Stairs. Department of Commerce, Bureau of the Census.
Birth Statistics for the registration area of the United States.
1916. Second annual report. 1918. 4'. 96 pages. Government Printing Offlce, Washington.
United States. Department of Commerce, Bureau of the Census.
Financial Statistics of States. 1917. 4°. 129 pages. 1918.
Government Printing Offlce, Washington.
Oxford Loose-Leaf Surgery. By Various Authors. Edited by F. F.
Burghard, and Alien B. Kanavel. In Ave volumes. Over 1800
illustrations. Vol. I. 1918. 8'. 971 pages. Oxford University Press. London; American Branch, New York.
Practical Physiological Chemistry. A Book Designed for Use in
Courses In Practical Physiological Chemistry in Schools of
Medicine and of Science. By Philip B. Hawk, M. S.. Ph. D.
Sixth edition, revised and enlarged. With two full-page
plates of absorption spectra in colors, four additional full-page
color plates and 18.S figures, of which 12 are in colors. 1918.
8°. 661 paRPs. P. Blaklston's Son & Co., Philadelphia.
The Hearts of Man. By R. M. Wilson, M. B. 1918. 12°. 182 pages.
Henry Frowde and Hodder & Stoughton, London. Oxford Uni.
verslty Press.
I nited Stales. War Department. Annual Report of the Surgeon
General, U. S. Army, to the Secretary of War. For the Fiscal
Year 1918. 8°. 735 pages. Government Printing Offlce,
Washington.
fnited States. Treasury Department. Annual Report of the Surgeon General of the Public Health Service of the United States.
For the Fiscal Year 1918. 8°. 373 pages. Government Printing Offlce, Washington.
184
[No. 340
THE MANUS MEDITATIONIS
By Charles Singer, Oxford
Man alone among animals knows that he must die, and
civilized man alone among the races of men. Yet we moderns,
with all the discoveries of science, all the complexity of
our social system and all the wonders of past history crowding
thick upon us, certainly ponder far less than our forefathers
upon our inevitable end. With the men of the Middle Ages
it was far otherwise. Their present world was a small thing
compared to ours and but a vestibule of the life to come. Mors
jamia vita. It was upon the life after death that their
thoughts were fixed and upon death as its portal. Death was
their obsession, and there were whole classes of men whose
current thoughts were of little but death and thereafter.
Every possible device was invoked to keep death ever before
the mind.
But the physician spends his life in a contest which he must
always lose at last and for which life is the forfeit. He, at
least, hardly needs to be reminded of the temporary character
of this life. Yet not so, thought our ancestors. They did not
hesitate to insert a memento mori even in a medical work.
Among the means adopted to keep mortality before men's
eyes was the manus meditationis, a method of illustrating,
by a tale of the fingers, the thinness of the partition that
separates the living from the dead. The manus meditationis
that we here reproduce was inserted by some fourteenth century scribe in a very valuable and interesting collection of
illustrated medical tracts now in the Bodleian Library. The
phrases are written along the five fingers of the hand, a phrase
for each phalanx and a terminal one for the nail. The phrases
form rough but not unmusical verse.
TEXT
Manus MEDrrAcioNES (sic!)
(1) Nescis quantum | Nescis quotiens | Quod deum offendisti
(2) Finis tuus amarus est | Uita tua breuis est | Uenisti in hunc
mundum cum peccato | Quod status tuus est miserabilis
(3) Nichil tecum afferes nisi quod fecisti | Uitam tuam non potes
prolongare | Mortem non potes evadere | Quod morieris
(4) Nescis quo deuenies | Nescis qualiter morieris | Nescis ubi
morieris | Quod hora mortis incerta est
(5) Cite obliuesceris | Quos relinquis parum facient pro te | Raro
facient pro te | Quod post banc uitam non est penetencia
fructuosa
Meditari debes.
TRANSLATION
In rendering a translation of this simple text we would call
attention to the use of the word facient in line 5. Facere has
sometimes in mediseval Latin the special sense of " to make a
prayer," " to say a mass," or simply " to pray " — Orare est
laborare.
The Hand of Meditation
(1) For that thou Itnowest not how greatly or how oft thou hast
offended God,
(2) For that thy end is bitter and thy life short, for that thou
earnest with sin into this world and thy condition is
miserable,
(3) For that thy deeds alone thou canst take with thee, for that
thou canst nor prolong thy life nor escape death, for die
thou must,
(4) For that thou knowest not whither thou goest nor place nor
time of thy deatli, for the hour of death is uncertain,
(5) For that soon forgotten thou wilt be, for that it is but little
and seldom that thy relicts will pray for thee, and for that
after this life repentance availeth nought,
Therefore meditate.
The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by the LORD BALTIMORE PRESS, Baltimore. Subscriptions. ?3.00
a vear (foreign postage, 50 cents), may be addressed to the pubUsherg, THE JOHNS HOPKIKS PRESS, BALTIMORE; single copies will be tent b»
moil for flfty cents each. Single copies may also be procured from the BALTIMORE NEWS CO., Baltimore.
BULLETIN
OF
THE JOHNS HOPKINS HOSPITAL
Entered ma Second-Class Matter it the Baltimore, Maryland, PostolHee
Acceptanee (or mailing at special rate a( postage provided (or in Section 1103, Act o( October 3, 1917. Authorized on July 3, 1918.
Vol. XXX— No. 341]
BALTIMORE. JULY, I9I9
[Price, 50 Ce nts
CON
PAGE
Some Memories of t!ie Development of the Medical Scliool ami
of Osier's .Ailvint.
By Henky .M. Thomas ISo
Osier as Chief of a Medical Clinic.
By Lewellys F. Barker ISO
.Some of the Karly Medical Work of Sir William Osier.
By W. T. CoU.ncilman 103
Osier as a Pathologist.
By William (i. MacCali.tm 1!'7
Osier, the Teacher.
By W. S. Thayer lliS
Osier and the Student.
By Thomas R. Brow.n 200
Osier and Patient.
By Thomas McCbae 201
Osier and the Tuberculosis Work of the Hospital.
By Louis Hamman 202
Influence on the Relation of Medicine in Canada and the United
States.
By Thomas B. FrTciiEn 204
TENTS
PAGE
Dslcr as a Citizen and His Relation to the Tuberculosis Crusade
' in Maryland.
I By Henry Barton .Iacods 205
J Osier's Influence on Other Medical Schools in Baltimore. His
1 Relation to the Medical Profession.
By Edward X. Brush , 208
Inlluence in Building up the Medical and Cliirurgical Faculty.
' By Hiram Woods 200
Osier and the Book and .lournal Club.
' By J. A. Chatard 211
Osier's Influence on the Library of the Medical and Cliirurgical
Faculty of the State of ilaryland.
By Marcia C. Xoves, Librarian 212
I Some Early Reminiscences of William Osier.
[ By He.nry M. Hurd 213
I Osier as I Knew Him in Philadelphia and in the Hopkins.
By Howard A. Kelly 21,">
Osier ns a Bibliophile.
By Thomas R. Boogs 210
Osier's Literary Style.
I By Edward X. Brush 217
Bibliography 210
SOME MEMORIES OF THE DEVELOPMENT OF THE MEDICAL
SCHOOL AND OF OSLER'S ADVENT
By IIenuy M. Thomas
In thinking of tlic early days of The Jolins Hopkins University and IIosj)ital and the development of the nicdital
school, my memories begin with the founder — Johns Hopkins.
As a small boy lietween 10 and I'i I sat on the same beiu h with
Johns Hopkins many Sunday mornings at the Friends' Meeting on P^utaw and Monument streets. I cannot remember that
he ever spoke to me, and I remember him merely as a rather
unkempt old gintlcninn. At that time he liad announced his
intentions for his double bequest, had, in 186t^, incorporated
the two institutions that were to Ijear his name, had niijiointed
his trustees, and had lujught the site for the hospital. Calloway Cheston. the president of the university board : Francis T.
King, president of the hospital board ; Francis White, James
Carey Thooias. James Carey, and other trustees, were also
constant attendants at tiie meeting, and it is pleasjint now to
think that in the congregation there were represented tlie
founder, his trustees, and the rising generation which was to
be benefited by tho bequest.*.
Johns Hopkins believed that his wealth had been given to
him for a purpo.-^-, and, to use a Friendly form of speech, that
he would bo " given to see '' how to dispose of it. He had asked
atlvice freely and much had lieen volunteered, and many of his
advisers have claimed that they suggested the objcct-s of his
Ix-quests and the forms which they should take, but 1 like to
think that the wise instructions that he gave to his trustees
were finally determined in meeting. The most important of
these for the development of the medical school was his direction in a letter to the hospital board, dated March 10, 1873,
186
[No. 341
that '' iu all your arrangements in relation to this hospital you
will bear constantly in mind that it is my wish and purpose
that the institution shall ultimately form a part of the medical
school of that university for which I have made ample provision by my will," so uniting forever the two bequests for the ,
furtherance of medical education.
Johus Hopkins died on December 24, 1873, and iu the early
part of 1875 the trustees received the bequests and entered into
active administration of the trusts. The first important decision of the university board was the wise and fortunate choice
of Daniel C. Oilman as president of the university. He came
to Baltimore May 1, 1875, and I can remember well the expectation and interest his coming aroused. He and his two
daughters took apartments at the old ilt. Yernon Hotel, and
for me a delightful friendship began.
Johns Hopkins chose his trustees well and left them untranuneled, and they in their turn gave President Oilman a
free hand. They had already determined upon the establishment of a real university, which, as Oilman once said, was to
supplement and not supplant existing institutions. In speaking of his first instructions which he received from the trustees,
he says:
Often in private conversations and in official interviews, I was
charged to hold up the highest standards, to think of nothing but
the best which was possible under the limitations of the new
establishment in a country where the idea of a university had not
been generally understood.
Iu furtherance of these objects. President Oilman, in the
summer of 1875, went abroad to visit the variotxs universities
and to consult with the leaders in education. Medical education was much in his mind, particularly the establishment of
the laboratories and courses of instruction in the fundamental
sciences which would be best fitted for the preliminary training
of medical students. The field was almost entirely unbroken,
and young men not yet 30 were selected for its cultivation —
Eowland in physics, Martin in biology, and Eemsen in chemistry. Rowland, although not then appointed to the chair of
physics, had accompanied Oilman to Europe to aid him in the
selection of physical apparatus and books. While on this
journey he found time to publish some articles in the Philosophical Magazine which Oilman, with characteristic promptness and prophetic vision, dated from The Johns Hopkins
University — the first university publications.
Oilman was inaugurated on February 22, 1876, and the
university received students and began instruction in the fall
of that year. Professor Huxley, who had taken much interest
in the proposed biological department, and who had recommended a favorite pupil of his — H. Newell Martin — as its
director, was in America and was asked to give an opening
lecture. In this lecture he spoke of the importance of biological studies, and particularly their relation to a properly
organized medical course. My father, who had selected me as
the son most available upon whom to experiment with this new
method of medical education, saw to it that I attended Oilman's inauguration and Huxley's opening lecture. I have no
recollection of the inaugural exercises, but I do remember
hearing Huxley at the Academy of Music, principally, I think,
on account of the storm of protest that followed. This protest
was directed against the emi^hasis which the new university
appeared to be giving to scientific research, especially in
biology, even the study of which was thought at that time to be
little less than impious, and was focused on the fact that
Huxley, the great champion of science, had been asked to
speak and that the lecture had not been ushered iu by prayer.
I believe that Mr. King and my father, both devoted religious
workers, were resi^onsible for this last circumstance. They
certainly were astounded by the public reaction to this entirely
consistent Quaker procedure.
Following the advice of Huxley and others the chemicalbiological course was designed, and was recommended to those
students who intended to take up the study of medicine; indeed, it was also called the preliminary medical course. It was
from the first the design of the university to establish the full
medical course as soon as the hospital should be completed,
and much thought was given to it. Martin and Eemsen were
recognized as forming the nucleus of the medical faculty.
At the opening of the fourth academic year, September,
1879, Professor Acland,then Begins Professor of Medicine at
Oxford, was expected- to give a- lecture embodying his advice
as to the proper co-ordination between the university and
hospital in the organization of an advanced medical school.
Unfortunately, on account of illness, he was unable to deliver
the address. His views, however, have been preserved in a
letter to the university and hospital authorities. How surprised he would have- been had he been told that it was from
this unborn medical school that his successor at Oxford was to
be chosen !
In the early days the university was a small, compact body,
made up, for the most part, of a young, active faculty, surI'ouuded by a group of advanced workers, called fellows, and
other post-graduate students, and a few rather over-powered
undergraduates. Every encouragement and opportunity was
given to research and to prompt publication of work accomplished. There was the closest sympathy among all the departments, and everyone knew and sympathized with the work of
the others. It was naturally around Martin that the idea of
the medical school germinated, and a more inspiring teacher
it would be hard to imagine. Besides the regular biological
courses, he gave lectures to medical students and practitioners
of the city, and graduates in medicine entered his laboratory
for special work.
The emphasis which the university had put upon men in
contrast to buildings had permitted it to function at once, and
to strike a remarkable pace in a very short time. With the
hospital it was different ; buildings were absolutely essential,
and even though Johns Hopkins before his death had instructed his hospital trustees to begin work, time was necessarily consumed in the formation of plans, so that it was not
until June of 1877 that these were adopted and the excavations
were begim.
The choice by the hospital board, in 1876, of Dr. John S.
Billings, surgeon of the United States Army, and librarian
I
THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1919
PLATE XXIII
/;^
WILLIAM OSLER IN 1906.
I'.lliili'il li) S.i.|;''iil.
1
I
JlLY. 1919]
JOHXS HOPKINS HOSPITAL BULLETIN
187
of the surgeon-general's office, as their medical adviser was
most fortunate, both as to the construction of the liospital
buildings and as to the future of tlie medical school. Dr. Billings was much in Baltimore, and his encyclopedic knowledge
of things medical was always at the service of the university
as well as the hospital. He supplemented Oilman, and made
with him a remarkable team. He was attached to the university academic staff as a lecturer on the history of medicine
and nmnicipal hygiene, although I do not think he gjue many
lectures until after the opening of the hospital.
Among the physicians who were attracted to Martin's laboratory was Wni. T. Councilman, who began work in 1878, just
after iiaving received his medical degree from the University
of Maryland, and who, after his return from Europe in 1882.
was made a fellow by courtesy, and was appointed associate in
patiiology in 1884. He busied himself about medical problems,
gave some courses in special subjects, and lectured at the
University of Maryland on pathology.
In 18T9. Wm. H. Howell came from the Baltimore City
College and entered the chemical-biological cour.«e and began
a career which was to mean much to the university and medical
School. He soon became a favorite pupil of ilartin's. and after
receiving his bachelor's degree, he was made in quick succession a fellow, an assistant, and then, in 1885, an associate in
biology, having received his Ph. D. the year before. He
resigned from the university in 1889, to return again as professor of physiology at the opening of the medical school.
I. in my capacity as experimental animal, was entered in
the university the same year, and I can well remember Howell
as the model student and also on the football field where be
made up for his light weight by the accuracy and neatness of
his tackling.
I look back ujion my course at the university witli tlie
greatest pleasure. To have been under such men as Martin,
Renisen, and Hastings in physics, to have read Shakespeare
with Sydney I^anier, and to have heard the lectures from the
noted men who were constantly coming to the university, could
not help being stimulating to a youth even though overoccupied with many athletic pursuits. It had been hoped by
tho.se of us who took the preliminary medical course that at
its completion the university would have started its medical
school, but this was not to be. The buildings of the hospital
were going up very slowly, and as there seemed no immediate
prospect of their comiiletion, we were forced to go elsewhere for
our medical in.Ktruction.
While at the University of Maryland. I attended Dr. Couik ilman's first lectures on pathologA'. and also took a course with
him in the biological laboratory in the histology of the nervous
system. We had excellent professors at the University of
Maryland, but it was the old lecture system, the only laboratories being the dis.«ecting room and a newly established
chemical laboratory. The students had practically no chance
of getting close to patients, and I was graduated without ever
having been instructed in physical diagnosis, and I received
the prize in obstetrics without ever having seen a woman in
labor I I took my medical degree in 188.5. By this time the
university was on the point of establishing its medical department. In the register for 1883-1884 it is announced that '' The
medical department of the university is soon to be organized.
Its plan is receiving the constant attention of the trustees, and
it will be made known before the completion of The Johns
Hopkins Hospital. The nucleus of a medical faculty has been
instituted as follows: The president of the university: J. S.
Billings, M. D., lecturer on hygiene: W. H. Welch, M. D.,
professor of pathology; Ira Itemsen, M. D., professor of chemistry; H. Newell Martin. M. D., professor of physiology."
In this somewhat casual way, the university announced the
epoch-making facts that it had recognized pathology as a full
university sul)ject, and had appointed Dr. Welch to fill the
chair. The first was the natural development of the university
idea in medicine, and the credit of the second has been claimed,
in a friendly rivalry between the university and the hospital,
both by Oilman and by Billings. However that may be, no
other choice now seems conceivable.
Dr. Welch's appointment was the first one that had to do
with practical medicine, and I remember my father's enthusiasm over it, for with it he felt that the university had
made a wonderful beginning in medical teaching. What a
wonderful beginning it was he was to learn later!
Welch gave his first course of lectures in Hopkins Hall in
February and ilarcii, 188G, on microorganisms in disease.
The hospital trustees allowed the university to furnish the
autopsy house as a pathological laboratory, and so the first of
the hospital buildings to be used was dedicated to the common
purpose of the two trusts. Dr. Councilman had been appointed
an a.ssociate in ])atlK)logy, and courses of instruction were
started on November 1, 188(i. Halstead came from New York
to work in the laboratory and Mall was apjiointed the first
fellow. Other students gathered, most of them graduates in
medicine, and when 1 returned from Europe at the end of the
year I joined the grou]). Those early days have often been
described, and it was, indeed, a rare privilege to have taken
part in them. As the hospital was not yet opened, the institution had to depend ujwn other sources for its autopsy material.
This was obtained for the most part from the City Hospital
at Bay View. In the reorganization of this charity, The .Tohns
Hopkins University had assumed the care of the insane, and
my father. Dr. Councilman and I were appointed visiting
physicians. Dr. Ct)uncilnian was also pathologist.
.\t this time everything seemed to point to the early opening
of the full medical school. The buildings of the hospital were
practically finislied, and there seemed to be no reason wliy they
should not be shortly opened. The university authorities were
completing their plans and Welch was on the spot. It was just
at this time that financial calamity overtook the university.
The Baltimore and Ohio lonmion stock, of which the university had nearly l.'j.OOO shares, dropped its dividend from
10 to 8 per cent in 188(i, to 4 per cent in 1887, and ceased
paying the next year; the university was struggling for life
and could not take on new obligations, so that the plans of the
medical schocd were indefinitely suspended. The hospital
income had not been affected as it was derived almost entirely
188
[No. 341
from real estate, and there had been no inroads on the capital
bj' the erection of the hospital buildings. It had, indeed,
increased, and the hospital had now become the rich member
of these organically joined twin bequests.
The time had come for the hospital to take up the work, but
for it to begin to function, men had to be found to organize
the various clinical departments. Above all, a physician-inchief had to be appointed and everything depended upon the
choice. The question was anxiously discussed by the two
boards of trustees and their advisers, and the little band of
students in the jDathological laboratory discussed the question
with critical, impotent anxiety. Now that adversity had fallen
on the university, what hope was there that the unbroken
series of phenomenal appointments could continue? Where
could a clinician be found to match Oilman, Billings, Martin,
Remsen, and Welch, and if found, would such a man come now
that the opening of the medical school in the near future was
less than probable ? We doubted, but we did not at that time
know Dr. Osier and how impossible it would have been for
him to have refused to add his strength to the endeavor to
bring to fruition the long-nourished idea of a real university
niedical school. He has given an account of his reaction to
the proposal. In speaking of Billings' visit to him in Philadelphia, he says: "Without sitting down, he asked me
abruptly, ' Will you take charge of the medical department
of The Johns Hopkins Hospital ? ' Without a moment's hesitation I answered, ' Yes.' ' See Welch about the details ; we
are to open very soon. I am very busy to-day ; good morning,'
and he was off, having been in my room not more than a couple
of minutes."
The appointment was made in the fall of 1888, and he was to
begin his service at the opening of the hospital, which was
announced for May, 1889. It soon became evident tliat
although it was easy to announce the opening day, it was quite
another thing to get the complicated mechanism of the hospital
organized and ready to function. In this emergency the hospital appealed to the university and induced Oilman to assume
the task. The work was colossal and the time was short, and it
speaks volumes for the estimation in which Oilman's organizing ability was held that no one doubted the result.
The formal opening occurred on May 7, 1889, and Osier,
with liis satellites, took his place as our guiding star. He
brought Lafleur from ]\Iontreal, Scott and Toulmin from
Philadelphia, and those of us who were able to do so joined the
ever-increasing group.
The hospital annexed Welch with his already organized
department of pathology-. Halsted was given charge of the
surgical department and the organization of the dispensary,
Kelly was brought in June from Philadelphia to take charge
of gynaecology, and in August Dr. Hurd, as superintendent,
took over from President Oilman the direction of the hospital.
The opening of the hospital was for the trustees, the faculty,
and above all for us expectant, impatient medical novices, the
beginning of the fulfillment of long-suppressed desires. For
me the reality far surpassed the fantasy of my dreams. In the
association that was to follow, which for my part was as close
as I could make it, Osier as a physician, teacher and friend,
constantly raised my preconceived ideal. Memories of this
time overwhelm me.
The dispensary was opened first and patients were admitted
to the wards from it, and Osier, surrounded by a few of us,
himself wrote the first dispensary history. Until the wards
were full he was constantly in the dispensary, organizing the
various subdepartments of medicine, for it was an unique
feature of the system that the services were continuous, and
that the various special departments were grouped under
either medicine or surgery. As it was in the early days of the
university, so it was with the hospital at the beginning.
Workers formed a closely united body. All that happened was
of interest to each of us. On the medical side Osier radiated
by his example and personality constant stimuli to careful
clinical work and investigation along all sorts of lines. He
pointed out problems, encouraged everj-one in what he desired
to do, and was more than liberal in his commendation of work
done. His absolute generosity threw open his whole clinical
material to the use of any one who had a problem. He urged
and assisted in the publication of the results, and saw to it that
the young men got the whole credit of the work when often it
should have gone to himself. Is it to be wondered at that such
a chief has such devoted followers ?
The Medical Society, the Journal Club, the Historical Club,
and other associations, were organized in quick succession.
Post-graduate courses were given, but the medical school of
the university seemed as far from beginning as ever. The
university trustees were not unmindful of the question, and
some of them in spite of the depleted income, were constantly
urging the establishment of the school. I have found among
my father's papers the notes of an earnest appeal on the subject
which he appears to have made to the Board of Trustees in
May, 1890. Certain women, several of whom were daughters
of trustees, who had from the first unsuccessfully sought admission for themselves and other women to the university, and
who had been told that it was planned to admit women to the
medical school when it should be established, collected money
and offered $100,000 to the trustees on condition that it should
be used to help the establishment of a medical school to which
women should be admitted on the same terms as men. On
October 29, 1890, the trustees made a minute accepting the
gift, nath the proviso, however, that the university should not
establish its medical school until an endowment of $500,000
had been secured, and that women who desired to enter should
receive their preliminary education somewhere else. Miss
Mary E. Garrett, who had contributed most of the original
Women's Medical Fund, completed the endowment on December 23, 1892, by a gift of $306,977. Leading up to tliis gift
there was a protracted three-sided discussion between Miss
Garrett and her friends, the Medical Faculty and the Board of
Trustees. The outlook for an agreement was often gloomy,
and only one who was in a position to know, as I was, something of the ideas of all three parties to the negotiation, can
realize on how many occasions the scheme came close to being
abandoned. In this discussion, together with Welch and
.IlLV. 1919]
189
Martin. Osier was deeply concerned. He had become very
restive uiuler the delay of the opening of the medical srhool,
complained to me on one occasion of what he called the dry
bones of post-graduate teaching, and even intimated that
unless something were done he might be forced to go wIktc
there were some real medical students.
The decision as insisted upon by Miss IJarrett. to lix permanently by the terms of the gift the conditions for admission
to the medical school at an unprecedenteil standard, required
no little courage, and although the results have abundantly
justified it. it was then thought that it would greatly limit
the number of students who would apply for admission. The
first class of IT, including three women, entered in the fall
of 1893. When, in the third year, they began to work in the
hospital, first in the dispensary and then in the wards. Osier's
genius as a medical teacher became more and more evident.
He saw to it that the students came into the closest contact witli
the patients in the dispensary, and he organized the hos|)ital
wards so that the fourth-year students took an essential part
in the management of the cases. Although this last liad been
the intention since the inception of the hospital, and the main
building had been designed to house 20 senior students, its
practical application met with opposition and presented difficulties, and it was Osier's insistence that threw open the wards
to the students, a fact, the thought of which. 1 think, always
gives him pleasure.
He did. indeed, put the students into the wards, but he did
not leave them there. He stayed with them, and if ever
medical students got clinical instruction on a university basis,
they did. It is not given to me to speak of Osier as a teacher,
for my chapter ends with the beginning of the medical school.
For me, and for others similarly situated, wlio had been reared
in the expectation of the new order in medical education, the
coming of Osier ushered in the complete realization of longdeferred hopes. He set for us a difficult goal, and helped and
cheered us on the way by his wise precepts, his kindly, friendly
commendation, his vigorous leadership, and more tlian all. by
simply being himself.
It is no fault of his that the finished product is no better,
but what good there is in me as a teacher and a physician I owe
to him, and on this, liis birthday. 1 lay it at his feet in grateful
acknowledgment.
OSLER AS CHIEF OF A MEDICAL CLINIC
Bv Lewellys F. Barker
Internal medicine, like other branches of science, though
making at all times some progress, is subject in its advance to
fits and starts, the result of unusual concatenations of events.
The ojiening of tlie medical clinic at The Johns Hopkins
Hospital in 1889 was an opportunity for helping on the science
and art of medicine that might amount to either much or little, \
depending upon its seizure. The time corresponded to the Hoodtide of natural science. Biology, physics and chemistry had
participated in the great rise. Medicine, always quick to
api)ly to its own service the results of investigations in tlie
fmidameutal sciences, had responded by estal)lishing a whole
series of special medical sciences (anatomy, histology, embryology, physiolog}', physiological chemistry, pharmacolog}', pathological anatomy and physiolog}-, bacteriology), to be studied
and taught by men who gave up their lives exclusively to their
promotion ; these sciences were to serve as a foundation upon
which a great superstructure of clinical science and art might
be built. The place to be filled, the professorship of medicine
in The Johns Hopkins University, which carried with it the
appointment as physician-in-chief to The Johns Hopkins Hospital, was in several ways unique, at least as far as medicine
in America was concerned. For, in the first place, according
to the will of Johns Hopkins, the well-endowed hospital was
designed to be an integral part of the medical school of an
endowed university, and funds were provided for salaries for
the leaders of the clinics as well as for the chiefs of other university departnu^nts, one of the circumstances that, combined
with others, led to the abandonment of the hitherto-prevailing
" proprietary medical .schools " and to their replacement by
medical schools organized as parts of great universities. In
the second ])lace, Tlie Jolins Hopkins University, through the
action of its trustees, and of its first president, Daniel C.
Oilman, had been organized, in all its departments, in the
interests of original research as well as of competent instruction; with distinguished investigators in the arts department
and with men like Jlartiu and Brooks in biology and physiology, Kowland in physics, Ecnisen in ciicmistry, and Welch
in patholog}', it was clear that capacity for personal research
and the power to stimulate others to engage in fruitful researches were regarded, along with ability to teach and to
organize, as essential requirements of the occujiants of chairs
in the university. .\nd, in the third place, the trustees of the
hospital, in consultation with the president of the university,
the professor of pathology, and Ur. John S. Billings of the
surgeon-general's library, had planned and built (out of
income from the endowment), a liosi)ital that, at the time of
its completion, offered better facilities for the organization
and conduct of clinical work than had heretofore been available in the United States. The ideals ihcrishcd in the university, the material cquii)mcnt at the hospitJil, the opportunities and possible rewards open to the clinical leaders who
might be appointed, combined to provide unparalleled places
for occupancy. If, then, for tbe.se positions clinical men could
l)e found, wlio, by native ability and experience, would measure
up to the extraordinary time and the unusual opportunities,
success in the highest sense for the new institution would seem
to be ensured. The chair of medicine is, by common consent,
the most important clinical chair in a university medical
school. For this professorship the university faculty recommended, and the trustees confirmed, the appointment of
190
[No. 341
Dr. William Osier, then engaged in teaching medicine in the
University of Pennsj'lvania and in consultation practice in
Philadelphia. A member of a distinguished Canadian family,
trained in medicine first in the University of Toronto and in
McGill University in Montreal, and, later, as a graduate student, in the clinics and laboratories of England, France and
Germany, interested and occupied in research and teaching in
histology, physiology, pathology and parasitology as well as in
internal medicine, and possessing personal qualities that even
in youth marked him as a potential leader of men, the appointee entered upon his work with an enthusiasm that was
stimulating, began to organize his department, selecting a
group of young men as assistants, and soon set an example in
practice, teaching and investigation that was contagious. The
office and the man were suited to one another. The time, the
place, and the person formed a happy conjuncture that was to
mean much for internal medicine in America and in the world.
Of the set of brief contributions here published concerning
Professor Osier's work in Baltimore, those dealing mth his
practice, his teaching, and his original inquiries are written
by others; the part assigned to me is the preparation of a
memorandum outlining the principles to which he, as the
organizer of a medical clinic, persistently adhered, and the
methods he employed in their practical application. He had
vei7 definite ideas of what a medical clinic should be and he
felt keenly the responsibility of seeing to it that the functions
of the clinic were faithfully ijerformed. For him, the welfare
of the patients who presented themselves in the clinic for
diagnosis and treatment came first; next, came into consideration how undergraduate and graduate students could best be
taught; and, finally, came solicitude that every opportunity
for contributing to the advance of our knowledge of internal
medicine should be eagerly seized. He took care to promote in
every way possible the material, the scientific, and the moral
interests of all who were associated with him in his work ; his
personal advantage concerned him but little, though to anyone
who aimed at such objects and achieved such purposes as he
did, a modicum of profit and a maximum of honor and
prestige were bound to accrue. The principles he fixed upon
and the methods he used to illustrate them were manifoldly
derived. In part they grew out of personal practical experience, in part they had their origin in other clinics in this
country and in Europe. Men who were familiar with clinical
work and clinicians in the larger centers of America, those
who had " walked the hospitals " of London and Edinburgh,
those who knew the laboratories and the clinical institutes of
Austria, Germany and Holland, and those who had visited the
clinics conducted by the best internists in Prance, had no
difficulty in recognizing the sources of certain of the features
of the organization of the medical service in Baltimore. Professor Osier's clinic synthesized diverse elements into a harmonious whole; it represented a new form, good in itself for
its time, and yet plastic enough to admit of remoulding at
later need. The limits of this article will permit of only brief
comment upon the plan of organization and upon the way it
was manasjed.
Where activities are complex, be they those of a factory, of a
business office, of a scientific laboratory, or of a medical or
surgical clinic, organization and management are two executive functions that must be properly exercised, if the work is to
be successful. Organization involves: (1) An investigation
of the conditions that exist and of the requirements of the
whole situation; (2) the planning of a scheme that will meet
the requirements, tliat will effectively and systematically correlate the activities of the working force, the materials, the
equipment and the working space, so that the functions of the
institution shall be competently, speedily and economically
performed; and (3) the actual installation of the system as
planned. Management, or the art of conducting an establishment after its organization has been devised and initiated,
involves : ( 1 ) The attainment of the results that are aimed at ;
(2) the overcoming of obstacles that are incident to the conditions under which the work has to be done; and (3) the
application of knowledge and skill in the training of the staff,
in the setting up and in the maintaining of standards, in the
providing of suitable incentives, and in the establishing of
right relationships between the leader and the led. The head
of an institution, or of a department, who creates an organization that is adequate, and who manages it with skill, demonstrates his executive capacity.
On Professor Osier's appointment as physician-in-chief to
The Johns Hopkins Hospital in 1888, he found certain conditions already exisflng that were to some extent determining,
at least as far as the general organization of the institution was
concerned. The buildings already completed included one for
general administration, -nith a building on each side of it for
private patients, a long row of public ward buildings behind, a
building for a general out-patient department, a nurses' home,
a pathological laboratory, a general kitchen and a laundry. In
other words, a " general hospital," in which medical and surgical patients (free and pay) were to be received, distributed and
treated, and in which, later on, medical students were to be
taught, had been constructed on the pavilion system. There
was no spatial concentration of the work of the single departments in separate institutes such as had already developed in
some of the European centers, or, as was later adopted in the
institutes built for psychiatry and pediatrics on the grounds
of The Johns Hopkins Hospital ; on the contrary, to pass from
some of his private patients in Ward B at the southwest corner
of the grounds to some of his public-ward patients at the
northeast corner, the internist and his staff were compelled to
walk through corridors that extended along two sides of a
square containing 14 acres ! As in most general hospitals, the
functions of general superintendency, financing, accounting,
nursing, purveying and housekeeping had been centralized,
and with them the heads of the clinical departments had but
little to do. But, thus relieved of much administrative detail,
the head of the medical department, who was appointed permanently and had a continuous service, was to have a large
degree of autonomy in the diagnosis and treatment of patients,
in the selection of his staff, in the character and amount of his
teachintr, and in the conduct of research. His staff was to con
J VIA. lit lit]
191
sist (1) of younger men who lived in tlie hospital and gave
their whole time to the department, and (2) of s^enior associates who lived outside, giving part of tlieir time to the
liospital and part to private practice. The chief of tlie medical
service was to l)e ])aid a salary in order that he might make the
work of the hospital and of the medical school his main occupation and interest, thougli he was permitted to supplement
his income and clinical experience hy private consultations.
The activities of the dilferent clinical departments were to be
correlated partly by the general superintendent of the hospital,
and partly by a medical advisory board that made reconiinondations to the trustees of the hospital. Wiien Professor Osier
arrived, the buildings, and the general plan of organization
already completed, had to be accepted as they were: the plans
of his department had to be drawn so as to fit into them.
It was fortunate that The Johns Hopkins Medical Scliool
was not opened until 1893 and that clinical instruction of
undergraduates did not begin until 1895, for six years were
thus available for perfecting the organization of tlie wards, the
outpatient department, the laboratories, the staff, the records,
the library, the hospital, the medical society, and the care of
patients in the hospital before the function of teaching undergraduates was added. Courses for post-graduate students
were, it is true, offered during this period, but the number of
candidates was small and the work was not burdensome. With
few patients at first, a small staff, and a limited amount of
post-graduate instruction, lei.«ure was given for making plans
(and for modifying them after small-scale trials in executing
them), for instituting standards, for writing a text-book that
concisely embodied the principles and practice of medicine and
that was destined to have an unprecedented distrilnitiou among
physicians and student.*, and. in general, for establishing traditions of the better sort in the clinic. With the organization
thu.s far planned and installed before the students of the
medical school entered upon their clinical work, it was a
relatively ea.sy matter to expand it and to adapt it to the functions of undergraduate instruction when the time for this
arrived.
^^'hen the definitive history of Professor Osier's work in
Baltimore is written, many details of liis analysis of the functions of the clinic, of his applications of the principle of
division of lalnir in the clinic, of his methods of selecting men,
of as.signing them to appropriate t<isks. and of motivating them
to high endeavor, and of the personal qualities through which
he exerted that profound and lasting influence upon patients,
students, assistants, and colleagues for which he is so widely
kno«-n, must be recorded. The .scope of the present memorandum will permit mention of only a few of the more outstanding features of his organization and management, of
those parts that made his clinic so successful a department of
a university teaching hospital as it is known to have been.
One important element of success in the new clinic was the
arrangement for a graded staff, particularly for a graded,
whole-time, resident staff, among the members of which the
responsihilties of the work were divided, not according to a
so-called "military type," but rather in the manner of the
so-called " composite functional type " of organization. The
professor of medicine (physieiau-in-chief to the hospital),
though giving most of his time to the work of the clinic, lived
outside the hospital, as did the associate professors who
" visited " the wards, the out-patient department, and the
laboratories. The resident physician, the assistant •resident
physicians, and the medical internes lived in the hospital and
were in close contact with the work always by day and as far
as was necessar)- also by night. The resident staff of the clinic
consisted of two parts: (1) A lower resident staff constituted
by the medical internes appointed for a single year, usually on
graduation with high standing from the medical school ; and
(2) an upper resident staff made up of the resi<lent physician
and several assistant resident physicians, usually men of exceptional promise, men who had already served as hospital internes
and who were willing to enter upon a more or less prolonged
resideat service, often of several years' duration, in order to
secure the best possible training for the " higher walks " of
internal medicine. This upper staff was chosen partly from
the lower staff, partly, in order to prevent " inbreeding,"
from members of the resident staffs of hospitals in distant
medical centers. The position of chief resident physician,
which carried with it large responsibilities and opportunities,
was a prize to be won only by men of exceptional ability, extensive experience, and favorable promise. Thus, those receiving it in Professor Osier's time, included Henry A. Lafleur
(1889-1891). William S. Thayer (1891-1898)," Thomas B.
Futeher (1898-1901), Thomas McCrae (1901-1904). and
Rufus I. Cole (1904-190G). The careers of these men during
their tenns of service and since illustrate on the one hand the
wisdom of him who selected them, and on the other the growthpromoting influence of the duties and authority attached to
the office. The assistant resident,*, even those who did not
later become chief resident physicians, often continued in ofTice
for several years. Such an ui)per resident staff, supported by
internes and by senior students, besides forming a whole-time
group of enthusiastic young internists for development under
ideal conditions, afforded an excellent working force for carrying on the routine of the wards, laboratories, and out-patient
department; this left the pliysician-in-chicf and his visiting
associates largely free for planning, standardizing, supervising
and controlling the practice in the clinic, for teaching, and for
promoting original iii(|uiries. The historian bent on analyzing
the conditions of achievement in Professor Osier's clinic will
do well to consider carefully the significance of this upper
resident staff.
A second characteristic feature of the medical clinic organized by Professor Osier was the introduction of more extensive
and more systematic courses of instruction in the j)racticaltechnical methods of gathering data regarding disturbances of
structure and function in the sick than had before been customary. The importance of careful hi story- taking and of
accurate physical diagnosis had been, it is true, generally
recognized : but the nnicbinery of instruction in these forms of
fact-accumulation had been inadequate in the majority of
medical clinics, and one of the first tasks of the new clinic con
192
[No. 341
sisted in planning and installing a better organization for this
purpose, and in seeing to it that the example set by all who
participated in the practical work of diagnosis in the clinic
was consistent with the methodological teaching. The most
distinctive advance made in instruction in technique was,
liowever^ the establishment of a systematic course in the application of the laboratory methods of chemistry, physics, and
biology to the study of patients. Students in their third year
of the medical school were not only taught the principles of
these methods, but for two or three afternoons throughout the
year were thoroughly drilled in the practical technique of these
methods, so that, when the course had been completed, each
student had attained to real skill in the use of all the more
important ways of examining clinically the blood, the stomach
juice, the feces, the urine, and the cerebrospinal fluid.
No medical school has yet devised a perfect system of training, and the graduates of The Johns Hopkins Medical School,
like those of other schools, doubtless exhibit certain special
defects, but by common consent, they are well-trained in the
methods of gathering clinical facts and especially in the
technical procedures of the clinical laboratory. By many it is
believed that, of the several contributions made by Professor
Osier to the organization of the clinic, the development of the
clinical laboratory and of the thorough education of students
by competent instructors in clinical laboratory work before
entering upon their duties in the medical wards is preponderant.
A third distinctive mark of the organization in Dr. Osier's
clinic was the arrangement by which each student of the
medical school became for a considerable period a member of
the group that actually did the work of the diagnosis of disease
and of the treatment of patients in the hospital. Thus each
student in his third year, after having had instruction in
history-taking and in the elements of physical diagnosis,
assisted, under the supervision and control of instructors, in
recording histories and in making physical examinations in the
out-patient department. More important still, through the
fourth year of the course, each third of the class acted successively for three months as " clinical clerks " in the stationary medical clinic, giving their whole time to the work of
the medical wards. Thus the medical staff was reinforced
during the entire school year by 30 student assistants, who,
under the eye of the resident staff, took the histories of all new
patients, assisted the internes in the making of the first
physical examinations, made all the clinical laboratory tests
on these patients, and accompanied their chief on morning
rounds. At these rounds, the clinical clerk gave orally an
epitome of the findings in the patient, watched the processes of
control examinations used by the professor, and participated
at the bedside in discussions of the pathological-physiological,
pathological-anatomical, and etiological bearings of the case.
He looked up recent articles on the subject and reported them
at later ward rounds, followed the patient to the operating
room if surgical procedures were indicated, watched the effects
of the treatment employed in the ease of each patient directly
assigned to him, and kept in touch with him during conva
lescence at his home after discharge from the hbspital, or in
the event of a fatal issue attended the autopsy and the pathological-clinical conference that followed it. The fact that
through all this he was regarded as an integral part of the
working group of the clinic, the knowledge that tlie anamneses
he registered and the results of laboratory tests he made became
a part of the permanent records of the hospital, the feeling of
responsibility he had when he realized that the diagnosis made
and the treatment instituted were based in part upon data
accumulated by him, the personal relationships established
between student and professor at the hospital and on delightful
Saturday nights at the professor's home at 1 West Franklin
Street — all this combined to make the time of the clinical
clerkship in Professor Osier's clinic a period of rich experience
and of intense stimulation, never to be forgotten by any pupil
who passed through it. Even in the more formal teaching of
the clinic, it was Professor Osier's custom to permit the
clinical clerk to have a share. Thus, at the main teaching
event of the week, the crowded Saturday clinic in the amphitheater, where all the students of the third and fourth year,
the whole resident staff, many of the visiting physicians of the
hospital, physicians of the town and medical men from a distance were assembled, the clinical clerk gave a part of the
clinic; he was always asked to tell the audience briefly (and
from memory unaided by notes) the main points of the
anamnesis of the patient and was called upon from time to
time throughout the hour to report on laboratory tests and
X-ray flndings, or to give his opinion of the significance of
some datum. The pupil-teacher thus grew accustomed to facing a large audience and to thinking and speaking on his feet,
an admirable preparation for some of the contingencies of later
professional life. The student-assistantships in the out-patient
department (in the third year) and the clinical-clerkships and
all that they implied (in the fourth year) were, then, vital
parts of the organization of The Johns Hopkins Medical
Clinic.
Though the organization of the clinic in Baltimore presented, as we have seen, an interesting combination of novel
features, no organization, no matter how well planned and
installed, can function effectively without the skilful application of the art of management, and in the art of management
the director of this clinic was to prove that he was a master.
Thoroughly familiar himself with the principles, methods and
problems of internal medicine, enthusiastic about, and for his
time well trained in, the preclinical sciences that are fundamental, he possessed that personal experience in his subject
and that superior ability that are always prerequisites to
competence as a manager and to the command of the respect of
those that are to lie managed. ' He understood human nature
and loved it, despite its faults and its frailties ; no chief ever
secured in greater measure the good-will and loyalty of his
staff. Though he could be firm on occasion, he rarely found
need to act as a strict disciplinarian. He was always cognizant
of the good qualities of those about him, and though not blind
to their defects he had learned that great lesson of suqcessful
management that, for most subordinates, a word of apprecia
THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1919
PLATE XXIV
tLlir '^'aint .IJnluit^ lluiphins Hnspital
July, 1919]
193
tion is of far greater value as a stimulus to good work than a
volume of carping critiiism. He possessed to an extraordinary
degree the capacity of making you feel tiiat lie was interested
in you and in your personal welfare ; to come into contact with
him mciuit, for most, the birth of a genuine affection for him.
He had an orderly mind and manner; he lauded punctuality
in a doctor and was always punctual himself. He seemed
never to be in a hurry and yet he wasted no time, ilany a man
recalling an interview that seemed leisurely when it occurred
has been surprised, on analyzing it afterward, to find how brief
it had been. He belonged to the first of the two groujis — tlic
" larks " and the " owls " — into which men have been playfully divided. He retired early and was an early riser. At
one time he lived for some months in tiie hospital and it is
asserted that men learned to set their watches at 10 p. m. l>y
the sound of his boots as they dropped on the floor outside his
door. His more important work was done in the morning
hours ; for him " great business must be wrought ere noon " ;
private consultations were relegated to the later hours of the
day. His power immediately to grasp the significaiup of situations, his ability to make quick decisions, his unfailing tact
and discretion, together with his wide .sympathies and his
lively sense of humor made it a pleasure to transact business
with him. His ideals he kept ever before him and was ambitious to realize them, and these ideals and this ambition
were alluring also to those whom he led. JIuch miglit be
written, were there space, of the ways in which he overcame
obstacles and met important emergencies, of the motives he
appealed to when he desired to excite men to action or to
arrive at a decision, and, in general, of thos-c traits of character
that act " directly by presence, and without means," or what
is sometimes called " jiersonal magnetism." Many of the
qualities that make for successful management, tliough easy
enough to recognize when tliey exist, arc difficult of analysis
and perplexing to tlie understanding. Some men are able to
secure control without contest; ''whether they stand or walk
or sit or wliatever thing they do," they can place men under
their power. Of such character-control and of prestige-control
Professor Osier had his full share. But, more importjint than
these, he had grasped, as it were intuitively, tiie newer principles of association and of group organization. A man of
many selves, he could enter into helpful association witli many
different groups, letting his mind interact witii the other
minds of each group for the purpose of arriving at ideas, feelings and impulses in common. Jlore than most he had learned
how to live with other men, to discuss without antagonism, to
secure co-operation by the subtle psychic process of reciprocal
penetration. In this lay the secret of his co-ordinating power.
He knew not only how to bring the various activities of his
clinic into proper relation with one another, but also how to
link the clinic with other departments of the university, with
the medical profession, with the public near and far, and
with national and international a.ssociations of different kinds.
Through his power as an organizer and as a manager Professor
Osier might, then, have trutlifully said, as did one of old, " I
magnify mine office." And it is precisely capacity for sudi
magnification of office that, along with ability to plan and to
direct, is a distinguishing criterium of the superior executive.
SOME OF THE EARLY MEDICAL WORK OF SIR WILLIAM OSLER
Bv W. T. COUXCILMAX
William Osier, the son of the Rev. F. L. Osier, was bom
in Tecumseh, Ontario, in 1849. He was one of a large family,
and his ancestors were a vigorous, long-lived race. He graduated from Trinity College, Toronto, in 1S68, began the study
of medicine in the University of Toronto, and after two years
went to McGill University, Montreal, where he received the
M. D. degree in 1872. From 1872 to 187 1 he studied abroad,
working in the various London clinics, in the laboratory of
University College, London, and in the laboratories and
clinics of Berlin and Vienna. He came in contact with many
eminent men, studied methods of work and of teaching, and
the influence of this period of European study is seen in his
after career. In 1873 he obtained the licentiate of the
College of Physicians of London, in 1878 he was made a
member of the college, and in 1884 was elected to the fellowship. In 1874 he returned to Montreal, was made lecturer
on the institutes of medicine, and shortly afterwards was
given the profes-sorship. Under the institutes of medicine
were comprised the courses in physiologA- and pathologv', the
latter limited to 20 lectures. At the end of 1874 he was made
physician to the Small-pox Hospital, and in the following year,
owing to the interest which he showed in comparative anatomy,
the professorship of helminthology, in the Veterinary School
of the University, was taken into his already full hands. I
shall discuss here only his early work, extending through the
first four years of the Montreal period.
Beyond the bare facts, we know but little of his early
education. In his various ^^Titings there are only scanty
allusions to it save in the Toronto address, in which he mentions three men who were his early teachers and to whom he
says he owes everything he has attained in life. These were
the Rev. W. A. Johnson, of Weston, Ontario; Dr. James
Bovell, of Trinity College, later professor of the institutes of
medicine in Toronto University, and Prof. Robert Palmer
Howard, of Montreal.
I have been able to learn but little of the Rev. W. A. Johnson, but it is evident that he was one of the many clergymen of
the Church of England who have sought in various scientific
pursuits a wider range of intellectual activity than is given by
their profos,«ion.* I have gained this conception of the
• The Scottish Church has produced very few of these men,
and they have been rare In America. However slnRular this may
seem, the reasons are obvious. The clerKy of the rhurrli of
England possessed a liberal education, and the taking of Orders
194
[No. 341
Reverend Johnson from two passages in the early writings of
Dr. Osier. In the first article jjublished by him (Canadian
Diatomaceae, Canadian Naturalist, 18T0) when he was a
student in Toronto, he thanks him for assistance in the use of
books and microscopical apparatus. In this article there is an
admirable description of the structure, mode of division and
propagation of the diatom, which is evidently based upon
observation. The mode of motion of the organisms is discussed and he is inclined to accept the hypothesis advocated by
Professor SchuJtze, of Bonn. At the close he gives a list of
105 diatoms which he had collected and classified, giving also
the localities where they were found and their frequency. He
must have been for a long time interested in the subject and
the organisms were collected over an extensive area. He gives
credit to Mr. Johnson for having given him several of the
specimens. He refers also to another clergj-man, tlie Rev. Mr.
Eeade, who had invented a prism by the use of which the
shell markings could be studied to better advantage, and wliich
was loaned to him by Professor Bovell. The article shows
familiarity with the microscope and capacity to use literature.
The second reference to Mr. Johnson I have found in an
article 12 years later (On Canadian Presh Water Polyzoa,
Canadian Naturalist, 1882) which was read before the Natural
History Society. There is here also an admirable description
of the organisms with the differentiation of the species, but its
main interest is in showing how early Osier — probably through
the influence of Mr. Johnson — ^became interested in the study
of nature. " In the sunmier of 1867, during a visit of my
friend, the Eev. W. A. Jolmson, of Weston, I showed him the
masses (the gelatinous aggregates of the Pectinatella magnifica of Leidy) and we agreed to subject them to examination
by the microscope, not having any idea as to their real nature.
Judge of our delight when we found the whole surface of the
jelly was composed of a collection of tiny animals of surpassing
beaut}', each of which thrust out to our view in the zoophyte
trough a crescent-shaped crown of tentacles." A fool>note
ppeaks of another clerg-jTuan, the Rev. Thomas Hincks, as the
distinguished authority on British polyzoa.
His second teacher. Dr. James Bovell, seems to have been
an interesting character. He was born in Barbados in ISIT,
went to England in 1834, studied at Guy's Hospital, and took
the medical degree in Glasgow in 1838. He then went to
did not demand any extensive preparation for the examinations.
Most of them had an assured living in pleasant country surroundings, and the dogma was simple, fixed, and did not admit of controversy. Proselyting was not actively pursued In the English
church, and the souls of their simple parishioners were not a
serious care. They must have found little intellectual stimulus
in the society of the country squires, and many of them were
perforce driven into the study of botany and other branches of
natural science. The Scottish church, on the other hand, demanded long and arduous preparation for the ministry, and most
of its members did not have the background of a liberal education. Like the Scottish character, the church was a fierce,
aggressive force, its dogma logical and uncompromising, and
its defence and extension Involved a constant controversy, which
left little time for the calm study of nature. In this country
the conflicts of the sects give sufficient intellectual diversion.
Dublin, studied under Stokes and Graves for several years and
after a severe attack of typhus fever, against the advice of his
friends, who predicted a brilliant medical career, returned to
Barbados. From there he went to Canada in 1848; took part
in the establishment of the medical faculty of Trinity College,
became Dean and Professor of the Institutes of Medicine, and
also Professor of Natural Theology. After the disruption of
this medical school he held a similar medical position in
Toronto University. In 1870 he returned to the West Indies
where he remained until his death. While there he took
orders in the English Church and published a book on Natural
Theologj'. He was regarded as an impractical, imiprovident
man, was loved by his students and friends and took great
delight in metaphysical discussions. Osier came tmder his
influence in Trinity College, and in Toronto University, and
he has dedicated to him the first pathological report of the
Montreal General Hospital. It is not improbable that, through
these two men and the atmosphere of liis home. Osier acquired
the interest in biblical and ecclesiastical literature which was
such a prominent characteristic of his later life.
The third of these men was Dr. Robert Palmer Howard,
professor of medicine in McGill University, whom Osier speaks
of as his second fatlier. He was a greatly respected teacher
and practitioner of medicine and exerted a wide influence, btit
he was not a prolific writer.
While in London, Osier published two articles from the
laboratory of University College. The first, " On the Action
of Atropia, Physostigma, and Curare on the Colorless Blood
Corpuscles," was read before the Royal Microscopical Society
in 1873, and published in its journal. Such a paper as this
was rather utiusual at the meetings of the society which were
mostly taken up with descriptions of microscopes, methods of
preparation of microscopic objects, etc. The object of the
investigation was to determine whether the antagonism between atropia and physostigma, which Fraser had shown to
exist, could be demonstrated in the behavior of colorless corpuscles under the microscope, and the result was negative. It
was interesting to find in the same volume with the paper of
Dr. Osier a long, interesting and scathing review of Bastian's
Beginnings of Life which had just appeared.
The second article, " An Account of Certain Organisms
Found in the Liquor Sanguinis," was published in 1874,
appearing in the Proceedings of the Royal Society. This
forms one of the most important of Dr. Osier's contributions
to medicine and demands a more detailed description in order
to do justice to the originality shown in this article. From
the massive literature on the subject four articles may be
singled out, each of which was an important contribution to
knowledge. In 1865, in the article of Max Schultze on the
blood, certain bodies afterwards known as blood plates were
for the first time adequately described; the second was the
article by Osier, the third by Bizzozero in 1882, in which he
gave a new method for their study and showed the part they
played in thrombus fonnation, and the fotirth by J. H. Wright
in 1910, who demonstrated their histogenesis. The name
blood plates, given to the liodies by Bizzozero, has been adopted.
July, 1919]
193
It would be difficult to say who lirst saw and described tliciu.
At this period the fresh uustaiiied blood was being actively
examined by many witli a view to the discovery of microorganisms which might be the cause of infectious diseases.
Zimmermann, in Rust's Magaziu f. d. gesannute Heilkunde in
1846, and again in Virchow's Archives, Vol. 18, I860, saw and
described the bodies as small globules which he regarded as the
elementary corpuscles from which the blood cells develop, but
his description was very vague and he did not sharply separate
tliem from other granules in tJie blood. The very remarkable
article on the blood cells by Max Schultze conceals by its title
" Ein Heizbare Objecttisch und seine Verwendung bei Untcrsuchxuigen des Blutes " (Arch. f. Mikro. Anatomic. Bd. I,
1865), tlie subject of the article much better than usually
happens, in spite of the ingenuity which is often displayed in
doing this. After a description of the varieties of the white
corpuscles, the accuracy of which excites our admiration even
now, he says " In the blood no constituent is without importance, and in conclusion I will call attention to a normal form
constituent of the human blood which up to the present has
been entirely neglected. I find in my blood and in the blood
of numerous persons of different ages more or less abundant,
irregular masses of colorless globules, the masses varjing in
size according to the number of globules which compo.se them.
The globules themselves are from one to two micra in diameter
and also occur .separately in the blood. I have found three,
four and even hundreds joined together, forming plaques of
irregular size, 80 or more micra in diameter. These structures,
on account of their irregular size and shape, give the impression of broken up tissue elements." *
This was the condition when young Osier was probably given
the subject for investigation in the laboratory. He showed
that these granular masses of Schultze were not present in the
circulating blood, but were formed at the moment of examination by a rapid aggregation of the single bodies. He showed
this by microscopic study of the blood, and also by the direct
examination in salt solution of small clippings from the
connective tissue of the rat in which he found the single bodies
and not the ma-sses of them, within the small blood vessels.
He also showed that the conception of their presence in the
blood in aggregations was imtenable because the masses could
not pass through the capillaries. He described the small
bodies as exhibiting amccboid activity and .saw filaments form
in connection with them, which were probably fibrin. The
article is admirable, clear and concisely expressed, with full
literature references. The next reference to the blood plates
is in an article "Infectious Endocarditis" (Seguin's Arch.,
1881), and here he anticipates Bizzozero's view of the part
they play in thrombus formation. " In one case of mitral
• I have quoted from this article for one reason T)ecause It was
used as a reference in the course of physiology given by Newell
Martin in 1S7S, and the plate when I opened the volume appeared
as a familiar friend. No one appreciated more than did Doctor
Osier the Importance of familiarlzlnR students with the oriprinal
sources of knowledge, and this was always done in Martin's
laboratory.
stenosis a fresh vegetation when teased showed many closely
packed spherules, some of which were larger than those met
with in the ulcerative form. [These were the masses of
micrococci.] I was greatly struck with the resemblajice which
certain of these bodies, in tliis instance, bore to the individual
elements of Schultze's granule ma,<ses — those peculiar, granular clumps common in the blood of some animals and of
impoverished * persons." In 1882 there appeared a further
article, " Ueber dcu dritten Formbestandteil des Blutes," in
the Centrall)latt f. d. med. Wisscnsch., No. 30, in which he
emphasized the part they played in the formation of thrombi
and a final article " On the Third Corpuscle of the Blood,''
iledical News, 1883, a ratiicr popular presentation of the
subject.
Osier returned to Montreal in 18'('4, bringing to his future
work a remarkable equipment. He was 25 years old, possessed
a vigorous healthy body, and a well-trained mind. His family
was well and favorably known in the community, which gives
no small advantage in a conservative society. He had received
a valuable education, probably more valuable thougli different
from that which men are now receiving. He had come into
close contact with men of high ideals and good methods of
work, he possessed the methods by which knowledge is obtained
and had already made important contributions which gave him
a reputation. He further had enthusiasm and the art of
inspiring this in his students, native kindness of heart, a
candid, open disposition, a great capacity not only for making
friends, but for arousing the feeling of affection, and a fine
sense of hiunor, never used to hurt, which made him a sought
and delightful companion. He wTote well and easily, expressed himself simply and clearly, leaving no doubt as to the
meaning, and the matter was well arranged. In spite of the
number of these early articles, they all show care in preparation. He had also great capacity for work, and ambition, witii
a definite end in view. For such a man there are always
opportunities waiting, and Osier found them in ilontreal, as
he would have found thcni anywhere, c\cn witli his friend
Bovell in Nevis.
In the latter part of 18M, in addition to his position in the
university, lie was made physician to the Small-pox Hospital,
which gave him opiwrtunities for clinical study and an interest
in the disease which he has always retained. With the salary
which the position gave he purchased micro.scopes for teaching
in the medical school. In 18T6 he published in the Canadian
^fcdical and Surgical Journal three articles on small-pox:
(1) "The Initial Rashes of Small-pox"; (2) "On Hemorrhagic Small-pox"; (3) "A Form of Hemorrhagic Smallpox," which are valuable confriliutions to our knowledge of
the di8ea.«e. They show accurate observation, good clinical
judgment and a marked power of differentiation of conditions
both clinical and pathological. He had studied skin diseases
with Tilbury Fox in England, and the influence of these
studies is shown here. It was an important work for him. for
•Osier did not usually use such ambiguous expressions: the
presence of such masses in the blood might be regarded as one
of the disadvantages of economic poverty.
196
[No. 341
in the small-pox hospital he first acquired the power of close
observation of skin lesions and the ability of differentiation
and description which was afterwards such a marked feature
in his clinical work.
A very interesting article appeared in the same journal in
1876, " On the Pathology of Miner's Lung." It is based upon
the examination of the lungs of a coal-miner who died in the
small-pox hospital, and in whom the condition was verj'
marked, and several other cases showing various degrees of the
same condition. It is a good piece of work, shows much
originality, and is to be regarded as the best article in English
on the disease, which was first described by Pearson in 1813.
In this article for the first time the large mononuclear phagocj'tes were differentiated from the smaller corpuscles, and
Osier showed that the large cells were those most actively concerned in the phagocytosis of the carbon. He says : " One
most curious specimen was observed. On an elongated piece
of carbon three cells were attached, one on either end and a
third in the middle, so that the whole had a striking resemblance to a dumb-bell. I could hardly credit this at first, until
by touching the top cover and causing the whole to roll over,
I quite satisfied myself that the ends of the rods were completely embedded in the corpuscles and the middle portion
entirely surrounded by another." His description of the
position of the carbon in the lungs and its relation to the
lymphatics is accurate. He gives a figure of a microscopic
piece of coal which was found and which showed the scalariform tissue of ferns, thus proving its origin, and another piece
with two holes representing the dotted cells of firwood. In
conclusion, there is an experimental study of the effect of
foreign bodies in the tissue made by the injection of India ink
into the axillae and lungs of kittens.
The study of the blood plates gave him a familiarity with
blood examination which he utilized in the study of anaemia,
and there are several papers on this in 1877. The first of
these, " A Case of Progressive Pernicious Anaemia," was published in association with Dr., Gardner in the Canadian Medical and Surgical Journal. It is probable that Osier -nTote the
paper and was responsible for the blood examination, and the
description of the autopsy, which showed the usual conditions
found in the disease. It is a good type of medical paper, the
descriptions of the blood and of the marrow changes are
accurate, and the relation between the blood changes and the
marrow, wliich had been described by Cohnheim in the same
year, is confirmed. An abstract of this article, with detailed
measurements of the various blood cells " Ueber die Beschaffenheit des Blutes und Knochenmarkes in d. progressiven
pernicioser Anamie" was published in the Centralblatt f. d.
med. Wissensch., 1877, No. 15, and a second article in the
same journal on the study of a second case. Another article
on the same subject, in which he was associated with Dr. Bell,
appeared in the Transactions of the Canadian Medical Association, and here he gives Addison the credit for having first
recognized and described the disease under the name of
idiopathic ansemia. There is a final article in the following
year, " Entwickelung von Blutkorperchen im Knochenmark
bei pernicioser Anamie," Centralblatt f. d. med. Wissensch.,
1878, in which he confirms Neimiann's results of the study of
blood formation in the marrow.
During this period also he wrote a number of articles on
comparative pathology, the first on " Verminous Bronchitis in
Dogs, with Description of a New Parasite " was published in
the Veterinarian, London, 1877. He found this parasite in
the bronchi in an epidemic among dogs in Montreal. He gives
an accurate description of the parasite, and the points of
differentiation. It has been accepted as an original description and credited to him, the name Filaria osleri being one of
its synonyms. The only mistake he made was in classing the
organism among the strongyli and not the filarise, the main
difference being that the strongylus is oviparous and the parasite described by him produces living embryos. The lobular
pneumonia which he found, associated with the presence of
the parasites in the bronchi, he referred to the inhalation of
inflammatory products produced by them. The paper closes
with a discussion of the mode of infection which he thought
was by the direct inhalation of the dried embryos and it would
have been more valuable had he subjected this theory to experimental test. There is also a paper on Trichina spiralis
(Canadian Journal of Medical Sciences, 1876) which gives
a good description of the disease and the life history of the
organism, but which does not add anything new, and there are
a number of other articles which appeared at intervals up to
the time he left Montreal for Philadelphia. In the last article,
" An Investigation Into the Pork Supply of Montreal," wliich
was conducted in association with one of his students in the
veterinary school, A. W. Clement, who was afterwards well
known in tlie early days of the pathological laboratory of the
Johns Hopkins, he speaks of having made 900 autopsies in
Montreal, in four of which trichinffi were found.
There are two interesting addresses in the period. The first
was to the graduating class in medicine in 1875. It was probably the habit of the faculty to place the burden of such an
address upon the youngest member. Eeading over this address,
one is conscious that Osier had very little interest in it. Probably he looked over other addresses given on similar occasions
and they must have been a very poor lot. He gives the usual
good advice to the students, telling them to keep up their
reading, to observe patients well, and even at this early period
introduces Sir Thomas Browne, but he does not use him
effectively. It seems by far the worst thing he ever published ;
there is no trace of humor in it, and no indication of the
remarkable power he showed in his later addresses.
The second address is of a totally different character. It
represents much more work and care in preparation, as though
Osier had concluded that giving addresses was to be part of his
future work and that they should be good. There are a number of quotations, many of them apt, the usual good advice to
students, and some really inspiring sentiments, well expressed.
For instance, " You will have moments when the way appears
rugged, and the outlook dark, but never fear; others have
succeeded in tlie face of the same difficulties, and with patience
and perseverance you will do so too. Banish the future. Live
July, 1919]
197
only for the hour and its allotted work. Think not of the
amount to be accomplished, the diflBculties to be overcome, or
the cud to be attained, but set earnestly at the little task at
your elbow, letting that be sutlicieut for the day, for surely our
plain duty is ' not to see what dimly lies at a distance, but to
do what lies clearly at hand.' " It is difficult to give a student
better advice than this. Of the family physician he says " But
while the soldier and the statesman win honor and fame, the
family physician will draw to himself the love and gratitude
of manifold hearts; he will have no enemies, martial or
political; and his labors, if directed by a wise and prudent
skill, will be for the welfare and benefit of all."
From 1872 to 1878 was a great period in medicine; it just
preceded the bacteriological era in whicli the nature of infection was established; Pasteur had completed his studies on
fermentation and the silk-worm disease and was in the midst
of his revolutionarj- work on anthrax ; Koch, an obscure
countr)' physician, was beginning his studies on bacteria and
developing the methods which made their scientific study
possible; Virchow was at the height of his fame; Cohnheim
and Weigert had begun in Breslau and in Lcipsic their remarkable work; a new university in Strasburg had just been established which became famed through its products ; physiology,
in England and under Ludwig in Leipsic, had taken a new
life; Lister in England was in the midst of the work which
revolutionized surgery; the modern medical clinic was slowly
being established, and medicine was becoming scientific, its
procedures based upon knowledge and not conjecture; new
ideals and methods in medical teaching were being everywhere
introduced; America was feeling the enormous stimulus of the
promise given in the estiiblishment of The Johns Hopkins
Tlniversity. Osier was under the stimulus of all the new life.
He^ could easily have become a great scientist, but he chose the
path which led to the formation of the great clinician which
he became ; a worthy associate of the great men wlio have made
English medicine famous.
OSLER AS A PATHOLOGIST
Bv William G. MacCallim
The statement may be safely ventured that no clinician in
English-sjwaking countries has had at his command such a
wide and detailed knowledge of morbid anatomy as Osier.
There may be different opinions as to the reasons for his greatness as a teacher, as a man among men and in other ways, but
hardly more than one opinion as to the foundation of his
greatness as a clinician.
In the two small volumes of Pathological Reports printed
at the McGill Universitj', in a complete collection of reprints
of his papers beginning in 1877, and in the first edition of his
Practice of Medicine, the development of his knowledge of
pathological anatomy may be clearly traced. Throughout
there is no diminution in his keen enthusiasm and little change
in the character of his interests, but there is an extraordinary
advance in the clarity of his ideas keeping pace with the discoveries of the European and other workers in the field of
patholog)'.
During a period of more than 40 years — years that have
witnessed the most phenomenal advances in medicine — his
attention was very largely devoted to these studies which were
constantly maintained as the basis of his more purely clinical
work.
Osier's training lay not iti chemistrj- — the growth of i)acteriology found him a spectator and experimental metiiods
seem to have had little attraction for him. Nor did he attempt
any protracted researches in patholog)' for its own .<ake. Instead his interest was and has always been in the observation of
rather gross and striking anatomical alterations usually on
account of the sjTnptoms which they produced and not with
the aim of investigating their minute details or their ultimate
causes. In all this he has shown himself critical and sane and
quite unwilling to pursue what seemed a fantastic theory
tinless convinced by definite proofs. He was skeptical of the
malarial organisms of Laveran for a time until he became
familiar with them himself and demonstrated them in this
country. He would not believe that the micrococci found in
acute endocarditis were anything more than accidental invaders until he had convinced himself by actual studies of the
valves.
But in his early days he did not wait for others to unearth
new facts. He pressed ahead alone in the investigation of
une.xplained phenoniciia and was perhaps the first to see clearly
the blood platelet which he described in 1874 as the third
corpuscle of the blood.
He was early in the field with his studies of the bone-marrow
in pernicious aiin?mia and evidently recognized megaloblasts
and other cells at a time when such recognition must have been
very difficult.
But from the beginning he appears to have been more readily
interested in the physical aspects of morbid anatomy, especially
in so far as there could be traced a chain of events. In the
first volmne of the McGill reports he describes a case of
idiopathic hypertrophy of the heart, the topogra])hy and effects
of various aneurysms, cases of phthisis, pneumonia, cancer,
ulcer of the duodenum, typhoid fever with perforation, incarceration of the ileum, etc. In the second volume is found a
series of similar miscellaneous cases. Some of the.se were
remarkable as, for cxam])lc, the instance of aneurysm of the
hepatic artery. It is to be noted that even in his discussion of
these cases he showed that the special literature of foreign
countries was quite at his commnnd. He met with a case of
hypertrophic cirrhosis of the liver — the first in his experience — and while he was studying it there appenrcd Hanot's
thesis, the importance of which in relation to his own case he
recognized at once. From this period at McGill University
where he performed a great many postmortem examinationa
198
[N"o. 341
and supervised them in tlie hands of students he acquired much
of his familiarity with morbid anatomy. It is his spirit of
serious research which has remained to inspire the splendid
work in pathologj' carried on ever since in that school and his
preparations formed the foundation of their magnificent
museum of pathological anatomy.
Osier was impressed from the beginning with the usefulness
of considering together a group or series of similar cases.
There is something statistical about this plan, but since no two
cases of any disease are precisely alike in all details, much
light comes from the study of a series. This method may be
traced through the work of his later years and in that of all of
his pupils. It is apparent in all the papers of his Philadelphia
and Baltimore periods and reveals his careful method of preserving minute notes on all he saw, for some of the recent
studies refer back to cases encountered in the Montreal days.
Comprehensive papers on endocarditis, tuberculous pleurisy,
peritonitis, pericarditis and abdominal tumors, followed and
later similar analyses of long series of cases of typhoid fever,
meningitis, erythema multiforme, Addison's disease, myxoedema, splenic anaemia, malaria and many other conditions.
In these there is a sustained and constant interest in the
pathological anatomical changes, but rather in their relation
to the general history and symptomatologj' of the disease than
for their own sake. The details of the causes and development
of the lesions are discussed only briefly, but an important outcome of such studies was in several instances the more definite
outlining of disease entities from the recognition of the repeated occurrence of the same group of symptoms and pathological alterations.
This has long been the first great step in the study of disease
and it is for this reason that many of the great names in
medicine are associated with the diseases in which they have
been the first to discern the constancy of the association of
several features. The ability to see these relations and to
connect a group of phenomena with a common cause is given to
few. It is only less difficult than to discover the hidden cause
of disease.
On the other hand, with diseases well recognized by everyone. Osier's interest in new manifestations and new combinations of symptoms or lesions has been unfailing. After the
long period of observation and study of typhoid fever in which
he associated with himself all the men on his staff he analyzed
the disease from every point of view. However, in these
studies only the grosser anatomical changes are considered and
there was no special advance in the knowledge of the bacteriology or immunity reactions of the disease.
Syphilis has always claimed much of his attention and
interest, although he has written little on it except in the form
of test-book articles and papers concerning aneurysms. Nevertheless, the multifarious manifestations of this disease have
formed a prominent subject in his teaching and he believed
that there was much in tlie statement that he who knew all of
syphilis knew nearly all of medicine.
In his later years he worked no longer at actual dissections
and no longer studied the details of pathological anatomy with
the microscope, but he never slipped into that state of confidence in unaided clinical diagnosis which would allow him
to remain away from the autopsy room. Instead he came there
not only to follow minutely the dissection of cases from his own
hospital service, but to learn what he could from those belonging to the surgical and other services. His presence was an inspiration that led us to great efforts toward careful work, and
his long experience and unfailing memory, which enabled him
to recall the conditions found in a whole series of similar cases,
gave us a background upon which the case under investigation
stood out.
The pathological anatomy of his text-book is of this quality
and it is for that reason that the students in pathology are told
to read it. No one has written more systematically, or more
concisely of the changes underlying the manifestations of
disease ; no one has recognized more clearly the boundary line
between the known and the imknown or sifted more judiciously
and unerringly the truth from error. His long habit of considering each disease on the basis of knowledge gained from
the analysis of a large series of cases has allowed him to estimate justly the relative frequency and importance of each
feature and to state them in the most helpful and orderly
sequence. This clearness of vision with regard to the actual
natural history of disease, always referring to a well-remembered series of cases, helped to make his teaching a memorable
delight to his students. His actual contributions to our knowledge of pathology are many and important, but even more
valuable to the science of medicine in general is his example,
in that he has built his clinical medicine solidly on a foundation of pathological anatomy.
OSLER, THE TEACHER
By W. S. Thater
Observe, record, tabulate, communicate.
Use your five senses. The art of the practice of medicine is
to be learned only by experience; 'tis not an inheritance; it
cannot be revealed. Learn to see, learn to hear, learn to feel,
learn to smell, and know that by practice alone can you become
expert. Medicine is learned by the bedside and not in the classroom. Let not your conceptions of the manifestations of
disease come from words heard in the lecture room or read
from the book. See, and then reason and compare and control.
But see first. No two eyes see the same thing. No two mirrors
give forth the same refiection. Let the word be your slave and
not your master.
Live in the ward. Do not waste the hours of daylight in
listening to that which you may read by night. But when you
have seen, read. And when you can, read the original descriptions of the masters who, with crude methods of study, saw
so clearly.
Eecord that which vou have seen; make a note at the time;
July, 191!)J
l!)!l
do uot wait. " The flighty purpose never is o'ertook, unless
the deed go with it."
Memory plays strange pranks with facts. The rotks and
fissures and gullies of the mountain-side melt quickly into the
smooth, blue outlines of the distant panorama. Viewed
through the perspective of memory, an unrecorded observation,
the vital details long since lost, easily changes its countenance
and sinks obediently into the frame fashioned by tlie fancy of
the moment.
Always note and record the unusual. Keep and compare
your observations. Communicate or publish short rxoU^s on
anything that is striking or new. Do not wast€ your time in
compilations, but when your observations are sufficient, do
not let tliem die with you. Study them, tabulate tiiem, seek
the points of contact which may reveal tlie underlying law.
Some tilings caji be learned only by statistical comparison. If
you have the good fortune to command a large clinic, remember that one of your chief duties is the tabulation and analysis
of the carefully recorded experience.
The collection and study of your own observations is much,
but he who works in his own small compartment leads, after
all, a restricted and circumscribed life. Go out among your
fellows, and learn of tliem. The good observer is not limited
to the large hospital. The modest country doctor may furnisli
you the vital link in your chain, and the simple rural practitioner is often a very wise man.
Respect your colleagues. Know that there is no more highminded body of men than the medical profession. Do not
judge your confreres by the reports of patients, well meaning,
perhaps, but often strangely and sadly misrepresenting. Xcvcr
let your tongue say a slighting word of a colleague. It is not
for you to judge. Let not your ear hear the sound of your
voice raised in unkind criticism or ridicule or condemnation
of a brother physician. If you do, j'ou can never again meet
that man face to face. Wait. Try to believe the best. Time
will generally show that the words you might liave spoken
would have Iwen unjust, would have injured a good man, and
lost you a friend, and then — silence is a powerful wcaimn.
When you have made and recorded the unusual or original
observation, or when you iiave accomplished a piece of researdi
in laboratory or ward, do not be satisfied with a verbal communication at a medical societ}-. Publish it. Place it on
permanent record as a short, concise note. Such communications are always of value.
Mix with your colleagues; learn to know them. But in
your relations with the profession and with the public, in
everything that pertains to medicine, consider the virtues of
taciturnity. Look out. Speak only when you have something
to say. Commit yourself only when you can and must. And
when you speak, assert only that of which you know. Beware
of words — they are dangerous things. They change color like
the chameleon, and they return like a boomerang. Do you
know the story of the young physician, about to enter ])ractice,
who was sent by his father to his old friend, Sir William
Stokes, for advice ? A pleasant conversation, and, at the door
way, a last word : " Charley, don't say too much." Then, at
the gate, a voice: "Charley, come back a minute: I'm very
fond of you, my boy ; don't do too much."
" Don't do too much." Keniember how much you do not
know. Do not pour strange medicines into your patients.
Our greatest assistance is given by simple physical and mental
means, and by the careful employment of such drugs as have
been adequately studied, with regard to the action of which we
have real information. Do not rashly use every new product of
which the peripatetic siren sings. C-onsidcr what surprising
reactions may occur in the laboratory from the careless mi.xing
of unknown substances. Be as considerate of your patient and
yourself as you are of the test-tube.
Familiarize yourself with tlie work of others and never fail
to give credit to the precursor. Let every student have full
recognition for his work. Never hide the work of others under
your own name. Sliould your assistant make an important
observation, let him publish it. Through your students and
your disciples will come your greatest honor.
Be prompt at your appointments; that is always possible.
Many are alwa)'s late at a consultation; few miss a train.
There is no excuse for tardiness.
Live a simple and a temperate life, that you may give all
your powers to your profession. Medicine is a jcahius mistress ; she will be satisfied with no less.
Save the fleeting minute; do not stop by the way. Leani
gracefully to dodge the bore. Strike first and quickly, and
before he has rec-overed from the blow, be gone; 'tis the only
way
If you can practice consistently all this, .... and then, if
you can bring into corridor and ward a light, springing step,
a kindly glance, a bright word to every one you meet, arm
passed within arm or thrown over the shoulder of the happy
student or colleague; a quick, droll, epigrammatic question,
observation or appellation that puts the patient at his ease or
brings a pleased blush to the face of tlie nurse; an apprehension that grasps in a minute the kernel of the situation, and
a memory teeming with instances and examples that throw
light on the question ; an unusual power of succinct statement
and picturesque expression, exercised quietly, modestly and
wholely without sensation ; if you can bring into the lecture
room an air of perfect simplicity and directness, and, behind
it all, have an every-ready store of the most apt and sometimes
surprising interjections that so light up and emphasize that
which you are setting forth tliat no one in tlie room can forget
it; if you can enter the sick-room with a song and an epigram,
an air of gaiety, an atmosphere that lifts the invalid instantly
out of his ills, that produces in the waiting hypochondriac so
pleasing a confusion of thought that the written list of questions and complaints, carefully compiled and treasured for the
moment of the visit, is almost invariably forgotten ; if the joy
of your visit can make half a ward forget tlie symptoms that it
fancied were important, until you are gone; if you can truly
love your fellow, and, having said evil of no man, lie loved by
all; if you can select a wife with a heart as big as your own.
200
[No. 341
whose generous welcome makes your tea-table a Mecca ; . . . .
if you can do all this, you may begin to be to others the teacher
that " the cliief " is to us !
An eye whose magic wakes the hidden springs
Of slumbering fancy in the weary mind,
A tongue that dances with the ready word
That lilce an arrow seeks its chosen goal,
And piercing all the barriers of care,
Opens the way to warming rays of hope.
A presence like the freshening breeze that as
It passes, sweeps the poisoned cloud aside.
An ear that 'mid the discords of the day
Swings to the basic harmonies of life.
A heart whose alchemy transforms the dross
Of dull suspicion to the gold of love.
A spirit like the fragrance of some flower
That lingers round the spot that this has graced.
To tell us that although the rose be plucked
And spread its perfume throughout distant halls.
The vestige of its sweetness quickens still
The conscience of the precinct where it bloomed.
OSLER AND THE STUDENT
By Thomas E. Beowx
In a lay sermon delivered before the Yale students a few
years ago in which Dr. Osier offered them " A way of life " —
" a path in which the wayfaring man cannot err, a life in daytight compartments, the main business of which is not to see
dimly at a distance, but to do what lies clearly at hand," and
which had been the starting point of his life-habit — he began
with two words which show more plainly than many pages
could his real relation to the student — for these two words
were " fellow students." In these words lay the real reason
for his unique and lasting influence upon all who studied with
him, for he, with his vast experience, his wonderful insight,
his profound knowledge, his poetic vision, his deep sympathy,
was still always at heart the student, always studying, always
delving more deeply into the mysteries of health and of disease,
giving always, yet always ready to receive, teaching, yet ever
ready to learn.
To those privileged to be his students in the early days of
the medical school — a truly golden age to each and every one
of the small, though ever growing group, he preached, as he
lived, a glorious philosophy of life, a joy in work, doing the
day's tasks, " living for the day and for the day's work," with
a wonderful belief in his fellowmen, never losing faith becau.se
some had failed him, giving without stint his best to everyone
with no thought that some might prove unworthy of the trust.
He felt with Goethe that "the classical is health, and the
romantic disease," and he strove for the one with the Greek
love of perfection, while for the other he had the passion of
the truly adventurous .spirit sailing on uncharted seas. To
us who were his students in the early days of The Johns Hopkins Medical School, his memory is so vivid, so fresh, that it
seems but as of yesterday when he worked and played in our
midst, and we have but to close our eyes to see him in fancy,
almost as clearly as we saw him in fact in the late 90's, the
great teacher and the great student in his manifold relations
to his students. Now we see him riding to the hospital in the
Monument Street car, and to the group about him prophecying
with keen yet ever kindly vision the ills — physical, mental and
spiritual of the derelicts en route to the dispensary, here in
the wards demonstrating the complex psychology of Giles de
la Tourette's disease, as exemplified by a poor bit of .sodden
humanity whose coprolalia but exemplified — in a way a bit
embarrassing at times it is true — the symptom-complex he was
discussing, or in an alcove ofP the ward playing with little
Theophilia as she was emerging from the night of cretinism
into the day of normal happy childhood imder his skillful
guidance; now in the class-room of the dispensary — for he
loved the polyclinic, and believed in its wonderful potentiality
as a teaching factor — with one deft touch solving a case of
great complexity, or bringing from his vast storehouse of
knowledge the one last link needed in a disease-picture
hitherto poorly understood, listening, suggesting, directing,
teaching, guiding both student and patient, and all the while
filling countless scraps of paper with the names of one of the
three great teachers of his youth ; now in the clinical laboratory
studying a blood specimen, and suggesting to the student some
line of original investigation which might, perhaps, light into
flame the doi-mant investigator and research worker ; now in
the autopsy room studying in death the puzzles that he had
helped to unravel during life ; now walking through the wards
and corridors of the hospital with a smile or an epigram for
every doctor and nurse who pasfsed, a kindly word, and his
ever-stimulatiHg psycliotherapy — encouragement, optimism,
hope — to every patient he saw ; in his myriad activities always
making each student feel that he also was but a student of
health and of disease, of men and of morals, and yet such a
student as to fire our minds, our souls and our bodies to renewed efforts so that we might, in some measure at lerast, prove
worthy of this fraternity. To us who were privileged to be his
students — his fellow students in those days, he was — and still
is — always our inspiration and always our model. In him the
fire burned so brightly that no dross nor tinsel could survive
its pure flame, and he was ever " our cloud by day, our pillar
of fire by night." With Bossuet he taught that " le bon sens
est le genie de I'humanite," and he gave to us " a golden age
which never rusts, a spring which never fades, eternal youth."
Always true to himself and to others, he made us think daily
of words of his beloved Plato " Whence has the progress of
cities and nations arisen if not from remarkable individuals
coming into the world we know not how and from causes over
which we have no control ? "
Is not the greatest tragedy of growing older the loss of our
illusions — the discovery sooner or later that so many of the
gods of our youth, Jove-like Olympians of those days when
our world was young and pregnant with possibilities, have,
after all, but feet of clay? But with "the chief" this could
July, 1919]
201
never be. The more we learned, the more wonderful his boundless knowledge seemed ; the wider our vision, the more limitless
his appeared.
Everyone who has ever been his student is. as it were, still
studying with him, or peripatetiiiilly following his footsteps
as he journeys through life, always teaching some new lesson
of niedieine or of living. Every honor that has befallen him
has enriched us and made us prouder of our brotherhood ; every
step upward or onward of his has made our paths easier and
the heights seem not so far away. We have rejoiced in his
happiness and in his honors, and perhaps he has been helped
in his sorrows by the knowledge that they are ours as well, for
he has shown us how work could be made play, and how the
real could be made ideal. Because of him our lives have been
better, our successes more real, our failures less hard to bear,
for through the tangled skein that sj)ells life each of us knows
that in him be bus, and will always have, a teacher, a friend,
and a true fellow student to tiic end of the ciiaptcr.
OSLER AND PATIENT
Bv TllcMAS ilcCliAE
111 all tile relations of physician to patients there are two
sides — the strictly medical and the personal. Some have a
blind spot for the latter, but taking the profession as a whole
these are in the minority. No one could work in close association with .Sir William Osier without realizing that both sides
were well developed in him. There
was always the desire to do the best for
the |>atient in a medical way, but the
personal aspect was never forgotten.
Patients were patients and not cases.
Interest in the personal side was much
in evidence and it was the exceptinn
for his patients to fail in a])])reciating
this. There was always a great charity
for the weakness of human nature ami
there were neither unkind nor hasty
judgments. We know how often in bis
addresses he has em])hasi/ed tlie imjK)rtanc-e of this quality.
To the writer was given the opjjortunity of knowing the relation of
Sir William Osier to the patient botii
by |)ersonal e.xperience and by the oltservation of others. The former came
by my having an attack of typhoid
fever while a Iwnse orticer in The
Johns Hopkins Hospital, .\fter the
pas.sage of years it is didicult to estimate in detail one's feelings towards
bis physician, but the main impression
left on my mind after a long interval is tiiat <>f alisohitc contidenec. His visits were usually short, but when he hail gone
there was a feeling that everything was all right. The visit
was nearly always marked by some cheering saying or amusing
quip.
One in<ident comes to memory with regard to the impression made by him on a patient many years ago; it is also an
exani|)le of curious coincidence. Hack in the eighties one of
my father's friends was stricken with a malady of which I
heard some of the <letaiis dis<-u8.<ed without realizing that they
were to \tc remembered. The patient had .\ddison's disea.se
with an unusual degree of pigmentation which attracted great
attention ami was naturally commented on by liis friends. I
remenii>ered hearing that lie iiad gone to the United States to
consult a ]iliysiciaii and had come back R'alizing tliat he could
not recover. These matters had apparently been comidetely
forgotten, but were recalled when 'i't years later the friend who
acconipanietl the patient on the journey said to me: "1 wonder if you
could bcl]) me to identify tiie physician wiiom .Mr. .\ consulted in I'iiilail('l|iiiiii. Ills nanic made little
iiiiprc»icin nil nic at tin' time." This
seemed ratlicr a (lillicult undertaking,
but 1 asked wliat lie remembered of the
visit. He gave the following details:
" The examiinition was very thorough ;
he strippeil ilr. .\ and went over him
from head to foot. He said very little.
(.\t this iKiint the thought of Sir Wililam came to my mind.) When Mr. .\
asked liim as to the outlook, he i^aid,
Do you think you have enougli of the
grace of (Jod to nnike a clergyman,' or
something like tliat. .\t any rate
Mr. .\ uiKlerstood the meaning which
wMs iiiirmicd ami commented with approval on the way in which it was conveyed." .Nftcrwards I asked Sir William if he was the physician, and found
I hat he was and that be rcmcmliered
the patient very well.
This brings up aiiolber of bis characteristics with regard
to patient.s — the marvellous nu'mory which he has of the details
regarding nnuiy of them. On oneiK-casion a physician brought
a patient to consult him. The ]>bysician began to give the
bistfiry when Sir William said : " I -saw Mr. — before with so
and .-^o " — mentioning the diagnosis. Both the physician and
the patient denied this until Sir William showinl them the
notes of the jtrevious visit. It seems almost impossible to
miagine that both should have fr)rgotten the consultation, but
such was the case. On nuuiy occasions patients came back to
the clinic after an interval of years and Sir William could give
the details of the bistorv at once.
303
[No. 341
In oue of his essays, which gives the title to a book, "Aequanimitas,"' he dwells on the importance of not permitting one's
poise to be disturbed or allowing the expression to show what
would be better concealed. He practised this in his daily
work and many who came in contact with him never realized
how much anxiety he often felt, but rarely displayed over
patients. This was particularly true if it was a case in which
a diagnosis had not been made and in which, therefore, the
best treatment was a question of doubt. One such instance
comes to mind of a young man with typhoid fever and severe
hemorrhages. In this case, of course, we were suspicious of
perforation. Sir William made a special trip to the hospital
at my request to try and settle this point. The decision was
that there was no positive evidence of perforation and exploration was delayed, but the signs of general peritonitis next day
showed our error. I remember well his words on the fallibility
of human judgment and of the sorrow that one felt when he
had judged wrongly.
His influence over patients was marked and especially over
those unfortunates whose nervous systems had suffered. As a
general rule he did not spend a great deal of time over them in
the hospital. However, the results came; in many cases no
doubt, largely by faith in him. It has been said by .some that
Sir William was not particularly interested in jDsychotherapy,
but one might say that he did not need to be — he practised it,
not always consciously, perhaps, but always effectively. He
had extraordinary patience with querulous patients and it was
very rarely that he ever became irritated with them. With the
jiatient who was ready to fight and be disagreeable he never
argued : " Glad to see you come and glad to see you go " was
a favorite answer.
Many interviews with jiatients come to memory. In one the
center of the stage was occupied by a nervous woman, to whom
something had been said in a very kindly way of the need of
self-control. With the tears flowing freely and a handkerchief
in active use she said : " Oh, Dr. Osier you misjudge me
cruelly." He, standing at the foot of her bed, replied with a
serious tone to his voice and a twinkle in his eye : " Madam,
I learned early in life never to judge any woman and tliat rule
I have strictly kept. Therefore, I cannot have misjudged you.
Good morning " — and he was away before she could frame a
reply. Later in the day the brunt of his hasty exit fell on me.
In a large private ward service it was not possible for him
to spend a long time with each patient. To his house officers
it was always a source of interest and a good lesson to observe
how he could get into and out of a patient's room without
giving a chance for the flood-gates of talk to open. Many
patients would lament that they had not been able to tell him
this or that. But with this he had a remarkable ability in
discerning when the patient needed a special interview and he
was always ready to give it.
There was one subject on which he would never listen to a
patient, and that wa.s when something was said which reflected
on another physician. When the patient began any such statements he showed his displeasure at once and if this was not
enough a very sharp rebuke followed. In fact this was about
the only thing whicli made him lose patience and was the rare
occasion of his showing sternness. The talkative patient was
a trial to him — and of whom is this not true ? He used to
have a very characteristic look when he escaped and I can
remember his delight, after a particularly trying interview of
the kind, when I quoted to him from " Kim " : " The husbands
of the talkative will have a great reward hereafter." However,
he was rarely caught twice by the same person.
Of one class of his patients a word may be said — the doctors.
He was consulted by many of the profession and especially in
the latter years in Baltimore. This had grown to be a heavy
burden, but one which he carried willingly. He never spared
himself or thought of his own convenience when something
was to be dime for a physician or a member of a physician's
family.
Of the attitude of patients towards Sir William much might
be said. Perhaps the most striking characteristic was absolute
confidence. There was the certainty that there would be no
failure from lack of skill or interest on his part. His cheerfulness had much to do with this and the ability to give the
desire to fight to those who had lost courage and hope. He
was always careful in giving an opinion to put matters simply,
so that the chance of misunderstanding would be as slight as
possible. In the consideration of what a patient should do he
always had in mind what he could do. It was a good lesson
to observe the care which he took to avoid saying anything in
the hearing of a patient which might cause disturbance or
increase anxiety. This was especially marked when the outlook was being discussed and seemed unfavorable. He never
forgot to be sure that the patient was not within hearing. In
all the giving of advice he was sparing of words and might be
described as one of those " who have not the infirmity, but the
virtue of taciturnity, and speak not out of the abundance, but
the well-weighed thoughts of their hearts.''
OSLER AND THE TUBERCULOSIS WORK OF THE HOSPITAL
Bv LoLis Hammax
Dr. Osier's interests were so universal that I fear I run grave
risk of contradiction in saying that he showed a particular
interest in tuberculosis. I came in contact very intimately
with his enthusiasm for tuberculosis study and perhaps for this
reason I exaggerate the position it held for him. Certainly
he never tired of reiterating to students the imi)ortiUice of a
thorough knowledge of the two great infectious diseases, tuberculosis and syphilis. From the beginning of his career as
physician-in-chief to this hospital he studied the tuberculous
patients with minute care. The first patient admitted to his
July, 1919]
203
medical service on Maj' 16, 1889, was suffering from tuberculous peritonitis and one of the first clinical papers he published
was upon this aspect of tuberculous disease. In 1903 I undertook at his request a study of all the cases of serous membrane
tuberculosis that liad been in tlie hospital up to that date and I
noted that many of the histories have copious notes dictated
by him.
That this interest in tuberculosis extended beyond the
details of clinical observation is shown by the establishment in
1898 of a special fund for the study of tuberculosis, the
initiative for its inuujriiration and much of the money coming
from Dr. Osier liimself. Dr. Charles D. Parfitt was appointed
to conduct the work and a laboratory was equi])ped to afford
him suitable opportunity for investigation. Unfortunately
after an active year, which gave promise of substantial contributions to the study of tuberculosis, Dr. Parfitt was taken
ill and the work was abandoned to be resumed some years later
in the laboratory of the Phipps dispensary.
A further evidence of Dr. Osier's unfailing interest in tuberculosis, and his zeal for the dissemination of tuberculosis knowledge amongst the students, is the foundation of the Tjaennec
Society in 1900. This was tlie first society in this country and,
as far as I know, the first in the world to devote \Uii\f to the
study of tuberculosis. I remember clearly the first meeting
of the society held in the fall of 1900 in the basement under
Ward G. Dr. Osier presided, outlining the aims of the society
and explaining the appropriateness of its name; a review of
Laennec's life and work followed. Since this date the society
has continued to liold regular meetings and it has proved itself
an important and stimulating center of tuberculosis interest
in the hospital. Unfortunately, there are no records of the
early meetings of the society, but I rememlier Dr. Osier's unfailing attendance at all the meetings and his brilliant and
stimulating discussions.
Shortly after the establishment of the Laennec Society
Dr. Osier with liis peculiar prescience of coming events inaugurated the home visiting of tuberculous patients registering
in the dispensary. At first this work was undertaken by
medical students. Blanche N. Epler, Adelaide Dutcher and
Elizabeth H. Blauvelt successively giving it their service. The
study of Miss Dutcher reported before the Laennec Society
and published in The Piiiladelphia iledical Journal, December
1, 1900, is, I believe, tlie first contril)ution in this countrj' to
lay the proper emphasis ujwn the importance of the jiome in
the spread of tulK-rculosis. From this modest beginning grew
the .subsequent study and care and supervision of tuberculous
patients in the dispensary. Dr. Osier soon enlisted the interest
of Mr. Victor Bloede in the work and through his generous
support a nurse was employed to visit and instruct patients
in their homes. At the same time under liis guidance the first
steps were taken towards establishing a special clinic for the
tuberculous. .Although no separate rooms were available for
this purpose, all tuberculous patients were put under the care
of Dr. Hennan Bruelle for detailed study and advice.
It would give a very incomplete impression of Dr. Osier's
tuberculosis interests to omit reference to his activities outside
of the hospital. He was always deeply concerned about the
social ap])lications of medical knowledge and he played a
prominent part in furthering and directing the awakening
interest in the control of tuberculosis as a disease of the ma.<ses.
For instance, he took a very active interest in tiie Tuberculosis
Exposition held in January, 190-1, under the auspices of the
State Board of Health, the first exposition of the kind held in
this country. Umler his infiuence a remarkable collection of
books on tuberculosis were displayed, illustrating the development of our knowledge of the disea.<e from Hippocrates to
modem times. Before the collection was dis]wrsed Dr. Osier
reviewed it with the medical students, illuminating eacli epoch
with his surprising knowledge of the historical aspects of the
subject.
In 1903 Mr. Henry Phipps learned of the work Dr. Osier
was trying to do with such modest equipment and generously
sent $10,000 to support his endeavors. The check came quite
unexpectedly and was the means for Dr. Osier to plan at once
to materialize one of his dreams. With great enthusiasm he
began to develop a special department for the study of tuberculosis and the care of tuberculous patients. Mr. Phipps'
additional gift of over $20,000 made it possible to remodel
the old stable standing between the dispensary and pathological
department buildings into a two-story structure with four
rooms on each floor. The building was formally opened at a
special meeting of the Laennec Society on February 21, 190."),
and the first patients were received on the first of March of the
.same year.
Dr. Osier left the liospital the year the tul)erculosis dispensary was opened, but his interest in the dc])artment never
ceased. Messages of encouragement and ai)i)reciation came at
irregular intervals. Whenever an article ajipearcd by a member of the staff, usually the first and always the dearest recognition was a postal or a brief note da-slicd off in his characti'ristic way. As the dispen.«ary gradually grew into a recognized
place in the medical clinic, at every turn of fortune there came
his clieering congratulation. It is impossible for me to look
back upon tho.se years without the deepest emotion. I do not
know if Dr. Osier ever appreciated what these crisp, kin<lly
messages flashed from abroad really meant for us, nor am I able
adequately to express all we felt. Certainly this much is true,
tijey were always the brightest ray of encouragement to our
work, the most comforting reward that made us forget the
long dreary hours of labor and the discouragement and doubt
that often assailed us.
Since the first few years the tuherc\iIosis dispensary iias
grown steadily in im])ortance. Further gifts from Mr. Phipps
allowed the hospital to adcl to the building in 190S, dnul)ling
its capacity. Ilecently the generosity of .Mr. Kenneth Dows
has further improved the building and lias jiut the research
department of the dispensary upon a sound footing. The
tuberculosis clinic is a ver\' different department now from the
modest dispensary arrangements of a physician without a room
to work in and with no other equipment but his st<'thoscopc.
But this is the fruit that has gro\m from tliat tiny seed of
interest and enthusiasm planted by Dr. Osier many years ago.
204
[No. 341
INFLUENCE ON THE RELATION OF MEDICINE IN CANADA
AND THE UNITED STATES
By Thomas B. Futcher
Sir William Osier has done more than any other member of
our profession to bring about cordial and intimate relationships between its members in the United States and Canada.
A Canadian by birth, a graduate of McGill University,
Canada's most distinguished medical representative, and a
man with a most magnetic personality and great breadth of
spnpathies and interests, it is only natural that he should
have exerted a most potent influence in encouraging close associations between the members of the profession in the two
countries. Particularly was this the case after his call to
Philadelphia in 188i, and to Baltimore in 1889. While this
bond has naturally been more intimate between internists, his
influence indirectly brought about a closer contact between the
members of the other specialties.
Altliough Osier was graduated in medicine from ilcGill
University, he was born at Teciunseh, Ontario, on July 13,
1849, and was educated at Trinity College, Toronto. Various
members of his family, leaders in their respective professions,
have resided in the latter city. As his reputation grew, it was
only natural that his influence on the profession in the two
older provinces of Canada should have been very great.
After his graduation from McGill in 1872, he sjjent the ue.xt
two years in research work abroad, at University College,
London, and at Berlin and Vienna, where he formed associations with such men as E. A. Schiifer, Virchow, Nothnagel
and others. While abroad, he published in 1873 his researches
on the blood platelets in which he established their corpuscular
character. Upon his return to Montreal in 1874, he was
appointed professor of the institutes of medicine, at McGill
University, a position he filled until 1884. During this period,
he was brought into intimate association with his old teacher,
Robert Palmer Howard, who was professor of medicine and
dean of the medical faculty, and with those able clinicians,
Ross and MacDonnell. His natural bent for research and
investigation, had been further stimulated by his experiences
abroad. A full appreciation of the importance of the microscope in medical research led, upon his return, to its more
extensive adoption in the laboratories of McGill. While there,
Osier laid the foundation of his keenness as a clinician, through
his recognizing the great importance of following the fatal
cases to the autopsy room, performing many of the necropsies
himself. These investigations resulted in the publication of
numerous important contributions to medical literature.
Among these may be mentioned his paper in which mycotic
aneurisms in association with ulcerative endocarditis were
described for the first time, and his account of the ball-valve
thrombus at the mitral orifice, which also was the first recorded
case.
He was very much interested in comparative pathology, and
performed many autopsies on lower animals with that keen
veterinarian, Clements, who later went to Baltimore, where he
died an untimely death from myocardial disease.
Many of Osier's students of this period are scattered
througliout Canada and the United States, and they look back
with 2ileasure and profit to the training and stimulus they
received under him at McGill. One of the powerful influences
he possesses was manifested, even in these early years, through
his readiness to report interesting observations before local
medical societies and provincial medical associations, and to
encourage others to do likewise.
Osier's contributions to medical literature while at McGill,
and his papers read before medical societies in the United
States, naturally attracted a great deal of attention, and, when
in 1884 the University of Pennsylvania was seeking the best
trained man to fill the chair of professor of clinical medicine,
Osier was its choice. While in Philadelphia he was brought
into close association with such men as Weir Mitchell, William
Pepper, Tyson, Musser, Keen, Wilson and others. His influence on medicine in the United States was very marked even
during this Philadelphia sojourn from 1884 to 1889. He was
one of the original members of the Association of American
Physicians, which was organized in 1886 with Francis A.
Delafield as its first president. He always took an active
interest in the annual meetings of the association, contributing
nimierous original papers and entering into the discussions.
He was himself its president in 1895.
While at the University of Pennsylvania, Osier's contributions to medical literature were nimierous and important.
Much of his material for his monograph on the " Cerebral
Palsies of Children," published in 1889, was gathered during
this period. His experience at Blockley, that wonderful storehouse of clinical and pathological material, provided him with
a mass of data later freely utilized in the preparation of his
text-book.
In 1889, as the construction of The Johns Hopkins Hospital
was nearing completion, the trustees of the university and
hospital, seeking the best man to fill the chair of professor of
medicine in the university, and the position as physician-inchief to the hospital, at once thought of Osier, who was then
considered the most brilliant clinician available. The offer
was tendered and accepted, and he was on duty when the first
patient was admitted to the hospital on May 10, 1889.
It was during his period of residence in Baltimore from
1889 to 1905 that Osier's influence on medicine in the United
States and Canada was chiefly exerted. In making appointments to his hospital staff, graduates of medical schools in both
the United States and Canada shared the privilege of working
under him. Owing to his close affiliations with teachers in the
Canadian medical schools, it was only natural that these men
should be appealed to from time to time to supply assistants
for its interne staff. His first resident physician was Lafleur,
of McGill, who during his tenure collaborated with Councilman in the publication of their important monograph on
amoebic dysentery. Lafleur, as have other assistants, returned
July, 1919]
JOHNS HOPKINS HOSPITAL BULLETIN 205
to Canada and carried with him to McGill and the Montreal
General Hospital the stimulus and methods acquired while
under Osier. Hewetson, also of McGill, soon followed Lafleur
as an assistant. The unfortunate development of tuberculosis
prevented him from pursuing what promised to be a brilliant
career. Thayer, of Harvard, who now holds the chair in
medicine on the whole-time basis, succeeded Lafleur as resident physician and served until 1901.
J. E. Graham, who was for many years professor of medicine
at Toronto University, an excellent clinician and a man much
beloved by his students, was a close personal friend of Osier.
Through him several Toronto University graduates became
assistants of the latter. Among these may be mentioned.
Barker, Parsons, Thomas McCrae, the late John McCrae —
the immortal composer of " In Flanders' Fields,'' Gwvn, and
the writer. It may be of interest to note that all these, with
one exception, were previously resident physicians during the
summer months at the Robert Garrett Hospital for Children
at Mt. Airy, Md., which was under the direction of Dr. Walter
B. Piatt. Barker, later succeeded Osier, as professor of medicine. The writer, and Thomas McCrae, in turn succeeded
Thayer as resident physicians. W. G. MacCalluni, now the
professor of pathology at Johns Hopkins, although a medical
graduate of this university, but a graduate in the aca'Hemic
department of the University of Toronto, was, after graduation, an assistant on Osier's staff. Mention is made of these
various Canadians to point out how Osier acted as a magnet to
draw them from across the border to Baltimore, and to emphasize the fact that they have, through their "chief," indirectly
constituted an important link helping to keep up intimatfi
associations between the profession on both sides of the line.
Following Tliomas McCrae, the resident physicians, with the
exception of B. A. Cohoe, a medical graduate of Toronto
University, who served from June to Septeniher, 1908, have
all been graduates of The Johns Hopkins Medical School.
They have been in succession, Rufus I. Cole, Charles P. Emerson, Thomas R. Boggs, Frank J. Sladen, Paul W. Clough and
the present occupant, Arthur L. Bloomfield. Cole was the only
one of these who served as resident physician during Osier's
occupancy of the chair of medicine, although Emerson and
Boggs were assistant resident physicians under him before he
left for Oxford, in 1905. Osier's ideals and influence have
been disseminated by this group of resident physi(Jians in tlie
various fields in which their activities have been ca.st.
The first edition of Osier's " Principles and Practice of
Medicine " appeared in 1892. This, and the subsequent seven
editions, have been the standard text-book in medicine used
by students and practitioners in both the United States and
Canada. The influence of this work, with the fascinating and
practical way in which the various diseases were treated, has
been very great on the professions of both countries. The same
can be said for the two editions of " Jlodern Medicine," of
which he was chief editor, Thomas McCrae being associated
with him.
Throughout Osier's professorship at Johns Hopkins, courses
to post-graduates were given yearly. The medical school was
not opened until 1893, and under-graduatc instruction in
medicine consequently did not begin until 1895, so that, up to
that year, post-graduate instruction was the only teaching
conducted in the medical wards. Osier's ward clinics and
clinical lectures were attended by physicians from all parts of
the United States and Canada. Members of the profession
rubbed shoulders, gained invaluable clinical experience, and
formed professional ties and friendships which have continued
ever since.
Although domiciled in the United States, the Canadian
profession always felt that it had a personal claim on Osier.
His trips to Canada to see his family in Toronto, to consult
with physicians, to read papers before societies in various parts
of the Dominion, and often to spend his vacation on the lower
St. Lawrence, enabled him to keep in close touch with the
profession of his native land and to exert a strong influence on
its members north of the border.
Almost as important a sphere of influence as The Johns
Hopkins Hospital was Osier's home at 1 West Franklin Street,
where physicians from both sides of the line were always welcome, and where they were ever made to feel at home by the
" chief " and his gracious wife, now Lady Osier.
In 1905 Osier was called to Oxford to occupy the chair of
Regius Professor of Jledicine in that university. His interest
in the medical profession of both countries has not a whit
abated. The home of Sir William and Lady Osier, at 13 Norham Gardens, has been almost a daily rendezvous for the khakiclad medical officers of the American and Canadian Expeditionary Forces during the last two years of the world's war.
OSLER AS A CITIZEN AND HIS RELATION TO THE TUBERCULOSIS
CRUSADE IN MARYLAND
]',v lIiNRY Barton Jacobs
Though Osier like Nathan Smith, Austin Flint and Marion
Sims and the philosophers of old is essentially a peripatetic,
a medical nomad, yet wherever his feet may take him. there
he establishes and identifies himself, interests himself in local
conditions and undertakes the responsibilities of citizenship.
In the course of his wanderings Baltimore has had the
privilege and the profit of halting his onward steps for fully
sixteen years. Here he came in the vigor of his promising 40
years, trained and ready, not to say anxious, to jump into the
life of his new surroundings. Many paths there are which lead
to useful citizenship — Osier cho.se one peculiarly his own, and
followed it consistently and unfailingly, guided only by the
unswerving conviction that whatever he might do to advance
and improve conditions in the profession to which he was
206
[No. 341
allied, in that way alone could he be of the greatest benefit,
not only to those immediately under his tutelage or care, but
to the city and to the nation at large. In his final address on
leaving Baltimore he says " I have lived my life in my beloved
profession I have never departed from my ambition to
be first of all a servant to my brethren."
The advancement and improvement of medicine and service to his fellows, therefore, is the primary path of his endeavor. The wayside results of such a course pursued with
intensity, with kindness, with sympathy, with laughter and
joke, with good fellowship and hospitality, also with hard
study and thought and work, diligently and persistently, year
by year, are quite unusual, and lead as is only natural to
wide friendships, extraordinary and general influence, both
with individuals and with peoples.
Scarcely had he arrived in Baltimore in the spring of 1889
when he was asked by the officers of the State ]\Iedical Association, the old Medical and Chirurgical Faculty of Maryland, to deliver the oration at the annual meeting of the
society to be held in April of that year. This invitation he
accepted, choosing for his topic " The License to Practice."
At this period it should be recalled there were in Baltimore
no less than four or five medical schools with two-year courses
of study for a degree to practice, and this degree the only
license required. The argument Dr. Osier made in his address was so cogent, so direct, so illustrative of the evil conditions existing that immediate steps were taken by the
leaders of the medical profession of the city and state to liave
prepared a legislative Bill for the appointment of medical
examiners whose duty it should be to examine candidates, and
to issue to the successful ones licenses to practice. This was
Dr. Osier's first effort in Maryland toward the advancement
and improvement of medicine, and coincidently his first pronounced effort in good citizenship. As a farther resultant the
University of Maryland decided to lengthen its course of
medical study and to raise its standard. Moreover, the
seed was growing so fast that in February, 1890, a meeting of
representatives of all the medical schools of Baltimore decided to request delegates, from the medical schools of the
country, to meet in JSTashville with the idea of raising the
standard of medical schools all over the United States. At
this conference an agreement was reached for a three-year
course and other reforms.
The Legislature of 1890 passed the Bill for the appointment of a board of medical examiners, a bill which looked
to the betterment of medical practice in Maryland and to
the general elimination of the numerous quacks and charlatans who had been permitted to carry on their trade in the
state. Unfortunately Governor Jackson did not give his approval, and so two years had to go by before its final adoption
by a new Legislature, and the signature of Governor Brown.
This was but the beginning of Dr. Osier's eiforts for better
state and municipal laws.
The almost unrestricted prevalence of typhoid fever in the
United States, particularly in Baltimore, was a source of
deep aggravation to him, and called for the use of all his
powers of voice and pen to bring light into the darkness, that
rational legislative measures might be inaugurated to restrict its incidence.
Baltimore at this time was without a general system for tlie
disposal of its sewage. Backyard privy vaults were nearly
universal. Dr. Osier was strongly of the belief that typlioid
fever would be greatly reduced with the introduction of a
proper and adequate sewerage system and a pure water supply.
Xote how vividly and forcefully he spoke at the meeting of
the Maryland Public Health Association held on November
13, 1897, upon the subject of mortality from typhoid fever
as related to these important city improvements :
The penalties of cruel neglect have been paid for 1896; the dole
of victims for 1897 is nearly complete, the sacrifices will number
again above 200. We cannot save the predestined ones of 1898, but
what of the succeeding years? From which families shall the
victims be selected? Who can say? This we can predict — they
will be of the fairest of our sons and of our daughters; they will
not be of the very young, or of the very old, but the youth in its
bloom, the man in the early years of his vigor, the girl just wakening into full life, the young woman just joying in the happiness of
her home. These will be offered to our Minotaur, these will be
made to pass through the fire of the accursed Moloch. This, to
our shame, we do with full knowledge, with an easy complacency
that only long years of sinning can give.
Such writing as tliis is not only convincing, but is intensely
moving, and must have played no small part in securing the
desired end which happily came before he was to leave our
city, a boon and a convenience to every member of the community, not to speak of the assthetics of the new order when
street and sidewalk gutters were no longer redolent with the
morning's dishwashings.
Whatever gives promise of adding to the stock of medical
knowledge immediately arouses Dr. Osier's enthusiasm.
Early he became interested in the amcebic theory of malaria.
Well do I remember his coming to the Massachusetts General Hospital in Boston to demonstrate amoebae in blood corJ)uscles to Dr. Fred. Shattuck, then the young medical attendant to that hospital. This must have been in 1887 or
1888. No effort of his for good citizenship, or for the advancement of medicine was more remunerative than the stimulus
he gave in this country to the solving of the problem of the
causation, cure and prevention of malaria, a disease which
had so sorely afflicted the people of states south of Mason
and Dixon's line. Baltimore became the prime center for its
study outside France and Italy, and Thayer's book written
in The Johns Hopkins Hospital from Osier's clinic marks a
salutary epoch in the history of this mosquito-borne infection.
Never was it out of Dr. Osier's mind that a better educated
and more widely read medical profession made for better living conditions of the people, greater civic comfort and diminished suffering and death, so in all ways possible he encouraged students and practitioners alike to greater learning.
To this end he insisted upon greater comradeship and larger
attendance upon medical societies where experiences could be
interchanged and interesting cases seen and discussed; he
also insisted upon enlarged librarj' facilities, and adequate
^
THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1919
PLATE XXV
1
si,i:it. I'.AiiT.
Wllllnm lh<' K..WI.T, Ciilllniimo roiBi-liMir I
I lore In I'lill hliii tliii!' mill wlii-n I hiiiii
The I'liiinti'rri'li |iri'»4'ntiii<'nl iif the niiin.
I fcrl hlH IM'I. I hi-iir hiK nrriiva whir.
Mnkc III thi' liKiii'l.v Kiiriiiinii- no ili'iiiiir,
Nnr nil II nniiiliiiillon liiy n linn
With which II II if Mivrnn liirilK Iipbiiii,
lli-nry Ihi- Kowlrr wim flmt Kiniifmr.
Ani'li'iiliix wii» A|Milli>» rhnwn mm.
I'.iil til ihiil oiiii hi' ni'ViT li'hl hU Imw,
.Ni.r illil lli-iihii.".iii» iiiiih 111 fiirci- hl« ni'l :
lliith siM-riis hiith Imiiirhil HkIit wmi.
Ills ninci'il wiinl?! 'iriil.-hl In Ihi'lr i|iinrry gn.
Ail hi'iirm lire hnMi-ii li.v hli mi>»hi'K yi't.
Il.\»ii. I,. (iii.iii:iisi.i:»:vK
f
July, 1919]
207
supplies of current medical magazines and standard books.
Under liis inspiration and leadership the old state society of
Maryland took on a new life, and its I'bnuy so long nuiuKlering on it*; shelves sprang into usefulness. To him more than
to any single man does the medical profession of Maryland
owe its present faculty building with its large and growing
library — a library in Mhich he took no less interest than in
his own. To this extent, then, we must think of him as
contributing enormously to the welfare of the community
through an enlightened profession influencing public opinion
in matters pertaining to health, sanitation, and general hygiene.
Xot less than his trenchant writing and speaking was Dr.
Osier's own personality of influence upon men and the community; so strikingly straightforward, so genial, even convivial, so playful in youthful spirit, so enthusiastic in helpfulness and sympathy, so painstaking and so wise, he .^oon
had both patients and acquaintances alike in an attitude of
devotion, almost. I might say, of adoration. And although
he took no otticial part in the civic affairs of the city, he
gained through his association in the medical profession, by
reason of his acknowledged eminence in that profession, and
through his friends and acquaintances, a leadership in the
affairs of the city and state which was most powerful and
beneficent even though it was exercised in an indirect way.
From the moment when Koch discovered the germ of
tuberculosis in 1882, Dr. Osier has never lost interest in this
disease. He dwelt upon it in his teaching and he insisted that
his students should be familiar with it. When in 1892 the
use of tuberculin was thougiit to be specific, he was among
the first in this countrv' in giving it a thorough trial in
the wards of the hospital. For greater encouragement to
the study of the disease, which so long has been such a fatal
enemy of mankind, he suggested and carried out the establishment of a society whose single purpose sliould be the consideration of the history and the various phases, clinical and
pathological, of tuberculosis, and this .society he named, after
the great French student of tuberculosis and discoverer of the
stethoscope — The Laentiec.
On November 14, 1899, Dr. Osier read an important paper
on the " Home Treatment of Pulmonary Tuberuclosis," at
the semi-annual meeting of the faculty at Westminster, and
on the same day and in the same place Dr. Charles S. Millet of
E. Bridgewater, Mass., described his outdoor sleeping porches
for tuberculous patients. This was the first public discussion
of the value of unlimited night air in the cure of consum])tion
and marks a new epoch in the metiiod of treatment. Incidentally I may remark that at this same meeting mention was
first made by Dr. Joseph E. Gichner of the need and desirability of a State Sanatorium in Maryland.
On April 19, 1901, at the invitation of Dr. Osier, Dr.
Lawrence F. Flick of Philadelphia came to Baltimore and
before the Clinical Society delivered an address on the " Registration of Tuberculosis," saying that Philadelphia and Xcw
York had already inaugurated such a provision. Dr. Osier
urged that Maryland should do likewise, as in this way the
location of cases could lie known to the health authorities
and such steps be taken as would be of advantage to the
patient and to the community.
By tlie end of the year 19111 there had arisen great interest
in the tuberculosis movement, and it was proiui.scd that the
Legislature of January, 19(i2, sliould pass new and vital laws
which should be of benefit to the whole people. To this end
a big meeting in McCoy Hall was proposed under the auspices
of the Maryland I'uljlic Health .Association, the Medical and
Chirurgicul Faculty of Maryland and the Laennec Society.
Dr. Osier's "fiery "' speech thrilled the audience:
Mr. Chairman and my long suffering, patient, inert fellowcitizens: .... now what is our condition in this city, and what
are we doing for the 10.000 consumptives who are living today
in our midst? We are doing, Mr. Mayor and fellow<itizens, not
one solitary thing that a modern civilized community should do.
Through the kindness of a couple of ladies — God bless them! —
I have been enabled in the past three or four years to have two of
the medical students of The Johns Hopkins University visit every
case of pulmonary consumption that has applied for admission to
the dispensary of our hospital, and I tell you now that the story
those students brought back is a disgrace to us as a city of
500,000 inhabitants. It is a story of dire desolation, want and
helplessness, and of hopeless imbecility in everything that should
be in our civic relation to the care of this disease.
He then argues for registration, disinfection after death or
removal, a State Sanatorium for curable cases and a hospital
for advanced cases, a sewerage system and a hospital for contagious diseases. This address and others made tiie same evening had an effect, to \rit : The Legislature of 1902 created a
Tuberculosis Commission, the Governor naming Dr. Thayer
as its chairman.
All that is progressive or worth while in the Tuberculosis
Crusade in Maryland followed thereafter; the commission
with its advi.'iors taking the initiative in beneficial measures.
At Dr. John S. Fulton's suggestion the commi.ssion decided
upon a tuljerculosis exposition in January, 1904, which
should show graphically and practically the general incidence
of tuberculosis, its methods of prevention and cure, its
jetiology and pathology, it.s relations to social and economic
problems, and a history of its study from the time of Hippocrates. Such an exposition for any single di.sease had never
before been attempted. I^ectures and demonstrations were
given and the attendance not only from Baltimore but from
the counties and from outside the state was remarkable. The
public was inten.sely interested and the exposition "demonstrated that it is both expedient and practicable to admit the
general public to free participation in the scientific knowledge
of tuberculosis." (Editorial, Md. Med. Jour.)
Dr. Osier was the moving spirit in this most successful
undertaking and it was he who invited the distinguished
speakers who were heard. As a result of this exposition, the
Legislature of 1904 passed laws requiring:
(1) Registration of tuberculosis in Marjland, and
(2) Providing means and measures to be administered by
the State Board of Health for the domestic prophylaxis of
consumptives.
Growing out of this exposition, too, was the formation, fol
208
[No. 341
lowing the suggestion of Dr. S. A. Knopf, of the National
Association for the Study and Prevention of Tuberculosis. In
this enterprise Dr. Osier had a leading part. In its organization he was made vice-president, and since his residence in
England has been continued one of the two honorary vicepresidents, Mr. Eoosevelt being the second.
In December, 190-4, the Maryland Association for the Prevention and Cure of Tuberculosis was formed and again to
this local movement Dr. Osier lent his interest and enthusiasm. His last effort for the tuberculosis cause in Baltimore
was to induce Mr. Phipps to give the sum of $10,000 for a
Tuberculosis Dispensary at The Johns Hopkins Hospital.
This was opened with addresses on February 21, 1905, Mr.
Phipps being present.
In reviewing thus briefly the activities of Sir William
Osier during his sixteen years in Baltimore, I realize how
inadequately I have been able to convey any idea of his great
work and influence, or the universal esteem, love and honor
in which he was held not only by the people of ilaryland, but
by the country at large. I cannot believe that any man ever
left our shores for a new work elsewhere more deeply and
sincerely missed by a larger army of friends. His address of
farewell delivered before the Medical and Chirurgical Faculty
of Maryland April 27, 1905 on " Unity, Peace and Concord"
typifies his attitude to all his fellows both professional and lay.
In closing he sums up this relationship in the one word which
he leaves as his benediction — Charity — and the greatest of all
is Charity.
OSLER'S INFLUENCE ON OTHER MEDICAL SCHOOLS IN BALTIMORE
HIS KELATION TO THE MEDICAL PROFESSION
Bv Edwaed K". Brush
To estimate correctly Osier's influence upon other medical
schools and upon professional thought and conduct would
require an inquiry into the methods of medical teaching in
vogue more than a quarter of a century ago, and into the social
and professional relations of the physicians of the city and
state toward each other.
At about the time of Osier's arrival in Baltimore to assume
the duties of physician-in-chief to The Johns Hopkins Hospitiil there was a movement on foot to improve and enlarge
the medical cui-riculum. The University of Maryland in 18S9
announced that after 1891 a compulsory three-year course
would be required in the medical department with a preliminary examination in English.
In March, 1890, a call was issued by the medical staff of
The Johns Hopkins Hospital, and the medical faculties of the
University of Maryland, The College of Physicians and
Surgeons, The Baltimore Medical College, The Baltimore
University and the Woman's Medical College for the organization of a medical college association with a view to the cooperation of all medical teaching bodies in bringing about a
three-year graded ccurse, written and oral examinations, a
preliminary examination in English and laboratory instruction
in chemistry, histology and pathology.
At the meeting of the Medical and Chirurgical Faculty in
1889 the annual address was given by Dr. Osier, who took for
his theme " The License to Practice," and undoubtedly this
address gave an impetus to a movement, already receiving
support, for higher medical education and a better qualified
student body.
My own connection with medical teaching in Baltimore did
not begin imtil eight years subsequent to this date, but I
realized before that period, and have had oceasior. to know
since, the great interest which Osier took in promoting reforms
in medical teaching not only here, but in the country at large,
the great and lasting influence of his advice, and above all, his
example as a teacher.
Trained as he had been as a laboratory man, realizing to the
fullest extent the results which flowed from his laboratory
studies and tlieir bearing upon the practical work of the
hospital ward and the consulting room, as well as in the lecture
hall, he urged the establishment of laboratories.
Thoroughly equipped laboratories, in charge of men thoroughly
equipped as teachers and investigators, is the most pressing want
to-day in the medical schools of this country.
The hospital was, from his point of view, a college — a place
of teaching, the most essential part of the machinery of a
medical school.
The systematic use of the resources of the hospital which he
inaugurated and which he urged upon other communities and
described in detail in his address before the New York
Academy of Medicine in 1903 found in the minds of the more
progressive teachers of the Baltimore schools a ready acceptance.
For those working in my own special field, it is gratifying
to believe that it was a few words spoken in his farewell address
at the university, February 22, 1905, which gave an impetus
that resulted in the establishment of a psychiatric clinic at the
hospital.
From his address at the dedication of the Wistar Institute
of Anatomy and Biology of the University of Pennsylvania,
1894, I take the following:
What, after all. is education but a subtle, slowly effected change,
due to the action upon us of the externals; of the written record
of great minds of all ages, of the beautiful and harmonious surroundings of nature and art, and of the lives good or ill of our
fellows — these alone educate us, these alone mould the developing
minds.
The whole career of Osier in Baltimore, his life here as a
teacher, hospital physician, consultant and citizen was devoted
to the better teaching of medicine, to better ideals in education; and from his life, from his example, proceeded influences
which not only moulded developing minds, but stimulated all
Jii.Y, 1919J
209
who had a real ambition, to teach and, in teaching, to learn
also, and develop.
To emphasize sufficiently his influence upon medical education is most difficult. One of his constant pleas for other
schools was for larger clinical advantages, and better use of
those alread)' provided. In 1897 in his address on Internal
Medicine as a Vocation, before the New York Academy of
Medicine, lie says :
To-day the serious problem confronts the professors in many of
our schools — how to teach practical medicine to large classes;
how to give them protracted and systematic ward instruction?
I know of no teacher in the country who controls enough clinical
material for the instruction of classes, say of 200 men, during the
third and fourth year.
Never a controversialist, none the less did he bear a large
share in the controversies of 30 or more years ago, which
preceded and eventually brought about the changes in the
methods of medical education which have taken place since
that time. His influence was exerted not in argument or
controversy, but in the force of e.xamplc, by the way in which he
lived his ideals and induced others to share them with him.
He studied " to be quiet " and do his " own business," " to
walk honestly toward them that are without " and one of his
chief pleasures was " to work among [us] as a friend sharing
actively in [our] manifold labors."
Some years ago I had occasion to apply to him a quotation from the presidential address of the late Dr. Charles M.
Ellis before the Medical and Chirurgical Faculty in 1898.
These words seem to me particularly appropriate to Dr. Osier :
Many [doctors] by reason of natural endowments and acquired
fitness elevate their lives to a professional plane on which it is
possible for an Intellectual life to develop; and on which it does
develop, not only to individual sufficiency, but to public usefulness
and a public influence, that on the one hand meets and supplies
public emergencies and, on the other, largely directs and controls
public thought and movement.
These words from what I know of tlic intimate and friendly
relations between the two men may well have been brought
to the mind of Dr. Ellis by his knowledge not only of the
intellectual life of Dr. Osier, but by his appreciation of the
controlling influence of his mind upon public tliought and
movement, particularly in professional circles.
Ver}' early in his residence in Baltimore, notwithstanding
that he " studied to be quiet," he became a by no means unimportant factor in the social life of Baltimore physicians.
He so regulated his work that he always had a certain
amoimt of time to give to his friends in social converse, or in
conference over the more serious things of their everyday lives
and work.
Ho appreciated the difficulties and perplexities wiiich surrounded the lives of many of his professional brethren and
many a burden has been made lighter, many dark hours brightened, by his wise and thoughtful advice and his cheering
optimism.
More than one doctor laboring amid discouragement and
the indifference of open opposition of his fellow-citizens, whose
lives he was manfully trying to make more tolerable, whose
surroiuidings he was endeavoring to make more healthful, has
found to his surprise that Osier had learned of what he supposed was unknown beyond the bounds of his own community,
and has received from him words of ciieer and commendation,
which were a powerful incentive to renewed effort, just when
all the uses of the world appeared to him "weary, stale, flat
and unprofitable."'
His farewell address " Unity, Peace and Concord " is an
eloquent recital of his consuming eagerness to be " a servant "
to his brethren to do all in his " power to help them."
He strove always to live in unity, peace and concord with
his fellows. He strove with none — not that none were worth
the strife, but because of a deep conviction of the hatefulness
of strife. Those wortli the strife he won by other and gentler
means, and bound them to him by the everla.<ting chains of
friendship.
In 1881 there was formed in Baltimore the Baltimore
Monthly Medical Reunion. It met at the home of members in
turn and around the dinner table and at the fireside many
friendships were made and consolidated. Very soon after
coming to Baltimore, Dr. Osier became a member of the
Reunion and always when he was present at the monthly
gatlicrings, as with The ^fcGregor, where Osier sat was " the
head of the table," the center of conversation, the focus of wit
and wisdom.
As in the past, so in the future in all that makes for truth
and righteousness, in all that holds forth liigh ideals, in all
that encourages culture and all tlie virtues of the Christian
gentleman and the ideal physician the name of Osier will bo
one to conjure with. From time to time, as on the present
occasion, his friends for many years, let us hope, will send
him greetings across the .«ca. He has given us the master word
and with that in our hearts all things are possible. Have we
not seen it exemplified in his life and character?
INFLUENCE IN BUILDING UP THE MEDICAL AND CHIRURGICAL
FACULTY
Bv Ilnt.vM Woods
" Influence in Building Up the Medical and Chirurgical
Faculty " is a theme one might approach from numerous
paths. So great was Dr. Osier's influence, in so many directions did it work, so broad was his conception of the possibilities for good in the organization, so keen his appreciation
of the obstacles to progress, some traditional, some personal,
that the many-sided subject is bound to appeal to his friends
in difl'erent ways. Adequate organization of the library ; revelation to the younger man of what the library even in those
days afforded; provision for the purchase of new books — these
210
[No. 341
are themes which have been selected for special review and
will be presented by others. I shall try to give some idea of
his work from another standpoint — that of personal influence.
Yet, with the selection of this special topic, I am aware that
I shall speak from my own personal impressions and memory
and may fail utterly to express the feelings of another just as
indebted to Dr. Osier as am I.
I have asked myself. What were Dr. Osier's basic thoughts
and principle in his work for, and devotion to, the State
Medical Society? He held the most influential position
medicine in Baltimore could give ; he had at command greater
powers than any one medical man had ever possessed in the
city ; his teaching and organization duties in the new medical
school were exacting enough to take all his time, and yet he
went to work on the state society in a way which soon gathered
recruits happy to work under — not his direction — but his
mind and heart. What led him to do it? I think he felt that
the biggest medical foundation Baltimore liad ever had ought
to benefit the existing profession. He thought there should
be a high valuation of the profession itself ; realization of the
obligation of self-improvement; a breaking-down of the
" middle wall of partition " between those, who, by a connection -with the new school, seemed to possess an advantage, more
or less adventitious, and those who foimd, or thought they did,
a definite obstacle to practice in the new Foundation. He felt
the meaning of " Unity." He told us of this — at least in
words — only on the eve of his departure. And yet he had told
us about it previously in a better way. Go over the papers he
lirouglit to the faculty meetings and the smaller gatherings of
the local society and you will, if I mistake not, see that he
presented the problems of disease, cause, prevention and cure,
as the same for tlie hard-worked country doctor, with little
time to read, and the man with hospital and laboratory
advantages, plus trained nurses and competent assistants. But
here the roads parted, in a sense. The practitioner brought
his experiences and difiiculties. Modern methods of investigation were not at his command. Dr. Osier felt that the man
with greater advantages should, in the first place, qualify himself to luiderstand the point of view of his less fortunately
placed colleag-ue, and then, from his greater advantages, make
up the deficiency.
Sometimes a chance thing makes a life-iong impression, and
such an occurrence has come back to me time and again. At a
society meeting typhoid fever was the topic. I believe I am
quoting accurately : " Typhoid fever, the monster that destroys the best of our sons and claims the fairest of our
daughters ; are we to let it continue or stop it ? " And then
followed a clear, scientific and yet almost a domestic demonstration of preventive measures which coiild be taken home
and taught to those who did not know, but who, if they knew,
might save their own and others' lives. This, I believe, was
Dr. Osier's motive force : aim to realize the other man's point
of views and his needs, and to reach these needs if he could.
But if such was the self-imposed task, success could come from
no wiser-than-thou attitude. There had to be a comradeship ;
not the assumed, patronizing variety, but the sort that cements
tlie minds and hearts of men earnest after the same thing —
knowledge. How many of us have met him browsing around
in tlie library, and soon foxmd ourselves just talking? Yet
from that talk we afterwards found we had gleaned a great
deal. It was from one such talk that I took away definite
impressions about the evils of narrow specialism. Again, after
we got to know him laetter, we would sometimes find him in
deep conversation with a beginner in medicine, or a man we
hardly knew, and we shied off. It was perfectly clear what he
was doing. But the comradeship was the real thing; there
was nothing professorial about it. This comradeship extended
beyond the confines of men who were active students for their
own good or those who needed prodding. It went after and
reached those > who had something to give, and who did not
know how to give it; maybe they did not know they had it.
There are matters of importance to the faculty and profession,
bearing others' names, which would never have come into being
without William Osier's realization of their importance and
pointing out the way to achievement. I cannot speak more
definitely; but men familiar with the faculty's history will
know. This comradeship went farther. It reached those who
for one reason or another had met nith little or no success.
It made them feel that in spite of what miight be termed
failure, honesty of purpose gave standing to a man in medicine
and brouglit him into unity with his brotliers upon wliom
fortune had smiled more kindly.
Work for the library, teaching its value by precept and
example, demonstrating the unity of the medical profession
and the spirit of comradeship soon won the esteem, confidence
and affection of men throughout our state. This feeling wa.*^,
possibly, best expressed in a telegram sent to Dr. Osier's
mother in April, 1905, when he was about to leave Baltimore.
The telegram was sent Ijy vote of the faculty at its annual
meeting and signed by the president, Samuel T. Earle. It
reads :
The greetings of the Medical and Chirurgical Faculty ot Maryland to Mrs. Osier, asking her to share their sentiments in taking
leave of William Osier, congratulating Mrs. Osier first on the
distinguished career of her son, but most on the innate qualities
which have endeared him to his associates in Maryland.
A few days later the following reply was received :
Mrs. Osier, who is unable from her great age to write, asked
me to express her heartfelt thanks to you for the very kind telegram of greeting sent through you from the Medical and Chirurgical Faculty of Maryland, and to say that the receipt of the
message gave her the greatest pleasure, more especially in the
expression of affection and appreciation called forth by the
personal qualities of her son, since these are, in her eyes, more
precious than all his honors.
She knows that it must be hard for him to sever his connection
with such kind confrrrrs. and she is sure that the friendships he
has made during his residence in the States will be among his
most cherished memories. I am, sir, yours sincerely,
jEiA.NNETTE OSLEB.
One w^ho had thrown his heart and soul into an enterprise
would be keenly disappointed if his work fell through in later
years. There seems no danger of this wliile there survive the
men who came under Dr. Osier's leadership. The funds
July, 1919]
211
obtained through his influence, and others, which have come
since, because of tiie spirit he put into the organization, are
keeping the faculty up to date. But these material things,
important as they are, would fail in tlieir purpose, unless
something else lived and permeated tlie faculty's life. I
mean tlie mental attitude wliich I have tried to present. It is
interesting to go over a book in a public library even if one
owns a copy himself. The latter he feels free to mark, but it
demands a certain amoimt of bad taste to mark passages in a
book which does not belong to you. However, this bad taste
does exist here and there and sometimes it may not be without
its advantages. It shows the other fellow's thought. Recently
I picked up " Aequanimitas " at the library and opened by
chance at the delightful es.say " Teacher and Student." That
a library-worn book like this should open right there is not
witliout significance. It means that there are youngsters
coming on now who are getting from the printed page some
of the things others got from personal intercourse. This
passage is marked with a heavy lead pencil :
The measure of value of a nation to the world is neither the
bushel nor the barrel, but mind: — wheat and pork, though useful
and necessary, are but dross in comparison with those intellectual
products which alone are imperishable.
In " Unity, Peace and Concord," written in 190.3, 13 years
after the essay to which allusion has been made. Dr. Osier
speaks of " the petition in the Litany in which we pray tliat
to the nations may be given unity, peace and concord." Then
follows this, which I do not attempt to summarize:
Century after century from the altars of Christendom this
most beautiful of all prayers has arisen from lips of men and
women, from the loyal souls who have refused to recognize its
hopelessness, with the war-drums ever sounding in their ears.
The desire for unity, the wish for peace, the lonKing for concord,
deeply implanted in the human heart, have stirred the most
powerful emotions of the race, and have been responsible for
some of its noblest actions. It is but a sentiment, you may say,
but is not the world ruled by feeling and by passion? .... As
with the nations at large, so with the nation in particular; as
with people, so with individuals, and as with our profession, so
with its members, this fine old prayer for unity, peace and concord, if in our hearts as well as on our lips, may help us to
realize its aspirations.
Now, 14 years later, wirli tlic world still "refusing" to
recognize its "hopelessness" and struggling toward the realization of permanent unity, peace and concord, these words
seem almost prophetic. From the " nations at large " through
successive steps, this great principle of unity, peace and
concord reaches the medical profession and " individual "
doctor. His comprehension and use of it will depend on his
relative valuation of the "barrel and bushel" and "mind."
Dr. Osier's method of upbuilding the faculty differed from
others' in that he aimed to inerea.*e the individual's receptivity
for what the faculty had to offer. So long as the faculty sees
its responsibility to offer only the best; so long as its members
appreciate the nature of wliat is offered and remember tliat
profit is a question of their own liearts and minds, there will
be no danger of deterioration ; but both are neccs.<ary. While
we are congratulating Dr. Osier and gratefully acknowledging
our debt to him, let us not forget what his cxam]de tiiught;
for it is only thus that we can keep what lie had .so large a
share in giving us.
OSLER AND THE BOOK AND JOURNAL CLUB
Bv J. A. Ch.vtard
Of all the varied activities and interests that occupied Sir
William Osier, while in Baltimore, possibly none appealed to
him personally, luid to the little group of supporters that lie
gathered about him in the early days of 189G, more than the
idea of getting together a few of the men of the profession at
periodic times for the discussion of old books on medical sul)jects and the presentation of papers on the historical side of
medicine. At the seme time the members, by their interest
in the work and by the voluntary sul)scri])tions olTered, helped
much in the improvement of the library of the Medical and
Chirurgical Faculty by the purclia.-ie of new books and journals.
In these early 90's the faculty was in a quiescent mood with
few regular meetings at which, for the most part, only routine
busine.<s was transacted. For lack of funds the librar}' was
much neglected and the book and journal files were far from
complete. This Dr. Osier saw and at once put his great
store of knowledge and earnestness, at the disposal of the
members of the faculty, with the result that the Book and
Journal Club was .soon in a flourishing condition.
Those of us who went to the early meetings can still remember the enthusiasm of Dr. Osier in his presentation of rare old
historical medical subjects or in the enlightening discussion
that he gave following someone else's ])aper. After some
time he would then sliow some of the fine old Iwoks illustrating
the talk, tho.«c books not infrequently coming from liis own
medical library.
But for one man's enthusiasm and zeal we might have
missed so many interesting tiilks on the " Hippocratic Writings," the " Plague of 1G30 in Milan," " Haney as an Embryologist," " Some Diseases Bearing the Names of Saints,"
"The Resurrectionists of London and Edinburgh," "The
Books of Vesalius," '' Assyrian Medicine," and last but not
least, our old friend Sir Thomas Browne. These and so many
other historical subjects he was instrumental in bringing
before us. leading us on to browse among the old masters
and find there the very things we may be looking for to-day.
During his presidency, the Book and Journal Club collected
over five thousand dollars by voluntary subscrijjtion and in
addition to paying for the binding of many journals, we were
able to pun-base annnally about 2T0 books and subscribe to
56 journals. To tho.<e of us who know how crippled the
313
[No. 341
finances of the faculty were at that time, and how little was
available for the library fund, this money from the Book and
Journal Club was a treasure indeed.
To the older members of the faculty his work and zeal for
their interests was of wonderful help and assistance, and liis
close association with them will always be looked back on
with the deepest and most lasting pleasure. To the younger,
some of whom are now among the older members of the
faculty who knew him at that time and worshipped from afar,
his example should be a help to be better students and workers.
To the youngest members of the faculty, who, alas, knew him
not, it becomes a duty to emulate his efforts in historical study
and so join in the company of those who can find that all is
not dry and musty in the old discolored books upon our shelves.
It is only by thus fostering and helping along a search for old
tniths that the newer ones assume a more crystalline appearance and we are better able to value them in the light of
advancing thought.
OSLER'S INFLUENCE ON THE LIBRARY OF THE MEDICAL AND
CHIRURGICAL FACULTY OF THE STATE OF MARYLAND
By Ma]:cia C. Noyes, Librarian
Associations of Dr. Osier are so interwoven with the library
of the Medical and Chirurgical Faculty that what we have
become is, in reality, but an expression of what we felt he
would have us be.
The name of Osier is writ large in the history of the library
from the time of his first connection with it in 1890 ; and the
impression made by his character on the
lives of those with whom he came in contact has been a powerful influence for
the betterment of medicine in ilaryland
and in the upbuilding of the state society
and its library.
Dr. Osier was elected a member of our
Library Committee in 1892 in which
year the committee reported difficulties,
financial and otherwise, in the management of this " most valued and noble
inheritance." Although never serving
as chairman, that he lent himself to the
surmounting of these difficulties we
know, and what was accomplished between 1893 and 1905, his tenure of office
on the Library Committee, is given, in
part, herewith.* From a collection of n
few thousand old books in 1892 it grew
to 14,590 volumes in 1905, and has
grown steadily ever since.
The library, which dates from 1830,
had been partially revived in 1881 and
was housed in rooms in the basement of
the old ]\Iaryland Historical Society in
1885; but it was Dr. Osier's interest
which brought about its renaissance and the purchase of and
its removal to the home at 847 N. Eutaw Street (Hamilton
Terrace) in 1895. After a year without proper supervision
it was owing to Dr. Osier, who personally saw to it, that the
Library Committee employed a trained worker and the present
LIBRARY
OF THE MEDICAL -aJ^D . .CHIRURGICAL FACULTY
OF THE ST T^ ^ ^'^^.rt^^OF MARYLAND
PURCHASED THROUGH T" IF
WILLIAM OSLER
TESTIMONIAL^FUND ,, :
FOR THE ADVANCEMENT OF MEDICINE
* When abroad for his annual outing, Dr. Osier always had the
needs of our Library in mind, and we owe many of its greatest
treasures to hisi interest. Some of these were a direct gift from
him, and others selected for purchase on the Frick Fund.
librarian took charge. To him we owe the founding of the
Charles Frick section of the library, in 1896, which was made
possible by the generosity of Messrs. William F. and Frank
Frick; and the establishment of the Book and Journal Club
at about the same time. These funds gave the Library a definite income for the first time in its history.
Dr. Osier was president of the Faculty
in 1896-1897, and in his presidential address, April, 1897, in outlining the purpose of, the Book and Journal Club, and
of the Frick memorial said : " I envy
Charles Frick the good fortune to go
down to the future generations in this
Faculty with his name linked to an important section of our library. Posthumously and by proxy, as it were,
tlnis to carry on, though dead, the work
lie was interested in while living, is the
nearest approach a man can make to
rheating the great enemy, and in
Charles Frick's case it is in a measure a
(•(impensation for the untimeliness of
Ills taking off." He also spoke of the
approaching centennial as follows : '" We
' :in try in the centennial year to obtain
1 proper endowment for the Faculty
hom our friendj among the citizens.
We shall need a larger hall, more in
keeping with the rank and work of the
profession of this city — quarters as complete as our brethren enjoy in Piiiladelphia and New York. And an endowment yielding a few thousand dollars annually is absolutely
essential for the proper development of the library." At the
centennial of the Faculty in 1899 he gave the first thousand
dollars toward such an endowment fund; and it may safely
be said that it was principally due to his influence that the
Charles M. Ellis bequest was made in 1910.
It was because of the widespread desire to honor Dr. Osier
that the present home of the library, at 1211 Cathedral Street,
became a fact in 1909 ; and because of a further expression of
July, 1919]
, JOHNS HOPKINS HOSPITAL BULLETIN
213
this desire that the Osier Testimonial Fiind for tlie purchase,
in his name, of books on medicine was presented to us in 1917.
It is singularly fitting that his name should be linked for all
time witli that of the Medical and Cliirurgical Faculty and
its librar}', for he delighted so keenly in the phrasing of the
old title — the chirurgical, so hard for the uninitated to pronounce — and in the usage of the word faculty instead of
society. The development of the library, to its fullest extent,
interested him beyond measure, for he was not only a lover,
but a user of books, and he insisted that his students should
learn the art. The familiar slip bearing his reference was
presented almost daily by some one of them, and our reading
room on Saturday afternoons became a rendezvous for students
and physicians who thought to meet him there to seek his
advice. In those days, the pausing of a hansom at the door,
if followed immediately by a cheery whistle, presaged his
advent to the initiated. Hardly a Saturday passed without
Dr. Osier coming to scan the shelves containing the new
journals and to browse among the books to be found in the
Charles Frick Reading Room.
Akin to his interest in books is his interest in medical
libraries in general, and he was intimately familiar with and
always a welcome guest at the library of the Surgeon General's
Office, the College of Physicians of Philadelphia, the New York
Academy of Medicine, the Boston Medical Library and the
library at McGill University, as well as the libraries in Baltimore and manv of the smaller medical libraries elsewhere.
some of which he fostered. He was not only familiar with tlie
books in tliese collections, but he knew intimately the catalogers and workers who do not usually come in contact with
the readers, as well as the librarians in charge.
This interest found expression in the founding, in conjunction with Dr. George M. Gould, of Philadelphia, of the Medical
Library Association in 1898. Owing to his generosity our
library was a member from the beginning, and has become an
influence in the medical world because of this membership and
our connection with the exchange of the association.
No one man has so left his imprint on the libraries of two
continents as has Sir William Osier, and a quotation from his
address "Books and ^fen " delivered in 1901 at tlie opening
of the new building of the Boston Medical Library, at 8 The
Fenway, simis up wliat his example has meant to this library
and Faculty:
It Is hard for me to speak of the value of libraries in terms
which would not seem exaggerated. Books have been my delight
these thirty years, and from them I have received incalculable
benefits For the teacher and the worker a great library
such as this is indispensable. They must know the world's best
work and know it at once For the general practitioner
a well-used library Is one of the few correctives of the premature
senility which is so apt to overtake him. Self-centered, selftaught, he leads a solitary life, and unless his everyday experience is controlled by careful reading or by the attrition of a
medical society it soon ceases to be of the slightest value and
becomes a mere accretion of isolated facts, without correlation.
SOME EARLY REMINISCENCES OF WILLIAM OSLER
Bv IIexry M. Hurd
In September, 1883, while on a vacation trip with a friend.
I stopped at Kingston, Ontario, and found my.«clf in a busy
throng of physicians in attendance upon the Canadian Medical
Association in annual session there. The physicians were
diligent in their attendance upon the meetings of the as.sociation, proud of their mutual calling and eager to advance it.
The secretary- of the organization, and one of the leading
spirits, was Dr. Osier, a resident of Montreal, a young man of
34 years, who then, as always, appeared younger. He knew in
person every physician present and was easily the guiding
force in the association. He participated freely in the discussions which followed the reading of papers and did not hesitate to express his mind freely and frankly on all important
questions. In the meetings there were the usual differences of
opinion between the rank and file of the profession and the
members of the medical examining board and verbal encounters sometimes took place between many men of different
minds. Osier spoke boldly and without reserve and had an
opinion upon all matters, but never seemed to excite ill feeling
or lasting resentment on the part of those who differed with
him. He was an excellent secretary and carefully watched
the progress of the special work of the meetings. He was
spare in figure, with a sharp, piercing eye, and although of
sallow complexion, was vigorous and in excellent health. He
was neatly and quietly, but carefully dressed and in manner
and bearing displayed the characteristics which I later learned
to recognize and appreciate as peculiar to him. One circumstance in the meeting attracted my attention in a special way ;
a prominent member read a paper entitled " The Conduct of
Medical Men Towards Each Otlier and Towards Each Others'
Patients," which displayed great wrong-headedness and perversity of feeling in reference to the relations of pliysicians to
each other in the matter of consultations over very ill patients.
He held tliat a physician was justified, when called in consultation, in getting control of his brother practitioner's
patient and concluded by saying: "Take all the ca.ses you
can get and keep them if you can without reference to the
rights of any other attending physician," He also deemed it
justifiable to report one's cases of operations or extraordinary
cures in tlie newspapers and inquired, "Why should not
medical men report their cases as well as a lawyer his speeches
or a clergyman his sermons? " When he had concluded reading his paper he was called sharply to order by several members
and referred to the Code of Ethics which existed in Canada to
govern the relations of physicians t/> each other. Whereupon
the offender announced that he had never seen any such code
and that it had no meaning to him. Dr. Osier sprang to his
feet and drew from his pocket a pamphlet copy of the Code of
21-1
[No. 341
Ethics wiiich he waved about his head and in a loud, clear
voice announced that he took great pleasure in supplying a
copy to his innocent and untutored friend and was glad to
learn that he had " sinned unwittingly through ignorance."
In 1889, when I came to Baltimore, I found Dr. Osier in
temporary charge of The Johns Hopkins Hospital, which had
been open in part for a few weeks. He lived at the hospital
and guided its work in company with Dr. Halsted and such
members of the early staff as Lafleur, Brockway, Clarke and
others. I remember on my first visit while walking along
Broadway in company with Osier and President Gilman, the
day being very hot, the latter, as usual, had an umbrella which
he used to protect himself against the rays of the sun. He
invited Osier to walk with him, who declined saying, " The
chill of nearly 40 Canadian winters is still in my veins and I
do not need any such shelter."
He was a delightful companion with children and took much
pleasure in conversing with them and even mystifying them
by detailing remarkable personal experiences and sometimes
tragedies. Once he invited two young girls to a luncheon at
his house on Monument Street, where his niece, now Mrs.
Abbott, kept house for him. He came late to luncheon and
explained his delay by the fact that he had been caught in a
down-pour of rain when crossing Monument Square which
had produced a flood sweeping him off his feet; that he had
escaped only after vigorous swimming and had barely saved
himself by grasping the shaft of the Washington Monument
with both arms. A more harrowing tale was that of the loss
of a young friend by falling from his row-boat into the
St. Lawrence Eiver. He explained that he might have rescued
her had he not resolved never to act hastily and without due
consideration. He had accordingly tossed up a coin to determine what his action should be. It fell adversely and he
rowed ashore alone weeping bitterly ! Fancy the difficulty of
duly impressing high moral precepts upon the young in tlie
light of such a confusing example. Children delighted in his
presence and were charmed by him, but \evy naturally were
always uncertain as to the logical nature of his conclusions
and equally puzzled by his apparent indifference to conventional conceptions of duty and obligation. There was also in
his attitude towards pupil nurses a similar light-hearted
irresponsibility which marked some portion of two addresses
to nurses to which reference is made later. It is possible,
however, to perceive that under the cloak of these apparent
trivialities there lurked a seriousness of purpose and a keen
desire to point a painful moral in a kindly way. AYitli
children, however, it was simply an expression of his ample
imagination and of his desire to please and puzzle them. Even
older people were sometimes at a loss to follow his moods and
strange fancies. He was invariably cheerful, hopeful, and
optimistic even under circumstances of discouragement and
doubt. I remember on one occasion one of his colleagues,
mystified by his imperturbability in a trying emergency said,
" Osier drop your mask, let us know what you actually think
of the situation," but no one ever did gain that knowledge.
Osier's habits of work, while he resided at The Johns Hopkins Hospital, were exemplary and somewhat unusual for a
man of literary taste. Such men are usually inclined to turn
night into day, but he rose promptly at 7 a. m., took his bath
and breakfast and was ready for work at 8 o'clock. He seemed
to have a faculty for setting his mental machinery in motion
immediately and accomplished effective work -svithout delay.
Wlien his secretary came he generally began to dictate and by
practice acquired great faciUty in terse and vigorous expression. This quality also was undoubtedly assisted by his
familiarity with King James's version of the Bible, the
Prayer Book, and Sir Thomas Browne. His method of the
preparation of the Principles of Medicine was worthy of
being followed by other writers. He gathered the literature
of any subject which he had on hand by judicious foraging in
his library and elsewhere. The volumes thus collected were
piled four square generally, open at the page to be consulted
upon the table, as long as room sufficed and later upon the
floor until movement about the room was much restricted. I
remember that when after seven months of strenuous labor
he completed the first draft of his treatise on medicine I
chanced to look into his room and found that it contained an
immense heap of books piled as high as the table like an
ancient sacrificial altar. The first draft was carefully revised
wdth no great amount of change in sentences and forms of
expression. Such changes as were made, however, did not
destroy the crisp, breezy style or the epigrammatic form of
expression which has always been characteristic of his literary
work. The book contained many personal references which
gave peculiar satisfaction to his friends l)y reason of the goodnatured personal touches he frequently gave to the cherished
beliefs and traditions which he did not share. I remember
in speaking of the use of turpentine in typhoid fever, he said,
" The routine administration of turpentine in typhoid fever
is a useless practice for the perpetuation of which, in this
generation, H. C. Wood is largely responsible." This somewhat pointed condemnation of a generally recognized method
of treatment at that time brought forth a vigorous rejoinder
from Dr. Wood in a medical journal, but fortunately there
was no loss of friendship on the part of either Osier or Wood.
Osier was also \ery scrupulous in fulfilling his duties in
attendance upon the meetings of medical societies. When
once informed by a student that he did not attend the meeting
of a medical society because he was not sure that he could get
anything out of it he replied, " Do you think I go for what
I can get out of it or for what I can put into it ? " Those who
knew him felt a deep impression that in all activities in
medical societies and in behalf of his students he labored solely
to inspire them with a love of work for its own sake and for
what he felt to be its final effect upon their growth and
development.
This fact was brought out in his relations to the Training
School for Nurses, established at the hospital in October, 1889,
which were of an ideal character. He had a warm friendship
for Miss Hampton, the organizer of the school and its first
principal, and also for Miss Nutting, her successor. He gave
THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1919
PLATE XXVI
Xi<
Taken in 19(i1.
Takkn in 191;
T.VKKN IN 1902.
Taken in I'JIS.
JrLY. 1919]
215
mueii assistance in tlio way of advice and in teaching and was
waimly interested in its success. He gave two graduating
addresses also, one entitled, " Nurse and Patient,"' and the
other, " Doctor and Nurse." He was appreciative of the work
of nurses and touched lightly and gracefully upon the mutual
relations of the nurse to her co-worker, the doctor, and to the
object of her care, the patient. There was, however, a suspicion of an attitude of reserve towards trainetl nurses as a
class a.s may be inferred by the quotations which preceded
these addresses when published. One, for example, had this
significant motto, from the Psalms of David, " I said I will
take heed to my ways that I offend not in my tongue. I will
keep my mouth as it were with a bridle.'' The other quotation
was from Sir Thomas Brownie, '' Think not silence the wisdom
of fools, but if rightly timeil the honor of wise men who have
not the infinnity, but the virtue, of taciturnity and speak not
out of the almndance, but the well-weighed thought!* of their
hearts. Such silence may be eloquence and speak thy worth
above the ])ower of words."
Osier in fact seemed always appreciative and helpful while
at tlie same time he had an air of detachment as one who was
endeavoring to sec whither the movement for the education of
nurses would ultimately lead. In the end I am sure that he
learned to understand and appreciate the work of the training
school and felt the great importance of it to physicians and to
the advance of the science of medicine.
OSLER AS I KNEW HLM IN PHILADELPHIA AND IN THE HOPKINS
Bv Howard A. Kelly
I find myself wondering, in these days of pleasant retrospection, now that our much loved friend Sir William Osier
is so splendidly rounding out his seventh decade, whether, of
all his friends here, I may not claim the credit of having
known him first.
I was living in Philadelphia up in the big mill district of
Kensington, culling a surgical out of a large general practice,
and at the same time keeping in close touch with things at the
University of Pennsylvania, for eight years my college, when
it became manifest that some fresh and stirring blood had
entered the college life.
The university, with so many eminent men camping on her
very doorstep in Philadelphia, and with that tendency to
nepotism, a form of paternal pride seen in all successful
institutions, had, as we younger men thought, driven John
Guiteras of brilliant promise in general medicine, away from
her doors to protect Pepper from rivalry, and now, not without
great hesitation as we understood, she had actually broken
her shackles, throwni traditions to the winds and inillcd
William Osier down from McGill in Montreal.
Fresh invigorating currents of life and new activities in our
stereotyped medical teachings began at once to manifest themselves, and every sturdy expectant youngster in short order
lined himself up a.s a satellite to the new star. Osier breezes
were felt everywhere in the old conservative medical center,
and yet it was not without some difficulties that he securely
established himself. Weir Mitchell, who had rea.«!on in his
later days to cultivate kindlier feelings towards the university
than in his young nianhcwd, was from the first Osier's devoted
and intimate friend, and one by one the faculty was won to
appreciate him, perhaps including even Pepper too, though I
am not so sure. My own life touched Osier's in the Kensington mill district in northeast Philadelphia. A.side from
anatomy and chemistry, I got most of my real medical education while a resident in the Episcopal Hospital and next in
the homes of the Kensington folk. Wood's physiological
therapeutics, and Still^'s didactic lectures on medicine seemed
deadly to me, and worst of all was Tyson's pathologj- elucidated
by Formad's quizzes. So it remained to get the education at
the bedside, and here Osier came to my aid. It was more than
a Sabl)ath day's journey in those days to go to Kensington
from the heart of the city; it was an hour in the street car,
and a long drive over bad, very bad, Philadelphia streets, but
Osier came and Agnew came with their lamps in their hands
to illuminate a few of the problems in the vast domain in which
all medical graduates are jiresumed to be experts.
I think the first patient that Osier saw w^as .suffering from
anorexia nenom, a condition wliich I had never seen before,
and of which I was ignorant. He stayed to dine in Norris
Square, and was particularly interested in my collection of
old medical books.
Then he was whisked away to Kaltimore, and then after a
year's time, I followed at his behest, glad to have a more
concentrated field of work.
Here I can add nothing, for his record is knowni and read
of all men, and what a blessing he, and Welch, and Halsted,
and Hurd proved to he in this community. I leave others to
appreciate Osier's skill as a medical man, and his love of the
classics. I always think of him first of all as one who brought
order out of the chaos in the medical profession of this city, a
great task effected by his kindly jier-^onality, his insight
into human nature, and the genuine affection he ever felt for
all men who were even half way good.
It was a .settled ])olicy of Osier's life never to speak ill of
any one but always lo find the good, and in that way he converted the hostile cam]) of Baltimore into a kindly family of
cooperating doctors.
Jleflicine here had fangs in the old days. Osier and Welch
more than any others drew them : and so made possiide medical
progress.
I want to lay claim to the gift of prophetic insight (a role
I doubt not in which many of my colleagues have anticipated
me) ; I had said from the first that Osier was bound for
London, and in the old days I longed to be ready to go with
216
[No. 341
him when he went. The outcome has exceeded, I think, all our
anticipations, and who but he would have maintained unabated
the same interest in all his old friends, and who else could
have turned the ocean into a highway, and his new position.
detached as it is from any vast clinical facilities, into a veritable medical Mecca for all our American medical world. That
many lustra may still be added to the kindly years of Lady and
Sir William Osier is the wish of many hearts.
OSLER AS A BIBLIOPHILE
By Thomas
Adequate treatment of this important side of Dr. Osiers
activities would far transcend the present writei-'s abilities and
the space allotted to this article. But it may be of some value
to discuss briefly Dr. Osier's interest in old books as reflected
in his informal talks with the students.
In looking back it seems to the writer that tlie interest in
the early editions was a development of the fundamental value
he placed in the study of the history and evolution of the
science and art of medicine, and that it was in connection with
his studies of the fathers of medicine in all times and countries
that he began that collection of first and rare editions which
has now reached such remarkable proportions.
WTien the plan of collecting the works of the founders of
British Medicine was first originated is unknown to the ^\Titer,
but it had already reached a large degree of perfection at the
time when the class of 1901 began to make the Saturday evening visits to the old house at No. 1 West Franklin Street.
Most of us will ever retain the delightful recollection of
those informal gatherings about tlie big table in the diningroom, when after the discussion of the week's work in the
wards was finished, " the chief " would bring out some of the
books from the special shelves devoted to the masters of
medicine and show us the first editions, tell us the story of
their discovery and acquisition, point out the notable passages,
and give the salient facts in the author's life history. For
many of us this was the beginning of our knowledge of the
histoi7 of medicine and of our own feeble attempts to follow
in his steps as collectors.
How reverently we handled and admired the rare little
volumes, of Linacre's grammar, or the spurious first edition
of the Eeligio, or Digby's Animadversions, with their choice
bindings by Riviere or Zaehnsdorff. How thrilled by the story
of the discovery of such a treasure on a York bookstall, bound
in with an Almanack and bought for half a crown. With what
delight we turned the pages of the tall copy of the Pseudoxia
Epidemica and dipped into the grave Sir Thomas's discussion
of the verity of the pictures of God, or the popular idea " that
elephants have no knees." A beautiful Aldine from Mead's
own library brought out the story of that great collector and
his testamentary instruction that his library be sold so that
others might have some of the pleasures of acquisition wliich
he had so much enjoyed. We were given a glimpse into the
special lore of the bibliophile, and learned something of the
work of the pioneer printers and of the great presses of a later
R. BOGGS
date. We learned a little of the fonts of type and the watermarks of papers, as well as the characteristics of the bindings
peculiar to certain periods. The nature of book auctions was
disclosed to us and we became familiar with the magic names
of Sotheby and Quaritch, until some of us found the perusal
of a good catalogue as exciting as a detective story. Still more
important, we heard about the more famous collections of
medical works, and began to project personal visits to the
Bodleian, the Royal College of Physicians and the Bibliotheque
Nationale.
But best of all and doubtless the ultimate object of all was
the gradual acquisition of an epitome of the history of medicine wliich has kept us interested ever since those days.
Moreover, it was not merely the cultural value of a knowledge of the beginnings of the profession, but the constant lesson
of the individual worker's triumph over handicaps of isolation,
poverty, ridicule or personal peril, to add some contribution
to the sum of knowledge, and the reiteration of the theme
that the painstaking and observant physician, even though
removed from the centers of learning and wide opportunity,
has in the past contributed fundamentally to the advancement
of knowledge, and may hope to do so in the future.
Again, Dr. Osier stimulated in us an interest in the medical
writers of the early days of our own country and showed how
much might be found by the investigation of the early journals
and books, and tlois has led to the substantial contributions by
his associates and pupils to the history of medicine in the
colonies, the United States and Canada.
In conclusion, another side of Dr. Osier's bibliophilic
activity must be noted, that is, his generous interest in the
medical libraries of the country. He was not satisfied to
acquire rare and interesting volumes for himself, but was
constantly giving such books to the various professional
libraries with which he had been associated; thus, McGill,
Boston, The College of Physicians in Philadelphia and our
own Maryland Faculty and Johns Hopkins have repeatedly
received valuable acquisitions from him or from others whom
he had induced to give rare volumes or even whole collections.
We are happy to know how vastly " the chief's " collection
has grown since he removed to the University of Oxford, so
that it is now one of the very best in existence. The catalogue,
bibliographic, biographic and literary, of this great collection
of the epoch-making works of science occupies most of his
leisure, and will form another great contribution to the
literature of medicine, second only to the immortal Practice.
I
July, 1919]
217
There are in connection with the task which has been
assigned to me many very pleasant aspects. To make a critical
analysis, to present a clear picture of Dr. Osier's literary style
demands, however, more time and space than are at my disposal and above all more ability as a literar}' critic than I am
endowed with.
In reading Dr. Osier's contributions to the literature of
medicine, as well as his occasional addresses and essays, I am
tempted to linger here and there, to point out the clarity of
expression, the simplicity and beautj* of diction and quote
passage after passage in illustration of my thesis. Sucli a
course would simplify the task before me because these quotations would show the author's style better than any powers of
description or any ability of analysis I possess.
In his purely scientific work, as for example, in "The
Principles and Practice of Medicine," the author's method and
his grasp of his subject are admirable. He follows the advice
of the friend of Cervantes when the author of Don Quixote
was in a quandary over the preparation of his preface,
" Nothing but pure nature is your business ; her you must
consult, and the closer you can imitate, your picture is the
better."
In my student days some one placed in my hands a copy
of Watson's Practice.* While it was not recommended as a
text-l)ook to follow as an exponent of the then recognized
principles of medical thought and practice, I found it one of
the easiest works to read and one from which I obtained much
of lasting value. Commenting upon this fact to my preceptor
I was told that I had fallen upon a book which possessed,
something not common in medical treatises, a good style.
The same is true of Osier's writings upon the strictly
scientific aspect of medicine. Unity, order, clarity of description and ease of diction abound throughout his text-book and
his various monographs. A master of his subject, liaving made
the nature of disease his business, he imparts his information
in such a manner that the reader at no time finds it difficult,
because of ambiguous phra.«eology or doubtful expression, to
grasp his meaning. ITis thoughts are "linked with the wants
of his readers," and by the invisible chains which bind mind to
mind, he and his reader become one.
The reader finrls that he has a message to imjjart, a principle
to establish, a rule of conduct to promulgate, and that be has
done so in a logical, attractive manner which compels attention ;
and that to my mind is the test and measure of good writing.
Another view of Osier as an author is revealed in his occasional addres-ses and essays. In the two volumes l)efore me —
" Aequanimitas and Other Addresses " and " An .\labama
Student and Other Biographical Addresses " — Osier's style in
all its directness, strength and grace is shown in full measure.
In these volumes, as in other addresses not therein con
• Lectures on the Principles and Practice of Physic. By ThomaB
Watson. M. D.. etc.. London. 1843.
OSLER'S LITERARY STYLE
By Edward N. Brush
taincd, notably his farewell to his professional associates and
friends in Maryland under the title " Unity, Peace and Concord," Osier exemplifies ButTon's dictum : " The style is the
man himself."
Sir Thomas Watson in his memorial of Latham, whose
" Lectures on Clinical Jledicine " are examples of the best
English style, says : " His letters are treasures of good sense,
of lively and epigrammatic comments on men and things and
of shrewd and weighty reflections, wise advice and affectionate
greetings"; and this can be with great trutli applied to the
addresses and essays of Dr. Osier. Lively, epigrammatic,
shrewd, weighty and affectionate are all terms which well suit
my purpose, which reveal the man through his writing.
" Talent alone cannot make a writer," says Emerson, " there
must be a man behind the book, a personality which by birth
and quality is pledged to the doctrines there set forth."
With Byron one "hates an author that's all author." In
Osier's case the author is all man, and the man reflects himself in his work. It is an easy task for those who liave had the
pleasure and advantage of intimate association with him to
invoke his presence when reading his addresses, as for example,
" Internal Medicine as a Vocation," " Medicine in the Nineteenth Century," " The Hospital as a College " and " The
Master Word in Medicine."
What, if any, are the secrets of Osier's style ; upon what does
it depend? The answer, I think, is simply a love for and
thorough mastery of good literature and a message to convey
full of high ideals. One William Harrison, writing in 1577,
speaks of " an excellent vein of \<Titing not bcforetinie regarded " which had become manifest in England. This he
intimates is tlie result not only of a knowledge on the part of
WTiters of their own tongue, but of an acquaintance with the
Latin and Greek apd often with French and Spanish.
This excellent vein of writing soon became the glory of the
Elizabethan age. The development of higher ideals in English
national life was rapidly followed, as well as fostered, by the
great authors of tlic age of England's literary glory. Style,
literarj' excellence, came to be recognized as desirable, and
reached its highest manifestation. Back of it all, however, were
the ideals which fostered and gave material for the expression
of literary style. There was an atmosphere of a great elevation
of ideals, public and private, and at the same time tangible
objects of national ambition and glory. England was " contending in the cause of the world as well as her own " and there
was an outburst of genius which found its counterpart in a
smaller degree many years later when England was contending
again the world-ambition of Napoleon.
Will a similar development follow the world's war out of
which we are just emerging?
When a man who has ideals and honesty of purpose and has
filled his mind with the productions of the master spirits of the
ages feels the call to write or speak, a beauty of literary style
almost inevitablv results.
218
[No. 341
What were the Pierian springs from which Osier drank,
from which he attained, as has been said of him, " a breadth of
learning and a knowledge of general literature that astound
one ? "
I would place first the English Bible. How often either by
direct quotation or paraphrase does one find in his addresses
and essays sentences and phrases from this well-spring of good
English.
Of a liberal knowledge of the classics abundant evidence is
found and a ready ability to take text, and illustration as well,
from mythology.
With the masters of the English tongue from the early dawn
of English literature till the present he has clearly dwelt on
terms of greatest intimacy.
That half hour devoted every day to commujiion with the
minds of the past finds lessons reflected in writing, but never
with any indication of servile copying. Osier's style is his own.
The last page of Aequanimitas has a list of books which
Osier has called a Bed-side Library for Medical Student*.
This is: 1. Old and Xew Testament; 2. Shakespeare; 3.
Montaigne; 4. Plutai ch's Lives ; 5. Marcus Aurelius ; 6. Epictetus; 7. Eeligio Medici; 8. Don Quixote; 9. Emerson; 10.
Oliver Wendell Holmes — Breakfast-Table Series.
John Brown, of Edinburgh (Horae Subsecivae, p. 400),
gives a list which he commends to the medical student. These
are " Shakespeare, Cervantes, Milton, Dryden, Pope, Cowper,
Montaigne, Addison, Defoe, Goldsmith, Fielding, Scott, Lamb,
Macaulay, Jeffrey, Sydney Smith, Helps and Thackeray."
Brown's list has nearly twice as many names as that given by
Osier, but in solid worth the shorter list outweights the longer.
Dr. Osier's list fulfills in brief compass the requirements of
a liberal education and presents to the reader examples of the
best in literature.
Reference has already been made to the fact that Dr. Osier
is reflected in his writings, that in the words of Taine " behind
the docmnent there was a man."
In this instance that man had for years exercised, as I have
tried to show elsewhere, a singular and powerful influence on
medical education, hospital methods and in binding together
for harmonious action the members of his profession.
He had encouraged the study of medical history and biography and found time in the midst of duties, which might well
have availed as an excuse from further intellectual labors, to
contribute in large measure to these subjects.
Always, with no false note, his cry has been for scientific
righteousness. He has had ideals and, as an idealist, he has
done what he has himself said other idealists have often done,
"gradually moulded to their will conditions the most adverse
and hopeless."
All of this and much more is reflected in the text of Osier's
writing, presented often in epigrammatic form, reinforced by
text and example from many sources, enlivened by a humor
that is irresistible.
No medical contributor to general literature since Holmes
has possessed the saving sense of humor to the degree shown
in Osier's writings and no one could have used it with greater
discrimination or more certain effect.
Often when apparently writing in a most humorous vein he
has been the most serious in his meaning, and how often and
with what delicate touch does he expose some of our human
faults and foibles. I yield to the temptation to quote here an
illustration of that to which I have just referred. " Curious,
odd compounds are these fellow-creatures, at whose mercy you
will be ; full of fads and eccentricities, of whims and fancies ;
but the more closely we study their little foibles of one sort
and another in the inner life which we see, the more surely is
the conviction borne in upon us of the likeness of their weaknesses to our own. The similarity would be intolerable if a
happy egotism did not often render us forgetful of it. Hence
the need of an infinite patience and an ever-tender charity
toward these fellow creatures; have they not to exercise the
same toward us ? "
To Osier's stylo may be applied part of his own estimate of
some of the older writers. Burton, Browne and Fuller : " A
rare quaintness, a love of odd conceits and the faculty of apt
illustration."
In his writings he reminds us of what he has said of Browne,
" The ehann of high thoughts clad in beautiful language may
win some readers to a love of good literature ; but beyond this
is a still greater advantage .... the Eeligio is full of the
counsels of perfection."
So, too, is there with Osier a charm of high thoughts clad in
beautiful language and always the " counsels of perfection."
Osier's literary work is yet unfinished, the three score years
and ten which he has attained have but ripened his judgment
and enlarged his field of vision. He has seen many of his ideals
become realities. The stress of the great world war has pressed
heavily upon him and brought to him a great sorrow. The
iron has entered into his soul. His future work will bear the
stamp of all these.
He has made his own estimate of the " princes of the blood "
in literature from our profession. He places Sir Thomas
Browne, Holmes and John Bro^^^l, of Edinburgh, in a group
high in the circle.
Osier possesses many things in common with these three in
literary style and in literary excellence, and deserves a place
in the same exalted iVllowship.
THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1919
PLATE XXVII
fTtf^j^
I
July, 1919]
219
BIELlOGRArHY
Sir William Osier's bibliography covers a period of 49 years
(18T0-1919). The 730 titles include both books and articles.
Many of these are in the library of The Johns Hopkins Hospital and have added value as being personal gifts from tlie
author.
1870
On Canadian diatomaces. Canad. Naturalist. Montreal. 1S70, n. s.,
V, 142-151.
In his: Published Mem. & Communicat.. Montreal, 1882, S".
(Collect, repr., 1872-1882, i. no. 1.]
1873
Action of certain reagents — atropia, physostigma and curare — on
the colorless blood-corpuscles. Quart. J. Micr. Sc, Lond.,
1873. n. s.. xiii. 307-.'?09.
In his: Published Mem. & Communicat., Montreal, 1882, 8'.
[Collect, repr. 1872-1882, I, no. 2.]
1874
An account of certain organisms occurring in the liquor sanguinis. (Rep. bv J. B. Sanderson.] Proc. Roy. Soc. Lond.,
1874. xxii. 391-398.
In his: Collect, repr., 1872-82, i, no. 3.
1875
Valedictory address to the graduates in medicine and surgery.
McGill University. Canada M. & S. J.. Montreal, 1874-75, iii,
433-438.
In his: Published Mem. & Communicat.. Montreal, 1882, 8°.
[Collect, repr, 1872-82. i, no. 4.]
1876
Introductory remarks to, and synopsis of, practical course on
Inatltutes of medicine. Canada M. & S. J., Montreal, 1875-76,
iv. 202-207.
On the pathology of miner's lung. Canada M. & S, J., Montreal.
1875-76. iv. 145-168.
In his: Collect, repr, 1872-82. 1. no. 7.
Case of scarlatina millaris. Canada M. & S. J., Montreal, 1875-76,
Iv, 49-54.
In his: Collect, repr., 1872-82, i, no. 5.
On the histology of leucocythemia. Canada M. & S. J.. Montreal,
1875-76. Iv, 439-477.
In his: Collect, repr. 1872-82, 1. no. 6.
Clinical notes on small-pox. I. The initial rashes. II. Htemorrhagic small-pox. III. A form of hjpmorrhagic small-pox.
Montreal. 187fi. Gazette P't'g House. 35 p., 8°.
Also: Canada M. & S. J., Montreal. 1876-77, v, 241; 2S9.
In his: Published .Mf-m. & Communicat., Montreal, 1882.
[Collect repr, 1872-82, 1, nos. 8, 9. 10.]
Trichina spiralis. Extract from a lecture on "Animal parasites
and their relation to public health." being one of the Somervllle lectures of the Natural history society. Canad. J. M. Sc.
Toronto, 1876. I. 134-13.->.
1877
Introductory lecture on the opening of the forty-fifth session of the
medical faculty. McOlll T'nlverslty. Oct. 1, 1877. Montreal,
IS77. Dawson Bros.. 19 p., 8°.
Also: Canada M. & S. J.. Montreal, 1877-78, vl, 193-210.
In his: Published .Mem. & Communicat. Montreal, 1882, 8'.
[Collect repr. 1872-82, I. no. 14.)
Verminous bronchitis in dogs; read before the Montreal Veterinary
Medical Association, March 29. Veterinarian. Lend., 1877, I,
387-397.
In his: Published Mem. & Communicat, Montreal. 1882, 8'.
(Collect, repr. 1872-82. 1, no. 12.]
Beschaffenheit des Rlutes und Knochenmarkes bcl pernlcioser
Anamie. Centralbl. f. d. med. Wissenscb., Berl.. 1877, xv, 498.
/» his: Published Mem. & Communicat, Montreal. 1882, 8".
[Collect repr. 1872-82. i, no. 18.)
Osier, W., and Bell, J.: Case of progressive pernicious aniemia.
Clinical report, by John Bell. Pathological report, with remarks, by William Osier Montreal, 1877, Lovell Print. & Publ.
Co., 12 p., 12°.
In his: Collect repr, 1872-82, i, no. 16.
Osier, W., and Gardner, W.: Case of progressive pernicious aniemla
(idiopathic of Addison). Canada M. & S. J., Montreal, 1876-77,
v, 385-404.
In his: Collect, repr, 1872-82, 1, no. 15.
Osier. W., and Gardner, \V.: Ueber die BeschafTenlieit des Blutes
und Knoclionmarkes in der progressiven perniciosen Anamie.
Centralbl. f. d. med. Wissenscli., Berl., 1877, xv, 258-260.
In his: Published Mem. & Communicat, Montreal, 1882, 8°.
[Collect repr. 1872-82, i, no. 17. J
1878
On the pathology of the so-called pig-typhoid. London. 1878, Bailli^re, Tindall & Cox, 20 p., 8°.
Vet. J. & Ann. Comp. Path.. I>ond.. 1878, vi, 385-402.
In his: Publislied Mem. & Communicat, Montreal, 1882.
[Collect, repr., 1S72-S2, i, no. 20. |
Over-strain of the heart, as illustrated by a case of hypertrophy,
dilatation and fatty degeneration of the heart, consequent upon
prolonged muscular exertion. Montreal, 1878, Gazette P't'g
House. 13 p., 8°.
Also: Canada M. & S. J., Montreal, 1877-78, vi, 385-395.
In his: Published Mem. & Communicat, Montreal, 1882, 8°.
[Collect repr. 1872-S2, i, no. 19.)
Phthisical cavities in left lung; gangrene of pulmonary tissue
about one of them. Canada M. & S. J., Montreal, 18'77-78, vi,
114.
Also: Montreal Gen. Hosp. Rep. (1876-77), 1878, i, 37.
Pleura. Small fibroid thickenings on visceral layer. Canada M.
& S. J.. Montreal. 1S77-7S. vi. 115-116.
Also: Montreal Gen. Hosp. Rep. (1876-77), 1878, i, 40-41.
Fracture of 1st and 2d ribs near vertebra>, from direct violence;
deep abscess of the neck; obliteration of subclavian artery;
empyema. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, 1,
11-12.
Necrosis of tibia. Ulcerative endocarditis, pyaemic pneumonia.
Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, 1, 12-13.
Necrosis of femur, pya-niic pnounionia; abscesses in superficial
muscles; pustular eruption on skin. Montreal Gen. Hosp.
Path. Rep. (1876-77), 1878, i, 13-14.
Primary cancer of bodies of 2d and 3d vertebrae and heads of
corresponding ribs on right side. Secondary masses In ribs,
liver and brain. Chronic phtlilsis. Lobar pneumonia. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878. 1, 1416.
A case of hypertrophy and dilatation of the heart; no valvular or
arterial disease; no clironlc kidney affection; hydrothorax;
pulmonary apoplexy: general venous stasis. Montreal Gen.
Hosp. Pat'h. Rep. (1876-77). 1878. i, 16-20.
Aneurism of commencement of thoracic aorta, unsuspected during
life: death from general tuberculosis. Montreal Gen. Hosp.
Path. Rep. (1876-77), 1878, i, 20-21.
Sacculated aneurism of ascending portion of arch of aorta; rupture into the right pleural sac. Montreal Gen. Hosp. Path. Rep.
(1876-77), 1S78, 1, 21.
Sacculated aneurism of aorta, at termination of the arch, unsuspected during life. Death from pneumonia. Montreal Gen.
Hosp. Path. Rep. (1876-77), 1878, 1, 22.
Aneurism of hepatic artery. Right branch almost obliterated.
Multiple abscesses In the liver. Montreal Gen. Hosp. Path.
Rep. ( 1876-77). 1878, I, 22-.30.
Aneurlsmal dilatation of branches of pulmonary artery on the
walls of phtlilsical cavities. Death from ha>mopty8l8. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, I, 30.
Aneurism at second bifurcation of the right midille cerebral
artery; rupture; extravasation of blood Into the Sylvian fissure, and laceration of substance of the teniporosphenoldal
lobe; death In 36 hours. Montreal Gen. Hosp. Path. Rep.
(l.>i76-77). 1878. I, 30-32.
220
[No. 341
1
Ossification of greater portion of mucous membrane of trachea.
Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 32.
Pneumonia of the upper lobe of the right lung; extensive meningeal inflammation. Montreal Gen. Hosp. Path. Rep. (1876-77),
1878, i, 33-34.
Almost entire hepatization of left lung; with small pneumonic
area in right. Extensive diphtheritic colitis. Montreal Gen.
Hosp. Path. Rep. (1876-77), 1878, i, 34.
Diabetes, phthisical cavity in right lung surrounded by hepatized
tissue. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i,
34-35.
Chronic phthisis, almost entire destruction of both lungs. Healthy
portion involved in a pneumonia. Montreal Gen. Hosp. Path.
Rep. (1876-77), 1878, i, 35.
Simple pneumonia of left lung, right-sided pleurisy. Montreal
Gen. Hosp. Path. Rep. (1876-77), 1878, i, 35.
Pneumonia of right lung, uniform involvement of pleura covering
it. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 35-37.
Fibroid contraction and induration of entire right lung; cavity at
apex; displacement of heart; hypertrophy with dilatation of
right chambers. Montreal Gen. Hosp. Path. Rep. (1876-77),
1878, i, 38-39.
Chronic phthisis: perforation of lungs; pneumothorax; dermoid
cyst of right ovary. Montreal Gen. Hosp. Path. Rep. (1876-77),
1878, i, 39-40.
Epithelioma of right side of tongue, extending from base to near
the apex. Removal of organ with galvanic gcraseur. Suppuration beneath cervical fascia. Pyjemia. Montreal Gen. Hosp.
Path. Rep. (1876-77), 1S7S, i, 41-42.
Chronic phthisis. Miliary tubercles in lungs and pharynx. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 42-43.
Cancer of the cardiac orifice, involving the oesophagus. Secondary
masses in other parts of the organ. Montreal Gen. Hosp. Path.
Rep. (1876-77), 1878, 1, 43-44.
Medullary cancer, involving the pyloric zone of the stomach;
perforation, peritonitis. Montreal Gen. Hosp. Path. Rep.
(1876-77), 1878, i, 44.
Passage of two feet of the ileum through a loop attached to the
sigmoid flexure. Montreal Gen. Hosp. Path. Rep. (1876-77),
1878, i, 45.
Round ulcer of duodenum. Montreal Gen. Hosp. Path. Rep. (187677), 1878, i, 45-46.
Perforation of typhoid ulcer during convalescence, owing to an
indiscretion in diet. Montreal Gen. Hosp. Path. Rep. (187677), 1878, i, 46.
Perforation of a deep ulcer at end of second week. Montreal Gen.
Hosp. Path. Rep. (1876-77), 1878, i, 46-47.
Typhoid fever. Perforation. Peritonitis. Montreal Gen. Hosp.
Path. Rep. (1876-77), 1878, i, 47.
Four round ulcers in the ileum. Peyer's patches not generally involved. Sliglit hypostatic pneumonia. Montreal Gen. Hosp.
Path. Rep. (1876-77), 1878, i, 48.
Slight swelling of Peyer's glands, only one small spot of ulceration.
Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 48.
Round ulcer of c<ecum, perforation, general peritonitis. Montreal
Gen. Hosp. Path. Rep. (1876-77), 1878, i, 49.
Abscesses in the mesentery. Suppuration of portal vein. Empyema.
Perforation of appendix, general peritonitis. Montreal Gen.
Hosp. Path. Rep. (1876-77), 1878, i, 51.
Acute tubercular inflammation of the peritoneum. Small caseous
mass in left lung. Right-sided pleurisy. General hyperplasia
of the bone marrow. Montreal Gen. Hosp. Path. Rep. (187677), 1878, i, 52-56.
Cirrhosis of liver, with enlargement; jaundice; no ascites; delirium tremens ( ?) ; erysipelas of the head. Montreal Gen. Hosp.
Path. Rep. (1876-77), 1878, i, 56-60.
Also: Canada M. & S. J., Montreal, 1877-78, vi, 249-253.
Syphilitic ulceration of left frontal bone; large node on left tibia;
gummata in liver. Montreal Gen. Hosp. Path. Rep. (1876-77),
1878, 1, 60-61.
Also- Canada M. & S. J., Montreal, 1877-78, vi, 253.
Primary cancer of the liver; ascites; jaundice; secondary mass in
tail of pancreas; small secondary nodules in kidneys. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 61-64.
Also: Canada M. & S. J., Montreal, 1877-78, vi, 254-256.
Cancer of neck of the gall-bladder and lymphatic glands in the
portal fissure; compression of the hepatic ducts; secondary
masses in liver; enormous distension of gall-bladder and
haemorrhage into it; gallstones. Montreal Gen. Hosp. Path.
Rep. (1876-77), 1878, i, 64-65.
Extensive abscesses in the mesentery, following typhoid fever.
Suppuration of the portal vein and its branches in the liver.
Empyema. Perforation of the appendix vermiformis; peritonitis; miliary tubercles in lungs. Amyloid degeneration of
spleen, liver, and mucous membrane of small intestine. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 65-71.
Tuberculous disease of right kidney, pelvis, ureter and bladder.
Tubercles in left kidney and lungs. Perforation of tuberculous
ulcer in bladder. Peritonitis. Montreal Gen. Hosp. Path. Rep.
(1876-77), 1878, i, 72-73.
Old scrofulous disease of right kidney, which is converted into
cysts. Recent affection of the left. Montreal Gen. Hosp. Path.
Rep. (1876-77), 1878, i, 73-74.
Old disease of the right kidney, which is converted into five or six
cysts, filled with a putty-like material. Extensive tuberculous
disease of the organ. Miliary tubercles in lungs. Albuminoid
spleen. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i,
74-75.
Suppuration about right kidney. Pysemic abscesses in elbows,
ankles and anterior mediastinum. Peritonitis. Pleurisy.
Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 75-76.
Stone in the bladder. Prostatic tumors around the urethral orifice.
Ulceration on mucous membrane. Pyelitis; ulceration of
apices of renal pyramids. Montreal Gen. Hosp. Path. Rep.
(1876-77), 1878, i, 76-77.
Epithelioma of cervix; obstruction of the canal; dilatation of the
uterine cavity. Pyometra. Montreal Gen. Hosp. Path. Rep.
(1876-77), 1878, i, 77-78.
Dermoid or piliferous cyst of right ovary. Chronic phthisis.
Pneumothorax. Montreal Gen. Hosp. Path. Rep. (1876-77),
1878, i, 78-79.
Small cavity and caseous masses in lung. General tuberculosis.
Meninges of brain unaffected; central softening. Spinal meninges extensively involved. Montreal Gen. Hosp. Path. Rep.
(1876-77), 1878, i, 79-81.
Meningeal affection slight. Ventricles distended, walls soft. Very
few miliary tubercles in the organs. Montreal Gen. Hosp.
Path. Rep. (1876-77), 1878, i, 81-82.
Meningeal affection very extensive on the cortex, slight at the base.
Ventricles large, walls not soft. Large caseous mass in left
lung. Miliary tubercles in lungs and on peritoneum. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 82-83.
Slight meningeal inflammation. One caseous mass and a few
tubercles in lungs. Old morbus coxae. Montreal Gen. Hosp.
Path. Rep. (1876-77), 1878, i, 84.
Profound anaemia without discoverable lesion. Fatty degeneration
of organs. Hyperplasia of bone-marrow. Montreal Gen. Hosp.
Path. Rep. (1876-77), 1878, i, 84-97.
Ueber die Entwickelung von Blutkorperchen im Knochenmark bei
pernicioser Anamie. [Berlin, 1878, L. Schumacher.] Centralbl. f. d. med. Wissensch., Berl., 1878, xvi, 465-467.
In his: Published Mem. & Communicat., Montreal, 1882, 8°.
[Collect, repr., 1872-82, i, no. 21.]
Osier, W., and Ross, G. : Aneurism of hepatic artery; multiple
abscesses of the liver. Canada M. & S. J., Montreal, 1877-78,
vi, 1-12.
In his: Collect, repr., 1872-82, i, no. 13.
1879
Case of obliteration of vena cava inferior, with great stenosis of
orifices of hepatic veins. J. Anat. & Physiol., Lond., 1878-79,
xiii, 291-304.
In his: Collect, repr., 1872-82, i, no. 24.
Two cases of rare kidney tumors. Canada M. Rec, Montreal, 1879,
vii, 164.
July,, 1919]
221
Miner's phthisis (Rep. by R. Dawson). Canada M. & S. J., Montreal. 1878-79. vii. 452-454.
Also; Montreal Gen. Hosp. Rep., 1880, 1, 297-299.
Acute Bright's disease in a child; remarkable persistence of bloodcorpuscles and casts in the urine after disappearance of
albumin. (Rep. by A. Henderson.) Canada M. & S. J., MonUeal, 1878-79, vii. 455.
Aphasia, with right-sided hemiplegia, coming on fifteen days after
delivery. [Rep. bv D. Mignault.] Canada M. & S. J., Montreal,
1878-79, vii, 492-493.
Acute rheumatism treated with salicylate of soda. Delirium apparently caused by the remedy. [Rep. by B. E. Maclcenzie. ]
Canada M. & S. J., Montreal, 1878-79, vii, 493-494.
Cobnheim's theory of tumors. Transl. and condensed from vol. I
of his Vorlesungen iiber allgemeine Pathologie (Lectures upon
general pathologj-). By Dr. Osier. Canada M. & S. J., Montreal, 1878-79, vii. 337-347; 398-408.
1880
Concussion of brain; temporary hemiplegia; general convulsions:
rapid recovery. [Rep. by Imrie.] Canada M. & S. J., Montreal,
1879-80, vili, 8.
Aggravated stuttering, following fall on the head. Canada M. &
S. J., Montreal. 1S79-S0, viii, 9.
Extreme irregularity of the heart [Rep. by E. J. Rogers.] Canada
M. & S. J., Montreal, 1S79-S0, viii, 9.
Chronic pleurisv: flattening of sides of chest Canada M. & S. J.,
Montreal, 1879-80, viii, 109-111.
Croup or diphtheria; which? Canada M. & S. J., Montreal. 1879-80,
vii!, 207-211.
In his: Collect repr., 1872-82, i, no. 23.
Three cases of brain disease. Canada M. & S. J., Montreal, 1879-80.
viii, 295; 346.
Anomalous case of pyn^mia; suppuration about tissues in left
Inferior carotid triangle; pya>mic abscess beneath tensor
vaginx femoris; pviemic infarcts in the lungs: septic pleurisy.
Canada M. & S. J.. Montreal, 1879-80. viii, 544-548.
Catalogue of a series of specimens illustrative of the morbid
anatomy of the brain and spinal cord. Exhibited at Ottawa
Meeting of Canada Medical Association, Sept. 1 and 2, 1880.
Case of congenital and progressive hypertrophy of the right upper
extremity. J. Anat & Physiol., Lond., 1879-80, xiv, 10-12.
In his: Collect repr., 1872-S2, i, no. 25.
Two cases of striated mvo-sarcoma of the kidnev. J. Anat. &
Physiol.. Lond.. 1879-80. xiv, 229-233.
In his: Collect repr., 1872-82, 1, no. 26.
Cases of cardiac abnormalities. Montreal Gen. Hosp. Rep., ISSO, i.
177-192.
In his: Collect, repr, 1872-82, i, no. 27.
On the condition of fusion of two segments of the semilunar valves.
Montreal Gen. Hosp. Rep., 1880, i, 233-242.
In his: Collect, repr., 1872-82, i, no. 28.
Wound of the central part of the 1st and 2d frontal convolutions
on left side. Montreal Gen. Hosp. Rep., 1880, i. 257-258.
Bullet wound of right frontal lobe; entire absence of cerebral
symptoms. Montreal Gen. Hosp. Rep., 1880, i, 258-260.
Cases of aneurism of the aorta. Montreal Gen. Hosp. Rep., 1S80, I,
260-265.
Aneurism of Innominate-rupture of saccular dilatation of aorta
into pericardium. Montreal Gen. Hosp. Rep., 1880, 1, 265-266.
Aneurism of splenic artery; perforation Into transverse colon.
Montreal Gen. Hosp. Rep.. 1880. I. 2r,6-268.
Small aneurism of renal artery. Montreal Gen. Hosp. Rep.. 1S80, 1,
268.
Four cases of intracranial aneurism. Montreal Gen. Hosp. Rep.,
1880, i. 268-27.5.
Aneurisms of braflches of pulmonary artery on wall of cavities:
hiemoptysis in chronic phthisis. Montreal Gen. Hosp. Rep.,
1880, i, 275-276.
Two cases of hypertrophy of the heart. Montreal Gen. Hosp. Rep.,
1880, I, 276-282.
Perforation of pulmonary artery by ulcer of left bronchus; sudden
death from hsemoptysis; chronic bronchitis, emphysema,
phthisis. Montreal Gen. Hosp. Rep., 18S0, i, 282-283.
Instance of four pulmonary valves. Montreal Gen. Hosp. Rep.,
1880, 1, 284.
Bayonet wound of left subclavian artery at its origin. Montreal
Gen. Hosp. Rep., 1880, i, 284.
Fatty degeneration of heart In diphtheria; sudden death on the
thirteenth day. Montreal Gen. Hosp. Rep., 1880, i, 285.
Two cases of thrombosis of pulmonary artery. Montreal Gen.
Hosp. Rep., 1880, i, 285-287.
Thrombosis of branches of right pulmonary artery. Montreal Gen.
Hosp. Rep., ISSO, 1, 287-290.
CEdema of right lung: hydrothorax of left pleura; contracted
kidneys. Montreal Gen. Hosp. Rep., ISSO, i. 290-291.
CEdema of left lung; morphia poisoning. Montreal Gen. Hosp.
Rep., ISSO. i, 291-292.
Pneumonia; ulcerative endocarditis; meningitis. Montreal Gen.
Hosp. Rep., 1880, i, 292-295.
Pneumonic phthisis. Montreal Gen. Hosp. Rep., 1880, i, 295-297.
Note on the occurrence of membrane in the trachea and bronchi in
diphtheria. Montreal Gen. Hosp. Rep., 1880, i, 299-300.
Foreign body in oesophagus; ulceration; perforation; retro-pharyn
geal and oesophageal abscess. Montreal Gen. Hosp. Rep., 1880,
1, 300-301.
Three cases of cancer of the stomach. Montreal Gen. Hosp. Rep.,
1880, I, 301-302.
Three cases of ulcer of the stomach. Montreal Gen. Hosp. Rep.,
1880, i, 304-306.
Three cases of simple ulcer of duodenum. Montreal Gen. Hosp.
Rep., 1S80, i, 306-311.
Typhoid fever: rapidly fatal, with nervous symptoms. Montreal
Gen. Hosp. Rep., 1880, i, 311-312.
Perforation of appendix vermiformis; circumscribed abscess: perforation of ileum; haemorrhage from bowels. Montreal Gen.
Hosp. Rep., 1880, I, 313-314.
Liver; hydatid cyst Montreal Gen. Hosp. Rep., 1880, i, 314-316.
Primary cancer of liver. Montreal Gen. Hosp. Rep., 1880, 1, 316-317.
Cirrhosis of liver; collateral circulation by means of an enlarged
umbilical vein; death from pneumonia. Montreal Gen. Hosp.
Rep., 1880, i, 317-318.
Pj-lephlebitis. Montreal Gen. Hosp. Rep., 1880, 1, 318-321.
Extensive scald of thorax; pneumonia; numerous spots of fatty
degeneration in kidneys. Montreal Gen. Hosp. Rep., 1880, i,
321-322.
Small contracted kidneys; left organ affected to an unusual
degree; right onlv Involved in the lower part; hypertrophy of
heart Montreal Gen. Hosp. Rep., 1880, 1, 322-324.
Large cirrhotic kidneys (congestedl ; hypertrophy of heart;
apoplexy. Montreal Gen. Hosp. Rep., 1880, 1, 324-325.
Sarcoma of left kidney. Montreal Gen. Hosp. Rep., 1880, I, 325-328.
Dermoid of ovary; ulcerative colitis. Montreal Gen. Hosp. Rep.,
1880, i, 328-329.
Cancer of neck of uterus; constriction of right ureter; pyoneph.-osls. Montreal Gen. Hosp. Rep., 1880, 1, 329-331.
Ruptured follicle in right ovary; peritonitis. Montreal Gen. Hosp.
Rep., 1880, i, 331-333.
Extra-uterine (abdominal) pregnancy. Montreal Gen. Hosp. Rep.,
1880, I. 333-335.
Cryptorchldlsmus. Montreal Gen. Hosp. Rep., 1880, 1, 335-33G.
Medullary sarcoma of axillary glands; secondary masses in heart,
lungs, stomach. Intestines, liver, spleen, kidneys, suprarenal
capsules, and pancreas. Montreal Gen. Hosp. Rep., 1880, 1,
336-339.
Sarcoma of retro-peritoneal glands: Lobsteln cancer. Montreal
Gen. Hosp. Rep., 1880, 1, 339-340.
Lympho-sarcoma of deep cervical glands, Involving the thyroid and
simulating goitre. Montreal Gen. Hosp. Rep., 1880, I, 340-342.
222
[No. 341
On Giacomini's method of preserving the brain. Med. Rec, N. Y.,
1880, xvii, 315-316.
On the systolic hrain murmur of children. Boston M. & S. J., 1880,
ciii, 29-30.
In Jiis: Collect, repr., 1872-82, i, no. 30.
On heredity in progressive muscular atrophy as illustrated in the
Farr family of Vermont. Arch. Med., N. Y., ISSO. iv, 316-320.
In his: Collect, repr., 1872-82, i, no. 33.
On a remarkable heart-murmur, heard at a distance from chestwall. Med. Times & Gaz.. Lond., ISSO, ii, 432.
In his: Collect, repr., 1S72-82, i, no. 34.
Lympho-sarcoma of deep cervical glands, involving the thyroid and
simulating goitre. Montreal Gen. Hosp. Rep., ISSO, i, 340-342.
Montreal General Hospital. Pathological reports. 1. (1876-77); 2.
(1877-79), Montreal. 1878-80. (2. report repr. from: Montreal Gen. Hosp. Rep., Clin. & Path., ISSO. i.)
1 and 2 also in his: Published Mem. & Communicat., Montreal,
1882.
[Collect, repr., 1872-82, 1, nos. 22 & 29.]
Osier, W., ed. Montreal General Hospital. Reports, clinical and
pathological, by the medical staff, v. i, Montreal. ISSO. Dawson
Brothers, 390 p., S".
18S1
On some points in the etiology and pathology of ulcerative endocarditis. Lond., 1881, J. W. Kolckmann. 8 p., 8°.
Tr. Internat. M. Cong., 7. sess., Lond.. 1881, i, 341-346.
In his: Collect, repr., 1882-92, ii, no. 44.
Renal cirrhosis; with special reference to its latency and to sudden, fatal manifestations occurring in its course. Toronto,
1881. Dudley & Barnes, 13 p., 8°.
Canada Lancet, Toronto, 1880, xiii, 353-359.
In his: Collect, repr., 1872-82, i, no. 42.
On some of the effects of the chronic impaction of gallstones in the
bile-passages, and on the " fievre intermittente hgpatique " of
Charcot. London, ISSl, Pardon & Sons, 15 p., 12°.
Med. Times & Gaz., Lond., 1881, ii, 111-114.
In his: Collect, repr., 1872-82, i, no. 41.
Cases of insular sclerosis. Canada M. & S. J., Montreal, 1880-81, ix,
1-11.
In his: Collect, repr., 1872-82, i, no. 31.
Case of medullary neuroma of the brain. J. Anat. & Physiol.,
Lond., 1880-81, xv, 217-225.
In his: Collect, repr., 1872-82, i, no. 35.
Retro-peritoneal cancer. Canada M. & S. J., Montreal, 1S80-81, ix,
161.
Brief description of the new physiological laboratory, McGill
College. Canada M. & S. J., Montreal, 1880-81, ix, 198-201.
Cases of Hodgkin's disease. Canada M. & S. J., Montreal. 1S80-S1,
ix, 385-397.
In his: Collect, repr., 1872-82, i, no. 37.
Clinical lecture on a case of fibroid phthisis. Delivered at the
Montreal General Hospital in the summer session course,
May 10, 1881. Canada M. & S. J., Montreal, 1880-81, ix. 641650.
In his: Collect, repr., 1872-82, i, no. 40.
Notes of the second demonstration in the morbid anatomy course
in McGill College. Canad. J. M. Sc, Toronto, 1881, vi, 350-353.
On delayed resolution in pneumonia. Canada Lancet, Toronto,
1880-81. xiii, 99-103.
In his: Collect, repr., 1872-82, i, no. 32.
Clinical lecture on idiopathic or pernicious auEemia. Canad. J. M.
Sc, Toronto, 1881, vj, 135-141.
In his: Collect, repr., 1872-82, i, no. 39.
Infectious (so-called ulcerative) endocarditis. Arch. Med., N. Y.,
1881, V, 44-68.
In his: Collect, repr., 1872-82, no. 36.
Ulcerative endocarditis. Bull. N. York. Path. Soc, 1881, 2. s., i,
29-33.
Notes on intestinal diverticula. Ann. Anat. & Surg., Brooklyn,
N. Y., 1881, iv, 202-207.
In his: Collect, repr., 1872-82, i, no. 43.
Published memoirs and communications. (To Jan. 1, 1882), Montreal, 1882, 8°.
Collected reprints. First series, 1872-1882. Montreal, 1882, 8°.
[" Published memoirs and communications " the same as " Collected reprints. First series."]
Clinical remarks on cases of inherited syphilis. Canada M. & S. J.,
Montreal, 1881-82, x, 588-592.
Clinical remarks on leucocythemia. Canada M. & S. J., Montreal,
18S1-S2, X, 719-727.
On the brains of criminals. With a description of the brains of two
murderers. Canada M. & S. J., Montreal, 1881-82, x, 38.5-398.
In his: Collect, repr., 1S82-92, ii, no. 45.
Case of obliteration of the portal vein (pylephlebitis adhesiva).
J. Anat. & Physiol., Loud., 1881-82. xvi, 208-216.
In his: Collect, repr., 1882-92, ii, no. 46.
XJeber den dritten Formbestandteil des Blutes. Centralbl. f. d.
med. Wissensch., Berl., 1882, xx, 529-531.
In his: Collect, repr., 1882-92, ii, no. 47.
Summer session clinics. No. 1. Cases of inherited syphilis. No. 2.
Acute Bright's disease. Nos. 3-4. Pneumonia. No. 5. Leucocytha?mia. Montreal, 1882. 44 p., 8°.
In his: Collect, repr., 1882-92, ii, no. 48.
A clinical lecture on empyema and its antiseptic treatment. Med.
News, Phila., 1882, xli, 113-115.
In his: Collect, repr., 1882-92, ii, no. 50.
Urcemic delirium and coma at a very early stage of interstitial
nephritis. Arch. Med., N. Y., 1882, vii, 213-215.
In his: Collect, repr., 1S82-92, ii, no. 51.
On certain parasites in the blood of the frog. Canad. Naturalist,
Montreal, 1882, x. 406-410.
In. his: Collect, repr., 1882-92, ii, no. 52.
On Canadian fresh-water polyzoa. Canad. Naturalist. Montreal,
1882, X, 399-405.
In his: Collect, repr., 1882-92, ii, no. 53.
On echinococcus disease in America. Am. J. M. Sc, Phila., 1882.
n. s., Ixxxiv, 475-480.
In his: Collect, repr., 1882-92, ii, no. 62.
Atheromatous plate and ulcers on arch of aorta. Med. News,
Phila., 1SS2, xl, 249.
Atheromatous abscess and aneurism of the right iliac artery; general atheroma. Med. News, Phila., 1882, xl, 250.
Fatty diarrhoea. Med. News, Phila., 1882, xli, 580.
Tapping the gall-bladder. Med. News, Phila., 1882, xli, 580.
Hsematemesis in chronic enlargement of the spleen. Med. News,
Phila., 1882. xli, 581.
Notes on cells containing red blood-corpuscles. Lancet, Lond.,
1882, i, 181.
1883
Cancer of ascending colon: extensive secondary growths in liver.
Canada M. & S. J., Montreal, 1882-83, xi, 28.
Obstinate quotidian ague. Canada M. & S. J., Montreal, 1882-83, xi,
29.
Clinical note on hasmatemesis in chronic splenic tumour. Canada
M. & S. J., Montreal, 1882-83. xi, 267-270.
Also: Canada M. Rec, Montreal, 1SS2-83, xi, 30.
Erosion of internal carotid in cavernous sinus six weeks after
a blow on the head ; fatal haemorrhage from the nose. Canada
M. & S. J., Montreal, 1882-83, xi, 357.
Aneurism of anterior communicating artery. Canada M. Rec,
Montreal, 1882-83, xi, 133.
Empyema discharging through lung; recovery. Canada M. Rec,
Montreal, 1882-83, xi, 223.
Aneurism of the anterior cerebral artery. Canada M. Rec, Montreal, 1882-83, xi, 241.
Clinical remarks on a case of Hodgkin's disease. Canada M. & S. J.,
Montreal. 1882-83, xi, 712-717.
In his: Collect, repr., 1882-92, ii, no. 55.
Preataxic tabes dorsalis. A clinical lecture delivered during the
summer session of the McGill Medical Faculty. Med. News,
Phila.. 1S83. xliii, 197-199.
Ill his: Collect, repr., 1882-92, ii, no. 56.
JULT, 1919]
223
The third corpuscle of the blood. Med. News, Phila.. 1883. xliii,
701-702.
In his: Collect, repr., 1SS2-92. li, no. 57.
On some natural modes of cure in empyema. A clinical lecture
delivered during the summer session of the McGill Medical
Faculty. .June 2it, ISS:!. Med. Rec. N. Y., 1S83, xxiv, 429-481.
In his: Collect, repr.. 1882-92, ii. no. 58.
Report on the brains of Richards and ORourlce. Canada M. & S. J.,
Montreal. 1882-83. xi. 461-466.
In his: Collect, repr., 1882-92, ii, no. 59.
Secondary myeloid disease of pleura and lung, lllust. M. & S.,
N. Y., 1883, ii, 117.
Clinical remarks on tlie nephritis of pregnancy. Canad. Pract.,
Toronto, 1883, viii. 133-137.
Thrombosis and embolism of the superior mesenteric artery. Med.
News. Phila., 1883, xlii, 693.
Scirrhus of pancreas: secondary colloid of lungs. Med. News,
Phila., 1883, xlii, 694.
Osier, W.. and Clement. A. W. Cestode tuberculosis. A successful
experiment in producing it in the calf. Am. Vet. Rev., N. Y.,
1882-83, vi. 6-10.
In his: Collect, repr, 1882-92, ii, no. 49.
Osier, W., and Clement, .\. W. An investigation into the parasites
in the porlt supply of Montreal. Montreal, 1883, Gazette Printing Co.. 14 p., 8 = .'
Also: Canada M. & S. J., Montreal, 1882-83, xi, 325-336.
In his: Collect, repr.. 1882-92, 11, no. 54.
1884
Ovarian cysts in an infant. Canada M. Rec, Montreal, 1883-84,
xii, 52.
Fibro-glioma of upper end of ascending frontal gyrus; Jacksonian
epilepsy of fourteen years' standing; the leg-centre. Canada
M. Rec., Montreal. 1883-84, xii, 82.
Aneurism of aorta; rupture into left bronchus. Canada M. Rec,
Montreal, 1883-84, xii, 98.
Cases of dysentery. Canada M. & S. J., 1883-84 xii, 330-333.
Syphilitic caries of inner table of skull; great thickening of
calvaria: compression and deformity of the brain. Med. News,
Phila.. 1884. xliv. 25.
Also: Canada .M. & S. J.. Montreal, 1883-84, xii, 351.
Also: Canada M. Rec, Montreal, 1883-84, xii, 78.
Remarks on clinical cases. Canada M. & S. J., Montreal, 1884-85,
xiil 328-333
In his: Collect repr., 1882-92, ii, no. 60.
A contribution to Jacksonian epilepsy and the situation of the leg
centre. Am. J. M. Sc, Phila., 1885, n. s., Ixxxix, 31-37.
In his: Collect, repr, 1882-92, ii, no. 61.
The Gulstonian lectures on malignant endocarditis. Delivered at
the Royal College of Physicians of London, March, 1885.
London, 1885, 31 p., 8'.
Also: Brit. M. J., Lond.. 1885, 1, 467-470; 522; 577.
Also: Lancet, I^nd., 1885, 1, 415; 459; 505.
Also: Med. News. Phila.. 1885, xlvi. 309-313; 337; 365.
In his: Collect, repr. 1882-92, II, no. 63.
Notes on the morbid anatomy of pneumonia. Canada M. & S. J.,
Montreal, 1884-85, xlii, 596-60.5.
In his: Collect, repr, 1882-92, II, no. 64.
Notes on fho mrvrWH onot^r.,.. «f »..-».. IJ » ^- • — ' J^
iiini.ifKiRAriiY (oMPii.Ki) nv
MINNIE WRIGHT BLOGG
LiniLVBIAN. JOHNS HOPKINS IIOSPITAI.
Specimen of aneurism of the aorta with rupture into the trachea in
two places, and perforation of the oesophagus. Boston M. &
S. J., 1885, cxii, 480.
Du dfveloppement de la profession mSdicale en Canada. I'uion
ni^d. du Canada, Montreal, 1885, xiv, 481-489; 529-539.
1886
The structure of certain gliomata. Phila. M. Times, 1885-86, xvl,
394.
Also: Med. News, Phila., 1886, xlviil, 220.
Aneurism of the cerebral arteries. Canada M. & S. J., Montreal,
1885-86, xiv, 660-666.
In his: Collect, repr., 1882-92, ii, no. 75.
A case of retro-peritoneal spindle-celled sarcoma with extensive
thrombotic and hemorrliagic changes. Med. News, Phila.,
1886. xlviii. 263.
In his: Collect, repr, 1882-92, ii, no. 69.
Spindle-celled sarcoma of the retro-peritoneum with extensive
thrombotic degeneration. N. York M. J.. 1886, xliii, 136.
Also.- Marvland -M. J.. Halt., 1885-86, xiv, 269-271.
Also: Semi-Month. J. Proc. Path. Soc, Phila., Wilmington, 1886,
i, 3.
Cartwright ' lectures. Delivered before the Association of Physicians and Surgeons, New York, March 23, 27, 30. 1886. On
certain problems of the blood corpuscles. 1. The blood plaque
or third corpuscle. 2. Degeneration and regeneration of the
corpuscles. 3. The relation of the corpuscles to coagulation.
Phila., 1886, 55 p., 8°.
Also: Med. News. Phila., 1886, xlviii, 365; 393; 421.
Also: Med. Rec. N. Y., 1886. xxix, 377; 405; 433.
Also: N. York M. J., 1886. xliii, 341; 369; 397.
In his: Collect, repr, 1882-92, ii, no. 71.
Abstracts of the Cartwright lectures on certain problems in the
phvsiology of the blood-corpuscles. Brit. M. J., Lond., 1886, i,
807; 861.
The bicuspid condition of the aortic valves. Tr. Ass. Am. Physicians. Phila., 1886, i, 185-192.
In his: Collect, repr, 1882-92, ii, no. 72.
On the use of arsenic in certain forms of anjemia. Detroit, 1886,
G. S. Davis, 14 p., 8°.
Also: Therap. Gaz., Detroit. 1886, 3. s., ii, 741-746.
Also: Coll. & Clin. Rec, Phila., 1886, vii, 231-233.
In his: Collect, repr, 1882-92, ii, no. 73.
Embolism of right middle cerebral artery; chronic nephritis. Med.
News, Phila., 1886, xlix, 554.
On the treatment of pleurisy with effusion by Hay's method.
[Abstr] Med. News, Phila., 1886, xlix, 645.
Pyopneumothorax subphrenlcus. Semi-.Month. J. Proc. Path. Soc,
Phila., Wilmington, 1886, I, 5.
The relation of the corpuscles to coagulation and thrombosis. Brit.
M. J., Lond., 1886, 1, 917-919.
Osier, W., and Henry. F. P. Atrophy of the stomach, with the
clinical features of progressive pernicious ana-mia. Am. J. M.
Sc, Phila., 1886. n. s., xci, 498-511.
In his: Collect, repr.. 1882-92, li, no. 70.
Osier, W., and Hughes, W'. Hiemorrhagic pancreatitis with
swelling of semilunar ganglia and Pacinian corpuscles. SemiMonth. J. Proc. Path. Soc, Phila., Wilmington, 1886. i, 7.
1887
Extracts from Pathological Society of PliUadelphla, 1885-1887, xllxlil, Philadelphia 11887), 69 p., 8°.
Duodenal ulcer; clinical and anatomical considerations based on
nine cases. Canada M. & S. .1.. .Montreal. 1886-87, xv, 449-461.
In his: Collect, repr. 1882-92, II. no. 74.
An address on the haematozoa of malaria. Brit. .M. .1.. lAtwi., 1887,
I, 556-562.
In his: Collect repr., 1882-92, II, no. 76.
Antlfebrin. Therap. Gaz., Detroit, 1887.. 3. s.. 111. 16.3-167.
In his: Collect, repr. 1882-92, II, no. 77.
The cardiac relations of chorea. Am. J. .M. Sc, Phila., 1887, n. s.,
xclv, 371-386.
In his: Collect, repr, 1882-92, II, no. 78.
224
[Xo. 341
Notes on hsemorrhagic infarction. Boston M. & S. J.. 1SS7, cxvii,
325-328.
Also: Tr. Ass. Am. Physicians, Phila., 1887, ii, 133-141.
In his: Collect, repr., 1882-92, ii, no. 79.
On the general etiology and symptoms of chorea, based on the
records of 410 cases at the Infirmary for Nervous Diseases,
Philadelphia. Med. News, Phila., 1887, Ii, 437; 465.
In his: Collect, repr., 1882-92, ii, no. SO.
Case of cholesteatoma of floor of third ventricle and of the iufundibulum. J. Nerv. & Ment. Dis., N. Y., 1887, xiv, 657-673.
In his: Collect, repr., 1882-92, ii, no. 81.
Hereditary angio-neurotic oedema. Am. J. M. Sc, Phila., 1888, n. s.,
xcv, 362-367.
In his: Collect, repr., 1882-92, Ii, no. 82.
Note on nitro-glycerine in epilepsy. J. Nerv. & Ment. Dis., N. Y.,
1888, n. s., xlii, 38-39.
In his: Collect, repr., 1882-92, ii, no. 83.
The diagnosis of small-pox. Med. Standard, Chicago, 1888, ill, 97.
In his: Collect, repr., 1882-92, ii, no. 84.
Glioma of the medulla oblongata. J. Nerv. & Ment. Dis., N. Y., 1888,
n. s., xiii, 172-176.
In his: Collect, repr., 1882-92, ii, no. 85.
The cerebral palsies of children. Med. News, Phila., 1888, liii, 29;
57; 85; 113; 141.
In his: Collect, repr., 1882-92, ii, no. 86.
Cases of diseases of the appendix and caecum. Med. & Surg. Reporter, Phila., 1888, lix, 419-422.
In his: Collect, repr., 1882-92, ii, no. 87.
Puerperal anaemia, and its treatment with arsenic. Boston JI. &
S. J., 1888, cxix, 454.
Also: North Car. M. J., Wilmington, 1888, xxii, 359-363.
In his: Collect, repr., 1882-92, ii, no. 88.
On the diagnosis of duodenal ulcer. Med. Rec, N. Y., 1888, xxxiv,
609-610.
In his: Collect, repr., 1882-92, ii, no. 89.
Note on pachymeningitis hemorrhagica. J. Nerv. & Ment. Dis.,
N. Y., 1888, n. s., xiii, 608-612.
Also: Med. News, Phila., 1888, liii, 563-565.
In his: Collect, repr., 1882-92, ii, no. 90.
On lesions of the conus medullaris and cauda equina, and on the
situation of the aho-vesical centre in man. Med. News, Phila.,
1888, liii, 669-671.
In his: Collect, repr., 1882-92, ii, no. 91.
On a form of purpura associated with articular, gastro-intestinal,
and renal symptoms. N. York M. J., 1888, xlviii, 675-677.
In his: Collect, repr., 1882-92, ii, no. 92.
An accouchement in a railway closet. Canada M. & S. J., Montreal,
1888, xvi, 377.
Also: Med. Rec, N. Y., 1888, xxxiii, 97.
Pulsating pleurisy. Tr. Ass. Am. Physicians, Phila., 1888, iii, 330
Also: Am. J. M. Sc, Phila., 1889, n. s., xcvii, 43-50.
In his: Collect, repr., 1882-92, ii, no. 95.
Enlargement and congestion of the right arm following exercise of
its muscles. Med. News, Phila., 1888, Iii, 330.
Also: J. Nerv. & Ment. Dis., N. Y., 1888, n. s., xiii, 246-248.
A case of local syncope and asphyxia of the fingers. J. Nerv. &
Ment. Dis., N. Y., 1888, n. s., xiii, 207-208.
1889
The cerebral palsies of children; a clinical study from the
Infirmary for Nervous Diseases, Philadelphia. Phila., 1SS9,
P. Blakiston, Son & Co., Ill p. 8°.
Aequanimitas. Valedictory remarks to the graduates in medicine
of the University of Pennsylvania, May 1, 1889. Phila., 1889,
W. F. Fell & Co., 10 p., 8°.
In his: Collect, repr., 1882-92, ii, no. 97.
The mortality of pneumonia. Phila., 1889, 7 p., 8°.
Also: Univ. M. Mag., Phila., 1888-89, 1, 77-82.
In his: Collect, repr., 1882-92, ii, no. 93.
Two cases of ulcerative endocarditis. Univ. M. Mag., Phila., 188889, 1, 31-32.
The mortality in pneumonia. Univ. M. Mag., Phila., 1888-89, i. 225.
Cancer of the stomach, extreme mobility of tumor. Univ. M. Mag.,
Phila., 1888-89, i, 368-370.
On the conditions of the brain suitable for operative interference.
[Abstr.] Univ. M. Mag., Phila., 1888-89, i, 465-468.
Also: Canad. Pract, Toronto, 1889, xiv, 165-167.
On certain symptoms of floating kidney. Montreal M. J., 1888-9,
xvii, 416-418.
The anatomical tubercle. Montreal M. J., 1888-9, xvii, 418.
Aortic aneurism; hemorrhage from the lungs. Phila. M. Times,
1888-9, xix, 223.
Typhlitis and appendicitis. Canada Lancet, Toronto, 1888-9, xxi,
193-196.
On phagocytes. An address before the Alumni Association of
Bellevue Hospital, New York, delivered April- 3, 1889. Med.
News, Phila., 1889, liv, 393; 421.
Also: Med. Rec, N. Y., 1889, xxxv, 393-399.
Also: N. York M. J., 1889, xlix, 393-400.
In his: Collect, repr., 1882-92, ii, no. 94.
Annual address. The license to practice. J. Am. M. Ass., Chicago, 1889, xii, 649-654.
Also: Maryland M. J., Bait., 1889, xxi, 61-67.
Also: Tr. M. & Chir. Pac. Maryland, Bait., 1889, 70-82.
In his: Collect, repr., 1882-92, ii, no. 96.
Note on intrathoracic growths developing from the thyroid gland.
Med. News, Phila., 1889, Iv, 257.
In his: Collect, repr., 1882-92, ii, no. 98.
On a case of simple idiopathic muscular atrophy, involving the
face and the scapulo-humeral muscles. Am. J. M. Sc, Phila.,
1889, n. s., xcviii, 261-265.
In his: Collect, repr., 1882-92, ii, no. 99.
Case of syphiloma of the cord of the Cauda equina; death from
diffuse central myelitis. J. Nerv. & Ment. Dis., N. Y., 1889,
n. s., xiv, 499-507.
In his: Collect, repr., 1882-92, ii, no. 100.
Idiocy and feeble-mindedness in relation to infantile hemiplegia;
a report of twenty-two cases at the Pennsylvania Institution
for Feeble-Minded Children. Alienist & Neurol., St. Louis,
1889, X, 16-23.
1890
On the value of Laveran's organisms in the diagnosis of malaria.
Johns Hopkins Hosp. Bull., Bait, 1889-90, i, II.
In his: Collect, repr., 1882-92, ii, no. 101.
On fever of hepatic origin, particularly the intermittent pyrexia
associated with gallstones. Johns Hopkins Hosp. Rep., Bait.,
1890, ii, 3-31.
In his: Collect, repr., 1882-92, li, no. 102.
Cases of post-febrile insanity. Johns Hopkins Hosp. Rep., Bait.,
1890. ii, 46-50.
In his: Collect, repr., 1882-92, ii, no. 103.
Rare forms of cardiac thrombi. Johns Hopkins Hosp. Rep., Bait.,
1890, ii, 56-61.
In his: Collect, repr., 1882-92, ii, no. 104.
Note on endocarditis in phthisis. Johns Hopkins Hosp. Rep.,
Bait, 1890, ii, 62-64.
In his: Collect repr., 1882-92, ii, no. 105.
Tubercular peritonitis; general considerations; tubercular abdominal tumors; curability. Johns Hopkins Hosp. Rep.,
Bait, 1890, ii, 67-113.
In his: Collect, repr., 1882-92, ii, no. 106.
Acute nephritis in typhoid fever. Johns Hopkins Hosp. Rep.,
Bait., 1890, ii, 119-128.
/)( his: Collect repr., 1882-92, ii, no. 107.
On the amceba in dvsenterv and in dysenteric liver abscess.
Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 53-54.
In his: Collect, repr., 1882-92, ii, no. 108.
On the form of convulsive tic associated with coprolalia, etc
Med. News, Phila., 1890, Ivii, 645-647.
In his: Collect repr., 1882-92, ii, no. 109.
On the symptoms of chronic obstruction of the common bile-duct
by gallstones. Ann. Surg., St. Louis, 1890, xi, 161-185.
Ueber die in Dvsenterie und dysenterischem Leberabscess vorhandene Amceba. Centralbl. f. Bacteriol. u. Parasitenkr.,
Jena., 1890, vii, 736-737.
July, 1919]
225
Multiple thrombi-multiple gangrene. (Proc. Johns Hopkins Hosp.
Med. Soc, Oct. 22, 18S9.) Johns Hopkins Hosp. Bull., Bait.,
1S89-90. i. 12.
Fatal hemorrhage into a large bronchocele. (Proc. Johns Hopkins Hosp. Med. Soc, Nov. 18, 1889.) Johns Hopkins Hosp.
Bull.. Bait, 1889-90, i, 23.
Congenital heart disease. (Proc. Johns Hopkins Hosp. Med. Soc,
Dec. 2, 1889.) Johns Hopkins Hosp. Bull., Bait., 1889-90,
i. 34.
Filaria sanguinis hominis. (Proc. Johns Hopkins Hosp. Med.
Soc, Jan. 6. 1890.) Johns Hopkins Hosp. Bull., Bait., 1889-90,
1. 48.
Weir Mitchell. Remarks on the occasion of the presentation to
the College of Physicians, Phila., of the portrait of Dr. S. Weir
Mitchell, April 22. 1890. Johns Hopkins Hosp. Bull., Bait.,
1889-90, i, 64.
Aortic InsufBciency. (Proc. Johns Hopkins Hosp. Med. Soc, Oct.
20, 1890.) Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 109.
Hereditary chorea. (Proc. Johns Hopkins Hosp. Med. Soc, Oct.
20. 1890.) Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 110.
In his: Collect, repr., 1882-92, ii, no. 114.
General bronchiectasis of left lung, foetid bronchitis: incision
of cavitv; death. (Proc. Johns Hopkins Hosp. Med. Soc,
Oct. 20, 'l890.) Johns Hopkins Hosp. Bull., Bait., 1889-90, 1,
109.
In his: Collect, repr.. 1882-92, ii. no. 115.
1891
A case of sensory aphasia; word-blindness with hemianopsia.
Am. J. M. Sc, Phila., 1891, n. s., cl, 219-224.
In his: Collect, repr., 1882-92, ii, no. 110.
Rudolf Vlrchow: the man and the student. Boston M. & S. J.,
1891, cxxv, 425-427.
Also: Johns Hopkins Univ. Circ, Bait., 1891, xi, 17-19.
In his: Collect repr., 1882-92, ii, no. 111.
Diagnosis of tuberculous broncho-pneumonia in children. Arch.
Pediat, Phila.. 1891, viii, 825-829.
Also: Tr. Am. Pediat Soc (N. Y.). 1892, iii, 25-29.
In his: Collect repr. 1882-92, no. 112.
Doctor and nurse: remarks to the first class of graduates from
the TrainiuK School for Nurses at The Johns Hopkins Hospital. Bait. 1891, J. Murphy & Co.. 11 p. 4°.
In his: Collect repr.. 1882-92, ii, no. 113.
Obstruction of the superior vena cava. (Proc. Johns Hopkins
Hosp. Med. Soc, Jan. 5, 1891.) Johns Hopkins Hosp. Bull.,
Bait, 1891, ii, 40.
In his: Collect repr., 1882-92, ii, no. 116.
Case of multiple cysticerci. (Proc. Johns Hopkins Hosp. .Med.
Soc. Feb. 2. 1891.) Johns Hopkins Hosp. Bull.. Bait, 1891,
ii, 61.
In his: Collect, repr., 1882-92, il, no. 117.
Disease of the coronary arteries: fibroid heart. Tr. Path. Soc.
Phila. (1887-9). 1891, xiv, 106-108.
Acute phthisis: erosion of a large branch of the pulmonary
artery; sudden fatal haemoptysis. Tr. Path. Soc. Phila.
(1887-9), 1891. xiv. 169.
The diagnosis of broncho-pneumonia (acute and chronic) from
tuberculosis. N. York M. J.. 1891. liv, 666.
Report on the Koch treatment in tuberculosis. Johns Hopkins
Hosp. Bull.. Bait, 1891, 11, 714.
Remarks on hysteria with paroxysmal Inspiratory spasm. (Proc
Johns Hopkins Hosp. .Med. Soc, Nov. 17, 1890.) Johns Hopkins Hosp. Bull., Bait, 1891, ii, 18.
Two cases of pernicious malaria. (Proc. Johns Hopkins Hosp.
Med. Soc. Oct. 5, 1891.) Johns Hopkins Hosp. Bull.. Bait.
1891, ii, 161-162.
1892
The principles and practice of medicine. Designed for the use
of practitioners and students of medicine. New York, 1892,
D. Appleton & Co., 1079 p. 8'.
Teacher and student. An address delivered on the occasion of
the opening of the new building of the College of .Medicine
and Surgery of the University of Minnesota. Minneapolis.
Oct 4, 1892, Bait. 1892, J. Murphy & Co., 22 p. 8°.
In his: Collect repr., 1882-92. Ii, no. 123.
Collected reprints. Second series. (January 1, 1882-January 1.
1892.) (Bait. 1892.] 8°.
Remarks on specialism. Boston M. & S. J., 1892, cxxvi, 457-459.
Also: .Med. News, Phila.. 1892, Ix, 542-544.
Also: Arch. Pediat. Phila., 1892, Ix, 481-488.
In his: Collect, repr., 1882-92, ii, no. 118.
The healing of tuberculosis. Climatologist, Phila., 1892, ii, 149153.
In his: Collect, repr., 1892-7, iii, no. 119.
On the association of congenital wry-neck, with marked facial
asymmetry. Arch. Pediat, N. Y., 1892, ix, 81-85.
In his: Collect repr., 1882-92, ii, no. 120.
Interstitial processes in the central nervous system. Tr. Cong.
Am. Phys. & Surg., 1891. N. Haven. 1S92, i'i, 144-146.
In his: Collect repr., 1892-7, iii. no. 121.
The cold-bath treatment of typhoid fever. Med. News, Phila.,
1892. Ixi. 628-631.
In his: Collect, repr., 1892-7, iii, no. 122.
Notes on the diagnosis and treatment of cholera. Med. News,
Phila., 1892, Ixi, 290.
License to practice. Northwest Lancet, St Paul, 1892, xii, 838.
An acute my.\oedematous condition occurring in goitre. (Proc.
Johns Hopkins Hosp. Med. Soc, Dec. 7, 1891.) Johns Hopkins Hosp. Bull., Bait. 1892, iii, 42.
Chronic cerebro-spinal meningitis. (Proc. Johns Hopkins Hosp.
Med. Soc. Oct. 17, 1892.) Johns Hopkins Hosp. Bull., Bait,
1892, iii, 119.
Localized pyo-pneumothorax. (Proc. Johns Hopkins Hosp. Med.
Soc, Oct 17, 1892.) Johns Hopkins Hosp. Bull., Bait, 1892,
iii, 19.
Note on arsenical neuritis following the use of Fowler's solution.
(s4.ilTn.18.) Montreal M. J., 1892-3, xxi, 721-724.
In his: Collect repr., 1892-7, iii, no. 130.
Note on a remarkable house epidemic of typhoid fever. Univ.
M. Mag., Phila., 1892-3, v, 522-524.
In his: Collect repr., 1892-7, iii, no. 131.
Tuberculous pericarditis. Am. J. M. Sc. Phila., 1893, n. s., cv,
20-27.
In his: Collect repr., 1892-7, lil. no. 124.
On dilatation of the colon in young children. Arch. Pediat, N. Y.,
1893, X, 111-119.
Also: (Proc. Johns Hopkins Hosp. Med. Soc, Jan. 16, 1893.)
Johns Hopkins Hosp. Bull., Bait, 1893, iv, 41-43.
In his: Collect, repr., 1892-7, iii, no. 125.
Physic and physicians as depicted in Plato. Boston M. & S. J.,
1893. cxxviii. 129; 153.
In his: Collect repr.. 1892-7. iii, no. 126.
Case of arterlo-venous aneurism of the axillary artery and vein
of fourteen years' duration. Ann. Surg., Phila., 1893, xvii,
37-40.
In his: Collect repr., 1892-7, ill, no. 127.
The chronic intermittent fever of endocarditis. Practitioner,
Lond., 1893, 1, 181-190.
In his: Collect, repr.. 1892-7, ill, no. 128.
Remarks on the varieties of chronic chorea, and a report upon
two families of the hereditary form, with one autopsy.
J. Nerv. & Ment Dls.. N. Y.. 1893. xx. 97-111.
In hts: Collect repr., 1892-7. iii. no. 129.
Cases of sub-phrenic abscess. Tr. Ass. Am. Physicians, Phila.,
1893. viii. 257-267.
Also: Canad. Pract, Toronto. 1893, xvlii, 565-574.
In his: Collect repr., 1892-7, ill. no. 132.
Shattuck lecture. Mass. Med. Soc, 1893. Tuberculous pleurisy.
Boston .M. & S. J.. 1893, cxxix. 53; 81; 109; 134.
Also: Med. Communicat. .Mass. .M. Soc, Boston, 1893, xvl,
49112.
In his: Collect repr., 1892-7, ill, no. 133.
Profound toxemia with slight tuberculous lesions. Med. News,
Phila., 1893, Ixiil, 632.
Jean Martin Charcot, memorial notice. Johns Hopkins Hosp.
Bull., Bait, 1893, iv. 87-88.
236
[No. 341
On sporadic cretinism in America. Tr. Am. J. Am. Physicians,
Pliila., 1893, viii, 380-398.
Also: Am. J. M. Sc, Plilla., 1893, n. s., cvi, 503-518.
In his: Collect, repr., 1892-7, iii, no. 136.
Notes on tuberculosis in children. Arch. Pediat., N. Y., 1893,
X 979-986.
In his: Collect, repr., 1892-7, iii. no. 137.
Hirt, Ludwig. The diseases of the nervous system. A text-book
for physicians and students. Transl. with permission of the
author by August Hoch, assisted by Frank R. Smith, with
an introduction by William Osier, N. Y., 1893. D. Appleton
& Co., 698 p. 8°.
1894
Lectures on the diagnosis of abdominal tumors, delivered to the
post-graduate class, Johns Hopkins University, 1893. New
York, 1894, D. Appleton & Co., 192 p. 8°.
Also: N. York M. J., 1894, lix, 129; 161; 193; 260; 385; 417;
481; 545; 577: Ix, 65; 97.
In his: Collect, repr., 1892-7, iii, no. 146.
On chorea and choreiform affections. Phila., P. Blakiston, Son
& Co., 1894, 125 p. 8°.
In his: Collect, repr., 1892-7, iii, no. 149.
Tuberculosis.
In: Am. Text-Bk. Dis. Child. (Starr), Phila., 1894, 94-126.
In his: Collect, repr., 1892-7, iii, no. 134.
Diseases of the blood.
In: Text-book Theory & Pract. Med. (Pepper), Phila., 1894, li,
182-233.
In his: Collect, repr., 1892-7, iii, no. 135.
Diseases of the suprarenal capsules and ductless glands.
In: Text-book Theory & Pract. Med. (Pepper), Phila., 1894, il,
234-246.
Toxaemia in tuberculosis. Practitioner, Lond., 1894, Iii, 26-30.
In his: Collect, repr., 1892-7, iii, no. 138.
Parotitis in pneumonia. Case of pericarditis treated by incision
and drainage. Univ. M. Mag., Phila., 1893-4, vi, 245-249.
In his: Collect, repr., 1892-7, iii, no. 139.
The army surgeon. An address delivered at the closing exercises of the Army Medical School, Washington, D. C, Feb.
28, 1894. Med. News, Phila., 1894, Ixiv, 3i8-322.
In his: Collect, repr., 1892-7, iii, no. 147.
The leaven of science. An address delivered at the opening of
the Wistar Institute of Anatomy and Biology of the University of Pennsylvania, May 21, 1894. Univ. M. Mag., Phila.,
1893-4, vi, 573-586.
In his: Collect, repr., 1892-7, iii, no. 148.
Oliver Wendell Holmes. Johns Hopkins Hosp. Bull., Bait., 1894,
V, 85-88.
In his: Collect, repr., 1892-7, iii, no. 150.
The heart in chorea minor. Med. Chron., Manchester, 1894, n. s.,
i, 321-332.
Clinical remarks on a case of typhoid fever, complicated with
bronchitis and laryngitis. Maryland M. J., Bait., 1894, xxxi,
1-3.
The registration of pulmonary tuberculosis. Phila. Polyclin.,
1S94, iii, 65.
Case of hereditary chorea. (Proc. Johns Hopkins Hosp. Med.
Soc, Oct. 1, 1894.) Johns Hopkins Hosp. Bull., Bait., 1894,
V, 119-120.
1895
The principles and practice of medicine. Designed for the use
of practitioners and students of medicine. 2. ed. New York,
1895, D. Appleton & Co., 1143 p. S".
Report on typhoid fever. I. General analysis and summary of
the cases. II. Treatment of typhoid fever. III. A study of
the fatal cases. IV. Notes on special features, symptoms
and complications. Johns Hopkins Hosp. Rep., Bait., 1894-5,
iv, 1-72.
In his: Collect, repr., 1892-7, iii, nos. 140-143.
On the neurosis following enteric fever, known as " the typhoid
spine." Johns Hopkins Hosp. Rep., 1894-5. iv, 73-82.
Also: Am. J. M. Sc, Phila., 1894. n. s., cvii, 23-30.
In his: Collect, repr., 1892-7, iii, no. 144.
Typhoid fever in Baltimore. Johns Hopkins Hosp. Rep., Bait.,
1894-5, iv, 159-167.
In his: Collect, repr., 1892-7, iii, no. 145.
Introductory remarks to course of clinical demonstrations on
typhoid fever. Maryland M. J., Bait., 1894-5, xxxii, 79-82.
In his: Collect, repr., 1892-7, iii, no. 151.
Cancer of the stomach with very rapid course. Univ. M. Mag.,
Phila., 1894-5, vii, 248-252.
In his: Collect, repr., 1892-7, iii, no. 152.
Teaching and thinking; the two functions of a medical school.
Montreal M. J., 1894-5, xxiii, 561-572.
In his: Collect, repr., 1892-7, iii, no. 153.
Case of sporadic cretinism (infantile myxcedema) treated successfully with thyroid extract. Arch. Pediat, N. Y., 1895,
xii, 105-108.
In his: Collect, repr., 1892-7, iii, no. 154.
Diseases, the direct or indirect result of infection. Text-book
Nerv. Dis. Am. Authors (Dercum), Phila., 1895, 203-226.
In his: Collect, repr., 1892-7, iii, no. 157.
Studies in typhoid fever; Five years' experience with the coldbath treatment. Johns Hopkins Hosp. Rep., Bait., 1895, v,
321-326.
Also: Canada M. Rec, Montreal, 1895-6, xxiv, 56-60.
Also: Med. News, Phila., 1895, Ixvii, 393-395.
Also: Canada Lancet, Toronto, 1895-6, xxviii, 261-263.
/n his: Collect, repr., 1892-7, iii, no. 158.
Studies in typhoid fever: Analysis and summary of the cases:
special features, symptoms, and complications; a study of
the fatal cases. Johns Hopkins Hosp. Rep., Bait., 1895, v,
281; 283; 459.
In his: Collect, repr., 1892-7, iii, no. 159.
Neuritis during and after typhoid fever. Johns Hopkins Hosp.
Rep., Bait., 1895, v, 397-416.
In his: Collect, repr., 1S92-7, iii, no. 160.
Chills in typhoid fever. Johns Hopkins Hosp. Rep., Bait., 1895,
V, 445-457.
In his: Collect, repr., 1892-7, iii, no. 161.
The practical value of Laveran's discoveries. Med. News, Phila.,
1895, Ixvli, 561-564.
In his: Collect, repr., 1S92-7, iii, no. 162.
On the visceral complications of erythema exudativum multiforme. Am. J. M. Sc, Phila., 1895, n. s., ex, 629-646.
Also: Select, essays and monog., Lond., 1897, 321-347. 8°.
In his: Collect, repr., 1892-7, iii, no. 163.
Case of cerebral hfemorrhage in a foetus. Teratologia, Lond. &
Edinb., 1895, ii, 13.
Hyperpyrexia in typhoid fever. (Proc. Johns Hopkins Hosp.
Med. Soc, Oct. 7, 1895.) Johns Hopkins Hosp. Bull., Bait.,
1895, vi, 143.
Abscess of the liver, perforating the lung. (Proc. Johns Hopkins
Hosp. Med. Soc, Oct. 7, 1895.) Johns Hopkins Hosp. Bull.,
Bait., 1895, vi, 144.
1896
An Alabama student. Baltimore, Friedenwald Co., 1896, 19 p.
12°.
Also: Johns Hopkins Hosp. Bull., Bait., 1896, vii, 6-11.
In his: Collect, repr., 1892-7, iii, no. 166.
Typhoid fever in country districts. Maryland M. J., Bait., 1895-6,
xxxiii, 55-62.
In his: Collect, repr., 1892-7, iii, no. 155.
Visible contractile tumor of the pylorus following ulcer of the
stomach. Montreal M. J., 1895-6, xxiv, 81-86.
In his: Collect, repr., 1892-7, iii, no. 156.
John Keats, the apothecary poet. Baltimore, Friedenwald Co.,
1896. 18 p. 12°.
Also: Johns Hopkins Hosp. Bull., Bait., 1896, vii, 11-16.
I7i his: Collect, repr., 1892-7, iii, no. 164.
Thomas Dover, M. D. (of Dover's powder), physician and buccaneer. Baltimore, Friedenwald Co., 1896. 18 p. 12°.
Also: Johns Hopkins Hosp. Bull.. Bait, 1896, vii, 1-6.
In his: Collect, repr., 1892-7, iii, no. 165.
Addison's disease. Med. Bull., Phila., 1896, xviii, 81-84.
In his: Collect, repr., 1892-7, iii, no. 168.
.TlI.V, 1!U!I
On the association of enormous heart hypertrophy, chronic proliferative peritonitis and recurring ascites, with adherent
pericardium. Arch. Pediat.. N. Y.. 1896, xiii, 1-10.
In his: Collect, repr, 1S92-7, iii. no. 169.
Hemiplegia in typhoid fever. J. Nerv. & Ment. Dis., N. Y.. 1S96,
n. s., xxi. 295-304.
In his: Collect, repr.. 1S92-7. iii, no. 170.
Diseases of the blood and the ductless glands.
In: Am. Text-book Applied Therap., Phlla., 1896. 902-927.
In his: Collect, repr., 1S92-7, iii, no. 171.
The cerebral complications of Raynaud's disease. Am. J. M.
Sc, Phila., 1896. n. s., cxii, 522-529.
In his: Collect, repr., 1S92-7, iii. no. 172.
Lectures on angina pectoris and allied states. N. York M. J..
1896. Ixiv. 177: 249; 2S1: 346.
In his: Collect, repr.. 1892-7. iii, no. 173.
The study of the fevers of the South. J. Am. M. Sc, Chicago,
1896, xxi, 999-1004.
Treatment of fevers. Maritime M. News, Halifax, 1896, viii,
183-186.
Association of American Medical Colleges. Bull. Am. Acad. M..
Easton, Pa., 1895-6, ii, 508-510.
Chills in typhoid fever. Vniv. M. Mag., Phila., 1895-6, viii. 77-85.
Pleuro-peritoneal tuberculosis. (Proc. Johns Hopkins Hosp. Med.
Soc. Nov. 4. 1896.) Johns Hopkins Hosp. Bull.. Bait.. 1896,
vli, 79.
Case of Addison's disease; death during treatment with the
suparenal extract. (Proc. Johns Hopkins Hosp. Med. Soc,
Oct 19, 1896.) Johns Hopkins riosp. Bull.. Bait.. 1896. vii.
208-209.
Ephemerides. 1895:
I. Introduction.
11. Heberden's nodes.
III. Geographical tongue.
IV. Buccal leucoplacia.
V. Acute gout in the United States.
VI. Calcification of the auricle.
VII. .Arthritis deformans in childhood.
VIII. I'nusual types of night-terrors; day-terrors.
IX. Tobacco angina.
X. Unusually persistent oxyuris.
XI. Is the coin sound' distinctive of pneumothorax?
XII. Head-swaying in children.
Montreal M. J.. 1895-6. xxlv, 518: 631: 694; 777; 877; 969.
1897
Lectures on angina pectoris and allied states. New York. 1897,
D. Appleton & Co.. 160 p. 8°.
Collected reprints. Third series. (January 1. 1892-January 1,
1897. [Bait., 1897.1
On six cases of AdJison's disease, with the report of a case
greatly benefited by the use of the suprarenal extract.
Internat. M. .Mag.. Phila.. 1896-7, v, 3-11.
In his: Collect, repr. 1892-7. ill. no. 167.
On the classification of the tics or habit movements. Arch.
Pediat.. N. Y.. 1897, xiv. 1-5.
In his: Collect, repr.. 18971302. Iv, no. 174.
On certain features in the prognosis of pneumonia. Am. J. M.
Sc, Phlla., 1897, n. s., cxill. 1-10.
Also: North Car. M. J.. Wilmington. 1897. xxxix. 295-307.
In his: Collect, repr.. 1897-1902, iv. no. 175.
Mitral stenosis: sudden death; ball thrombus in the left auricle.
Montreal M. J.. 1896-7. xxv. 729-731.
In his: Collect repr.. 1897-1902. iv, no. 176.
The diagnosis of malarial fever. Med. News. N. Y., 1897. Ixx,
289-292.
In his: Collect repr.. 1897-1902. iv. no. 177.
On certain unusual forms of paraesthetic meralgla. J. Nerv. &
Ment. Dis.. N. Y.. 1897. xxlv. 131-137.
In his: Collect repr. 1897-1902, iv. no. 178.
The functions of a state faculty. President's address delivered
before the Medical and Chirurgical Faculty of Maryland, at
the 99th annual session, Baltimore. Md. April 27, 1897.
Marvland M. J.. Bait, 1897. xxxvii, 73-77. Tr M. & Chlr Fac
Maryland. Bait. 1897. 21-29.
In his: Collect repr. 1897-1902. iv, no. 179.
A case of leprosy, with exhibition of patient. Maryland M. J.,
Bait. 1897. xxxvii, 417-419.
Hemorrhage from the bowels in typhoid fever. Maryland M. J.,
Bait. 1896-7, xxxvi, 73-75.
Ephemerides. 1897:
XIII. Rheumatic neuritis associated with subcutaneous fibroid nodules.
XIV. Bright's disease or myxoedema.
XV. Remarkable noisy expiration in chronic emphysema.
XVI. Chills and fevers in post-partum ansemia.
XVII. Linese albicantes.
XVIIl. Two cases of general bromidrosis.
XIX. Vertigo and ocular defects.
Montreal M. J.. 1896-7, xxv. 642; 794: 890; 952.
A clinical lecture on the ball-valve gall-stone in the common duct.
Lancet Lond.. 1897. i. 1319-1323.
7k his: Collect, repr. 1897-1902, iv, no. 180.
Nurse and patient An address. Baltimore. 1897. J. Murphy &
Co., 17 p. 8°.
In his: Collect repr. 1897-1902. iv. no. 181.
Influence of Louis on American medicine. Johns Hopkins Hosp.
Bull.. Bait, 1897. viii, 161-167.
In his: Collect repr, 1897-1902, iv. no. 182.
British medicine in Greater Britain. The address in medicine
at the British Medical Association. Montreal, meeting. Boston M. & S. J.. 1S97, cxxxvii, 221-227.
.llso; Med. News, N. Y., 1897, Ixxi, 293-301.
Also: Med. Rec, N. Y., 1897, Hi, 333-340.
Also: Montreal M. J.. 1897. xxvi. 186-203.
In his: Collect, repr. 1897-1902. iv. no. 183.
Hepatic complications of typhoid fever. Tr. Ass. Am. Physicians,
Phila.. 1897. xii. 378-398.
Also: Edinb. M. J.. 1897. n. s. ii. 423-439.
In his: Collect repr. 1897-1902. iv, no. 184.
Internal medicine as a vocation. Med. News. N. Y.. 1897. Ixxi.
660-663.
In his: Collect, repr., 1897-1902. iv, no. 185.
Pneumonia; a review of the cases studied by the third and
fourth classes, Johns Hopkins Hospital, session of 1896-97.
Nat. M. Rev., Wash.. 1897-8, vii, 177-180.
In his: Collect, repr, 1897-1902, iv, no. 186.
Occasional notes on American medical classics; introductory
lecture to a course of clinical observations in the Pennsylvania Hospital, delivered there on the 3d of December, 1776.
bv Dr Thomas Bond. Univ. M. Mag.. Phila., 1897-8, x. 136140.
In his: Collect repr. 1897-1902. iv. no. 187.
Sporadic cretinism in America. Am. J. M. Sc, Phlla., 1897,
cxlv. 377-401.
.4 Mo; Tr. Cong. Am. Phys. & Surg., N. Haven, 1897, Iv, 169-206.
In his: Collect repr.. 1897-1902. iv. no. 188.
Address In medicine. Brit M. J., Lond.. 1897. 11, 576-581.
.4/80 [Abstrl: Lancet. Lond.. 1897. ii. 584-589.
Also: Brit M. Ass. Dally J., Montreal. 1897. Part 3, 42-50.
Address In medicine, at the sixty-fifth annual meeting of the
British Medical Association. Montreal, Aug, 31 to Sept 4,
1897. J. Am. M. Ass., Chicago. 1897. xxlx, 507-512.
U-i medicine anglalse dans la Nouvelle Angleterre. [Trans.]
Union mM. du Canada. Montreal. 1897, xxvi, 595-599.
Relapses in typhoid fever. J. Am. M. Ass.. Chicago, 1897, xxlx,
97.
The disguises of typhoid fever Galllard's M. J., N. Y., 1897.
Ixiv, 350-352.
Tuberculosis. Syst Pract M. (Loomis), N. Y. & Phila., 1897, 1,
731-848.
228
[Xo. 341
1898
The principles and practice of medicine. Designed for tbe use
of practitioners and students of medicine. 3. ed. New York,
1898, D. Appleton & Co., IISI p. 8°.
Spontaneous pneumothorax. Maryland M. J., Bait., 1897-8,
xxxviii, 461-463.
Pneumonia. J. Pract. Med., N. Y.. 1897-8. viii, 308-311.
On chronic symmetrical enlargement of the salivary and lachrymal glands. Am. J. M. Sc, Phila., 1898, cxv, 27-30.
In his: Collect, repr., 1897-1902, iv, 189.
On some of the intestinal features of typhoid fever. Phila. M. J.,
1898, i. 30-32.
In his: Collect, repr., 1897-1902, iv, no. 190.
Ein Fall von Fistula cesophago-pleuro-thoracica. Arch. f. Verdauungskr., Berl., 1898, iii, 383-386.
In his: Collect, repr., 1897-1902, iv, no. 191.
The relation of typhoid mortality and sewerage. Maryland M. J.,
Bait., 1897-8, xxxviii, 217-218.
In his: Collect, repr., 1897-1902, iv, no. 192.
Leprosy in the United States, with the report of a case. Johns
Hopkins Hosp. Bull., Bait., 1898. ix, 47-49.
In his: Collect, repr., 1S97-1902, iv, no. 193.
On diffuse scleroderma; with special reference to diagnosis, and
to the use of the thyroid-gland extract. J. Cutan. & Genitourin. Dis., N. Y., 1898, xvi, 49; 127.
In his: Collect, repr., 1897-1902, iv, no. 194.
Cerebral features of pneumonia. Maryland M. J., Bait., 1897-8,
xxxviii, 381-383.
In his: Collect, repr., 1897-1902, iv, no. 195.
Cerebro-spinal fever. Maryland M. J., Bait., 1898, xxxix, 717-723.
In his: Collect, repr., 1897-1902, iv, no. 196.
The arthritis of cerebro-spinal fever. Boston M. & S. J.. 1898,
cxxxix, 641-643.
In his: Collect, repr., 1897-1902, iv, no. 197.
Ephemerides, 1897:
XX. The blood coagulation time in jaundice.
XXI. Facial paralysis with herpes zoster.
XXII. Paralysis of the ocular muscles in albuminuria.
Montreal M. J., 1898, xxvii, 36-38.
Tuberculosis. Am. Text-Bk. Dis. Child. (Starr), 2. ed. Phila.,
1898, 270-302.
On the study of pneumonia. St. Paul M. J., St. Paul, Minn., 1899.
i, 5-9.
In Ms: Collect, repr., 1897-1902, iv, no. 198.
The problem of typhoid fever in the United States. Baltimore,
1899, J. Murphv Co., 13 p. 8°.
Also: Albany M. Ann.. 1899, xx, 121-130.
Also: Med. News, N. Y., 1899, Ixxiv, 225-229.
In his: Collect, repr., 1897-1902, iv, no. 199.
An acute myxoedematous condition with tachycardia, glycosuria,
metena, mania, and death. J. Nerv. & Ment. Dis., N. Y., 1899,
xxvi, 65-71.
In his: Collect, repr., 1897-1902, iv, no. 200.
The clinical features of sporadic trichinosis. Am. J. M. Sc, Phila.,
1899, n. s., cxvii, 251-265.
In his: Collect, repr., 1897-1902, iv, no. 201.
In memoriam, William Pepper. Phila. M. J., 1899, iii, 607-611.
In his: Collect, repr., 1897-1902, iv, no. 202.
Chronic splenic enlargement with recurring gastrointestinal
haemorrhages. Edinb. M. J., 1899, n. s., v, 441-453.
In his: Collect, repr., 1897-1902, iv, no. 204.
Cavendish lecture. On the etiology and diagnosis of cerebrospinal fever. [London, 1899.] 46 p. 8°.
Also: West. Lond. M. J., Lond., 1899, iv, 145-188.
Also: Brit. M. J., Lond., 1899. i. 1517-1529.
Also: Boston M. & S. J., 1899, cxli, 1; 32.
Also: Canad. Pract. & Rev., Toronto, 1899, xxv [xxiv], 447-455.
Also: Lancet, Lond., 1899, i. 1699-1709.
.4;so; Phila. M. J., 1899, iv, 26-41.
In his: Collect, repr., 1897-1902, iv, no. 205.
After twenty-five years. An address at the opening of the session
of the medical faculty, McGill University, Sept. 21, 1899.
Montreal M. J., 1899, xxviii, 823-833.
In his: Collect, repr., 1897-1902, iv, no. 206.
The diagnosis of typhoid fever. A discussion at the New York
State Medical Association, October 25, 1899. N. York M. J.,
1899, Ixx, 673-676.
In his: Collect, repr., 1897-1902, iv, no. 207.
Clinical remarks on hypertrophic cirrhosis of the liver with
bronzing of the skin: hfemochromatosls. Brit. M. J., Lond.,
1899, ii, 1595-1596.
In his: Collect, repr., 1897-1902, iv, no. 208.
On the medical tests for admission to the public services (Discussion). Brit. M. J., Lond., 1899, ii, 574.
The preventive and remedial treatment of tuberculosis (Discussion). Brit. M. J., Lond., 1899, ii, 1155.
Blood parasites of frogs. N. York M. J., 1S99, Ixix, 63.
Clinical microscopy at Johns Hopkins Medical School, Baltimore,
United States of America. Brit. M. J., Lond., 1899, i, 69-70.
1900
On splenic anapmia. Am. J. M. Sc, Phila.. 1900, n. s., cxix, 54-73.
In his: Collect, repr., 1897-1902, iv, no. 209.
The home treatment of consumption. Maryland M. J., Bait., 1900,
xliii, 8-12.
Also: Med. Mirror, St. Louis. 1900, xi, 165-169.
In his: Collect, repr., 1897-1902. iv, no. 210.
A case of multiple gangrene in malarial fever. Johns Hopkins
Hosp. Bull., Bait, 1900, xi, 41-42.
In his: Collect, repr., 1897-1902, iv, no. 211.
The visceral lesions of the erythema group. Brit. J. Dermat,
Lond., 1900, xii, 227-245.
In his: Collect, repr., 1897-1902, iv, no. 213.
An address on the importance of post-graduate studv. Lancet,
Lond., 1900, ii, 73-75.
In his: Collect, repr., 1897-1902, iv, no. 214.
Elisha Barlett, a Rhode Island philosopher. An address delivered
before the Rhode Island Medical Society, Dec. 7, 1899. With
an appendix containing Dr. Bartlett's sketch of Hippocrates.
Providence, 1900, Snow & Furnham, 43 p. 8°.
Also: Boston M. & S. J., 1900, cxlii, 49; 77.
In his: Collect, repr., 1897-1902, iv, no. 215.
An address on John Locke as a physician. Delivered before the
Students' Societies of the Medical Department of the Universitv of Pennsylvania on Jan. 16, 1900. Lancet. Lond., 1900,
ii, 1115-1123.
In his: Collect, repr., 1897-1902, iv, no. 216.
Hemiplegia in typhoid fever. Johns Hopkins Hosp. Rep., Bait.,
1900, viii, 363-371.
In his: Collect, repr., 1897-1902, iv, no. 217.
Hepatic complications of typhoid fever. Johns Hopkins Hosp.
Rep., Bait., 1900, viii, 373-383.
In his: Collect, repr., 1897-1902, iv, no. 218.
Analysis and general summary of the cases [of typhoid feverl
from 1889-1899. Johns Hopkins Hosp. Rep., Bait., 1900, viii,
421-422.
In his: Collect, repr., 1897-1902, iv, no. 219.
Special features, symptoms and complications [of typhoid fever].
Johns Hopkins Hosp, Rep.. Bait., 1900, viii, 423-486.
In his: Collect, repr., 1897-1902, iv, no. 220.
On the study of tuberculosis. Phila. M. J., 1900. vi, 1029-1030.
In his: Collect, repr., 1897-1902, iv, no. 221.
General summary of the cases of typhoid fever in The Johns
Hopkins Hospital for ten years. Phila. M. J., 1900, vi, 696-697.
Fatal angina pectoris without lesions of the coronary arteries in
a young man. Med. News, N. Y., 1900, Ixxvii, 974-976.
The centenary of the Royal College of Surgeons (Correspondence). Maryland M. J., Bait., 1900, xliii, 520-522.
Osier, W., & McCrae, T. Cancer of the stomach. A clinical study.
Phila., 1900, P. Blakiston's Son & Co., 157 p. 8°.
Osier, W., & McCrae, T. Cancer of the stomach in the young.
N. York M. J., 1900, Ixxi, 581-585.
ll LV. l!ll!l|
Osier, W., & McCrae, T. A study of the blood in cancer of the
stomach. N. York M. J., 1900, Ixxi, 757-761.
Osier, W., & McCrae, T. Latent cancer of the stomach. Phila.
M. J., 1900, V, 245-247.
In his: Collect, repr., 1897-1902, iv, no. 212.
1901
The principles and practice of medicine. Designed for the use of
practitioners and students of medicine. 4. ed. New York,
1901, D. Appleton & Co., 1182 p. S^
Sporadic cretinism (infantile and juvenile myxoedema).
In: Cvcl. Dis. Child., M. & S. (Keating), Phila., 1901, v, 359-371.
In his: Collect, repr., 1897-1902, iv, 203.
Cerebro-spinal fever.
In: Cvcl. Dis. Child., M. & S. (Keating). Phila., 1901, v, 13331351.
Surgical intervention In perforation in typhoid fever. Phila.
M. J.. 1901. vii, 138.
On perforation and perforative peritonitis in typhoid fever. Phila.
M. J., 1901, vii, 116-119.
Also: St. Louis M. & S. J., 1901, Ixxx, 254-264.
In his: Collect, repr., 1S97-1902, iv, no. 222. .
Books and men. Remarks made at the opening of the new build• ing of the Boston Medical Library, January 12, 1901. Boston
M. & S. J.. 1901, cxliv. 60-61.
In his: Collect repr., 1897-1902, iv, no. 223.
The past century, its progress in great subjects. Medicine.
In: Sun, \. Y.. 1901. Jan. 27.
In his: Collect, repr., 1897-1902, iv, no. 224.
The progress of medicine in the nineteenth century. [New York,
1901. 8M
In: Progr. Cent. New York & Lond., 1901, 173-214, 8°.
[" The progress of medicine" the same as "The past century".]
A plea for the more careful study of the symptoms of perforation
in typhoid fever with a view to early operation. Lancet.
Lond., 1901. i, 386-387.
In his: Collect, repr., 1897-1902, iv, no. 225.
The medical aspects of carcinoma of the breast, with a note on the
spontaneous disappearance of secondary growths. Am. Med..
Phila., 1901, i, 17; 63.
In his: Collect, repr.. 1897-1902, iv, no. 226.
Hemorrhage In chronic Jaundice (Correspondence). Am. Med.,
Phila.. 1901, i, 152.
On the advantages of a trace of albumin and a few tube casts in
the urine of certain men above fifty vears of age. N. York
M. J., 1901. Ixxiv, 949-950.
Also: Indian M. Rec. Calcutta, 1902, xxii. 92-93.
In his: Collect, repr., 1897-1902, iv. no. 227.
Congenital absence of the abdominal muscles, with distended and
hypertrophied urinary bladder. Johns Hopkins Hosp. Bull.,
Bait., 1901, xli. 331-333.
In his: Collect, repr.. 1897-1902, iv. no. 228.
On a family form of recurring epistaxis, associated with multiple
telangiectases of the skin and mucous membranes. Johns
Hopkins Hosp. Bull.. Bait., 1901. xil. 33,3-337.
In his: Collect, repr.. 1897-1902. iv, no. 229.
The natural method of teaching the subject of medicine. J. Am.
M. Ass., Chicago, 1901, xxxvl, 1673-1679.
The study of internal medicine. .Med. News, N. Y., 1901, Ixxvlli,
645-647.
The spinal form of arthritis deformans. Remarks introductory to
a discussion on the subject. Tr. Ass. Am. Phvsicians, Phila.,
1901, xvl. 687-689.
1902
The principles and practice of medicine. Designer! for the use
of practitioners and students of medicine. 5. ed. New York,
1902, D. Appleton ft Co., Iii79 p. 8°.
Collected reprints. Fourth series. (January 1, 1897-January 1,
1902. (Bait, 1902.)
On the diagnosis of bilateral cystic kidney. Am. Med., Phila.,
1902, ill, 463-464.
In his: Collect, repr., 1902-1907, v, no. 230.
On amebic abscess of the liver. Med. News, N. Y., 1902, Ixxx.
673-677.
In his: Collect, repr., 1902-1907, v, no. 231.
Amebic dysentery. Therap. Gaz., Detroit, 1902, 3, s., xviii, 217-218.
Also: Proc. Phila. Co. M. Soc, Phila., 1902, n. s., iv, 44-46.
In his: Collect, repr., 1902-1907, v, no. 232.
Note on the occurrence of ascites in solid abdominal tumors.
Phila. M. J.. 1902, ix, 928-929.
In his: Collect, repr., 1902-1907, v. no. 233.
Alfred Stills. I'niv. Penn. Med. Bull., Phila., 1902, xv, 126-132.
In his: Collect, repr., 1902-1907, v, no. 234.
Notes on aneurism. J. Am. M. Ass., Chicago, 1902, xxxviii, 14831486.
In his: Collect, repr., 1902-1907, v, no. 235.
On heredity in bilateral cystic kidney. Am. Med., Phila., 1902,
iii, 951.
In his: Collect, repr., 1902-1907, v, no. 236.
Some aspects of .American medical bibliography. .Address at the
meeting of the Association of .Medical Librarians, Sarato.ga,
June 10, 1902. Bull. Ass. .M. Librar., Bait., 1902, i, 19-32.
Also: Am. .Med., Phila., 1902, iv, 424-427.
In his: Collect, repr., 1902-1907, v, no. 237.
Chauvinism in medicine. An address before the Canadian Medical Association, .Montreal, Sept. 17, 1902. Phila. M. J., 1902,
X. 432-439.
In his: Collect, repr., 1902-1»07, v, no. 238.
On splenic amemia. [Second paper.] Am. J. M. Sc, Phila., 1902,
cxxiv, 751-770.
Also: Tr, Ass. Am. Physicians, Phila., 1902, xvii, 429-456.
In his: Collect, repr., 1902-1907, v, no. 239.
William Beaumont. A pioneer American physiologist. An address
before the St. Louis Medical Society, Oct. 4, 1902. St. Louis,
1902, 29 p. 8'.
.4/so.- J. Am. M. Ass., Chicago. 1902. xxxix. 12231231.
In his: Collect, repr., 1902-1907, v, no. 240.
A note on the treating of the history of medicine. Grit. M. J.,
Lond., 1902, ii, 93.
Intermittent claudication. Montreal M. J., 1902, xxxi, 81-86.
A visit to the Hunterian Library at Glasgow. Bull. Ass. M.
Librar., Bait., 1902, i, 20-23.
Case of leukaemia. Virginia M. Semi-Month.. Richmond, 1902-3,
vii, 540.
On the need of a radical reform in our methods of teaching senior
students. Med. News. N. Y., 1903, Ixxxii, 49-53.
In his: Collect, repr., 1902-1907, v, no. 241.
Aneurism of the descending thoracic aorta. Phila., 1903, J. B
Lippincott Co., 40 p. 8°.
Also: Internal. Clin., Phila., 1903, 13. s., i, 1-40,
In his: Collect, repr., 1902-1907. v, no. 242.
On the educational value of the medical society. Boston M. &
S. J., 1903, cxivili, 275-279.
In his: Collect, repr., 1902-1907, v, no. 243.
A case of chronic purpuric erythema (eight years' duration) with
pigmentation of skin and enlargement of liver and spleen.
J. Cutan. Dis. incl. Syph., N. Y., 1903, xxi, 297-302.
In his: Collect, repr., 1902-1907, v, no. 244.
On obliteration of the superior vena cava. Johns Hopkins Hosp.
Bull.. Bait., 1903, xiv. 169175.
In his: Collect, repr., 1902-1907, v, no. 245.
On the so-called Stokes-Adams disease (slow pulse with syncopal
attacks, etc.). Uincet. Lond., 1903, li, 516-524.
In his: Collect, repr.. 1902-1907, v, no. 246.
Chronic cyanosis with polvcvlha>mia and enlarged spleen: a new
clinical entity. Am. J. .M. Sc, Phila., 1903, n. s.. cxxvl, 187-201.
.4/so; Tr. Ass. Am. Physicians, Phila., 1903, xvill, 299-325.
In his: Collect, repr.. 19021907, v, no. 247,
The master-word in medicine. An address to medical students
on the occasion of the opening of the new buildings of the
Medical Faculty of the Tniversity of Toronto, Oct. 1, 1903,
Baltimore, 1903, J. Murphv Co.. 33 p. 8'.
Also: Brit. M. J.. Lond., 1903. II. 1196-1200.
Also: Canad. J. M. & S.. Toronto, 1903, xlv, 333-347.
Also: Montreal .M. J.. 1903, xxxll. 771-785.
Also: Johns Hopkins Hosp. Bull., Bait., 1904, xv. 1-7.
In his: Collect, repr., 19021907, v, no. 248.
230
[Xo. 341
Typhoid fever and tuberculosis. Am. Med., Phila., 1903, vi, 10151016.
In his: Collect, repr., 1902-1907, v, no. 249.
The home in its relation to the tuberculosis problem. Med. News,
N. Y., 1903, Ixxxiii, 1105-1110.
In his: Collect, repr., 1902-1907, v. no. 250.
On the visceral manifestations of the erythema group of skin
diseases. Tr. Ass. Am. Physicians, Phila., 1903, xviii, 599-624.
Also: Am. J. M. Sc, Phila., 1904, cxxvii, 1-23.
In his: Collect, repr., 1902-1907, v, no. 251.
Diabetes in infancy. Phila. M. J., 1903, xi, 538.
The significance of cutaneous angiomata, Med. News. N. Y., 1903.
Ixxxii, 91.
The varieties of linese albicantes. Med. News, N. Y., 1903, Ixxxiii,
904.
Aneurism of upper part of thoracic aorta. (Proc. Johns Hopkins
Hosp. Med. Soc. Oct. 20, 1902.) Johns Hopkins Hosp. Bull.,
Bait., 1903, xiv, 85.
Certain forms of cyanosis with polycythsemia. (Proc. Johns
Hopkins Hosp. Med. Soc, Nov. 17, 1902.) Johns Hopkins
Hosp. Bull.. 1903, xiv. 91.
Also: Maryland M. J., Bait, 1903, xlvi, 81-82.
Two cases of cirrhosis of the liver in children. (Proc. Johns Hopkins Hosp. Med. Soc, March 16, 1903.) Johns Hopkins Hosp.
Bull., Bait., 1903, xiv, 322.
1904
Aequanimitas, with other addresses to medical students, nurses
and practitioners of medicine. Phila., 1904, P. Blakiston's Son
& Co. 389 p. 12°.
The same. Lond., 1904, H. K. Lewis, 389 p. 12°.
The Ingersoll lecture, 1904. Science and immortality. Boston,
1904, Houghton, Mifflin & Co. 60 p. 12°.
The " phthisiologia " of Richard Morton, M. D. Med. Libr. & Hist.
J., Brooklyn, 1904. ii, 1-7.
In his: Collect, repr., 1902-1907, v, no. 252.
Ochronosis: the pigmentation of cartilages, sclerotics. and skin
in alkaptonuria. Lancet. Lond., 1904, i, 10-11.
In his: Collect, repr., 1902-1907, v. no. 253.
On the surgical importance of the visceral crises in the erythema
group of skin diseases. Am. J. M. Sc, Phila. & N. Y., 1904,
n. s., cxxvii, 751-754.
Also: Johns Hopkins Hosp. Bull., Bait., 1904, xv. 259-261.
In his: Collect, repr., 1902-1907, v, no. 254.
Angina pectoris and arterio-sclerosis. J. Am. M. Ass., Chicago,
1904, xliii, 775.
Chronic cyanotic polycythemia with enlarged spleen. Brit. M. J.,
Lond., 1904, i, 121.
Korsakoff's disease. N. York M. J. [etc.], 1904, ixxix, 570.
Vasomotor mottling. (Proc Johns Hopkins Hosp. Med. Soc,
Nov. 16, 1903.) Johns Hopkins Hosp. Bull., Bait., 1904, xv, 66.
Aneurism of arch of aorta and innominate. (Proc. Johns Hopkins
Hosp, Med. Soc, Nov. 16, 1903.) Johns Hopkins Hosp. Bull.,
Bait., 1904, xv, 66.
Remarks at the unveiling of the memorial tablet to Dr. Jesse AV.
Lazear. Johns Hopkins Hosp. Bull., Bait., 1904, xv, 3S7-388.
The home in its relation to the tuberculosis problem. Sanitarian,
N. Y., 1904, lii, 322-336.
Also: Canada Lancet, Toronto, 1904-5, xxxviii, 600-612.
1905
The principles and practice of medicine, designed for the use of
practitioners and students of medicine. 6. ed. N. Y. & Lond.,
1905, D. Appleton & Co. 1143 p. 8°.
Counsels and ideals from the writings of ... . [Selected and
edited by C. N. B., Camac] Bost. & N. Y.. 1905, Houghton,
Mifflin & Co. 277 p. 12°.
Unity, peace, and concord; a farewell address to the medical profession of the United States. Oxford, 1905, H. Hart, 22 p. 8°.
Also: J. Am. M. Ass., Chicago, 1905, xiv, 365-369.
Also: St. Louis M. Rev.. 1905, lii, 112-116.
Also: Maryland M. J., Bait., 1905, xlviii, 412-422.
In his: Collect, repr., 1902-1907, v, no. 255.
The student life. A farewell address to Canadian and American
medical students. Oxford [1905.] H. Hart. 32 p. 8°.
Also: Canada Lancet, Toronto, 1905-6, xxxix, 121-138.
Also: Med. News, N. Y., 1905, Ixxxvii, 625-633.
Also: St. Louis M. Rev., 1905, lii, 273-283.
In his: Collect, repr., 1902-1907, v, no. 256. •
Aneurism of the abdominal aorta. Lancet, Lond., 1905, ii, 10891096.
In his: Collect, repr., 1902-1907, v, no. 257.
Acute tuberculous pneumonia. Brooklyn M. J., 1905, xix, 57-61.
The home in its relation to the tuberculosis problem. Rev. internat. de la tuberc. Par., 1905, vii, 403-413.
Also: Rep. Henry Phipps Inst, study .... tuberculosis, Phila.,
1905, i, 141-154.
Also: Am. J. Tuberc, Detroit, 1905, i, 9-15.
An address on Sir Thomas Browne. Brit. M. J., Lond., 1905, ii,
993-998.
The Royal Dental Hospital of London: address. Lancet, Lond.,
1905, ii, 1210.
Valedictory address at Johns Hopkins University. J. Am. M. Ass.,
Chicago, 1905, xliv, 705-710.
Biliary cirrhosis of family type. (Proc. Johns Hopkins Hosp.
Med. Soc, Nov. 7, 1904). Johns Hopkins Hosp. Bull., Bait.,
1905, xvi, 112-113.
Report of a case of ulcerative endocarditis, with embolism of the
aorta. (Proc. Johns Hopkins Hosp. Med. Soc, Dec. 19, 1904).
Johns Hopkins Hosp. Bull., Bait.. 1905, xvi, 118.
Report of a case of arterio-venous aneurism of the thigh. (Proc.
Johns Hopkins Hosp. Med. Soc, Dec. 19, 1904). Johns Hopkins Hosp. Bull., Bait., 1905, xvi, 119.
A case of arterio-venous aneurism. (Proc. Johns Hopkins Hosp.
Med. Soc, Jan. 16, 1905). Johns Hopkins Hosp. Bull., Bait.,
1905, xvi, 146.
Resume of history of blood platelets. (Proc. Johns Hopkins Hosp.
Med. Soc, March 6, 1905). Johns Hopkins Hosp. Bull., Bait.,
1905, xvi, 200.
A letter to graduates of The Johns Hopkins Medical School. Johns
Hopkins Hosp. Bull., Bait, 1905, xvi, 410.
1906
Aequanimitas, with other addresses to medical students, nurses,
and practitioners of medicine, 2. ed. with three additional
addresses. Phila., 1906, P. Blakiston's Son & Co., 475 p. 8°.
The same, Lond., 1906, H. K. Lewis, 485 p. 8°.
Convulsions in typhoid fever. Practitioner, Lond., 1906, Ixxvi,
1-8.
In his: Collect repr., 1902-1907, v, no. 258.
On the medical aspects of carcinoma of the breast. Brit. M. J.,
Lond., 1906, i, 1-4.
In his: Collect repr., 1902-1907, v, no. 259.
Angina pectoris as an early symptom in aneurism of the aorta.
Med. Chron., Manchester, 1906, xliv, 69-79.
In his: Collect, repr., 1902-1907, v, no. 260.
Religio medici. An address delivered at Guy's Hospital, October,
1905, Lond., 1906, Chiswick Press, 31 p. 8°.
Also: Library, Lond., 1906, vii, 1-31.
In his: Collect repr., 1902-1907, v, no. 261.
The growth of truth as illustrated in the discovery of the circulation of the blood. Being the Harveian oration delivered at
the Royal College of Physicians, London, October 18, 1906.
Lond., 1906, H. Frowde. 44 p. 8°.
Also: Brit. M. J., Lond., 1906, ii, 1077-1084.
Also: Lancet, Lond., 1906, ii, 1113-1120.
Also: Boston M. & S. J., 1906, civ, 491-502.
In his: Collect repr., 1902-1907, v, no. 262.
Pracastorius. Proc. Charaka Club, N. Y., 1906, Ii, 5-20.
In his: Collect repr., 1902-1907, v, no. 263.
Address of the Vice-President. Nat. Ass. Study & Prevent. Tuberculosis, Trans., N. Y., 1906, i, 20-27.
John Radcliffe [the first possessor of the " gold-headed cane."]
Johns Hopkins Hosp. Bull. Bait., 1906, xvii, 163-165.
Jilt, 1919]
231
1907
Collected reprints. Fifth series. (January 1, 1902-January 1,
1907.) (Bait, 1907.1
The Royal Medical Society of Edinburgh: particularly its relations with the profession of the United States and Canada.
Scot. M. & S. J., Edinb.. 1907, xx, 239-246.
Cerebrospinal fever. Edinb. M. J., 1907, n. s.. xxi, 199-204.
The earlv diagnosis of cancer of the stomach. Brit. M. J., Lond.,
190", i, 746.
On the library of a medical school. Johns Hopkins Hosp. Bull.,
Bait.. 1907. xviii, 109-111.
On telangiectasis circumscripta universalis. Johns Hopkins Hosp.
Bull., Bait., 1907. xviii, 401-403.
A clinical lecture on abdominal tumors associated with disease of
the testicle. Lancet, Lond.. 1907. i, 1409-1412.
Note on the use of a medical journal. West. Canada M. J.. Winnipeg. 1907. i. 1-3.
The reserves of life. St. Mary's Hosp. Gaz., Lond., 1907, xiii. 95-98.
The evolution of internal medicine.
In: Mod. .Med. (Osier). Phila. & N. Y.. 1907. i. p. xv-xxxiv.
Osier. W., & Churchman. J. W. Svphilis.
In: Mod. .Med. (Osier), Phila. & N. Y.. 1907, iii, 436-521.
Osier, W., & McCrae. T.. eds. Modern medicine, its theory and
practice. In original contributions by American and foreign
authors, v. 1-3. Phila. & N. Y.. 1907, Lea Brothers & Co., 8°.
Osier. W. \ct nl.]. Discussion on the diagnosis of acute pancreatitis. (Abstr.l Brit. M. J.. Lond.. 1907. ii. 1132-1135.
Krehl, Ludolf. Principles of clinical pathology. A text-book for
students and physicians. Authorized transl. from the 4. German ed. by Walter Hewlett, with an introduction by William
Osier. 2. ed. Phila. & Lond. 1907. J. B. Lippincott Co.
520 p. S'.
Quarterly (The) Journal of Medicine. Edited by William Osier
let al.]. Oxford. 1907. V. 1. roy. 8'.
Thomas Linacre. Cambridge. 1908, University Press, 64 p. 11 pi.
12°.
An Alabama student, and other biographical essays. N. Y., 1908,
Oxford Univ. Press, Am. Branch. 334 p. 8 .
La pratique de la m^decine. Traduction frauQaise sur la 6' Edition
par M. Solomon et Louis Lazard. Preface du Dr. Pierre Marie.
Par.. 1908. G. Steinheil. 12.30 p. 8°.
On multiple hereditary telangiectasis with recurring haemorrhages.
Quart. J. Med., Oxford, 1907-8, 1. 53-58.
Splenic polycythaemia with cvanosis. Proc. Rov. Soc. .Med.. I..ond..
1907-8. 1. Clin. Sect.. 41-43.
A clinical lecture on erythema (polycythemia with cyanosis,
maladie de Vaquez). Lancet, Lond.. 1908. i. 143-146.
Note on French and German for medical students. Lancet, Lond.,
1908, It, 957.
Splenic enlargements other than leukemic. Brit. M. J.. Lond.,
1908. ii. 1151-1154.
Remarks on the functions of an out-patient department Brit.
M. J.. Lond.. 1908. i. 1470-1473.
Also: St. I^uls M. Rev.. 1908. Iviil. 344-346.
Chronic Infectious endocarditis. Quart. J. Med . Oxford. 1908-9.
II. 219-230.
Also: Tribune med., N. Y.. 1909, I, v. 29.
Endocardites infectieuses chronlques. Bull, el m6m. Soc. m^'-d. d.
h6p. de Par, 1908. 3. s.. xxv. 794-796.
Also: Tribune m«d.. Par. 1908. n. s., xl. 773.
The pneumococcus Infections. Clin. J.. Lend.. 1907-8. xxxi, 295-301.
Also: Tr .M. Soc, Lond.. 1909. xxxi, 93-116.
Historical note on hereditary chorea. Neurographs. Brooklyn,
1908. 1. 113-116.
Vienna after thirty-four years. J. Am. M. Ass.. Chicago, 1908,
1, 1523-1525.
Acute endocarditis.
In: Mod. Med. (Osier), Phila. & N. Y., 1908, iv, 133-150.
Diseases of the arteries.
In: Mod. Med. (Osier), Phila. & N. Y.. 1908, Iv, 426-447.
Aneuo'sm.
In: Mod. Med. (Osier). Phila. & N, Y.. 1908, iv. 448-502.
Osier. W.. & Gibson. A. G. Diseases of the valves of the heart.
In: Mod. Med. (Osier), Phila. & N. Y.. 1908. iv. 205-269.
Osier. W., & McCrae. T., eds. Modern medicine, its theory and
practice. In original contributions by American and foreign
authors, v. 4-5, Phila. & N. Y., 1908. Lea & Feblger 8°.
1909
The principles and practice of medicine, designed for the use of
practitioners and students of medicine. 7. ed., N. Y. & Lond.,
1909. D. Appleton & Co.. 1143 p., 8°.
Lehrbuch der internen Medizin. Aus dem Engllschen iibersetzt
und fiir deutsche Verhaltnisse erganzt und bearbeitet von
Priv.-Doz. Dr. Edmund Hoke, mit einem Vorwort von ober
sanitatsrat und Hofrat Prof. Dr. R. v. Jaksch. Berlin & Wlen,
1909. Urban & Schwarzenberg, 879 p., 8°.
De la paralvsie du nerf recurrent gauche dans les affections
mitrales.' Arch. d. mal. du cceur [etcl. Par, 1909, Ii, 73-76.
Paralvsis of the left recurrent laryngeal nerve In mitral-valve
disease. Montreal M. J., 1909. xxxviii. 79-83.
Remarks on the medical library in post-graduate work. Brit.
M. J.. Lond.. 1909, Ii, 925-928.
Schorstein lecture on syphilis and aneurysm. Brit M. J., Lond..
1909. ii. 1509-1514.
The treatment of disease. Lond.. 1909. H. Frowde, 26 p.. 8°.
Also: Brit M. J., Lond.. 1909. ii. 185-189.
Also: Canad. Lancet. Toronto, 1908-9, xlii, 896-912.
Note on the relation of the capillary blood-vessels in purpura.
Lancet, Lond.. 1909. i. 1385.
An address on the nation and the tropics. Delivered at the London
School of Tropical Medicine on Oct 26. 1909. Lancet, Lond.,
1909. ii. 1401-1406.
Impressions of Paris. J. Am. M. Ass.. Chicago, 1909, Hi, 701; 771.
Old and new. Annual oration on the occasion of the opening of
the new building of the .Medical and Chirurgical Faculty of
Maryland, .May 13, 1909. J. .Am. M. Ass., Chicago, 1909, llii.
4-8.
In: 'Sys't. Med. (Allbutt & Rolleslon). Lond., 1909, vl, 620-681.
Raynaud's disease.
In: Mod. Med. (Osier), Phila. & N. Y.. 1909, vi, 625-647.
Angioneurotic oedema; Quincke's disease.
In: Mod. Med. (Osier), Phila. & N. Y., 1909. vi. 648-664.
Diffuse scleroderma; ervthromelalgia.
In: Mod. Med. (Osier), Phila. & N. Y., 1909. vl. 665-682.
Osier, W.. & Keith. A. Stokes-Adams disease.
In: Syst Med. (Allbutt & Rolleston). Lond.. 1909. vi, 130-156.
Osier. W.. & McCrae. T.. eds. Modern medicine. Its theory and
practice. In original contributions by American and foreign
authors, v. 6. Phila. & X. Y., 1909, Lea & Feblger, 799 p.. 8°.
1910
The principles and practice of medicine, transl. by Philip B.
Cousland. 7. ed. (Chinese text] Shanghai. 1910. Presby. Mis.
Press. 8°.
In memorlam. Dr John Hewetson. 1867-1910. Johns Hopkins
Hosp. Bull.. Bait. 1910. xxi. .357.
Michael Servetus. Johns Hopkins Hosp. Bull., Bait, 1910. xxi.
Also transl.: Deutsche Rev., Stuttg. u. Leipz., 1909, Iv, 328-347.
Certain vasomotor, sensory, and muscular phenomena associated
with cervical rib. Am. J. M. Sc. Phila. & N. Y.. 1910. cxxxix,
469-472.
The Lumlelan lectures on angina pectoris. Lancet. Lond., 1910,
I. 697; 839; 97.'!.
Female hipmophillacs and de novo cases of hsemophllla. Lancet,
Lond., 1910. I. 1226.
332
[Xo. 341
The faith that heals. Brit. M. J., Lond.. 1910. ii. 1470-1472.
The pupil symptoms in thoracic aneurysm: a clinical lecture:
Radcliffe Infirmary. Practitioner, Lond., 1910, Ixxxiv, 417-422.
Ueber angina pectoris. AUg. Wien. med. Ztg.. 1910, Iv, 435.
Osier, W., & McCrae, T., eds. Modern medicine, its theory and
practice. In original contributions by American and foreign
authors, v. 7, Phila. & N. Y., 1910, Lea & Febiger, 969 p., 8°.
1911
Man's redemption of man. Am. Mag., N. Y., 1910-11, Ixxi, 246-252.
Transient attacks of aphasia and paralyses in states of high blood
pressure and arteriosclerosis. Canad. M. Ass. J., Toronto,
1911, i, 919-926.
An address on the hospital unit in university work. Lancet, Lond.,
1911, i, 211-213.
Also: Northumberland & Durham M. J., Newcastle-upon-Tyne,
1910, xviii, 178-189.
Remarks on organization in the profession. Brit. M. J., Lond.,
1911, i, 237-239.
Treatment; introductory address. Nat. Ass. Prev. Consumpt. Tr.,
Lond., 1911, 119-123.
The pathological institute of a general hospital. Glasgow M. J.,
1911, Ixxvi, 321-333.
Sir Astley Cooper's case of ligature of the abdominal aorta. Guy's
Hosp. Gaz., Lond., 1911, xxv, 277.
Sulle telangiectasie emorragiche ereditarie. Riforma med., Napoli,
1911, xxvii, 57-58.
Vallery-Radot, Rene, The life of Pasteur. Transl. from the French
by Mrs. R. D. Devonshire; with a foreword bv Sir William
Osier, 2 v. Lond., 1911, Constable & Co. 242 p., port; 271 p., S°.
1912
The principles and practice of medicine. S. ed., rev. with the
assistance of Thomas McCrae. N. Y. & Lond., 1912. D. Appleton & Co., 1250 p., 8°.
A Drake monument. Lancet-Clinic, Cincin., 1912, cvii, 421.
Dr. Robert Fletcher. Bristol M.-Chir. J., 1912, xxx. 289-294, port.
High blood pressure. Its associations, advantages and disadvantages. Brit. M. J., Lond., 1912, ii, 1173-1177.
Chronic infectious endocarditis, with an early history like splenic
anemia. Interstate M. J., St. Louis, 1912, xix, 103-107.
Men and books:
I. Nicolaus Steno. Canad. M. Ass. J., Toronto. 1912, ii, 67-68.
II. Les collections artistiques de la Faculte de Medecine de Paris.
Ibid.. 68-69.
III. Samuel Wilkes.
Ibid., 70-71.
IV. Jean Astruc and the higher criticism.
Ibid., 151-152.
V. Two Frenchmen on laughter.
Ibid., 152-155.
VI. An incident in the life of Harvey.
Ibid., 246-247.
Vn. Letters of Laennec.
Ibid., 247-248.
VIII. Dr. Payne's library.
Ibid.. 248-249.
IX. The funeral of Lord Lister.
Ibid., 343-344.
X. Gui Patin.
Ibid.. 429-430.
XI. George Bodington.
Ibid., 526-527.
XII. Histoire de la Charite.
Ibid., 527-528.
XIII. The school of Physic. Dublin.
Ibid.. 833-835.
XIV. Kelly's American Medical Biography.
Ibid., 938-939.
XV. The works of John Caius.
Ibid., 1034-1036.
XVI. "William Beaumont.
Ibid., 1136-1138.
Meyer, Jesse S.. Life and letters of Dr. William Beaumont, including hitherto unpublished data concerning the case of Alexis
St. Martin. With an introduction bv Sir William Osier.
St. Lous, 1912. C. V. Mosby Co., 342 p. port, roy., 8".
Man's redemption of man. A lay sermon, McEwan Hall, Edinburgh. Sunday, July 2, 1910. N. York, 1913. P. B. Hoeber,
63 p., 24°.
A way of life. 2. impression. Lond., 1913, Constable & Co., 62 p.,
16°.
Address on examinations, examiners and examinees. Brit. M. J.,
Lond., 1913, ii, 946-948.
Also: Lancet, Lond., 1913, ii, 1047-1050.
Also: Dublin J. M. Sc, 1913, cxxxvi, 313-327.
An arterio-venous aneurysm of the axillary vessels of 30 years'
duration. Lancet, Lond., 1913, ii, 1248.
Specialism in the general hospital. Johns Hopkins Hosp. Bull.,
Bait., 1913, xxiv, 167-171.
Also: Johns Hopkins Alumni Mag., Bait., 1913, i, 275-286.
Case illustrating circulatory disturbance with cervical rib. Proc.
Roy. Soc. Med., Lond., 1912-13, vi, Clin. Sect. 9-12.
[Introductory remarks on history of medicine.] Med. Mag., Lond.,
1913, xxii, 35.
A down survey manuscript of William Petty. Med. Mag., Lond.,
1913. xxii. 36-39.
Also: Proc. Roy. Soc. Med., Lond., 1912-13, vi. Sect. Hist. Med.,
2-5.
Presidential address, British Hospitals Association. Med. Mag.,
Lond., 1913, xxii, 368-372.
Men and books:
XVII. The young Laennec. Canad. M. Ass. J., Toronto, 1913,
iii, 137-140.
XVIII. Mediaeval Medicine.
Ibid., 140-141.
XIX. Robert Fletcher.
Ibid., 227-228.
XX. Jaques Benigne Winslow.
Ibid., 319-321.
XXI. Aristotle, Greek Thinkers by Gempera, vol. iv.
Ibid., 416-417.
XXII. Dr. Slop.
Ibid.. 612-613.
XXIII. John Shaw Billings.
Ibid., 613-616.
Osier, Sir W., & McCrae, T., eds. Modern medicine; its theory and
practice. In original contributions by American and foreign
authors. 2. ed. v. 1. Phila. & N. Y., 1913, Lea & Febiger,
1122 p., 8°.
Osier, Sir W., AVelch. W. H., [et al.^ Memorial meeting in honor
of John Shaw Billings. Bull. N. Y., Public Library, 1913, xvii,
511-535.
Also: [Abstr.] Library J., N. Y., 1913, xxxviii, 334-338.
1914
Bacilli and bullets. N. Y., 1914, Oxford Univ., 8 p., 12°.
A way of life. An address to Yale students Sunday evening. April
20, 1913. N. York, 1914. P. B. Hoeber, 62 p., 24°.
Syphilis of the liver with the picture of Banti's disease. Proc.
Roy. Soc. Med., Lond., 1913-14, vii, Med. Sect., 1-7.
Splenomegaly; two attacks of hsmatemesis; irregular liver.
Proc. Roy. Soc. Med., Lond., 1913-14, vii, Clin. Sect., 108.
Suggested scheme for the restoration of the tomb of Avicenna.
Proc. Roy. Soc. Med., Lond., 1913-14, vii. Sect. Hist. Med., 280.
Medical notes on England at war. J. Am. M. Ass., Chicago, 1914,
Ixiii, 2303-2305.
The proposed general catalogue of incunabula. Bull. Med. Library
Ass., Bait, 1914, iii, 45-48.
Men and books:
XXIV. Israel and medicine. Canad. M. Ass. J., Toronto, 1914,
iv, 729-733.
XXV. " Looking back." 1889.
Ibid.. 1012-1014.
XXVI. Nathan Smith.
Ibid., 1109-1111.
An address on the medical clinic: a retrospect and a forecast.
Brit. M. J., Lond., 1914. i, 10-16.
.Il I.Y. 1!11!»]
233
Early printed medical books. Brit. M. J., Lond., 1914, i, 205.
Also: Lancet, Lond.. 1914, 1, 255.
The visceral lesions of purpura and allied conditions. Brit M. J.,
Lond.. 1914, i. 517-525.
Some MSS. and books in the Bodleian Library illustrating the
evolution of British surgery. Brit. M. J., Lond., 1914, i, 825
826.
An address at the new pathological laboratory at the Royal Mineral
Water Hospital, Bath. Brit. M. J., Lond., 1914, i, 13141315.
Also: Lancet, Lond., 1914. i, 16S9-1690.
Bacilli and bullets: an address to the otticers and men in the camps
at Churn. Brit. .M. J.. Lond., 1914, ii, 569-570.
Also: Med. Mag.. Lond., 1914, xxiii. 580-583.
Sir James Y. Simpson and anesthesia (Correspondence). Lancet,
Lond., 1914, ii, 1067.
Long and anipsthesia (Correspondence). Lancet, Lond., 1914. ii,
1219-1220.
Syphilis of the liver with the picture of Banti's disease
Lond., 1914, xliii, 462-464.
Clin. J.,
Brit. M. J., Lond., 1914. i,
Appreciation of Silas Weir Mitchell.
120-121.
The war and typhoid fever. Brit. M. J., Lond., 1914, ii. 909-913.
Also: Tr. Soc. Trop. M. & Hyg., Lond., 1914-15, viii, 45-74.
Osier. Sir W., & Churchman, J. W., S.vphilis.
In: .Mod. .Med., 2. ed. (Osier & McCrae), Phlla. & N. Y., 1914. ii,
144-215.
Osier, Sir W.. & McCrae, T., eds.. Modern medicine, its theory
and practice. In original contributions by American and
foreign authors. 2. ed., v. 2-3, Phila. & N. Y., 1914, Lea &
Febiger, 8'.
1915
Science and war. Oxford, 1915, Clarendon Press, 40 p., 8°.
Special discussion on the epidemiologv- of cerebrospinal meningitis.
Proc. Rov. Soc. Med., Lond., 1914-15, viii, Epidemiol. & State
Med., 41 45.
The Jonathan Hutchinson iconography. A preliminary note.
Johns Hopkins Hosp. Bull., Bait., 1915, xxvi, 82.
A tribute to Dr. Edward L. Trudeau; a medical pioneer. Am.
Med., Burlington, Vt. & S. Y., 1915, n. s., x, 20.
Remarks on the diagnosis of polycystic kidney. Internat. Clin.,
Phila.. 1915, 25. s.. i, 1-5.
The coming of age of internal medicine in America. Internat.
Clin., Phila.. 1915. 25. s., iv, 1-5.
Remarks on arterio-venous aneurysm. Lancet, Lond., 1915, i,
949-955.
Note on acute infectious jaundice. Lancet, Lond., 1915, ii, 605.
An address on science and war. Delivered at the University of
Leeds Medical School on October 1, 1915. Lancet, Lond., 1915,
11, 795-801.
Cold-bite + muscle-Inertia = trench-foot. Lancet, Lond., 1915, 11,
1368.
Medical notes on England at war. J. Am. M. Ass., Chicago, 1915,
Ixlv. 679-680; 1512-1513; 2001-2002.
Also: West Canada M. J.. Winnipeg. 1915, ix, 59-65.
Also: Dominion M. Month,. 1915. xliv. 41; 125.
Remarks on cerebrospinal fever in camps and barracks. Brit.
M. J., Lond., 1915. i. 189.
Discussion on the treatment of cerebrospinal meningitis. Brit.
M. J.. Lond.. 1915, ii, 604.
Acute endocarditis.
In: Mod. Med. 2. ed.
148-165.
Diseases of the arteries.
In: .Mod. .Med. 2. ed. (Osier & McCrae), Phlla. & S. Y., 1915, iv.
449-471.
(Osier & McCrae). Phila. & N. Y., 1915, iv,
Aneurism.
In: Mod. Med. 2.
472-525.
ed. (Osier & McCrae), Phila. & .\. Y., 1915. iv.
Raynaud's disease.
In: Mod. Med., 2. ed. (Osier & McCrae), Phila. & N. Y., 1915,
iv. 975-997.
.\ngioneurotic ttdema. Quincke's disease.
In: .Mod. .Med. 2. ed. (Osier & McCrae), Phila. & X. Y., 1915. iv,
99S-1013.
Diffuse scleroderma. Erythromelalgia.
In: Mod. Med. 2. ed. (Osier & McCrae). Phila. & N. Y., 1915, iv,
1014-1031.
Osier, Sir W., & Gibson. A. C, Diseases of the valves of the heart.
In: Mod. Med. 2. ed. (Osier & McCrae), Phila. & N. Y., 1915, iv,
212-274.
Osier. Sir W., & McCrae, T.. cds. Modern medicine, its theory and
practice. In original contributions by .American and foreign
authors. 2. ed., v. 4-5, Phila. & X. Y., 1915, Lea & Febiger, 8°.
Macmichael, William, The gold-headed cane; with an introduction
by Sir William Osier; and a preface by F. K. Packard. N. Y.,
1915. P. B. Hteber, 261 p., 8\
1916
Science and war; an address delivered at the University of Leeds
Medical School. N. Y., 1916, Oxford Univ. Press, 39 p., 8°.
Discussion on paratyphoid fever. Proc. Roy. Soc. Med., Lond.,
1915-16. ix. .Med. Sect., 38.
An address on the tuberculous soldier. Lancet, Lond., 1916, ii,
220-221.
Local tetanus (Correspondence). Lancet, Lond., 1916, ii, 877.
Osier, Sir W.. Brown. W. L., {et al.] Discussion on trench nephritis. Proc. Roy. Soc. Med., Lond., 1915-16, ix, Med. & Therap.
& Pharmacol. Sect., 1-xl.
Osier. Sir W.. Robb, G., [et al.] Discussion on the treatment of
cerebrospinal meningitis. Proc. Ro.v. Soc. Med., Lond., 1915-16,
ix. Therap. & Pharmacol. Sect., 1-26.
Osier, Sir W.. Rolleston. H. D., |p/ al.] Treatment of cerebrospinal
meningitis. Practitioner. Lond., 1916, xcvi, 1-18.
1917
The campaign against syphilis. Delivered before the Medical
Society of London. May 14, 1917. Lancet, Lond., 1917, 1,
787-792.
Also: Brit. M. J., Lond., 1917. i. 694-696.
The problem of the crippled. Recalled to Life, Lond., 1917, i, 265.
War wastage: a note of warning to examiners of recruits. J.Am.
M. Ass., Chicago, 1917, Ixix, 290.
Recurrence or redeposit of cancer? Brit. M. J., Lond., 1917. i. 455.
1918
Essai de bibliographie hippique. Edinburgh & Lond., 1918, W.
Green & Son, 4 p., 8°.
The science of librarianship. Bull. Med. Library, Ass. Bait., 191718, vii. 70-74.
Typhoid spine. Bull. Canadian Army M. Corps, 1918. I, 78-79.
Graduated exercise in prognosis. Lancet, Lond., 1918, 1, 231.
The primary examination for the P. R. C. S. Eng.: an appeal to
the President of the Koyal College of Surgeons. Lancet, Lond.,
1918. I, 715.
Medicine In America (Speech to University Extension Students,
summer meeting at Cambridge). The Hospital, Lond., 1918,
Ixlv, 433.
Trench fever: a critical analysis of the report of the American
Commission. Lancet, Lond.. 1918. ii, 496-499.
1919
Observations on the severe anaemias of pregnancy and the postpartum sUte. Brit. M. J., Lond.. 1919, i, 1-3.
Influenzal pneumonia: bilateral rigidity, spinal meningitis with
hiembrrbage Into the tbeca vertebralis and nerve roots. Lancet. Lond., 1919. i. 501.
234
[No. 341
THE JOHNS HOPKINS HOSPITAL REPORTS
VOLUME I. 423 pages, 99 plates.
VOLUME II. 570 pages, with 28 plates and figures.
VOLUME III. 766 pages, with 69 plates and figures.
VOLUME IV. 504 pages, 33 charts and illustrations.
VOLUME V. 480 pages, with 32 charts and illustrations.
The Malarial Fevers of Baltimore. By W. S. Thayeh. M. D.. and
J. Hewetson. M. I). „ T, ». r>
A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.
Studies in Typhoid Fever.
By William Oslee, M. D.. with additional papers hy G. Bldmee. M. D.,
Simon Flexner. M. D., Walter Reed, M. D., and H. C. Parsons, M. D.
VOLUME VI. 414 pages, with 79 plates and figures.
VOLUME VII, 637 pages with illustrations.
VOLUME VIII. 562 pages with illustrations.
VOLUME IX. 1060 pages, 66 plates and 210 other illustrations.
Contributions to the Science of Medicine,
Dedicated by his Pupils to William Heney Welch, on the twenty-fifth
anniversary of his Doctorate. This volume contains 38 separate
papers.
VOLUME X. 516 pages, 12 plates and 25 charts,
VOLUME XI. 555 pages, with 38 charts and illustrations.
VOLUME XII. 648 pages, 12 plates and other illustrations.
VOLUME XIII, 605 pages, with 6 plates, 201 figures, and 1 colored chart.
VOLUME XIV. 632 pages, with 97 figures.
Studies in Genito-Urinary Surgery.
The Treatment of Prostatic Hypertrophy by Conservative Perineal Pro^
• - ' .ilts based on a detailed
14
An nualvsis of cases and
cases. "By Hugh H.
G, M. D.
The Johns
Eecto-Urethral Fist'ulie.' Description 'of New Procedures for their Prevention and Cure. By Hugh H. Young. M. D. , ^^ „ , , . .
The Early Diagnosis and Radical Cure of Carcinoma of the Prostate, being
a study of 40 cases and presentation of a radical operation which
w.is carried out in four cases. By Hugh II. Young, M. D.
VOLUME XV. 542 pages, with 87 illustrations.
Twelve papers on pneumonia. By Des. Chatard, Fabyan, Emerson,
Marshall, McCrae, Steiner, Howard and Hanes. ., ,, r. a
A Study of Diarrhea in Children. J. H. Mason Knox, Jr., M. D., and
Edwin H. Schorer. M. D. _
Skin Transplantation. By John Staige Davis, M
Epidemic Cerobrospinal Meningitis
Hopkins Hospital. By Frank .
VOLUME XVI. 670 pages with 151 figures.
Studies in the Eiperimental Production of Tuberculosis in the GenitoITrinnry Organs. By George Walker, M. D.
The Effect on Breeding of the Removal of the Prostate Gland or of the
Vesicula; Seminales. or of Both; together with Observations on the
Condition of the Testes after such Operations on ^Vhite Rats. By
George Walker, M. D. „ ,, ^^
Scalping Accidents. By John Staige Davis. M. D. , „. v., «„„„„
Obstruction of the Inferior Vena Cava with a Report of Eighteen Cases.
By J. Hall Pleasants, M. D. „ ^. m  .  rt
Physiological and Pharmacological Studies on Cardiac Tonicity in Mammals. By Percival Douglas Cameron. M. D.
VOLUME XVII. 586 pages with 21 plates and 136 figures.
Free Thrombi and Ball Thrombi in the Heart. By Joseph H. Hewitt,
Benzol as a Leucotoxin. By Lawrence Selling. MD.
Primary Carcinoma of the Liver. By Milton C. >Mxternitz. >I- P;^
The St.atistical Experience Data of The Johns Hoi.kins Hospital, Baltimore,
Md.. 1S92-1911. By Frederick L. Hoffman, LL. D., F. b.S.
The Origin and Development of the Lymphatic System. By Florence R.
The Nud'ei Tiibe'ris Laterales and the So-called Ganglion Opticum Basale.
hv Edward F. Malone. M. D. „ t, t c, .„„„
Venous Thrombosis During Myocardial Insufficiency. By Frank J. Sladen,
M. D,. and Milton C. Winternitz, M. D » , r. tt „„„ n
Leuk,i>mia of the Fowl: Spontaneous and Experimental. By Harry L.
Schmeisser, M. D.
VOLUME XVIII. 445 pages with 124 figures.
Fasciculus I.
By
W. GOODrASTDRE,
By E. W. Good
A Study of a Toxic Substance of the Pancreas.
M. D., and George Clark, M. D.
Old Age In Relation to Cell-overgrowth and Cancer.
PASTURE, M. D., and G. B. Wislocki, M. D. .
The Effect of Removal of the Spleen Upon Metabolism in Dogs; Preliminary Report. By J. H. King. M. D. t>„ t h
The Effect of Removal of the Spleen Upon Blood Transfusion By J. H.
King. M. D.. B. M. Bernheim. M. D.. and A. T. Jone.s, JLD.
<?tiidieson Parathvroid Tetany. Bv D. Wright Wilson, M. D., Thornton
Stearns, M. D., J. H. Janney,' Jr., M. D., and Madge DeG. Thurlow,
Some Observations on the Effect of Feeding Glands of Internal Secretion
to Chicks. By M. C. Winternitz, M. D.
By
Bj
Spontaneous and Experimental Leukaemia in the Fowl.
Schmeisser. M. D.
Studies on the Relation of Fowl Typhoid to Leuktemia of the Fowl.
M. C. Winternitz. M. D., and II. C. Schmeisser. M. D.
Hyaline Degeneration of the Islands of Langerhans in Pancreatic Diabetes.
By M. C. Winternitz. M. D.
Generalized Miliary Tuberculosis Resulting from Extension of a Tubercular
Pericarditis Into the Right Auricle. By M. C. Winternitz, M. D.
Acute Suppurative Hypophvsitis as a Complication of Purulent Sphenoidal
Sinusitis. By T. R. Boggs, M. D., and M. C. Winternitz. M. D.
A Case of Pulmonary Moniliasis in the United States. By T. R. Boggs.
M. D., and M. C. Pincoffs, M. D.
Gaucher's Disease (A Report of Two Cases in Infancy). By J. H. M.
Knox, M. D., H. R. Wahl, M. D., and H. C. Schmeisser. M. D.
A Fatal Case of Multiple Primary Carcinomata. By E. D. Plass, M. D.
Congenital Obliteration of the Bile-ducts. By James B. Holmes, M. D.
Multiple Abscesses of the Brain in Infancy. By James B. Holmes, M. D.
Gastric Carcinoma in a Woman of Twenty-six Years. By R. G. Hussey,
M. D.
Subdiaphragmatic Abscess with Rupture Into the Peritoneal Cavity Following Induced Pneumothorax for Pulmonary Haemorrhage. By R. G.
Hussey. M. D.
Heart Block Caused by Gumma of the Septum. By E. W. Bridgeman,
M. D., and H. C. Schmeisser, M. D.
Analysis of Autopsy Records.
A. The Johns Hopkins Hospital. (Table Showing Percentage of
Autopsies.)
B. The City Hospitals, Bay View. (Table Showing Percentage of
Autopsies.)
" The Monday Conferences."
the Staff of the Department of Pathology.
Fasciculus II.
The R61e of the Autopsy in the Medicine of To-day. By M. C. Winternitz,
M. D.
Experimental Nephropathy in the Dog. Lesions Produced by Injection
of B. brnnchisepticus into the Renal Artery. By M. C. Winternitz,
M. D.. and William C. Quinby. M. D.
Mesarteritis of the Pulmonary Artery. By M. C. Winternitz, M. D., and
H. C. Schmeisser, M. D. ,.,„,,..
A Clinical and Pathological Study of Two Cases of Miliary Tuberculosis of
the Choroid. By Robert L. Randolph, M. D., and H. C. Schmeisser,
The Blood-vessels of the Heart Valves. By Stanhope Bayne-Jones, M. D.
Equilibria in Precipitin Reactions. By Stanhope Bayne-Jones, M. D.
Carcinoma of the Pleura with Hypertrophic Osteoarthropathy. Report of
a Case with a Description of the Histology of the Bone Lesion. By
Stanhope Bayne-Jones, M. D, ^ ,,_,.,. „
The Interrelation of the Surviving Heart and Pancreas of the Dog in Sugar
Metabolism. By Admont H. Clark. M. D.
Congenital Atresia of the Esophagus with Tracheo-Esophageal Fistula
Associated with Fused Kidney. A Case Report and A Summary of the
Literature on Congenital Anomalies of the Esophagus. By E. D.
Plass M D
Ectopia Cordis, with a Report of a Case in a Fifteen-Month-Old Infant.
Bv James B. Holmes, M. D. „ , „ ^
Studies in the Mechanism of Absorption from the Colon. By bAMOEL
Goldschmidt. M. D., and A. B. Dayton. M. D. „ ^ ... .
Report of Two Fatal Cases Following Percy's Low Heat Treatment of
Carcinoma of the Uterus. By V. N. Leonard, M. D., and A. B. Dayton.
The Relationship in Typhoid Between Splenic Infarcts and Peritonitis
Unassociatcd with Intestinal Perforation. By A. B. Dayton, M. D.
Left Duodenal Hernia. By A. B. Dayton. M. D.
Histological as Related to Physiological and Chemical Differences in Certain Muscles of the Cat. By H. Hays Bullard, M. D.
A Method of Clearing Frozen Sections. By H. Hays Bullard. m. u.
On the Occurrence and Significance of Fat in the Muscle Fibers of the
Atrio-Ventricular System. By H. Hays Bullard^ M. D.
Studies on the Metabolism of Cells in 
Acids for Embyonic Chicken Cells.
The Significance of the Lunula ' of 'the Nail. By Montrose T. Burrows,
The Oxygen Pressure Necessary for Tissue Activity.
The Functional' Relation of Intercellular Substances in the Body to Certain Structures in the Egg Cell and Unicellular Organisms. By
Studies'^on'"the Grow'th 'o? c'el'ls in vitro. The Cultivation of Bladder and
Prostate Tumors Outside the Body. By Montrose T. Burrows, M. D.,
J. Edward Burns. M. D.. and YosHio Sczukl, M. D
The Study of a Small Outbreak of Poliomyelitis in an Apartment House,
Occu'rring in the Course of an Epidemic in a Large City. By Montrose
T Burrows, M. D.. and Edwards A. Park. M. D.
Papilloma of the Larynx. Report of a Case
Resultant Chronic Diffuse Thyroiditis.
Analysis of Autopsy Records.
Autopsy Statistics.
(a) Bay View.
(b) Johns Hopkins Hospital.
Report of the Photographic Department.
General Improvements.
_. The Toxicity of a-Amino
By Montrose T. Burrows, M. D.,
By Montrose
==Contents==
Kortnation of Sinfile-Ovum Twins. (Illustrated.)
By Oeobi:k L. Streeteb 235
Changes in Skin Sensitiveness to TiilxTrulin Durin<; Epidemic
Intluenza.
By Abthvb L. Bloomfield and .Iohn G. Mateeb . 238
Hemorrhage into a I'oetscarlatinal Orvioal Ahseess. Ligation
of tlie Common Carotid. Recovery.
By T. M. Rivers 240
Analysit) of C^rdirospinal Fluids of Cats with Menin<;<-al
Infections.
Bv Lloyd D. Felto.x 242
Horace (Jreen and His Prohanf;. (Illustrated.)
lir Wii.MAM Snow XIii.i.kr
PAOB
. 246
The Correlation of X-Uay Findinjrs and Physical Signs in the
Chest in I'ncomplicated Epidemic Intluen/a. (Illustrated.)
By Abthi'r L. Uloomkielu and Chahi.ks A. Waters . 252
Dr. tieorge Peirce
By .1. H. -Ma.so.n K.nox, .Ir.
Books Received
254
258
FORMATION OF SINGLE-OVUM TWINS
By (iKOKGE L. Streetkr,
PrjHirliiietil of Embryology, Carnegie Inslilutioii of Washington
It ha.< recently been the writer'!; privilege to study the
Mateer ovum, a very young, weil-preserveil specimen containing twin embryos. The larger eml)ryo is in the primitivegroove stage, having an embryonic plate 0.92 mm. long and
0.78 mm. wide. In it.« form and attachment to the chorionic
tnembrane it is entirely normal and, judging from the best
criteria we have at i)re.'*nt, it ha.-; a development of about 17
days.' The smaller embryo consist* of an amniotic vesicle
0.1 mm. in its largest internal diameter, and a yolk-vesicle
(0.03 mm. internal diameter) slightly detached from it, the
two being suspended in the l<H)st> me.>;enc)iyme in the region of
the bmly-stalk of the co-twin. The position of these vesicles
and their relation to the larger embryo are shown in Fig. 1.
The chorionic membrane with its villi and troplu.blast can be
rect»giiized above, while below is shown the yolk-sac of the
larger embryo, cut transversely through the region of the
bo<Iy-stfllk, Among the loose strands of parietal mesoblast
intervening Ix-tween these can be seen the two defaclierl vesicles
wliich together constitute the very much smaller twin.
The detailed structure of the amniotic vesicle of the smaller
embryo is shown in Fig. 2, where its wall can be seen to be made
' For a complete desrription of this embryo aee " A human
embryo (Mateer) of the presomite period." Contributions to
Embryology. Vol. 9, 1919. Carnegie Inst. Wash.. Pub. No. 272.
up of an ectodermal layer clearly subdivided into amniotic
ectoderm and a thicker plate Ik'Iow of embryonic ectoderm,
which is to form the embryonic shield. The ectodermal layer
is everywhere surrounded by an irregular membranous layer
of mestMlerm. The wall of the yolk-sac consists of a single
layer of endo<lermal cells (see Fig. 3) and, like the amnion, is
inclosed in a layer of mesodermal tissue. In general form the
anmiotic vesicle appears to be normal and corres|)onds in many
respects to those seen in the ova describeil by I'eters, Fetzer.
Jung and Strahi-Heneke. It ditTers from those, however, in
being itimpleti'ly detachetl from the y<dk-sac, and in this
respect is jirobably abnormal.
Among the first 2.">00 s|)ecimens in the Carnegie Knibryological (\)llection liicre are 4.1 instances of twinnitig, which is
about what would be expected in that number of births if we
assume the fretiueiicy to vary between 1 and 2 per cent. In
nine of these specimens the embryos are not over 20 mm.
long — that is, less than eight weeks old — but in only two arc
they under 5 mm. One of the.se is the Mati-er specimen which
I am describing; the other is a patliological s|)ecinien ( N'o.
S2.5) which was obtained by Dr. Cecil Vest at ojieration for
tubal pregnancy. In this case the tube contained two chorions
undergoing hydatiform degeneration. Sections of these show
respective internal iliameters of M x 12 mm. and 14x10 mm.
236
[Fo. 342
Neitlier chorion contains an amnion, and in only one is there
any remnant of an embryo (a nodule 2.5 mm. long). In size
and character the chorions correspond to those seen in normal
ova about four weeks old. The specimen represents, therefore,
about the same stage of development as the Watt (1915)
twins, .in which there were 17-19 paired somites. The
Ohidester specimen (mentioned by Newman, 1917, p. 68) was
at first thought to be twins, one embryo having a development
of one month, while the other was supposedly in the primitive
eS^'^^ rT^^^-^s^^w,.
•-Mk^
Fid. 1. — Section of the Mateer ovum showing yolk-sac
and body-stalk of the primary embryo, between which
and the chorionic membrane are two small ectodermic
vesicles constituting the amniotic and yolk vesicles of
a twin embryo. X 34.
streak stage. Subsequent study, however, has shown that the
smaller structure was not really a twin. If, then, we disregard
this specimen, that of Watt constitutes the youngest re])orted
case of human twinning.
The Mateer ovum is considerably younger than the Watt
specimen. Whereas the latter is in the stage of 17 somites, the
primary Mateer embryo is in the presomite stage and has only
jtist acquired a primitive groove, while the accompanying twin
lias attained an even lesser degree of development. Tlie fact.
therefore, that it affords the earliest picture of twin formation
that has thus far been seen, lends to this specimen a particular
interest. Furthermore, it possesses additional importance
in that it shows this early stage of the twinning process in a
single ovum. Both the Watt specimen and No. 835, mentioned
above, are double-ovum twins.
i
»^^ X .
Fig. 2. — Amniotic vesicle of the twin embryo showing the thicker embryonic plate
below already differentiated from the thinner amniotic ectoderm. The vesicle is surrounded by an irregular membranous layer
of mesoderm, X 400.
The exact character of the mechanism by which human
twins are derived from a single ovum is still unknown. There
are, however, certain mammals in which polyembryony is the
normal occurrence, and where it has been possible to obtain all
the stages of tlie process. This is the case in the nine-banded
armadillo which has been carefully studied by Newman ( 1917 )
and Patterson (1913). According to these authors, at a time
Fig. 3. — Yolk-sac of twin
embryo enclosed by an irregular layer of mesoderm.
X 400.
when the single amniotic vesicle has reached a considerable
amount of differentiation there occurs a physiological isolation of four secondary areas in its wall which undergo iude])endent growth and development, giving rise to four individual embryos with a common anmion. This departs from
the conditions existing in human twins, since in the latter
there are two separate amnions. This is also the case in sheep.
Adqust, 1919]
237
Very young sheep twins, iio» more tlian seven days old, have
been described by Asshcton. His specimen consists of a blastocyst 0.9 X O.T mm., coutainini; two germinal areas, each
apparently perfect and presumably capable of forming a perfect cmbrvo. They were completely separated and in each
of them the embryonic mtiss consisted of a compact cluster of
ectodermal cells with a thin endodermal membrane extending
a short distance from its margins — the uncompletinl yolk-sac.
There was a slight difference in size between the two areas and
both were smaller than normal germinal areas in the same
stage of development. Assheton regarded liis specimen as
having been produced by fission, or a mechanical splitting apart
of the original germinal mass, at the time of the formation of
the blastodermic vesicle, which he thinks is rendered more
likely in such animals as the sheep, in which the cavity of the
blastocyst is produced by an irregular cleft formation which
tends to subdi%idc the embryonic mass. The direction of the
line of fission was a matter of concern to Assheton, who thought
that only sagittal fission could produce twins and double
monsters. Transverse fission separating primary and secondary centers of growth of the embryo he believes to be
incapable of producing embryos that would subsequently grow
and develop.
Although aj)[)arently meeting the requirements in the sheep,
it is not probable that this simple mechanical explanation presented by Assheton will be sufficient to explain certjvin features
of the problem occurring in other forms. There is doubtless,
as Xewman argues, a large physiological element which is not
to be explainc<l on morphological grounds. In this connection
reference may be made to the interesting experiments of Ijewis
(1910), who found that small lateral fragments of the
medullary plate in the region of the hind-brain, when transplanted, tend to develop individually into a bilaterally symmetrical medulla oblongata, with a characteristic ventricle,
roof, and the typical arrangement of white and gray substance.
In my own experiments on the otocyst I always found that
fractional parts of the otic cup, when transplanted, tend to
form comjdetely closed vesicles, although in this organ there is
marked predetermination of ti.«sue. We should, therefore,
naturally expect that sub<]ivision into two masses of such a
primitive and undifferentiated tissue as the embryonic node
would result in the formation of two embryos having all the
potentialities of the original node.
The earliest stage of development that has been observed in
the human embryo is the one described by Miller. In his
specimen the embryo, or embryonic node, consists of a solid
cell mass undergoing cleft formation preliminary to the opening up of the amniotic ca\-ity. The embryo and the tissue
from which the c.xocteloni is formed arc inclosed by a trojihobla«tic shell of ectoderm possessing irregular syncytial loops
which tend to enclose the large blood lacun<-F surrounding the
ovum, there being as yet no villi. This stage is shown in
Fig. 5. A. Instead of a single embryo, as was the case in the
Miller specimen, the embryonic node is represented as having
subdivided into two masses — that is, as having given off a
hypothetical twin. It is conceivable that the chances of the
secondary bud reacliing maturity would depend upon how
large a share of the original mass is contributed to it. If the
twin is as large as the priuuiry embryo their chances of developing in an orderly manner would be equal, and this is presumably the case in most instiinces of identical twins, ^^^le^e
the secondary bud is merely a fragment of the original mass we
should expect that, like the fragments of medullary plate in
the Lewis experiments, there would be some degree of differentiation; but the process of development would soon be
arrested, and at term the stunted bud would be found as a
small epithelial cyst on the placenta near the attachment of
Fio. 5. — ^Schematic drawing, showing tlic probable stops in tlie
formation of a single-ovum twin. The 3tage.s are drawn at the
same scale of enlargement so that they may be directly compared.
A. Stage corresponding to the Miller specimen, showing a hypothetical twin budding off from the primary embryonic node.
B. Stage corresponding to the Bryce-Teacher specimen. C. The
Mateer specimen. The relatively small size of the twin In this
specimen, and the detachment of the yolk sac from the amniotic
vesicle are Indications of arrest In development.
the timbilical cord. In case the twin-bud is only partially
detached from the ])rimary node there would exist the basis
for the various types of double monsters an<l teratomata.
A slightly more advanced stage is schematically shown in
Fig. 5, B, which may be compared to the conditions existing
in the well-known Bryce-Teacher specimen. Here, both
embryonic mas-^es have developed into ectodermal (amniotic)
vesicles, and at the same time small yolk-sacs are forming
near them and j)nibably from cells derived from their wall.
The transition from stage B to stage C may be readily followed,
338
[No. 342
the latter showing the conditions existing in the Mateer specimen. Here the size of the cav-ity of the yolk-sac has surpassed
that of the amnion, a definite body-stalk has formed, and near
it are the two vesicles constituting the twin, which, as compared with the primary embryo, is considerably retarded in
Fui. 4. — Photographs of the twin (above) and the primary
embryo (below), talten at the same enlargement (lOO diameters)
and through similar portions of the embryonic plate.
development. It is probable that under usual conditions the
two embryos would be approximately of the same size, and the
small size of the twin is to be accounted for by the incompleteness of the bud given off from the primary embryonic node.
A comparison of sections made through the amniotic vesicle of
the twin and through a corresponding region of the primary
embryo, as shown in Fig. 4, would indicate that the former was
essentially normal in form though much retarded in development. The complete detachment of the yolk-sac justifies us,
however, in considering it as abnormal. If the pregnancy had
not terminated in this case it is probable that the larger embryo
would have gone on to maturity and the smaller one would
have remained stationary in the form of two minute epithelial
vesicles and been entirely overlooked.
In closing I would call the particular attention of obstetricians to this point, for it is probable that a careful search at
the placental attachment of the umbilical cord would frequently reveal the presence of similar minute epithelial
vesicles, the remains of stunted twins. We might thus find
that the tendency toward twinning in man is even greater than
is now supposed.
REFERENCES CITED
Assheton, R., 1898. An account of a blastodermic vesicle of the
sheep of the seventh day, with twin germinal areas. Jour. Anat
and Physiol., XXXII, 362.
Bryce, T. H. and J. H. Teacher, 1908. Contributions to the
study of the early development and imbedding of the human
ovum. Glasgow.
Lewis, W. H., 1910. Localization and regeneration in the
neural plate of amphibian embryos. Anat. Rec, IV, 19.3.
Miller, J. W., 1913. Corpus luteum und Schwangerschaft. Das
jiingste operativ erhaltene menschliche Ei. Berlin klin. Wochenschr., L. S65.
Newman, H. H., 1917. The biology of twins (mammals). University of Chicago Press.
Patterson, J. T., 1913. Polyembryonic development of Tatusla
novemcincta. Jour. Morph., XXIV, 559.
Streeter, G. L., 1914. Experimental evidence concerning the
determination of posture of the membranous labyrinth In amphibian embryos. Jour. Exper. Zool.. XVI.
Watt, J. C, 1915. Description of two young twin human
embryos with 17-19 paired somites. Contributions to Embryology,
Vol. 2, Carnegie Inst. Wash., Pub. No. 222.
CHANGES IN SKIN SENSITIVENESS TO TUBERCULIN DURING
EPIDEMIC INFLUENZA
By Aethue L. Bloomfield and John G. Mateee
(From the Medical Clinic, of The Johns Hopkins Hospital and University)
The disappearance of the cutaaieous tuberculin reaction in
measles was systematically studied in 1908 by von Pirquet'
following an observation of Preisich.^ Fifty-nine children all
failed to show skin sensitiveness during the exanthematic stage
of the disease. A few observations made at the time of onset
showed that the reaction disappeared for from one to four
days before the eruption, to reappear gradually after from the
fifth to the tenth day. Von Pirquet lays great stress on the specificity of the absence of the reaction in measles, pointing out
that it does not disappear in scarlet fever, epidemic meningitis,
typhoid fever or German measles. He associates the phenomenon with the tendency of tuberculosis to become more
active after measles and explains it by assuming a disappear
ance of " ergins " — hypothetical substances which unit* with
tuberculin in the tissues to produce the reaction. Griiner '
performed subcutaneous tests in children with measles and
showed that with relatively large doses (1 mg.) a reaction
could be elicited even during the eruptive stage. He calculated, however, that the skin sensitiveness was reduced about
one thousand-fold. The observation of von Pirquet has been
confirmed repeatedly in measles, but we have been unable to
find reports of any similar constant abolition of tuberculin
skin sensitiveness in other acute infectious diseases except
during stages of agonal collapse.
During the recent epidemic of influenza we were struck by
the remarkably low leucocyte counts encountered even in mild
AuGiST, 1919]
239
or ambulatory ca^s. This suggested that at least some of the
reactive processes of the body were in abeyance. It seemed of
interest, therefore, to study skin sensitiveness in this disease.
The present report deals w-ith tlie results of cutaneous tuberculin tests in 19 consecutive cases of epidemic influenza studied
in The Johns Hopkins Hospital during January luid February, 1919. The diagnosis was based on the symptoms, the
presence of hyperemic phenomena of the skin tuid mucous
membranes, the character and duration of the febrile reaction,
and the leucopenia.* It should be emphasized that most of the
cases were mild and that the disappearance of the skin reaction
was in no way associated witli general collapse. Three of the
patients developed bronchopneumonia, but all made imeventful
recoveries. Xono of them showed clinical signs of active
tuberculosis.
Old tuberculin furnished by the tuberculosis dispensary of
the hospital wjus used. Two drops were placed on the forearm
about 5 cm. apart. Linear scarification witli a dull scalpel
was done through the drops of tuberculin after a control
scratch had been made distal to them. The tuberculin wa.'*
allowed to dry on the arm. The tests were all made l)y the
same observers and read at one-, two- and three-day intervals,
the character and e.xtent of the redness and induration being
noted. Tests were done during the febrile stage and after the
temperature had become normal.
RESULTS
The results of the tests are summarized in Table I. It is
apparent that skin .sensitiveness to tuberculin was absent in
every case but one, both mild and severe, during the fel)rile
stage. During convalescence reactivity returned in 89.4 per
cent of the cases, which corresponds to what one would e.xpcct
in a group of normal individuals of the same age. The return
to maximum reactivity was gradual in most cases, as sliown
by successive tests. In two patients a positive skin test was
not obtained during the period of observation, even after the
temperature had l)een normal for from six to eight days.
It should be emphasized that, as in measles, more delicate
tests, such as the subcutaneous, would probably show reactivity
to be simply depressed and not entirely obliterated, and on this
basis the cases may be divided into several groups. In ten
of them th? first test made during the febrile stage failed to
elicit any sign of reaction, w^hereas during convalescence the
test was markedly positive. In six cases in which the t(>nijierature became normal on the day on which the test was do/ic, or
on the following day, slight grmles of reddening and in<luration appeared about the test scratches. These were regarded
as delayed and depressed reactions, inasmuch as all these
patients later responded with prompt, strongly positive reactions. It may be that in some of those cases the response was
intensified by increased hyper.sensitiveness following the first
test. In one instance of moderately severe typical influenza
there was a positive test during the febrile stiige. The
same degree of reaction was observed in this patient during
convalescence.
TABLE I
Summary of Resilts of Tiberculix Skin-Tests i.n Epide.mic
ixfluexza
No. Per cent.
Total cases studied 19
Cases giving a positive reaction while fever
was present 1 5.2
Cases giving a positive reaction after the
febrile stage 17 89.4
Lengrtb of time (days) after temperature ha<l become normal before
the skin test became positive
1
2
3
4
5
6
11
Number of cases
3
4
2
2
3
1
1
DISCUSSION
Although the literature on alterations of the skin test during
acute infectious diseases is meager, it has been generally
believed that measles stands out as the only disease in which
a constant depression occurs. It is of interest, therefore, to
find somewhat similar results in e])idemic influenza. Beyond
j)ointing out this fact, it seems diflScult to associate the phenomenon in the two diseases, despite certain rather striking
analogies which exist between them.* It would seem wise,
however, to restudy in detail the changes in .skin sensitiveness
in other acute febrile di.seascs, injismuch !is similar conditions
may perhaps be found to exist.
REFERENCES
1. Von Pirquet: Deutsche med. Wchnschr.. 1908, XXIV, 1297.
2. Preisich: Quoted by von Pirquet. loc. cit.
3. Gruner: Miinch. med. Wchnschr., 1909, LVI, 1G81.
4. Bloomfleld, A. L., and Harrop. O. A.. Jr.: Bull. Johns Hopkins Hosp., 1919, XXX. 1.
Note. — Since this article went to press a paper has become
accessible (E. Schltfer: Monatschrift fur Kinderh., 1918, XV,
189) dealing with the same question. The writer di<l skin tests
on 64 children with "influenza." In 61 the test was negative, in
three It was weakly positive. Of 28 reexamined during convalescence, three developed positive tests.
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240
[No. 342
HAEMORRHAGE INTO A POSTSCARLATINAL CERVICAL ABSCESS.
LIGATION OF THE COMMON CAROTID. RECOVERY
By T. M. RivEKS
On December 1, 1916, B. M., of North Carolina, female,
five and a half years of age, vomited and had a slight fever.
Two days later, a doctor was called, who found her severely
prostrated. A small membrane was seen on the right tonsil
and 15,000 units of diphtheria antitoxin were given intramuscularly. On December 5, the patient's temperature rose
to 101° F., but was normal or subnormal from that time imtil
her admission to the hospital. Her father developed a sore
throat one week after the onset of her illness and a culture
from his throat was reported positive for diphtheria bacilli
by the bacteriologist of the North Carolina State Board of
Health. A culture was not made from the child's throat
before admission to the hospital.
About December 5, the cervical glands began to swell. The
patient again began to vomit, became stuporous and did not
pass urine for 56 hours. After this interval, a small amount
of urine was passed which contained a great deal of albumin.
Her condition remained about the same until the third week,
when a diffuse, dull, red maculo-papular rash appeared, three
days before admission. She was considered by her physician
to have nephritis following diphtheria and was brought to
Baltimore to be admitted to the hospital for that reason.
On admission to the Harriet Lane Home of The Johns
Hopkins Hospital, December 23, her temperature was 99° F.,
pulse 110, respiration 22. The patient was drowsy and emaciated. The tongue was heavily coated. The breath was exceedingly foul. Part of the tonsil, soft palate and posterior pillar
on the right side had sloughed, leaving a ragged hole lined
with greenish-white pus. The glands on both sides of the neck
were enlarged. There was a mass the size of a lemon, deeply
situated below the angle of the jaw on the right side, that was
obscurely fluctuating and was obviously an abscess. The liver
was two fingerbreadths below the costal margin. Over the
body and extremities there was a worm-eaten desquamation.
The skin of the palms and the soles was very dry and later
desquamated in a way typical of scarlet fever. There was also
a diffuse maculo-papular eruption over the body and the
extremities which was evidently urticarial in character.
White blood count, 31,000. Blood culture, no growth.
Throat culture, negative for diphtheria bacilli, but showed
long chains of streptococci. Urine: clear; acid; specific
gravity, 1.020; albumin, 3 gm. per liter; sugar, absent; hyaline and granular easts; pus cells, red blood cells and epithelial
cells.
Shortly after admission the cervical abscess was opened by
means of a small puncture and at least two oimces of pus were
obtained from which a hemolytic streptococcus was grown.
' From the Department of Pediatrics, The Johns Hopkins University and the Harriet Lane Home of The Johns Hopkins
Hospital.
The patient seemed to be doing well tmtil lip. m., December 26, when she was found in a large pool of blood, exsanguinated, pulseless and gasping for breath. The bleeding had
stopped spontaneously and the wound was not disturbed. A
subcutaneous injection of 300 c. c. of physiological salt solution was given immediately and within two hours the patient
received intravenously 225 c. c. of citrated blood from the
mother.
There was another haemorrhage of about two ounces at
7 a. m. and at 11 a. m. on the following day. At 1 p. m. blood
began to spurt from the wound. Dr. Dandy, the resident
surgeon, enlarged the incision into the abscess and found an
erosion of the lingual and the external carotid arteries and
the internal jugular vein and that the haemorrhage was from
these three sources. A ligature was placed around the common
carotid and the bleeding from the internal jugular was controlled by packing. The child was greatly exsanguinated and
she received a few moments after Ligation of the common
carotid 150 c. c. of citrated blood which had been kept on ice
since the transfusion the night before. After the transfusion
she rallied immediately. Her pulse became very irregular,
however, and remained so for two weeks. There was sugar in
the urine for one week after the operation, but the blood sugar
was always normal.
On December 28 her hfemoglobin was 40 per cent (Sahli).
An area of erysipelas developed above the wound and spread
over the right side of face. On the 29th she again received
200 c. c. of citrated blood. On the 30th her haemoglobin was
58 per cent (Sahli). Both ear drums were punctured, releasing pus.
On January 1, 1917, another large haemorrhage took place
through the wound. Evidently the ligature on the common
carotid had sloughed through. The bleeding, however, was
successfully controlled by pressure and the patient again
received 150 c. c. of citrated blood. On January 3 her ha?moglobin was 40 per cent (Sahli).
The patient developed generalized oedema, insensibility to
pain, waxy flexibility, Chvostek's sign, a double Babinski,
exaggerated reflexes, double ankle clonus and a distinct loss of
memory for recent events. Gradually she improved. The
wound healed slowly under treatment with Dakin's solution.
On January 22, an internal strabismus of the right eye
appeared, which cleared up in a week. The patient was discharged from the hospital February 2, 1917, well, with normal
urinary findings. She has been heard from several times since
and continues well.
Adenitis with abscess formation, especially about the neck,
is one of the complications of scarlet fever. At times the blood
vessels are eroded and severe hemorrhages take place. The
bleeding may come from an opened abscess or it may occur from
the ear or throusjh the mouth and nose. Veins and arteries are
August, 1919]
241
King.
J. de Bal.
8 .Gordon.
9 'othrey.
10 Blood.
11 Bittertbr.
U 'sarret.
IS Mill.
14 Dtptnt.
15 lfondi»re.
I« Sedrwiek.
17 Brown.
18 UctciKe.
1» McDonmld.
to Brown.
tl Hale.
8 NicboHi.
a Hymn.
t4 HOber.
tS LoTcgroTc.
it iWfrt.
t; Budrr.
28 Hoamer,
t» Ptpp«r.
80 Mahomeil.
31 M.y.
•o HinnemOller.
iDternal carotid
(f)
Internal jugalar
«• 1-,
Internal jugular.
Internal jugular.
Internal jugular.
External carotid.
Internal jugular.
Internal jugular.
Internal jugular.
Branch interna]
maxillary artery
Internal jugular.
Internal jugular.
Internal carotid?
Internal jugular.
Artery.
Internal jugular.
Internal carotid.
Artery?
Vein?
S External carotid.
F.iternal jugular.
Lateral linul.
Artery.
Branch of carotid.
i Internal carotid.
Internal carotid ?
Bled from ear and mouth ; 10
d:iya later common carotid
ligated, but bleeding continued at intervala (or 3i
weeks. Recovery.
Blood spurted at times from
ear for i neeks. reaultiog in
death.
All died.
Died after bleeding five d;
Abscess opened and (
blood obtained. Later
dischareed from anotl
Opening. Recovery.
Bled from abscess cavity 10
days after it was opened.
Common carotid ligated,
which controlled the hxmorrhage. Child died later.
Died.
One died after bleedinfc
throueb abscess cavity and
through mouth. The other
bled to death through the
mouth.
Recovered.
Died.
I
Bled to death in three days.
Bled to death eleven days afterl
abscess cavity was opened.
Died after bleeding 10 days.
jBled to death in 2 minutes.
Tumor mass on side of
S-Y»8.
1-No.
Yes.
Yes.
Bled about a pint from
between thi' anterior and
posterior pillars on left aide
of throat. Recovered.
Bled through mouth. RC'
covcry after ligation of left
common carotid.
Hemorrhage controlled bv
ligation of common carotid.
Died.
jBled from left ear. Left common carotid ligated. Recovery.
Bled to death through ear and
I mouth.
Yes.
Yes.
involved about equally. Haemorrhage under such circumstances is very serious and few of the cases recover. Most of
the authentic cases on record are tabulated liere.
BIBLIOGRAPHY
1. Syme: Edinburgh Med. & Surg. J., 1833, XXXIX, 319.
2. Porter: See Kennedy (3).
3. Kennedy: Some Account of the Epidemic of Scarlatina
which Prevailed in Dublin, from 1834 to 1842, inclusive; with
Observations. Dublin, Fannin & Co., 1843.
4. King: London & Edinburgh Mon. Jour. Med. Sc, 1843, III,
177.
5. de Bal: Jour. d. connaissances m^dico-chirurgicales, Paris,
1845, XIII. 158.
6. Bloxam: Med. Press, Dublin, 1843, IX. 181.
7. Hughes: Med. Press. Dublin, 1846, XV, 241.
8. Gordon: See Hughes (7).
S. Oshrey: See Hughes (7).
10. Blood: See Hughes (7).
11. Battersby: See Hughes (7).
12. Barrett: Lancet, Lond., 1847, I, 287.
13. -Mill: Edinburgh Med. & Surg. Jour., 1841. LV, 125.
14. D^peret: L'Union m^dicale, Paris, 1850, IV, 414.
15. Mondidre: Revue medicale, 1842, I, 1S2. Original article not
read, reference obtained from: Von Noirot, Histoire de la Scarlatine, Paris, 1847, 216 and 217.
16. Sedgwick: Med. Gaz. Lend., 1851, XLVIII, 581.
17. Brown: Med. Gaz. Lond.. 1851, XLVIII, 887.
18. Metcalfe: N. Y. Med. Times, 1852, I, 35.
19. McDonald: See Metcalfe, (18).
20. Brown: Association Med. Jour., Lond., 1854, II, 991.
21. Hale: Lond. Jour. Med., 1850, II, 720.
22. Nicholls: St. Georges Hosp. Rep., Lond., 1869, IV, 211.
23. Hymes: Lancet, Lond., 1870, II, 431.
24. Huber: Arch. f. klin. Med., Leipz., 1871, VIII, 422.
25. Lovegrove: Lancet, Lond., 1870, I, 729.
26. West: See Lovegrove (25).
27. Baader: Correspondenz-bl. f. Schweizer Aerzte. Basel, 1875,
V. 614.
28. Rosmer: Bost. Med. & Surg. J., 1878, XCIX. 835.
29. Pepper: Trans. Clin. Soc. Lond., 1883, XVI, 21.
30. .Mahomed: Ibid. (Discussion.)
31. May: Ann. Surg., 1885, I, 559.
32. Hannemiiller: Gefassarrosionen im Verlaufe von Scharlach,
Kiel, 1901.
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243
[No. 342
ANALYSIS OF CEREBROSPINAL FLUIDS OF CATS WITH
MENINGEAL INFECTIONS
By Lloyd D. Felton,
Contract Surgeon, U. S. Army
(From The Army H euro-Surgical Laboratory, The Johns Hopkins Medical School, Baltimore, Md.)
BOOKS RECEIVED
Interstate Commerce Commission. Thirty-second Annual Report
of the Interstate Commerce Commission. December 1, 1918.
8°. 192 pages. Government Printing Office. \^'ashington.
The Medical Association oj the Isthmian Canal Zone. Proceedings, January, 1917, to June, 1917. Vol. X, part I. Published
by the Health Department, the Panama Canal. 1918. 8°.
149 pages. Panama Canal Press, Mount Hope, C. Z.
Surgical Treatment. A Practical Treatise on the Therapy of Surgical Disease for the Use of Practitioners and Students of
Surgery. By James Peter Warbasse. M. D. In three volumes
with 2400 illustrations. Volume I. 947 pages: volume II. 829
pages. 1918. 8°. W. B. Saunders Company, Philadelphia
and London.
Paper Work of the Medical Department of the United States Army.
A Guide for Administrative Work. By Ralph W. Webster,
M. D., Ph. D. Approved for publication by direction of the
Surgeon General of the U. S. Army. 1918. 8°. 541 pages.
P. Blakiston's Son & Co., Philadelphia.
Hygiene in Mexico. A Study of Sanitary and Educational Problems. By Alberto J. Pani, C. E. Translated by Ernest L.
de Gogorza. 1917. 12°. 206 pages. G. P. Putnam's Sons.
New York and London.
Saint Thomas's Hospital Reports. New Series. Vol. XLIV. 1915.
Edited by Dr. J. J. Perkins and Sir Charles A. Ballance,
K. C. M. G., C. B., M. V. O. 1918. S". 141 pages. J. & A.
Churchill, London.
The Humane Society of the Cotnmonwcalth of Massachu^sctts. An
Historical Review, 1785-1916. By M. A. DeWolfe Howe. With
illustrations. 1918. 8°. 398 pages. Printed for the Humane
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Library of Conprcss. Report of the Librarian of Congress and
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191 pages. Government Printing Office, Washington.
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BULLETIN
OF
==Contents==
InsuBceptiliility of Man to Inoculation with Hlood from
Measles Paticnt.s.
By AxDRKw Watson Sem-ards 2.1
The Ri'ile of the X-Ray in the Diagnosis of Long-Staniiinj^
Kenal Tuhert-ulo.sis. (Illustrate<l.)
By .1. A. C. COL.ST0N and Charles A. Waters . . . 208
In Mcmoriam — Admont Halscy Clark. (Illustrated.)
Bv William G. MacCalli'm 272
Heminiscences of Two Epochs— Anxsthesia and Asepsis.
(Illustrated.)
By Stephen- Smith 273
Notes on the Group of Symptoms Designated as KfTort
Syndrome.
By E. W. Bridgman 279
Notes on New Books. 284
Books Received 285
INSUSCEPTIBILITY OF MAN TO INOCULATION WITH BLOOD FROM
MEASLES PATIENTS
Jiv AxDKKW \\at.sox .Sei.i.aki>.<. -Major, ^1. ('., U. .S. A.
(From Bnsr Hospitals. Camp Devens. Mass.. and Camp Mcadr, Md.)
INTRODUCTION
III congivsti'd (•omimiiiitit'.-; tlie sanitarian experiences greater
• lillieulty in the c-ontrol of disease.-^ of tlie res])iratory tract than
in the ease of those infections in wiiich tlie portal of entry is
liy way of the alimentary canal. From the stantlpoiiit of e|iideniiologj-, measles should certainly he classified with the
respiratory di.sea.ses; it takes a prominent place ainon<; the
most liiphly communicalilc infections, heintr excelled, perhaps,
only by pneumonic plague. In the mobilization of recruits
even the uncomplicated ca.ses of measles may produce a high
iion-ctFective rate; in addition to this disadvantage the .<erious
l>ulmonnry com])lications of the disease render desirable
the development of a protective immunization against the
jiriniary infection. Investigations for this purpose would
require the inoculation of human subjects on a basis which is
necessarily more or less experimental in character. Indeed,
of the serious infections of man, the virus of measlejj like that
of scarlet fever and yellow fever* can I)e definitely identifieil
only by the inoculation of suseeptilde human individuals.
Ihiring the recent military emergency, a need and an opportunity arose for the investigation of measles such as would not
occur in civil life. Accordingly, Colonel Frederick F. Hus.>iell
recommi'iided to (ieneral William C. (torgas and to General
Meritte W. Ireland the study in human volunteers of the ques
* In a recent communication Xogui hi reports the discovery of
the etiologlc agent of yellow fever.'
tion of prophylactic inoculation against niea.<les. In time of
need the individual soldier was found ready and willing to
offer his services and to accept such risk a.s was inherent in
these inoculations. A precedent for this type of work has
been firmly established; the conditions in army life seem
especially favorable for the ilcvelojinu'iit of preventive medicine
as evidenced by the ])rogress in the control of yellow fever,
of typhoid anil of trciiih fever.
LITERATURE
Iluiiian liiaculdliun.s. — .\ccurate records of the cxperimcnlal
production of measles in man are meager in the extreme. The
easy recognition of the disease by it-s clinical syini)tonis would
.seem to render of interest the investigations conducted before
the bacteriologic era. P'or example, Alayr' in 18.12 reporteil
the occurrence of measles afti'r an incubation period of two
weeks in two of three subjects inoculated on the nasal mucous
membrane with nasal .secretions of a jiatient. I n another ex])erinient, Mayr reports that mild but typical attacks were produced in each of six subject.s by introducing into the skin
the 8era|)ing8 from a morbillous lesion. The incubation period
is not stated ; no mention is made of any precautions to avoid
spontaneous infection,
Kecently Ilerrman' (1!>1">) inoculated 10 infants under
five months of age on the na.<al mucous membrane with nasal
secretions from cases of measles. This was done, not with the
258
[Xo. 343
idea of producing the disease but with the expectation of establishing an immunity, taking advantage of the relatively
high insusceptibility of infants to measles in the first few
months of life. None of these 40 infants developed any
definite symptoms. About 1 to 2 years later, 4 of these children came in intimate contact with measles cases and two
were reinoculated without developing the disease.
The first experimental inoculations of blood were performed by Hektoen* in 1905; this observer conducted two
independent tests and reported an attack of measles in each
instance. Blood for inoculation was taken during the eruptive stage and was incubated before injection, for one day at
37° C. in ascitic broth (1 part ascitic fluid to 2 parts meat
infusion broth). In one patient the specimen of blood was
withdrawn 6 hours and in the other 30 hours after the eruption had appeared. Moderate quantities (3 c. e. and 2.5 c. c.)
were inoculated into flasks of ascitic broth (50 and 75 c. c.
.amounts). After incubation for 24 hours, this mixture was
apparently sterile; there was no evidence of secondary contamination or of any multiplication of the virus of measles as
indicated by the gross appearance, by microscopical examination and by the subsequent results of sub-inoculation on a
variety of media. Accordingly subcutaneous injections were
made (4 and 5 c. e.) into two volunteers and apparently a
mild but typical attack of measles developed in each case after
an incubation period of about two weeks. This volume of
broth culture represents a calculated quantity of blood serum
of approximately 0.1 c. c. All viruses known to multiply in
culture media produce either macroscopic or microscopic evidence of their growth ; both manifestations appear in the vast
majority of cases. It would seem from these results, therefore, that a very small amount of measles blood is infective
and that it retains its virulence for at least a day in vitro at
incubator temperature. Such a conclusion is of far-reaching
importance. In the investigation of a disease of unknown
etiology a great advantage is achieved by the isolation of its
virus in a relatively concentrated form uneontaminated by
other micro-organisms; one is then in possession of suitable
material for the investigation of fundamental features sucli
as immunization of the natural host, transmission to other
species and studies in morphology and cultivation. Practically the entire superstructure of modern experimental work
in measles rests on these two experimental cases. One may
call attention more especially to the reported transmission of
the disease to monkeys by inoculations of blood and the isolation of a micrococcus from the blood stream by TunniclifiE.'
Inoculation of Monkeys. — Of the recent investigators, Anderson and Goldberger ° were the first to report the successful
inoculation of monkeys with measles. Two of their conclusions
are of especial interest in connection with the data reported in
this paper, namely: (1) that the blood of early cases is infective and (2) that the virus of the disease as it occurs in the
blood is capable of passing a Berkefeld filter.
DESCRIPTION OP EXPERIMENTAL WORK
In arranging the preliminary protocol of the following work,
the reported transmission of measles by the inoculation of
blood was accepted as a basis for the first series of injections,
arrangements being made to conduct a control for confirming
the findings concerning the infectivity of the blood. In order
to provide a secure foundation for the more elaborate and timeconsuming experiments it was expected in the course of these
investigations to obtain information concerning the constancv
with which the blood of individual cases is infective, the minimal quantity which suffices to produce the disease and also
tlie extreme limits during which the virus may be demonstrated in the blood. Inasmuch as a very favorable control for
the first series of inoculations failed, the question of the
infectivity of the blood in measles was accepted as the primary
problem; the ultimate object of these investigations consists
in determining whether a method of active immunization can
be developed, without producing a serious reaction. Injections
of blood from jjatients in various stages of the disease have
been made into supposedly susceptible individuals but no symptoms of measles appeared in any instance. Two individuals
who had been injected with blood were siibsequently inoculated on the mucous membrane of the upper respiratory tract
with nasal secretions of an early case of measles but no symptoms developed. There is some reason to believe that these
individuals were protected by the preliminary injection of
blood.
Arrangements and Preparations for Inoculations. — Those
investigations were conducted at Camp Devens, Mass., and
at Camp ileade, Md. Camp Devens covers an area of
approximately 16^ square miles with a normal capacity for
35,000 to 45,000 troops. The Base Hospital is situated at
the extreme end of the cantonment opposite the principal entrance to the reservation. The wards of the hospital itself
together with the essential accessory buildings such as the
quarters and barracks for officers, nurses, and enlisted personnel, as well as the drill and recreation field, occupy an area of
approximately 2 J square miles; this section is separated from
the nearest barracks for troops of the line by a distance of about
}, mile. The normal capacity of the hospital is 2000 patients
which in a time of emergency has been trebled. At the time of
these investigations approximately 1000 troops of the enlisted
personnel were assigned to the base hospital. Volunteers were
obtained largely from this group of enlisted men since the
majority of the medical officers had already been exposed to
measles; a considerable proportion of these men had not
come in contact with patients, being assigned to duty in the
barracks and quarters, in the offices and on fatigue work out
of doors. Conditions at Camp Meade were fundamentally
identical with those at Camp Devens. The work was transferred to Camp Meade, partly for the purpose of obtaining
volunteers from the more isolated rural communities, the
majority of the volunteers at Camp Devens having come from
the smaller towns.
Precautions Concerning Volunteers. — In the accciitiiiui^ o!'
volunteers for inoculation with measles there are two cardinal
Septemukk, 1!)I!»|
259
factors which outweigh all other lousiderations, namely : (1)
the •leiieral iiealtli of the iiulividual with special consideration
of the respiratory tract and ('i ) the assurance tiiat the adult in
question has never had a recojrniznhle attack of measles.
Under ordinary circumstances the virus of measles per se
d<K?s not produce serious results in normal individuals; its disastrous effects arise from the secondary infections. The most
important of these are the pneumonias es|)ccially those from
the pneumococcus, the tuiiercle bacillus and the luemolytic
streptococcus as in the winter of 1!)1T-1S. In addition to
thoroufjh physical examination, si)ecial attention was ^'iven
to the points indicated in the followinof outline in order to
secure the fullest |>o}:sibIe protection for llie volunteer> :
I. Bacteriolofrical cultures of throats (several examinations at intervals of three to four days) for.
1. Tla-molytic streptococcus.
•.i. I'neumococcus (any type).
3. Jleningococcus.
1. Diphtheria liacilli.
5. Pfeiffer Ijacillus.
II. Precautions ajEraiiist tuberculosis,
1. History.
2. Physical examination.
3. .\-ray findinsis.
III. Anatomii-al examination of,
1. Tonsils.
'i. Sinuses.
3. Middle ear.
I\'. Special isolation for acceptable individuals in orcler to
protect them from intercurrent infections and
from s])ontaneous infection with measles.
\'. Special nursinjf by per.sons of Ion;; experience with
measles for any individuals contractiiiij the
disease.
If a prospective volunteer showed any of the preceding;
or^'anisms in the cultural examination of the throat and nasopharv'nx he was at once eliminated from consideration reftardless of whether the orpanism in question subsequently disaj)peared. A comparatively larpe proportion of individuals
proved to be unsuitable either on account of the presence of
the hfemolj-tic streptococcus or the pneumococcus. Only a few
were rejected on account of a suspected latent tuberculosis.
The anatomical examination of the tonsils seemed distinctly
inifwrtant. Imlividuals who bad had an infection of the tonsils at all recently were not considered becau.«e, especially under
these circumstances, cultural examination of the surface of
the gland gives little information concerning the flora contained within the tonsillar crypt**. In view of the dilliculty
of rigidly excluding the presence of the ha-molytic streptncoccus by bacteriologic examinations it seemed much safer
to conduct these inoculations at a time when infections with
this micro-organism were not prevalent in camp. As a practical test of the significance of cultural examinations, licvy
and Alexander' have noted a very low incidence of complications due to the ha?molytic streptococcus in measles cases wha«e
throat cultures were negative for this organism.
Proper isolation i)osscs.ses a two-fold importance. In the
first place it was very neces.sary (hat volunteers found free of
l)athogenic micro-organisms should be jirotected from accidental contamination, especially by carriers ; secondly, it is of
course essential to provide against the possibility of spontaneous infectidii with measles. With these objects in view, the
acceptal)le volunteers were segregated in a ward removed as far
as circumstances would permit from the wauls reserved for
cases of measles, a distance of aiiout i mile. Satisfactory isolation over the rather long period of these experiments was
rendered comparatively simple by the discipline developed in
military life and by the faithful cooperation of the volunteers
themselves. The attendants on the ward for the volunteers
were restricted from seeing any i)atients, but they were not
required to isolate themselves. By observing the precautions
just outlined, it was felt that the possible dangers inherent in
these inoculations would be reduced to a minimum.
Probably the greatest <lilficulty in these investigations consists in the selection of susceptible adults; in the large cities
only a very small proportion of individuals, perhaps 5 per cent,
come to adult life without having contracted measles. Age
per se confers no innnunity. Moreover, the disease runs a
clinical course which is remarkal)ly true to form. Unrecognized attacks such as abortive cases without a rasJi constitute, if
they occur at all, virtually a negligible factor. The chief
difficulty arises from the fact that little or no dependence can
be placed on the .statement of even the educated adult that he
has never had measles. Information was obtained according
to the following plan : A census of the detachment was taken
and tho.so individuals were at once eliminated who reported
having had either measles," German measles," or scarlet fever.f
These three diseases were included on account of possible errors
in diagnosis. A limited number were sure that tliey had had
none of these infections; tiie parents of these men were consulted. At Camp Devens this was done, whenever possible, by
the individual himself in person ; at Camp ^leade a letter was
sent to the family of the soldier. Inquiry was made in the first
place concerning the individual him.'^elf, and secondly, whether
he had been ex])osed to measles through its occurrence in other
members of the family. After this information was obtained,
an ojjportunity to volunteer was given to the men in wlio.«e
eases the replies from the parents were satisfac-tory, provided
that the preliminary bacteriologic examination of the individual was negative. The first cultures were made while the
history was being ohtaineil; the final examinations were comI)leted only after the individual hail volunteered and had been
isolated.
The general ])lan of the inoculations was designed with the
jturpose of eliciting the desired information concerning the
virus of measles with the production, however, of only an absolutely minimal number of cases of the di.«ease. By employing
large series of volunteers, the experimental data could have been
obtained ra])idly on an extensive scale but only at the cost of
(A detailed report of tills census will appear in Thn Afililary
Surgeon.
260
[K'o. 343
increased risk to the individuals. With the passing of the
military emergency, less attention was given to the time consumed in tliese experiments, the primary object being to avoid
the possible production of measles in man without obtaining
results proportionate to the serious responsibility of human
experimentation.
PRELIMINARY INOCULATIONS OF HUMAN SUBJECTS
Selection of Measles Cases. — There are two essential criteria
which must be met in the selection of measles cases for subinoculation of normal individuals: (1) the patient must be
secured in relatively early stages of the disease and (2) he
must be free from all other infections, notably syphilis. At
the beginning of this work, the collection of blood specimens
was purposely delayed until after the rash had appeared ; although the blood might, very possibly, be more infective in the
pre-eruptive stage, it seemed advisable to duplicate conditions which had previously given positive results in human
experimentation.
For the exclusion of syphilis, dependence was placed on a
thorough history in all its aspects, clinical examination and
the Wassermann test.
Preliminary Inoculations. — The first inoculations were designed to give preliminary information on the following points :
(1) Whether the serum alone, free from red cells, contains
the virus of measles.
(2) Whether the organism of measles will pass through a
Berkefeld filter.
(3) Whether a series of injections of patient's and con
valescent's serum would immunize a human suliject
without producing an attack of the disease.
(4) Whether a previous attack of measles confers complete
immunity or whether a modified attack might result
in a partially immune subject with possible attenuation of the virus.
For these inoculations, blood was taken from a moderately
severe case of measles 12 hours after the first appearance of
the rash. At this time the Koplik spots had already disappeared, the eruption was profuse over the face, back and chest,
less intense over the abdomen and only a few scattered spots had
appeared on the thighs.
Immediately after collection, one portion of the blood was
defibrinated and another was centrifuged for the collection of
serum. Part of this serum was mixed with an equal volume
of fresh serum obtained from a typical case of measles 10 days
after the temperature had returned to normal. Another
portion of the original serum was diluted with nine parts of
physiological saline ; one portion of the diluted serum was kept
at room temperature for a control and the remainder was
heavily inoculated with B. prodigiosiw and passed through
a Berkefeld filter (so-called N).t
This was an old filter, much worn, which on several previous
tests had successfully held back B. prodigiosus. When immersed
t The gradations of Berkefeld filters into coarse, medium and
fine (V-N-W) was found frequently to bear little relation to their
actual porosity.
in water, an additional pressure of 50 mm. of mercury was suflBcient to force a fine stream of air through this filter. The time
employed in filtering 25 c. c. of the diluted serum was 30 minutes
and the pressure was 40 to 50 mm. of mercury; the room temperature was 22° C. Twelve cubic centimeters of the filtrate
were inoculated in varying amounts on agar plates and into flasks
of broth; the culture media subsequently showed no evidence of
growth.
The following subcutaneous injections were made into susceptible individuals: For convenience the susceptible men will be
designated by a Roman numeral and the immunes by a letter.
One volunteer (I) received 5 c. c. of diluted serum (1-10) unfiltered and kept at room temperature one hour; another (II) received 10 c. c. of filtered serum (1-10 dilution) one hour after
collection of the blood; a third (III) received 0.5 c. c. of a mixture of equal parts of patient's and convalescent's sera (undiluted)
after incubation for one hour at 37° C.
An immune (A) wlio had measles 28 years previously received
7 c. c. of defibrinated patient's blood 1% hours after collection.
Xone of these four individuals developed any symptoms of
measles. Xeither did any local changes appear at the site of
injection except in the individual who received 7 c. c. of
defibrinated blood ; in this subject a day alter the injection,
moderate tenderness on piressure developed accompanied by
slight erythema over the injected area. These symptoms
persisted for tliree days.
The chief interest in these negative results centers in the
control individual who was expected to contract measles. The
delay of one hour before injecting this serum and also the
absence of red cells might be regarded as factors contributing
toward the negative result. It would appear from previous
work that the blood retains its infectivity in vitro for at least a
day. As regards the red cells, as far as we know, all diseases
caused by parasites of the red corpuscles are transmitted by
insects whereas droplet infection constitutes the accepted mode
of transmission in measles.
The failure of filtered measles serum to infect an apparently
susceptible human subject must be borne in mind in connection
with the positive result reported by Goldberger and Anderson °
upon the inoculation of monkeys with filtered serum. These
investigators conducted four experiments; in the first two,
the results were negative; in the third, one of four monkeys
presented slight symptoms only; in the fourth experiment
one of two monkeys developed an eruption 21 days after inoculation. These authors conclude that the virus of measles is
capable of passing through a Berkefeld candle. Xo details are
given concerning the size of the filter employed or the manner
in which the filtration was controlled and conducted.
For the mixture of measles serum and convalescent patient's
serum, it was originally intended to conduct a long series of
injections gradually eliminating the convalescent patient's
serum. It was also intended to hyper-immunize by several
intravenous injections of measles serum the immune (A)
who failed to develop symptoms after receiving a large quantity
of blood subcutaneously. After an interval of one month, a
second injection was given consisting of 1 c. c. of serum intravenously. This was collected from a patient 15 hours after
the appearance of the rash. X'o symptoms of any kind resulted
from this intravenous inoculation. This work was then sus
September, 191i)]
JOHNS HOPKINS HOSPIT^VL BULLETIN
261
pended pending confirmation of the existence of the virus of
measles in the circulating blood.
INOCULATION OF SUSCEPTIBLE INDIVIDUALS WITH
MEASLES BLOOD
Inociiliition of Dt'fibriniiltil Bhtod and of lilvoil I ncttbalcd in
Ascitic Broth. — The remaiiuler of the work with susceptible
individuals has been restricted to an attcnii)t to transmit
measles by the injection of patient's blood. Dclil)rinated blood
was injected subcutaneousl}- into two men. Cultures of patient's blood in ascitic broth were inoculated in two other men.
This duplication of a method for which successful results have
been reported seemed essential in view of the negative result
following the inoculation of serum without preliminary incubation. None of these four subjects developed measles ; neither
did any symptoms appear that could be definitely attributed
to the injections. Tlie details are as follows :
Deflbrinated blood from an early case of measles, 12 hours
after the appearance of the rash, was injected subcutaneously in
2 c. c. quantities in the interscapular area, after a delay of 15
minutes, into two susceptible volunteers. The patient's blood
(4 c. c.) without defibrination was added to ascitic broth (50 c. c. )
consisting of two parts of meat infusion and 1 part of ascitic
tluid. The broth was prepared without the addition of sugar and
its reaction to phenolphthalein was equivalent to 1 per cent of
normal acid. The ascitic fluid was yellow in color, sp. gr. 1.018
and was free from bile pigments. Repeated aerobic and anaerobic cultures showed no evidence of growth; the ascitic fluid was
therefore used without preliminary sterilization. In the culture
medium prepared by Hektoen the ascitic fluid was heated at
55° C. for 54 minutes. Differences of an altogether minor nature
probably occurred also in the reaction and composition of the
broth and ascitic fluid which was employed.
This medium inoculated with the patient's blood showed no
evidence of growth after 24 hours' incubation; accordingly, two
susceptible men (VI and VII) were inoculated subcutaneously in
the interscapular area with 10 c. c. of this mixture of blood in
ascitic broth, the mixture being shaken to include corpuscles as
well as serum. This quantity represents about 0.2 c. c. of patient's
serum.
During the incubation period these men were observed with
special reference to:
1. Development of symptoms in the upper respiratory tract.
2. Occurrence of Koplik spots.
."?. Body teniporature.
4. Total and diffcreniial leucocyte count.
A record of the temperature by mouth and of the pulse and respiration was taken as a routine at four-hourly intervals during
the day. The entire surface of the body was examined for culanoous rashes, since, after inoculation, the initial lesions might
appear first not necessarily on the face or chest, but on any part
of the body. All of these individuals remained essentially free
from symptoms.
fnorulalion witli Skin Lrsion.i. — After an interval of :Vi days
one of the men injected with defibrinated blood (IV) and
ani)tl)er (Vll) injected with blwid incul)ated in broth were
re-inoculated i»y smearing the mucous membranes of the eyes,
nose and throat with freshly cxciscil morbiJlous skin lesions.
These inwulations pos.^essed a two-fnld interest in that a positive result would demonstrate that the virus of the di.-^easc
is present in the skin lesions and that these individuals who
were refractory to an injection of iilood were nevertheless sus
ceptible to the disease. No definite symptoms developed. In
view of these negative results, the question arose of testing
experimentally the .-iusceptibility of these men by inoculating
the upper respiratory tract with secretions from the nmcous
membranes of active cases. The injections of blood, however,
had been made from only one case of measles, a single specimen
of blood having been taken. Therefore, if the use of nasal
secretions should produce measles in one of these subjects, it
would only establish that, in a single case of measles, one
specimen of blood at a given stage of the disease did not prove
infective for a susceptible host. It seemed desirable to defer
tests of susceptibility until individuals could be inoculated with
blood from several stages of the disease and preferably from
more than one patient.
Inoculation of Blood from Pre-Erupiive and Eruplire
Stages. — Accordingly for the next step, two susceptibles were
inoculated on two successive days with blood taken before and
after the appearance of the eruption. Control inoculations were
made simultaneously into two immunes. Blood for these injections was secured from two patients; specimens were obtained from one case 30 hours and again six hours before the
ap])earance of the rash and from the other six hours before and
18 hours after the rash appeared. None of tlicso four subjects
developed any symptoms of measles.
Of the two susceptibles selected for these injections, one
(IX) gave unusually good evidence that he had never contracted measles. This individual had grown up on a farm in
West Virginia and had alwavs lived at home. He was 'ifi years
of age being the sixth of 8 children of whom the youngest
was 20 years and the eldest 38 years of age. Information
was received from the mother and the eldest sister to the
elTect that measles had never occurred in the household.
Then in adult life several older and younger brothers and
sisters left home and contracted measles. Of the five older
members of the family, the eldest sister contracted measles
in 1910; two brothers, tlio second and third members of the
family, developed measles in March, 1917 ; the fourth member,
a brother, has not had measles; a sister, who was the liftli child,
developed measles in 1908. Of the two younger children one,
a sister, 20 years of age, has never had measles; the other, a
brother, 24 years of age, did not develop measles until he
enlisted in the army, having contracted tlie disease at Camp
Shelby, ifiss., in December, 1917.
On enlisting this volunteer (I.\) was assigned to tlu! medical detachment, working exclusively in the officers' quarters.
lie entered the hospital only on a single occasion, to visit a
friend ill with tonsillitis.
In view of the prevalence of measles in the canttniments it
might seem that no su.sccptible individual could escape infection for any length of time. However, there has been a
slight but constant incidence of measles at the ports of debarkation even among the troops returning from overseas, notwithstanding the fact that measles has been widely distriliutcd
throughout the training camps of this country.
The two immunes were injected in order to test the protection alTorded by an attack of measles and also to control
262
[Xo. 343
any minor symptoms that might appear in the susceptibles,
such as slight changes in the body temperature and in the
leucocyte picture. One of these immunes (A) had already
been inoculated with blood on two occasions and with secretions from the mucous membranes of patients; the results
were negative. The other immune (B) probably had had
measles more than 30 years ago and had not previously received
any injections in the course of these experiments.
For these inoculations of blood, very favorable cases of measles
were obtained during a small epidemic which developed in a
country district outside of the camp. Two adult patients were
selected. Blood from each of these cases was mixed with 2 per cent
sodium citrate in physiological saline; the two specimens of
citrated blood were pooled and the mixture was injected into each
subject; 24 hours later a second specimen of blood was collected
in the same way from each patient and the injections were repeated. Each subject received injections of blood from two
patients at two periods of the disease, i. e.. the equivalent of four
Injections in all. On the first day 10 c. c. of blood were taken from
each patient, and mixed with an equal volume of citrate solution.
On examination, the first patient showed numerous Koplik spots
at this time and six hours later the rash appeared. The temperature was 102.8°. The second patient showed only a few isolated
Koplik spots and the rash appeared 30 hours later. The temperature was 99°. These two specimens of citrated blood were mixed:
each of the two susceptibles (VIII and IX) and the two immunes
(A and B) were then injected with 6 c. c. of the resulting mixture,
the injection being given in part subcutaneously and in part intramuscularly in the gluteal region. The maximum period of time
elapsing between the withdrawal and the injection of the blood
was 45 minutes tor the first and 15 minutes for the second patient.
A duplicate of these injections was made on the next day, 10 c. c.
of blood being taken from each case and mixed with 7 c. c. of 2 per
cent citrate solution. At this time the Koplik spots had disappeared in the more advanced case; the rash, which had appeared
18 hours previousl.v, was almost confluent over the face, well developed over the chest and very sparse over the abdomen. In the
second patient, the Koplik spots were abundant at this time and
the rash appeared six hours later. The temperature was 102.2°.
After these specimens of citrated blood had been mixed, the same
men (VIII, IX, A and B) were injected with 6 c. c. quantities in
the same manner in the gluteal region on the opposite side; the
time elapsing between the withdrawal and the injection of the
blood for the first case, i. e.. the one in which tlie rash had developed, was 40 minutes and for the second case. 10 minutes. These
injections were made subcutaneously and intramuscularly in order
to duplicate in the first place the manner of inoculation for which
successful results had already been reported. It seemed entirely
possible that a virus might find better protection for itself in the
subcutaneous tissues than when exposed to the fluids and cells
of the blood stream. An intravenous injection in addition to those
into the tissues was not made in order to determine whether a
rash, if one developed, would appear first at the site of inoculation
or on the face as in the spontaneous disease. To facilitate these
observations the site of inoculation was changed from the interscapular to the gluteal region.
Some slight local reactions followed these injections. .Vt
the site of inoculation one of the two susceptibles (VIII)
developed well-marked induration appearing eight days after
the first injection, persisting very definitely for four days and
gradually disappearing during the next 48 hours. In this
individual the induration was bi-lateral; in the other (IX)
slight induration without any well-defined margin developed at
the site of the second injection. This also appeared 8 days
after the first injection but persisted for only 48 hours. In
one of these men (VIII) a very transient erythema appeared
for a few hours over the area of induration, on one side only,
on the 10th and again on the 11th day after injection. Xeither
of the two immunes developed any local induration. One of
these immunes (A) on being inoculated in a similar manner
5| months previously developed a local induration entirely
analogous to these two susceptibles. The local reaction,
therefore, to the finst injection of measles blood varied slightly
in the two immunes.
SUSCEPTIBILITY TESTS
When it became apparent that no symptoms of measles
would develop from these injections of blood, arrangements
were made to test the susceptibility of these men by inoculating
the mucous membranes of the eyes, nose and throat with the
secretions from tlie mucous membranes of an early case of
measles.
A favorable patient was found for these inoculations. A child,
five years of age, the daughter of a physician was exposed to
measles by the occurrence of an attack in an older sister. During the incubation period in this child, examinations were made
of the nose and throat for pathogenic microorganisms, especially
the pneumococcus and the hjemolytic streptococcus. None were
found and as far as secondary invaders were concerned, the secretions were regarded as satisfactory. Twelve days after exposure
the patient developed a moderate conjunctivitis and coryza accompanied by a temperature of 100°. During the next two days, the
temperature was practically normal but on the following morning,
15 days after exposure, it rose to 102.5° -with a marked increase in
the conjunctival and respiratory symptoms. A few Koplik spots
were present. On the following morning these symptoms persisted and profuse eruption appeared over the face spreading
gradually downward over the body in the course of the next 48
hours.
Inoculations with secretions from the mucous membranes
were carried out on the two susceptibles (VIII and IX), on
one of the immunes (A) and on another immune (C) who
had not previously received any injections. The latter, a man,
23 years of age, had had measles nine years before. Twenty
days after the last injection of blood, these four individuals
(VIII, IX, A and C) were inoculated on the mucous membranes of the eyes and nose with the lachrymal secretions and
also on the nose and throat with the nasal secretions of the patient. This inoculation was performed on the day of the preeruptive rise in temperature in the child, i. e., 12 days after
exposure and four days before the eruption. A similar inoculation was made on the day before the eruption, i. e., on the
15th day after exposure. On this occasion, in addition to
duplicating the previous inoculations, the buccal secretions
were thoroughly rubbed over the mucous membranes of the
mouth and throat of the four subjects. On both days all of
the.se inoculations were made with a sterile cotton swab slightly
moistened with physiological saline. This was rubbed rather
firmly over the mucous menihrane of the patient and then
immediately over the mucous mcmlirane of the subject, a fresh
swab being used for each inoculation. On both occasions the
September, 1919]
263
four subjects were in the same room with the patient ; on tlie
(lav of the first inoeuhitions, the patient not being confinecl
to the bed was allowed to play with these men three-quarters
of an hour.
Intrarenoits Injeclion of liloutl. — In addition to these inoculations with secretions of the mucous membranes, one more
susceptible (X) was inoculated with measles blood. A s]iccinien was taken from this same child within from li tn 10
hours after the appearance of the rash ; 0..5 c. c. was injcited
subcutaneouslv and l.-"i c. c. intravenously immediately after
withdrawal before the blood had time to clot.
Neither the intravenous injection of blood nor the inoculations of the secretion ]iroduced. in these five subjects, any
respiratory symptoms or any rash. Only insifrnificant fluctuations occurred in the temperature and in the total and ditfcrential leucocyte count.
For the susceptibility tests in tliese men it might naturally
be e.\jx'cted that control inoculationswould have been conducted
with a susceptible individual who had not had any previous
inoculations of blood. The production of measles in a control case would furnish some additional evidence but certainly
would not in any sense afford proof that these men were susceptible and had been immunized by the injections of measles
blood.
In rlrawing conclusions concerning these inoculations of
blo<jd and mucous secretions in these susceptible men, there
are two unknown factors to be determined, namely :
(1) Whether the individuals in question (VIII and IX)
at the conclusion of the inoculations were immune
and if so
(*) Whether the immunity was conferred by the injection
of blood or acquired possibly through a previous attack of measles.
The results of the .susceptibility tests leave little doubt but
that these men were immune; they were exposed to natural
infection by an early case of measles and they were al.so thoroughly inoculated artificially. The high degree of communicability characteristic of the disease leaves little room to
suppo.se that these men might be infected by exposure now to a
second ca.se. The evidence of susceptibility of one of these
volunteers ( I .\ ) is icrtainly much more concrete than the general argument.s that can be lirought in favor of a ])revious attack
of measles. It woulil seem di>tinctly j)ossible that the injection
of idood had jiroduced an artive immunity.
.1 priori one would not ex])ect that sulistantial immunity
could be obtainol without the production of marked local or
general symptoms. However, in the case of varicella, Iless
and I'nger' re])ort active immunizjition by the intravenous
injection of the +++++
CONTENTSs of vesicles without the production of
subjective symptoms. It is noteworthy, however, that control
individuals inoculated on the muious membranes faile<l to
develop varicella. Kecent work by IJichartlson and Connor,'
though affording no final proof, suggests the possibility of
obtaining active imnninity against measles without the production of definite symptoms.
Lastly it should be emphasized that conclusive demonstration of the non-infectivity of measles blood ujion injection into
a susceptible individual would still fail to prove the absence of the virus of the disease in the circulating blood. It
is very doui)tful, for example, whether a susceptible human
being would be infected by the injection of a moderate amount
of blood of a typhoid patient taken during the stage of bacteriannia. It is a theoretical possibility that the blood of a measles
patient might reproduce the disease when inoculated on the
mucous membranes though not upon injection into the body
tissues.
For the sake of convenience, the inoculations rcjiortcd in the
preceding jiagcs have been collected in the following taldc:
TABLE OF INOCULATIONS
SusceptiblF I.
Susceptible II.
1 month later.
21 months after
2d injection.
2 months after
3tl injection.
1 day after 4th
injection.
3 oeelis after 4th
injection.
31 weeks after
4th injection.
Susceptible V.
Susceptible VI.
Susceptible VII.
3 weeks later.
Susceptible VIII.
1 day later.
3 weeks later.
3| weeks later.
Susccptibit IX.
Susceptible X.
Immune 11.
Blood serum, eruptive sta^e.
Dellbrinated blood, eruptive stage.
Blood serum, eruptive stage.
Mucous secretions, eruptive stage.
Citrated blood, pre-eruptive stage.
Citrated blood, pre-eruptive and
eruptive sta}<e.
Mucous secretions, pre-eruptive
stage.
Mucous secretions, pre-eruptive
stage.
Deflbrinated blood, eruptive stage.
Blood, eruptive stage, incubated
in broth.
Rubeolous skin lesion.
Citratcil blood of two patients,
^ta^•.•
Citrated blood of two patients,
preemptive and eruptive stages.
Mucous secretions, pre-eruptive
stage.
Mucous secretions, pre-eruptive
stage.
Duplicate of 4 inoculations of
Susceptible VIII.
Whole blood, eruptive stage.
DupliealK of the flrst and second
injections of VIII and IX.
Duplicate of the tbir<l ami fourth
injections of VIII and 1\.
'Calculated amouiK.
0.6 c.c.
0.6 c.c.
Subcutaneous.
Subcutaneous.
Subcutaneous.
•8 c.c.
•8 c.c.
Subcutaneous.
Intravenous.
On mucous membranes.
I Subcutaneous and
I intramuscular.
Jn mucous mem*
branes.
3n mucous mem
Subcula
On nnicous m<
brane.
Subcutaneous.
Subcutaneous.
Subcutaneous.
On mucous membrane.
Subcutaneous and
intramuscular.
Subcutiincuus and
intramuscular.
On mucous membrane.
On mucous membrane.
CONTROL INOCULATIONS
Injeclion of Ascitic Urolh and Xormal Blood. — For I be intensive inoculation of susccjitible individuals with measles
blood it might .seem only natural t« have included the injection
of measles blood incubated in ascitic broth in addition to the
other injections. .\ control series of injections, however, had
already shown that normal blood in ascitic broth was not
altogether free from toxic action.
The same lot of broth an<l ascitic fluid already described for the
incubation of measles blood was mixed with normal human blood
264
[^'o. 343
(4 c. c. to 50 c. c. of ascitic brotli) and incubated for 24 hours.
Quantities of 5 to 7 c. c. were injected subcutaneously into 10
individuals; six remained practically free from symptoms. Of the
other four, one immediately after injection maintained a temperature of 99° to 99.5° for nine days; another, six days after injection,
developed a temperature of 100.2° accompanied by a few large
papules over the forehead and a moderate degree of inflammation
of the pharynx; the two others, nine days after injection, developed temperatures of 100° and 101° with definite pharyngeal
symptoms but unaccompanied by any rash.
In a second group of controls with the same technique but with
another lot of broth and of ascitic fluid, the reactions were similar
but rather less marked. Of 10 individuals, three remained entirely
without symptoms. The results in the others were as follows:
in two cases, 10 days after injection, the maximum temperature in
one was 99.8° and In the other 100.2°; three other cases reacted
much earlier, the temperature in one on the fifth day being 100°
and in the other two 99.4° on the sixth day. One case presented a
slight rise in temperature on several days as follows, 99.2° on the
fourth and fifth days, 99.4° on the sixth day. On these days, this
man also developed a fairly extensive maculopapular eruption appearing first over the chest and then over the arms. When his
temperature returned to normal the rash faded leaving pigmented
areas which gradually desquamated. Another subject on the third,
fourth and fifth days after injection developed a well-marked
erythema which was widely distributed over the chest, back,
abdomen and extremities. The temperature continued normal,
except on the 13th day when it rose to 99.4°. In this second group
of controls the leucocytes were counted whenever a rise in temperature occurred, but no leucopcenias were observed.
The-se reactions, though ver_y mild, indicate the advisability
of conducting control inoculations when similar injections
are performed to test for the presence of a virus; this is
especially true in view of the difficulty of duplicating exactly
a rather complex culture medium. Although these symptoms
did not .simulate measles in any way, nevertheless the interpretation of atypical temperature curves or rashes might be confusing; the detection of a pre-eruptive rise in temperature
might be very difficult when complicated by the possible effects
of ascitic broth.
CLINICAL EVIDENCE
Intra-uterine Infection. — Medical literature, especially the
text-books, frequently contain the statement that pregnant
mothers, having contracted measles, occasionally give birth to
a child with a fully developed rash. These reports of intrauterine infection do not bear complete evidence of authenticity.
In many instances, satisfactory evidence is lacking for the
diagnosis of measles especially in the child ; in other cases, the
period elapsing after birth before the rash appears is sufficiently long to permit of extra-uterine infection. Although the
cases are comparatively rare, it appears, on the other hand,
that a pregnant mother developing measles at term does not
ordinarily infect the child in utero. Lastly, the development
of measles in a new-bom child would not harmonize with the
view that infants during the first three months of life are
immune from the disease. This apparent discrepancy might
be explained by Herrman's " statement that children of susceptible mothers are not immune from measles, a view, however, which is not supported by the natural immunity of infants to some other acute infections, notably scarlet fever
and diphtheria.
Characteristics of tlie Eruption. — The question whether the
virus of measles gains access to the circulating blood requires
for a completely satisfactory answer the explanation of a
striking clinical symptom. A priori the remarkably constant
appearance of the rash widely spread over the body would
seem obviously to point to the distribution of the virus by the
blood-stream. Unlike the rashes of other infections, of serum
disease and of the food and drug intoxications, the eruption
of measles always appears first on the upper part of the body,
commonly on the face, from where it spreads steadily downward over the trunk and arms reaching the lower extremities
on the second or third day. This phenomenon is very striking
and very constant. It has been recognized as one of the distinguishing features of the eruption of measles. The average
l^eriod for this progress over the body is usually stated as two
or three days with extreme limits of one to five days. In a
fairly definite but less striking manner the eruption fades in
the order of its appearance ; thus the rash often almost disappears on the face before it is fully developed on the feet.
Virtually no explanation has been suggested for this characteristic progress of the skin eruption. Von Pirquet,*" assuming
that the virus is present in the blood stream, advances the
view that the rash is a manifestation of allergic and that the
order of appearance of the skin lesions is directly proportional
to their distance from the heart and great vessels. In support
of this view, figures are given in detail of the distance from
the skin lesions by way of the arteries to the heart. It is very
difficult to conceive of any explanation that is consistent with
the mechanical features of the circulatory system. Moreover,
other exanthems which certainly are distributed by the bloodstream do not progress in this manner over the body. A
notable example is small-pox; the portal of entry is probably
similar to that of measles, but one commonly examines the
palms for the first nodules. Von Pirquet departs widely from
the accepted views in considering that the rash of small-pox
resembles measles in its origin and progress over the body.
Possibly the lymphatic system offers a more satisfactory
basis than the circulating blood for the explanation both of
the usual point of origin of the rash and its subsequent distribution. The mucous membrane of the upper respiratory
tract and of the eyes may safely be regarded as the portal of
entry of the virus of measles and the seat of the primary
lesion. Notwithstanding some variation in individual cases
as well as some minor differences of opinion, the skiu lesions
usually appear first on the face. It is conceivable that the virus
travels by way of the lymphatics not unlike tlie primary infection of the nasal mucous membrane in leprosy with the
subsequent involvement of the skin of the face. The gradual
progress of the measles rash has certain features in common
with the spread of erysipelas, an infection which travels by
way of the lymphatics. The plexus of lymphatics forming a
complete network over the body would furnish anatomical
communications consistent with the distribution of the rash.
The valves of the lymphatic system which normally direct the
flow of lymph in certain definite channels would not necessarily
constitute an effective barrier against the spread of an infec
SErTK.MUKR, 1!»l!t|
265
tious agent; a rapidly multiplying virus could conceivably
grow airaiust this feeble current of lympli and also grow
throujili the delicate valves.
The preeedinj: discussion has been based on the hypothesis
that the niorbillous cxanthem is produced, not by an extracellular toxin but l)y the action of the virtis of the disease itself.
in a manner analogous to what occurs in small-pox and chickenpox. A toxin could hardly distribute itself cither by the blood
stream or by the lymphatics in a manner that would explain
the symptoms observed in measles. The virus of the disease, if
it is distributed by the lymphatics, would almost inevitably
be swept into the blood stream where it might readily persist
teni]K)ranly even though it did not multiply. The clinical evidence, however, can only be regarded as suggestive; experimental proof must be obtained before any final decision is
permissible. The ultimate explanation of the progress of the
rash of measles will be of distinct interest and value.
DISCUSSION OF RESULTS
There is. unfortunately, a striking discrepancy between tiio
negative results following these inoculations of measles blood
and the successful experiments previously reported uiulcr
essentially similar conditions. A careful examination of the
data recorded in this paper has failed to suggest any correlation of these diametrically opposite results. Eight apparently susceptible individuals have been inoculated with blood
in various ways but none developed measles. In the selection
of measles patients for these inoculations, the diagnosis both
of the disease it'elf, especially during an epidemic, and also
the stage of the disease offers little difficulty. In any negative
results in adults the crucial factor is the question of susceptibility. While some of these eight individuals may in reality
have been immune, it .seems that, at the least, several of them
must have been susceptible. As already suggested, the two
who received intensive inoculations of measles blood and
responded negatively to susceptibility tests may have been
immunized by the injections; if one is not willing to consider
the possibility of inununization there still rcn)ain six other
cases requiring explanation.
There are certain points of especial interest concerning the
two exjierimental cases reported by Ilektoen. The extremely
small quantity of serum, approximately 0.1 c. c, employed by
this author constituted one of the significant features of his
experiment. A few but not many infections can be readily
reproduced by the injwtion of minimal quantities of blood.
In cattle plag\ie as little as ]/(iO c. c. of blood may prove infective : " Marehoux, .Salimbeni and Simond " produced yellow
fever with <>.l c. c. of serum.
It will be recalled that these successful experiments witii
measles were conducted prior to our knowledge of scrum sickness: however, only homologous proteins were employed and
typical serum-disease can therefore be eliminated. In the
control tests reiwrted in this paper the injection of mixtures
of normal blood, ascitic fluid and broth produced a slight
temperature and rash in occasional instances, but in no case I
could the symptoms have been confused clinically with
measles.
Spontaneotis Infections. — Sporadic cases of measles may develop so insidiously that even with careful isolation, the
possibility of spontaneous infection during experimental
inoculations must be borne in mind. A typical illustration
occurred at the base hospital at Camp Dcvens, JIass. A patient had been in the general wards of the hospital for two
months ; during this period it was not possible to trace any contact with a case of measles. lie was then transferred to the
p.sychopathic ward where, after thorougli isolation for one
month he developed a typical attack of measles. The tcmperaturechart showeda characteristieprc-eruptive rise accompanied
by conjunctivitis and toryza. The symptoms increased ; Koplik spots appeared, the temperature rose again, a characteristic
rash developed followed by the usual pigmentation. It was
not possible to locate any third person who might have carried
the infection to this patient. Such examples are, however, so
rare that it is by no means plausilde that both of Ilektoen's
cases could be explained in this manner. This is especially
true in view of the fact that the experimental subjects in
question underwent a period of isolation much longer than the
normal incubation time of the disease before any injections
were made and they were subsequently carefully jirotected from
spontaneous exposure.
The diagnosis of these experimental cases was ba.sed essentially on the rise in temperature after a typical period of incul)ation and the development of a definite rash. In both patients
the rash started on the face. In one case the progress of the
rash over the body is described; its distribution was almost
complete in about five hours. This period would be extremely
short for spontaneous measles, being much more characteristic
of rubella. Infomiation concerning the lymphatic glands in
these patients would have been of some value in differentiating
these two diseases. Although the injections were made over
the chest and over the back it is of interest to note that the
rasii appeared first on the face just as when the virus enters
the body by way of the mucous membrane. In one of these
ca.ses a typical bran-like desquamation is descrii)ed.
Respiratory sym])tonis were al)sent in one of these cases, a
feature which has led TJstvedt" to .suggest the possibility of
doui)t concerning the diagnosis of measles. However, it is
not at ail surprising that the nnicous membrane of the respiratory tract should escape involvement when one considers that
the portal of entry and very jiossibly the seat of the primary
lesion was changed from the mucous membranes to the body
tissues. Such absence of respiratory involvement in measles
iiiorulala would constitute a hopeful point in securing active
inmiunization without running the risk of i)ulmonary coml)lications. Likcwi.<c. from the standjioint of protective inoculation, it is encouraging to note that evidence of malaise was
absent altogether in one patient and very mild in the other.
It is noteworthy that the charts in neither case exhibit any
pre-cruptive rise in temperature, a characteristic which though
very common is not constant in spontaneous infections and it
is eertainlv not an essential criterion for the diagnosis of
266
[No. 343
measles inoculata. It is desirable that certain deficieucies
concerning these cases should be supplied, more especially the
observations concerning the leucocyte count and the occurrence of Koplik spots. This information would be helpful
in the differential diagnosis.
In some respects, therefore, these experimental cases differed
from the usual course of spontaneous measles notably in the
rapidity of the spread of the rash, in the absence of a preeruptive rise in temperature, in the absence of respiratory
symptoms in one case and of malaise in the other. Such
modifications, however, are of an essentially minor nature
and might readily be explained as the result of the subcutaneous injection as contrasted with spontaneous infection.
The occurrence of such modifications in the disease, however,
would require thorough confirmation.
General Considerations. — Some of the infectious diseases of
man can be readily transmitted from infected to susceptible
individuals by the injection of blood; such transmission has
been fully demonstrated for yeUow fever," malaria" and
trench fever." According to the conclusions of Hektoen this
same statement would also apply to measles. To appreciate
fully its importance, it must be clearly borne in mind that for
trench fever, malaria and yellow fever the natural portal of
entry is through the skin; in measles the primary lesion
occurs in the mucous membrane. By radically altering the
portal of entry or the seat of the primary lesion of a given virus
remarkable changes may be produced in its effect even on a
highly susceptible host ; the vibrio of Asiatic cholera produces
infection when ingested by way of the alimentarj- tract but
relatively large amounts of living and virulent cultures can
be injected subcutaneoush' with impunity.
After noting certain definite exceptions it would seem possible to develop some general rules concerning fundamental
principles involved in the artificial immunization against any
given infection. Precise data, from the very nature of the
subject, are not available on account of the difficulty of obtaining information concerning the infectivity of pathogenic
micro-organisms for man. The subject may be conveniently
considered imder three headings :
1. For those infections in which the mucous memlrane constitutes the portal of entry and in vjhich the classical lesions
of the disease are in general limited to the tissues accessible bi/
direct continuity, the causative organism may in many instances be injected subcutaneously in a- viable condition in
moderate dosage with impunity.
In the case of bacillary dysentery and Asiatic cholera, living
attenuated cultures of the causative organism have been used
freely by subcutaneous injection as a vaccine. For the pneumococcus, Cecil and Blake,§ at the Army Medical School, have
recently demonstrated in monkeys {Macacus sy rictus) that as
little as one-millionth of a cubic centimeter of a broth culture
may produce a fatal pneumonia upon intratracheal injection.
The subcutaneous injection of one-thousandth of a cubic
centimeter of the same culture may or may not produce a
§ Personal communication.
seisticaemia. In either case, those animals which recover possess a distinct immunity. In the case of B. diphtherice virulent
strains growing on a wound usually produce no symptoms in
man. From the clinical evidence one would not expect that
the hypothetical organisms of whooping cough and of influenza
would produce an infection upon subcutaneous injection.
2. As a corollary to the first statement, when, the natural
portal of entry of a pathogenic organism occurs through the
skin, then artificial injection into the tissues or blood stream
causes an infection which reproduces the typical manifestation
of the spontaneous disease.
Of the more important diseases in which the portal of entry
occurs through the skin we may consider bubonic ])lague,
tetanus, glanders, anthrax, malaria, trypanosomiasis, hydrophobia, kala azar, relapsing fever, typhus fever, yellow fever,
dengue fever, trench fever and the spotted fever of the Kocky
^Mountains. In the case of plague, malaria, yellow fever,
trench fever, typhus and probably dengue, it has been demonstrated experimentally that the subcutaneous or intramuscular
injection of the virus, in virulent form, reproduces the typical
features of the spontaneous diseases ; a similar result could be
confidently expected in the remainder of the diseases just
mentioned.
The disease, plague, occupies a position of an intermediate
type which is unique. B. pestis exhibits the characteristic of
possessing two distinct portals of entry resulting in the production of two clinical types of disease, the pneumonic and
the buljonic form of plague. If insect transmission of
B. pestis were unknown, bubonic plague would not occur spontaneously; experimentally it could be designated appropriately
as plague inoculata inasmuch as it differs markedly from the
pneumonic form.
3. For those infections in which the virus enters by way of
the mucous membrane and gives rise to metastatic lesions in
other tissues of the body, the injection of the virus into the
body tissues usually produces an infection; sometimes the
essential clinical characteristics of the disease are duplicated,
but in other instances a modified infection results quite unlike
the spontaneous disease.
The first and third groups must be looked upon merely as
extremes between which there can be no sharp dividing line ;
for instance, typhoid fever constitutes a somewhat intermediate example. Although B. typhosus can infect in moderately small numbers by way of the mucous membrane, nevertheless, living cultures can be injected subcutaneously with
the production of nothing more than a local reaction.
The meningococcus, M. melitensis, Treponema pallidum and
the causative organism of poliomyelitis may conveniently be
considered together. Injection of monkeys with the virus
of poliomyelitis and the accidental injection of man with
T. pallidum have produced typical infections; similar results
could probably be obtained with the meningococcus and with
M. melitensis, two organisms which produce little or no local
lesion on their passage through the mucous membrane.
Small-pox and chicken-pox present important conditions
for consideration. AVhen the virus of small-pox is inoculated
September, 1919]
267
on the skin instead of on the nnicous membranes, small-pox
inoculata develops and the disease, as it occurs spontaneously,
cannot be reproduced in this manner. According to Hess and
TJnger ' the virus of chicken-pox, when injected intravenously,
gives rise to no symptoms but apparently reproduces some
immunity.
E.xceptional conditions occur in two of the diseases of lower
animals. In cattle plague extensive primary lesions occur on
the mucous membrane of the intestinal tract and eventually
a septiciBmia develops. Experimentally the virus behaves in
an almost unique manner in that small doses of blood
injected subcutancously set up a fatal infection. Besson"
states that the influence of tlie site of injection of the bacillus
of -symptoniatic anthrax is very marked. A dose of the virus
which will kill an ox on injection into the cellular tissues of
the body will produce merely a benign infection when injected into the connective tissues of the neck, tail or ear and is
followed by permanent immunity.
In the preceding discussion the objection may at once be
raised that the normal healthy adult can readily withstand the
inoculation of a few living and fully virulent pathogenic
organisms. A distinct step would be gained if it can be shown
that those organisms which normally enter the body through
the skin can, as far as injections into the tissues are concerned,
set up an infection from the introduction of much smaller
numbers than in the case of those micro-organisms which first
infect the mucous membranes. In attempting prophylactic
immunization against a given disease it is fundamentally
nece.ssarj- to consider the natural portal of entry of tlie virus
in question.
RESUME
An eifort has I)cen made to determine whetlicr the virus of
measles exists in the circulating blood of a patient, permitting
the transfer of the disease from man to man by the inoculation
of blood. The prominent data bearing directly on this subject are:
(1) The successful transmission in two cases previously
reported by Hektoen,
(2) The failure in eight instances recorded in this paper
to transmit measles by the injection of blood,
(3) The clinical phenomenon of the origin of the rash on
the face or upper part of the body with its gradual
progress downward requiring from one to three days
to complete this march.
The symptoms of the t^vo experimental eases that have been
reported were not entirely characteristic of the classical type
of measles. Although the disease varies extremely little in its
clinical manifestations, distinct modifications might readily
occur under experimental conditions.
As regards the negative results obtained in these eight
individuals, the principle difficulty arises in establishing, by
the clinical history, the susceptiliilitj- of an adult to a disea.«e
so generally prevalent as measles. In some of the men who
were inoculated the circumstantial evidence of susceptibility
was unusually strong.
Failure to transmit the disease by the injection of blood
does not preclude the existence of the virus in the blood stream
even in moderate amount. There is some evidence that these
men not only failed to become infected but that they were
actively immunized by the injection of blood ; .such an assumption would, of course, presuppose the existence of the virus
in the blood stream. Indeed the agent which excites the rash
might readily gain access at least temporarily to the bloodstream regardless of whether its distribution takes place by
the lymphatics or by the circulating blood.
The constant origin of the eruption on the upper part of the
body and its gradual and orderly extension downward is quite
unlike the development of eruptions in which the virus is
known to be distributed by the circulating blood.
Measles originates as an infection of the respiratory and
conjunctival mucous membranes and the virus does not set
up metastatic infections in the viscera of the body in the spontaneous disease. Failure to reproduce the disease by subcutaneous injection of the virus is in keeping with the behavior of several other pathogenic micro-organisms of the
respiratory and gastro-intestinal tract.
The virus of measles per se does not produce serious effects,
but one attack of the disease gives rise to a well-marked immunity. With appropriate isolation of the virus it would seem
that a substantial active immunity should be obtainalile with
a minimum of inconvenience to the individual.
CONCLUSIONS
1 . The question of the transfer of measles from man to man
by the injection of a patient's blood is entirely reopened by
the eight successive negative inoculations recorded in this
paper.
2. The failure to transmit the disea.se in this manner does
not necessarily exclude the possibility of the occurrence of the
virus of the disease in the circulating blood; some evidence
was obtained indicating the possibility of producing active
iniinunity by the injection of ])aticnfs blood.
This experimental study of measles by the inoculation of volunteers was authorized by General Gorgas and General Ireland at the
request ot Colonel Frederick F. Russell. The ofllcors and men
volunteering for this work signed the following statement:
" I hereby volunteer as a subject for inoculation with measles In
order to promote the work undertaken In the United States Army
for securing a protective inoculation against this disease."
Having seen the serious consequences ot measles In camp
life, these men, for no reward to themselves, gladly accepted the
risk inherent In these inoculations simply from a desire to be of
service. Throughout this work they co-operated cheerfully and
conscientiously in carrying out the long isolation essential during
these investigations.
The Surgeon General's recognition of their services was made
by Colonel Russell in the following letter:
" The Surgeon General has been informed of the fact that you
volunteered for the measles Investigation. He desires me to express to you his appreciation of the patriotism and devotion to
duty that you have shown and to assure you that your contribution to the cause is appreciated by him just a.s much as was the
bravery of the men who went into the fight In France."
It is a pleasure to acknowledge the constant co-operation of
Colonel Frederick F. Russell throughout these investigations. I
268
[No. 343
am especially indebted to Lieutenant-Colonel Channing Frothingham for his assistance at Camp Devens and to Lieutenant-Colonel
Henry J. Nicliols for his kind co-operation at Camp Meade and at
M'ashington, D. C.
BIBLIOGRAPHY
1. Noguchi. H.: Etiology of Yellow Fever. Jour. Exper. Med.,
1919, XXIX; 547.
2. Mayr. F.: Beobachtungen iiber Maseru. Ztschr. d. k. k.
Gesellsch. zu Wien, 1S52, I, 6.
3. Herrman, C: Immunization against Measles. Arch. Pediat.,
1915, XXXII, 503.
4. Hektoen, L. : Experimental Measles. Jour. Infect. Dis., 1905,
II, 23S.
5. Tunnicliff, R.: Observations on the Bacteriology and Immune
Reactions of Rubeola and Rubella. Jour. Infect. Dis., 191S.
XXII, 462.
6. Anderson, J. F. and Goldberger, J.: Experimental Measles
in the Monkey. Public Health Reports, 1911. XXVI, 847 and 887.
Goldberger, J. and Anderson, J. F.: The Nature of the Virus
of Measles. Jour. Am. Med. Assn., 1911, LVII, 971.
7. Levy, R. L. and Alexander, H. L.: The Predisposition of
Streptococcus Carriers to the Complications of Measles. Jour.
Am. Med. Assn., 1918, LXX, 1827.
8. Hess, A. F. and Unger, L. J.: A Protective Therapy for Varicella. Am. Jour. Dis. Children, 1918, XVI, ii.
9. Richardson, D. L. and Connor, H.: Jour. Am. Med. Assn.,
1919, LXXII, 1046.
10. V. Pirquet, C: Das Bild der Maseru auf der Aeusseren
Haut. Ztschr. f. Kinderh., Orig., 1913, VI, 1
11. Nicolle, M. and Adil-Bey: Etudes sur la peste bovine. Ann.
de rinst. Pasteur, 1901, XV, 715.
12. Marchoux, Salimbeni and Slmond: La fievre jaune. Ann.
de I'inst. Pasteur, 1903, XVII, 665.
13. Ustvedt, Y.: Norsk Magazin f. Laegevidensk, 1906, LXVII,
128.
14. Di Mattel, E.: Beltrag zum Studium der experimentellen
malarischen Infection am Menschen und an Thieren. Arch. f.
Hyg., 1895, XXII, 191.
15. McNee. J. W., Renshaw, A. and Brunt, E. H.: Trench Fever.
Brit. Med. Jour., 1916, I, 225.
Strong, R. P., et ah: Trench Fever. Oxford University
Press, 1918.
16. Besson, A.: Practical Bacteriology. Trans, by Hutchens,
H. J., Fifth Ed., 1913, 553.
THE ROLE OF THE X-RAY IN THE DIAGNOSIS OF LONG-STANDING
RENAL TUBERCULOSIS
By J. A. ('. CoL,sroN and Charles A. Wateds
(From the James Buchanan Brady Urological Institu-te, The Johns Hopkins Husijital. BcUimore. Md.
The progress which lias been made in the htst decade in the
investigation of diseases of the urinary tract, thanks to the
use of the cystoscope and ureteral catheter, has made possible
a differentiation of lesions which before that time had been
unrecognizable.
There is no disease of the kidney which can be more certainly diagnosed by the use of these modern methods than
renal tuberculosis. The demonstration of diminution in the
renal function, together with the presence of pus cells and of
tubercle bacilli in the catheterized specimen of urine collected
from one side, leaves no possibility of doubt as to the condition with which one has to deal.
In the majority of cases a diagnosis is possible by the use
of these methods. But in many cases of renal tuberculosis,
especially those of long duration, cystoscopy and ureteral
catherization are impossible on account of the changes which
have taken place in the bladder mucosa. It may be impossible
to recognize the ureteral orifices or they may not admit the
ureteral catheter; and there are also some cases in whicli
extensive ulcerative processes have led to such contracture oL"
the bladder as to make the introduction of the cystoscope impossible or too paiuful for the patient to bear. In many of
these cases, although tubercle bacilli may be demonstrable
in the bladder urine, owing to the fact that the ureters cannot
be catheterized, it is impossible to determine in which kidney
the lesion is located, because it must be remembered that in
most cases of renal tuberculosis there are a few definite symptoms referred to the kidney itself.
When it is possible to introduce the ureteral catheter, the
diagnosis is usually easy, but there are types of long-standing
chronic tuberculous processes with sluggish ulceration in which
only a few pus cells can be demonstrated and tubercle bacilli
may not be found even in repeated catheterized specimens.
In some cases in which the disease has progressed to complete destruction of the kidney terminating in caseation and
deposition of calcium salts — the so-called auto-nephrectomy — the deposition of calcium salts will east a shadow on the
x-ray negative varying in density in proportion to the extent
of the process. It is in just these cases where for any of the
above reasons a definite diagnosis cannot be made that the
s-ray will often be the determining factor in the recognition
of the lesion.
When the normal kidney substance has been largely replaced
by calcified caseation, a complete outline of the kidney and even
the ureter may be seen on the x-ray plate and in sudi cases
a definite diagnosis can be made immediately without the
demonstration of tubercle bacilli and without recourse to
ureteral catheterization except to determine the integrity of the
opposite kidney.
It should, therefore, be a routine procedure to precede cystoscopy and ureteral catherization by plain x-ray examination
of the urinary sy.stem in all suspected cases of renal tuberculosis.
When the calcification is limited to a single area in the
kidney there may be .some difficulty in differentiating this
process from calculus, but a critical c.bservation of the
September, 1919]
269
density, shape and position of the shadow, will leave little
room for doubt. Where tlie kidney has been completely
destroyed, the charaeteristie lobular appearance of the shadows
due to the caloitied caseous cavities is very definite and is never
seen in any other type of kidney lesion.
By means of stereoscopic plates the iiulividiial abscess
cavities can be dearly distinj;uished from each other, provided,
of course, that the process has been of a duration long enough
to produce deposition of calcium salts in the areas of caseation. Calcification of the ureter is rare, but when it does
appear it is perfectly characteristic, the ureter showing on
the negative as a dense shadow, tiie calcification involving the
upfwr portion, the lower portion or indeed its entire course.
In addition to what is shown by the sclerosis of the ureter
itself, a shadow may be cast by the caseous material which is
sometimes seen filling the lumen of the ureter and which
represents the +++++
CONTENTSs of the cavities in the kidneys.
The fact that calcification occurs as a late process in renal
tuberculosis and that this calcification will show an opacity on
the x-ray plate has long been known, but tlie practical value of
this simple method has been too little emphasized.
During the past few years several cases of renal tuberculosis have been recognized at the Brady Urological Institute
from the x-ray plate alone, and a summary of some of the more
interesting of these cases will be given in order to emphasize
the value of the routine x-ray examination.
Case 1. — A physician, aged 39. was seen in 1907. The family and
past histories were unimportant. The patient had had attaclts
of duU pain in the back and left flank at the age of fourteen
which were diagnosed at that time as indigestion. He first
noticed frequency and burning on urination at tlie age of twenty
associated with hematuria. He lost some weight, had chills and
fever and was incapacitated for about one year. A careful urinary
examination was apparently not done at this time. The blood,
however, soon disappeared and the frequency was greatly improved by instillations of silver nitrate. The dull pain in the
back and left side, however, persisted, varying in intensity from
time to time, and this was the patient's only complaint when he
came for consultation.
The physical examination was negative and there was no tenderness In the region of the kidney nor could either kidney be
felt. The urine was clear and contained no shreds or pus cells
and on this account no examination for tubercle bacilli was
made. There was evidence of a chronic prostatitis on rectal
examination and the prostatic secretion contained an excess
of pus cells.
The patient improved under prostatic massage, irrigation, instillation and dilatations of the prostatic urethra, until the pain
completely disappeared. He was then referred to a gastrointestinal consultant and in the course of an x-ray examination of the
gastro-lnteatinal tract following the ingestion of bismuth a remarkable shadow was seen in the region of the left kidney. This
shadow occupied the position of the kidney and showed a definitely lobulated appearance. Nothing similar had been seen
at the Johns Hopkins Hospital at this time and a positive diagnosis was not made. Cystoscopic examination showed a normal
bladder with the exception that the left ureter could not be seen.
The right ureter was easily catheterizcd and the specimen obtained was normal. A diagnosis of ureteral stricture with destruction of the left kidney was made, but the tuberculous nature of
the process was not recognized.
The patient went to a western clinic where a nephrectomy was
done and the kidney substance was found to have been entirely
replaced by caseation and masses of calcification.
A letter dated April, 1919, states that the patient has been
" free from pain and a great deal better siiue the operation."
The correct diagnosis of this case should have been made from
the x-ray alone, but at this time no similar shadow had been seen
in the x-ray department. The entirely negative urinary examinations and the fact that the patient responded so well to local
treatment were also confusing factors which contributed to the
failure to recognize the true nature of the process. (Fig. 1,
Case 1.)
Ca.se 2. — A male, aged 24, consulted Dr. Geraghty in June. 1914,
complaining of frequent urination. His father and two uncles
had died of pulmonary tuberculosis. The past history was unimportant.
Frequency with burning had existed for the past two years with
little or no improvement, at times associated with terminal hematuria. There was also at times a dull aching pain in the back
mostly on the left side. A left epididymitis had appeared two
years before, followed ten months later by a right epididymitis.
On examination there were no evidences of pulmonary tuberculosis. Neither kidney could be felt. The left testicle was normal; the epididymis was thickened at the globus minor where
it was adherent to a scar in the scrotum. The right testicle and
epididymis were much obscured and the globus minor was firmly
adherent to a scar in the lower portion of the scrotum. The
vasa defeiientia were normal. The urine contained some pus
cells but no tubercle bacilli.
Ci/siosropic examination showed a contracted bladder. The
mucosa showed some areas of reddening especially in the trigone,
but there was no active tuberculosis. The right ureter was seen
but it was impossible to catheterize because the cystoscope could
not be introduced far enough to permit a ureteral catheter to
enter it. The left ureteral orifice could not be seen.
Plain x-ray examination showed a definite dense shadow occupying the region of the left kidney. This shadow suggested a
lobular form, but it also presented a somewhat granular appearance. The ureter, which was not enlarged, could also be
I)lainly seen in its entire course from the kidney over the pelvic
brim to the bladder.
A diagnosis of left renal tuberculosis was made and nephrectomy was done by Dr. Geraghty. Convalescence was uneventful.
The kidney was lobular, twice the normal size and had been
entirely converted into a cheesy mass. The ureter was very
thick and fibrous, its lumen entirely filled with caseous material
and practically obliterated. (Fig. 2, Case 2.)
Cask 3. — A man, aged 24, came for a consultation in June,
1914, complaining of frequent urination. The patient's father
an<l two uncles had died of pulmonary tuberculosis. The past
history was unimportant. The patient had first had frequency,
strangury and hematuria two years before and shortly after the
onset a left epididymcctomy was done for epididymitis. A year
and a half later the left testicle was removed on account of
a persistent sinus.
Since this date the frequency liad persisted and there had
been pains in the region of the bladder but none in either kidney
region.
Physical examination revealed no signs of pulmonary tuberculosis, the left kidney was palpable but not tender. Rectal examination revealed irregular induration of the left lobo of the
prostate and seminal vesicle.
Plain x-ray examination showed both kidneys definitely outlined and larger than normal. A definite, rounded mass was
seen in the region of the left kidney which closely resembled
270
[Xo. 343
the shadow of a stone. On the right side there was a definite,
lobulated irregular shadow not so dense as that on the left side
but much larger, the process evidently involving the left kidney
more than the right.
Cystoscopy showed a reddened trigone and some areas of
cystitis but no active ulceration. The ureters were easily catheterized and the specimens from each side contained a few pus
cells and a few large colon-like bacilli. The 'phthalein excretion
from each side was 18 per cent. No tubercle bacilli could be
found in these specimens, nor had any been demonstrated in
the bladder urine after repeated examination. A guinea-pig
innoculation was also negative.
A pyelogram showed a normal right pelvis, the calyces being
somewhat elongated, the superior caljic extending as far as the
shadow seen on this side. The ureter was not dilated. The left
pelvis was normal but the calyces were greatly elongated and
extended out so that they more or less surrounded the oval shadow previously seen on this side. The results of this examination tended to support the tentative diagnosis of calcified tuberculous areas in each kidney.
It was decided to explore the left kidney to determine definitely
the nature of the shadow. At operation. Dr. Geraghty immediately confirmed the tentative diagnosis from the appearance of
the kidney delivered in the wound. On account of the involvement of the right side the kidney was replaced and the wound
closed. Convalescence was uneventful. (Fig. 3, Case 3.)
Case 4. — Physician, aged 41. This patient was seen by us
in a base hospital in France having been referred on account of
hematuria. His mother had died of pulmonary tuberculosis. His
past history was negative except for a left empyema in 1903.
He had noticed blood in his urine first in 1S98 and this had continued for about two years with few or no bladder symptoms.
The diagnosis of prostatitis had been made and local treatment
given. In 1902, blood had reappeared in his urine and continued
for a short time. In 1906 for the same symptom the patient had
gone to a western clinic where cystoscopy was performed but
it was found impossible to catheterize the right ureter. From
this time on the same slight frequency of urination had persisted. Following the exposure incident to foreign service the
hematuria had reappeared in October, 191S. Physical examination was negative except for the scar of the empyema operation.
Examination of the urine showed numerous pus cells and red
blood cells but no tubercle bacilli.
Cystoscopic examination showed a small ulcerated area on the
anterior bladder wall and rather marked injection of the trigone.
The left ureter was readily catheterized but no definite right
ureteral orifice could be made out in spite of repeated attempts.
The urine from the left kidney was normal.
A definite diagnosis could not be made but tuberculosis of the
right kidney was suspected and the patient invalided home to
the States for further study.
On entrance to the Brady Urological Clinic after repeated examination of the urine a few tubercle bacilli were found, the
cystoscopic findings were corroborated and the plain x-ray examination showed a clear outline of both kidneys, the right
kidney being smaller and the shadow remarkably opaque. On
careful observation a definite dense lobulated appearance was
seen and the ureter which was distinctly opaque could be easily
made out in its course to the bladder.
In the plain x-ray of the pelvis the lower end of the right
ureter showed the same distinct opacity and its shadow could
be seen coursing over the brim of the pelvis. The outline of
the left kidney showed no opacities and the organ could be
definitely seen to have undergone compensatory hypertrophy.
From the characteristic dense lobular shadows seen in the
plain x-rays and the demonstration of tubercle bacilli in the
urine a diagnosis of right renal tuberculosis was made and a
nephrectomy was performed by Dr. Geraghty, December 13, 1919.
Convalescence was uneventful.
The kidney was found to be entirely destroyed, all kidney
substance having been replaced by caseated masses separated
from one another by thin layers of fibrous tissue. The ureter
was entirely obliterated.
This case was evidently one of very long standing, slowly
progressing, the initial symptoms dating back twenty years. In
spite of this long duration the bladder had become only very
slightly involved and tubercle bacilli were found only on one
occasion among many examinations.
It is this type of slowly progressing lesion which results most
commonly in the so-called auto-nephrectomy and it is in just this
class of lesions that calcium salts are deposited in amounts large
enough to permit a diagnosis to be made from the plain x-ray
plate positive. (Fig. 4, Case 4; Fig. 5, Case 4.)
Case 5. — A man, aged 46, entered the Brady Urological Institute in May, 1919, having been referred with a diagnosis of
left renal tuberculosis. His family history was negative. At
the age of nineteen an abscess of the left testicle had been
opened and eighteen months later two abscesses had been opened
in the right lumbar region. Six years before he came to us a
severe attack of renal colic on the right side had been followed
by the passage of a small calculus and four years later a similar attack occurred on the same side. There had been no frequency, hematuria or pain on urination, but the patient had had a
dull aching pain in the region of the left kidney and soreness
in the left hip for the past few years. The patient was seen
about one year before but the left ureter could not be catheterized.
Physical examination was negative except for slight tenderness elicited on deep pressure over the left kidney. Neither
kidney could be felt on account of the thick abdominal wall.
The scars of the old abscesses in the right lumbar region were
well healed. The urine was clear, contained no pus cells and
no tubercle bacilli.
Stereoscopic x-ray plates were taken qf the left kidney and
the whole organ was represented by a series of lobulated shadows
which without doubt represented the calcification of the individual areas of caseation. Nine such lobules could be easily
counted on the stereoscopic plates. The shadow of the right
kidney showed that it had undergone compensatory hypertrophy.
There were also evidences of an old healed tuberculous process
involving the first, second and third lumbar vertebrae. The
total function as measured by an intramuscular injection of
'phthalein was normal. The patient was advised to return later
for nephrectomy.
Although operation has not as yet been carried out on this
patient there can be no doubt as to the diagnosis or as to the
integrity of the right kidney. One may also assume that the
left ureter has been occluded and that the process commonly
called auto-nephrectomy has also occurred in this case. (Fig. 6.
Case 5.)
A dogmatic classification of the shadows cast liy various
types of tuberculous kidneys cannot be made and all graduations may occur, from the small indefinite shadow cast by a
calcified, tuberculous area about a calyx, to the beautiful
lobulated shadow which results from a completely destroyerl
kidney, consisting entirely of calcified abscess cavities. The
x-ray of such a kidney is quite unmistakable, but the smaller,
indefinite shadows which may be seen are occasionally difiicult
to differentiate from renal calculi and also from various extrarenal shadows such, for example, as the +++++
CONTENTSs of the intes
THE JOHNS HOPKINS HOSPITAL BULLETIN, SEPTEMBER. 1919
PLATE XXXIl
1 (Case I I. -rlKirarii risiic lobiilatrd appearance of a kidnoy conily destroyed.
Fio. 3 (Case 111 ).— Comi'li t. d.sini<tion of the upper pole with beginnins deposition of calpiiini sails in lower pole of a kidn.'V not yet
completely destroyed.
Fii;. 2 (Case III.— Typical mottled appi'arance due to the Irregular
diposition of calcium salts in a kidney completely destroyed. The outline of the ureter is plainly seen.
Fio. 4 (Ca.se IV».— Completely occluded kidney with d. portion of
calcium salts througliout Its entire extent.
I lit
THE JOHNS HOPKINS HOSPITAL BULLETIN, SEPTEMBER. 1919
PLATE XXXIIl
Fu.. ".- Drawing of tlie stereoscopic plates of
Case V, showing the clear differentiation of the
individual calcified lobules.
Kiti. 5 (Case IV I. — Cak-ilication of the lower end of ihe ureter in
Case IV. Same side.
Kii.. 6 (Case Vi. — Kidiuy i ..lui.i. ;• r. ..;-; i ..;•• .i. -....wing typical lobulated form
with deposition of calciiini salts in the caseated areas. Old healed tuberculous
process of the twelfth thoracic and first and second lumbar vertebrae.
September, 1919]
2V^i
tine, calcified glands, gallstones, etc. It must also be
remembered tliat the extent of tlie shadow on the x-ray plate
does not represent the extent of involvement of the kidney and
many kidneys have been seen, on removal, totally destroyed,
which, on x-ray examination, showed only small indefinite
shadows, or none at all.
The presence of a true renal caKulus, in association with
renal tuberculosis is rare, but several sucli cases have been seen
in which a calcium oxalate stone occupied Ihe pelvis of a tuberculous kidney. In all probability such a stone arises from the
deposition of calcium salts in a tuberculous ulceration of a
calyx. We have seen several cases of early tuberculosis in
which the only focus found in the kidney after the operation
was an ulceration of a single calyx. In a few of these cases
there was a definite deposition of calcium salts and it is easily
conceivable that a small portion of such a calcified area could
break off, fall into the pelvis and form the nucleus of a large
stone.
Such a stone gives a picture quite different from that occasionally encountered when a tuberculous area in a kidney,
wrongly diagnosed as a stone, is exposed at operation. If an
attempt is made to remove the supposed stone it will be found
to consist of a grumous, putty-like material which cannot be
taken out as a whole. If such a condition is encountered and
its true nature recognized at operation, it is far better to do
a nephrectomy provided previous studies have demonstrated
that tlie remaining kidney is normal. However, if the x-ray
shows the presence of similar areas in the remaining kidney
or if the evidence of its involvement has been demonstrated, no
operative procedure should be attempted, as the trauma incident to operation may very readily convert a slowly progressing,
partially walled-o(T process into an acute exacerbation or may
even lead to a general miliary tuberculosis.
It is not tlie purpose of this paper to discuss the very great
assistance of the data which may be obtained from the pyelogram and cystogram. In an occasional case when sufficient
information cannot be obtained by other means, a diagnosis
can be made by these studies. It has been the practice at tiie
Brady Clinic, however, to refrain from a ])yelographic study
if a definite diagnosis of renal tuberculosis can be made by
the usual methods. There have been no bad results following
this method but we have not felt that in cases where the
diagnosis was already certain the additional instrumentation
was justified.
CONCLUSION
(1) X-ray studies of the entire urinary tract should be
carried out in all cases of suspected renal tuberculosis.
(2) In some cases, when other methods of examination have
failed, a definite diagnosis of renal tuberculosis can be made
from the plain x-ray alone but, whenever possible, catheterization of the other ureter sliould be done to establish the integrity
of the opposite kidney.
(3) The shadows depend entirely upon tlie amount of calcification which has taken place in the diseased kidney.
(4) Various types of shadows may be seen in tiie plain
x-ray of a tuberculous kidney varying from the indefinite
shadows cast by small areas of calcification to the characteristic lobulated shadow wliiih is typical of a completely destroyed kidney.
(5) Pyelography and cystography may clear up the situation
in some cases but these procedures should not be carried out
if a diagnosis can be made by other and simpler methods.
Note. — Since this article was written a paper by Braasch
and Olson (Roentgenographic Diagnosis in Renal Tuberculosis,
Surgery, Gynecology and Obstetrics, XXVI II, 6, p. 5551) has appeared in which virtually Hie same conclusion has been reached.
BIBLIOGRAPHY
1. Striiter: Zeltschr. f. Rbntgenk.. 1908, p. 41.
2. Mankiewicz: Deutsche Med. Woch., 1908, p. 1290.
3. Grassner-Hurter: Zeltschr. f. Rontgenk., 1910, p. 376.
4. Fenwick: The value of expert radiography and cystoscopy
In the detection of obsolesced tubercle kidney. Brit. Med. Journal. July 3, 1919, Vol. 2, p. 16.
5. Dietlen: Zeitschr. t. Rontgenk., 1911, p. 85.
6. Casper: Zeitschr. t. Urol., 1913, VII, p. 532.
7. Marlon: Une nouvelle cause d'erreur dans la radlographle
des calculs du rein. Jour. d'Urol., 1912, 1, p. 655.
8. Papin: Localisation de la tuberculose rfinale par la radiographic. Archives urologiques de la cllnlque de Nechar, fasc.
2, juin, 1913. p. 177.
9. Heitz-Boycr: Exclusion parllelle dans un rein tuberculeuif
avec urines clalres. Jour. d'Urol. 1914, V, p. 297.
10. Plllet: Tuberculose r^nale a forme anormale. Jour. d'Urol.
1914, V. p. 595.
11. Legueu. Papln and Malngot: Exploration radlographique
de I'apparell urinairo. Paris, 1913.
12. O'Nell: Renal tuberculosis. Cabot's Modern Urology,
Vol. II.
13. Ratine: Tuberculose rOnale. Encyclopfdle Francalse d'urologle. Paris. 1914, t. 2.
REPRINT OF THE OSLER NUMBER OF THE BULLETIN
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reprinted and sold for $1.00 per copy. All those interested in securing copies should send in their orders promptly to
The Johxs Hopkins Press, Baltimore, Md.
[No. 343
IN MEMORIAM
ADMONT HALSEY CLARK
Bv William G. MacCallum
A memorial meeting was held on June 9, 1919, in the
lecture room of the Pathological Laboratory of The Johns
Hopkins University to uncover a tablet placed there by
colleagues and friends to the memory of Dr. Admout H. Clark,
associate professor of patholog)', who died on October 13, 1918.
The admiration and affection of all who had known him were
expressed in brief addresses by Dr. Welch, Dr. Howell,
Dr. Sabin and Dr. MacCalhun. The following short biographical sketch was read :
Admont Halsey Clark, the eldest child of Cyrus Alonzo and
Harriet Gulick Clark, was born near Kyoto, Japan, on August
25, 1888. His father, who came from Genesee County, New
York, had graduated as a minister at Oberlin College. His
mother, whose family, the Gulicks, had for generations been
missionaries, was born in the Caroline Islands.
Their married life has been almost entirely spent in missionary work in Japan and there Admont lived and went to
school until he was 13 years old. After that he was sent to
America to be educated and came to live with his mother's
sister and her husband, who is Professor Jewett, of Oberlin
College. With them he remained through his school and college life, becoming deeply attached to this aunt and uncle who
in some degree took the place of his distant parents.
All through his student career, both at Oberlin and later in
the medical school, he earned money by every kind of outside
work to support himself. Nevertheless, he found time enough
for his studies to stand well in his classes, and playtime enough
to excel at athletic sports. He was a particularly good player
at football and was on the University and the Maryland State
teams. JIusic, too, he loved and during this whole time he
studied the violin and learned to play it very well, so that later
he derived great pleasure from taking part in trios and
quartets.
After his graduation at Olierlin College in 1910 he formed
one of a party of biologists on an expedition to Point Pelee on
Lake Erie to observe the migratory flight of birds and to learn
whether they flew boldly across great bodies of water or tried
to take advantage of the islands scattered across the lake. Here
he contracted typhoid fever which was so severe that he lost a
whole year before entering The Johns Hopkins Medical School
in 1911. During part of this time, however, he acted as
assistant in chemistry at Oberlin College.
When fully recovered, he began work with a new zest. At
college he had taken up scientific subjects, showing especial
interest in chemistry toward which he had probably been led by
Professor Jewett. Again he stood high in his class and, in
addition, he proved to be one of the men who can and must
work on special problems which carry them beyond the routine
work of the class.
Each year he seems to have been hard at work on one or
more problems, as his published papers show. In the first year
he worked under Dr. Sabin's direction on the development of
tlie lymphatics, in the second under Dr. Whipple on the
chemical tests of the function of the liver. In his fourth year
he substituted as interne in the hospital for two months and
there devised and worked out a method for studying venous
pressure in disease. He graduated with the degree of Doctor
of Medicine in 1915 and entered immediately the department
of pathology where each year he advanced, beginning as an
assistant and becoming successively instructor, associate and
associate professor of pathology.
In these positions he showed liis ability to carry out serious
investigations independently and proceeded to a long and most
laborious study of the internal secretion of the pancreas in its
relation to sugar metabolism. This was brilliantly successful
in demonstrating the presence of a secretion essential to the
consumption of sugar by the beating heart.
Nest he turned to the study of the filtrable toxin which he
and Pelton had produced by growing the hemolytic streptococcus in blood. They completed and published a short paper
on this subject, but much more work was planned to control
and confirm their results. At the same time and before this
he was working in a more leisurely way on the effect of diet
upon the healing of wounds and had obtained some interesting
results which were left in the form of notes from which
IMrs. Clark has WTitten and published his paper.
He was married at Portland, Maine, on July 9, 1917, to
Jliss Janet Howell, and his daughter, Anne Janet, was born
on May 15, 1918. This was a j'ear of extraordinary happiness
for him. Since December, 1917, he had held a commission as
first lieutenant in the medical reserve corps of tlie army and
was very anxious to be assigned to active service, but the
surgeon-general's office, recognizing the importance of his
work on the streptococcus, supported it generously and kept
him in Baltimore. In the autumn there came the epidemic of
influenza and he was one of the many stricken. He appeared
to recover from its first effects and returned to the laboratory
for a day or two, but then developed a streptococcal pneumonia
from which he died on October 13, 1918. His loss was among
the greatest caused by that terrific epidemic.
Clark was a young man, prematurely slightly gray with an
honest face and bearing which captivated everyone at once.
He was so intelligent, so completely trustworthy and so
efficient that there was never any hesitation in entrusting to
him, when occasion demanded, the whole charge of the department, nor was there the slightest doubt of the propriety of his
extraordinarily rapid advancement to the place of associate
professor only three years after his graduation from the
I medical school.
THE JOHNS HOPKINS HOSPITAL BULLETIN. SEPTEMBER, 1919
PLATE XXXIV
^^7-2-'
Admont Hai.sky Clahk.
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^EP~ - -1 '' y "^^^^^^^^^^^^^^H
i
Lj-i
THE JOHNS HOPKINS HOSPITAL BULLETIN, SEPTEMBER, 1919
PLATE XXXV
September, 1919]
273
Aside from his undoubted ability iu the routine work of such
a department and his deserved jwpuhirity amonj: the students
and assistants who recojrnized at once his value as a teacher,
he had a jrrcat talent for tlie investigation of the problems
which interested him. Genius is a much misused word and
can hardly bo applied to Clark, because he was essentially well
balanced and sane and went about his work upon a carefully
devised plan which partook of genius only in that he had great
enthusiasm, an almost unlimited capacity for concentrated
work and a remarkalde quality of efficiency. He worked early
and late, even moving a bed into one of the rooms of the
laboratory in the summer, when his wife and child were away,
so that he could stay there continually and watch his experiments at night. When he constructed apparatus with much
difficult glass-blowing and grinding of stopcocks, it worked.
When he carried out a series of experiments to prove a point,
they worked and there were few if any false steps. Foresight
and rational judgment as to the relative importance of necessary evidence helped him greatly to advance. His problems
were large and complicated and their solution involved long
and difficult experiment'; — especially in the case of the pancreatic secretion, where he had to perfuse a surviving pancreas
and a surviving and beating heart, analyzing the fluid from
time to time as it passed ; and it was only with very perfect
apparatus, all of which he constructed himself, that it could
be done. It was thoroughly good work and full of the most
brilliant promise. He was only 30 when he died.
His interests were by no means limited to the laboratory.
He loved the outdoor life, and all games and sports, but more
especially, perhaps, the life of the woods with shooting and
fishing. His vacations during his course at the medical school
were spent working at summer camps for his uncle. Dr. Luther
Gulick. and his honeymoon was a camping and lishing trip on
Lake Temagami. He seems to have had the same skill in everytliing he did in the woods that he showed in the laboratory.
His loss is a very great one not only to us who knew and
admired him, but also to science. He seemed destined to do
great things.
His published papers were as follows :
On the Fate of the Jugular L}inph Sacs and the Development of the Lymph Channels in the Xeck of the Pig. .;Vmer.
Jour, of Anatomy, l!il>, XIY, 4:.
Tests for Hepatic Function and Disease Under Experimental Conditions. (Wliipple, Peightal & Clark.) Johns
Hopkins Hosp. Bull., 1913, XXTV, 243.
A Study of the Diagnostic and Prognostic Significance of
Venous Pressure Observations in Cardiac Disease. Arch. Int.
Med., 1915, XVI, 587.
The Interrelation of the Surviving Heart and Pancreas of
the Dog in Sugar Metabolism. Jour. Exp. Med., 1916, XXIV,
621.
The Same. Second Paper. Ibid, 1917, XXVI, 721.
A Filtrable Toxin Produce of the Hivmolytie Streptococcus.
(Clark and Felton.) Jour. Amer. Med. Assoc, 1918, LXXI,
1048.
The Effect of Diet on the Healing of Wounds. Johns Hopkins Hosp. Bull., 1919, XXX, 117.
REMINISCENCES OF TWO EPOCHS-AN/ESTHESIA AND ASEPSIS
By Stephen- Smith, A. M., M. D.. LL. D., Xew York
The development of an art is characterized by a succession
of events each of which signifies progress. These events may,
singly, appear unimportant, but, as Sir James Paget truthfully remarks, " Closely studied they are links in an endless
chain of events leading to a higher development as we witness
in the embrjo." In this chain of events there occasionally
occurs one which far transcends others in the radical and
fundamental changes which it effects in the practice of the art
under review. It stands a beacon light which illumines with
ever-increasing brilliancy the pathway of the humblest practisor. Such an event creates an epoch — " .\ point of time from
which succeeding years are numbered " (Cent. Diet.) .
Baas, the eminent historian of medicine, regards epochs as
the es.<ential features of the development of an art and from
an educational viewpoint urges that they be studied by every
practiser. Impressively he remarks:
An acquaintance with the views and knowlctlKe of epochs submerged in the shoreless ocean of time, free.s the mind from the
fetters and currents of the day with Its often oppressive reatraints.
widens the horizon for a glance into the past, and an insight
into the present of human activity, deepens the view for a comprehension of the ideas which guided the earlier and more recent
physicians, and gives on the other band to our daily professional
labor a high consecration.
Though two of the most remarkable epochs in the history
of surgery — ana-sthesia and asepsis — occurred within my personal experience, it is unfortunately true that with the profession at large the views and knowledge of these great events
have long been submerged in the shoreless ocean of time.
This general ignorance of the great events in the recent
history of surgery is due to tlie failure of the schools to include
in their courses of instruction a wcll-devisod system of teaching the " views and knowledge of epochs." No department
of science has a more interesting and instructive history than
medicine, inasmuch as every advance tends to the betterment
of the race. My experience as a teacher for many years emphasized the fact that students are not only greatly interested
in historical incidents connected with the subject, but that
thoiic incidents proved suggestive to the memory wlien the
subject was recalled in actual jiractice in later life.
Deeply impressed with the truth and moral significance of
the historian's sentiments and their quite general application,
it has occurred to me that it would he peculiarly appropriate
to the present occasion if I recalled some of my experiences
374
[No. 343
and observations on the introduction of these two greatest
epochs in the history of surger)'.
ANAESTHESIA
October 16, 1846
When I entered tlie office of Prof. Frank H. Hamilton, of
Buffalo, N'ew York, in May, 1847, as a student of medicine,
ansesthesia was on trial. Though it bore the impriraature of
the surgeons of the Massachusetts General Hospital, headed by
the honored name of Dr. John C. Warren, several deaths had
been reported during its use, which served to make conservative surgeons cautious. Prof. Hamilton was of that class and
he resorted to ansssthesia only occasionally and in cases believed
to be especially adapted to its use. This fact gave me ample
opportunity to compare the old-time method with that promised by the new discovery.
The first operation without anesthesia that I witnessed was
so disquieting on account of the sufferings of the patient that
I was nearly driven from the profession. Its cruelty was so
shocking to my untrained nervous system that I begged to be
excused from attending another operation, but the professor,
made merry of my sensitiveness, assuring me that the most
successful surgeons had fainted at the first operation but that
in the " long run " extreme sympathy for tiie patient made a
cautious and conservative operator. The case referred to
illustrates the ordinary operative proceedings in hospital practice at that time :
The patient was a workman from a shop and was suffering
from a strangulated hernia. No other preparation was made
than to remove his exterior clothing and sponge the surface
over the hernia. The surgeon came in haste, put on a hospital apron and urged haste in bringing the patient to the
table. Several strong-armed attendants were selected to hold
the patient if he made resistance. AVith a conspicuous display
of the knife the surgeon made his first incision with lightning
rapidity which was followed by the violent screams and struggles of the patient and a volley of oaths. It required several
minutes to place him again in position and meantime the
surgeon, with knife poised in the air, awaited nervously an
interval when he could cut twice in the same place. A second
incision intensified the shrieks and efforts of the patient to
escape from the table. All was now indescribable confusion,
but the attendants succeeded in overcoming the patient now
exhausted by his struggles and shock and at length the exciting
tragedy came to an end, witb all parties completely exhausted.
That this is not an overdrawn description of every day operations in the great hospitals of the country I will quote a reliable
author's experience, the patient being a woman :
She Is cheered hy kind words, and the information that it will
soon be over She is enjoined to be calm and to keep quiet
and still But of what avail are all her attempts at fortitude! At the first clear crisp cut of the scalpel, agonizing screams
burst from her and with convulsive struggles she endeavors to
leap from the table. But the force is nigh. Strong men throw
themselves upon her and pinion her limbs. Shrieks upon shrieks
make their horrible way into the stillness of the room until the
heart of the boldest sinks in his bosom like a lump of lead. At
length it is finished, and prostrated with pain, weak from her
exertions and bruised by the violence used, she is borne from the
amphitheatre to her bed in the ward to recover from exhaustion.
The screams and struggles of patients submitted to operation, which we then heard and witnessed, were but the echo
down the ages of those heard when the primitive surgeon first
applied the " chipped-knife "' to human flesh to remove the
broken fragment of a war missile. There were screams and
struggles in the home of Moses when Zipporah, his highbrow
Midianite wife " Took a flint and cut off' the fore-skin of her
son " (Ex. iv. 24). There were abundant screams and struggles in the Jewish families when " Joshua made himself knives
of flint and circumcised the children of Israel " (Joshua v. 3).
Pain and suffering was regarded as the chief obstacle to success in operative surgery from the time of that first operation
with the knife or flint. Even Hippocrates, in lofty phrase,
expressed the prevailing sentiment : Divinum est opus sedare
dolorem.
Two methods of mitigating suffering seem to have been suggested to primitive surgeons, viz.:
1. Celerity of operation to diminish the time of suffering,
and,
2. The discovery of an agent which would safely cause insensibility.
CELERITY OF OPERATION
Of these two methods the first was the most practical, as it
involved no danger, and was, therefore, adopted at once.
Successful celerity of operation required two conditions: (1)
Such a variety of instruments as may be necessary to meet
promptly every possible emergency; (2) Dexterity in the use
of instruments. Fortunately the early Huns and Egyptians,
by nature and training, were especially adapted to devise the
instruments and use them dexterously — conditions necessary
to success in celerity of operation.
In the field of invention the oriental excelled. Centuries
before the Christian Era we have descriptions of instruments
in familiar use by Plindus and Egyptians which in perfection
of finish and adaptation to special uses are equal to the " kit "
of the modern surgeon. For example, the forceps devised to
extract the fragments of the rude missiles employed in the
tribal wars were thus described by a contemporary writer:
They ought to be about nine inches long; their mouths be
respectively like those of a lion, tiger, wolf, hyena, bear, elephant, cat, hare, antelope, crow, heron, dog, jay, vulture, falcon,
owl, kite, cock, crouch, the bee, rat, mouse or bullock. Each
half must be united to the other by a nail of the form of a lentil
seed being bent inwards at the handles like the elephant-driver's
hook.
There was also tlie same great variety of probes and tubular
instrvmients each being designed to meet a special emergency
during the operation. The following directions in preparation
for an operation illustrate the care exercised by the primitive
surgeon to render a rapid operation safe:
A surgeon contemplating to operate .... should first have
ready the following: blunt instruments (forceps, etc.), sharp
instruments, potential cauteries, horns, catheters, leeches, a dry
SETTEilBEK, 1919]
275
gourd, a cauterizing needle, stuffing materials, fat, milk, oil,
string, board, bandage, honey, soothing decoctions, injections,
lotions, fan, cold and warm water, a frying pan, able, steady and
attached servants. During the operation let the patient be
seated, who has taken very little food, offered sacrifices and made
ablutions, with his face towards the East. The surgeon should
stand with his face toward him and plunge his instrument after
the proper incision until matter comes out, and withdraw it,
avoiding vital parts, vessels, muscles, articulations, bones and
arteries .... Boldness, rapidity of action, sharp instruments,
operation without trembling, fear or doubt, are always praiseworthy of the surgeon.
As a ' show-fad "' dexterity in the u.<e of instruments was at
its climax when I entered the profession. At hospital clinics
attended by students operators performed fantastic tricks with
instruments often brandishing them in the air when about
to make an incision. An amputation was a favorite occasion
for these displays of dexterity. The Catlin, glittering for a
moment above the head of the operator, was plunged through
the limb and with one artistic sweep made the flaps or coml>leted a circular operation. After several aerial gyrations the
saw severed the bone as if driven by electricity. The fall of
the amputated part was greeted with tumultuous applause by
the excited students. The operator acknowledged the compliment with a formal bow. The clinics of these operators were
as popular as tiieatrical performances and about as instructive.
Celerity of o|icration as I witnessed it, while accomjilishing
little in the mitigation of the sufferings of the victims of
operation, often had \ery serious features. Wounds of blood
vessels and nerves, puncture of viscera and similar accidents
not unfrequently occurred in the clinics of operators famous
for the display of dexterity and celerity. The movement of
a struggling patient at the moment the operator plunged his
knife resulted in wounding the femoral artery. Puncture of
the urinary bladder and intestines, division of im])ortant
nerves and similar accidents were reported from clinics. These
acc-idents usually were the interesting feature of the operation,
as they tested the ability of the operator to meet the emergency.
The accident itself did not reflect upon the operator's skill but
was attributed to the unfortunate movement of the ]iatient at
that critic-al moment when the surgeon was to exhibit his
ilexterity. Thus the tragedy that resulted in a coroner's ini|iiest contributed to the reputation of the operator as a most
.-kilful surgeon.
AN AN.ESTHETIC
-Mlusions to the u.se of " pain-killing " agents are frequent
in medical histon,- from prehistoric periods. In general their
discovery has l>een accidental as in the ca.<c of ga.ses from the
earth. More frequently the narcotizing agent was foiind in
vegetables, the poppy, the mandragora, l)elladonna, hyoscyamus. cannabis Indica, etc. Cutting operations without pain
under the narcotizing effect of these vegetables are mentioned
by many writers at different periwls. Homer describes two
operations in that picturesque style which suggests that he
must have been present and witne.«.sed them. He says :
Machon was summoned to remove an arrow which was driven
through the belt of Menelaus, King of Sparta: he extracted the
arrow from the well-fitted belt, but while it was being extracted
the sharp barbs were broken: then he loosed the variegated belt
and the girdle beneath and the plated belt beneath, which the
brass-workers had forged, when he perceived the wound where
the bitter shaft had fallen: having sucked out the blood, he skilfully sprinkled on it soothing remedies.
Eurypylus wounded with an arrow in the thigh called upon
Patroclus to remove it. Patroclus, laying him at length, cut out
with a knife the bitter, sharp arrow from the thigh, and washed
the black blood from it with warm water. Tlien he applied a
bitter pain-assuaging root, rubbing it between his hands, which
checked all his pains: the wound indeed dried up, the bleeding
having ceased.
The following prescription for making the famous anaesthetic of Theoderic (1-378) illustrates the efforts to discover an
anaesthetic :
Take of opium and the juice of unripe mulberry, of hyoscyamus,
of the juice of the hemlock, of the juice of the leaves of the
mandragora, of the juice of the wood ivy. of the juice of the
forest mulberry, of the seeds of lettuce, of the seed of the burdock,
which has large and round apples, and of the water-hemlock,
each one ounce: mix the whole of these in a brazen vessel, and
then in it place a new sponge, and let the whole boil, and as long
as the sun on the dog-days, till it [the sponge] consumes it all,
and let it be boiled away in it. As often as there is need of it,
place this same sponge in warm water for one hour, and let it
be applied to the nostrils till he who is to be operated on has
fallen asleep and in this state let the operation be performed.
When this is finished, in order to rouse him place another dipped
In vinegar, frequently to his nose. Or let juice of the roots of
fenigreek be squirted into his nostrils. Presently he awakens.
The story of the researches and efforts to discover a reliable
and safe ana'sthetic does not differ from that attending the
introduction of all great epochs. Repeatedly the di.-covery
was announced and the prize seemed won, only to be followed
by a disa])pointment the more depressing because so often
repeated. Indeed, these disappointments had so crystallized
professional opinion against the possibility of di.«covering a
safe and reliable ana-sthetic that on the very eve of its announcement the most eminent surgical authority of tlie period,
Velpeau, thus voiced the ])revailing .sentiment of the profession (1839) :
To escape pain in surgical operations is a chimera which we
are not permitted to look for in our day. A cutting instrument
and pain in operative medicine arc two words which never present themselve's. the one without the other. In the mind of
patients, and it is necessary for us surgeons to admit their
association.
It is creditable to the profession that the cliief otistncle to
an earlier discovery of a safe and reliable ana'sthetic was the
fear of fatal results in making the necessary tests on human
subjects. l?icc. author of the " Trials of a I'ublic Henefactor."
remarks :
It Is probable the deadly results which must have often ensued
from their use, the long-continued depre.islon which they exert
upon the nervous sy.sleni, the confirmed stupor and the congestiona and other accidents which are so liable to follow, all conspired to prevent their use, or even examination.
The only interesting feature in the centuries of search for
an anesthetic relates to the incidents by which the inhalation
276
[No. 343
of nitrous oxide gas (laughing-gas) led to the discovery of
scientific ansesthesia. In 1799, Sir Humphrey Davy, then au
assistant in the " Pneumatic Institution " of Dr. Beddoes,
Penzance, England, experimented with nitrous oxide gas and
described in a familiar way its exhilarating and intoxicating
effects. He even used it for the relief of pain in the head and
teeth and finally suggested its possible use in surgical operations :
As nitrous oxide in its extensive operations seems capable of
destroying pliysical pain, it may probably be used with advantage
in surgical operations in which no great effusion of blood takes
place.
The suggestion of Davy was so natural that it is surprising
that nearly half a century elapsed before the subject again attracted attention, though nitrous oxide (laughing-gas) was
in popular use for amusement in social circles.
The circumstances attending the actual employment of
nitrous oxide to allay the pain of a surgical operation not only
fulfilled Davy's prediction, but gave to our country the great
honor of discovering a safe and reliable ana?sthetic and also
of placing anaesthesia on a scientific basis.
Dr. Crawford Williamson Long (1815-1878) of Danielsville, Ga., a graduate of the medical department of the University of Pennsylvania, was impressed, while attending an
exhibition of "laughing-gas," with its power of causing a harmless delirium, and ventured to test its effects personally. In
his performances under its influence he received a painful
injury of his leg of which he was not conscious until he had
recovered from the effects of the gas. Like Davy he became
imbued with the idea that surgical operations might be performed without pain while a person was in this state of delirium. Long seems to have been a very unpretentious practiser of his profession in a small rural town quite remote from
even the current medical topics. He engaged in general practice
and performed all the surgical operations that came under his
observation. In 1842 he first operated on a patient under the
control of nitrous oxide and removed a tumor from the neck
of a lady without pain. Subsequently he used this gas in his
operations but did not think the method of sufficient importance to publish an account of it until the question of priority
of discovery of an antesthetie became the subject of Congressional inquiry on the petition of Dr. W. T. G. Morton, of
Boston, 1847.
In 1844 nitrous oxide attracted the attention of Horace
Wells, a dentist of Hartford, Conn., in the same manner it
had Davy and Long, while being used as a " laughing-gas."
AVells tested it by having a tooth extracted while under its
influence and on returning to consciousness, exclaimed : " A
new era in dentistry." He adopted it in practice and related
his experience to Dr. W. T. G. Morton, a dentist of Boston
and former partner in business. Morton was an enterprising young man who recognized the importance of the new
treatment, if it really proved to be capable of accomplishing
the objects claimed. He, therefore, thoroughly tested it and
became convinced of its value in the practice of dentistry, the
logical result of this conclusion being that it would prove
equally valuable in the field of operative surgery. To test this
question by high authority Morton applied to Dr. John
Collins Warren then at the head of the surgical staff of the
Massachusetts General Hospital. The day fixed for a trial
operation was October 16, 1846. The operation was advertised
widely and a notable gathering of the most distinguished
members of the profession in Boston and vicinity was in attendance.
Prior to the date of the operation Jlorton had been advised
by a chemist. Dr. Jackson, that sulphuric ether had the same
effect as nitrous oxide and was more manageable. Accordingly
Morton prepared to give this gas which occasioned a few
minutes delay in his arrival at the hospital. This delay was
construed by the skeptics in the audience as a complete failure
of Morton to meet the test, and when he appeared a few minutes
later he was greeted with derisive laughter. Even Dr. Warren
had apologetically informed the audience that he had little
faith in the alleged anEesthetic.
The operation, the removal of a vascular tumor of the neck,
was a complete success. A profound silence fell upon the witnesses of a great epoch in surgery as Dr. Warren declared in
homely phrase, " Gentlemen ! This is no humbug." This
announcement, heard around the world, ushered into human
history the great epoch — Anjssthesia — freedom from pain in
the practice of operative medicine.
ASEPSIS
1867
The discovery of a safe and reliable antesthetic seemed
to cut the cords which restrained the progress of operative
surgery and this branch of practice went forward in leaps
and bounds. Medical periodicals were filled with descriptions
of new, unheard of, and even unthinkable operations, and the
clinics became interesting for the novelty of the operations
and the perfection of details, now so much more carefully
completed.
THE ANTISEPTIC PRINCIPLE
1867
But important as was the reform in the manual of the operation, it was painfully apparent that in the final summary of
results the mortality of operated wounds had not diminished.
The chief element of disaster, suppuration, still remained in
full force and determined by its relative intensity the final
result. Of this fact I had an opportunity for ample experience. On entering the Bellevue Hospital Resident Staff
(1850) my duty as the junior member was to carry the
" pus-pail," the receptacle into which the senior surgeons
placed the pus-saturated dressings. Two and often three
times daily he had to renew these dressings, each change attended by great suffering and exhaustion. I vividly recall
our painful disappointment on witnessing the gradual failure
of the vital powers of patients with such an outflow of pus.
Daily the visiting surgeon examined the pus to see if it was
not becoming " laudable " and pressed iron tonics, but the final
result was general infection.
Septembeh, 1919]
277
From the time of Hippocrates there were two scliools of
surgeons based on the question of the treatment of wounds
with and without pus. Althougii pus was almost universally
present in healing wounds, still there were occasional instances
where the wound healed witiiout any discharge, but remained
dry throughout the process. This incident gave rise to two
methods of treatment, the " dry " and the " wet," the former
being our healing by " first intention,'" and the latter by suppuration or granulation (second intention). Though the
intuitive genius of Hippocrates led him to teach healing by
the " first intention," as the correct practice, he was violently
opposed in the schools of Greece, and the '"wet" treatment
prevailed, its advocates regarding it important even to apply
irritating dressings when pus was not freely secreted. These
two schools continued to our time, the " wet " method being
generally taught in the colleges and practised in the hospitals.
Pus was not regarded as injurious to the wound except when
of unhealthy quality and it was the quality, not the quantity,
that interested the surgeon. Good pus was thick like cream
and was called " laudable pus " ; it was thought to indicate
healthy healing. Practically we had a continuation of the old
controversy of the healing of wounds by " first intention,"
the " dry method," or by suppuration, the " wet method."
Lister's series of experiments by which he demonstrated
the element in pus which renders it prejudicial to the healing of
wounds, and the discovery of an etTective remedy by which
that element can be rendered inert from the moment of operation, are the most brilliant in the annals of science. Impressed with the fact that he had a mortality of 45 per cent
in his cases of amputation, though great care was exercised
to protect the wound, his mind recalled Pasteur's theory that
microorganisms arc the cause of putrefaction and that in his
observations putrefaction was present only when there was
suppuration. He at once began experiments to test the truth
of the theory of Pasteur by employing such agencies as he
could command to destroy any germs present and still not
harm the wound. He was finally led to the use of carlwlic acid
which proved satisfactorv'.
Lister began his experiments in ISC).! and priiilcd his first
])aper entitled. " On the Antisejitic Principle in the Practice
of Surger}-." in 1S(!7. No one but a contemporary of that
period can realize the storm of criticism and ridicule wiiich
greeted the author of that paper. He was accused of not iwing
original in his work : of not obtaining k'tter results than the
old method of practice; of rendering operations tedious; of
employing childish and ridiculous apparatus and dressings.
Lister answered his critics by the performance of new and
more incredible operations without pus or fever and in the
meantime ini[)roved the details. His reported excision of a
knee-joint. ISTS. and wiring a fractured patella. 188:?. without
suppuration, brought to a climax the amazement of older
surgeons at his jiretensions. liut what aitpcaled to the elders
as recklessness inspired the juniors with a commendable desire
to test the truth of his statement-s in actual practice. I introduced the practice into the wards of Bellevue Hospital greatly
to the disgust of many of my colleagues who refused even to
visit the wards where the patients were under treatment.
I had the satisfaction, however, of a visit of Mr. Lister
himself, while on a tour in this country, who generously commended my work and in his autobiography gives me the credit
of introducing asepsis.
On visiting Lord Lister at his London residence in 1894,
I found him quite pessimistic as to the then state of asepsis.
He remarked that he believed true asepsis was rarely practised. " Why," he said, " I was in Berlin a few days ago and
at the urgent request of friends attended the clinic of a noted
a.*eptic surgeon. All his methods were excellent but on becoming confused in the operation he stopped, scratched his
head, and completed the operation without sterilizing his
fingers. That was an infected wound and its suppuration will
be attributed to the failure of asepsis."
On relating this incident to a former house surgeon to
Lister's ward while he was experimenting with diU'erent
agents, he said : '" Lister was very much subject to pers])iration especially when intently engaged in an operation, and I
have often seen the sweat of his face fall into the wound
without attracting his attention." Lister's great success, even
under such unfavorable conditions, depended, probably, upon
the thoroughness with which he finally applied disinfectants,
for he dwelt especially upon that feature of aseptic treatment.
AX.KSTHESIA AXU ASEPSIS
18G7
With the introduction of asci>sis into practice the art,
operative medicine, became a true science. The entire process
was governed by rules which ensured success. Compare Lister's statement that his best results in amputations showed
a mortality of 4-5 per cent in 18C4-18GG by the best methods
then in use, with a recent report of a hospital in New York
that in fifty consecutive cases of laparotomy, involving many
varieties of intra-abdominal affection, 100 per cent of the
patients made a good recovery.
It was very gratifying to me to learn of the following incident which occurred at the Bellevue Hospital recently where
pus reigned supreme prior to 1867. A professor in one of the
medical schools wished to exhibit a specimen of fresh pus to
his class and naturally directed the messenger to apply at
Bellevue Hospital. On making his errand known he was
informed that pus in operation wounds had long since disappeared from the wards. Prior to the year 18G7 healing by first
intention in that ho.spital Mas neither expected nor .sought
by the surgeojis. One of the most distinguished operators
merely brought the surfaces of tiie wound together with
adhesive strips and placed the wound in such a position that
the pus would flow into a vessel, thus avoiding tlie necessity of frequent renewal of the dressings.
Now all is changed. Healing by first intention is always
sought and the presence of pus in operation wounds is a severe
reflection upon the care and skill of the staff in charge. But
perhajts the greatest and most l)eneficent result of the im
378
[No. 343
proved methods of treatment in operative surgery in this
ansesthetic-aseptic era is the rapid convalescence of patients.
The operation which formerly was the beginning of the end,
owing to the exhaustion due to the suppuration which ensued,
is now the beginning of a rapid convalescence. The feeble,
nervous sufferer whose heart nearly ceased its action on the
thought of an operation now approaches the operating room
with a firm stej), a normal pulse, and mounts the table with a
smile. As operations under the old-time system were illustrated by the description of concrete cases, the vast improvement effected by the combined methods of ana?sthesia and
asepsis will be most thoroughly appreciated by a similar report of cases treated according to the principles established
by these great epochs.
A young woman, aged 18, had suffered from a suppurative
disease of the knee-joint five years, and was reduced in vitality
to a helpless state. Her fear of an operation rendered her
nervous system so sensitive that she had attacks of fainting
when an operation was mentioned in her presence. And yet
delay of an operation seemed more dangerous than its possible
fatal results. A medical friend suggested the preparation for
the operation be made in an adjoining room and he would visit
her as chaplain and induce her to inhale chloroform to unconsciousness when she could be quietly removed to the
operating table.
The ruse worked admirably. The patient was delighted
with the perfumery, as the physician called it, and required
but three or four inhalations to become insensible. Excision
was performed, requiring an hour to complete it and its
aseptic dressings, but her pulse continued good under the
influence of hypodermic injections of heart stimulants. For
several days she was in ignorance of the operation and was
surprised that she had no longer pain in the knee but occasionally in her toes. One morning she saw a spot of blood on the
sheet over the knee and was greatly alarmed as she had been
told there was danger of fatal hemorrhage. On being assured
that there was no danger and that the operation had been performed and she was recovering, she became frantic with joy. A
vigorous appetite now developed and with freedom from pain
and refreshing sleep, her rapid recovery was daily noticeable.
The first dressing mad-e was on the twenty-ninth day and there
was only slight yellow staining but no pus. She had gained
eight pounds in weight.
The following incident led me to adopt a method of anaesthetizing very feeble patients which has proved very serviceable. I was aiding a colleague in an operation for cancer of
the breast on an old lady who was very fat, with a feeble intermittent pulse and nervous excitement. She had been prepared
in the usual way with purgatives and simple diet. She had
taken but little ether when her face became purple, her pulse
disappeared and after a struggle to restore her she was pronounced dead.
It happened that I bad a duplicate of this case on which I
was to operate on the following day. I was so shocked by
this experience that I delayed the operation and studied the
situation. The result was the conclusion that probably these
patients' feeble and intermittent heart-action was due to overlaying and interstitial fat and required supporting rather
than the depressing treatment then employed. Though this
indication could be met by hypodermic heart stimulants 1
recalled two facts that determined my course, viz.: (1) Larre)',
in his memoirs of the Napoleonic wars advised operations on
soldiers while they are drunk, for they neither fear nor feel
pain, and (2) hot milk is a quick nutrient and sustains a weak
heart. Here were the remedial agents which my patient
required to prevent fatal collapse.
After preparatory treatment I directed that at 8 o'clock
on the day of the operation which was at 3 o'clock, the patient
should receive one ounce of hot whiskey in a glass of hot milk,
and the same must be repeated at 10 and 13 o'clock unless
she was much disturbed. On visiting my patient at three
o'clock on the day of the operation I found her in a most
satisfactory condition. She had not required the stimulant
the third time, having become quite excited about the details
of the operation which had taken fantastic forms in her enlivened but disordered imagination.
On entering the ward she greeted me with some affectionate
tenns, expressed her delight that the operation was about to
be performed and wished she could see the medical students
present. Her face was flushed, eyes suffused, skin warm and
her pulse full and regular at ninety-six. She came under the
influence of the anaesthetic without a struggle and required an
amount estimated at one-tenth that ordinarily given, the whiskey having already secured partial anaesthesia as Larrey suggested when he ordered wounded soldiers to be operated on
while drunk. The pulse remained at ninety-six during the
time occupied by the operation and the application of the
aseptic dressings. She made an unusually rapid recovery,
the pulse continued at ninety-six for several days; her appetite became vigorous ; her happiness that the operation was over
was extreme. But one dressing was employed and when it was
removed there was no sign of pus and only the yellow staining
of serum.
During the many years that I have used tliis anaesthetic, hot
milk and whiskey, I have not seen a patient fear an operation,
nor suffer from shock or collapse.
I trust these desultory reminiscences of the introduction of
the two greatest epochs in human history may lead us to a
proper appreciation of the labors, trials and skill of the surgeons of the pre-an£esthetic period, who amid the heartbreaking screams and uncontrollable struggles of patients
devised and successfully performed the great operations wliich
adorn the annals of surgery.
There is a profound truth in the remark of the historian,
that " such knowledge widens the horizon, for a glauce into the
past, and an insight into the present of human activity, deepens
the view for a comprehension of the ideas which guided the
earlier and more recent physicians, and gives on the other hand
to our daily professional labor a high consecration."
September, 1919]
279
NOTES ON THE GROUP OF SYMPTOMS DESIGNATED AS EFFORT
SYNDROME
Bv E. W. Bridgmax,
Instnirliir in Mnlirine. The Jolt us Ihipkit'.-' Medical ^School (Itecerilly ( 'iijitinii, Meilical Corps. ('. .S. Ariiii/ )
A little less than three years ago, when the stage was being
set for the comedy entitled " The Second Mexican War," the
writer was called into military service and assigned to the duty
of physically examining the Maryliuid militia before its federalization. It was his first experience in the examination of
large numbers of men and several interesting lessons were
forthcoming which were later to prove most valuable. In the
first place, an opportunity was afforded to appreciate the wide
range of what may fairly be called the norm of the cardiovascular system. The prevalence of apical and conus systolic
nmrnmrs. the presence of short, scratchy, systolic murmurs
near the sternum, the intensity of the second sounds at the base
of the heart and their relation to age, third sounds, presystolic
snunils, sharp clicks heard only in systole near tlie apex of tlu'
heart, tlie relation of posture to the jwsition of the apex — all,
witii many other variations, are subjects well worth individual
discussion, which may be dismissed here with the remark
that for a proper valuation of such findings a competent knowledge of the normal is indispensable. Secondly, the variation in
the pulse-rates of healthy individuals was noteworthy, and the
dependence of this rate upon the condition of the mind and
body was emphasized. Thus, tachycardia might be foimd in
certain healthy young men who, having been told by a physician
that they had heart trouble, did not believe they could pass
the examination ; or, again, men suffering from venereal infection and fearing its discovery might show an increased pulserate. Confirmed neurasthenics, a few men who had been
forced into sen-ice by the jilws of their friends, those who were
doubtful of their right to expose dependents to the charity of
the world, any of these soldiers might appear for examination
with a rapid heart. The association of certain organic physical
diseases generally of an infectious character with tachycardia
waa constantly exemplified in the men with early or outspoken
tuberculosis, bronchitis, or even with furunculosis.
A mentiil note was made of the high percentage of infected
gums and carious teeth among the otherwise healthy and welldeveloited farmers, while the underdevelopment of the clerk
group of the city men was conspicuous. One company having
been re<-ently organizetl in the vicinity of the m<)l)ilization
camp was still below the numerical standard, and on the day
before the examination, its officers, dependent for their positions upon the acceptance of the company by the anny. collectetl a lot of young l)oys to supply the deficit. These lads
claimed 18 years, but many of them were evidently younger.
During the three weeks of my duty at this camp, quite a
number of men appeared at the hospital for re-examination
because they were unable to perform their daily tasks. Many
were young boys, a bit shaky, a little short of breath, with
acro-cyanosis of the extremities, sweating freely, and often
complaining of sharp pains which they localized in the precordial region. A second physical examination, less hurried,
disclosed nothing further of importance and it seemed that
one was witnessing the attcm])t of a youth to do a man's work
and the subsequent natural exhaustion. At the same time,
others, many of whom had i)cen noted as underdevelojjed on
the first examination, returned with similar complaints — they
also had given out.
The rest of the summer was spent at the Artillery School at
Tobyhanna where the Yale batteries and a few national guard
organizations were training. During this period a few men
were brought up for examination because they had not been
able to stand the hard work — they had become irritable, did
not get along with their fellows, and had lost weight. During
the examination, they were apt to be a little shaky, the perspiration would roll down from their arm-pits, although the
weather was comfortably cool; some degree of tachycardia was
generally noted, and in response to slight exercise the rate
would become excessive. Some of the soldiers had, in the
course of the summer, slight attacks of tonsillitis or average
colds of a few days' duration. It was interesting to follow
these men. Whereas some of them went back to duty after a
few days in the hospital and soon forgot their illness, others
would remain below par for several weeks and have difficulty
in doing the work that had caused them no discomfort before
they had become sick. A few men showed a sensitive vago.sympathetic balance, and were apt to faint in the ranks during
a protracted muster. The different vaccinations were administered at this camp, and it was not infrequent to have in line
husky, strong soldiers who were obviously afraid — the skin
cold and clammy, with rapid heart and panting res])iration.
Others, i)latantly brave, would faint from the prick of tlie
needle.
The result of the .summer's work was an aijjircciation of the
infinite variations that arc to be found among individuals —
the variation in the sensitiveness of their reflex arcs, the variations in their bodily and mental reaction to physical and
p.sychical trauma and so fortli. Indeed each individual is so
different in his bodily make-up and in his reaction to out.-iide
stimuli that the normal is very difficult to delineate and
standardization becomes |)ractically imjiossible.
Some of you have taken part in athletics at college, and will
recall |)crsonal ext)erienccs similar to those that the writer
himself remembers. Often, immediately before a footl)all
game or his race in a track meet, he suffered what now sometimes comes l)ack in the form of a nigl^tmare. Although, in
excellent physical condition, he would go out on the field all
Btremble, with his heart racing and trying to l)eat its way
throu^rh the chest, breath short and insufficient l)ecause of
280
[Xo. 343
a suffocative band that seemed to constrict the lower thorax
and to prevent the ingress of air. Occasionally, after some
particularly inspiring speech from a well-wishing alumnus, he
would go out sweating profusely, with involuntary micturition,
and even crying. The actual start of the game was always
suflBeient to bring back the normal functioning of the body.
Again, you may remember your own condition or have seen
others at the end of a short period of extreme bodily exertion, as
at the end of a hard race for a quarter of a mile. Some men become pale with slight bluing of the mucous membranes, the
cheeks sunken, trembling, occasionally fainting; others quite
purple with puffed cheeks, watery eyes, nauseated even to vomiting, and often with blood-tinged sputum — both groups representing the signs of acute fatigue, the result of extreme
exertion.
How often in the course of a wearing season does the coach
tell one of his men that he is overtrained ! The man is irritable, has lost weight, is not sleeping, his pulse-rate is sensitive
to slight exertion, he is constantly sweating in cool weather,
his general physical strength is decreasing, and he cannot
approach his average record; while his team-mates are doing
well and are improving under exactly the same work. Eest
and a change of scene may soon return the overtrained man to
his former condition, but the trainer has been to blame for the
loss of time ; he was treating all his athletes according to one
standard, and this cannot be done with success. It is generally
known that the captain of an athletic team is rarely so good
during his tenure of office as he was the season before when he
did not have to worry about the condition of the whole team in
addition to performing his own individual work. It mav even
become necessary to send such a man away to continue his
training by himself.
Experience in the training of track men develops the opinion
that there are two outspoken tj-pes of athletes with nmnberless
gradations between, the one capable of supreme concentration
of energy for a short period of time, the dash man, the other
slow-going and very resistant to fatigue ; the former nervous,
high strung, the hyperthyroid type, the latter steady and
plodding, a successful long-distance runner. The training of
the two groups should be quite different. The training of the
sensitive dash man is always difficult. His work reflects his
mental attitude^ and the worry of a failure in recitations will
be recorded by the reduction in his speed, whereas the phlegmatic distance runner plods along comparatively uninfluenced
by his surroundings. Reverse these men, and the long-distance
man is a failure in the sprints and the dash man will not only
be unsuccessful in his new work but may also develop typical
signs of efort syndrome.
One more observation from the field of athletics. Perhaps
some of you have gone back some time after you left college,
and have been asked by some enthusiastic coach to change your
clothes and line up on the scrubs or to take out the hurdlers and
show them some of the fine points of that race. All of us hate
to admit that we are getting old, and perchance you have tried
to do what you could. Just one such attempt may teach you
the symptoms of effort syndrome and, in that event, you become
very sympathetic towards individuals suffering with this condition. The writer attempted such work within a few years
of active athletic participation, at a time when he was in fair
condition from tennis playing. Pride kept him from acknowledging failure before the crowd, and he kept up his unusual
exercise for an hour or so ; but for days afterwards he felt the
effects — not only stiffness, but shortness of breath, untoward
pulse acceleration, trembling, and precordial pain on slight
exertion.
The same general reaction may be experienced during convalescence from even a slight infection. Those of you who
have had influenza appreciate the long period that may elapse
before you can comfortably perform your daily tasks. A
physical examination may reveal no abnormality, but short
walks are very tiring, and any continued mental labor is
exhausting. Protracted asthenia after tonsillitis or slight colds
is not infrequent in the medical dispensary.
It is an interesting fact, in this condition, that, bar an
untoward accident such as an embolus or a ruptured valve,
athletes or patients convalescent from acute disease never die
during the period of activity. The will-power of individuals
varies, and some men endure discomfort and withstand bodily
punishment to a greater degree than others, but the limit in
every case is always short of complete exhaustion of any organ
of the body. This fact is intimately associated with some sort
of protective mechanism of which the nervous system plays an
important part and in wliich the resulting physical signs are
manifested to different degrees as well as in different ways.
These observations serve as examples of conditions in which
the symptom-complex called efort syndrome may obtain. Suggestions are made which point to a similarity of these signs to
those manifested by the body in fear and in acute exhaustion.
In June of 1917, the writer was sent with The Johns Hopkins Unit to France where he was stationed for eight months
in a base hospital. Here several facts were generally appreciated. The preliminary physical examination of the early
recruits had been unsatisfactory, and for a while many of the
patients were men who should never have been admitted to the
service. There were not a few examples of dementia precox,
constitutional inferiority, grave neurasthenia, besides organic
physical diseases. Many of these men showed, in addition to
the signs peculiar to the individual organic disease, sym])toms
comparable to those already described. Then there were
soldiers who had had no previous training, and who broke down
under the strenuous physical demands which were especially
exacting in the face of the poor housing facilities and unsatisfactory hygienic surroimdings. There were cases of tuberculosis, infectious arthritis, horrible teeth, old infected tonsils,
and similar chronic infections, and many of these men showed
the same excessive reaction to exercise. iMany soldiers who had
come to base hospitals with acute diseases such as pneumonia,
aciite bronchitis, or acute tonsillitis and who had been discharged apparently well, had returned to the hospital with
symptoms of fatigue on slight exertion. These symptoms were
very apt to be referred by the battalion medical officers to the
cardiovascular system because of the rapid heart or tlie sliortness of breath. Moreover, the lack of knowledge on the part of
Septkmiiek, 1919 1
281
many medical officers of the range of the findings in the normal
heart, cjuised, in face of symptoms so commonly associated
with cardiac disease, a patliological interpretation of conus
murmurs or third sounds, and the [)atient would be told that
he had heart disease. After the wcasional man sulTering from
organic disease had been weeded out and disposed of, and the
better diagnosis of effort syndrome made, it was found that
there was no satisfactory arrangement for the treatment or
disposition of sui-h patients. As the demand for acute beds
increased, some of them would be sent back to duty, while
others would be transferred to other base liospitals where they
would lie around for a few weeks and tlien again be put on the
active list. Or tliey might sigain be regarded as sulFcrcrs from
organic heart disease, be put to beil and given digitalis. After
this treatment, they would generally get out again with their
symptoms made worse, which more tlian ever convinced the
patients that they were suffering from heart trouble which
could not be cured. Such a belief always militated against the
patient being willing to take active exercise.
When the medical consulting staff was established under
tieneral \V. S. Thayer, an effort was made to rectify this
unfortuinite condition and thereby avoid the resulting vicious
circle in transportation, as a consequence of wiiich tliese
.soldiers were spending most of their time in transit to and
from the front line. Convalescent camps were to be established
where treatment could be carried on intelligently, and where
more protracted study of these patients might be made. At
this time the writer was .«ent to England where he was attiiched
to the British Military Heart Hospital which was doing excellent work under the direction of Dr. Thomas Lewis. Here
were to be found the most extreme tyjies of effort syndrome
listed under the British medical nomenclature — disordered
action of the heart. Dr. Ijewis's work was fundamental. He
showed that graduated exercises furnished a method for the
functional testing of individuals and their subsequent classification for different degrees of physical work. This treatment,
furthermore, proved to have an important curative value, so
that he sent many of his patients back to front-line duty. The
British medical corps was unfortunate in not having a psychiatric division, and, indeed, there was no special hospital in
England for the treatment of psychoneuroscs. A patient was
either demented, whereupon he was sent to an insane asylum,
or he wiLs mentally correct. Such treatment a.s could be
accorded the functional mental disorders was, as a rule, oidy
that found in any base hospitjil conducted by a busy staff which
must first meet the demands of the acutely ill. The treatment
for the p.syclioneurotics was just the same as for the cases of
effort syndrome, but this lack of differentiation furnishes one
of the ex[)lanations of the high jjcrcentages of D. A. H. cases
among the British. Dr. Lewis was preaching the gospel
throughout England that these patients were made worse by
l)eing put to bed and being given digitalis; but it was slow
work, and the general lack of knowledge as to what physical
signs of the cardio-va.«cular .system coulil he classified under
the normal was a great handicap to overcome. Moreover, England was short of man power; uuderdevelopcd men had to be
used for front-line duty, convalescence from acute infections
was apt to be too short, and underaged as well as overaged men
were constantly exjw.sed to the demands of campaigning.
Again, his hospital was well away from the firing line, and, as
a result, his patients had passed through a series of base
hos])it^ds before he saw them, and by tiiat time they had l)e(ome
thoroughly convinced, from their diagnosis cards and from
information ol)tained from difi'erent medical officers, tliat they
iiad delinite lieart trouble, whicli, to tiieir minds, was incurable,
("ertaiidy the sul)jective !iym|)toms strengthened that conception, and, moreover, four years of warfare had deprived some
of them of any excess enthusiasm for staying in tiie army if
there were any fair way of getting out.
Dr. Lewis and his staff had made many careful studies of
their patients.' Controlled pharmaeo-dynamic tesfj^ were employed with the following results: Atropin showed no difference between patient and control. Apocodeine generally gave
a greater pulse-rate rise and there was a more marked
cutaneous reaction in the patient group. Amyl nitrite had the
same result. Pilocarpin ])roduced more marked reaction
among the jjatients. Digitalis had no more i)ower to control
the pulse-rate of the patients than of the controls, and the
subjective symjjtoms were uninfiuenced. Adrenalin, on the
other hand, showed that the patients had a definite susccpti-*
bility to this drug so far as subjective symptoms go, but the
rise in pulse-rate and blood pressure was about the same in the
two groups. Another interesting study showed that the
]3atients were ajit to require a longer period after measured
exercise before tlieir pulse-rate lost its increase — five minutes,
often, as compared to two minutes in the average control.
X-rays and electrocardiograms showed no essential difference
in the two groups. All in all, the work suggested that the disorder had to do with the peripheral nerves rather tlian with
the central nervous sj'stem, and there seemed to lie a !iy])ersensitiveness of the sympatlietic with no cliange in the vagal
system.
After a stay of two moiitiis in England, the writer was .sent
inick to France and assigned to duty at Convalescent Camp
Number Two. This camp was the convalescent section for a
large ba.se hospital group, and had a capacity of 2000 patients.
The work was very active and, at first, was complicated by the
considerable amount of organization that was to be expected
in the estai)lishment of a new system. (Jraduated exercises
were instituted under military discipline, so that each ])aticnt
was tested as to his ca|)acity for work ailTl was not discharged
to front-line duty unless he was able to jierform comparable
work. Each patient was carefully studied during his stay and
any indicated laboratory tests were made. Mr)reover, a followup system was instituted wliich enal)icd us to arrive at definite
conclusions alxiut the method of treatment, and (•ontrolle<i the
results.
The writer has sunnnarizccl the first .1000 ca.se-histories, and
some of the findings have a direct liearing on the discussion of
effort syndrome. Ninety-one jier cent of all patients were sent
back to full duty, ami 3 per cent were returned to l)a.«e hospitids
for operation or for treatment wbich would jirobably later
282
[No. 343
admit their discharge in Class A. About 1| per cent of all
cases were reclassified with the diagnosis of effort syndrome.
This group was made up in equal proportions from patients
with varying diagnoses on admission. That is, the effort syndrome cases were found just as frequently among patients who
had had influenza or pneumonia, as among those who had
been gassed. Every patient was especially studied for symptoms of hyperthyroidism. Only three cases of exopthalmic
goitre were found among the 5000 under discussion, and, outside of these, only an occasional soldier showed struma,
adenoma, diarrhoea, or any eye signs beyond a slight von
Graefe. Nearly all the effort syndrome group showed a
slightly accelerated pulse-rate, excessive sweating, restlessness,
and dermatographia. Further signs that might be ascribed to
hyperthyroidism were not conspicuous among these men.
The majority of patients on admission, especially those who
had been suffering from an acute infection, sliowed what might
be called effort syndrome. But these signs, in most instances,
disappeared after treatment, and rarely reappeared after the
patient's return to duty. In this connection it is interesting to
compare the duration of the patients' stay in hospital before
and after the establishment of convalescent camps. The functional test afforded by graduated exercises proved that, in
general, the period which had been allowed in base hospitals
for convalescence was too short. The average case of pneumonia needed eight weeks instead of the five permitted before
discharge; mumps required 39 days instead of 18; herniotomies seven weeks instead of three and a half, and so forth.
In all probability it was to this prolongation of the period
allowed for convalescence that such favorable rejjorts from tlie
" follow up " system were due.''
Of these 5000 cases the diagnosis of anxiety neurosis was
made in 192. It would lead far afield to enter into a discussion of this disorder and its relation to fear ; however, many of
these patients showed symptoms quite similar to those of effort
syndrome. The recovery of these soldiers was very slow,
necessitating, on an average, seven weeks. They needed much
more individual care than did the general run of patients, and
the success of the treatment depended, in large part, upon the
ability of the individual ward doctors to handle psychoneurotics. A good many of them certainly had a psychasthenic
basis, or at least had a weakened will-power. But there, again,
the extremes of normal are hard to mark out, and, moreover,
the degree of psychic shock had been extremely variable. One
hundred and sixty or *3 per cent were sent back to front-line
duty and 4 per cent were returned to the base hospitals for
operations or because the patients had contracted some acute
infection. That is, 13 per cent were reclassified as compared
with the general percentage for the 5000 cases of 6 per cent
reclassified. On discharge many of these reclassified men
showed symptoms of effort syndrome in varying degrees. Of
the 80 patients admitted with the diagnosis of exhaustion,
95 per cent were sent back to the front lines. They had required an average of six weeks in the hospitals and camp, but
after recovery they " carried on " normally in their original
commands. Many of this group had shown signs of effort
syndrome on admission.
Not far from our camp was a hospital devoted entirely to the
treatment of war psychoses. As a result of exchange visits,
the physicians of both places learned to appreciate the similarity of the symjjtoms to be found in both establishments.
In many instances we agreed that the original diagnosis had
depended in large part upon the specialty of the physician who
had first seen the case — the psychiatrist favoring the diagnosis
of anxiety neurosis, the cardio-vascular man, effort syndrome.
At first the psychiatrists had claimed, and jirobably correctly,
that their specialty was fundamentally concerned, but they
became less insistent that such patients should be sent to their
hospital when they came to appreciate that we all were treating
these soldiers in much the same way. Indeed, after the
armistice, when the psychiatrist in charge had issued an order
that no cases of war psychoses should be sent to the states, and
when the disposition of these patients became a problem, the
psychiatrists began to unload on us and we received numerous
soldiers from their hospital with the combination diagnosis
of (1) effort syndrome; (2) anxiety neurosis. We rather felt
that this order of diagnosis should have been reversed, but
such a change would have only started a vicious circle of
transportation wliich, of course, would liave been foolish. It
seems fair, then, to assert that individuals vary as to their
power of resistance to psychic trauma, and that many individuals after prolonged i^sychic trauma may show signs of
effort syndrome.
With this accumulated information, it is interesting to
speculate as to the cause of effort syndrome. Many investigators believe that these patients are suffering from a definite
disease, and are endeavoring to find a single etiological basis.
Probably such efforts will never be successful, and it seems
rather that effort syndrome is a name for a medical wastebasket whose +++++
CONTENTSs must be carefully sorted into etiological
groups. Some of these groups are very easily understood —
those with a definite physical basis. Under this caption appear
convalescents, both those from recent acute infections and those
whose original period of convalescence was so short that tliey
were subsequently returned to the hospital for continued treatment. Effort syndrome after exhaustion seems reasonable, as
does that in association with actual physical disease — tuberculosis, tonsillitis, exopthalmic goitre, and so forth. Another
sample is furnished by hyperthyroidism where, in addition to
the symptoms of effort syndrome, there should be further signs
incriminating the thyroid — diarrhcea, struma, adenoma.
It is possible to conceive of psychical conditions whicli may
induce the symptoms of effort syndrome. Acute fear gives
such symptoms; patients who are constitutionally inferior,
those exposed to prolonged psychic trauma, perhaps another
group — individuals the victims of chronic fear— all of these
patients might be regarded as supplying an etiological basis
fairly well understood. It is certainly true that men, who had
been on the front-line for a year with no discomfort, might
receive a culminating psychic shock that would induce the onset of their symptoms.
There are, however, many cases which are not so easily
understood, and do not seem to belong to any of these different
etiological groups. It is possible that we are here dealing with
September, 1919]
283
the training of track men on a large scale. Just as putting all
athletes to running long distances will develop the symptoms
of effort syndrome, so submitting large numbers of young men
to the protracted training of a recruit, where individuality is
entirely disregarded, will show a number of men wiio give out.
The phlegmatic distance man and the nervous dash man are
fundamentally different people, with different bodily makeups. Til" gradations between the two extremes are limitless.
To designate diseases, names are employed. These niuues
describe maladies which are different, with different etiology,
different pathology and different courses. If this view as to
the multijilicity of etiological factors is conceded, then effort
sjTidrome is no more a correct diagnosis than is jaundice or
tachycardia. To all the names for this condition, which, by
the way. have been applied by cardio-vascular specialists rather
than by internists, to these names — irritable heart, disordered
action of the heart, neuro-circulatory asthenia, effort syndrome — it would be foolish to add others. But it does seem
worth while to endeavor to go back of a prominent symptom
and to attempt a primary diagnosis, and allow the symptomgroup to l»e secondary. At our camp, where we all believed in
the multiplicity of causes, such effort was made, and more and
more we employed siuh combination diagnoses as the following: Protracted convalescence, effort spidrome; exhaustion,
effort sradrome; j)sychasthenia, effort syndrome; an.\icty
neurosis, effort syndrome, and so forth. It is this reason
which prompted the choice of a title for these notes, not effort
syndrome, but the group of symptoms designated as effort
fyndrome.
Just a word as to the pathological physiology of this condition.
What is the actual construction of this protective mechanism? It is not yet evident. Perhaps explanations will be
forthcoming some day from the physiologists. The proces-ses
involved in effort syndrome may well be related to those in
fatigue or fear. Barcroft has shown that patients with effort
syndrome are not benefited by the oxygen chamber — a treatment with the purpi)se of oxydizing any fatigue products that
may have been accumulated in the body. Nor have we, as yet,
any proof that, as in fatigue, there are definite chemical .substances concerned. Other studies suggest that the endocrine
glands play a part, and different hypotheses have been evolved
on this basis. Dr. Cannon's conception of the mechanism of
fear' — an adrenalina-mia due to nervous stimulation of the adrenal glands — is most attractive, and it is very unfortunate for
our peace of mind that his hypothesis has not been substantiated by the work of other investigators. In this connection it
is important to rememlx;r that, while exhaustion in some way is
brought about by the accumulation of metabolic products
together with a depletion of energ}- producing substances, the
initial action of these same substances is distinctly physiological and provides an inerea.«ed capacity of the body for work.
The demarcation between the helpful and the harmful is not
sharp. In the same way. it is not at all impossible that the
symptoms of effort syndrome are the result of a perversion or
an overaction of a normal bodily mechanism.
It is hardly worth while to enter into a discussion of the
thjToid and its relationship to effort syndrome. It is all too
speculative. But it is a fact that nearly everyone has started
out in their work with these patients with the idea that the
thyroid was etiologically concerned. Excluding the definite
cases of exo])thalmic goitre and cases of hypertliyroidism with
actual localizing sjmptoms, it may well be that the thyroid is
concerned with the production of some of the symptoms of
effort syndrome, but there is no investigation yet forthcoming
that has proved it to be fundamental. Treatment, directed to
this special organ, would be symptomatic treatment, and, in a
way, would be comparable to the extirpation of the liver in
cases of pneumonia that show jaundice. The jaundice, in
great part, would be cured, but there would be no improvement
in the pneumonia.
Wliile it may be that the importance of effort syndrome has
been overestimated, and although it is possible that such a
diagnosis is often a confession of failure on the part of the
examining physician, the discussion is valuable. From it
comes a conclusion which has been well expressed by DaCosta.*
" In bringing this inquiry to an end, I may bo permitted to
point out what I believe to be its chief interest and value. To
the medical officer it may be of service as investigating a form
of cardiac disorder which every severe or protracted campaign
is sure to develop. And, from a military point of view, further,
it enforces the lessons, how important it is not to send back
soldiers, just convalescent from fevers or other acute maladies,
too soon to active work. It suggests that their equipments be
such as will not unnecessarily constrict, and thus retard or
prevent recovery ; that recruits, especially very young ones, be,
so far as practicable, exercised and trained in marches and
accustomed to fatigue before they arc called ujmn to imdergo
the wear and tear of actual warfare, and it exhibits some of the
dangers incident to the incessant and rapid maneruvcring of
troops. True, on a movement executed on the double quick
may depend the issue of a battle ; a forced march may determine the fate of a nation ; and the time can never come when
purely physical considerations can forbid either one or the
other, or dictate how often they may be ordered. But every
commander should be made aware that in so using his men he
is rendering some unfit for further duty, impairing others, and
thus be led to count the cost of the frequent use of such active
movements as carefully as he would the holding of a particular
part of a line or the a.ssault on another." To this excellent
summary, a few personal impressions might be added by way
of conclusion.
1. The effort st/iulrome is not a di.sease entity, but signifies
a variety of symi)toms resulting from different etiological
factors, among which constitutional variation in individuals
should be emphasized.
2. Prophylaxis is important to consider and among helpful
procedures to this end a suflicicntly prolonged period of convalescence is pre-eminent.
3. All recruits as well as convalescents from medical and
surgical conditions should be subjected to competent functional tests before they are sent to front-line duty. Graduated
exercises afford such a method of examination, and act, more
384
[No. 343
over, as a therapeutic procedure, besides ofEering a good basis
for the reclassitication of soldiers.
4. Physicians in their constant thought uf the pathological
are often not thorough]}' appreciative of the normal findings
of, especially, the cardio-vascular and nervous systems.
5. The effort syndrome represents findings of varying and
often slight changes from the normal which are by no means
confined to soldiers, but are to be found constautly in the clinic
of every physician.
REFERENCES
1. Medical Research Committee (Dr. Thomas Lewis): Reports
upon soldiers returned as cases of " Disordered action of the
heart " or " Valvular disease of the heart."
2. Bridgman, E. W. : Notes on the duration of normal convalescence. Arch. Int. Med. — to be published.
3. Cannon, W. B.: Bodily changes in pain, hunger, fear, and
rage. Appleton and Co., 1916.
4. DaCosta, J. M.; On irritable heart; a clinical study of a
form of functional cardiac disorder and its consequences. Amer.
Jour. Med. Sciences, 1S71, LXl, 1.
NOTES ON NEW BOOKS
Quarterly Medical Clinics. A Series of Consecutive Clinical
Demonstrations and Lectures. By Frank Smithies, M. D.
Vol. I, No. I. Cloth $2.25, paper $1.50. (St. Louis: Medicine
and Surgery Publishing Company, 1919.)
A large group of physicians throughout the country, especially
those located away from the main centers, have always felt keenly
the difficulty of keeping in touch with up-to-date methods in clinical medicine. To meet this demand, during the last few years a
number of publications have sprung up, devoted to the teaching
of medicine by the method of case histories and clinics. It is with
interest, therefore, that we read the latest offering in this direction — the Medical Clinics of Dr. Frank Smithies.
In criticizing a work of this sort, one should have clearly in
mind the purpose for which it is intended — to aid the student and
the general practitioner. As the writer himself states in the
preface, much of the material is elementary and treated along
simple lines; but. at the same time, we find in these clinics well
presented cases, with concise summaries of modern views as to
etiology and treatment, together with sections on the technique
of diagnostic and therapeutic procedures. Fifteen cases are taken
up in the first volume, which deals mainly with abdominal diseases but also with other conditions. The general plan is well
illustrated by Case 5, an instance of pernicious anemia. The
history, examination and study of the case are first presented,
followed by a section on differential diagnosis, and a discussion
of severe chronic anemias in general, with particular reference
to the changes in the hematopoietic system. Next comes a section
on treatment, with a discussion of methods of transfusion and of
testing the compatibility of the donor's blood. Finally, certain
laboratory methods are given in detail.
The book is attractively gotten up, the material is arranged in
convenient form and there are numerous excellent illustrations
and diagrams. The value of the material would be considerably
enhanced by the addition of a brief index. A. L. B.
Human Intestinal Protozoa in the Near East. By C. M. Wenton
and F. W. O'CoxxoR. (London: John Bale. Sons and
Danielsson, 1017.)
This monograph of 210 pages represents a collection of four
papers which appeared in the Journal of the Royal Army Medical
Corps during the early months of 1917, to which has been added a
fifth section made up of the clinical histories of patients studied
and treated for intestinal protozoa. The authors have carried out
an enormous amount of well-planned work, having studied almost
3000 cases, repeatedly examining many of the patients, and it Is
the result of this work that is reported. It is pleasing to note that
their observations have confirmed almost all of the facts heretofore considered established in regard to protozoan infections of the
intestine, and comforting to one with less experience that even
these observers with such opportunities for studying the problem
must still write, " It is often quite impossible to distinguish
unencysted forms of E. histolytica from E. coli." Section IV
detailing experiments with flies as carriers is most interesting,
indeed startling, and may well be calculated to discourage casual
travel in the regions in which this work was done. For instance, of
two hundred flies caught at random in different localities in Alexandria, in the droppings of fifteen was found one or more of the
following: cysts of E. histolytica. E. coli, Lamblia intestinalis, the
oocyst of a coccidium, and eggs of Taenia saginata, Ankylostoma
duodenale, Trichuris trichuria, Heteroplyes, and Bilharzia. In
another section therapeusis is discussed and the results obtained
are enlightening but rather discouraging. Two intestinal flagellates and an amoeba are described which the autliors believe have
not been described before.
This monograph is a definite contribution to the subject of intestinal protozoa. The authors have used a splendid opporl unity
to good advantage. The subject matter is well presented, it makes
interesting reading, and there is a good index. F. A, E.
The Soldier's Heart and the Effort Syndrome. By Tiiojias Lewis.
Cloth $2.25. (London and Nciv York: Shaw and Sons. Paul
B. Hocbcr. 19 IS).
Dr. Lewis has been the leader in the recognition and treatment
of that recently acknowledged relative of all disease — Effort
Syndrome. At Hampstead and later at Colchester, he taught his
rational and practical views of the handling of heart disease, a
medical condition that accounted for 10 per cent of all discharges
from the British army. This experience and advice he sums up in
clear, straight-forward language in the present book, " primarily
written with the intention of helping medical officers of recruiting,
discharging and pensioning boards, and medical officers in charge
of patients." It has, however, more than a military application, for it discusses the methods of physical examination of the
cardio-vascular system from a somewhat novel view-point.
Many times 1 have heard Dr. Lewis bewail time lost in insignificant discussions of some of the manifold variations of the
text-book pictures of health or disease! Test the patient's ability
to perform exercise, functionally try him out! The arm.v could not
use a healthy heart in a man constitutionally inferior, whereas a
slightly diseased heart in an otherwise healthy body was utilizable. We physicians are apt to overlook this practical problem in
civilian life, and many a patient is consigned to a life of invalidism
because of a heart condition that has been recognized as not
normal. The reserve power of the vascular system is enormous,
and even a badly affected heart can be intelligently managed so as
to satisfy the demands of a controlled life. Perhaps the greatest
lesson in Dr. Lewis's book is a new approach to the old story that
many variations make up the normal. It is rarely possible to
diagnose disease by one finding, and there is a general tendency
to ascribe too much importance to the presence of sounds that are
not encompassed in the regulation " lub-dupp " of the text-book.
Careful physicians may not follow Dr. Lewis in his statement that
accurate delineation of the heart's size by percussion is not possible, but his valuation of test exercise is not too high and is well
worth the careful thought of all medical men. E. W. B.
SJeptember. 1919]
JOHNS HOPKIXS HOSPITAL BULLETIN
285
BOOKS RECEIVED
United States, Navy Department, Bureau of iledicine and Surgery.
Annual Report of the Surgeon General. U. S. Navy Chief of the
Bureau of Medicine and Surgery to the Secretary of the Navy
for the Fiscal Year, 1918. 8=. 267 pages. Government Printing Office, Washington.
United States. Department of Commerce. Bureau of the Census.
Census of the Virgin Islands of the United States, 1917. Prepared under the supervision of Eugene F. Hartley. 1918. S'.
174 pages. Government Printing Office, Washington.
American Oynccologival Society. Transactions. Vol. 43. For the
year 1918. 8\ 480 pages. Wni. J. Dornan, Philadelphia.
American Ophthalmotogical Society. Transactions. Vol. XVI,
191S. 8°. 412 pages. American Ophthalmological Society,
Philadelphia.
A Century of Scieiu-e in America. With Special Reference to the
American Journal of Science, 1818-1918. By Edward Salisbury
Dana, Charles Schuchert. Herbert E. Gregory. Joseph Barrell,
George Otis Smith, Richard Swann Lull, Louis V. Pirsson,
William E. Ford. R. B. Sosman, Horace L. Wells. Harry W.
Foote. Leigh Page, Wesley R. Coe, and George L. Goodale.
1918. S'. 458 pages. Yale University Press. New Haven;
Humphrey Milford, Oxford University Press. London.
The Rockefeller Foundation. Annual Report, 1917. 8°. 377
pages. New Y'ork City.
Guy's Hospital Reports. Edited by F. J. Steward. M. S. and
Herbert French, M. D. Vol. LXIX being Vol. LIV of the Third
Series. 1918. 8". 276 pages. J. & A. Churchill, London.
Quarterly Medical Clinics. A Series of Consecutive Clinical Demonstrations and Lectures. By Frank Smithies, M. D. Vol. 1,
No. 1, January. 1919. 8 = . 188 pages. Medicine and Surgery
Publiahing Company, Inc., Metropolitan Building, St. Louis.
Public Health Reports. Issued Weekly by the United States Public
Health Service. Containing Information of the Current
Prevalence of Disease, the Occurrence of Epidemics. Sanitary
Legislation, and Related Subjects. Vol. 32, Part 2. Nos. 27 52,
July-December, 1917. 8°. Government Printing Office. Washington, 1918.
Rockefeller Institute for Medical Research. Monograph No. 9.
The Use of Blood Agar for the Study of Streptococci. By
James Howard Brown. 1919. 4°. 122 pages. New York.
Surgical Treatment. A Practical Treatise on the Therapy of
Surgical Diseases for the Use of Practitioners and Students of
Surgery. By James Peter Warbasse, M. D. In three volumes,
with 2400 illustrations. Vol. III. 1919. 8°. 861 pages. W. B.
Saunders Company, Philadelphia and London.
Complric Index to Volumes I. II. and III of Warbasse's Surgiral
Treatment. 1919. S'. 123 pages. W. B. Saunders Company,
Philadelphia and London.
Oilbcrtut Anglicu.i. Medicine of the Thirteenth Century. By
Henr>- E. Handerson. A. M. M. D. With a Biography of the
Author. 1918. 8°. 77 pages. The Cleveland Medical Library
Association, Cleveland, Ohio.
Human Infection Carriers. Their Significance, Recognition and
Management By Charles E. Simon, B. A.. M. D. 1919. 8'.
250 pages. Lea & Febigcr. Philadelphia and New York.
Michigan Slate Board of Health. Forty-aixth Annual Report of
the Secretary of the State Board of Health of ilie State of
Michigan for the Fiscal Year Ending June 30, 1918. 8'. 180
pages. Fort Wayne Printing Company, Fort Wayne, Indiana.
1919.
Clinical Microscopy and Chemistry. By F. A. McJunkin, M. A.,
M. D. Illustrated. 1919. 8°. 470 pages. W. B. Saunders
Company, Philadelphia and London.
Essentials of Surgery. A Textbook of Surgery for Students and
Graduate Nurses and for Those Interested in the Care of the
Sick. By Archibald Leete McDonald, M. D. 46 illustrations.
Lippincotfs Nursing Manuals, 1919. 8°. 265 pages. J. B.
Lippincott Company, Philadelphia and London.
Tuberculosis of the Lymphatic System. By Walter Bradford
Metcalf. M. D. 1919. 8°. 216 pages. The Macmillan Company, New York.
The Early Treatment of War Wounds. By Colonel H. M. W. Gray.
1919. 8°. 299 pages. Henry FYowde; Hodder & Stoughton,
London. Oxford University Press, American Branch, New
York.
Lice and Their Menace to Man. By Lieut. L. L. Lloyd, R. A. M. C.
(T.) With a chapter on Trench Fever. By Major W. Byam,
R. A. M. C. 1919. 8'. 130 page;;. Henry Frowde; Hodder
& Stoughton, London. Oxford University Press, American
Branch, New York.
The Operative Treatment of Chronic Intestinal Stasis. By Sir
W. Arbuthnot Lane, Bart, C. B. Fourth edition revised and
enlarged. 1918. 8°. 328 pages. Henry Frowde; Hodder
& Stoughton, London. Oxford University Press, American
Branch, New York.
Surgical Clinics of Chicago. Vol. 3, No. 1. With 75 illustrations.
1919. 8°. 236 pages. W. B. Saunders Company, Philadelphia
and London.
The Whole Truth About Alcohol. By George Elliot Flint With
an Introduction by Dr. Abraham Jacobi. 1919. 12°. 294
pages. Macmillan Company, New York.
.Military Surgery of the Ear. Xose and Throat. By Hanau W.
Loeb, M. D. Medical War Manual No. 8. 1918. 24°. 176
pages. Lea & Febiger, Philadelphia and New York.
Vegetative Keurology. The Anatomy, Physiology, Pharmacodynamics and Pathology of the Sympathetic and Autonomic
Nervous Systems. By Dr. Heinrich Hlgier. Authorized translation by Walter .Max Kraus, A. M.. M. D. Nervous and Mental
Disease Monograph Series No. 27. 1919. 8°. 144 pages.
Nervous and Mental Disease Publishing Co., New York and
Washington.
A Study of the Mental Life of the Child. By Dr. H. Von HugHellmuth. Translated from the German by James J. Putnam,
M. D. and .Mabel Stevens. B. S. Nervous and Mental Disease
Monograph Series No. 29. 1919. 8°. 154 pages. Nervous
and Mental Disease Publishing Company, Washington.
The Anatomy of the Peripheral Serves. By A. Melville Paterson,
M. D., F. R. C. S. 1919. 8°. 165 pages. Oxford Medical Publications. Henry Frowde; Hodder & Stoughton, London.
Surgiral Aspects of Typhoid and Paratyphoid Fevers. Founded
on the Huntcrian Lecture for 1917 — Amplified and Revised.
By A. E. Webb-Johnson, D. S. O. With foreword by Lieut.General T. H. Goodwin, C. B., C. M. G., D. S. O. 1919. 8°. 190
pages. Henry Frowde: Hodder & Stoughton, London.
A TcTt-Book of Biology. For Students In General, Medical and
Technical Courses. By William Martin Smallwood. Ph. D.
(Harvard) Third edition, enlarged and thoroughly revised.
Illustrated with 235 engravings and S plates in color and
monochrome. 1918. 8°. 30C pages. LeLa & Febiger, Philadelphia and New York.
286
[No. 343
THE JOHNS HOPKINS HOSPITAL KEPORTS
VOLTTME I. 423 pages, 99 plates.
VOLUME II. 570 pages, with 28 plates and figures.
VOLUME III. 766 pages, with 69 plates and figures.
VOLUME IV. 504 pages, 33 charts and illustrations.
VOLUME V. 480 pages, with 32 charts and illustrations.
The Miilnrial Fevers of Baltimore. By W. S. Thayek, M. D.. and
J. Hewetson. M. D.
A Study of some Fatal Cases of Malaria. By Lewellys P. Barker. 11. B.
Studies in Typhoid Fever.
By William Osler, M. D., with additional papers by G. Blumer. M. D.,
Simon Flexner, M. D.. Walter Heed, M. D., and II. C. Parso.ns. M. D.
VOLUME VI. 414 pages, with 79 plates and figures.
VOLUME VII. 537 pages with illustrations.
VOLUME VIII. 552 pages with illustrations.
VOLUME IX. 1060 pages, 66 plates and 210 other illustrations.
Contributions to the Science of Medicine.
Dedicated by Ms Pupils to William Henky Welch, on the twenty-fifth
anniversary of his Doctorate. This volume contains 38 separate
papers.
VOLUME X. 516 pages, 12 plates and 25 charts.
VOLUME XI. 555 pages, with 38 charts and illustrations.
VOLUME XII. 648 pages, 12 plates and other illustrations.
VOLUME XIII. 605 pages, with 6 plates, 201 figures, and 1 colored chart.
VOLUME XIV. 632 pages, with 97 figures.
Studies in Genito-Urinary Surgery.
The Treatment of Prostatic Hypertrophy by Conservative Perineal Prostatectomy. An analysis of cnses and results based on a detailed
report of 145 cases. By Hugh H. Young, M. D.
Recto-Urethral Fistulee. Description of New Procedures for their Prevention and Cure. By Hugh H. Young. M. D.
The Early Diagnosis and Radical Cure of Carcinoma of the Prostate, being
a study of 40 cases and presentation of a radical operation which
was carried out in tour cases. By Hugh H. Young, M. D.
VOLUME XV. 542 pages, with 87 Illustrations.
Twelve papers on pneumonia- By Dns. Ciiatard, Fabyan, Emerson,
Marshall, McCrae. Steiner, Howard and Hanes.
A Study of Diarrhoea in Children. J. H. Mason Knox, Jr., M. D., and
Edwin H, Schorer, M. D.
Skin Transplantation. By John Staige Davis, M. D.
Epidemic Cerebrospinal Meningitis and Serum Therapy at The Johns
Hopkins Hospital. By Frank J. Sladen, M. D.
VOLUME XVI. 670 pages with 151 figures.
Studies in the Experimental Production of Tuberculosis in the Genitourinary Organs. Bv George Walker. M. D.
The Effect on Breeding of the Removal of the Prostate Gland or of the
Vesiculae Seminales. or of Both : together with Observations on the
Condition of the Testes after such Operations on White Rats. By
George Walker, M. D.
Scalping Accidents. By .John Staige Davis, M. D.
Obstruction of the Interior Vena Cava with a Report of Eighteen Cases.
By J. Hall Pleasants. M. D.
Physiological and Pharmacological Studies on Cardiac Tonicity In Mammals. By Percival Douglas Cameron, M. D.
VOLUME XVII. 686 pages with 21 plates and 136 figures.
Free Thrombi and Ball Thrombi in the Heart. By Joseph H. Hewitt,
M. D.
Benzol as a Leucotoxin. By Lawrence Selling. M. D.
Primary Carcinoma of the Liver. By Milton C. Winternitz, M. D.
The Statistical Experience Data of The Johns Hopkins Hospital. Baltimore,
Md.. 1892-1911. By Frederick L. Hoffman. LL. D., F. S. S.
The Origin and Development of the Lymphatic System. By Florence R.
Sarin. M. D.
The Nuclei Tuberis Laterales and the So-called Ganglion Opticum Basale.
By Edward F. Malone, M. D.
Venous Thrombosis During Myocardial InsufBciency. By Frank J. Sladen.
M. D., and Milton C. Winternitz. M. D.
Leuk-Temia of the Fowl : Spontaneous and Experimental, By Harry C.
SCHMEISSER. M. D.
VOLUME XVIII. 445 pages with 124 figures.
Fasciculus I.
A Study of a Toxic Substance of the I'ancroas. By E. W. Goodpasture.
M. "D.. and (Ieorge Clakk. M. D.
Old Age in Relation to Cell-overgrowth and Cancer. By E. W. Goodpasture, M. D., and G. B. WiSLOCKi. M. D.
The Effect of Removal of the Spleen Upon Metabolism in Dogs ; Preliminary Report. By J. H. King. M. D.
The Effect of Removal of the Spleen Upon Blood Transfusion. By J. H.
King, M. D.. B. M. Bernheim. M. D.. and A. T. Jones, M. D.
Studies on Parathvroid Tetany. By D. Wright Wilson, M. D., Thornton
Stearns, M. D., J. H. Janney, Jr., M. D., and Madge DeG. Thcblow,
M. D.
Some Observations on the Effect of Feeding Glands of Internal Secretion
to Chicks. By M. C. Winternitz, M. D.
Spontaneous and Experimental Leukaemia in the Fowl. By H. C.
SCHMEISSEII. M. D.
Studies on the Relation of Fowl Typhoid to LeukEemia of the Fowl. Bj
M. C. Winternitz. M. D., and U. C. Schmeisser, M. D.
Hyaline Degeneration of the Islands of Langerhans in Pancreatic Diabetes.
By M. C. Winternitz. M. D.
Generalized Miliary Tuberculosis Resulting from Extension of a Tubercular
Pericarditis Into the Right Auricle. By M. C. Winternitz. M. D.
Acute Suppurative Hypophysitis as a Complication of Purulent Sphenoidal
Sinusitis. By T. R. BoGGS. M. D.. and M. C. Winternitz, M. D.
A Case of Pulmonary Moniliasis in the United States. By T. R. BoGGS,
M. D., and M, C. Pincokfs, M. D.
Gaucher's Disease (A Report of Two Cases in Infancy). By J. H. M.
Knox, M. D., H. R. Wahl. M. D., and H. C. Schmeisser, M. D.
A Fatal Case of Multiple Primary Carcinomata. By E. D. Plass, M. D.
Congenital Obliteration of the Bile-ducts. By James B. Holmes. M. D.
Multiple Abscesses of the Brain in Infancy. By James B. Holmes. M. D.
Gastric Carcinoma in a Woman of Twenty-six Years. By R. G. Hussey,
M. D.
Subdiaphragmatic Abscess with Rupture Into the Peritoneal Cavity Following Induced I'ncumothorax for Pulmonary Iliemorrhage. By R. G
Hussey, M. D.
Heart Block Caused by Gumma of the Septum. By E. W. Bridgeman,
M. D., and H. C. Schmeisser, M. D.
Analysis of Autopsy Records.
A. The Johns Hopkins Hospital. (Table Showing I'ercentage of
Autopsies.)
B. The City Hospitals, Bay View. (Table Showing Percentage of
Autopsies.)
'* The Monday Conferences."
Clinical Representatives on the Staff of the Department of Pathology.
Donation.
Fasciculus II.
The ROle of the Autopsy in the Medicine of To-day. By M. C. Winternitz,
M, D.
Experimental Nephropathy in the Dog. Lesions Produced by Injection
of B. hronchisepticus into the Renal Artery. By M. C. Winternitz.
M. D.. and William C. Quinby. M. D.
Mesarteritis of the Pulmonary Artery. By M. C. Winternitz, M. D., and
H. C. Schmeisser. M. D.
A Clinical and Pathological Study of Two Cases of Miliary Tuberculosis of
the Choroid. By Robert L. Randolph, M. D., and H. C. Schmeisser,
M. D.
The Blood-vessels of the Heart Valves. By Stanhope Bayne-Jones, M. D.
Equilibria in Precipitin Reactions. By Stanhope Bayne-Jones, M. D.
Carcinoma of the Pleura with Hypertrophic Osteoarthropathy. Report of
a Case with a Description of the Histology of the Bone Lesion. By
Stanhoi'E Bayne-Jones. M. D.
The Interrelation of the Surviving Heart and Pancreas of the Dog in Sugar
Metabolism. By Admont H. Clark, M. D.
Congenital Atresia of the Esophagus with Tracheo-Esophageal Fistula
Associated with Fused Kidney. A Case Report and A Summary of the
Literature on Congenital Anomalies of the Esophagus. By E. D.
Plass M. D.
Ectopia Cordis, with a Report of a Case in a Fifteen-Month-Old Infant.
By James B. Holmes, M.D.
Studies in the Mechanism of Absorption from the Colon. By Samuel
Gni.DSCHMiDT. M. D., and A. B. Dayton. M. D.
Report of Two Fatal Cases Following Percy's Low Heat Treatment of
Carcinoma of the Uterus. By V. N. Leonard, M. D., and A. B. Dayton,
M. D.
The Relationship in Typhoid Between Splenic Infarcts and Peritonitis
I'nassnciatorl with Intestinal Perforation. By A. B. Dayton, M. D.
Left Duodenal Hernia. By A. B. Dayton, M. D.
Histological as Related to Physiological and Chemical Differences in Certain Muscles of the Cat. By H. Hays Bullard, M. D.
A Method of Clearing Frozen Sections. By H. Hays Bullard. M. D.
On the Occurrence and Significance of Fat in the Muscle Fibers of the
Atrio-Ventricular System. By H. Hays Bullard. M. D.
Studies on the Metabolism of Colls in vitro. 1. The Toxicity of a-Amino
Acids for Embyonic Chicken Cells. By Montrose T. Burrows, M. D.,
and Clarence A. Neymaxn. M. n.
The Significance of the Lunula of the Nail. By Montrose T. Burrows,
M. D.
The Oxygen Pressure Necessary for Tissue Activity. By Montrose T.
Burrows, M. H.
The Functional Relation of Intercellular Substances in the Body to Certain Structures in the Egg Cell and Unicellular Organisms. By
Montrose T. Burrows. M. D.
Studies on the Growth of Cells in vitro. The Cultivation of Bladder and
Prostate Tumors Outside the Body. By Montrose T. Burrows, M. D.,
J. Edward Burns, M. D., and Yosmo Suzukl. M. D.
The Study of a Small Outbreak of I'oliomyelitis in an Apartment House,
Occurring in the Course of an Epidemic in a Large City. By Montrose
T. Burrows. M. D.. and Edwards A. Park. M. D.
Papilloma of the Larvnx. Report of a Case Treated with Radium with
Resultant Chronic Diffuse Thyroiditis. By William C. Duffy, M. D.
Analysis of Autopsy Records.
Autopsy Statistics.
(n) Bav View.
(b) Johns Hopkins Hospital.
Report of the Photographic Department.
General Improvements.
Donations.
The set of eighteen volumes will be sold, bound in cloth, for $100.00 net.
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Orders should be addressed to The Johns Hopkins Press, Baltimore. Md.
The Johns Hopkins Hospital Bulletins are issued monthly. They are printed ly the LORD BALTIMORE PRESS, Baltimore. Subscriptions, $3.00
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BULLETIN
OF
THE JOHNS HOPKINS HOSPITAL
Entered aa Second-Clan Matter at the Baltimore, Uarj-land, PostofBcc
Aecertaace (or mailing at ipecial rate ol postage provided tor in Section 1103, Act of October S, 1917. Aothorized on Jul7 S, 1818.
Vol. XXX— No. 344]
BALTIMORE. OCTOBER, 1919
IPrlce, 50 Cents
CONT
PAGE
Dr. Howard A. Kelly. Professor of Gynecology in Tlie .Tohns
Hopkin-i University and Uynecologistin-Cliief to The .Tolins
Hopkin.s Ho>|)ital. (Illustrated.)
By TiloM.\s S. CiLLEN 287
Bibliography of Howard A. Kelly, M. D., LL. D., Hon. F. R. C. S.
By MiNMK U'BiGiiT Hlogo 293
Chronic Pemphigus Vegetans of Several Years' Ouration.
(Illustrated.)
Bv Lewellts F. Babkeb and David W. Cabteb, Jb. . 302
ENTS
.Studies oil Blood Sugar. IV. Klfects upon the Blood Sugar of
the Repeated Ingestion of Glucose.
By Lori.s Hammax and I. I. HinsciiMAN ....
Benzine Poisoning, with Report of a Chronic Case.
By RrssELL L. Haden, M. D
The Reaction of Monkeys to the Inoculation of Measles Blood.
By -Andrew Watso.n Seli.aru.s
Xotes on Xew Books, .314
Books Received . 315
30G
301
.1
DR. HOWARD A. KELLY
PROFESSOR OF (rYNECOLOGY IN THE JOHNS HOPKINS UNIVERSITY AND
GYNECOLOGIST-IN-CHIEF TO THE JOHNS HOPKINS HOSPITAL
Bv Thomas S. Cullen
Howard Atwood Kelly was born in Camden, New Jersey, on
Febniary 20, 1858. He received his bachelor's dejrrce at the
University of Pennsylvania in 1877 and graduated in medicine
from the same university in 1882. He settled in Philadel|)hia
and early attracted attention by his marked success in iiandliii^ cases therctofure .<up|)o^ed to l)e inoperable.
During the year 1882-83 Dr. Kelly, while a roi^ident physician in the Episcopal Hospital, built up a remarkably good
gynecological dispensary clinic, demonstrating what might be
accomplished by paying especial attention to this group of
hitherto much neglected cases. After his interneship was completed he began practice in an office on West Front Street in
Philadelphia, and established a modest hospital on D Street
consisting of two rooms on the second Hoor of a two-story
house; Mrs. Wood, the wife of a working-man, taking care of
the patients.
In 1^84 the young surgeon removed his hospital to a threestory hou.-io on Cumberland Street, and a year and a half later
to Xorris .Square to a four-story hou.'se on Diamond Street.
Here the new hospital grew rapidly and became the Kensington Hospital. Established in 1883, it was incor[)orated in
1887, and has been supported by voluntary contributions. At
this period Dr. Kelly took up his residence on Hancock Street
across the square from the hospital.
Dr. Kelly has always been an indefatigable worker and his
e.nrly labors in Philndelfihia, especially in the Kensington
Ifospifal. are vividly remembered to this day. Thus, when an
important post became vacant in the University of Pennsylvania and several men were being considered for the position.
Dr. Osier, when asked whom he favored, replied, " I am
backing the Kensington colt." ' With his characteristic excellent judgment of men, he had picked out Dr. Kelly as a man
of exceptional promise and it was little wonder that a short
time later Kelly was called from the University of Pennsylvania to The .Johns Hopkins Hospital to become its first professor of gynecology and obstetrics.
'Since the above was written the following note has been received by Ijr. Hurd from Dr. Csler;
"The circumstances were these: Goodell had re.slgnod. and
there was no end of discussion as to who should take his place.
On several occasions I had gone to Kensington to see Kelly operate, and 1 happened to mention to Pepper that I had never seen
anylMdy do abdominal work with the same skill. He knew of
Kelly, but had not, I believe, seen him operate, which he Immediately arranged to do. Then one evening at tlie Biological Club,
Horatio Wood and Mitchell were discussing Goodell's successor,
and I said that Pepper and I were backing a dark horse — a Kensington colt. With that. Leidy chipped In with a remark that if
it was young Howard Kelly, his former prosector, he would iMick
him heartily. This is how I remember the story.
•' How extraordinarily successful he has been! Only those of us
who know the work as It was, realize how much the profession
(and the public) owes to such men as Kelly. \
288
[No. 34-t
Kelly went abroad for the first time in 1886, visiting England, Scotland and Germany. Among the well-known men
whom he met were : Brennecke, in Magdeburg ; Sanger, in
Leipzig ; Sehroeder and Martin, in Berlin : Fehling, in Basle ;
Hegar, in Freiburg: Koeberle, in Strasburg; and Berry Hart,
in Edinburgh.
While in England Dr. Kelly attended the meeting of the
British Medical Association at Brighton. Lawson Tait gave
the address on surgery; his topic was gall-bladder surgery.
Kelly was invited to take part in the proceedings of the gjnecological section and reported a case in which he had diagnosed
and removed an unruptured extra-uterine pregnancy. Tait,
who at this period was studying extra-uterine cases, in discussion claimed that the diagnosis was a matter of " expert
instinct " and therefore hardly attainable by the average man.
Kelly in reply pointed out that in his case the signs were:
a definite cessation of the menses, a small tumor to the right
of the uterus, gradually increasing in size month by month
and very tender, followed by a cessation of growth and a
gradual shrinkage; at operation an unruptured right tubal
pregnancy was found. Tait remarked that he did not concur
in the " cock-sure diagnosis " of the young man and made light
of his communication. Thus, early in his career, the future
leader of American gj-necology had an encounter with the
then dominant figure in abdominal surgery in England.
In 1888 he again visited Europe, this time in company with
Hunter Robb and Constantine Goodell. In Berlin he met
Virchow, secured permission to work on cadavers in the
Charite and spent much time in determining from an anatomical standpoint just how the ureters could best be catheterized. From Berlin the party went to Prague and saw
Pawlik catheterize the ureters through the water-filled bladder.
In 1889 he returned to Germany on a still more important
mission. On June 27, he was married to Letitia Bredow in the
Danzig Cathedral.
In 1888 Dr. Kelly was appointed associate professor of
obstetrics in the University of Pennsylvania and held this
position until his departure for Baltimore, in 1889.
In 1889, at the age of 31, he entered upon his duties as
professor of gynecology and obstetrics in The Johns Hopkins
University and as gynecologist and obstetrician-in-chief to
The Johns Hopkins Hospital. At that time The Johns Hopkins Medical School was still a thing of the future, but the
hospital and pathological laboratory were already giving
courses to a large number of medical men and surgeons who
came to do postgraduate work.
In these early days Dr. Kelly's hospital \"ork was limited exclusively to gynecology, for as yet no accommodations had been
.supplied for obstetrical cases. Witli the opening of tlie medical
school in 1893 it became imperative to provide facilities for
caring for obstetrical patients. This branch was gradually
developed by the efforts of Dr. J. Whitridge Williams, and
in 1899 the two important branches, gynecologj' and obstetrics,
were separated and became independent departments. From
then on Dr. Kelly concentrated all his endeavors to the develop
ment of gynecology. Garrison terms Professor Kelly " a recognized leader of his science in America." He adds :
He was a pioneer in the use of cocaine anesthesia (1884), in the
treatment of retroflexion of the uterus by suspension (1887), in
the introduction of the operations of nephro-ureterectomy, nephroureterocystectomy, vertical bisection of the cervix for tumors and
inflammation, and ideal appendectomy; the procedures of aeroscopic examination of the bladder and catheterization of the
ureters, exploration of the rectum and sigmoid flexure, diagnosis
of ureteral and renal calculi by wax-tipped bougies, diagnosis of
hydronephrosis by injection and measurement of the capacity of
the renal pelvis, operation on the kidney by the superior lumbar
triangle, treatment of malignant tumors by radium, and various
improvements in the treatment of vesico-vaginal fistulae. He is
the inventor of the Kelly pad, new rectal and vesical specula, and
his Operative Gynecology (1898) and Medical Gynecology (1908).
both illustrated with Max Brodel's drawings, are full of improvements in the science which have made these books among the best
American Treatises of the time.
He is also known by his valuable historical contributions on
hypnotism, American gynecology, appendicitis, vesico-vaginal
fistula, medical botanists, medical illustration, and American
medical biography (1912). His "Stereo-Clinic" (1910-13) is a
permanent photographic record of recent surgical procedures.
The tendency of recent gynecology to become merged into general abdominal surgery has been wittily signalized by Dr. Kelly
as follows:
" The vital question which now affects gynecology is this: Is
she destined to live a spinster all her days? For we see her on one
hand courted by her obstetrical ancestor, who seeks to draw her
once more into an unholy, unfruitful alliance, destined to rob her
of virility, to be rocked into innocuous desuetude for the rest of
her days' in the obstetric cradle, sucking the withered ancestral
finger in the vain hope of nourishment (with apology for mixed
metaphor). On the other hand, we see her wooed by a vigorous,
manly suitor. General Surgery, seeking to allure her from her
autonomy into his own house, under his own name, obliterating
her identity.'' "
No one connected with Tlie Johns Hopkins Hospital has
written more or has added more to the knowledge of his
department than has Dr. Kelly. A glance at his bibliography
will give the reader a fair idea of the magnitude of his work.
Here it is only possible to mention his more important papers.
The first article from his pen was entitled " Some Eare and
New Anomalies in Man ; with Three Cases of Double Femoral
Artery" (1882).
Among his subsequent papers we find " An Ovarian Cyst
Weighing One Hundred and Sixteen Pounds Successfully Removed "(1885) ; " Hysterorrhaphy "(1886) ; " Extra-Uterine
Pregnancy" (1886); "Asepsis Not Antisepsis" (1886);
'' Csesarean Section " (1888) ; and " Palpation of the Ureters
in the Female" (1888).
In The Johns Hopkins Hospital Bulletin of January.
1890, appears his article on " Hysterorrhaphy." This operation
was a marked improvement on the method hitherto employed
to hold up the retroverted or retrofiexed uterus, and remained
in vogue for nearly 20 years, after which Dr. Kelly himself
abandoned it for the improved method of shortening the round
ligaments — a method which holds the uterus up equally well
^Garrison, History of Medicine, 2. ed.. Phila., W. B. Saunders,
1917, 639-640.
THE JOHNS HOPKINS HOSPITAL BULLETIN. OCTOBER, 1919
PLATE XXXVI
I Hi IIOWAWD A. KKM.V
Professor of Gviucology in Tli.- Johns Hopkins University and Cynerologistin-Chlet
to The Johns Hopkins Hospital for thirty years— from the opening of the Hospital In
18S9 to 1919.
OCTOBEK, 1919]
289
and which is rarely, if ever, followed by difficulties at childbirth.
From his article " The Gynecological Operating Room in
The Johns Hopkins Hospital, and the Antiseptic ajul Aseptic
Bules in Force," published in 1890, we get a pleasant glimpse
of Uie plan of proi-edure followed in the pioneer days of the
hospital. One can hardly realize that at that time after nearly
every abdominal operation a glass drainage-tube was used for
several days and that each day this glass tube was not only
pumped out with a syringe to which a rubber tube was
attached, but once a day the tube was turned around in order
that the omentum might not insinuate itself tli rough the small
holes in it and become fixed.
Dr. Kelly's interest in the \ireteral work continued and in
1892 we find a paper entitled " My Recent Ureteral Work."
In 1892 he devoted much time to the study of the bladder and
ureter and in these investigations he was assisted by Albert L.
Stavelv, William W. Russell, Thomas S. CuUen and John G.
Clark.'
The Bulletin' for 1893 contains the results of his labors
under the title " The Examination of the Female Bladder and
the Catheterization of tlie Ureters under Direct Inspection."
For years he had been catheterizing the ureters with varjnng
success by paijiation, or as he called it by the '' fishing
method." Dissatisfied, however, \vith this relatively blind
method, he decided to put the patient in the knee-chest posture
and introduce a tube into the bladder hoping that this viscus
would balloon out as the vagina does when the speculum is
introduced. This procedure succeeded admirably and he was
able to see clearly not only the ureteral orifices, but also nearly
all parts of the bladder. At once he grasped the possibilities
of this method of studying the bladder and ureters in women
and immediately developed and perfected the necessary instruments. This armamentarium was so complete that hardly
another instrument, vesical or ureteral, has been added since.
To Dr. Kelly alone belongs the credit of not only discovering,
but also of working out in detail this fundamental and important method of gaining an insight into the secrets of the
bladder, ureters and kidneys. The procedure has been adopted
throughout the world.'
Profiting by his experience in distending the bladder with
air when the patient was in the knee-chest posture, he applied
the same principle to the inspection of the rectum, and finding the exposure equally good he had a series of proctoscopes
made. These varied in length and caliber and enabled the
surgeon to inspect the rectum and sigmoid for a distance of
from eight to ten inches and to bring clearly into view pathological conditions that otherwise would have been overlooked.
Proctologists agree that the Kelly method has aided tliem
greatly in the study and treatment of diseases of the rectum.'
In no department of abdominal surgery has there been
greater advance tlian in the handling of uterine myomata.
• A more detailed report of this method appeared In the American
Journal of Obstetrics for 1894.
*"A New Method of Examination and Treatment of Dtaeasea
of the Rectum and Sigmoid Flexure." Annalt of Surgery. 1895.
In the early days of the hospital it was customary to place a
rubber ligature around the growth and then cut the tumor
away. Sometimes the stump would slip through the rubber
ligature and alarming hemorrhage would follow. Many surgeons must be credited with a share in simplifying the
technique of removing the myomatous uterus, but Kelly's " left
and right method " must be regarded as one of the most important advaJices in the simplification of such hysterectomy
cases.'
In The Johns IIopki.vs Hospital Bulletin of 1898 there
appeared an article by Dr. Kelly entitled " The Catheterization of the Ureters in the Male through an Open Cystoscope
with the Bladder Distended with Air by Posture." The
cystoscope wiis similar to his female cystoscope, but a good deal
longer. With this instrument the late Dr. James Brown, a
pioneer urologist, demonstrated catheterization of the ureters
in the male before The Johns Hopkins Hospital Medical
Society.
Probably one of the most practical operations independently
devised by Dr. Kelly was the apron method ' of treating complete perineal tears. I say independently, because in the
Atneri^^an Journal of Obstetrics, 1899, XL, 515, Dr. Kelly
says : " I find, through the kindness of Dr. Chadwick, that
Dr. Wanoii has some time since described the apron method
of treating complete tears and I desire to accord him full
credit."
In 1899 Dr. Kelly digressed to write a paper on "The
Recognition of the Poisonous Serpents of North America."
He had long been interested in snakes and for several years
many of his visitors had entered his library on Eutaw Place
very cautiously, not knowing just what surprise might be in
store for them. No one who was at that memorable meeting
of The Johns Hopkins Hospital Jlcdical Society the night he
spoke on snakes will ever forget the tenseness of the audience ;
some of the brave ones sat up near the front apparently unconcerned, while the more timid migrated to the back seats,
some actually sitting on the backs of the seats. When Dr. Kelly
grasped a large diamond-headed rattler by the nape of the
neck with his left liand, held tiie tail in his right hand and with
the inde.\ finger of his right hand pointed out the more important marks on the snake's head, a shudder ran through the
audience. A sigh of relief was clearly audible when the snake
had been put back into the bag. At this moment, however,
through the bag it bit Dr. Kelly's finger and the audience
awaited breatblessly and in alarm for the after effects.
Dr. Kelly sucked his finger, looked very pale, but went right
along with his talk. In a few minutes the meeting closed and
he returned home none the worse for his experience. A few
hours before the meeting the snake had been teased and had
discharged nearly all, if not all, of its venom.
'For a detailed description of this method soe: "Hysterectomy and HyFtero-Salplngo-Oophorectomy by Continuou-s Incision
from Left to Itlght or from Right to Lett." J. H. H. Buli.ctin,
1896.
"This method was described In the Journal of the American
Medical Association, 1898, XXXT. 1469.
290
[No. 344
In 1899 Dr. Kelly published a timely paper entitled " The
Exploration of the Abdomen as an Adjunct to Every CeUotomy." We now know that when the abdomen is opened it
should be most carefully explored to see that no pathological
lesion has been overlooked. In 1899 few realized liow essential
was a systematic examination of the abdominal cavity.
In 1900 he published another epoch-making paper entitled
" Ureteral Calculus ; its Diagnosis by Means of the WaxTipped Bougie, Escape of the Calculus per vias naturalcs After
Forcible Dilatation of the Ureteral Orifice." Here was a
method that gave positive evidence in the majority of cases
when a stone was present in the iireter and usually when one
existed in the pelvis or in the kidney. At the present day the
X-ray will generally reveal stones in the kidney, in the pelvis
and in the ureter, but every now and then the wax-tip will show
a tell-tale scratch-mark when the X-ray has failed to give any
e-\adence of the existing calculus. The Kelly scratch-mark
method is a most valuable detector of stone ; it is here to stay.
In the past nearly all pelvic surgeons have encountered dense
pelvic inflammatory masses so glued to one another and to the
pelvic wall that their removal has been fraught with the
greatest difficulty. In 1900, under the title " The Removal of
Pelvic Inflammatory Masses by the Abdomen after Bisection
of the Uterus," Dr. Kelly gave us a method that enables us to
handle otherwise inoperable cases.'
In 1910 Dr. Kelly contributed to Surgery, Gynecology and
Oh-^tetrics a paper entitled " Lipectomy, an Operation for
Removal of Redundant Fat from the Abdominal Wall." In
this operation a large wedge of the redundant fat is removed
and the edges of the wo\md in the fat and skin are then
approximated. Wliile this simple operation has given many
a patient physical relief, it has a more important sphere of
usefulness. Take, for example, a patient with a superabundance of fat in the lower abdomen who may have at the same
time a carcinoma of the body of the uterus. In order to expose
the uterus satisfactorily a very long abdominal incision must
be made and the distance from the surface to the pelvis is very
great. By a preliminary lipectomy the thick abdomen is converted into a very thin one at the site of the operation and the
litems can then be removed with comparative ease.
For years Dr. Kelly has been interested in the surgical treatment of cancer and was often troubled by the large number
of inoperable cases presenting themselves in the clinic. He
became impressed by the work of Wickham, who was a personal friend, and within a short time began the use of radium.
He presented a paper on radium at a meeting of the Baltimore
Medical Society, April 11, 1913, which was published in the
Maryland Medical Joui-nal in June, 1913, imder the title
"A Talk on Radium." In Internation-al Clinics in 1914 we
find another interesting article by Dr. Kelly entitled " What
Radium can Do," and in the Journal of the American Medical
Association of the same year, " Radium in the Treatment of
' After publication of tlie approved metliod. Dr. Kelly found that
his procedure had been anticipated by Dr. J. L. Faure, of Paris.
His method, however, was devised without any knowledge of
Dr. Faure's work.
Uterine Hemorrhage and Fibroid Tumors," by Dr. Kelly
and Dr. Curtis F. Burnam. In the Journal of the American
Medical Association in 1915 Kelly and Burnam gave their
results with " Radium in the Treatment of Carcinomas of the
Cervix Uteri and Vagina." In 1918, Professor Kelly contributed to Surgery, Gynecology and Obstetrics a paper entitled " Two Hundred and Ten Fibroid Tumors Treated by
Radium."
From boyhood, Dr. Kelly has been greatly interested in
natural history and in outdoor life and has been particularly
fond of mineralogy. He spent several summers in Mexico
looking carefully into the subject of mining and the extraction
of precious metals. The knowledge thus obtained proved most
valuable when it was definitely determined that there were
deposits of radium in Colorado. Secretary Lane, of the Department of the Interior, was quick to see what an ample
supply of radium would mean to the people of this country in
the treatment of cancer. Dr. Kelly and Dr. James P. Douglas,
of New York, imdertook to extract radium from the Colorado
deposits and Secretary Lane, with wise foresight, placed at
their disposal the best brains of the mining experts in his
department. Professor Joseph A. Holmes, head of the Bureau
of Mines, rendered invaluable service in all phases of the
project.
Dr. Douglas gave his share of the radium thus obtained to
the General Memorial Hospital of New York, and Dr. Kelly's
share came to Baltimore. Kelly and his associate, Burnam,
have five grams, the largest single supply of radium in the
world. The Johns Hopkins Hospital is imder many obligations to them for their liberality in giving free radium treatment to many poor but worthy people who have needed such
jjrocedures at the hospital in recent years.
Let us now turn to the books published by Dr. Kelly. In
1898 there appeared from the Appleton press " Operative Gynecology," in two large volumes, which covered the subject in such
a manner that it instantly commanded the attention of the
surgical world both here and abroad. It was no stereotyped
production; every page breathed the individuality of the
author and portrayed his methods and his ideas. It also embodied the many new and improved operations that he had
devised.
Shortly after Kelly decided to publish " Operative Gynecology " he asked the late Professor Franklin P. Mall where
lie could procure a good artist and received the name of Max
Brodel, who had made excellent illustrations for Professor
Karl Ludwig, the famous physiologist of Leipsic. In 1894
ho secured his services. Brodel took hold with enthusiasm
and with tmusual fidelity pictured Kelly's operative procedures and also the gross and microscopic specimens. Not
only that, he brought into the pictures such a marked degree
of artistic finish that the illustrations elicited unstinted praise.
By this book the professor of gynecology, already well-known,
became the recognized leader in his specialty, and Brodel's
illustrations set a new standard for medical illustrations in the
United States. " Operative Gynecology " had numerous printings and a new edition appeared in 1906.
THE JOHNS HOPKINS HOSPITAL BULLETIN, OCTOBER, 1919
PLATE XXXVII
DR. HOWARD
Dr Kelly at 31. wheii ho entered upun liij. (Uni.^ as ITofessor of
GynecoloKV and Obstetrirs in The .lolins Hopkins Inivpislty and as
CJynecologist and Obstetridanin-Chlef lo The Johns Hopkins Hospital.
October, 1919]
In 1905 there appeared a large volume entitled " The
Vermiform Apjicndix." The authors were Dr. Kelly and
Dr. Elizabeth Ilurdon. This work is a mine of information
and the subject has been considered from every sUnidpoint.
It goes thoroughly into the pathology and describes the operative technique in a lucid manner. Chai)ters on embryology
and anatomy are furnished in large part by Max Brcidel, and
there is an excellent bibliograpiiy. Altogether it is the best
work that has ever appeared on the subject; in fact it is nearly
the last word on the appendix.
In 1906 Dr. Kelly's volume on " Walter Reed and Yellow
Fever " was published. Those who were at The Johns Hopkins Hospital in the early days really felt that Reed belonged
to the Hopkins group. It was there that lie worked with
William H. Weldi ; it was there that we learned to love Reed,
for his unassuming manner, his sterling worth and his delightful companionship. It seems but yesterday that we saw him
at Union Station in Baltimore when he had come down from
his summer home at Blue Ridge on his way to New York,
there to catch the l)oat for Havana to study yellow fever. lu
one interested in the study of yellow fever, in the vicissitudes
in the building of the Panama Canal, and in the life of the
charming and brilliant scientist, this book will touch a sympathetic chord. To those of us who knew Reed it has been an
inspiration.
" GjTieeology and .\bdoniinal Surgery ", by Howard A.
Kelly and Charles P. Xoble, was published by Saunders. The
first volume appeared in 1907, the second in 1908. The
editors wrote extensively on the subjects in which they were
particularly interested and for the remaining chapters were
fortunate in securing surgeons peculiarly well adapted to
treat of their special subjects. The chapters on gynecological
fVitholopy are esfieeially valuable, being written by Dr. Elizabeth Hurdon of the gynecological department of The Johns
Hopkins Hospital. " Kelly-Noble " has had an extensive and
well-merited recognition by tlie profession.
Dr. Kelly's " Medical Gynecolog)' " appeared in 1908. It
was a work of nearly seven liundred pages and was in reality
the counterpart of " Operative Gynecology "; but it appealed
more especially to the general practitioner. It contained much
that was of necessity omitted in " Operative Gynecologj' "; it
has had a wide distribution, numerous printings being required and a second edition in 1912.
In 1909 Kelly and Cullen publislied " Myomata of the
Uterus," a volume of over seven hundred jiages devoted to an
analysis of nearly seventeen hundred cases of ut«^rine myomata
occurring in The Johns Hopkins Hospital and in other hospitals with which the authors were connected. The development of myomatJi, their various degenerations, the condition
of the uterine mucosa and of the adnexa were thoroughly considered, and the various operative procedures necessary were
given in detail. The excellent drawings rejjroduced in this
volume were made by Hermann Becker and August Horn.
Kelly has always been interested in liis fellow-men and
particularly in those who have had a large share in bringing
American medicine to tlie forefront. In jiis operating room he
has had the rare privilege of coming in contact with physicians
and surgeons from all parts of the country. In tlie social hours
following the day's labor the conversation frequently drifted
to a consideration of tiie lives of the outstanding men
both past and present who had lived in the neighborhood of
his guests. As a result he decided to gather in book-form
short biographies of the eminent medical men and enlisted the
hearty co-operation of prominent persons in all parts of the
coimtry who helped him to obtain the names of deceased
physicians and surgeons and often funiislied sketches of tlieir
lives.
The " Cyclopedia of American Medical Biograpliy," comprising the lives of about eleven hmidred eminent deceased
phj'sicians and surgeons from lClO-1910, publislied in 1912,
contains a wealth of material which will become more and
more appreciated as the years pass. In a biography whore
many judges pass upon the names of those wlio shoulil lie
included, some omissions are inevitable. Kelly has for several
years been laboring industriously over a new edition. He has
been most appreciative of the constructive criticism that has
been accorded the first edition, as it has already enabled him to
add a number of biographies omitted in the work when first
published. The American profesison is under many obligations to Dr. Kelly for gatliering together in book-form the life
liistories of the medical men of the past, men of whom tliis
country is so justly proud.
Kelly's " History of Gynecology," found in his " Cyclopedia
of American Medical Biography," is a not^iblo piece of work.
Dr. Garrison says of it: " The best account of American gynecology is the essay by Howard A. Kelly in the introduction
to his ' Cyclopedia of American Jledical Biogra])hy.' "'
One hardly expects to find a surgeon writing on botany or
botanists, but those who have been privileged to spend one or
more sunmiers witli Dr. Kelly in the backwoods of Canada
and have watched ids eiitliusiasm in the study of ])lant and
animal life were not surjirised to see his attractive little book
" Some American Medical Botanists in Our Botanical Nomenclature," publislied in 1914.
Long i)efore Kelly came to Baltimdrc and wliilc hi' was still
laboring in Kensington he was deeply interested in the study
of the bladder, ureter and kidney and from the jireceding
pages we have learned what a large share he has had in the
development of bladder, ureteral and kidney surgery. As the
years went on his interest in this field grew more inten.se and
the results of his experience are to be found in " Diseases of
the Kidneys, Ureters and Bladder, with Special Reference
to the Diseases in Women," brought out by Dr. Kelly and
Dr. Curtis V. Burnam in 1914.
In the early days of the hospital Dr. Kdly Ijccame
acquaintefl with Anthony S. ilurray. an enthusiastic amateur
photographer, who came to the hospital each operating day to
photogra])h the various steps of the o])eration and frequently
the pathnlogical specimens. Mr. JIurray was beloved by every
one who came in contact with him and at once became an im
• Garrison, History of .Medicine, 2. ed.. Plilla., W. B. Saunders.
I!tl7. p. 801.
293
[No. 344
portant member of the happy gynecological family. Many of
his photographs were nsed in Dr. Kelly's early papers and in
articles published by other members of the staff. Mr. Murray
also made many excellent lantern slides which were used in
our teaching courses and at the various medical meetings.
Dr. Kelly, largely as a result of Murray's enthusiasm and
excellent work, became much impressed with the value of
photography as an adjunct in teaching surgery and had stereopictures made, so that students could follow clearly the steps
of the various operations. Finally, he decided that it would
be an admirable idea to have the operations of individual
operators photographed in this manner, and thus started the
" Stereo-Clinics." The work of operators in various parts
of the country has been brought out in stereo-form so that to
date tliere have been 43 sections issued. These have been published by the Southworth Company under Dr. Kelly's direction and have enabled many a surgeon in the quiet of his study
to obtain a clear view of each step in a given operation. The
idea proved most practical and the results have been beyond
Dr. Kell3''s sanguine expectations. In his enthusiastic prosecution of this work he visited many parts of this country and
also England and Scotland in search of interesting and instructive subjects.
One can never forget the delightful evenings of The Johns
Hopkins Hospital Historical Society. In the early days meetings were held in the library of the hospital and later when
the attendance increased, in a large room vinder Ward H. It
was a rare privilege to listen to Osier, Welch, Kelly, and
others who brought with them treasured volumes. After these
had been described and passed around, the speaker usually
gave a short account of the author, of the school with which
he had been associated and frequently of his confreres.
Dr. Kelly thus presented many books and read numerous
papers before the Historical Society.
Among the biographical sketches whicli he lias published
are: "Horatio Keese Holmes," 1897; '".lules Loniaire, the
First to Recognize the True Nature of AVcmnd Infection and
Inflannuation, and the First to Use Carbolic Acid in Medicine
and Surgery," 1901; "James Carroll," 1908; " Frore
Jacques," 1908; "Theodore Caldwell Janeway." 1918;
"Joseph Price," 1918; and "A Tribute to Dr. W. W. Keen,"
1918. Kelly's paper on John R. Yoimg attracted unusual
attention, as few had any appreciation of the fundamental
work that this Marylander had accomplished. Recently
Dr. Kelly gave an interesting paper on Florence Nightingale
and presented to The Johns Hopkins Training School for
Nurses a richly bound volume containing seven of her unpublished letters.
Dr. Kelly has been accorded distinguished recognition both
in this countrv' and abroad. He is an honorary fellow of the
Chicago Gynecological Association; he was President of the
Southern Surgical and Gynecological Association, one of the
most active surgical societies in the United States, in 1907;
President of the American Gynecological Society in 1912 ; Fellow of the British Gynecological Society ; Honorary Fellow of
the Obstetrical Society of London, of the (Glasgow Obstetrical
and Gynecological Society, of the Royal College of Surgeons,
Edinburgh, and of the Royal Academy of Medicine in Ireland.
He is a member of the Association Frangaise d'Urologie,
Paris; of the Societe d'Obstetrique, de GjTiecologie et de
Pediatric de Paris, and of the Gesellschaft der Aerzte in
Wien. He is honorary member of the Societa Italiana di
Ostetricia e Ginecologia, Roma; of the Gesellschaft fiir Geburtshiilfe zu Leipzig, and other societies. He was honored
with an LL. D. by the University of Aberdeen in 1906, by the
Washington and Lee University in 1906 and by his alma
mater, the University of Pennsylvania, in 1907.
Dr. Kelly's generosity has been strikingly shown in his
gifts to The Johns Hopkins Hospital. In 1905 he learned
that the extensive collection of portraits collected by the late
Dr. G. F. Fisher, of Sing Sing, was offered for sale. Fisher,
a medical historian, an eminent practitioner and collector of
books, had also accumulated valuable engravings and portraits
of the leaders in medicine both in this country and in the old
world. His medical library was secured for Vassar Hospital
and Dr. Kelly obtained the large collection of portraits and
engravings and presented them to The Johns Hopkins
Hospital.
In 1897 Dr. Kelly gave to The Johns Hopkins Hospital
the sum of $5000 for a much needed addition to the gynecological operating roem.
In 1901, in order to furnish additional accommodations for
patients recovering from gynecological operations and to
secure facilities for an examining room and laboratory in connection with the gynecological ward. Dr. Kelly, gave to the
hospital the sum of $10,000. For two years Dr. Kelly also
paid the salary of a visiting nurse for the care of patient.«
discharged from the hospital.
Probably the most valuable gift made by Dr. Kelly to The
Johns Hopkins Hospital was that of a choice collection of
books from his library. An extended reference to this gift
appeared in Thk Johns Hopkixs Hospital Bulletin, 1915.
page 415, and is as follows: " During the past year, through
the unparalleled liborality of Professor Kelly upward of fo\ir
thousand volumes of books, periodicals, monographs and theses
from his private library have been presented to The Johns
Hopkins Hospital and placed on the shelves of the library,
ilanv of them, and, in fact, the majority, are books connected
with his own special work in gynecology and obstetrics, and
represent his zeal as a collector while pursuing his special
studies. They include the best treatises upon these important
branches of study in German, French and English, and are
invaluable for the student of medicine and the physician.
They comprise many very rare works also in anatomy, medicine and general surgery, and bear remarkable testimony to
the breadth of the donor's interest in the whole science of
medicine." "
A word of a jiersonal nature is appropriate in such a tribute
as this. Kelly, in his relations with the members of his
hospital staff, has always been most kind and considerate. He
"There are many editions of Avicenna, Boerhaave, Celsus, Falloppio, Galen, Hippocrates, Vesalius; and works of Argelata, Aristoteles, Fracastorius, Haller, Harvey. Malpighi, Rhazes, Spigelius,
Sylvius, and others.
OCTOBEB, 1919]
293
has placed responsibilities upon them and has treated them as
friends and younger brothers ratlier than as assistants. He
has given them material aid in prosecuting studies in this
country or abroad and has often assisted them iu bearing the
expense of the publication of books and their illustrations.
Many of his assistants have spent one or two years as internes,
a year each as second assistant, and first assistant, and iinally
a year or more as resident. Under these circumstances it is
not strange that many excellent men have been developed by
him, who are now occupying prominent places in Baltimore
and in other parts of the country. Among tliese may be mentioned: Hunter Kobb, late of Cleveland; A. L. Stavely, in
Washington ; W. \V. Russell, in Baltimore ; John G. Clark, in
Philadelphia; Thomas S. Cullen, in Baltimore; Otto G.
Ramsay, at Yale (until his untimely deatli) ; Ernest J. Stokes,
in North Carolina; G. Brown Miller, in Washington; G. L.
Hunner, in Baltimore; B. J. Schenck. in Detroit; John A.
Sampson, in Albany; Curtis F. Burnam, iu Baltimore; Henry
T. Hatchins and Stephen Eushmore, in Boston; E. H. Rich
ardson, in Baltimore; E. K. Cullen, in Detroit; Elizabeth
Ilurdon, in Baltimore, and many others.
The activities of Dr. Kelly have not been confined to his
profession. He has been much interested in many problems of
a religious and philanthropic character which have occupied
no small share of his time ixnd thoughts. He has also been a
liberal contributor to many worthy philanthropic and religious
enterprises.
He has taken, as a rule, a vacation of at least two months
everj- year and for many years has occupied a delightful and
simple camp in Canada. Here he has wandered through the
woods, studied wild flowers and mushrooms, has taken long
canoe trips and has maintained his record as a long-distance
swimmer. In this way he has recruited and conserved his
wonderful physical energy.
In his retirement from the active management of the
Gynecological Department of The Johns Hopkins Hospital,
he carries with him the cordial good wishes of his colleagues,
associates, pupils and friends.
BIBLIOGRAPHY OF HOWARD A. KELLY, M. IX, LL. D., HON. F. R. C. S.
PREP.\BED BY
MINNIE WRIGHT BLOGG
I.lllB.Mtl.VN, THK JOHNS HOPKINS llOSl'ITAI.
Dr. Kelly's bibliography covers the i)eriod from 1882 to 1910
inclusive. The lis.") titles include books, pamphlets and journal articles. Most of these are in the Library of The Johns
Hopkins Hospital and are of sjiecial value as gifts from
I>r. Kelly.
1882
Was the thoracic duct injured in tlie case of President Garfield?
(Correspondence). Med. News, PMla., 18S2. xl, SO.
Some rare and new auomalios in man; with tliree cases of double
femoral artery. Am. J. M. Sc, Phila., 1882, n. s., Ixxxili,
138-142.
1883
Uterus septus bicollis. .Med. News, Phila.. ISS.T, xlil. 4U.
On a method of postmortem examination of the tlioracic and abdominal viscera. Through vagina, perineum, and rectum, and
without incision of the abdominal parletes. .Med. News. Phila.,
188.-!, xlii, 733-734.
.Med. News, Phila.,
An Improved attachment for the head-mirror.
1883, xlUl, 390.
On the mapping out of visceral diseases, in an aniline color, on
the surface of the body. (Correspondence). Med. News.
Phila.. 1.S8.!. xliil, 417-418.
The use of oleale of aconltla as a local anodvne. Med. News.
Phila.. 1883, xliil, 702-703.
The occurrence of the Ascarls Mystax (Rudolplii) in the human
body: with a case. Am. J. M. Sc. Phila.. 1884, n. a.. Ixxxvill,
483-486.
The external use of the oleate of aconltla. (Correspondence).
Med. News, Phila., 1884, xllv, 201-202.
Death from a pes.sary. .Med. News, Phila., 1884. xlv, 4.'?0.
On the anesthetic use of the hydrochlorate of cocaine upon parta
of the body other than the eye. Med. .News. Pliila., 1884,
xlv, 713-714.
1885
An ovarian cyst weighing one hundred and sixteen pounds successfully removed. Am. J. Obst.. N. Y. 1885, xvlli, 795-798.
Cocaine in diphtheria. Med. News, Phila.. 1S85, xlvi, 455.
1S8C
A case of removal of two sessile cervical fibroid tumors by abdominal section. Am. J. Obst., N. Y., 1886, xix, 44-49.
Hydro-salpinx with congenital deficiency of tubes and broad
ligaments. Am. J. Obst. N. Y., 188G, xix, 618.
Also: .Med. & Surg. Reporter, Phila., 1886, liv, 712.
Cellulitic contraction of right broad ligament with disappearance
of the meso-salpinx, and coherence of ovary and tube. J. Am.
M. Ass., Chicago, 1886, vi, 677.
Hysterorrhaphy, or the suspension by suture of a viciously posed
uterus. .1. Am. M. .\ss,, Chicago, ISSti, vii, 660.
Also: Med. .News. Phila., 1SS6, xlix, 636.
Ha^matoma of the ovary, with adherent Fallopian tube. N. York
M. J., 1886, xliil, 222.
Also: Am. J. Obst., N. Y., 1886, xix, 503-504.
Extra-uterine pregnancy; complete removal of the sac and +++++
CONTENTSs: recovery. N. Yorl< M. J., 1886, xliil, 617-619.
Also: J. Am. M. Ass. Chicago, 1886, vl, 668-670.
.l/»o; Med. & surg. Reporter, Phila.. 1886, liv, 803-806.
Ovarian tumor that weighed at normal 100 pounds. Maryland
.M. J., Bait., 1886, xv, 49.
Ovaries and tubes from a case of chronic ovaritis; salpingitis and
pelvic peritonitis: also tlie right ovary and tube from a case
of cellulitic contraction of riglit broad ligament witli disappearance of tlie mesosalpinx and rolierence of ovary and tube.
Maryland M. J., Bait., 1886, xv, 49-51.
Also: Am. J. Obst., N. Y.. 1886, xix, 838-841.
A unique ca.se of extra-uterine pregnancy: complete removal of
the sac and +++++
CONTENTSs: recovery. With a critical examination
of the cases of faradic feticide and remarks upon its dangers
by R. P. Harris. .Marvland .M. J.. Bait., 1886, xv, 51-54.
Also: Am. .1. Obst.. N. V., 1886. xix, 841-843.
Asepsis not antisepsis; a plea for principles, not paraphernalia,
in laparotomy. .Maryland .M. J., Bait., 1X.S6, xv, 110-112.
Also: N. York M. J., 18S6. xliil, 672-674.
Also: Am. J. Obst., N. Y., 1886, xix, 1076-1079.
The Munich meeting of the German Gynecological Congress.
(Correspondence). Med. News, Phila., 1886, xUx, 81-82,
294
[No. 344
Gonorrhosal tubo-ovarlan abscess; right side; laparotomy; removal of Fallopian tube and ovary; recovery. Med. News,
Phila., 1S86, xlix, 205-207.
Also: Am. J. Obst., N. Y., 1886, xix, 1169.
The obstetrical section of the British Medical Association. (Correspondence). Med. News, Phila., 18S6, xlix, 276-278.
GynEecological operations in Germany. Med. News, Phila., 1886,
xlix, 301-304.
Hematoma of the ovary, with adherent Fallopian tube. N. York
M. J., 1886, xliii, 222.
1887
Hysterorrhaphy. Am. J. Obst., N. Y., 1887, xx, 33-46.
Perineal and ovariotomy cushions. Am. J. Obst., N. Y., 1887, xx,
1029-1031.
Results of some general work in abdominal surgery, performed
during seven and one-half months of 1886. Proc. Phila.
Co. M. Soc, 1887, Phila., 1888, vlii, 43-50.
Also: Polyelin., Phila., 18S7, iv.
Pelvic measurements. Obst. Gaz., Cincin., 1887, x, 123.
Measuring the conjugata vera. Med. News, Phila., 1887, 1, 277-278.
A contribution to hepato-phlebotomy. Med. News, Phila., 1887,
1, 617-619.
Removal of the uterus through the vagina. Med. News, Phila.,
1887, li, 276-277.
De rhysterorrhaphie (nouvelle operation pour le redressement
de I'uterus retroflechi). [Abstr. transl. by E. Thomas, from:
Am. J. Obst., N. Y.] Gaz. de gynec. Par., 1887, ii, 65-70.
Results of some general work in abdominal surgery, with cases
and specimens. Med. & Surg. Reporter, Phila., 1887, Ivi,
425-429.
A new leg-holder, securing a perfect lithotomy posture without
assistants. Med. & Surg. Reporter, Phila., 1887, Ivi, 747.
Letter from Leipzig. Med. & Surg. Reporter, Phila., 1887, Ivii,
210-211.
Also: Pittsburgh M. Rev., 1887, ii.
Letter from Bremen. [" Gynecologist " tour through Germany in
1887.] Pittsburgh M. Rev., 1887, ii.
Injuries and lacerations of the perineum and pelvic floor.
In: Syst. Pract. Gynec. (Mann), Phila., 1888, ii, 719-778.
Remarks on Alexander's operation. Ann. Gynaec, Bost., 1887-8,
1, 142.
Hysterorrhaphy. Am. J. M. Sc, Phila.,
n. s., xcv, 468-481.
Removal of the uterine appendages for disease in which pain
is a prominent symptom. Med. News, Phila., 1888, lii, 36-39.
Also: Proc. Phila. Co. M. Soc. 1887, Phila., 1888, viii, 278-289.
Also: Maryland M. J., Bait., 1887-88, xviii, 226-231.
A case of Caesarean section. Med. News, Phila., 1888, liil, 320-322.
Also: Am. J. Obst., N. Y., 1888, xxi, 1193.
Also: Polyclinic, Phila., 1888-89, vi, 117.
An aseptic two-way uterine catheter. Med. News, Phila., 1S88, lii.
326-327.
Also: Am. J. Obst., N. Y.. 1888, xxi, 721.
The Whitechapel murders. (Correspondence). Med. News, Phila
1888, liii, 430-431.
Resuscitation of the asphyxiated new-born child. Am. J Obst
N. Y., 1888, xxi, 419-420; 421.
A cotton packer. Ibid., 721.
Knife-blade tenaculum. Ibid., 942-944.
A self-retaining speculum. Ibid.. 945.
Operation upon a laceration of the cervix and perineum: peritonitis; abdominal section; death. Med. & Surg. Reporter,
Phila., 1888, Iviii, 489-491.
Rubber cushions for surgical purposes. N. York M. J., 1S8S, xlvii
104-105.
Also: Med. & Surg. Reporter, Phila., 1888, Iviil, 145.
Notes explanatory of sixty-six consecutive abdominal sections
recorded herewith. Pittsburgh, M. Rev., 1888, ii, 25; 35.
Palpation of the ureters in the female. Tr. Am. Gynec. Soc.,
Phila., 1888, xiii, 50-65.
Also: Am. J. Obst., N. Y., 1888, xxi, 1032-1034.
Discussion on the new Csesarean section. Tr. Am. Gynec. Soc,
1888, xiii, 130-141.
[Remarks on Blaikie's directions for exercise.] N. York M. J.,
1888, xlvii, 136.
Description of a new pad for general surgical purposes. N. York
M. J., 1888, xlvii, 473.
1889
Report of twenty-five abdominal sections performed for the most
part in the Kensington Hospital for Women, since the summer
of 1888. Univ. M. Mag., Phila., 1888-9, i, 400-407.
Cholocystorrhaphy, followed by cholocystotomy: evacuation of one
hundred and eighty-eight gall-stones; recoverv. Ann. Gynec,
Bost., 1888-89, ii, 517-519.
Also: Am. J. Obst., 1889, xxil, 1191-1193.
A new method of performing hysteromyomectomy. Am. J. Obst.,
N. Y., 1889, xxii, 375-385.
Hysteromyomectomy. Boston M. & S. J., 1889, cxx, 40-41.
Carcinoma of the corpus uteri. Obst. Gaz., Cincin., 1889, xii, 57.
Glass catheters. Am. J. Obst., N. Y., 1889, xxii, 184-185.
Kelly, H. A. & Robb, H. Craniotomy for hydrocephalus, with the
use of the obstetric pad. Univ. M. Mag., Phila., 1888-89, i,
514-519.
1890
Diseases of the ovaries and tubes.
In: Cycl. Dis. Child., M. & S. (Keating), Phila., 1890, iii,
731-740.
On hysterorrhaphy. Johns Hopkins Hosp. Bull., Bait., 1889-90,
i, 17-19.
Ligation of varicose ovarian veins. Ibid., 23.
The more remote results of removing the ovaries and tubes. Ibid.,
57-58.
Hysteromyomectomy. Ibid., 96.
Tubercular peritonitis [operation.] Ibid., 96-97.
A consideration of three successful Csesarean sections in Philadelphia. Am. J. Obst., N. Y., 1890, xxiii, 225-246.
Supra-vaginal hysterectomy. Hysteromyomectomy with suspension of the stump in the lower angle of the abdominal incision.
Med. News, Phila., 1890, Ivi, 695-698.
Treatment of recto-vaginal fistulae. (Editorial). Med. News,
Phila., 1890, Ivii, 516-517.
CephalhEematoma. A case of sub-pericranial blood-tumor in the
new-born child. Med. News, Phila., 1S90, Ivii. 229-231.
A successful Csesarean section for a large bony tumor choking the
pelvis. Med. & Surg. Reporter, Phila., 1890, Ixii, 100-106.
The gynecological operating room in The Jolms Hopkins Hospital,
and the antiseptic and aseptic rules in force. Jolins Hopkins
Hosp. Rep., Bait., 1890, ii, 131-139.
Tlie report of the' autopsies in two cases dying in tlie Gynecological wards without operation. Johns Hopkins Hosp. Rep.,
Bait, 1890, ii, 167-176.
Composite temperature and pulse cliarts of forty cases of abdominal section. Johns Hopkins Hosp. Rep., Bait., 1890,
ii, 177-183.
The gonococcus in pyosalpinx. Johns Hopkins Hosp. Rep., oalt.,
1890, ii, 195-200.
Tuberculosis of the Fallopian tubes and peritoneum; ovarian
tumor: removal of the ovaries and Fallopian tubes with
drainage, followed by recovery; demonstration of the tubercle
bacillus in sections of the tube. Johns Hopkins Hosp. Rep.,
Bait., 1890, ii, 201-204.
General gynecological operations from October 15, 1889, to March 4,
1890. Jolms Hopkins Hosp. Rep., Bait., 1890. ii, 205-215.
Ligature of the trunks of the uterine and ovarian arteries as a
means of cliecking hemorrliage from tlie uterus and broad
ligaments in abdominal operations. Johns Hopkins Hosp.
Rep., Bait., 1890, ii, 220-223.
OrroBER, 1919]
295
Elephantiasis of. the clitoris. Johns Hopkins Hosp. Rep., Bait.,
1890. ii, 227-230.
Kolpo-ureterotoniy; incision of the ureter through the vagina,
for the treatment of ureteral stricture. Johns Hopkins Hosp.
Rep., Dalt., 1890. ii. 234-242.
Record of deaths following gynecological operations. Abstracted
from the recoriis of the pathological department. Johns Hopkins Hosp. Rep.. Bait., 1890, ii. 243-252.
Extra-uterine pregnancy. Review and discussion. Paper read
before the Obstetrical and Gynecological Society of Baltimore
City. January 14 and February 11, 1890. Tr. Obst. & Gynec.
Soc., Bait.. 1S90. 33-48.
Vaginal puncture and drainage for pelvic abscess. An address
before the Gynecological and Obstetrical Society of Washington, December 5. 1890. (Not published).
Cephalaematoma verum externum; sub-pericranial blood-tumor
of the new-born. Tr. Am. Gynec. Soc. Phila., 1890, xv. lS9-2(i9.
Kelly, H. A. & Ghriskey, A. A. Report of the urinary examination
of ninety-one g\-necological cases. Johns Hopkins Hosp. Rep.,
Bait., 1890, ii, 216-219.
Kelly, H. .\. & Robb. H. The laparotomies performed in the
gynecological department from October 16. 1889, to March 3,
1890. Johns Hopkins Hosp. Rep., Bait, 1890, ii, 141-166.
A death caused by a uterine dilator, with some remarks as to the
proper method of using the dilator. Am. J. Obst., N. Y.,
1891. xxiv, 42-46.
The palpation of normal ovaries. Am. J. Obst., X. Y., 1891, xxiv,
129-142.
The steps of the Csesarean section; the do's and the don't's.
Am. J. Obst., N. Y., 1891. xxiv, 532-544.
Hand disinfection. Am. J. Obst., N. Y., 1891, xxiv, 1414-1419.
The ideal dressing for the abdominal wound. Am. J. Obst, N. Y.,
1891, xxiv, 1439-1441.
Abstracts from " The picture of Philadelphia." etc. Read before
the Historical Societv of the Johns Hopkins Hospital. Med.
News, Phila.. 1891. Iviii. 19T-198.
Cancer of the cervix uteri in the negress; physometra in the
negress. due to cancer: mania following operation; recovery.
Tr. South. Surg. & Gynec. Ass., 1890. Phila., 1891, iii, 386-390.
Antisepsis and asepsis before and after major gynecological
operations. Am. J. M. Sc, Phila., 1891, n. s., ci, 44-55.
Letter to Dr. G. H. Kirwan. |The modern treatment of wounds.
by G. H. Kirwan. 1 Lehigh Valley M. .'Mag.. 1890-1891, ii,
213-214.
Report from Gynecological Clinic. (A case of tubercular peritonitis treated with Koch's lymph). Johns Hopkins Hosp.
Bull., Bait, 1891, il, 15.
Twin pregnancy. Breech and transverse presentation. The
placentae and the membranes. (Proc. Johns Hopkins Hosp.
.Med. Soc., Dec. 15, 1890). Ibid.. 44.
The treatment of large myomatous tumors of the uterus. Myomotomy and hysteromyomectomy. Ibid., 45-49.
A case of ronser^'atlve Ca^sarean section. (Proc. Johns Hopkins
Hosp. .Med. Soc., Feb. 2, 1891). Ibid.. 62.
Israel Sparhlus'.s Gynecology. (Proc. Johns Hopkins Hosp. HIat
Club, Oct. 12. 18911. Ibid.. 164.
My fourth Csesarean section. N. York M. J., 1891, 1111. 500-503.
1892
Diseases of the broad ligaments, tubes, and ovaries.
In: Syst. Pract Therap. (Hare). Phila.. 1892. Ill, 80.'',-834.
The ministry of nursing. An address delivered to the second
class of nurses graduating at The Johns Hopkins Hospital,
June 3, 1892. Bait.. 1S92. Griffln, Curley & Co., 14 p. 8°.
A letter to my a-sststant on the method of securing asepsis In the
preparation of Instruments, ligatures, and dressings in my
private office. Am. J. Obst, N. Y., 1892, xxv. 184-189.
The ureteral catheter. Am. J. Obst., N. Y., 1892, xxv, 768-771.
Clinical report of cystectomy for polycystic ovarian tumor. Med.
& Surg. Reporter, Phila., 1892, Ixvii, 241-246.
Confinement on the obstetric pad. Med. Rec, N. Y., 1892, xlii, 663.
Gynwcological technique; a brief summary of the principles involved, as well as the technique of the gyniecological operations
performed in The Jolins Hopkins Hospital; the significance of
the operation and its technical surroundings to gyna-cological
practice. N. York J. Gynaec. & Obst, 1892, ii, 667-674.
Address to nurses. Delivered at the third annual commencement
of the Training School for Nurses of Wilkes Barre City
Hospital, July 1, 1892.
In: Rep. 3d ann. comm. Training School for Nurses, Wilkes
Barre City Hosp., 1892.
Presentation of Foesius' Hippocrates. (Proc. Johns Hopkins Hosp.
Hist Club, March 14, 1892). Johns Hopkins Hosp. Bull.,
Bait, 1892, iii, 43.
On methods of illustrating lectures with a lantern-slide exhibition
of injuries at the vaginal outlet. Times & Reg.. Phila., 1892,
xxiv, 649-650. i
1S93
Drainage in abdominal surgery. Practice, Richmond, 1893. viii,
69-70.
My recent ureteral work. Ann. Gyna?c. & Pediat, Phila., 1892-93,
vi, 449-460.
Catheterization of the ureters. Ann. Gyna?c. & Paediat., Phila.,
1892-93, vi, 641-644.
The ethical side of the operation of oophorectomy. Am. J. Obst.,
N. Y., 1893, xxvii, 206-208.
Glass trocars for tapping large ovarian cysts. Am. J. Obst.,
N. Y., 1893, xxvii, 581.
The best needle holder. Am. J. Obst., N. Y., 1893, xxvii, 870-872.
The examination of the female bladder and the catheterization
of the ureters under direct inspection. Johns Hopkins Hosp.
Bull., Bait., 1893, iv, 101102.
Extra-uterine pregnancy treated by vaginal incision. Johns
Hopkins Hosp. Bull., Bait., 1893, iv, 109.
A case of uterus duplex solidus. with atresia of the vagina and
cervix. Johns Hopkins Hosp. Bull., Bait., 1893, iv. 109-110.
Exhibition of a convalescent case of peritonitis due to ruptured
tubal abscess. Johns Hopkins Hosp. Bull., Bait, 1893, iv,
111-112.
Suspensio uteri. J. Am. M. Ass., Chicago, 1893, xxi, 332-333.
Prolapsus uteri. N. Am. Pract, Chicago, 1893, v, 337-347.
The early treatment of carcinoma uteri. N. York M. J., 1893,
Iviii, 433-434.
The examination under anjesthesia: its uses and its limitations.
N. York M. J., 1893, Iviii, 617-618.
A preliminarv report on the morphology of ovarian and myomatous
tumors. N. York J. Gyniec. & Obst, 1893, ill, 465-484.
Also: Tr. South. Surg. & Gynec. Ass., 1892. Phila., 1893, v, 211-217.
Al.w: Am. J. Obst.. N. Y., 1893, xxvii. 31U-312.
Epitome of an address on sepsis, antisepsis and asepsis, in relation
to operative gjnecology. Tr. M. Soc, N. Y., Phila., 1893,
375-377.
Abstract of a paper on urinalysis in gyntecology. Am. Med. Surg.
Bull., N. Y.. 1893, vl. 934-93.5.
.i;so.- Am. J. Obst.. N. Y.. 1S93, xxviil, 429-431.
1894
The technique of gynecological operations.
In: Am. TextBk. Gynec. (Baldy), Phila., 1S94, 54-80.
I.rf»ceratlons of the soft parts.
In: Am. Text-Bk. Gynec (Baldy). Phila., 1894, 245-266.
Genital fistul-T.
In: Am. Text-Bk. Gynec. (Baldy), Phila.. 1894, 267-277.
Diseases of the urethra, bladder, and ureters.
In: Am. Text-Bk. Gynec (Baldy), Phila., 1894, 615-659.
The gynecological operating room. Johns Hopkins Hosp. Rep.,
Bait, 1S92-4. ill, 301-302.
An external direct method of measuring the conjugata vera,
Johns Hopkins Hosp. Kep., Bait., 1892-94, 111, 303-309.
296
[Xo. 3-1
Prolapsus uteri without vesical diverticulum, and with anterior
enterocele. Ibid., 311-320.
Lipoma of the labium majus. IMd., 321-326.
Deviations of the rectum and sigmoid flexure associated with
constipation a source of error in gynecological diagnosis.
Ibid.. 327-342.
Operations for the suspension of the retroflexed uterus. Ibid..
343-35S.
Gynecological operations not involving coeliotomy. Tabulated by
A. L. Stavely. Ibid.. 377-410.
The employment of an artificial retro-position of the uterus in
covering extensive denuded areas about the pelvic floor.
• Ibid., 411-417.
Some sources of hemorrhage in abdominal pelvic operations.
Ibid., 419-422.
Traumatic atresia of the vagina with haematokolpos and hsema
tometra. Ibid., 429-431.
Resuscitation in chloroform asphyxia. Ibid.. 507-508.
Abdominal operations performed in the gynecological department
from March 5, 1890, to December 17, 1892. Ibid.. 547-673.
A study of intra-abdominal pressure with practical deductions.
Cleveland M. Gaz., 1893-94, ix. 239-247.
.The diagnosis of pelvic inflammatory diseases. Ann. Gynsec. &
Pediat., Phila., 1893-94, vii, 185-190.
Uretero-ureteral anastomosis; uretero-ureterostomy. [Remarks by
Dr. Bloodgood.] Johns Hopkins Hosp. Bull., Bait., 1893,
iv, 89-90.
Also: Ann. Surg., Phila., 1894, xix, 70-77.
The direct examination of the female bladder with elevated pelvis;
the catheterization of the ureters under direct inspection,
with and without elevation of the pelvis. Am. J. Obst., N. Y.,
1894, xxix, 1-19.
Also: Johns Hopkins Hosp. Bull., Bait., 1894, v, 16.
The cystoscope. Am. J. Obst, N. Y., 1894, xxx, 85-90.
Resuscitation, from impending death due to concealed hemorrhage,
bv an infusion of a litre of normal salt solution centrally
into the radial artery. Am. J. Obst.. N. Y., 1894. xxx, 184-189.
Electric illumination of the field in abdominal surgery. Am. J.
Obst., N. Y., 1894, xxx, 348-353.
The advantage of atmospheric distention of tlie rectum, with
dislodgment of the small intestines, in the bimanual examination of uterus, ovaries, and tubes. Am. J. Obst., N. Y.,
1894, xxix, 607-610.
An improved lock for paired instruments. Ann. Surg., Phila..
1894, xix, 231-235.
Dysmenorrhoea. N. York J. GynaE'C. & Obst., 1894, iv, 408-411.
Also: Tr. M. Soc. N. Y., Albany, 1894, 177-181.
Introduction of bougies into the ureters preceding hysterectomy
and the removal of densely-adherent structures adjacent to
the ureter. (Proc. Johns Hopkins Hosp. Med. Soc. Dec. IS,
1893.) Johns Hopkins Hosp. Bull., Bait., 1894, v. 17.
Lantern slides as an aid to clinical teaching. (Proc. Johns Hopkins Hosp. Med. Soc, Jan. 15, 1894). Ibid.. 35.
The methods employed in securing statistical tables for Emmet's
Gynecology. Exhibition of original tables presented by
Dr. Emmet. (Proc. Johns Hopkins Hosp. M. Soc, Feb. 19,
1894). Ibid., 51-52.
Ligation of both internal iliac arteries for hemorrhage in hysterectomy for carcinoma uteri. (Proc. Johns Hopkins Hosp.
M. Soc, March 5, 1894). Ibid.. 53-54.
Myoma complicating pregnancy and preventing delivery. PorroCiesarean operation modified by dropping the pedicle. (Proc.
Johns Hopkins Hosp. Med. Soc, April 2, 1894). Ibid., 80-81.
Infusion of normal saline solution in connection with gynecological operations and the accidental hemorrhages of parturition. (Proc. Johns Hopkins Hosp. Med. Soc, April 2,
1894). Ibid., 81-82.
Recent results in hysteromyomectomy. (Proc. Johns Hopkins
Hosp. Med. Soc, May 7, 1894). Ibid.. 99-100.
Ureterotomy. Ibid., 137.
A new method of exploring the rectum and sigmoid flexure Ibid .
137-138.
Recent results in hysteromyomectomy. The direct examination
of the female bladder and catheterization of the ureters under
direct inspection, [n. p., 1894, vel subseg.^ 8°.
Kelly, H. A., & Cullen, T. S. Record of deaths occurring in the
gynecological department from June 6. 1890, to May 4. 1892.
Abstracted from the autopsy notes of the pathological department. Johns Hopkins Hosp. Rep., Bait., 1892-94, iii, 675-762.
Kelly, H. A. & Sherwood, Mary. One hundred cases of ovariotomy
performed on women over seventy years of age. Ibid., 509-545.
1895
Extra-uterine pregnancy.
In: Am. Text-Bk. Obst. (Norris & Dickinson). Phila., 1895,
273-294.
Diseases of the female bladder and urethra.
In: Twentieth Cent. Pract., N. Y.. 1895, i, 663-726.
Diagnosis of ureteral and renal diseases in women. J. Am. M.
Ass., Chicago, 1895, xxv, 272-274.
Suspensio uteri — the proper method of performing it, and its
results. (Abstr.) J. Am. Med. Ass., Chicago, 1895, xxv, 318.
Suspension of the uterus; the operative treatment of retroflexion
based on a consideration of 200 cases. J. Am. M. Ass., Chicago,
1895, xxv, 1079-1081.
Diagnosis of renal calculus in women. Med. News, Phila., 1895,
Ixvii, 593-596.
Gonorrhoeal pyelitis and pyo-ureter cured by irrigation. Johns
Hopkins Hosp. Bull., Bait., 1895 vi, 19-21.
Uretero-cystostomy performed seven weeks after vaginal hysterectomy. Ibid., 27-28.
Sigmoido-proctostomy; an anastomosis of the lumen of the sigmoid
fiexure through the lateral wall of the rectum at the pelvic
floor, without suture. Ibid., 30-31.
Also: Mathews' M. Quart, Louisville, 1895, ii, 212-216.
A new method of examination and treatment of diseases of the
rectum and sigmoid flexure. Ann. Surg., Phila., 1895, xxi.
468-478.
Also: [Abstr.] Centralb. f. Chir.. Leipz.. 1895. xx, 961-962.
"Female" or woman. (Correspondence). Am. J. Obst., N. Y..
1895, xxxi. 394.
Also: Pittsburgh M. Rev.. 1895, ix, 160.
Tlie renal catheter and its use in the diagnosis and treatment
of renal diseases. Tr. Am. Gynec. Soc, Phila., 1895, xx, 20-29.
Also: Boston M. & S. J., 1895, cxxxiii, 469.
Also: Am. J. Obst., N. Y., 1895, xxxii, 120-123.
1896
State regulation of the social evil. Washington, 1896, Puritv
Publ. Co., 15 p. 8°.
Personal purity. Health Mag., Wash., 1895-96, iii, 590-596.
A criticism on Prof. Howard A. Kelly and his discoveries in the
domain of urinary diseases, by W. Rubeska. M. D. My work
on the diseases of the urinary tract in women. Being a reply
to the above. (Correspondence). Am. J. Obst., N. Y., 189G,
xxxiii, 394-405.
Meine Arbeit iiber die Krankheiten der weiblichen Harnwege.
Antwort auf Mittheilungen des Herrn Prof. W. Rubeska.
Centralbl. f. Gynak., Leipz., 1896, xx, 489-498.
Five cases of ovariotomy in women over seventy vears of ago.
Am. J. Obst, N. Y., 1896, xxxiv, 222-227.
A reply to Prof. Pawlik's claim to the discovery of my method of
examining the bladder and catheterizing the ureters in women.
Am. J. Obst, N. Y., 1896, xxxiv, 259-261.
Delivery by traction on the scalp of the child. Am. J. Obst,
N. Y., 1896, xxxiv, 356-357.
Conservatism in ovariotomy. J. Am. M. Ass.. Chicago, 1896,
xxvi, 249-251.
Unchastity and credibility. (Letter to the editor of the Journal
of the American Medical Assoi-iation ) . J. Am. M. Ass.,
Chicago, 1896, xxvi, 992-993.
The treatment of large vesico-vaginal fistula-. Johns Hopkins
Hosp. Bull., Bait, 1896, vii, 29-30.
Also: Am. J. Obst, N. Y., 1896, xxxiii, 930-931.
OCTOBKB, 19191
297
Nephro-ureterectomy; extirpation of the kidney and ureter simultaneously. Jolins Hopkins Hosp. Bull., Bait., 1896, vii, 31-37.
The treatment of pyo-ureteritis and pyonephrosis by ureteral
and renal catheters. Ibid.. 48-50.
Women in medicine. Ibid., 50-52.
The treatment of ectopic pregnancy by vaginal puncture. (Proc.
Johns Hopkins Hosp. Med. Soc., Oct. 19, 189ti). Ibid.. 209-211.
Hysteromyomectomy and hystero-salpingo-oophorcctomy by continuous incision from left to right or from right to left. Tr.
South. Surg. & Gynec. Ass., 1895. Phila., 1896, viii, 133-138.
Also: Johns Hopkins Hosp. Bull., Bait.. 1896. vii, 27-29.
The treatment of extra-uterine pregnancy, ruptured in early
months, bv vaginal puncture and drainage. Am. Gvnec. &
Obst. J., N. Y.. 1896. ix, 129-151.
Also: Tr. Am. Gynec. Soc. Phila., 1896, xxi. 180-208.
Also: Am. J. Obst.. N. Y.. 1896, xxxiv, 103-105.
The treatment of backward displacements of the uterus. Am. J.
M. Sc. Phila., 1896, n. s., cxii, 629-649.
[Letter to the editor of the Medical Sews in regard to Dr. Pryor's
article, entitled "A new and rapid method of dealing with
intra-ligamentary fibromyomata.") Med. News, N. Y., 1896,
Ixviii, 501.
Some recent important advances in the diagnosis and treatment
of urinary diseases in women. Pittsburgh M. Rev., 1896, x, 1-8.
Abdominal hysterectomy for fibroma uteri. South. Pract., Nashville. 1896, xvili, 7-21.
Entgegnung an Prof. Dr. Pawlik. Centralbl. f. Gynak.. Leipz.,
1896. XX. 1266-1273.
Use of the renal catheter in the diagnosis of stone in the kidnf^y.
Maryland M. J., Bait., 1896, xxxv, 100.
The Johns Hopkins Medical Students. (Correspondence). Pittsburgh M. Rev., 1896, x, 315.
Ovarian cysts weighing over one hundred pounds. Read at the
Johns Hopkins Hospital Medical Society. May 18. 1S96. (Not
published).
1897
The sources and diagnosis of pyuria. Med. News. N. Y., 1897,
Ixxi. 756-761.
Also: Tr. South. Surg. & Gynec. Ass., 1897, Phila., 1898, x, 99-124.
Also: Am. J. Surg. & Gyna?c.. St. Louis, 1S98-99. xi, 5.5-56.
Excision of a parovarian cyst without removal of its ovary or tube.
Johns Hopkins Hosp. Bull., Bait., 1897. viii, 50-51.
Horatio Reese Holmes, 1856 96. Tr. Am. Gvnec. Soc, Pliila.,
1897, xxll, 310-312.
The conservative treatment of myomatous uteri. J. Am. M. Ass..
Cbicaeo, 1897, xxix. 668-669.
Operative treatment of pelvic inflammatory disease. Compt. rend.
Cong, period, internal, de gyn^c. et d'obst. 2. sess., 1896.
Geneve. 1897. 133-150.
Address before the Central College of Physicians and Surgeons of
Indianapolis on method of ureteral catheterization. Indiana
M. J.. 1897. xvl. 211-214.
Kelly. H. A. & Ramsay, O. De Tusage du catheter rfinal dans le
diagnostic et le traitement des maladies des reins et des
uret^res. Rev. de gyn€c. et de chlr. abd.. Par., 1897, 823-842.
Kelly, H. A.. Noble. C. P. [«•/ a/.). Abdominal hysterectomy for
fibroma uteri. South. Pract.. Naslivllle. 1897. xix. 7-21.
Operative gynecology.
557 p. 24 pi. 8 .
1898
v. N. Y., 1898. D. Appleton & Co. .".si p.
Conservation of the ovary In hysterectomy and hvrilero-mvomectomy. Brit. M. J.. Lond.. 1898, I, 288-291.
Ureteral anastomosis.
725-741.
Am. Gyntec. & Obst. J,
N. Y.. 1898, xll.
Am. J.
The hand basins in use In surgical operating rooms
Obst., N. Y., 1898. xxxvl. 188-193.
The preservation of the hymen. Am. J. Obst.. N. Y., 1898, xxxvii,
7-14.
The catheterization of the ureters In the male through an open
cystoscope with the bladder distended with air by posture.
Johns Hopkins Hosp. Bull., Bait., 1898, ix, 62.
A preliminary report upon the examination of the bladder and
the catheterization of ureters in men. Ann. Surg., Phila..
1898, xxvii, 71-73.
Cystoscopy and catheterization of the ureters in the male. Ann.
Surg., Phila., 1898, xxvii, 475-486.
Catgut sutures and ligatures. Med. News, N. Y., 1898, Ixxiil,
293-294.
Bact^riologie de I'appareil gfnital de la femme. Tr. S. Bonnet,'
Semaine gyn6c.. Par., 1898, ill, 268.
Principes g^n^raux concernant les operations plastiques. [Transl.l
Semaine gyn^c. Par.. 1898, ill, 353-356.
The treatment of complete rupture of the perineum by dissecting
out the sphincter muscle and its direct union by buried
sutures. J. Am. M. Ass., Chicago, 1898, xxxi, 1469.
Also: Maryland M. J.. Bait.. 1899, xli, 29.
Also: Memphis Lancet, 1899, ii, 29-32.
.ilso: Am. J. Obst., N. Y., 1899, xxxix, 216-217.
Discussion on the papers of Drs. Smith and Pryor. Tr. Am.
Gynec Soc, Phila., 1898, xxiii, .59-61.
Abtlominal myomectomy. /&i(/., 221-239.
Discussion: Should non-absorbable ligatures be discarded in
gynecological surgery. Ibid., 262-2G5.
Discussion on the papers of Drs. Dudley and Bovee. Ibid.. 284-286.
Kelly. H. A., & MacCalluni. W. G. Pneumaturia. J. Am. M. Ass.,
Chicago. 1898, xxxi, 375-381.
1899
The operation for complete tear of the perineum. Am. J. Obst.,
N. Y., 1899, xl, 202-213.
Also: Tr. Am. Gynec. Soc, 1S99, xxiv. l.Sfi-202.
Some new instruments to facilitate the operation of myomectomv.
Am. J. Obst., N. Y., 1899, xl, 218-221.
A new handle and grip for scissors for plastic and other delicate
work. Ibid., 229-233.
The use of the renal catheter in determining the seat of obscure
pain in the side. Ibid.. 328-334.
The reflux of air into the ureters through the air-distended bladder
in the knee-breast posture. Ibid.. 468-470.
The apron method of treating complete tear of the perineum.
(Correspondence). Ibid.. 515.
A curette for cervical cancer. Ibid.. 829-830.
The dissection and liberation of the sphincter and muscle followed
by its direct suture in cases of complete tear of the perineum,
with a splinting suture passing between the outer and inner
margins of the muscle. Johns Hopkins Hosp. Bull., Bait.,
1899, X, 1-7.
A new operation for vesico-vaginal fistula. (Proc Johns Hopkins
Hosp. Med. Soc, Feb. 6, 1899.) Ibid.. 115.
New use for renal catheters. (Proc. Johns Hopkins Hosp. Med.
Soc, Feb. 20. 1 899.) 76id.. 116.
Report of gynecological cases: I. Extensive destruction of the
sphincter; II. Carcinoma uteri; III. Excessive growth of fat.
(Proc Johns Hopkins Hosp. Med. Soc.) Ibid.. 196-197.
The recognition of the poisonous serpents of North America.
Ibid., 217-221.
Further uses of the ureteral catheter. Maryland M. J., Bait.,
1899, xll, 141.
A new operation for vesicovaginal fistula. Ibid.. 106.
A new method of treating complete tear of the rectovaginal
septum by turning down an apron into the rectum and by
burled suture tlirougli the sphincter muscle. Med. News. N. Y.,
1899, Ixxv, 334-335.
The exploration of the abdomen as an adjunct to every celiotomy.
Mod. News, N. Y.. 1899. Ixxv, 784-788.
Also: Ann. Gynec & Pcdlat., Bost., 1900, xili, 322-324.
1900
An Improved vesical speculum.
818-823.
Am. J. Obst., N. Y . 1900, xll,
298
[Xo. 344
The evolution of my technique in the treatment of fibroid uterine
tumors. Am. J. Obst., N. Y., 1900, xlii, 289-307.
Also: Tr. Am. Gynec. Soc, Phila., 1900, xxv, 207-221.
The removal of pelvic inflammatory masses by the abdomen after
bisection of the uterus. Am. J. Obst., N. Y., 1900, xlii, 818-839.
Also: Nashville J. M. & S., 1900, Ixxxviii, 208-211.
Also: Am. J. Surg. & Gynec, St. Louis, 1901, xiv, 91-92.
Also: Ann. Gynec. & Pediat., Boston, 1901, xiv, 174-177.
Also: Johns Hopkins Hosp. Bull., Bait., 1901, xii, 1-4.
A new method of making applications to the vaginal vault, and
a new instrument to facilitate cleansing the vagina in leucorrlicea. Am. Gynec. & Obst. J., N. Y., 1900, xvi, 193-195.
Notes on an improved method of removing the cancerous uterus
by the vagina. Johns Hopkins Hosp. Bull., Bait., 1900, xi,
55-56.
A preliminary report on the surgical treatment of complicated
fibroid tumors of the womb, with a description of two methods
of operating. Ibid., 56-58.
Poisonous snakes. (Proc. Johns Hopkins Hosp. Med. Soc, Feb. 5,
1900.) Johns Hopkins Hosp. Bull., Bait, 1900, xi, 73.
Uncontaminated urine. Ibid., 91-92.
A note on a series of new vesical specula. Ibid.. 93.
Ureteral calculus; its diagnosis by means of the wax-tipped bougie.
Escape of the calculus per rias naturales after forcible dilatation of the ureteral orifice. J. Am. M. Ass., Chicago, 1900
xxxiv, 515-517.
The present status of operations for cancerous uteri Ibid 12151220.
Resection and anastomosis of the divided ureter J Am M Ass
Chicago, 1900, xxxv, 860-863.
A rapid and simple operation for gall-stones found by exploring
the abdomen in the course of a lower abdominal operation
Med. News, N. Y., 1900, Ixxvii, 959-963.
What precautions shall we take to avoid leaving foreign bodies
in the abdomen after operations? N. York M. J., 1900, Ixxi,
Normal prophylactic appendectomv. Med. Rev St Louis 1900
xli, 207.
Medical Sermonets, No. 21. A plea for the humanities in nursini?
Phila. M. J., 1900, vi, 179-180.
Methods of teaching gynecology. Phila. M. J., 1900 vi 391-393
Also: Indian M. Rec, Calcutta. 1901, xx. 105-107. '
Gynecology, its present, past and future. Phila. M. J. 1900 vi
550-551. » , .
Kelly H. A.. & Brown, T. R. A note on the use of nitrous oxid and
ether as an anaesthetic Phila. M. J., 1900, vi. 869-871.
1901
Diseases of the ovaries and Fallopian tubes
In: Cyel. Dis. Child., M. & S. (Keating). Phila., 1901, v, 906-930.
Necessity of employing the newer methods of diagnosis in rectal
??^ol'r°^''-^' diseases. Tr. Am. Surg. Ass., Phila., 1901, xix,
Kircher et Lemaire 1658-1900. Rev. de gvnec. et de chir abd
Par., 1901, V, 829-850.
Erythrism from external stem pessary. Am. J Obst N Y 1901
xliii, 72. .  •.
A new and better method of opening and of draining the bladder
in women. Am. J. Obst., N. Y., 1901, xliv, 23-25.
Scratch-marks on the wax-tipped catheter as a means of determining the presence of stone in the kidney and in the ureter
Am. J. Obst., N. Y., 1901, xliv, 441-454.
How to deal with the vermiform appendix. Some forms of
complicated appendicitis. Am. Med., Phila., 1901," i, 109-110.
A historical note upon diptera as carriers of diseases Pare
Declat. Johns Hopkins Hosp. Bull.. Bait., 1901, xii, 240-242.'
Drainage of the bladder and cystoscopic examinations. Johns
Hopkins Hosp. Bull., Bait, 1901, xii, 298.
Jules Lemaire. The first to recognize the true nature of wound
infection and inflammation, and the first to use carbolic acid
in medicine and surgery. J. Am. M. 'Ass., Chicago, 1901,
xxxvi, 1083-1088.
Discussion of Dr. A. H. Cordier's paper " Post-operative hemorrhage." J. Am. M. Ass., Chicago, 1901, xxxvii, 18.
Some further notes on the extension of the principle of bisection
in abdominal surgery. St. Paul M. J., 1901, iii, 380-386.
Kelly, H. A. & Faure, J. L. L'extirpation des masses inflamma' toires pelviennes par I'abdomen, apres hemisection de I'uterus.
[Trad.] Gynecologie, Par., 1901, v, 260-279.
1902
Extra-uterine pregnancy.
In: Am. Text-Bk. Obst., 2. ed. (Norris & Dickinson), Phila.,
1902, 324-346.
Nephrectomy; panhystero-myomectomy, with double salpingooophorectomy and appendicectomy; fixation of right kidney;
suspension of uterus, with resection of a corpus-luteum
haematoma; salpingo-oophorectomy, followed by resection of
the sigmoid for carcinoma. Internat. Clin., Phila., 1902. 12. s.,
ii, 232-246.
Some notes upon the management of a modern private hospital.
Internat Clin., Phila., 1902, 12. s., ii, 261-273.
The mimicry of pregnancy bv fibroid and ovarian tumors. Am.
Gynec, N. Y., 1902, i, 449-462.
Further notes on the uses of the wax-tipped catheter in the
diagnosis of stone in the kidney or ureter. Am. J. Obst.,
N. Y., 1902, xlvi, 66-70.
On methods of incising, searching, and suturing the kidney.
Brit. M. J., Lond., 1902, i, 256-261.
Exhibition of a case of pelvic tuberculosis. Johns Hopkins Hosp.
Bull., Bait., 1902, xiii, 141-142.
The treatment of vesico-vaginal and recto-vaginal fistulas high
up in the vagina. Johns Hopkins Hosp. Bull., Bait., 1902,
xiii, 73-74.
Also: Indian M. Rec, Calcutta, 1902, xxii, 632-634.
The true spirit of the nursing profession. An address at the
annual meeting of the visiting nurse association of Baltimore.
Johns Hopkins Nurses Alumnae Mag.. Bait. 1901-2, i. 117-119.
The advantages of the knee-chest posture in some operations upon
the vesical end of the ureters. J. Am. M. Ass., Chicago, 1902,
xxxix, 291-293.
Stricture of the ureter. J. Am. M. Ass.. Chicago, 1902, xxxix,
363-368.
Under what circumstances is it advisable to remove the vermiform
appendix when the abdomen is opened for other reasons?
J. Am. M. Ass., Chicago. 1902, xxxix, 1019-1021.
Labia urethrse and Skene's glands. Am. Med. Phila., 1903. vi,
429-431; 465-468.
.ilso: Ann. Gynec. & Pediat., Bost, 1903, xvi, 104-108.
Removal of vesical papilloma through an incision in the septum
with the patient in the knee-chest posture. Am. J. Obst.,
N. Y., 1903, xlvii, 28-31.
Instruments for use through cylindrical rectal specula with the
patient in the knee-chest posture. Ann. Surg., Phila., 1903,
xxxvii, 924-927.
Les debuts de I'histoire de I'appendicite en France. Bull, et
mem. Soc. de chir. de Par., 1903, n. s., xxix, 632-649.
Also: Presse med.. Par., 1903, i, 437-441.
The early history of appendicitis in Great Britain. Glasgow
M. J., 1903, Ix, 81-97.
The selection of methods in abdominal hysterectomy. Glasgow
M. J.. 1903, Ix, 241-254.
Also: J. Ubst & Gynec. Brit. Emp., Lond., 1903. iv. 343-354.
A method of sequestrating the urinary bladder in extensive operations involving its peritoneal surfaces. Johns Hopkins Hosp.
Bull., Bait, 1903, xiv, 96-98.
The danger of methods often used at present in dusting waitingrooms, cars, and other public places. J. Am. M. Ass., Chicago,
1903, xli, 861-862.
October, 1919]
299
Indications for particular methods In extirpating the diseased
pelvic viscera. Lancet, Ix)nd., 1903, ii, 30-32.
The expansion of a specialty. Med. Rec., N. Y.. 1903, Ixiii. 693-698.
1904
My experience with the renal catheter as a means of detecting
renal and ureteral calculi. Am, J. Urol., N. Y., 1904, i, 14-21.
Ideal method of removing the vermiform appendix. Am. Med.,
Phila., 1904, viii. 1123-1125.
Myomectomy in its relation to pregnancy. (Proc, Johns Hopkins
Hosp. .Med. Soc. March 7, 1904.) Johns Hopkins Hosp. Bull.,
Bait.. 1904. XV. 259.
The piezometer, an instrument for measuring resistances. Ibid.,
293.
Injuries to the rectum caused by gynecologic examinations. J.
Am. M. Ass., Chicago, 1904, xliii, 1604-1606.
The treatment of simple rectal fistula by excision and suture without cutting tlie external sphincter muscle. Med News, N. Y.,
1904, Ixxxv. 640.
Rubber cushions for general surgical gynecological and obstetrical
use. Med. News, N. Y., 1904, Ixxxiv, 699-700.
Verletzungen des Rectums bei gynakologischen Untersuchungen.
Berl. klin-therap. Wchnschr., 1904, i. 775-778.
AUo: Wien klin-therap.. Wchnschr, 1904, xl. 775-778.
1905
Kelly, H. A. & Hurdon. E. The vermiform appendix and its
diseases. Phila., 1905. W. B. Saunders & Co. 848 p. 3 pi.
roy. 8°.
The great opportunity of the physician and the nurse. An address
delivered at a service for physicians and nurses, Nov. 19,
1905, N. Y. 1905, Loizeaux Bros., 15 p., 32°.
The uterine curette. Am. J. Obst.. N. Y., 1905, li, 662.
The treatment of the nonmalignant strictures of the rectum. Am.
Med., Phila., 1905, x, 479-480.
Some surgical notes on tuberculosis of the kidnev. Brit. GvnEPC.
J.. Lond., 1905, xxi, 130-153.
AUo: Brit. M. J., Lond., 1905, i, 1319-1323.
.4Jso; Lancet, Lond., 1905. i. 1630-1632.
Also: Med. Press & Circ, Lond., 1905, n. s., Ixxix, 663-668.
The surgical treatment of renal tuberculosis. Dominion M. Month.,
Toronto, 1905, xxiv, 125-132.
What is the right attitude of the medical profession toward the
social evil? J. Am. M. Ass., Chicago, 1905, xliv, 679-681.
The best way to treat the social evil. Med. News, N. Y., 1905,
Ixxxvi, 1157-1163.
The treatment of pyelitis. Med. Rec, N. Y., 1905, Ixvii. 521-524.
Professor Smith on the Jersey mosquito. (Proc. .lolins Hopkins
Hosp. Med. Soc, Nov. 21. 1904.) Johns Hopkins Hosp. Bull,,
Bait.. 1905, xvi, 115116.
1906
Operative gj-necology. 2. ed. revised and enlarged. 2. v. N. Y. &
Lend., 1906. D. Appleton & Co. 680 p. 5 pi. 656 p. 17 pi. 8'.
Walter Reed and yellow fever. N. Y., 1906. McClure, Philips &
Co. 293 p. 12 pi. 12'.
The treatment of cystitis. Canada I.,ancct, Toronto, 1905 6, xxxix,
385-398.
Also: Maritime M. News. Halifax, 1905, xvil, 445: 1906, xvlll, 17.
Also: Canad. J. M. & S., Toronto, 1906, xix, 67-82.
Also: Canad. Prar. & Rev., Toronto. 1906, xxxi. f;i-7."..
Also: Old Dominion M. Month., Toronto, 1906, xxvi, 1-16.
The aseptic removal of an Infected fibroid uterus. Am. J. Obst.,
N. Y., 1906, liil, 493.
The use of a steel comb for dissection in the axilla. Ann. Surg.,
Phila., 1906, xliv, 104-105.
Two cases of stricture of the ureter: two caaes of hydronephrotlc
renal pelvis successfully treated by plication. Johns Hopkins
Hosp. Bull . Bait., 1906, xvil, 173175.
The regulation of prostitution. J. Am. M. Ass., Chicago, 1906,
xlvi, 397-401.
Resections of the bladder in rebellious cystitis. N. York State
J. M., N. Y., 1906, vi, 145-148.
Starvation and locking the bowels for from ten days to two weeks
in complete tear cases. Tr. South. Surg. & Gynec. Ass., 1905,
Phila.. 1906, xviii, 95-107.
.4Jso.- Surg. Gynec. & Obst., Chicago, 1906, ii, 179-181.
The suprapubic route in operating for vesical fistulae. Tr Am
Gynec Soc, Phila., 1906, xxxi, 225-253.
! In mcmoriam. Arthur Weir Johnstone, M. D. (1853-1895). Tr.
Am. Gynec. Soc, 1906, xxxi, 427-430.
Some lessons from the life of Major Walter Reed. Med. Libr &
Hist. J.. Brooklyn, 1906, iv, 332-338.
A satisfactory vesical evaeuator. Surg. Gynec. £ Obst., Chicago
1906, iii, 330.
ed. N. Y.. 1907. McClure,
Walter Reed and yellow fever.
Philips & Co., 310 p., 12°.
Kelly, H. A., & Noble, C. P., eds. Gynecology and abdominal
surgery. Vol. 1. Phila. & Lond., 1907, W. B. Saunders Co
859 p., 8°.
Byron Robinson and his work. Am. M. Compend., Toledo, 1907,
xxiii. 3-4.
Success in life. Jeffersonian, Phila., 1906-7, viii, 86-98.
A g>'necological clinic — A case of stricture of the ureter due to
stone, causing severe attacks of colicky pain and finally
demanding operative interference: the removal of the kidney.
Am. J. Clin. M., Chicago, 1907, xiv, 737-740.
The protection of tlie innocent. Am. J. Obst., N. Y., 1907, Iv, 477-481.
Remarks on dermographic tracings in clinical demonstrations.
Internat. J. Surg., N. Y„ 1907, xx, 188.
On a method of preserving outlines of visceral lesions on nainsook
or Suisse material. Jolins Hopkins Hosp. Bull., Bait., 1907,
xviii, 120-122.
Bimanual vibratory palpation. J. Am. M. Ass., Chicago, 1907,
xlviii, 1841.
Mensuration in urinary diseases. Tr. Am. Gvnec. Soc, Phila.,
1907, xxxii, 302-346.
Surgical treatment of tuberculosis of the kidney. Surg. Gynec
& Obst., Chicago, 1907, iv, 257-262.
The lesson of little things: the conquest of yellow fever. Youth's
Companion, Bost., 1907, Ixxxi, 15.
1908
Medical gynecology. N. Y., 1908. D. Appleton & Co. 676 p. 8°.
Kelly, H. A., and Noble, C. P., eds. Gynecology and abdominal
surgery. Vol. 11. Phila. & Lond., 1908, W. B. Saunders Co.,
862 p., 8°.
Anuria and nephrostomy by the ureter. Johns Hopkins Hosp.
Bull., Bait, 1908, xix, 48.
The barred road to anatomy. Ibid.. 196-201.
Art applied to medicine and surgery. [Illustrated.) Tr. South.
Surg. & Gynec Ass., 1907. N. Orleans, 190S, xx, 1-18.
My faith. Appleton's Mag., N. Y.. 1908, xl, 722-724,
Out of uncertainty and doubt, into faith. (Leaflet). [An abridgement of " My faith."]
A personal testimony. (Loaflot). [.\n abridgement of "My
faitli.")
On Bible study. A letter to a friend. Our Hope, N. Y,, 1908
(October).
James Carroll, 1854-1907. Proc. Wash. Acad. Sc, 1908, x, 204-207.
Kelly, H, A. \rt nl.]. James Carroll. M. D., U. S. A., 1854-1907.
Johns Hopkins Hosp. Bull., Bait, 1908, xix, 1-12.
Appondiritis and other diseases of the vermiform appi^ndix Pliila
& Lond., 1909, J. B. LIppincott Co. 502 p. 8°.
300
[No. 344
Kelly, H. A., & Cullen, T. S. Myomata of the uterus. Phila., 1909.
W. B. Saunders Co. 723 p. 8°.
Frere Jacques. Aesculapian, N. Y., 190S-9, i, 145-1.51.
Amputation of the uterus in the corpus to preserve the menstrual
function. Am. J. Obst., N. Y.. 1909, lix, 570-581.
Also: Tr. Am. Gynec. Soc, Phila., 1909, xxxiv, 536-549.
The fat appendix. Ann. Surg., Phila., 1909, 1, 474-476.
Post-operative psychoses. Surg. Gynec. & Obst., Chicago, 1909,
ix, 515-521.
Also: Tr. Am. Gynec. Soc, Phila., 1909, xxxiv, 426-455.
Also: Am. J. Obst.. N. Y., 1909, lix, 1035-1037.
McDowell's successors in America. Tr. Am. Gynec. Soc, Phila.,
1909, xxxiv, 592-599.
1910
Treatment of an anteuterine pelvic abscess by sequestration and
drainage. Am. J. Obst., N. Y., 1910, Ixi, 921-925.
An operation for umbilical hernia. Ann. Surg., Phila., 1910, li.
694-696.
A chart to aid In the treatment of cystitis by distentions of the
bladder. Ann. Surg., Phila., 1910, 111, 664-667.
Transurethral operations in women. J. Am. M. Ass.. Chicago, 1910,
liv, 1606-1607.
Oral prophylaxis. Dominion Dent. J., Toronto, 1910, xxii, 563-570.
Suspensio uteri. Klin.-therap. Wchnschr., Berl., 1910, xvll, 916-918.
The ebb and flow of hypnotism since 1660. Maryland M. J.,
Bait., 1910, lii. 81-97.
Social diseases and their prevention. Social Dis., N. Y., 1910, 1,
No. 3, 12-25.
The gj'necological examination and topical treatment.
In: Stereo-Clinic, Troy, N. Y., 1910, Sect, i, 2-38, 24 stereos.
Removal of a dermoid cyst of the ovary. Ibid.. Sect, iii, 2-11,
7 stereos.
Vaginal incision and drainage for pelvic abscess. Ibid.. Sect, iii,
2-17, 12 stereos.
Abdominal hysterectomy for a fibroid uterus. Ibid., Sect, iv,
2-42, 25 stereos.
Bisection for the removal of a large dermoid cyst. Ibid., Sect, v,
2-48, 4 stereos.
The relaxed vaginal outlet. Ibid.. Sect, vi, 2-64, 49 stereos.
Examining and recording a pelvic or other abdominal tumor.
Ibid., Sect, vil, 2-14, 9 stereos.
Dilatation and curettage. Ibid.. Sect, vii, 2-28, 15 stereos.
Removal of the vermiform appendix. Ibid., Sect, ix, 2-26, 18 stereos.
Closing incisions in the renal pelvis. Surg. Gynec. & Obst,
Chicago, 1910, xi, 201-202.
Excision of the fat of the abdominal wall; lipectomy. Surg.
Gynec. & Obst., Chicago, 1910, x, 229-231.
Movable kidney and neurasthenia. Tr. Am. Surg. Ass., Phila.,
1910, xxviii, 513-524.
Incisions in the abdominal wall to expose the kidney: incisions
in the kidnev to explore its pelvis. Tr. South. Surg. &
Gynec. Ass., 1909, [Phila.], 1910, xxii, 294-306.
Operations for hydronephrosis. Tr. Am. Urol. Ass., 1909, Brookline, 1910, iii, 377-395.
A physician's view of Christ's miracles. Sunday School Times,
Phila., 1910, lii, 133.
Bible readers and Bible perusers. Bible Student and Teacher,
N. Y., 1910, xiii, 11-13.
Two great questions addressed to every man and the Bible
answers. Bible Student and Teacher, N. Y., 1910, xiii, 266-268.
Some opening verses in Luke. Bible Record, N. Y., 1910, vii, 229230.
1911
Pyuria. Am. J. Surg., N. Y., 1911, xxv, 1-5.
The abdominal incision — the removal of the wedge of skin and fat
to facilitate intra-abdominal operations. Ann. Surg., Phila.,
1911, Uii, 364-366.
Graduated dilatation of the uretero-vesical orifice and the ureter
above It. Canad. M. Ass. J., 1911, n. s., 1, 849-858.
Abdominal pain. Interstate M. J., St. Louis, 1911, xviii, 194-196.
A new and simple method of removing a renal calculus. .1. Am.
M. Ass., Chicago, 1911, Ivii, 19-20.
Some American medical botanists. J. Am. M. Ass., Chicago, 1911,
Iviii, 437-441.
Also: Bull. Soc N. Hist, Chicago, 1911-12, i, 1-14.
Carcinoma of the clitoris.
In: Stereo-Clinic, Troy, N. Y., 1911, Sect, xx, 2-10, 8 stereos.
Hsematoma of the vulva. Ibid.. Sect, xx, 2-7, 5 stereos.
Removal of cyst of Bartholin's gland. Ibid., Sect, xx, 2-8, 4 stereos.
The best method of exposing the interior of the bladder in suprapubic operations. Surg. Gynec. & Obst., Chicago, 1911, xii,
30-33.
Also: Tr. South. Surg. & Gynec. Ass., Nashville, 1911, xxiii.
64-71.
Getting up early after grave surgical operations. Surg. Gynec. &
Obst., Chicago, 1911. xiii, 78-79.
Boys, are you trying for the prize? Youth's Instructor. 1911.
lix, 16 and IS.
Kelly. H. A. & Burnam. C. F. Reply to " A criticism of the technique of ureteral catheterization of Dr. Howard A. Kelly"
Am. J. Surg., N. Y., 1911, xxv, 220-222.
1912
Medical gynecology. 2. ed. N. Y., 1912. D. Appleton & Co.
713 p. 8°.
Walter Reed and yellow fever. Rev. ed. Bait., 1912. Med. Stand.
Book Co. 329 p. 12°.
A cyclopedia of American medical biography, comprising the lives
of eminent deceased physicians and surgeons from 1610-1910.
Illustrated with portraits. 2 v. Phila. & Lond., 1912. W. B.
Saunders Co. roy. 8".
The treatment of incontinence of urine in women. Therap. Gaz.
[etc], Detroit, 1912, 3. s., xxviii, 685-687.
The history of the vesicovaginal fistula; an address. Tr. Am.
Gynec. Soc, Phila., 1912, xxxvil, 3-29.
To convert sentiment into action in fighting vice. [Baltimore],
1912. 41 p. 8°.
The Influence of segregation upon prostitution and upon the public.
[Phila.T, 1912. 15 p. 8°.
Also: Med. Press. & Circ, Lond., 1912, n. s., xciv, 158-162.
Some scattered thoughts on the prostitution question and about
the attitude of our judges and our police. Social Dis., N. Y.,
1912, No. 3, 13-34.
The social evil: what is the Church doing? The Living Church.
1912. 449-451 (July 27).
1913
Success in life. Jeft'ersonian, Phila., 1912-13, xiv, 1-9.
Talk on radium, delivered at the Medico-Chirurgical Faculty,
April 11, 1913. Maryland M. J., Bait., 1913, Ivi, 151-154.
The allotment of renal and ureteral stones in shadow diagram of
the body. Old Dominion J. M. & S., Richmond, 1913, xvi,
229-231.
Status praesens of the prostitution question. Tr. xv, Internat
Cong. Hyg. & Demog. . . . , Wash. (1912), 1913, iv, 663-673.
Incontinence of urine in women. Urol. & Cutan. Rev.. St. Louis,
1913, xvii, 291-293.
The treatment of cancer with radium. An interview with
Dr. Howard A. Kelly, of Baltimore. Reported by Burton J.
Hendrick. Am. Rev. of Rev., N. Y., 1913, xlviii, 722-726.
-Address delivered at dedication of new building Oct. 16. 1913
[Univ. of Nebraska I. Proc, 4. Ann. Alumni Week, U. of N.,
Coll. of Med., Omaha, 1913.
Dr. Howard Kelly's appeal for Church civic service. Address at
the New York Probation and Protective Association. Tlie
Survey, N. Y., 1913, xxx, 118-119.
W October, 1919 J
301
Illustrated immorality. [Appeal for pictures.] (Communicationa.) The Survey. N. Y.. 1913. xxx, 151.
Letter on Miss Eberle's white slave statuette. (Communications.)
The Survey. N. Y.. 1913. xxx. 312.
Commercialized vice must go. N. American. Phila., 19 1:; (Feb. 15).
Kelly. H. A. & Lewis, R. M. Skiagraphic demonstration of vesical
tumors. Surg. Gynec. & Obst.. Chicago. 1913, xvi. 308-312.
Kelly. H. A. & Lewis, R. M. Silver iodine emulsion: a new medium
for skiagraphy of the urinary tract. Ibid., 707-708.
Kelly. H. A. & Neel, J. C. Carcinoma of the cervix of the uterus.
Johns Hopkins Hosp. Bull.. Bait.. 1913, xxiv. 231-242.
Kelly, H. A. & Neel, J. C. Cauterization of "inoperable" carcinoma of the cervix of the uterus. Johns Hopkins Hosp.
Bull.. Bait.. 1913, xxiv. 372-375.
1914
Some American medical botanists commemorated in our botanical
nomenclature. Troy, N. Y., 1914. The Southworth Co. 215
p. S".
Kelly, H. A. & Burnara. C. F. Diseases of the kidneys, ureters and
bladder, with special reference to the diseases in women.
2 V. N. Y. & Lond., 1914. D. Appleton & Co. 582 p. 652 p. S°.
What radium can do. Internal. Clin., Phila., 1914, 24. s.. iv, 41-43.
Radium in surgery. South. Calif. Pract., Los Angeles, 1914.
xxix. 31-34.
The treatment of vesical fistuls at the vaginal vault following
surgical operations. Tr. South. Surg. & Gynec. Ass., 1913,
Atlanta. 1914, xxvi. 93-99.
A wonderful surgeon. [Theodor Kocher.] Am. Mag.. N. Y., 1914.
Ixxvii. 59.
Smo and Drin — an Allegory. Union Signal. Evanston, 111., Ifll4,
xl, 5 and 7.
Kelly, H. A. & Burnara, C. F. Radium in the treatment of uterine
hsemorrhago and fibroid tumors. J. Am. M. Ass., Chicago.
1914. Ixiii. 622-628.
Kelly, H. A. & Dumm. W. M. Urinary incontinence in women,
without manifest injury to the bladder: a report of cases.
Surg. Gynec. & Obst., Chicago, 1914, xviii. 444-450.
Kelly, H. A. & Lewis. R. M. Diagnosis of the particular forms of
hydronephrosis due to movable kidney. Surg. Gynec. & Obst.,
Chicago, 1914, xix, 601-603.
Suspension of the kidney. Trov. N. Y.. 1915. The Southworth Co.,
21 p. 4'.
In: Stereo-Clinic, Sect. xxix.
History of retrodisplacements of the uterus. Surg. Gynec. & Obst.,
Chicago, 1915, xx. 598-599.
The treatment of cancer by radium. Maryland .M. J.. Halt.. 1915,
Iviil. 161-163.
The radium treatment of fibroid tumors. Tr. South. Surg. &
Gynec. Ass., 1914, Ashvllle, 1915, xxvil, 230-235.
Also: Surg. Gynec. & Obst.. Chicago, 1915, xx. 271-273.
Auto touring for civic righteousness. Christian Advocate. N. Y.,
1915. xc, 712-713.
The virgin birth. Our Hope. N. Y., 1915 (October).
Kelly, H. A. & Burnam. C. F. Radium in the treatment of carcinomas of the cervix uteri and vagina. J. Am. M. Ass.. Chicago,
1915, Ixv. 1874-1878.
Also: Radium. Pittsburgh. 1916, vl, 73-82.
1916
Some radium achievements. Am. J. Surg., N. Y.. 1916. xxx. 73-77.
Radium therapy in cancer of the uterus. Tr. Am. Gynec. Soc.,
Phila., 1916, xli, 532-541.
Treatment of fibroid tumors with radium. Women's M. J., Cincinnati, 1916. xxvi. 1-3.
Radiotherapy. Tr. M. Ass.. Alabama. 1916.
The double shame of Baltimore, her unpublished vice report her
indifTerence. Delaware State M. J.. Wilmington, 1916, vll', 2-5.
.4/ao.- Reprinted for wider circulation by Howard A. Kelly, M. D.
A surgeon's view of Billy Sunday, Surgeon. Sunday School Times
Phila., 1916, Ivlii. 249.
Baker. E. C. Victims . . . . : with an introd. bv Howard A Kellv
Bait, 1916. 20 p. ,S .
Kelly, H. A. & Burnam. C. F. A rfsum^ of results in the radium
treatment of three hundred and forty-seven cases of cancer of
the uterus and vagina. Am. J. Obst.. N. Y., 1916. Ixxiv, 326.
Kelly. H. A. & Neill. W. Caiiterization and fulguration of bladder
tumors. J. Am. M. Ass.. Chicago, 1916, Ixvi. 721-723.
Methods and results of radium treatment of uterine hemorrhage
due to other causes than malignancy. Tr. Am. Gynec Soc
Phila.. 1917. xlii, 408-423.
Also: Am. J. Obst., N. Y., 1917. Ixxvi. 513.
Fibroid tumors of the uterus treated witli radium Charlotte
IX. CI M. J.. 1918. Ixxvii 135-137.
John R. Young, pioneer American physiologist. Johns Hopkins
Hosp. Bull., Bait., 1918. xxix, 186-191.
Fibroid tumors and radium. Virginia M. Month.. Richmond. 1918
xlv. 1-3.
Two liundred and ten fibroid tumors treated by radium. Surg.
Gynec. & Obst.. Chicago. 1918. xxvii, 402-409.
Also: Tr. Am. Gynec. Soc, Phila.. 1918, xliii. 317-335.
Theodore Caldwell Janeway, 1872-1917. Boston M. & S. J., 1918,
clxxix, 597-599.
Joseph Price, 1853-1911. Boston M. & S. J.. 1918. clxxix, 681-684.
John Herr Musser, 1856-1912. Boston M. & S. J.. 1918, clxxix, 772.
Dr. Keen on medical research. Science, N. Y.. & Lancaster, Pa ,
1918, n. s., xlvii, 419.
Whiskey and the "flu." Manufacturers Record. 1918. Ixxiv. 72n.
A message to my three boys who have enlisted. The Evangelical,
1918. 8-9 (January 2).
When a nation prays then victory will come. The Evangelical.
1918 (February 6).
How radium's rays point to Christ. When nature speaks in a
sparkling parable. The Sunday School Times. 1918. 109
(F'ebruary 23).
1919
American medical biography. Bait., 1919, Norman. Remington Co.
[In Press.]
The treatment of papillary tumors of the bladder in women.
Am. J. Obst.. N. Y.. 1919, Ixxx, 328-335.
Reginald Heber Fitz, 1S43-1913. Boston M. & S. J., 1919, clxxx,
75-77.
The treatment of uterine hemorrhages from the mmlern viewpoint. Therap.. Gaz., Detroit. 1919, xUll, 229-233.
Dilatation and curettement. Therap. Gaz„ Detroit, 1019, xliii.
305-314.
The early recognition and treatment of cancer — the duty and the
opportunity of the general practitioner. Therap. Gaz., Detroit. 1919, xllll, 381-389.
Muahrooms and toadstools. Therap. Gaz.. Detroit, 1919. xliii.
465-478.
Cancer of the uterus. Therap. Gaz., Detroit, 1919, xliii. 611-621.
A tribute to Sir William Osier. South. M. J.. Birmingham. Ala..
1919, xli, 346-347.
Osier as I knew him In Philadelphia and in the Hopkins. Johns
Hopkins Hosp. Bull., Halt.. 1919, xxx, 215-216.
Address delivered before the World's Conference of Anti-Saloon
I.*ague Workers, Washington. I). C, June 4. 1919. Bait., 1919.
Anti-Saloon League of Maryland. 12 p. 10°.
DATE OF PUBLICATION NOT ASCERTAINED
On Bible study. New York. n. d.. Loizeaux Bros.. 14 p. 32°.
302
[No. 344
Then and now. New York, n. d., Loizeaux Bros., 8 p. 12°.
The Sabbath and the body. Educational campaign for Sunday
Schools and young people's societies. Lesson 2. Philadelphia
Sabbath Association.
On Bible study. Daily Bible leaflet No. 3. World's Morning
Watch, Clitton-Springs, N. Y.
What a great doctor says. American Sunday School Union, Phila.
In favor of votes for women.
Testimonio personal.
Many articles by Dr. Kelly signed " H. A. K." appear regularly in
the Christian Citizen.
CHRONIC PEMPHIGUS VEGETANS OF SEVERAL YEARS' DURATION
By Lewellys F. Barker,
Professor of Clinical Medicine, Johns Hopkins University, Baltimore,
AND
David W. Caeter, Jr.
{Formerly Resident Physician in Charge of the Private Ward Service, Johns Hopkins Hospital), Dallas, Texas
Though pemphigus vegetans is described as terminating
fatally usually within one year from onset, a few eases of long
duration are known, notably one recorded by Neumann of
ten years' duration and another of similar duration described
by Kobner in 1894. We have recently had under observation,
in the private ward of this hospital, a patient who has already
suffered from the disease for more than five years and who is
still living, the condition exhibiting remarkable remissions
and exacerbations. The malady is so rare and its nature is
so obscure that even single cases that deviate in any way from
the ordinary type should be recorded in the hope that data
may gradually be accumulated that will clear up the mysterjthat still enshrouds the disease.
Pemphigus vegetans was clearly differentiated and first
described as a clinical entity by Neumann' in 1886. The
first English ease to be reported was the well-known one of
Crocker' (1889). In 1891 Hyde' described the first case
recognized in America. A fatal case from our clinic was
reported with careful clinical history, autopsy findings, together with histological and bacteriological examinations, in
1903, by Hamburger and Eubel.* They reviewed the literature thoroughly and showed the gradual differentiation of the
diseases once grouped together as " pemphigus." No review
of the development of our knowledge of the disease is included, therefore, in the present paper.
Personal Observations
The case to be reported here is that of a young, tmmarried
\\'oman, age 20, born in the United States, who was admitted
to the medical service of the private wards, Johns Hopkins
Hospital, on July 2, 1917. She complained of a " skin eruption " and of " colitis."
The family history was negative. One paternal aunt had
died of cancer. There was no history of any skin disease in
the family.
Syph., Wien,
'Neumann: Vierteljahrschrift tiir Dermatol.
1886, p. 159.
'Crocker: Brit. M. J., 1889, I.
'Hyde, J. N.: J. Cutan. Dis., 1891. IX. 412-456.
•Hamburger, L. P., and Rubel, M.: Bull. Johns Hopkins Hosp.,
1903, XIV, 63-70.
As to her own past history, the patient had never been robust.
She had the usual diseases of childhood without complications. At the age of three years, she suffered from " intestinal
indigestion " and a diagnosis of " follicular colitis " was
made ; and at the age of six, she is said to have had a similar
attack, during which she had abdominal pain, " indigestion,"
diarrhea, and blood in the stools. Whenever she has been
" run-down," from childhood on, she has had somewhat similar intestinal attacks. For some time past, she has had a
chronic conjunctivitis and blepharitis. Her habits and mode
of life have been normal. She has made a practice of sleeping out-of-doors.
About six years prior to admission the patient lived for a
time in Constantinople. While there she had digestive disturbances, and on the way home to the United States a most
distressing " urticaria " developed. Somewhat later she was
" covered with an eruption much like that present at the time
of admission."
There has been some intestinal trouble ever since her trip
abroad. Thus, in 1913, the patient was seriously ill for some
time with " colitis." In 1914, an appendectomy was performed, followed by general improvement. In August, 1915,
lesions appeared in the mouth; in November, 1915, the eyes
became inflamed and in December of the same year lesions
reappeared in the mouth and also made their appearance on
the external genitals (vulva) for the first time. A diagnosis
of " herpes " was made at this time ; but, later on, the opinion
was that the lesions were luetic in origin and the patient received numerous intravenous injections of salvarsan. In
August, 1916, another physician made the diagnosis of " neurotic herpes," but he also soon changed his opinion and made
the diagnosis of syphilis, treating the patient accordingly.
There was some improvement following this arsenical treatment. In October, 1916, the lesions, which were described as
" superficial ulcerations developing after small blisters had
burst," reappeared in the mouth and about the vulva. Another
series of intravenous injections was administered and five
weeks later the lesions had disappeared. In December, 1916.
ulcerative lesions again appeared in the mouth. In April of
the following year, 1917, lesions in the throat were troublesome and tliose on the vulva were also noticeable, but were
THE JOHNS HOPKINS HOSPITAL BULLETIN, OCTOBER, 1919
PLATE XXXVIII
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' ' ' !'• " I'liigus vegetans. The appearanre of the axillary lesions on January 6, 1918, is here shown.
OCTOBEB, 1919]
303
not pronount-ed until May when the severe attack that led
till' patient to apply for treatment at tlii;; h(is]iital beu^jin.
Physical Examination. — At the time of admission, the physilal examination showed a marked degree of emaciation, the
patient being 3() pounds below her calculated ideal weight.
There was sliglit pallor of the skin and mucous membranes.
The eyes showed a >light conjunctivitis and a moderate degree
of blepharitis. On the lips, palate and pharyn.v tliere was
extensive superticial ulceration, which, over the lips, had
involved the adjoining skin and had gone on to crust formation. The examination of the genitalia showed extensive excoriations of the labia majora, labia minora and vaginal
mucosa. Tlie labial lesions varied in size, all the way from
-small isolated vesicles to areas 1.5 to 2 cm. in diameter. The
edges of the larger lesions were definitely elevated and consisted of clo.'^ely-.-^et vesicles containing turliid fluid. The
lesions were covered with a foul, mucoid discharge. The inflammatory areola about the lesions was slight. There was no
general glandular enlargement and the spleen was not palpable. The remainder of the physical examination showed no
significant abnormality. The temperature was !»!t.6° F. and
the pulse-rate 00. The patient complained mudi of pain in
the region of the vulva and in the throat. She could not eat
and was rapidly losing weight.
Laboratory Examinations. — At the time of admission (July,
1917) the blood examination showed: Hemoglobin 60 per
cent (Sahli). and 1.").800 leucocytes. An examination made
a month later showed R. B. C, 4,600,000 ; W. B. C, 8 100 ;
lib. (.'^ahli), 81 i)er cent. In February, the examination
showed K. B. C. I,o00,000; W. B. C, 8200; Hb. (Sahli), 88
per cent; and in the differential count PM. X., 68 per cent:
I'M. B., 0.0 per cent ; PM. E., 1.5 per cent; S. M., 18 per cent;
L. M., 12 per cent : Trans., l.o per cent.
The examination of the stools chemically and microscopically was negative.
The urine on a number of examinations was normal, except
for the presence, occa.«ionally, of a trace of alliumin.
The Wassermann test of the blood-serum was negative on
two occasions, as it had previously always been.
A culture for bacteria, made from the mouth lesions, showed
no unusual organisms, though colonies, chiefly of Slaphijloroccus aureus, grew out. Smears made fr')m the lii>s, mucous
membrane of the checks and pharyngeal pillars were all quite
similar, showing only a few cocci and bacilli. There was nothing suggestive of the organisms that are found in Vincent's
angina; there were no bacilli that resembled B. diphtheria'.
nor were any pathogenic moulds found.
Roentgenogrnms of the ga-strointestinal tract showed a large,
ptosed, cowhorn-shaped stomach, which was drawn well over
to the right and downward. There was sluggish peristalsis
and delayed emptying time. There were, however, no filling
defects. There was some cecal sta-sis, enteroptosis and evidence
of (post-operative?) adhesions in the lower right quadrant.
No.<te and Throat Report. — An examination made by Dr. S.
J. Crowe on July 6 showed moderate enlargement of the
posterior cervical lymph glands and superficial ulieration of
the soft palate, of both tonsils, pharynx and cheeks. The
larynx and naso-pharynx were not involved in the ulcerative
process. The paranasal sinuses showed no evidence of
infection.
Xeuroloijical and F.fi/chic Examination. — There were no
ol)jective disturbances of sensation, and subjectively only pain
and some itching were complained of. Motility and reflexes
were normal. Psychically, the jiatient reacted normally in
l>eriods of remission, though during periods of exacerbation
she was depressed, irritable and capricious.
I'rotein-Sensitization Tests. — In order to rule out, if possil)le, all the ordinary proteins (foods, pollens, etc.) that act
as causes of allergic states, cutaneous test-s were made with egg,
cocoa, casein, peas, barley, wheat (bread), potato, golden-rod
pollen, rag-weed pollen, tiniotliy pollen, Iiorse-dander, and
staphylococci. The results were all negative.
Course in the Hospital. — About three weeks after admission
tlie patient developed an outspoken diarrhea. At this time a
considerable amount of mucus and several large blood-clots
were found in the stools. Microscopically, there were numerous leucocytes, fatty acid crj-stals, neutral fat and some muscle
fibers in the feces. Cultures of the stool and of the washed
mucus showed only the colon bacillus. Because many of the
stools were large, light-colored and pultaceous, a quantitative
diastase determination was niaile. The quantity present was
above the normal minimum.
Throughout tiie patient's stay in the hospital, the diarrhea
and intestinal symptoms, the colicky pains, the vague abdominal distress and the " indigestion "' were the most distressing symptoms, causing more trouble at most times than
the skin lesions." There were seldom less than three, and often
as many as ten, stools a day. Occasionally, there were attacks
of vomiting, the vomitus being at times blood-tinged.
By the first of August the lesions in the mouth had disappeared and those about the vulva were much improved. On
this date groups of several small vesicles were seen on the
hard palate. The fluid was clear and small in amount. Each
vesicle was surrounded i)y a slight erythematous areola. The
vesicles did not persist for more than 21 hours and, after
rupturing, coalesced to form very superficial ulcers varying
in size from .25 to 1.5 cm. in diameter. The ulcers were
grayish-white in color and seemed to be covered with a pellicle,
the surrounding areola was slight. At this stage, the resemblance to the mucous patches of syphilis was striking.
Ten days after the reappearance of those in the mouth two
symmetrical lesions developed on the breasts. These attained
the size of a quarter and resembled closely the lesions of the
vulva, except that there was more inflammatory reaction about
them and less discharge from the surface. They persisted for
three weeks, disappeared spontaneously and left no scars.
About the time of the development of tlie brea-st lesions the
patient's temperature became elevated, reaching 102.6° F. It
subsided within 48 hours. This was the only febrile episode
of moment A blood culture made at this time showed no
growth. Xo adequate explanation of the fever was arrived at.
304
[No. 344
About the last of August, 1917, there developed pain on
defecation and the amount of blood and mucus in the stools
increased. A proctoscopic examination at this time showed a
superficial ulcerated area, rather dark blue in color ; it covered
the entire circumference of the rectum and extended upward
about four inches, where it merged with mucosa of normal
appearance. Ten days later the appearance of the rectal
mucosa was again normal.
During September, October and the first half of November,
tlie patient was somewhat better. The lesions recurred from
time to time in the mouth, but were transient. There were
brief attacks of diarrhea, but the abdominal pain was less disturbing than it had been.
About the third week in November, extensive ulceration
again occurred in the mouth; the lesions about the vulva,
which had almost cleared up, became more extensive and
painful ; several small lesions appeared in the left axilla ; the
diarrhea became more intractable. The body-weight which
had increased from 107^ pounds to 129^ pounds began, at
this time, to decrease, and the patient lost steadily up to the
time of her discharge from the hospital.
The axillary lesions appeared first as groups of small vesicles.
They ruptured, coalesced and formed very superficial ulcers.
At no time were any true bullae seen.
The lesions on the vulva and in the axilla progressed steadily
and the condition of the axilla on January 6 is shown in Pig. 1
(colored drawing). Fig. 3 (a photograph) shows the appearance of the vulval lesions on January 21, 1918.
During February, 1918, the axillary lesions spread, covering the entire axilla and extending down the thoracic wall for
several centimeters. The perigenital lesions spread, extending over the mons veneris and down the thighs for a short
distance. As the lesions progressed, the granulomatous and
vegetative character became more evident. The edges were
definitely elevated and had a " rolled " appearance. The
secretion from the large lesions was abundant, fOul, yellowish
in color and mucoid. A number of small lesions now appeared
over the face, abdomen and buttocks, but they were of short
duration.
Two weeks before discharge from the hospital, which was
on March 12, 1918, a distinct improvement in the condition
of the lesions had set in. They no longer increased in size,
were less elevated and there was less discharge from them.
The diarrhea continued, however, to be troublesome. The
body-weight was 112-| pounds, only five pounds more than on
admission.
Subsequent Course. — Upon discharge from the hospital, the
patient returned to the care of Dr. J. A. Fordyce, under whom
she had previously been for a time. He has kindly supplied
us with the following information :
For three or four weeks she seemed very much better, but about
May 1, 1918, she became decidedly worse again. There was an
extensive outbreak of lesions about the vulva, thighs and lower
part of the abdomen. About the middle of May, lesions appeared
over the scalp, neck, back and chest and intractable diarrhea again
developed.
When seen by one of us on June 1, 1918, the patient's condition appeared to be worse than at any time previous. There
was marked pallor and emaciation; the lesions were more
extensive than ever and the process appeared to be very active.
Later she improved somewhat, and left New York City for
her home. On September 25, 1918, the patient's mother
wrote :
She has not suffered so acutely as she did from the attack she
had in New York, but the trouble never clears up and now the
outbreak is more extensive than ever before. Twice her head has
been entirely free from the eruption, and then it has broken out
again; now it is clearing for the third time. She has had a great
deal of digestive trouble
The patient has not been seen by us since, but in response
to a note of inquiry, we learned at the end of January, 1919,
that she was again having a remission, attributed this time to
Christian Science. She says in her letter :
You will be glad to hear that, though I am not entirely well,
I have every hope of being so, having been so far healed through
Christian Science as to be able to be about and lead a normal life.
When I was desperately ill last fall and no one held out any hope
of my recovery. Dr. , an old friend of my father's, advised
my turning to Christian Science. I was prejudiced against Science
and was too weak at the time to be troubled, but I am firmly convinced that I was literally pulled from the brink of the grave by
the power of prayer. Certainly, all medical means had been exhausted. Later, when I was still very ill, I turned to Christian
Science and have since steadily improved.
Histological Study. — On January 21, 1918, a bit of the
cutaneous lesion, indicated by the arrow in Fig. 2, together
with some of the surrounding normal tissue was excised for
histological study. The sections were stained for acid-fast
organisms, for ordinary bacteria, by Gram's method, and by
the Levaditi method for spirochetes. An examination of these
sections failed to show any bacteria or parasites.
The following is a report on the histology by Dr. I. K. Pels,
of the Department of Dermatology :
The sections are stained with hematoxylin and eosin. With the
low power one sees a marked thickening and irregularity of the
rete layer. The striking features of the section are the dilatation
of the lymph spaces and blood-vessels, with marked infiltrations,
especially about the latter, and extending in particular to the
vessels deep down in the corium. In one place there is marked
edema of the papillary layer, with a suggestion of beginning
vesicle formation. The adnexa of the skin appear normal.
Under the high power one sees that the rete is thickened irregularly with some hyperkeratosis, acanthosis, and elongation of the
rete pegs. The granular layer is increased in thickness in certain
places. There is some edema of the prickle-cell layer and occasional infiltration with small mononuclear cells. The pars papillaris shows in some places a marked edema. There is dilatation
of lymph-vessels and blood-vessels, and there are also many large
lymph spaces. In one area the papillae have been entirely obliterated, apparently through pressure. There is marked infiltration
with mononuclear cells; these are collected particularly around
blood-vessels; the infiltration, in some instances, extends to a
level directly beneath the rete layer. There is some edema in the
corium. There are many small blood-vessels, probably newly
formed. No marked changes are to be made out in the elastic or
connective-tissue fibers. The blood-vessels are enlarged, but there
is no definite endarteritis to be seen. The walls of the arteries.
ii THE JOHNS HOPKINS HOSPITAL BULLETIN. OCTOBER, 1919
PLATE XXXIX
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however, are thickened, and there is a suggestion of occlusion of
some small vessels. Many of the vessels are filled with red bloodcells and there is a marked cellular infiltration of the vessel walls
and of the tissues just outside them. Even the deepest bloodvessels of the cerium show a perivascular exudate of round cells.
The infiltration cells consist for the most part of small
mononuclear elements, but there are a few polymorphonuclear
cells, some of which have a reddish-staining protoplasm, suggesting an eosinophilic granular +++++
CONTENTS. There are. also, a few
plasma-cells. Mast-cells were not seen (special stain required).
My impression is that we are dealing with an inflammatory reaction, sub-acute in type, with formation of new vessels, giving rise
to a granuloma. There is, on the part of the blood-vessels, apparently a reaction to some agent causing extravasation of cells
with edema and subsequent enlargement and thickening of the
rete layer. It is not a picture of syphilis or of tuberculosis; it
corresponds more to the histologic picture of pemphigus vegetans.
2'realment. — During the patient's long stay of oiglit and
a half months in the hospital many and various local and
general measures were tried. None had any directly curative
effect upon the lesions of the skin and mucous membranes.
Upon admission, the most urgent indication stx-mcd to be
to overcome the emaciation, anemia and diarrhea. With this
in view, the patient was kept in bed, in charge of a special
nurse, and placed upon a bland diet to which liberal amounts
of milk and cream were added. Dilute hydrochloric acid,
Blaud's pills and various anti-diarrhcal mi.xtures were also
u.*ed. There wa.s a steady gain in weight and improvement in
the anemia until the last severe attack began i^hortly before slie
left the hospital. For the intestinal condition, yeast was tried
for a wiiile. half a cake twice a day. without any apparent
effect. Later, hj-podermic injections of emetine hydrochloride
were given, but no improvement followed.
Locally, many different ointments, lotions and dusting
j>owders were used ; aside from alleviating the pain temporarily, they were of no value.
Several courses of sodium cacodylatc, in larger and in
smaller doses, were given. No definite effect upon the lesions
was observed.
In November, autohemothcrapy was tried, the patient re<eiving two injections of whole blood. This treatment had to
Ik; given up l)ecause of the patient's condition.
In January, radium (180 mgm.) was ap]>licd to the axillary
lesions by Dr. Curtis Burnam for ;3.j minutes. There was
no ob.eervabic effect.
In Feliruarj-, two intravenous injections of arsphcnaniine
(0.4 and 0.5 gm.) were given. Early in March the axillary
lesions were twice treated with x-rays. Following the arsenical
and Roentgen-ray treatments both the axillary and vulval
lesions improvcfl markedly. There was also great improvement in the patient's general condition, but six weeks later the
eruption was more widespread than ever before.
Throughout the cour.sc, most benefit was derived from
general upbuilding measures and, perhaps, from injections of
salvarsan (or arsphenamine). though remissions and exacerbations seemed to recur quite independently of any therapy.
Discussion. — We have had, then, under our ob.«ervation,
over a long period, a young woman who has suffered from a
remarkable form of vesiculo-ulcerative, granulomatous process,
which has involved the skin and mucous membranes, which has
exhibited a marked tendency to spontaneous remissions and
exacerbations, and has proved refractory to all kinds of
therapy thus far employed.
That the diagnosis of chronic pemphigus vegetans is a
correct one seems certain from: (1) The character of the
lesions and especially their resemblance to those of syphilis
(for which, as in so many cases of pemphigus vegetans, the
disease was for a time mistaken) ; (2) the clinical course of
the case; (3) the histological examination of the excised
tissue; and (4) the exclusion of tuberculosis, syphilis and
other common causes of granulomat<^)Us processes. In this
diagnosis. Dr. J. A. Fordyce, of New York, and Dr. J. W.
Lord and Dr. I. R. Pels, of Baltimore, all experienced dermatologists, concur.
Certain features, it is true, made one hesitate, at first, to
make a diagnosis of pemphigus vegetans. Thus, as Dr. Fordyce pointed out, it is uncommon in pemphigus vegetans to
have the lesion remain localized for so long a time to the oral
mucosa and the genital organs ; and, besides, the lesions seemed
to be deeper than in most cases of pemphigus. For these
reasons, the diagnosis of " Periadenitis mucosa necrotica
recurrens " (see Sutton's Text-book) was seriously considered ;
but. as Dr. Fordyce emphasizes, the character and the localization of the lesions, the chronic course and the resistance to
all therapeutic measures employed, confirm the diagnosis of
pemphigus vegetans. Jloreover, the histological study revealed a perivascular granulomatous infiltration rather than
a periadenitis.
What can be the etiology of this remarkable malady? Wc
have been unable to answer this question satisfactorily, though
there are several features that have interested us especially;
the.<e may give clues to etiology ;in(l spur us on to further
studies in similar cases.
Thus, in the first place, though the disease docs not apjicar
to be contagious (in the sense in which this word is ordinarily
used), still there is much to make us believe that it is due to
a chronic infection. Its resemblance, clinically, to syphilis,
the episodic ])yrexias and transitory Icucocytoses that accompany it, the chronicity and resistance to therapy, the tendency
of the lesions to eccentric extension, and the histolr)gical picture
of a granulomatous process (similar to, but not identical with,
granulomatous processes due to known infectious agents like
the Treponema pallidum of syphilis, the Trepunema pertenue
of yaws, the Bacillus tuberculosis, the liacilhis mallei, the
Ji. rhinoscleromatis, the Bnfillus leprw, the Slreplothric.es,
the Sporotrichum schenckii, the Cryptococcus (/ilchrislii (of
so-called blastomycetic dermatitis) and the Posadasia esseriforme (of coccidioidal granuloma or the San Joaquin Valh-y
di.sease), are all features that make us su.'spect strongly that
ue must h> dealing u-ith soinr chronic hnctcritil infection or
jmrasitic invasion.
In the second place, one must he struck with the elective
affinities of the disease-process for certain parts of the skin
and mucous membranes. Thus, though any part of the skin
306
[No. 344
may be involved, the disease shows an especial tendency to
attack the perigenital region, the inguinal regions, and the
axillEe. Again, the mucous membrane most often attacked
first is that of the mouth and throat, though it is not uncommon to have the vagina and the rectum also involved. In our
patient, besides the rectal involvement, there had been a history of " colitis " and of severe gastrointestinal attacks from
earliest life on, a point that may be of some importance. Our
patient suffered also from chronic conjunctivitis and blepharitis; in a case described hy Ludmg (1897) the preputial sac
and urethra were first affected ; and in Hamburger and Kubel's
case, hoarseness due to the involvement of the laryngeal
mucosa was the first symptom. These sit^s of predilection of
the lesions can, of course, be no accident, and we shall doubtless, sometime, find an explanation of them.
In the third place, we lay a good deal of stress upon the fact
that, in the lesions, the infiltration of the tissues with small
mononuclear cells is predominantly perivascular. The chemotactic influence, exerted upon the small mononuclear elements
(and to a slight extent upon the polymorphonuclear elements),
is chiefly localized (in the corium of the affected areas of skin)
in the immediate neighborhood of the blood-vessels. Though
this does not prove that the causative microorganisms are
similarly situated, the fact is suggestive.
In the fourth place, the occurrence of marl-ed exacerbations
and remissiotis in the course of the disease pi-esents a striking
analogy with what we knoiv of recrudescences a7id ameliorations in some of the treponemal diseases, especially syphilis
and yaws. Though analogies of this sort are not to be taken
too seriously, we must, in a grave disease like pemphigus
vegetans, pay close attention even to straws, in the hope that
tliey may show us which way the wind blows.
STUDIES ON BLOOD SUGAR
IV. EFFECTS UPON THE BLOOD SUGAR OF THE REPEATED INGESTION
OF GLUCOSE
Louis Hamman and I. I. Hirschman
In a previous communication the authors ' have demonstrated the blood sugar response to the ingestion of a single
large dose of glucose in normal persons and in others suffering
from various diseases. For this study 100 grams of glucose
were administered in the early morning after the night fast
and the blood sugar and urine sugar estimated at short intervals thereafter. It was demonstrated that there are two
important types of reaction, the normal type and the diabetic
type, and still a third type, not nearly so clearly distinguished
as these two, the reaction of increased carbohydrate tolerance.
Although the reaction in normal persons varies in different
individuals and in the same individual under different circumstances, its general characters are as follows: the blood sugar
rises rapidly, but seldom exceeds 0.15 per cent; it falls somewhat more slowly to the original level, the whole reaction
being over in less than two hours. In diabetics the rise is
liigher and longer sustained. If the blood sugar surpasses
0.18 per cent, sugar usually appears in the urine, but sometimes it appears at a somewhat lower level and at other times
it fails to appear even though 0.2 per cent of blood sugar is
exceeded. From two to five hours pass before the blood sugar
reaches the original fasting level. When tlie carbohydrate
tolerance is increased, there is only an insignificant rise in the
lilood sugar, wliich has usually a low fasting level.
Epstein " and Woodyat ' have raised the objection that these
variations in blood sugar following the ingestion of glucose
represent not real variations in the sugar +++++
CONTENTS of the blood,
but apparent variations due to changing blood volume. This
possibihty had suggested itself to us, but the investigations
of Mosenthal and Hiller ' show conclusively that there is no
constant relation between variations in blood sugar percentage
and the water +++++
CONTENTS of the blood. Indeed, these two factors
show such bizarre relations that the one surely cannot depend
entirely upon the other.
There is every possible gradation in the response to glucose
ingestion, from the low insignificant curve of high glucose
tolerance to the extreme and prolonged curve obtained in
severe diabetes. However, the so-called diabetic curve is not
peculiar to diabetes, for similar curves, though usually not so
extreme, are obtained in nephritis, in hyperthyroidism and in
many other conditions of lowered carbohydrate tolerance.
These innumerable gradations force upon us the conviction
that disturbances of carbohydrate tolerance are quantitative,
not qualitative, variations. In other words, that diabetes
represents functionally a disturbed, not an altered, mechanism
of carbohydrate control.
For many years investigators have sought to distinguish
between the glucosuria of diabetes and the glycosurias due to
a great variety of other conditions. Of the many distinguishing marks that have been proposed only two '' are still urged
as pertinent, namely, the paradoxical law of Allen and the
diuretic effect of sugar in diabetes. Under normal conditions,
when sugar is injected intravenously in large quantity, it acts
as a diuretic ; administered otherwise, it diminishes the output
of urine. In diabetes sugar acts as a diuretic by whatever
route it be administered. But although this distinction is true
for normal and totally diabetic animals, it is only relatively
true for human beings. The ease with which sugar acts as a
diuretic depends upon the degree of diabetes; in mild cases
conditions are much nearer tlie normal than in the completely
diabetic. In other words, the ease with which sugar produces
diuresis depends directly upon the degree of carbohydrate
tolerance and it varies with this tolerance. Here again tlie
distinction is purely quantitative and the varying diuretic
October. 1919]
307
t'ffett of sugar surely eaunot be pointed out as a mark of di?^tim-tion between dialietes and other glycosurias. How convincingly the ol)scrvations of Woodyat and his co-workers '
eonfirm this statement! By carefully measured and timed
intravenous injections of glucose the tolerance of an individual
ean be accurately detenwined and sugar begins to act as a
diuretic when tliis limit is overstepped.
It follows, then, that the only remaining feature that can be
drawn upon to point a qualitative distinction between diabetes
and other glycosurias is Allen's paradoxical law. Allen '
enunciates this Unv in these words: " Whereas in normal individuals the more sugar is given the more is utilized, the reverse
is true in diabetes." .\pparently this law was enunciated to
lit conditions in totally diabetic animals to which it applies
aptly enough, but if we understand properly what is meant by
the law. it is not applicable to diabetes in human beings.
A\"hen carbohydrate tolerance is reduced only mildly the level
of tolerance is by no means ai)solute. For instance, if the ingestion of SO grams of glucose be followed by the excretion of
1 gram of glucose in tlie urine, the ingestion of 100 grams will
not caus«> an excretion of 51 grams. Far from it! Sudi experiments liave been frequently made and only a small jiroportion of the excess iuis been recovered from the urine. Only
when excessive amount,-; of glucose are administered intravenously and at a uniform rate is the proportion of excretion
constant. Here again the difference seems distinctly to be
quantitative and not qualitative.
It occurred to us that further important evidence bearing
upon this point could be obtained by testing the reaction of
patients to the repeated ingestion of glucose. If there be a
qualitative difference in the utilization of glucose by normal
l>ersons and by diabetics, such tests should certainly give evidence of the difference. The only observations upon this point
that we were able to find in the literature are a few experiments
upon rabbits reported i)y Bang. In normal rabl)its Bang'
finds that the .second administration of a certain do.^c of gluco.se given during the decline of the reaction from the first
administration is followed by a much less marked reaction
than was the first.
EXPERIMENTAL RESULTS
In normal persons the administration of a second dose of
glucose immediately after the reaction to the first dose produces a much less marked reaction upon the blood sugar than
did the first dose. The protocols of experiments I and II
illustrate this.
Experiment I
E. L. C, male, single. Age: 28. Healthy physician.
Blood luKir Iririr t'r
nc »
Time
pfr cent c. c. per hour gran
» !«
8.30
0.086
9
Glucose :
100 grams In 300 c. c. water.
9.00
0.118 88
9.30
0.110 74
10.30
0.087 162
Glucose:
100 grams In 300 c. c. water.
11.00
0.087 150
11.30
0.078 150
12.30
0.096 111
niood lugar Urine Urine auKar
Time per cent c. c. per hour grams per hour
Glucose: 100 grams in 300 c. c. water.
1.00 0.080 31
1.30 0.087 26
2.30 0.094 ' 26
Experiment II
B. H.. male, single. Age: 29. Healthy physician. The patient,
when previously tested, had shown a low renal threshold; that is,
sugar had appeared in the urine when the blood sugar reached
0.14 per cent.
Blood sufrar I'riue Tritie siiRar
Time percent e. *•. per hour firunis iier hour
9.15 0.110 28
9.16 Glucose: 100 grams in 300 c. c. water.
9.45 0.162 28 Trace
10.15 0.127 30 Trace
10.45 0.130 26
10.50 Glucose: 100 grams in 300 c. c. water.
11.20 O.no 28
11.50 0.122 21
12.20 0.115 26
These experiments indicate that the mechanism of carbohydrate utilization, once stimulated, works more efTiciently
than when called upon abruptly to manage large amounts of
glucose. Probably to this fact is largely due the better utilization of sugar slowly absorbed, and the almost unlimited power
of the body to utilize starch.
In diabetics the same difference is observed as in normal
persons, although the difference is not so marked. The following protocols illustrate this point:
ExrERI.MF.NT III
A. B.. male, white, married. Age: 46. Dispensary No. 467.")0.
A moderately severe diabetic who had become sugar-free on a
carbohydrate free diet.
Time
8.25
8.30
9.00
9.32
10.30
11.30
11.35
12.05
12.30
1.30
2.30
Blood suRar
per cent
0.161
tTr
Trine sugar
. c. per hour K:rams per hon
42
Glucose: 20 grams in 300 c. c. water.
0.205 51 0.3
0.244 5ti 1.57
0.196 45 0.9
0.180 68 0.66
Glucose: 20 grams in 300 c. c. water.
0.161 63 0.23
0.188 55 0.26
0.205 117 0.44
0.164 113 0.34
EXI'ERIMKNT IV
A. T., male, white, married. Age: 4ii. Hospital No. .^7026.
Diagnosis: Hypertension, myocardial insufflclency. emphysema,
artprlo-sclerosls, diabetes mcllltus, obesity. The patient had only
a small amount of sugar in the urine, easily controlled by a
moderate regulation of the diet.
Time
8.35
8.38
9.10
9.42
10.45
11.15
Blood auitar
per ci'iit
Irin
- hour
Irin
0.150 4
Glucose: 100 grams In :U)0 c. c. water.
0.206 .1
0.272 33 0.68
0.222 76 2.66
0.190 49 1.63
308
[No. 344
Ur
Urine sugar
grams per hour
Time per cent c. c. per hou
11.18 Glucose: 100 grams In 300 c. c. water.
11.45 0.212 41 1.36
12.27 0.209 54 1.69
12.57 0.173 37 0.56
Per.sons with lowered carbohydrate tolerance but without
outspoken diabetes react in a similar way. Even if the second
dose of glucose be much larger than the first the reaction following is not so marked.
Experiment V
W. G., male, white, single. Age: 47. Hospital No. 36926. The
patient had a mild infection of unknown cause and mental symptoms. No definite medical diagnosis had been made. Sugar had
never been found in the urine on ordinary ward diet.
Time
Blood sugar
per cent c
Urine
c. per Iiour
Urine su
grams pe
8.40
0.120
8.5
8.49
Glucose: 50 grams
in 300 c. c.
water.
9.20
0.176
314
9.53
0.200
463
1.7
10.55
0.166
242
O.S
10.57
Glucose: 50 grams
in 300 c. c.
water.
11.30
0.178
246
0.5
12.00
0.136
132
0.6
12.45
0.130
79
Experiment
VI
J. H., male, black, married. Age: 39. Surgical No. 42151.
Diagnosis: Exophthalmic goitre, adenoma of thyroid. No sugar
had been found in the urine on the usual ward diet.
Blood sugar Urine Urine sugar
Time per cent c. c. per liour grams per hour
8.30 0.097 36
Glucose: 100 grams in 300 c. c. water.
9.00 0.130 64
9.30 0.196 31
10.05 0.177 73
10.45 0.161 49
11.00 Glucose: 100 grams in 300 c. c. water.
11.30 0.173 57
12.00 0.164 142
12.30 0.148
1.00 0.116 25
Experiment VII
Aurelius N.. male, white, married. Age: 37. Medical No. 36828.
Diagnosis: Bilateral facial palsy, psychoneurosis. No sugar appeared in the urine on the ordinary ward diet.
Blood sugar Urine Urine sugar
Time per cent c. c. per hour grams per liour
8.25 0.093
8.30 Glucose: 100 grams in 300 c. c. water.
9.00 0.161 32
9.30 0.096 97
10.05 0.100 129
10.07 Glucose: 150 grams in 300 c. c. water.
10.35 0.148 84
11.05 0.097 60
11.36 0.094 114
In the following patient the utilization of glucose is normal,
although a small amount of sugar appears in the urine. The
patient has a low renal tlireshold, that is, a mild gi-ade of renal
diabetes.
Urinn Urine sugar
. c. per hour grains per hour
43
Experiment VIII
W. A. C, male, white, married. Age: 36. Diagnosis: Hyperthyroidism, psychoneurosis, renal diabetes. Small amount of sugar
occasionally found in urine. A good deal of sugar in the urine
after the ingestion of 75 grams of glucose.
Blood sugar
Time per cent
8.30 0.088
8.40 Glucose: 100 grams in 300 c. c. water.
9.10 0.125 92 Trace
9.35 Glucose: 100 grams in 300 c. c. water.
9.43 0.105 251 0.2
10.10 0.085 658
10.50 0.084 216
11.40 0.084 68
It was found in testing several patients that they reacted to
levulose in the same way that they did to glucose, only that the
blood sugar rise was less marked. For instance, the diabetic
whose response to glucose is detailed in experiment III gave
the following response to levulose :
Experiment IX
A. B., (same patient as In Experiment III). Male, white,
married. Age: 46. Dispensary No. 46750. A moderately severe
diabetic who liad become sugar-free on a carbohydrate diet.
Blood sugar Urine Urine sugar
Time per cent c. c. per hour grams per hour
8.30 0.167 66
8.34 Levulose: 20 grams in 300 c. c. water.
9.01 0.177 36
9.33 0.194 68 0.5
10.32 0.177 150
11.00 0.177 329
11.02 Levulose: 20 grams in 300 c. c. water.
11.35 0.167 178
12.10 0.184 103
1.00 0.184 144
CONCLUSIONS
1. The ingestion of glucose in some way stimulates the
mechanism of carbohydrate disposal so that the repeated ingestion of the same amount causes a less marked hyperglycemia.
2. The same stimulating effect is noted in diabetes; the
second dose is followed by a less marked hyperglycemia and
glycosuria. However, the difference between the effects of the
two doses is less marked than in -normals and varies in different stages of the disease. Possibly, when the diabetes is
very severe, the difference may completely vanish.
3. In renal glucosuria the normal stimulating effect of the
ingestion of glucose is retained.
4. Levulose produces a much less marked hyperglycemia
and glycosuria than does an equal amount of glucose.
5. The difference in the reaction of the normal and the
diabetic is a quantitative not a qualitative difference.
REFERENCES
1. Hamman and Hirschman: Archiv. Intern. Med., 1917, XX, 761.
2. Epstein: Discussion: Soc. for Clinical Inves., May, 1916.
3. Woodyat: Discussion: Assoc. American Phys., May, 1917.
4. Mosenthal and Hiller: Jour. Eiolog. Chem., 1916. XXVIII, 197.
5. Joslin: Treatment of diabetes mellitus, 2d Edition, 1917.
6 Woodyat, Sansum and Wilder: Jour. Am. Med. Assn., 1915,
LXV, 2067.
7. Allen: Glycosuria and diabetes, 1913, Harvard Univ. Press.
8. Bang: Der Blutzucker, Wiesbaden, 1913.
OCTOBEB, 1919]
309
BENZINE POISONING, WITH REPORT OF A CHRONIC CASE
By RissKi.i. L. ir.viiKX, M. D.. Detroit. Midi.
(From the Medical Clinic of The Johns Hopkins Hospital)
Benzine rarely causes poisoning, although it is largely used
in the industrial world, especially for vulcanizing rubber, driving motors, cleaning, and as a drier in paints. Poisoning may
be caused by eitlier drinking or inhaling large amounts of the
substance. The absorption of small quantities seldom produces ill effects.
Benzine is a product of petroleum. It is not to be confused
with benzene or benzol which is obtained by the fractional distillation of coal tar. It is not a chemically pure body, but
consi.<ts of that part of petroleum which distills over between
70° and 90° C. The mixture is made up of hydrocarbons of
the general formula CnH^,„. but consists principally of hesane,
C«H,j, and heptane, C;H,„.
Numerous e.vperiments have been made to determine the
physiologic and toxic effects of benzine. Lehman ' found that
the inhalation of fumes by animals caused an irritation of the
respiratory mucosa, muscular twitchings, and a slowly increasing narcosis. Felix ' experimented on prisoners in Bucharest,
administering benzine as one would chloroform for anesthesia.
Small doses produced nausea, smarting of tlie conjunctivje,
and, in some cases, buniing in the chest and drowsiness. Larger
doses caxised sleep and anesthesia, succeeded by nausea, vomiting, headache, dizziness, depression, and drowsiness, llontalti,' after the internal administration of certain quantities,
noted vomiting, uncomfortable feelings in the stomach, difficult breailiing, miosis, muscle tremors, and symptoms of
paralysis of the central nervous system. He concluded that
gastrointestinal and cerebral toxic syni])toins are characteristic
for benzine into.xication. The action he thought to be due to
the aflinity of benzine for the fat, cholesterin, and lecithin
group, which causes a change in the ganglion cells.
Hamilton ' interviewed nine interior house-painters who
had experienced the effects of using a quick-drj-iug paint containing large quantities of benzine in small and practically
unventilated nxmis. Dizziness, headache, spots before the
eyes, dryness with choking in the throat, and burning of the
eyelids were complained of by all, while some also had nausea,
vomiting, pains in various parts of the aljdomen, and dysuria.
In .several instances the worst discomfort developed on leaving
work, the dizziness and staggering coming on in the open air.
A number of cases of acute poisoning are recordeil in the
literature; some in children who had drunk the benzine, while
others had resulted from inhaling large amounts of the funics,
usually in cleaning tanks or vats in which there was very little
ventilation. The symptoms noted as resulting from jtoisoning
from drinking lienzine have been cyanosis, miosis, weak pulse,
uncon.<ciousne.ss, and convulsions. Friediger* has collectetl
14 ca.«es of poisoning by it, eight of which resulted in death.
The fatal cases were all in children. Autopsy in all cases
showed hemorrhages into the lungs.
The most prominent symptom in all cases of acute poisoning from the inhalation of fumes, according to Wichern,* is
the muscle tremor which may take the form of tonic or clonic
cramps, the victims remaining almost without interruption in
a condition of shaking fit. Wichern describes two cases: A
workman was overcome by the fumes and fell into a tank of
benzine. He was unconscious and showed wide, inactive
pupils, spasticity, acrocyanosis, chills, and vomiting. In a
second case, developing in a cleaning establishment, the
symptoms were similar. Wichem states that in animal experiments muscle tremor is prominent also. Other observers
have reported cases similar to those of Wichern. Peters '
describes tlie occurrence of retrobulbar neuritis in a girl of
14, the daughter of a glove-cleaner, who was addicted to the
habit of inhaling benzine. The child was apathetic, stubborn,
and learned slowly.
Chronic benzine poisoning seems to be of rare occurrence.
According to Hamilton, ordinary' workmen in American oil
fields and refineries show no ill effects. Russian writers state
that much ill health is caused by the constant inlialation of
benzine fumes in establishments where the working conditions
are bad. Only four cases of chronic poisoning are to be found
in the literature, all occurring in a rubber factorj', and two
of which are reported in detail by Dorendorf.' The first man
after eight months in the factory began to have tearing pains
in the muscles and joints of the extremities. Later he suffered
from fibrillary twitching of the tongue and a fine tremor of
the hands. After a rest he went back to work. Sixteen
months later he returned to the hospital complaining of pressure in the head, weak memory, difficulty in speaking, anorexia,
a feeling of heaviness in the limbs, and a feeling of cold in
the right hand and leg. Examination .showed psychic depression, hesitant speech, weakness of the right hand, hyperactive
knee reflexes, and active tremor of the tongue, eyelids, and
hand. The blood was normal except for the presence of free
pigment. The second man wa,s a worker in the vulcanizing
room. A few weeks after beginning work he lost his appetite,
he l)egan to suffer from constipation, later from diarrhea, and
linally from vomiting. He complained of iieadache and insomnia and had to stop work on account of colicky pains. He
also had drawing i)aiiis in both arms and a sense of a leaden
weight in the right arm with a feeling of coldness and formication. Examination showed tlie knee reflexes to be much
increased and there was an after-tremor of the knee tendon.
Striking the patella tendon evoked a contraction of the epigastric muscles and diapliragm. There was also tremor of
the hands and tongue. Free pigment was found in the blood
plasma, as in the first case. Dorendorf states that two other
men were found in the same factory presenting similar symptoms. He allowed guinea-pigs to breathe the fumes of benzine
310
[No. 344
daily and found that they developed paresis and died in convulsions in 15 days.
The following case has been observed by us at The Johns
Hopkins Hospital :
J. H. N., a white man, age 42, by occupation a cleaner in a llthographing factory, was admitted to the hospital October 4, 1915,
complaining of weakness and dizziness.
Family History. — His father and four brothers died of pulmonary tuberculosis, but the patient has not been associated with
his family for 25 years.
Previous Personal History. — The general health has been good
up to two years ago. He had pneumonia at 28 and malaria
twice yearly for 10 years. He has not had an attack of malaria
for the past eight years. During the past four years he has
had at times severe night sweats with cough lasting for three
to four weeks. The last attack occurred two weeks before admission. He has never been jaundiced until his present illness.
He had dysentery with blood and mucus in the stools In Cuba in
1S97. Three years ago his appendix was removed and his right
kidney suspended. For 11 years previous to this operation he had
had attacks of abdominal pain with a sensation of a sliding mass
in the abdomen.
Present Illness. — The patient states that he has not been strong
since the operation, but in July, 1914, he felt fairly well except
for some weakness. Two months after beginning his present
work he began to have generalized pains over his abdomen with
nausea and vomiting after meals. He also had a feeling in his
head which he describes as a " compression on the inside " or a
"presslng-ln like." On October 1, 1914, he went to a hospital.
At this time he also had a feeling of heaviness in the arms and
legs, which made them feel like leaden weights. These symptoms
cleared up. but on going back to work the nausea, vomiting, and
dizziness returned and have become progressively worse. The
nausea and dizziness have often been so severe that he has had to
leave work. He has been gradually losing strength, the weakness
before admission being so extreme that It often took an hour to
walk to his home when it had ordinarily required only 12 minutes.
At times he has fallen in the stree;. For the past three months
he has been getting drowsy, his memory has been falling, and he
has had difficulty in thinking. He has had a feeling of coldness
in his legs for the past two months, which he describes as a feeling " as if menthol were rubbed on them." He has had shooting
pains In the arms with cramp in the muscles ending in hyperextension of the fingers. Recently he has had spontaneous
cramps of other muscles. His legs felt as if " a thousand needles
were stuck In them." The sense of heaviness of the limbs continued until they felt like " bags of cement." He has noticed,
also, tremor of the fingers and eyelids and failing memory: his
head has not felt clear, and the left ear feels as if bubbles were
flowing out of It. During all this time the nausea, vomiting,
dizziness, and weakness have been progressive. He has had some
dimness of vision. Five weeks before entering the hospital he
noticed that his urine was becoming dark. Two days ago someone
told him that he was jaundiced. He has had marked anorexia
and constipation.
Physical Examination. — The patient is undernourished and
looks sick. He is very dull mentally, and answers questions
slowly. He does not seem able to think clearly. The lips are
cyanosed. There is well-marked jaundice of the skin and mucous
membranes. There is a sweetish odor to the breath. The pupils
are equal and active. There is no glandular enlargement. There
are signs of fibroid changes at both apices. The heart is negative.
Blood pressure 100/65. The liver edge extends two fingerbreadths below the costal margin and is firm and tender. The
spleen is palpable. The tendon reflexes are very active everywhere, but equal on the two sides. When the patella tendon on
one side Is struck there is a contraction of the thigh muscles on
the opposite side. The superficial reflexes are present. Babinskl
and Oppenhelm negative. There is no clonus; sensory examination is negative.
Laboratory Examination. — Wassermann (blood) negative.
Sputum negative for tubercle bacilli. The urine had a specific
gravity of 1022 and was negative throughout except for an occasional trace of albumin and a positive bile test on admission.
Blood (October 6): R. B. C, 4,332,000; "W. B. C, 4550; Hb., 77
per cent; differential: P. M. N., 54.6 per cent; P. M. E., 2.6 per
cent; S. M., 33.3 per cent; L. M., 5.0 per cent; trans., 3.0 per cent;
unclassified, 1.3 per cent. Gastric analysis: Free HCL, 44 per
cent, and total acidity, 72 per cent. The stool was dark brown
and gave a positive bile test. There were no parasites or ova.
On October 8 the white blood cells were 5400. A Calmette tuberculin test was negative with 1 per cent and 5 per cent. Four
other blood counts showed the white blood cells to be below 5000.
A second test meal was given with the same findings as in the
first. On November 23 the white cells had risen to 7280.
Course in Hospital.— The symptoms rapidly disappeared. The
reflexes continued active for a long while. At times striking the
patella tendon would cause a contraction of nearly all the larger
muscle groups. The jaundice and cyanosis cleared up. He gained
weight rapidly and no longer had difficulty in thinking. He was
discharged from the hospital November 23, 1915. At this time
the reflexes were moderately exaggerated. Examination otherwise was negative. When seen several months later there had
been no return of the symptoms.
The factory at which the patient worked was visited. It
was found that the lithographing rolls were dropped into a
trough, six feet long and one foot wide, filled with benzine,
and scrubbed clean. About two gallons of benzine evaporated
from the trough daily. The room in which the work was
done was large, btit from the nature of the lithographing inks
it had to be tightly closed to prevent the ink from drying.
The patient had worked for over a year five hours daily at
this trough where he was continually inhaling the fumes. No
other workmen showed signs of benzine intoxication, but there
were no otliers engaged in the same kind of work.
Formerly each printer had been required to clean the rolls
from hi.< machine, and this took only a few minutes each day.
The patient had been cleaning all the rolls for the entire
factory.
SUMMARY
Chronic benzine poisoning is uncommon, but may occur.
The symptoms complained of are referable almost entirely to
the gastrointestinal tract and the central nervous system.
REFERENCES.
1. Quoted by Hamilton.
2. Quoted by Zornlaib: Wien. Med. Wchnschr., 1906, LVI, 366.
3. Hamilton: Kober and Hanson, Diseases of Occupation and
Vocational Hygiene, Phil., 1916.
4. Friediger: Miinch. Med. Wchnschr., 1912, LIX, 252.
5. Wichern: Miinch. Med. Wchnschr., 1909, LVI, 2.
6. Peters: Deut. Med. Wchnschr., 1900, XXVI. 249.
7. Dorendorf: Miinch. Med. AYchnschr., 1901, XLVIII. 236.
October, 1919]
311
THE REACTION OF MONKEYS TO THE INOCULATION OF
MEASLES BLOOD
By Andrew A\'atsox SellvViids,
-1/(i>or, M. C. U. S. A.
(From the Base Hospital. Camp Meade, Md.)
In attempting the transmission of an iul'eutious disoiu^e from
man to lower animals it is not to be expected, in the case of a
refractory species, tiiat the typical clinical sj-mptoms will be
reproduced exactly. A distinct advance has been aceomplisiied if one can obtain regularly even a single characteristic
feature of the diseiu^e; a definite reaction occurring with reasonable constancy as the rt>sult of inoculation of the virus
would enable one to determine many of the essential characteristics of the disease in question. Such reactions have i)ecn
described as the result of the inoculation of monkeys with tlie
l)lood of measles patient.s; one may mention more especially
reports of the occurrence of rashes, of leucopa-nia and of
Koplik spots. Wentworth and myself attempted to confirm
tin's work.' The rcsult.< of tiie intensive inoculation of a small
group of monkeys were very discouraging ^nd led to the conclusion that tlie reactions were too indefinite ami inconstant
to permit the practical use of monkeys in testing the lilood of
jiatients for the virus of measles. The present note will record
.some further observations on the question whether the occasional slight and indefinite symptoms observed in monkeys
represent a reaction to the virus of measles. It is of theoretical
interest to determine whether the virus of the disease can at
times multiply and produce minor symptoms in an occasional
individual animal.
Summary of Literature. — Josias ' in 189S reported the successful transmission of mea.sles to tliree monkeys (" Sajous capucin "
and "Sajous robustus"). These animals were inoculated on tlie
mucou.s membrane with the mucous secretions from cases in full
eruption and one monkey received in aildition an injection of
blood. The incubation periods were 27 days. 1.'! days and II days,
respectively, in these three animals; the rash was not remarkable, and the rise in temperature was not striking. .Anderson and
Goldbcrger' were the first investigators to report the infection of
monkeys with measles by the Injection of blood alone. Successful rf-aults were obtained in all species tested, namely. Macacus
rhesus, eynomoltius and ninii us. The work was carried out on an
extensive scale. The symptoms observed most commonly consisted of coryza and rhinitis, slight rash, malaise and occasionally
some febrile disturbances. The rash was sometimes pink, sometimes copper-colored; it appeared, as a rule. 10 days after injection though the extreme limits varied widely, being from seven
days to 21 and possibly 26 days. The febrile disturbance, in
those experiments in which the temperature reaction was described in detail. wa,s extremely slight, being Insufllcieut of Itself
to permit a diagnosU. .Moreover. It is noteworthy that sometimes
the febrile period and the eruptive period did not coincide. In
working with secretions from the mucous membranes these authors
produced symptoms by subcutaneous injection of the secretions,
but not by inoculation on the mucous membranes of monkeys.
Hektoen and Eggers • Inoculated three monkeys with blood from
measles patients. Each of these animals developed more or less
leucopwnia though, as emphasized by these authors, the leucocyte
count in normal monkeys fluctuates rather widely and without
any apparent cause. Two of the three animals remained free from
any rash; the other developed a faint eruption about the eyes and
the groin 15 days after injection. No Koplik spots wore found.
Subinoculations were made from monkey to monkey in three
instances under conditions which were not especially favorable;
the results were not striking.
Lucas and Prizer' injected two monkeys with blood from a preemptive case of measles. They noted a subsequent leucopoenia,
and the development of Koplik spots ten days after injection. On
subinoculatiou of two other monkeys, one also developed Koplik
spots ten days after injection. No definite rashes developed, but
these animals showed a tran.sient erythema limited to the face.
In one animal an erythema and a conjunctivitis were noted as
occurring three days after the appearance of Koplik spots and one
day after the administration of ether. No febrile reactions developed in any of these animals.
Tunnicliff reported the development of a leucopoenia in a
monkey injected with measles blood, whereas a control monkey
maintained a normal white count after the injection of normal
blood. No mention is made of the occurrence of any rash or
other symptoms of measles.
Nicolle and Conseil ' injected one monkey (M. sinicus) with
measles blood withdrawn 24 hours before the appearance of the
eruption. A rise in temperature occurred, but no mention is made
of any rash.
Jurgelunas " inoculated monkeys with blood of measles patients,
with secretions from the mucous membranes and exposed some
animals in a measles ward. The results were essentially negative.
Especial attention was given to the nasal secretions; of the animals
inoculated with blood, one died 11 days after injection from an
undetermined cause; another received only a subcutaneous Injection; for a third, the blood tor injection was not taken until the
second day of the patient's rash.
From this summary it is seen tiiut there are definite reports
of the successful tran.smission of measles to monkeys. Attempts to infect other animals have been uniformly disappointing. According to the literature, all of the important
features of measles have been reproduced in monkeys, namely,
the rash, Ko])lik spots, leucopoenia, respiratory sj-mptoms,
fever and malaise. It is rather striking, however, that no
single investigator has ever obtained all of these features in any
single individual or even in a series of animals. Moreover,
there is no single symptom which appears at all constantly.
The periods of incui)ation vary widely. Even under favorable
conditions a large proportion of animals remain entirely
normal.
EXPERIMENTAL WORK
In the course of some investigations involving the inoculation of Inimaii volunteers, advantage was taken of the opportunity to conduct simultaneous injections of monkeys, thereby
permitting a compari.son of the results obtained in a refractory
and in a highly su.«ceptible species.
Injection of Blood. — .Specimens of blood were collected in
an ap])roximately equal volume of citrate solution from two
cases of measles in the pre-emptive stage. The two specimens
of citrated blood were mixed and injected as follows: 4 c. e.
were injected into each of two adult monkeys {Macacun
rhesus), half being given subctitnneously and the rest intrapi-ritfiiieally ; c. c. of the mixed specimens were injected into
313
[No. 344
each of two susceptible liuman volunteers, part of the material
being given subcutaneously and the remainder intramuscularly. On the next day, blood was again taken from each of
the measles patients; one had developed a rash 18 hours previously and the other was free from any eruption, the rash
appearing six hours later. The specimens of blood were mixed
and injected as on the preceding days into the two animals
and also into the volunteers.* The relative dosage and the
mode of injection for the monkeys, therefore, differed from
that employed in the volunteers; it seemed desirable for the
inoculations of the monkeys to adhere to conditions which
would give the maximal opportunity for producing an infection.
These monkeys were examined for any evidences of respiratory symptoms, of malaise, of an exanthem and also Koplik
spots. The temperatures (rectal) were taken twice daily, at
about 9 o'clock in the morning and at 4 o'clock in the afternoon, before the feeding periods. The white counts were made,
as a routine, in the morning only. Xeither animal developed
any significant rise in temperature. Ehesus I showed a low
leucocyte count which persisted for only two days and did not
appear until the 11th day after injection. Ehesus II developed a leucopcenia which began on the sixth day after injection and persisted for three or four days. The counts in
this animal subsequently became complicated by the development of a severe pneumonia. The records are as follows :
INOCULATIONS OF MONKEYS WITH MEASLES BLOOD
Days
Rhesus I
Rhesus II
after
first
Temp.
White
count
Temp.
White
count
Additional
observations on
lation
A.M.
P.M.
A.M.
P.M.
1
101.2
18,900
101.8
13,900
2
99.0
102.0
11,100
100.4
102.2
10,700
3
99.4
101.8
10,100
101.8
101.0
18,500
*
101.0
102.4
11,800
102.0
102.0
10,000
5
101.2
102.0
12,600
100.6
102.0
11,800
6
8
100.8
101. a
100.8
102.2
101.8
101.2
14,900
13,1001-2
8,300
9,7001
9,500
102.2
102.4
101.2
102.8
102.0
101.8
6,500
6,6001
5,200
5,6001
6,400
At noon, temperature 102.4.
Count, 6,300.
Bleil for inoculation of volunteer.
9
10
100.8
101.6
102.4
4,700
7,4001-3
7,400
101.6
101.2
102.0
7,900
6,0001
9,900
At noon, temperature 102.0.
Count 7,700.
11
12
101.4
101.2
101. S
102.6
4,400
4,000
5,700
4,6001
7,800
102.8
101.0
103.6
101.4
11,110
10,8001
12,600
Room temperature, forenoon
65% in afternoon SO'.
Slight rash.
13
101.6
102.0
101.0
102.0
8,200
Slight rash.
14
100.9
102.2
9,200
100.0
101.0
6,400
15
101.4
102.0
8,900
100.0
100.0
6,000
Early signs of pneumonia.
16
100.6
101.0
8,300
99.4
99.8
6,600
Definite pneumonia.
17
100.6
102.2
17,300
98. 8
100.6
18,400
Critically in.
18
102.0
102.2
13,900
101.0
9,400
Critically ill.
20
101.2
14,500
100.8
44,000
Marked improvement by crisis.
1 White counts in atte
= At noon, temperature 101.0, <
=1 At noon, temperatur
* The precautions observed in the protection and selection of the
volunteers (VIII and IX). as well as the details concerning their
inoculation, are given in the September number of this Bulletin.
Ehesus I developed no respiratory or constitutional symptoms and no evidence of an exanthem or of Koplik spots.
Ehesus II was bled on the second day of his leucopcenia and
at the beginning of the seventh day after the first of his two
inoculations. Three c. c. of blood were mixed with 2 c. c. of
2.5 per cent sodium citrate in physiological saline and injected
intramuscularly and subcutaneously in the gluteal region into
a susceptible himian volimteer. No local or general symptoms
developed; the temperature and white count remained normal.
Ehesus II at the beginning of the 12th day after the first
injection developed a faint but distinct rash over the face and
uppermost part of the thorax. In some areas, especially over
the chest, a diffuse erythematous blush was present. Around
the eyes and nose there occurred discrete macules from 1 to
2 mm. in diameter; these were especially marked around the
hair follicles. Moderate but definite malaise was present on
this day only. On the second day the rash faded almost completely, leaving beliind only very slightly pigmented areas ; by
the third day this pigmentation had disappeared. On the
next day an outspoken and very severe pneumonia developed,
probably as the result of the deep and prolonged etherization
employed during the collection of blood in the previous week.
A blood culture, taken after the pneumonia was fully developed, showed no growth.
The rash developing in this animal after an incubation
period corresponding to that in human eases was in no way
characteristic of the exanthem as it occurs in man. However,
it is not to be expected that the skin eruptions developing in
a lower animal would necessarily conform to the human exanthem. This consideration greatly increases the difficulty
of determining whether an atypical rash is due to the virus of
measles. The principal points bearing on the inter[jretation
of this exanthem are :
1. The period of incubation.
2. The results of the inoculation of blood from the monkey
into a susceptible individual.
3. The behavior of susceptible human volunteers inoculated
with the same specimen of blood which was injected into the
monkeys.
4. The exclusion of other factors.
The period of incubation in this animal, 12 daj's, would
conform very well with the diagnosis of measles.
The. negative result of the inoculation of blood from tlio
monkey into man might be explained on two grounds; either
the supposedly susceptible volunteer may in reality have been
immune or the single specimen of monkey's blood may not
have been taken at the most favorable period for transmitting
the disease.
The absence of any symptoms in the two volunteers inoculated from the same specimen of blood that was used for
the monkeys does not constitute final proof, but it speaks very
strongly against ascribing this rash to the virus of measles.
It does not seem plausible that a highly refractory animal
would be overwhelmed by a large inoculation intrapehtoneally,
if an extremely susceptible host escapes infection after a
moderately large subcutaneous and intramuscular injection.
OCTOBEK, 191 9 J
313
Of other factors which might give rise to a rash under the
conditions of the experiment the question of serum sickness
requires consideration. This possibility is importiint, even
thougli anaphyhixis has not been described in monkeys; and
serum rashes, which are presimiably a manifestation of anaphylaxis, have not been produced in lower animals. The two
conditions, measles and serum sickness, have certain features
in common. In either condition, the constitutional symptoms
may be very mild. The incubation periods are almost identical, the 12th day being known as the critical day in serum
disease. The rash of serum disease is altogether protean in
character; the e.xantliem under discussion resembled serum
rashes more closely than the eruption of measles.
The eruption in monkeys does not occur constantly after
the injection of measles blood. Indeed, the indefinite character of the rash and its comparatively low incidence considerably increases the difficulty of determining its cause.
There are certain points which would favor the view that the
rashes observed by Anderson and Goldberger were not due to
serum disease. These authors report that several monkeys developed no rasli when injected with moderately large amounts
of liuman blood from advanced cases of measles which presumably did not contain the virus of the disease. Moreover, in
performing subinoculations, a rash sometimes developed when
monkeys were injected with the blood of other monkeys ; from
their description it would seem that these rashes were less
striking than tho.^e obtained with measles blood from human
cases. Anderson and Goldberger also observed rashes after
the inoculation of nasal secretions, thereby affording conditions in which anaphylactic manifestations would not occur.
These rashes developed only in animals injected subcutaneously with secretions; two monkeys inoculated on the mucous
membranes developed no symptoms. The possibility of producing bacterial septicicmia by these injections must be borne
in mind ; in one instance it was noted that, at the time a rash
appeared, blood cultures showed the presence of a micrococcus.
It seemed desirable to test the possibility of producing a
serum rash in monkeys. Human serum was employed for one
group of animals and, in order to obtain more favorable conditions for the production of anaphylaxis, another set was
injected with normal horse serum. Ten animals in all were
inoculated. Eight of these (Macacus syriclus) had received
no previous treatment with serum; the two (.V. rliesm) which
were injected with measles blood were reinjected with normal
serimi. All of the animals were injected intravenously and
the majority also received intraperitoneal or subcutaneous injections either at the time of the intravenous injection or after
an interval of one or two days. A.«suming that .serum sickness
represents a reaction between antigen and antib<jdy it was
considered that the injection of large amounts of serum by
different routes would afford a maximal opportunity for the
coexistence of antigen and antibody within the organism.
Observations were continued over a period of three weeks.
Of these ten animals six remained entirely negative and four
developed a very faint erytliematous blush eight to ten days
after injection. This appearetl on the face and uppermost part
of the chest, persisting for two or three days. It disappeared
on pressure and was not followed by pigmentation or desquamation. Some of these animals showed slight loss of appetite
at this time, but there was no definite evidence of malaise.
The erj-thcma in Rhesus II appeared 10 days after the second
injection and persisted for three days. The s}'mptoms were
less definite than after his first injection with measles blood.
These two rhesus monkeys were of the same size and apparently
the same age; one reacted slightly both to the injections of
measles blood and normal blood, while the other reacted to
neither. The second injection of human serum in these animals
produced no clinical symptoms of anaphylactic shock.
The following table gives the details of these injections :
INJECTIONS OK MONKliVS WITl
SERIM
Species
of
monkey
Material
injected
Amount injected
Serial
number
= =
c =
Result
1
10 weeks later
2
10 weeks later
3 days later
3
2 days later
2 (lays later
&
6
1 day later
7
1 day later
8
I Hay later
9
10
I day later
.V. rhesus
!U. rhesus
.V. syriclus
.V. si/rictus
M. syriclus
M. syrictus
M. syriclus
M. syrirlus
M. syriclus
M. syriclus
Measles
blood
Human
serum
Mrasles
blood
Human
serum
Human
Human
scrum
Human
Human
Human
serum
Horse
serum
Horse
serum
Horse
serum
Horse
serum
Horse
serum
Horse.
scrum
Horse
serum
Horse
scrum
Horse
serum
Horse
Ic.c.
None
Ic.c.
None
None
3c.c.
None
2c.c.
None
None
Ic.c.
None
None
None
None
None
Sec.
None
None
c.c.
None
Ic.c.
None
10 c.c.
None
1 c.c.
Sec.
n c.c.
None
None
10 c.c.
None
10 c.c.
8 c.c.
10 c.c.
None
None
IC c.c.
None
6 c.c.
None
Sec.
None
7 c.c.
None
Sec.
None
Sec.
S c.c.
None
See
None
See
None
7 c.c.
See
None
No effect.
No effect .
Deflnite rash.
Slight erythema
10 days later.
, Slight erythema
8 days later.
No effect.
No effect.
1 Slight erythema
r 8 days later.
Slight erythimn
days later.
J- No effect.
No effect.
> No effect.
The slight erythema produced in some of these animals was
by no means sufficient to permit of its interpretation as a
siTuin rash : the symptoms, however, did appear to correspond
fairly well with some of the indefinite rashes to which some
authors attach significance in the diagnosis of measles. A
very slight reaction is sufficient to complicate the interpretation of the delicate and inconstant effect resulting from the
injection of measles blood.
SUMMARY
I. Blood from two early cases of measles in the pre-eruptive
and later in the early eruptive stage was injected subcutaneously and intraperitoneal ly into two monkeys. One
314
[No. 344
animal remained free from symptoms; the other developed a
moderate leucopoenia and later a slight rash.
2. A portion of the same specimen of measles blood was injected subcutaneously and intramuscularly into two susceptible human volunteers. Xo symptoms resulted.
3. A specimen of blood from the monkey which subsequently developed a rash was injected into a susceptible volimteer, but produced no symptoms.
4. Normal serum injected into monkeys was followed by a
very slight erj'thema appearing about eight to ten days after
injection in four of ten animals.
5. The weight of evidence in these experiments is against
the interpretation of the symptoms in this monkey as representing a reaction to the virus of measles.
LITERATURE
1. Sellarda, A. W., and Wentwortli, J. A.: Bull. Johns Hopkins
Hosp., 1919, XXX, 57.
2. Josias, A.: Tribune med., 1898, XXIX, 211.
3. Anderson, J. F., and Goldberger, J.: Pub. Health Rep., 1911,
XXVI, 847, 887; Jour. Amer. Med. Assn., 1911, LVII, 113, 476, 971,
1612.
4. Hektoen, L., and Eggers, H. E. : Jour. Amer. Med. Assn.,
1911. LVII, 1833.
5. Lucas, W. P., and Prizer, E. L. : Jour. Med. Research, 1912,
XXVI, 181.
6. TunniclifE, R.: Jour. Infect. Dis., 1912, XI, 474.
7. Nicolle, C, and Conseil, E.: Compt. rend. acad. sclen., 1911,
CLIII, 1522.
8. Jurgelunas, A.: Centralbl. £. Bakteriol., Orig., 1914, LXXII,
483.
NOTES ON NEW BOOKS
The Nervous Heart. By R. M. Wilson and J. H. Carboll. (London: Henry Froude; Hodder and Stoughton, 1019.)
The book represents an attempt to explain " Disordered Action
of the Heart " (D. A. H.) , as well as post-febrile ' functional heart
disorders " by disturbances of the nervous control of the heart.
The basic theories need more proof before the deductions can be
accepted. Nothing new is added to the prognosis or treatment of
the functional heart disorders described.
V. R. M.
Burns and Their Treatment. By J. M. H. Macleoii. Cloth. $2.00.
(London: Henry Froude; Hodder and Stoughton, 191S.)
The subject of burns and especially their treatment is always
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has given us a brief and excellent epitome of the modern conception of burns. Better still, the fact that he has recorded his personal experiences based on contact with a vast amount of material
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In the eleven chapters the different aspects of the subject are
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The fact that the author is a dermatologist of note makes his
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The subject matter is attractively presented. The book has been
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I. R. P.
A Study of the Mental Life of the Child. By Dr. H. Vox HuGHellmuth. Paper, $2.00. (Washington: Nervous and Mental
Disease Publishing Company, 1919.)
The author divides her study into two periods, the period of
infancy and the period of play. Thirty-nine pages are devoted to
the former, the rest of the book to the latter. It is not possible
to summarize the detailed observations which are found throughout the book, or to refer to the author's interpretations of many
of the phenomena of childhood, but the chief value of the book
lies in these detailed observations, and in the endeavor to interpret them in terms of the actual driving forces of human life.
In discussing the child as he actually is, there is no topic
censored, and thus in a way we have the most honest book on
child psychology available. The author, however, goes even
further than showing lack of embarrassment in dealing with the
sexual life of the child, with its interest in matters of the toilet
and so on; she exhibits the Freudian tendency to identify pleasure
with sexual pleasure, and thus a sexual interpretation of very
doubtful validity is given to many phenomena. She comes to her
topic steeped in the Freudian dogmas, sharing the tendency of
the Freudian School to generalize, to push hypothesis to an extreme, and to equate hypothesis with actual observation of fact.
Notwithstanding this extreme attitude, which to some extent
distorts its proportions, the book is one that deserves the serious
study of any one interested in the psychology of childhood.
C. McF. C.
Physiology and Biochemistry in Modern Medicine. By J. J. R.
MACLEOD. (St. Louis: C. V. Mosby Company, 191S.)
This book is intended by the author to be " an advanced text in
physiology for those about to enter upon their clinical instruction
and, at the same time, a review for those of a maturer clinical
experience who may desire to seek the physiological interpretation
of diseased conditions." It is published in an attractive form and
contains many good illustrations. The treatment of the subject
matter is, in general, clear, and would appear to be well done for
the reader for whom it is intended. Of particular present day
interest from the point of view of the clinician are those sections
dealing with the respiration, the circulation, and the excretion of
urine. The book is a most praiseworthy production, and deserves
a wide reading among those who have at heart the closer union of
physiology and the allied sciences with clinical medicine.
H.
THE JOHNS HOPKINS HOSPITAL BTILIETIN.
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pages. F. A. Davis Company, Philadelphia; Stanley PhillipB,
London.
The Don Quixote of Psychiatry. By Victor Robinson.
339 pages. Historico-Medlcal Press, New York.
1919. 8°
316
[No. 344
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VOLUME IV. 504 pages, 33 charts and illustrations.
VOLUME V. 480 pages, with 32 charts and Illustrations.
The Mal.nrl.il Fevers of Baltimore. By W. S. Thayek, M. D., and
J. Hewetson. M. D.
A Study of some Fatal C.ises of Malaria. By Lewellts F. Barker. M. B.
Studies in Typhoid Fever.
By William Osleb. M. D., with additional papers by G. Blomer. M. D..
Simon Flexnek. M. D., Walter Reed, M. D., and H. C. Parsons, M. D.
VOLUME VI. 414 pages, with 79 plates and figures.
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anniversary of his Doctorate. This volume contains 3S separate
papers.
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VOLUME XIV. 632 pages, with 97 figures.
Studies in Genito-Urinary Surgery.
The Treatment of Prostatic Hypertrophy by Conservative Perineal Prostatectomy. An analysis of cases and results based on a detailed
report of 145 cases. By Hugh H. YotiNG, M. D.
Recto-Urethral Fistulse. Description of New Procedures for their Prevention and Cure. By Hugh H. YonNG. M. D.
The Early Diagnosis and Radical Cure of Carcinoma of the Prostate, being
a study of 40 cases and presentation of a radical operation which
was carried out in four cases. By Hugh H. Young, II. D.
VOLUME XV. 542 pages, with 87 illustrations.
Twelve papers on pneumonia. By Drs. Chatard. Fabyan, Emerson,
Marshall, McCrae, Steiner. Howard and Hanes.
A Study of Diarrhoea in Children. J. H. Mason Knox, Jr., M. D., and
Edwin H. Schoker, M. D.
Skin Transplantation. By John Staigb Davis, M. D.
Epidemic Cerebrospinal MeniuKitis and Serum Therapy at The Johns
Hopkins Hospital. By Frank J. Sladen, M. D.
VOLUME XVI. 670 pages with 151 figures.
Studies in the Experimental Production of Tuberculosis in the Genitourinary Organs. By George Walker. M. D.
The Effect on Breeding of the Removal of the Prostate Gland or of the
Vesiculse Seminales. or of Both ; together with Observations on the
Condition of the Testes after such Operations on White Rats. By
George Walker, M. D.
Scalping Accidents. By John Staige Davis. M. D.
Obstruction of the Inferior Vena Cava with a Report of Eighteen Cases.
Bv J. Hall I'leasants, M. D.
Physiological and Pharmacological Studies on Cardiac Tonicity in Mammals. By Percival Douglas Cameron. M. D.
VOLUME XVII. 586 pages with 21 plates and 136 figures.
Free Thrombi and Ball Thrombi in the Heart. By Joseph H. Hewitt,
M. D.
Benzol as a Leuootoxin. By Lawrence Selling. M. D.
Primary Carcinoma of the Liver. By Milton C. Wintebnitz, M. D.
The Statistical Experience Data of The Johns Hopkins Hospital. Baltimore,
Md., 1802-1911. By Frederick L. Hoffman, LL. D., F. S. S.
The Origin and Development of the Lymphatic System. By Florence R.
Sabin, M. D.
The Nuclei Tuberis Laterales and the So-called Ganglion Opticum Basale.
Bv Edward F. Malone. M. D.
Venous Thrombosis During Myocardial Insufficiency. By Frank J. Sladen.
M. D., and Milton C. Winternitz. M. D.
Leuliiemla of the Fowl : Spontaneous and Experimental. By Harry C.
Schmeisser, M. D.
VOLUME XVIII. 445 pages with 124 figures.
Fasciculus I.
A Study of a Toxic Substance of the Pancreas. By E. W. GoODrASTCRE,
M.'D.. and George Clark. M. D.
Old Age in Relation to Cell-overgrowth and Cancer. By E. W. Goodpasture. M. I)., and G. B. Wislocki. M. D.
The Effect of Removal of the Spleen Upon Metabolism in Dogs ; Preliminary Report. By J. H. King. M. D.
The Effect of Removal of the Spleen Upon Blood Transfusion. By J. H.
King, M. D., B. M. Bernheim, M. D., and A. T. Jones, M. D.
Studies on I'arathvroid Tetany. By D. Wright Wilson, M. D.. Thornton
Stearns, M. D.. J. H. Janney, Jr., M. D.. and Madge DeG. Thdrlow,
M. D.
Some Observations on the Effect of Feeding Glands of Internal Secretion
to Chicks. Bv M. C. Wintebnitz, M. D.
Bj
Spontaneous and Experimental Leukaemia in the Fowl. By H.
Schmeisser, M, D.
Studies on the Relation of Fowl Typhoid to Leukaemia of the Fowl.
M. C. Winternitz, M. D., and U. C. Schmeisser, M. D.
Hyaline Degeneration of the Islands of Langerhans in Pancreatic Diabetes.
By M. C. Winternitz. M. D.
Generalized Miliary Tuberculosis Resulting from Extension of a Tubercular
Pericarditis Into the Right Auricle. By M. C. Winternitz, M. D.
Acute Suppurative Hypophysitis as a Complication of Purulent Sphenoidal
Sinusitis. By T. R. Boggs. M. D.. and M. C. Winternitz, M. D.
A Case of Pulmonary Moniliasis in the United States. By T. R. BoGOS,
M.D., and M. C. Pincokfs, M. D.
Gaucher's Disease (A Report of Two Cases In Infancy). By J. H. M.
Knox. M. D., H. R. Wahl. -M. D., and H. C. Schmeisser, M. D.
A Fatal Case of Multiple Primary Carcinomata. Bv E. D. Plass, M. D.
Congenital Obliteration of the Bile-ducts. By James B. Holmes, M. D.
Multiple Abscesses of the Brain in Infancy. By James B. Holmes. M. D.
Gastric Carcinoma in a Woman of Twenty-six Years. By R. G. HcssEY,
M. D.
Subdiaphragmatic Abscess with Rupture Into the Peritoneal Cavity Following Induced I'neumothorax for Pulmonary Haemorrhage. By E. G.
HussEY, M. D.
Heart Block Caused by Gumma of the Septum. By E. W. Bridgeman,
M. D., and H. C. Schmeisser. .M. D.
Analysis of Autopsy Records.
A. The Johns Hopkins Hospital. (Table Showing Percentage of
Autopsies.!
B. The City Hospitals, Bay View. (Table Showing Percentage of
Autopsies.)
'* The Monday Conferences."
Clinical Representatives on the Staff of the Department of Pathology.
Donation.
Fasciculus II.
The R61e of the Autopsy in the Medicine of To-day. Bv M. C. Winternitz,
M. D.
Experimental Nephropathy in the Dog. Lesions Produced by Injection
of B. bronchisepticus into the Renal Artery. By M. C. Winternitz,
M. D.. and William C. Qoinby. M. D.
Mesarteritis of the Pulmonary Artery. By M. C. Winternitz, M. D., and
H. C. Schmeisser, M. D.
A Clinical and Pathological Study of Two Cases of Miliary Tuberculosis of
the Choroid. By Robert L. Randolph, M. D., and H. C. Schmeisser,
M. D.
The Blood-vessels of the Heart Valves. By Stanhope Bayne-Jones. M. D.
Equilibria in Precipitin Reactions. By Stanhope Bayne-Jones, M. D.
Carcinoma of the Pleura with Hypertrophic Osteoarthropathy. Report of
a Case with a Description of the Histology of the Bone Lesion. By
Stanhope Bayne-Jones. M. D,
The Interrelation of the Surviving Heart and Pancreas of the Dog in Sugar
Metabolism. By Admont H. Clark. M. D.
Congenital Atresia of the Esophagus with Tracheo-Esophageal Fistula
Associated with Fused Kidney. A Case Report and A Summary of the
Literature on Congenital Anomalies of the Esophagus. By E. D.
Plass. M. D.
Ectopia Cordis, with a Report of a Case in a Fifteen-Month-Old Infant.
Bv James B. Holmes, M. D.
Studies in the Mechanism of Absorption from the Colon. By Samuel
Goldsciimidt, M. D., and A. B. Dayto.v. M. D.
Report of Two Fatal Cases Following Percy's Low Heat Treatment of
Carcinoma of the Uterus. Bv V. N. Leonard, M. D., and A. B. Dayton,
M. D.
The Relationship in Typhoid Between Splenic Infarcts and Peritonitis
Unassociated with Intestinal I>erforation. By A. B. Dayton, M. D.
Left Duodenal Hernia. By A. B. Dayton. M. D.
Histological as Related to Physiological and Chemical Differences in Certain Muscles of the Cat. By H. Hays Buli.ard, M. D.
.\ Method of Clearing Frozen Sections. By H. Hays Bullard. M. D.
On the Occurrence and Significance of Fat in the Muscle Fibers of the
Atrio-Ventricular System. By H. Hays Bullard. M. D.
Studies on the Metabolism of Cells in vitro. 1. The Toxicity of o-Amino
Acids for Embyonic Chicken Cells. By Montrose T. Burrows, M. D.,
and Clarence A. Neymann, M. D.
The Significance of the Lunula of the Nail. By Montrose T. Burrows,
M. D.
The Oxygen Pressure Necessary for Tissue Activity. By Montrose T.
Burrows. M. D.
The Functional Relation of Intercellular Substances in the Body to Certain Structures in the Egg Cell and Unicellular Organisms. By
Montrose T. Burrows. M. D.
Studies on the Growth of Cells in vitfo. The Cultivation of Bladder and
Prostate Tumors Outside the Body. By Montrose T. Burrows, M. D.,
J. Edward Burns. M. D., and Y'oshio Suzukl. SI. D.
The Study of a Small Outbreak of Poliomyelitis in an Apartment House.
Occurring in the Course of an Epidemic in a Large City. By Montrose
T Burrows, M. D.. and Edwards A. Park. M. D.
Papilloma of the I.arynx. Report of a Case Treated with Radium with
Resultant Chronic Diffuse Thyroiditis. By William C. Duffy. M. D.
Analysis of Autopsy Records.
Autopsy Statistics.
(a) Bay View.
(b) Johns Hopkins Hospital.
Report of the Photographic Department.
General Improvements.
Donations.
BALTIMORE, NOVEMBER, 1919
==Contents==
The Fate of Baotcriii Introduced into the Upper Air Passages.
By ARTnuR L. Hi.ooiiFiEi.D 317
The Influenza Bacillus in Paranasal Sinus Infections.
By S. .1. Crowe and \V. S. Thackkr-Nevili.e . . . 322
Meniiigoi'oci-us Pnt-uniunia. I. The Occurrence of Post-Influenzal Pneumonia in Wliich the Diplococcus Intracellularis
Meningitidis Was Isolated. From Ohservations at Camp
Coetqiiidon. A. E. F., France.
By M. L. Holm and Wilbubt C. Davison .... 324
Meningococcus Pneumonia. II. Tlie Epidemiology of Postinfluenzal Pneumonia in Wliicli the Diplococcus Intracellularis Meningitidis Was Isolated. From Observations at
Camp Coetquidon, A. K. F., France. (lUustratt d.)
By Wn.BURT C. Daviso.v. M. L. Holm and Robert V. B.
Emmons 329
The Occurrence of the Pfeifl'er Bacillus in Measles.
By Andrew Watson Sei.i.ards and Krnest Sturm . . 331
The Reaction of the Leucocytes in Ejjidcmic Influenza.
By Beverly Douglas ,338
Books Received . 340
THE FATE OF BACTERLV INTRODUCED INTO THE UPPER AIR
PASSAGES
By -Artiiir Ti. Bi.oomfield
(From the Medical CHnic. The Johns Hopkins University and Hospital.)
In considcrinfT the pathogenesis of infectious diseases in
which the portal of entry is in the upper respiratory tract,
three factors must be reckoned with : first, the means wliereby
the virus is conveyed to the individual; secondly, the fate of
the organism from the time it reaches the mouth or nose
until it is eliminated or until invasion takes place; and third,
the actual invasion of the virus into the body. Although
many details of the mode of conveyance of bacteria from one
host to another have been adequately determined, we possos.s
little exact information about the localization, prowth and
disposal of such orpani.<ms, and the factors which determine
a longer or shorter period of survival in the upper air passages before or after invasion has taken place. Studies of
contact infection and of carrier incidence and persistence
under various conditions afford indirect information, which
is, however, inadequate to solve the detailed problems of
particular infections. By actually introducinf: bacteria into
the ujjper air pas.«,i:.'es in such a way that the do.sc, exact
time and site of inoculation, and other conditions can be
controlled, and by studyinfr the fate of such organisms, it
seems probable that knowledge of the details of the spread
of bacteria and of the development of the carrier state can
be extended.
It seemed advisable to make a preliminary study of the
fate of non-pathogenic organisms before employing possible
disea.se producers. To be satisfactory for this purpose, an
organism was sought which was non-pathogenic, not normally
jircsent in the upper air passages of man, which could be
readily grown on simjile media, which could be easily recognized both in culture and in smear, and which would not be
overgrown in culture by the normal mouth flora. After
examining a number of strains, a sarcina lutea was selected
as fulfilling those criteria. The organism employed * had
tlip following characteristics:
Morphology. — Rather small sarclnfp, varying In size, occurring
for the niost part In regular packets, singly or in pairs, but sometimes In Irregular groups. They measure 0.66 to 1.13 microns in
20-hour cultures on plain agar.
Motility. — Non-motile.
Btaining Properties. — Gram positive.
Cultural Characteristics.^Agar slant. Growth lemon yellow,
at first translucent and rather dull, later, opaque and bright In
color, rather thick, raised.
Agar Colonies, — Round with smooth edges, lemon yellow,
opaque: f^urface smooth and glistening. Under low power — margin
smooth, sharply defined, surface finely granular, color yellowish
grey.
• The culture was kindly supplied by Dr. W. W. Ford.
318
[No. 345
Broth. — Liquid clouded at first with small amount of viscid
sediment; later, liquid clear, with large amount of sediment,
very viscid and stringy, yellow, no pellicle.
Peptone Solution. — Less growth than in broth.
Litmus milk. — Unchanged.
Pigment formation often not marked until after the lapse of
48 hours; on very acid or alkaline media, or when grown with
certain other organisms, pigment formation may be very slight,
but there is always a definite yellowish tint.
The organism grows well in mixed culture with the bacteria
usually present in the mouth, and it does not tend to be overgrown except in occasional Instances in which a " spreader "
rapidly covers the entire plate. The colonies of sarcina lutea
grow well side by side with, and at times partly superimposed on,
those of the mouth bacteria.
This organism was not found in the air passages of any of the
controls; and it is entirely non-pathogenic for human beings.
METHODS
Individuals were selected who.?e mouths and upper air
passages presented no acute disease or abnormality other than
those usually encountered, such as pyorrhea, dental caries,
adherent tonsils, and minor grades of septal or turbinate
deformity. From the point of view of this experiment, they
could be regarded as normal. The patients were kept under
direct observation during the first hour of the experiment and
for the most part took nothing by mouth during this time.
The inoculations were always made several hours after eating,
when the mouth was free from gross food particles.
Solid masses of a 24-hour growth of sarcina lutea on plain
agar were swabbed on the selected site, and cultures taken
at regular intervals thereafter. They were made for the most
part by scraping the mucous membrane with a heavy platinum loop, 0.5 cm. in diameter, and rubbing up the mucus
obtained in this way in a drop of sterile salt solution. This
was spread over several agar plates in varjing dilutions. It
was foimd that many more organisms were recovered by this
method than by the usual swab technique. There was usually
a uniform discrete spread of colonies. This point is emphasized because we feel that overgrowth in the plates was eliminated and that we obtained a true representation of the
percentage of viable organisms present in the swab. The
plates were kept for at least a week and the organisms identified by the appearance of colonies and by smears.
Experiment I. — Sarcina lutea was swabbed on the tongue and
cultures were made immediately, and at 10-minute, 1-hour, 24-hour
and 4S-hour intervals. The results are summarized in Table I.
Summary. — Sarcina lutea swabbed on the tongue disappeared
very rapidly. Only a few colonies could be recovered from the
site of Inoculation after ten minutes, and practically none at the
end of one hour. Simultaneous cultures from the pharynx, except
in one ir stance, yielded only a few colonies during the first ten
minutes.
Experiment II. — Sarcina lutea was swabbed on the nasal mucosa
and cultures made immediately and at 10-minute, 1-hour. 24-hour
and 48-hour intervals. The results are summarized in Table II.
Summary/. — Sarcina lutea swabbed on the nasal mucosa persisted longer than on the tongue, but in only one of five cases
could a few colonies (7) be recovered after 24 hours. In spite
of the heavy inoculation, only a few colonies could be obtained
in nasopharynx cultures made simultaneously with the nose
cultures.
Experiment III. — Sarcina lutea was introduced into tonsil crypts
and cultures were made immediately, and after 10-minute, 1-hour,
24-hour and 48-hour Intervals. The results are summarized in
Table III.
Summary. — Sarcina lutea introduced in large amounts into
tonsillar crypts could no longer be recovered after 24 hours, and
even at the end of an hour the organisms had disappeared in two
out of four cases. There seemed to be no tendency toward the
development of a carrier state.
THE MECHANISM FOR DISPOSAL OF BACTERIA IN THE
UPPER AIR PASSAGES
Despite the frequent presence of pathogenic bacteria in
the upper air passages, both in health and in disease, it is
clear that a highly effective mechanism is present in these
localities which, except under extraordinary conditions, protects against invasion by foreign organisms. Were this not
so, it is obvious that the spread of such organisms would
soon become universal among the human race, with an attendant high incidence of disease. The effectiveness of this
protective mechanism varies with various bacteria, and with
the same bacteria at various times, as illustrated by the epidemiological facts of Iniman disease. The details, however,
of its action in particular instances of infection have not been
completely worked out. A survey of the literature discloses
studies on a number of factors which probably combine in
making up the complex protective mechanism of the upper
air passages. These factors may be classified as : (1) Mechanical (including the flushing action of secretions with the associated acts of swallowing and the ejection of nasal and mouth
secretions) ; (3) chemical (including the effects of the reaction of the mouth and nose secretions with other possible
bacterial inhibitory factors) ; and (3) biological (including
such processes as phagocji:osis and the effect of bacteria already present on the invader). These factors can be most
conveniently discussed from a topographical standpoint.
The Conjunctivce. — Maxcy ' states that the lachrymal secretion has no bactericidal action. Stort " found that colon bacilli
instilled into the conjunctival sac of rabbits could no longer
be recovered in culture after one hour. If the lachrymal
duct were tied, the bacteria persisted in the conjunctiva for
a much longer time. He concludes, therefore, that the organisms are swept rapidly into the duct, and that the mechanism
for preserving the normal sterility of the eye — at least in the
case of the organism studied — was a mechanical one, and
not dependent on bacterial inhibitory action of the secretions.
Maxcy ' was able in man to recover B. prodigiosus from the
nose within five minutes after it had been introduced into
the conjunctival sac.
The Nasal Passages. — Although the nasal secretion is normally scant, still the mucous surfaces are constantly moistened. The cilia of the epithelium and the secretion of the
mucous membranes and that discharged into the nose from
the lachrymal duct create a steady current toward the posterior nares.^ Furthermore, the configuration of the nasal
cavities is such that bacteria and foreign particles are for the
most part arrested near the anterior nares. Thus, cultures
made in normal individuals vield large numbers of organisms
November, 1919]
319
TABLE I.— FATE OF SARCINA LUTEA SWABBED ON THE TONGUE
Name
OlaKnoais and
*«re
Procedure
Number of coloniea of sarcina lutra per plate recovered from
Consul, and pharynx
Con
trol
Date
lAimediately
After 10
min.
After
Ihr.
After
24 bra.
After
48 hra.
inoculation
1
1
1
0.
1
c
1
B
1
1
S
1
a.
3
9
1
<•
ja
June 10.
M. Cardiac. compcn-'oO
eated. .Mouth in
average condition.
Scarred tonsils.
i slant S. L.
swabbed on
anterior half
of tongue.
Plate
almost
pure
S. L.
00
Plate
about
JS.L.
60
1
8
No
S. L.
No
S. L
No No
S.L. S.L
No
S.L.
No
S.L.
No
S.L.
Took nothing by
mouth until' after
1-hour culture.
June 10.
G. Tuberculous poly- l.'i
'• serositis. Mouth
' clean. Ragged tonsils.
* slant S. L. 50
swabbed on
anterior half
of tongue. 1
2
6
No
S. L.
7
Nv
S. L.
No
S. L.
No
S.L.
No
S.L.
No
S.L.
No
S.L.
No
S.L.
Took small amount
of liciiiid between
second and third
cultures.
Jane 8.
Mo. Cardiac, cnmpen- 60
sated. Mouth in
average condition.
1
i slant S. L. ' x
swablied on Almost
anterior half pure
of tongue. plate.
10
ISO
No
S. L.
No
S. L.
No
S. L.
No
S.L.
No
S.L.
No
S.L.
No
S.L.
No
S.L.
No
S.L.
Took small amount
of water between
second and third
cultures.
May 31.
H. Cardiac, compen- 1 30
sated. Mouth in 1
average condition. 1
» slant S. L. =c
swabbed on Plate
anterior half almost
of tongiie. pure.
No
S. L.
No
S. L.
No
S. L.
No
S. L.
No
S. L.
No
S. L.
No No
S. L.S. L.
No
S.L.
No
S.L.
No
S.L.
May 31.
L.
Cardiac, compen- 50
sated. Mouth in
average condition.
i slant S. L.
swabbed on
anterior half
of tongue.
00
Plate
3
A few
cols.
S. L.
(confluent).
4
No
S. L.
No
S. L.
N'o
S.L.
No
S. L.
No
S.L.
No
S.L.
No
S.L.
No
S.L.
May 31.
D.
Nephritis. Mouth 40
in average condi- | |
tion. 1 !
1 1
i slant S. L. oc
swabbed on Plate
anterior half almost
of tongue. 1 pure.
No
S. L.
1
No
S. L.
No
S. L.
No
S. L.
No
S.L.
No No
S. L.S. L.
No
S. L.
No
S.L.
No
S.L.
Took water between
second and third
cultures.
TABLE II.— FATE OF SAUCIN'A LUTEA SWABBED ON NASAL MUCOSA
June 21
June 19.. B
Abdominal aneur- 3S
ism. Nose and
mouth normal.
i Cardiac, compen- 60
I sated. Nose and
mouth normal.
Cardiac,
compen
sated.
\ose and
mouth
normal.
Scarred
tonsils.
Cardiac,
compen
sated.
Nose and
mouth
normal.
Large
scarred
tonsils.
} agar slant of
S.L. swablied
on nasal septum.
Number of colonies of sarcina lutea per plate recovered from
no8o and nasopharynx
00 I No
About S. L.
i the
plate
is S.L.
No
About S. L,
i the
plate
is S.L.
} agar slant of » No _
S.L. swabbed About S. L. About
on nasal sep- i the
turn. I plate |
is S.L.
4 agar slant of I oo
S.L. swablied .\bout
on nasal septum.
No
S. L.
if the
plate I
isS.L.'
C
No
S. L,
i. of
plate
is S.L
Psychoneurosis.
Nose and mouth
normal.
12 i agar slant of « No No S. L. 3
S.L. swabbed About S. L.l
on nasal sep- 1 of
I tum. I plate
I IS S.L.
i 20 : i agar slant of I « I No oo No
S.L. swabbed About S.L. About S.L.
on nasal sep- i of I i of
I tum. , plate plate |
About
i the
plate
is S.L
About
i the
plate
is S.L
6
No S. L,
No
S.L
No
S.L.
No
S.L.
No
S.L.
No No
S. L.S. L
No
S.L.
No No
S. L.S. L
No I No
S. L.S. L.
No
S.L.
No
S.L,
No
S. L.
plate
is S.L.
plate
Is S. L.l
No
S.L.
No No No No
8. L. S.L. S.L. .S.L.
No
S.L,
No
S. L.
Control
culture
before
noculution
No S. L.
No
S.L
No
r.S. L
No S. L.
No S. L.
Took nothing by
month until aft»r
the l-hoiir culture.
Took nothing by
mouth until after
the 1-hour culture.
Drank water after
the 10-minuto culture.
Drank water after
thelO-minute culture.
Took nothing by
mouth until after
the Ihour culture.
320
at the nasal orifices and few or none from the deeper nasal
passages.' Maxcy' recovered B. prodigiosus from the nasopharynx 15 minutes after instilling it into the conjuuctiva.
and we found sarcina lutea in the pharynx 10 minutes after
swabbing it on the anterior part of the septum.
With regard to the bacterial inhibitory effect of the nasal
secretions, the literature is contradictory, some writers finding a marked inhibitory action and others failing to do so.
Variations in the method of collecting and diluting the secretions, in the organism used, and in the method of plating,
may account for these discrepancies. Kligler ' has shown
recently that small amounts of nasal secretions added to cidture media at times promoted the growth of organisms such
as maningococci. He believes this action to be due to
" vitamins.'^ The experiments of Calvino,' however, which
approximate most closely natural conditions, indicate that
the nasal mucosa is an imfavorable medium at least for some
types of organism.
It seems clear, therefore, that the normal tendency is to
preserve sterility of the deeper nasal passages and that no
true permanent nasal flora exists.
The Mouth and Throat. — The mouth affords an especially
favorable opportunity for some types of bacterial growth ; food
particles, carious teeth, desquamated epithelium and saliva
furnish media whose effectiveness is attested by the enormous
numbers of bacteria constantly present even in so-called clean
and well-kept mouths. There is, however, a continuous shift
in the " normal " flora, so that cultures made from the same
individual on successive days may yield different quantitative
and qualitative results. Such variations are to be expecterl
with changing food and fluid intake and variations in mouth
hygiene. Furthermore, the abundant salivary and moutli
secretions with the constant flushing effect of ingested fluids,
swallowing and expectoration, undoubtedly constitute a cleansinjc mechanism.
[No. 345 J
saliva and^|
With regard to the bacterial inhibitory effect of saliva and'
mouth secretions in vivo, no satisfactory data are at hand,
althougli numerous test-tube experiments are on record. Thus,
Sanarelli ' found that streptococci, staphylococci, M. tetragenus and cholera spirilla were rapidly destroyed by fresh
filtered saliva in vitro, unless an enormous number of organisms were used. The pneumococcus, on the other hand, throve
in saliva better than in broth. Barnes ' using a similar
method, found that saliva had no bactericidal action on streptococci or pneumococci. Variations in the results of such
experiments are to be expected under various experimental
conditions.
The importance of the normal mouth flora in over-growing
and suppressing invading pathogenic organisms is indicated
only in an indirect way. On artificial media, meningococci,
pneumococci and influenza bacilli grow well in certain pro])ortions with the normal mouth organisms. They may, however, be rapidly overgrown by " spreaders," particularly of
the aerobic spore-bearing types. It is possible that such
organisms may actually exert a similar effect in the mouth,
although this is not directly demonstrated.
It is clear, therefore, that a complex mechanism exists in
the upper air passages, which under certain conditions suffices
to dispose of invading pathogenic microorganisms. The details of its operations are obviously variable, and as is to be
expected, it often breaks down. Thus, such factors as dosage
of the organism, local pathological processes or aoatomical
anomalies, variations in the biological activities of the organisms themselves, may play a part in explaining why certain
bacteria may gain a foothold at one time; and at another, or
in a different individual, be promptly wiped out. From the
standpoint of epidemiology it seems more profitable, therefore, to observe the actual fate of organisms introduced into
the upper air passages than to try to anal3'ze their exact
method of disposal.
TABLE III.— FATE OF SARCINA LUTEA INTRODUCED INTO TONSILLAR CRYPTS
Date
Name
June 26.
C.
June 26.
F.
June 25.
M.
June 25.
Fi.
Diagnosis and i
Syphilis. Nose and
moutli essentially
normal. Small, clean
tonsils with sealed
orypts.
Hodgkin's disease.
Large, ragged tonsils.
Cardiac, compensated. Large, ragged
tonsils with open
crypts.
Tuberculous pericarditis. Large, scarred adherent tonsils.
i agar slant of
S. L. introduced
int o a tonsil
crypt.
i agar slant of
S. L. introduced
into a tonsi 1
crypt.
i agar slant of
S. L. introduced
into a tonsil
crypt.
i agar slant of
S. L. introduced
into a tonsil
crypt.
Number of colo
;s per plate of sarcina lutea recovered
from tonsil crypt
(Almost
pure
plate.)
(Almost
pure
plate.)
(Almost
pure
plate.)
(Almost ' (Almost
pi.re I pure
plate.) I plate.)
No S. L.
(Almost
pure
plate.)
No
S. L.
No
S. L.
No S. L. No
3. L.
No
S. L.
No
S. L.
No
S. L.
No
S. L.
No
S. L.
No S. L.
Took nothing by mouth
until after the 1-hour
culture.
Took nothing by mouth
until after the 1-hour
culture.
Took nothing by mouth
until after the 1-hour
culture.
Took nothing by mouth
until after the 1-hour
culture.
XOVEMBER, 1919]
321
None the less, an attempt was made to determine, at least
approximately, the mechanism which led to the rapid disappearance of sarcina lutea. The reaction of the mouth secretions, the etfect of moiluuiical cleansing, and bacterial
inhibitory clTccts of the mouth secretions were studied.
1. Effect of the Reaction of Mouth Secretions. — Saliva
and mouth secretions were collected from each of the patients
inoculated with sarcina lutea. The mucous membranes were
siTa|)ed with a larfje platinum loop, after which the patient
expectorated the saliva which had accumulated in the mouth.
The entire mixture was diluted with an equal amount of
fresh, sterile distilled water, and tlie reaction immediately
tested. The colorimetric comparison method, as now generally used in bacteriological work * was employed with phcnolsulphonephthalein and alizarin as indicators. The pll of the
various specimens is indii-ntcil in tlie I'ollowini: tabli(Table IV).
T.ABLE IV
pH ok Spkcimk.ns Of- Salha from I.NDiviDrALS Ixocn.ATa) With
Sakcina Lutea
pll or Siiliva pH after staiulirig
Name iinmcihittelv oiip hour
Mo 5.9 5.9
G 5.9 —
H 5.9 —
P. 6.0 6.0
Mu 6.0 —
L. 7.0 6.9
F. 7.0 7.0
D 7.2 7.1
T 7.2 7.0
Ho. 7.3 —
Gr 7.4 7.1
Pi 7.6 7.3
Ma 7.6 —
The range of growth of sarcina lutea was next tested.
Tubes of plain agar with reaction adjusted from pll 5.0 —
to 8.0-1- were inoculated. Sarcina grew with equal luxuriance on all the tubes within this range. It seems clear, therefore, that the reaction of the mouth secretions cannot alone
accoimt for the disposal of sarcina lutea.
2. Mechanical Influences. — .\n attemjit was made to asiertain to what extent the normal wiisliing processes in the nuiuth
TABLE V
BAt'n;RiAL Coi'.NTS fbom Tongue Befork and Affeb Iiuiioatixo
Mouth With Salt Solutio.n
Name
Ko. cols, from I loop
of tongue acrapinics
before irrigation
No. cola, from 1 loop
of tongue scrapings
immediatf'lv after
irrigation
No. cola, from 1 loop
of tongue KCrjpinpgs
lOmin. after mouth
irrigation
B
M
ICOO
00
800
Plate contains about
as manycoluiiiesas
before.'
so
00
serve to remove organisms present. The mouth was thoroughly
rinsed with one liter of sterile salt solution. The patient
tcKiperated in making this washing effective by churning the
fluid in the mouth and scraping the tongue with the teeth.
Such an irrigation would be expected to remove more organisms than the ordinary acts of swallowing and expectoration.
The tongue was scraped with a large platinum loop just
before and just after the washing and at subsequent intervals. The loop of scrapings was diluted and plated in a standard manner. In no case was it possible to nnluce the
bacterial count by more than 50 per cent, even by such exten
TABLE VI.— EFFECT OF SALIVA ON THE GROWTH OK SARCINA LUTEA
One standard loop
from each tube
plated at following
tntcrrali
O.t c.c. saliva
0.2 c. c. auapenalon
S. L. + 0.2 c. c. aalt
solution
0.2 c. c. suspension of
mixol mouth bacteria
+ U.2 c. c. suspension
8. L.
0.2 c. c. saliva +
0.2 c. c. auapenalon
S. L.
0.2 c. c. saliva +
0.1 c. c. suspension
S. L.
:. saliva +
. suspension
Imineiliat«lv
About 500 roU.
of various kinds '
About 300 cols,
of variouH kinds,
1 hour .\bout .'iOO cols, i
of variouK kinds.
S baun.
About 2()U cols,
of various kinds.
M hours About .500 cols. \
of various kinds.
oD cols. S. L.
00 colft. S. L.
00 cols. S. I.,, witb 00 coIk. S. ].•. witb « cols. S.L. with 2<'>0 rols. S. L.
1 about 50 cols. I a few muutli a few mouth { Mouth biicteria.
mouth bacteria. | bacteria. bacteria.
00 cols. S.L. with 1 About \ as many 10 cols. S. L. No S. L. Mouth
about 50 cols. I colonies S. L. an (appeared iift- bacteiiii.
mouth bacteria. I in previous pla- er -18 Imurs).
te, with a good .Mouth bac
I ' miiny mouth tcria.
I bacteria.
o3 cols. S. I>. with 2 ciiIh. S. L. (ap- 1 col. S. I,, (ap- Xo S. L. Mouth
about 100 cols. pi-ared after •!« penred nft<'r 4 , bacteria,
mouth bacteria. Iiours), with days). .Mouth
a good many bacteria.
mouth bacteria.
X coIh. S. L. with ' Ko .'^. L. Mouth No S. L. .Moutli No S. I.. MomII,
about 100 cols. bacteria. bacteria. Iiititirin.
moutli bacteria.
X cols. S. L. with ! No S. L. .Mouth , No S. L. Mouth No S. L. Mouth
about iOO cols, i bacteria. bacteria. bacteria,
mouth bacteria.
100 cols. S. L.
Mouth bacteria.
1 col. S. L. (appeareil after 4
days). Mouth
bacteria.
7 cols. S. L. (appeareil after 3
days).
No S. L, .Mouth
bacteria.
Xo S. L. Mouth
bacteria.
322
[]Sro. 345 J
seen. Xo^f
sive irrigation. It seems, therefore, that mechanical processes
alone cannot adequately account for the rapid disappearance
of sarcina lutea. Table V shows an illustrative protocol.
3. The Inhibitory Ejfect Upon Bacteria Exerted by the
Mouth Secretions and Saliva. — An attempt was made to reproduce the conditions present in the mouth as nearly as possible
by the following method. 0.2 c. c. of fresh saliva was placed in
each of a series of tubes. To each was added decreasing
amounts of a thick suspension of sarcina lutea. One standard
loop of the mixture of saliva and sarcina lutea was removed
from each tube immediately and at various intervals, and
plated on plain agar plates. The results which coincided in
numerous experiments with various specimens of saliva, except
as to slight quantitative variations, are illustrated by the
following typical protocol (Table VI).
From this protocol, the following facts are apparent:
1. Cultures made from a specimen of saliva at various
intervals up to 24 hours yielded about the same number and
kind of organisms.
2. Cultures made at various intervals up to 84 hours from
a suspension of sarcina lutea in salt solution yielded the same
number of colonies.
3. Cultures made at various intervals up to 84 hours from
a mixed suspension of mouth flora and of sarcina lutea yielded
the various organisms in about the same proportions. Sarcina lutea was not overgrown or inhibited.
4. Cultures made at intervals up to 24 hours from suspensions of varying concentration of sarcina lutea in saliva
yielded rapidly decreasing numbers of colonies of sarcina
lutea. The number was miich reduced in 15 minutes, only
an occasional organism could be recovered after 1 hour, and
none after 2 hours. Furthermore, the growth of the few
organisms obtained after the first culture was inhibited for
intervals of 1 to 4 days before the colonies appeared in the
plates.
Smears were made from each tube in the above exjieriment
at 15-minute, 1-hour and 2-hour intervals. After 15 minutes,
abundant sarcinse were seen in all tubes. They were normal in staining qualities and in groiiping. After 1 hour
the smears from the mixtures of saliva and sarcina lutea
showed the sarcinse to stain poorly and to be pale and gran
ular. After 2 hours few definite organisms could be seen. Ifi
agglutination was apparent. The organisms from the control
tubes stained normally.
It may be concluded, therefore, that saliva exerts a rapid
bactericidal effect on this organism and that this effect is
independent of the bacteria normally present in the saliva.
DISCUSSION
The general result of these experiments indicates that
even after a short period of time it is usually impossible to
recover sarcina lutea swabbed in large amounts on the tongue,
nasal mucosa, or into the crypts of the tonsils. Disappearance from the nose was somewhat slower than from the other
sites; in only one instance could any organisms be recovered
after 24 hours, and in no case after two days. Cultures
made in this way do not, of course, prove the complete
absence of the organism in the mouth and nose, but the
general trend of the quantitative relations indicates a rapid
disappearance. The fact that the estimated dose of 50 to 100
billion organisms was vastly greater than that in any natural
infection, indicates the remarkable efficiency of the mechanism present in the upper air passages for disposing of this
organism. An analysis of the possible factors active in effecting this disposal indicated that reaction of mouth secretions,
mechanical cleansing, and the mouth bacteria play little if any
part, but that the saliva and mouth secretions exert a prompt
and marked bactericidal effect.
Similar methods are being used in studying the fate of
other organisms introduced into the upper air passages.
REFERENCES
1. Maxcy, Kenneth F.: Journal A. M. A., 1919, LXXII, 636.
2. Stort, A. G.: Arch. f. Hyg., 1891, XIII, 395.
3. Piersol, G. A.: Human Anatomy, 1906, p. 1416.
4. Hasslauer: Centralbl. f. Bakteriol., 1906, ]. Abt.. Ref. Bd.
XXXVII, p. 1.
5. Kligler, I. J.: Jour. Exp. Med., 1919, XXX. 31.
6. Calvino, V. E. M.: Arch. Itallano di otologia, etc., 1899, VIII,
169.
7. Sanarelli: Centralbl. f. Bakteriol., 1891, 1 Abt., X, 25.
8. Barnes, B. S.: Trans. Chicago Path. See, 1907-09, VIII, 249.
9. Clark, W. M., and Lubs, H. A.: Jour. Bacteriol., 1917, II, 1.
THE INFLUENZA BACILLUS IN PARANASAL SINUS INFECTIONS
By S. J. Ckowe and W. S. Thacker-Neville, Baltimore
(From the Departments of Surgery and Pathology of The Johns Hoitkins Medical School.)
There is some difference of opinion as to the nature of the
organism primarily responsible for the influenzal epidemic
of 1918-1919. Pfeiffer's bacillus was found in a sufficient
number of cases to raise the question as to whether it was
the primary agent, or, like the streptococcus and pneumococcus, a secondary invader.
We were interested to determine whether or not this bacillus occurred more frequently in a series of infected nasal
sinuses observed immediately following the epidemic, than
in a series of such cases observed during a period when there \
was no epidemic. During the height of the epidemic in Baltimore, it was impossible, owing to the press of work, and the I
scarcity of skilled help, to make bacteriological examinations j
of the infected sinuses. Within six weeks after the epidemic j
had subsided, however, one of us (Neville) undertook a careful bacteriological study of every case of "maxillary sinusj
infection treated at The Johns Hopkins Hospital. We limited]
our studv to the maxillarv sinus, because this cavitv is the
NOVEMBEB, 1919]
323
one most frequently affected, and because the material for
culture can be obtained from this situation with less risk of
contamination than from the ethmoidal, frontal or sphenoidal
cells.
We present for comparison two series of cases. The first
series of seventy includes every case of accessory nasal sinus
infection treated at The Jolms Hopkins Hospital during the
years 1913-1918. in which we have a report on the cultures
made from the antrum.* Of these 70 observations, made during a period when there was no epidemic of influenza, we
have 15 cases in which the influenza bacillus was found in the
antrum. The 30 cases of the second series were all observed
during February. March and April of 1919. In eight of
these cases we found B. influenzce in the antrum. It is of
interest that the percentage of cases in which the influenza
bacillus was found in the antrum is about the same in each
group.
The material for culture is obtained by a very simple
method. A small piece of cotton on the end of a steel applicator is moistened with a 20 per cent solution of cocaine
and 1 : 1000 adrenalin. The excess of cocaine is removed
by pressing the cotton between two layers of gauze ; this will
insure against s}-mptoms of cocaine poisoning. A small piece
of cotton moistened with cocaine and adrenalin is also placed
between the anterior end of the inferior turbinate and the
septum, and both are left in place for ten or fifteen minutes.
A curved trochar, a small rubber ear syringe, a nasal speculum
and a finger bowl are then boiled for at least five minutes.
The patient's nose is cleansed of all visible discharge. The
trochar is passed under the anterior end of the inferior turbinate into the antrum, and the stilette removed. The patient
bends 90° forward, and often the pus will drop from the
cannula. If not, air or a few drops of sterile salt solution
are blown into the antrum with the rubber syringe, and the
material returning through the cannula is caught in a sterile
test-tube. It is important that enough adrenalin be u.«cd to
make the procedure absolutely bloodless, for we have found,
in agreement with Rivers, that a few drops of blood mixed
with the material obtained for culture will inhibit the growth
of the influenza bacillus.'
The bacteriological technique employed is as follows : The
material is plated immediately on agar containing defibrinated rabbit's blood, and the plates are incubated at 37° C.
for twenty-four hours. The various colonies are tiien examined in stained smears and transferred to blood-agar slants.
After twenty-four hours the colonies showing the cultural
characteristics of the streptococcus and pneumococcus are differentiated by Xcufeld's bile soluble test. The pneumococci
are grouped according to the method of Avery, Chickcriiig.
Cole and I)ochez.' The serum used was obtained from tlie
• It was formerly our custom to take cultures from Infected
Blnoses (chiefly at operation) on cotton swabs. These swabs were
sent to the regular bacteriological laboratory of the hospital but
had often completely dried up before reaching the laboratory.
This accounts for the comparatively small number In which we
have a bacteriological report.
Rockefeller Institute. The influenza bacillus grows freely on
blood-agar but not at all on plain agar. This differentiates it
from the micrococcus catarrhalis. This latter organism may
be differentiated from other gram-negative cocci by the use of
Hiss's serum sugar media, and the Elser and Huntoon
classification.
In the first series of 70 cases observed during the period
from 1912 to 1918, the influenza bacillus was found in the
antrum in 15 cases (21 per cent). The streptococcus was
found in 33 cases (47 per cent) ; in 10 of these the organism
was hipmolytic. The pneumococcus occurred 12 times (17
per cent). The staphylococcus was found in 16 cases (22
per cent) , in one of which it was haemolytic ; the proteus was
found once : and the diphtheria bacillus twice.
In the second scries of 30 cases observed during the three
months immediately following the subsidence of the influenzal
epidemic, the influenza bacillus was found in the antrum in
eight cases (26 per cent). The streptococcus was again the
predominating organism (14 cases, or 46 per cent) ; of these
14 cases, in four it was haeniolytic. The following organisms
were occasionally found : the ha?raolytic staphylococcus in
four cases, the pneumococcus in three cases, the micrococcus
catarrhalis in two cases, and a gram-negative diphtheroid
bacillus in three cases. The diphtheria bacillus was found
in one case, the bacillus lactis .Tprogenes once, and the proteus
vulgaris in two cases.
The influenza bacillus was recovered from the antrum in
pure culture in four cases. In four other cases it was found
associated with other organisms: streptococcus ha?molyticus,
streptococcus mucosus, micrococcus catarrhalis, micrococcus
tetragenus, and the staphylococcus albus. The ha^molytio
staphylococcus occurred four times, once in pure culture. The
staphylococcus albus was found in eight ca.=es, but was probably in each case a contamination from the nasal cavity.f
The pneumococcus was recovered in three cases (in two Type
III and in one Type IV), twice in pure culture, once mixed
with a staphylococcus albus.
t The healthy nasal cavity is apparently a normal habitat for
the staphylococcus albus. We toolc cultures from the middle
turbinate In seven individuals with clinically normal nasal cavities. A little mucus was obtained from the middle turbinate
with a platinum loop and implanted on plates of rabbit bloodagar. We found: staphylococcus albus 01 per cent; diphtheroids,
41 per cent; pneumococcus, Type IV, 16 per cent; micrococcus
catarrhalis, 8.9 per cent.
Park and Wright, In 1898, took cultures with a platinum loop
from far back In the nose and showed that the nasal secretion has
no bacteriocidal action. Of 3C examinations only six were sterile.
The predominating organism was the staphylococcus.
Hasslauer' In 1902, made bacteriological examinations from the
normal na.sal cavities of 111 Individuals. He found: staphylococcus in 2.T per rent: pneiimoroccus In 20 per cent; streptococcus
in 17 per cent; diphtheroid In 1.T per cent.
He also investigated the bacteriological +++++
CONTENTS of the nasal
discharge In 78 cases with a coryza and found much the same
varieties of organisms in both healthy and pathological nasal
cavities. The only difference was that they were far more numerous In infected nasal cavities.
324
[No. 345
CONCLUSIONS
1. The influenza bacillus was found in infected maxillary
sinuses in practically the same percentage (21 per cent) in a
series of cases observed during a period of six years when
there was no epidemic, as in a second series observed immediately following the epidemic in Baltimore during the
winter of 1918-1919 (26 per cent).
2. The influenza bacillus is not infrequently found in
pure culture in the antrum.
3. Clinically B. influenzw is a pyogenic organism.
4. The predominating organism in all antrum infections
is the streptococcus.
5. We infer from these observations that the influenza bacillus, like the streptococcus and pneumocoecus, is a secondary
invader, and not the primary cause of the disease known as
influenza.
LITERATURE
1. Rivers, T. R.: The effect of different bloods on the growth of
B. influenza;. Johns Hopkins Hosp. Bull. Balto., 1916, XXX, 129
131. [B. influenza: grows better on rabbit blood- and cat blood-agar
than on human blood-agar; and defibrinated human blood and
normal human serum are very bactericidal for the strains of
influenza bacillus studied as compared with defibrinated rabbit
blood, normal rabbit serum and normal guinea-pig serum.]
2. Avery, Chickering, Cole and Dochez: Acute lobar pneumonia.
Monogr. Rockefeller Inst. M. Research, N. Y., 1917, No. VII, p. 25.
3. Hasslauer, W. : Die Bakterienflora der gesunden und kranken
Nasenschleimhaut. Centralbl. f. Bakteriol., 1. Abt., Jena., 1902,
XXXIII, 47-51.
Gibson, G. H., Bowman, B., and Connor, J. I.: Etiology of influenza, Brit. M. J., Lond., 1919, I, 331-335. [The influenza epidemic
was due to a minute flltrable microorganism of coccoid shape
grown by Noguchi's cultural methods.]
Lewis, C. T., and Turner, A. L. Suppuration in the accessory
sinuses of nose: a bacteriological and clinical research. Edin. M.
J., 1905, n. s., XVIII, 395-421; ibidem., 1910, n. s. IV, 293-318. [In 43
antral cultures taken without reference to an influenza epidemic
the influenza bacillus was recovered three times. In another series
of 57 cases it was recovered once. In both series streptococcus,
pneumocoecus and staphylococcus were the chief organisms found.]
MacCallum, W. G.: The pathology of the pneumonia in the
United States army camps during the winter of 1917-1918. Monogr.
Rockefeller Inst. M. Research, N. Y., 1919, No. X, 140. [Of 48 cases
of pneumonia of influenzal origin 16 contained the influenza
bacillus in the bronchioles and occasionally in the alveoli. In six
other cases the B. influenza: was found in the sputum.]
MENINGOCOCCUS PNEUMONIA. I
THE OCCURRENCE OF POST-INFLUENZAL PNEUMONIA IN WHICH THE DIPLOCOCCUS
INTRACELLULARIS MENINGITIDIS WAS ISOLATED. FROM OBSERVATIONS
AT CAMP COETQUIDON, A. E. F., FRANCE
By M. L. Holm, Lansing, Mich.
Major, Medical Reserve Corps, U. S. Armi/ (Discharged), Director of Lahoratory at Camp Hospital Xo. 15, A. E. F.
WiLBURT C. Davison, Baltimore, Md.
Captain, Medical Corps, U. S. Army (Discliarycd), Assistant to Director, Base Lahoratory, Base .Section Xo. 1, A. E. F.
Whatever may be the cause of primary influenza, it would
seem that the secondary' pneumonia may be caused by difl'erent
organisms in different regions. As MacCallum' has pointed
out, this variation " may depend on an endemic or epidemic
distribution of organi.sms as inhabitants of the nasopharynx."
Pneumococci,' streptococci ' and staphylococci ' have been
the most frequent secondary invaders and evidence now
appears '• * '• "• '• ' that the diplococcus intracellularis meningitidis (Weichselbaum) may produce fatal pneumonia. The
cases reported in this paper were studied at Camp Hospital
Xo. 15, Camp Coetquidon, Base Section No. 1, A. E. F.,
France, during the epidemic of influenza from September 1,
1918, to February 15, 1919.* Table I shows the total number
of cases of influenza, pneumonia and cerebrospinal meningitis
admitted to the hospital during this period.
* Prior to September 1, 1918, there had been but three deaths in
this hospital due to the epidemic. They occurred in the last week
of August, 1918. Cultures from the lung tissue at autopsy
showed B. influenza; pneumocoecus Type III and pneumocoecus
Type II, respectively. They are not included in this study be
Prior to the outbreak of the epidemic of influenza, there
were no cases of meningococcus meningitis in the hospital.
It will be noted that coincident with the occurrence of meningococcus pneumonia, there occurred a considerable number
of meningococcus meningitis cases.
The presence of influenza at Camp Coetquidon was first
noted about September 1, 1918, and many cases of pneumonia
cause other data for comparison are not available. This study was
terminated on February 15, 1919, because the evacuation of troops,
begun at that time, rendered records for comparison unreliable
and difficult to secure. On February 15. 1919, there were still
eight cases in the hospital diagnosed as meningococcus pneumonia.
These are included among the total cases recorded but their final
disposition is not included.
Camp Coetquidon was an artillery training area occupied by
troops which arrived from the United States during the latter part
of August, September and October. 1918, and remained until February 15, 1919. These together with the permanent camp personnel
numbered approximately as follows: September, 16,657; October,
19,177; November, 16,303; December, 12,850; January, 13,9S
February, 14,780.
XOVEMBER, 1919]
325
developed. On Sept<?nil)er 3, 1918, bacteriological cultures at
autopsy from the lungs of a case of pneumonia showed a pure
growth of meningococci (Type A Pasteur). A description of
the bacteriological and serological technique employed is
appended. On Scpteml)er G, 1918, a similar case showed
meningococcus Type 15 in the lung culture. Both cases
occurred early in the epidemic, the patients were in the same
ward at the same time, but tlie fact that different types of
meningococci were isolated would seem to preclude tlie possil)ility of cither of the two cases having been infected from the
other or that both were infected from the same source.
On September V\ and 15 meningococci were recovered from
the sputa of two ])ncumonia cases.
TABLE I
Sept.
Oct.
Nor.
Dee.
Jan.
Feb. (i)
Total!
Cases of influenza admitted
847
263
170
38
80
112
1510
to hoopital.
Total cases of pneumonia ad
136
107
53
2!
36
30
403
mitted to liospital.
Total deatlis from pneumonia.
27
30
12
3
6
78
Cases of pneumonia showing
20
15
27
2
13
8
85
meningococci in sputum.
Deaths from pneumonia show
6
3
6
U
1
5
23
ing menin^'ococci in lungs
at autopsr.
Cases of meninROCoccus nicn
4
7
/
3
1
22
inpitis.
Deaths from meningococcus
4
2
3
3
1
13
meningitis.
E.XPLANATION OF TABLE I
Total ea»t» of pneumonia include pneuraonius due to all causes. Many cases admitted aa Induenaa developed pneumonia after admission. Such cases are recorded
aapoeumonia and not influenza.
Cases 0/ pneumonia ihou-inff meningococci are inc'uded among the total cases of
pneumonia. This croup, however, d.jes not include any of the cases in which cerebrospinal menincritis was present.
Total deathi from pneumonia include all deaths from pneumonia. The deaths
from pneumonia showing meningococci are included in this group.
Catei of meningoeoecuM meninffitis include all cases of cerebrospinal meningitis
Caused by meningococci, with or without pneumonia involvement.
It seemed, tlicii. tliat the possibility of the meningococcus
Ijcing an important factor in the epidemic was worthy of careful investigation. Cultures were therefore taken (September
19, 1918) from the throats of all respiratory cases in the
hospital. Among lit thus cultured meningococci (Type B
Pasteur) were isolated from seven patients, six of whom had
pneumonia.
On September 20, 22, 23, 25, 27 and 29 throat and sputum
cultures of meningococci were recovered from 12 additional
cases of pneumonia.
During the period studied, 78 ca.«es of pneumonia came to
autopsy. Cultures on blood agar were made from sections of
the various parts of the affected lungs in all ca-ses. The findings arc of interest here for the purposes of comparing the
frequency and the association of the various species of bacteria
found during the epidemic. >[oningococci were recovered
from the lung tissue in a total of 'i'.\ cases (in pure culture
in 7 cases and in mi.xed culture in IG). The complete bacteriological results in these 78 pneumonia autopsies are
recorded in Table II.
The majorit)' of the meningococci isolated were Pasteur
Type B and were also agglutinated by Gordon's meningococcus
sera, Types II and IV (corresponding to the Rockefeller Institute normal meningococcus). The cultural and serological
findings in tliese cultures were confirmed at Base Jjaboratory
Xo. 1 at St. Xazaire and at the Central Medical Laboratorj'
at Dijon.*
In our experience, ilespite certain contradictory statements
in the literature in regard to the correlation of the American,
English and French classification of meningococcus t)7>es.
Lieut.-Col. Gordon's Types I and III and the Rockefeller
Bactekia Isolated from the Lungs at Autopsy from 78 Cases or
Pneumonia at Camp HosriTAL No. 15, A. E. F., Fbance
B. influenstr
Pure cultures 7 cases
♦Mixed " 23 " , assoc
Total " 30 ••
TMeningococcus. . .11 times
Pneur
. neumococcus IV 7 times
•iated with-! f^trept. hemolytic. times
I Strept. vir 1 time
I It. tulierculosis. . . 1 time
Pneumococci IV
Pure cultures 11 cases, HI. influenza 7 times
*Mi\ed " 14 " , associated with-! Strept. hcmol ... . 4 times
Total " 25 " , I Meningococcus . . 3 times
Meningococci
Pure cultures 7 cases,
Mixed " 16 " , associated with
Total " 23 " ,
rn. inlluen/.a 11 times
.Strept. hemol. . . . fi times
Pneuniococcus IV 7 times
Strept. vir I time
H. tulH-rculosis. . . 1 time
Streptococcus hemolyticus
Pure cultures !( cases.
Mixed
Total
{ n. influenza. . . .
Pneumococci IV
20
associated w ith-| Meningococci .
I B. tul>erculo8i8.
B. tuberculosis
Pure cases,
Mixed " , associated
Total 6 " ,
fstaphylococcus..
.,, Strept. hcmolvt.
with -; . ,. ' .
I Strept. vir
I H. inllucn?;!' . . . .
I tunes
times
times
times
times
times
time
time
Streptococcus viridans 2 ca.«c8 ~1
Staphylococcus aureus 2
Pneumococcus I 1 case
Streptococcus mucosus 1
Itacillus aerogenes capsulatus. . . I "
Staphylococcus alhus 1 "
Associated with other organisms as indicated
*Uixetl cultures refer to two or more species of bacteria
Institute paranormal sera usually agglutinate tlie same cultures as Pasteur Type A. Colonel Gordon's sera II and IV
and the Rockefeller Institute normal meningococcus scrum
usually agglutinate the same cultures as Pasteur Tyjie B.
Pasteur Types C and I) are rare.
Gram-stained smears of the sputa from the pneumonia cases
in which mcningoiocci were isolated showed so many intracellular gram-negative diplocwci as to resemble smears of
spinal fluids from acute cases of meningococcus meningitis.
CLINICAL COURSE OF MENINGOCOCCUS PNEUMONIA
In the severe ca.ses the onset was usually acute, after a period
of indisposition la.sting from a few days to a week. Inuring
the prodromal period there was generally a history of chills,
• Thanks are due to CapUin E. H. Mason, M. C, U. S. Army, for
assistance In conflrming these cultures.
326
[Xo. 345
Days
Hosp.
Laboratory findings durir
g illness
Autopsy
fin<dings
Case
Organization
Urine
W. B. c.
Blood
cultures.
Sputum cultures
Date of
death
Lung gross anatomy
t Lung cultures
topsy
number
V. F
133 d F. A.
2
Alb. and casts
6400
^eg.
Mixed
9/3
Lobar pneumonia..
Meningo. A.
25
T. R
44th Engrs.
141st F. A.
a
12
Alb. and casts
4400
7000
Neg.
Neg.
B. inf
9/6
9/21
Bronchopneumonia .
Bronchopneumonia .
Meningo. B.
Meningo. B.
28
J.B
Meningo. B
36
S.C
114th T.M.B.
6
13!i00^
^o.g.
Pneumo IV. . .
9/22
Bronchopneumonia .
Meningo. B.
Pueum. IV.
38
J. O'N. . .
61st Engrs.
7
7600
N«g.
B. inf
9/25
Lobar pneumonia,
bronchiolitis.
Sup.*
Meningo. B.
44
C. S
141st F. A.
2
9/29
Lobar pneumonia. .
Meningo. B.
Pneum. IV,
49
A. C
141st F. A.
17
4400
Neg.
Meningo. B. diphtheroid.
10/3
Bronchopneumonia,
bronchiolitis.
Sup.
B. inf. Meningo. B.
57
M. D....
141st A. T.
7
9600
Neg.
Meningo. B
10/3
Lobar pneumonia. .
Meningo. B.
Strept. vir.
58
R.S
329th F. A.
6
9400
Neg.
Meningo. B
10/8
Lobar pneumonia..
Meningo. B.
66
W. C...
329th F. A.
11
f6200\
\ 9000 J
Neg.
B. inf. Pneu. IV.
10/24
Bronchopneumonia,
bronchiolitis.
Sup.
B. inf. Jloningo. B.
86
R. C
328th F. A.
2
Alb. and casts
5400
Neg.
B. inf
10/27
Bronchopneumonia .
B. inf. Meningo. B.
89
F. N
329th F. A.
3
4200
Nee
11/2
Bronchopneumonia,
lung.
Wet
B. inf. Meningo. A.
B. P
Vet. Hosp.
3
Alb. and casts
2200
Neg.
B. inf
11/3
Bronchopneumonia,
lung.
Wet
B. inf. Men
98
ingo.
L. F
330th F. A.
9
Alb. and casts
r 2600 \
14200/
Neg.
B. inf
11/4
Bronchopneumonia..
B. inf. Meningo. C.
100
O.A
113th A. T.
8
Alb. and casts
18400
Neg.
Meningo
11/9
Bronchopneumonia,
bronchiolitis.
Sup.
Meningo.
Strept.
hemol.
105
E.N
Vet. Hosp.
11
Alb. and casts
8000
Neg.
Meningo
11/13
Bronchopneumonia,
bronchiolitis.
Sup.
B. inf. Meningo.
106
A. P
131st F. A.
13
Alb. and casts
J 9200 1
1 20,400 C
Neg.
B. inf. Meningo. .
11/23
Empyema. Bronchopneumonia. Sup. bronchiolitis.
B. inf. Meningo. Strept.
hemol.
111
C. G
133d F. A.
9
Alb. and casts
2200
Neg.
Meningo. B
1/29
Bronchopneumonia,
bronchiolitis.
Sup.
Meningo. B.
124
G.S
133d F. A.
6
Alb. and casts
/11,200\
\25,000J
Neg.
Pneu. IV'. Meningo.
2/1
Bronchopneumonia,
bronchiolitis.
Sup.
Meningo. B.
Pneu. IV.
125
A.J
7 th Vet.
Hosp.
8
Alb. and casts
r5200"\
1 9600 J
Neg.
B. inf. Meningococcus
2/1
Broncliopneunionia.
bronchiolitis.
Sup.
Meningo. B.
127
J. D
132d F. A.
3
Alb. and casts
7200
Neg.
Meningo. B
2/3
Broncliopneunionia.
bronchiolitis.
Sup.
Meningo. B.
B. inf.
128
D.K
705th M.T.C.
6
Alb. and casts
ri400\
1 4400 J"
Neg.
Meningococcus. . .
2/3
Lobar pneumonia. .
Meningo. C.
B. int.
129
R. L
P. W. 38.
It)
Alb. and casts
7800
Neg.
2/4
Bronchopneumonia,
bronchiolitis.
Sup.
Meningo. A.
B. inf.
130
* Sup. Bronch. = Suppurative Bronchiolitis. + Predomiimting org,i
coriled under lung cultures.
November, 1919]
32^
fever, headache, cough, pain in the chest and general malaise.
The skin was pale blue. The patient looked very toxie; the
chest examination showed variable areas of dullness and
numerous moist rales, quite generally distributed. A few
cases showed distinct lobar consolidation. The temperature
was 103°-106°, pulse 85-100, respiration 25-30. The urine
showed albumin and casts, usually early in the disease. The
blood findings were negative blood cultures and a normal or
reduced white cell count. The sputum was at first thin and
watery, but rapidly changed to a creamy white which, on
microscopic examination, showed numerous pus cells and
gram-negative diplococci. Severe cases grew rapidly worse;
the cyanosis increased; the lung consolidation extended and
the patient died within a few days. Among those who survived the first week, there appeared to be a marked tendency
toward suppurative bronchiolitis and protracted recover}-. As
the areas of consolidation diminished, the bronchioles filled
with thick muco-purulent secretions ; marked emphysema frequently developed ; such patients showed marked evidence of
dysphonia. At this stage, there was usually a marked rise in
the white cell count. Later in the disease, the meningococci
in the sputum became considerably reduced and other organisms correspondingly more prominent.*
AUTOPSY KIXDIXGS IN MENINGOCOCCUS PNEUMONIA
The lung findings at autopsy were usually of the bronchopneumonic type with numerous points in the consolidated
areas that exuded purulent fluid on pressure. Six cases were
distinctly lobar in distribution. On section, the consolidated
areas showed a peculiar pale violet color that appeared almost
characteristic of meningococcus pneumonia. The pleura was
generally quite free from exudate and the pleural surfaces were
generally dry. Fibrinous pericarditis was present with very
little increase of pericardial fluid. Endocarditis occurred in
over half of the ca.ses. Cloudy swelling of the liver, acute
splenic tumor and parenchymatous nephritis were constant.
The abdominal recti muscles were found ruptured in five cases.
The upper bronchi were generally inflamed and covered with
creamy pus. Meningococci were always found to be most
numerous in the purulent exudate from the bronchioles.
Cultures from the pericardium and pleural cavities never
showed meningococci. One patient dcveloiwd an empyema
from which a pure culture of streptococcus hemolyticus was
recovered from the fluid; yet, the lung cultures showed great
predominence of meningococci. Jlcningococci were never
recovered from any of the accessory sinuses. B. influemce
was recovered from the sphenoidal cells in pure cultures in
four cases.
Table III shows the laboratory findings in tiie 23 fatal cases
of meningococcus pneumonia (without cerebrospinal involvement) .
That virulent meningococci were prevalent among the troops
in Camp Coetquidon is shown liy the f a< t tiiat from Siptombcr
1, 1918, to February 15, 1919, 22 cases of cerebrospinal meningitis developed with 13 deaths. The meningococci isolated
were of similar type to those found in the lung tissue of the
meningococcus pneumonia cases.
BACTERIOLOGICAL FINDINGS IN CASES OP MENINGOCOCCUS
MENINGITIS
Of tlie 22 cases of meningococcus meningitis that occurred
during this period, blood cultures were taken in 16 with three
positive results. The positive results were all obtained from
early cases; and no positive blood cultures were obtained after
the first day of tlie disease. In one case the spinal fluid was
clear at the time the positive blood culture was secured. In
this culture, the meningococci numbered 2 per c. c, yet on the
following day, when the spinal fluid showed a high-cell count
and numerous meningococci, a second blood culture gave
negative results.
Spinal fluid cultures all gave positive results at tlie time
the first turbid fluid was secured. In nearly all cases, however, cultures failed to grow meningococci after the third or
fourth day, even though the white cell count remained high
for much longer periods.
Panophthalmitis developed in one case and meningococci
were recovered from the eye after enucleation. Among the
13 cases that came to autopsy, meningococci were recovered
from the ventricles or base of the brain in six and from the
pericardium in two cases. There was distinct evidence of
pneumonic involvement in ten cases, from whidi cultures from
section of the involved lung showed meningococci* in six
cases (four times alone and twice associated with B. infiuenzw) .
The other four ca.ses gave lung cultures of streptococcus hemolyticus, pneumococcus Type IV, pneumobacilli and staphyloc-occus aureus, respectively. Eighteen meningococcus cultures, secured from cases of cerebrospinal meningitis that were
typed, proved to be Type B Pasteur.
M eninfiococcii.s Carriers. — During the progress of the epidemic, efforts were made to segregate the carriers of meningococci in the various organizations that were showing tlie
greatest number of cases. The carrier rate varied greatly at
different times and in different barracks at the same time, the
general rate being much higher early in tiie epidemic than
later. Some of these carrier surveys were made on groups of
men too small to furni.sh reliable figures. Rut four sun'cys
were made at different times on fairly large numbers of men
as follows:
Time
Numbpr of men
cultur«<l
Carriers found
Percentile
Sept. 20/18
r)rt. 20/18
Dec. 6/18
Feb. 10/18
llfiO
22Sfi
I2.-.J
ll!IO
198
2S0
110
f.O
10
12
8
5
•Thanks are due Captain W. M. Rhett. M. C. and the Medical
Staff of Camp Hospital No. 15 for much of the clinical data.
These figures are of interest because they show an unusually
high meningococcus carrier rate while the epidemiological
waves were at their highest. The greatest number of carriers
generally appeared to be present in the barracks where
328
[No. 345
respiratory affections were most numerous. Carriers isolated
were reeultured twice each week. Very few of them continued
to be carriers over prolonged periods and no so-called " permanent carriers " were found during the investigation.
DISCUSSION
It will be observed that in this series meningococci rank
third among the bacteria found most frequently in the lungs at
autopsy in cases of pneumonia, being exceeded only by pneumocoeci and B. influenzae. However, if cerebrospinal meningitis cases be included, the meningococcus becomes the most
frequently found organism in the lesions causing death during
the epidemic. Out of 50 strains of meningococci typed from
carriers selected at random 44 were Type B, four Type C, and
two Type A Pasteur. Eighteen cases of cerebrospinal meningitis were caused by Type B meningococcus. Xineteen autopsy
cultures from cases of meningococcus pneumonia showed 14
Type B, three Type A, and two Type C Pasteur. It is, therefore, evident that the prevailing type of meningococcus during
this period was Type B Pasteur and was responsible for all of
the meningitis cases as well as the larger proportion of meningococcus pneumonia cases. The frequent association of meningococci with B. influenzcB is of special interest. On artificial
media, the two organisms grow together exceedingly well. The
possibility of a symbiotic pathogenicity of these organisms is
worthy of further study.
CONCLUSIONS
1. That meningococci were an important factor in the causation of post-influential pneumonia at Camp Coetquidon,
from September 1, 1918, to February 15, 1919.
8. That the meningococci present in the lungs in cases of
meningococcus pneumonia were essentially the same tj-pe of
organisms as those found in the spinal fluids in cases of
epidemic cerebrospinal meningitis.
3. That cases of meningococcus pneumonia may arise from
contact with cases of meningococcus cerebrospinal meningitis
and vice versa.
4. The meningococci may produce either bronchopneumonia
or lobar pneumonia.
TECHNIQUE OF BACTERIOLOGICAL EXAMINATIONS
Blood Cultures. — Eoutine blood cultures were made on all
cases of pneumonia. The medium used for such routine cultures was prepared as follows: Peptone, 10.0; salt, 5.0;
glucose, 5.0; beef infusion, 1000.0. This was titrated to
-1-0.4 acidity to phenolphthalein ; tubed in large test-tubes and
sterilized in an autoclave at 30 pounds for 15 minutes.
Blood for culture was drawn from one of the arm veins with
a sterile 10 c. c. syringe. This amount of blood was then
injected into 40 c. c. of medium after which the mixture was
incubated for 72 hours, unless growth occurred earlier. This
method gave good results with pneumoeocci, streptococci and
B. influenzce, but trial cultures with meningococci were
unsatisfactory.
Blood cultures for meningococci were made on a medium
prepared by adding 2 per cent agar to the above-mentioned
bouillon and sterilizing as before. This medium was melted
and cooled to 45° C. The amount of blood drawn for each
culture was 10 e. c. as before. This was mixed with 30 c. c.
of the melted medium and poured into sterile petri dishes,
allowed to set and placed inverted in the incubator for 72 hours
unless growth occurred earlier.
Cultures of spinal fluids and sputa were made on a petri dish
medium prepared by adding 2 per cent of fresh sterile human
blood (kept fluid by citration) to the previously mentioned
agar medium, after melting and cooling to 50° C. This was
poured into sterile petri dishes and allowed to set. Spinal
fluids were collected in sterile test-tubes and centrifuged.
Preliminary examinations were made by microscopic examination of smears stained by Gram's method. Cultures were made
Ijy smearing the centrifuged sediment over the surface of the
l)lood agar plates and incubating over night.
Sputa were obtained by having the patient cough and collecting the material directly into a sterile petri dish, from
wliich direct smears were stained by Gram's method and
examined. Cultures from sputum were made by selecting
representative portions, smearing on blood-agar plates and
incubating over night.
Agglutinaiion Tests. — The sera used for preliminary' agglutinations were Ijederle's and the Rockefeller polyvalent antimeningococcus serum. The sera used for type determinations
were Pasteur Institute Types A, B and C. All routine
agglutinations were read macroscopically. The standard dilution was 1 : 50. Colonies resembling meningococci were
smeared and stained by Gram's method and if found to be
gram-negative diplococci, agglutination tests were made with
standard sera. Subcidtures, whenever necessary, were made
by subculturing suspicious colonies either on Loeffler serum
tubes or on blood-agar plates. The suspected colonies were
emulsified with normal saline and this emulsion was mixed
in equal proportion with polyvalent antimeningococcus serum
diluted 1:25 with normal saline. A control tube containing
normal saline instead of the antimeningococcus serum was
set up in each case. In the early part of our work, control
tubes made with normal horse serum were also set up. Later,
these were discarded. The tubes containing the above mixtures were incubated for four hours at 37° C.
Positive cases were typed by substituting Pasteur Institute
antimeningococcus sera A, B and C for polyvalent serum,
using the same dilutions, controls and temperature of incubation as used for the preliminary agglutinations.
REFERENCES
1. MacCallum, W. G.: Journal A. M. A., March 8, 1919, LXXII,
720-23.
2. Chickering, H. T., and Park, J. H., Jr.: Jour. A. M. A., March
1, 1919, LXXII, 617-626.
3. Jacobitz: Zeitschr. f. Hyg., 1907, LVI, 175-192.
4. Gordon, M. H. (Temp. Hon. Lt.-Col. R. A. M. C): Personal
communication.
NOVEMBEB, 1919]
329
5. A few cases of pneumonia In which meningococci have been
isolated have been reported in army cantonments in the U. S. A.
6. Fletcher, W.: Lancet, Jan. IS, 1919, I. No. 3, 104. Meningococcus bronchopneumonia in influenza.
7. Kinnicutt, R., and Dinger. C. A. L.: Am. Jour. Me^lical
Sciences, Sept., 1919, CLVIII, No. 3. 360-369. Isolation of the
meningococcus from cases of so-called influenza.
8. Meader, P. M., Means. J. H.. Hopkins, J. G.: Am. Jour. Medical Sciences, Sept.. 1919. CLVIII. No. 3. 370-397. " Account of an
Epidemic of Influenza .VmonK .American Troops in England."
9. Osier, \V. : Principles and Practice of Medicine. Sth ed. p. 113.
' This was found in eight of the Boston cases and in one it was
so extensive that it could have been mistaken for the ordinary
croupous pneumonia."
MENINGOCOCCUS PNEUMONIA. II
THE EPIDEMIOLOGY OF POSTINFLUENZAL PNEUMONIA IN WHICH THE DIPLOCOCCUS INTRACELLULAHIS MENINGITIDIS WAS ISOLATED. FROM OBSERVATIONS AT CAMP COETQUIDON, A. E. P., FRANCE
By WiLBiitT C. Davison, Baltimore, lid.
Captain, Medical Corps, U. S. Army (Discharged)
ir. L. Holm, Lansing, Mich.
Major. Medical Reserve Corps, U. S. Armij {Discharged)
AND
EoBEKT V. B. Emmons, B. A., Ilanible, England
Medical Corps, U. S. Army {Dijfcharged)
Because of the occurrence of the cases of meningococcus
pneumonia described in the preceding paper,' the Base Surgeon, Base Section No. 1, A. E. F., France, requested us to
investigate the epidemiology of this condition.
This study includes all of the bacteriological examinations
made at Camp Hospital No. 15, Camp Coetquidon, A. E. F.,
Situation of ni(
Receiving wards ! 102
Other hospital wardb 450
Discharged patients 596
Contarts in barracks of UUt , 261
Field Artillery.
Contartii in barracks of 142d I 86
Field Artillery.
Contacts in barracks of 114tli 'SO
Trench Motor Battery.
Contacts in barraksof I14tii 6
Ammunition Train. 1
ToUl 1573
Number found
positive. I. f.
with raeninfrococci in the
rbinophftrynx
Perccntanre of
positive or
carrier rate
8 per cent.
7 per cent.
14 pi-r cent.
14 per cent.
1» per cent.
20 per cent.
per cent.
12 per cent.
* Tlw grnt majorjtr of tbne cirrieri were of the temportrr claaa. Of 162 menlncococcua carriers cultured on the third daj only 37 were found poiitlre. Of IWcarriera
mt the next examination the aixth day only 15 were poaltlve.
France, of contacts of meningococcus pneumonia and meningococcus meningitis cases during the latter part of Scptenil)er
and the early part of October, 1918.
In order to determine whether the incidence of these ca-sea
was due to contact or infection in the hospital or in the barracks, cultures from the rhinopharyn.x were taken : ( 1 1 from
' See p. 324 of this issue.
every new patient at the time he was received into the hospital; (2) from all patients and attendants in the hospital; (3)
from all patients at the time of their discharge from the hospital, and (4) from all contacts of recent cases of meningococcus
meningitis in the barracks.
Until their cultures were reported negative, patients were
held in strict quarantine in special wards of the hospital and
discharged patients and contacts were held in " working quarantine " in the barrack.s, i. e., they could drill and mingle with
other troops out of doors but had to sleep in isolated barracks.
In all, 1573 dilTerent patients, attendants, and contacts were
cultured. Cultures were repeated at three-day intervals on all
men found harboring meningococci until two successive negative cultures were obtained.
In Table I the results of these cultures are summarized.
The numbers of cases of cerebro-spinal meningitis and
pneumonia from which meningococci were recovered and the
number of carriers found in each organization as a result of
the surveys of patients in hospit.jil and of contacts in barracks
are indicated in Tabic II.
SUMMARY
From the necropsy and cultural investigations described in
the preceding paper (Meningococcus Pneumonia I), there can
be no doubt that the post-influenzal pneumonia in Camp
Coetquidon was due in at least 23 cases to infection with the
meningococcus. This conclusion is further substantiated by
the epidemiology. The IJOth, 141st and M2d brigades of
field artillery came from Camp Beauregard (Ix)uisiana) in
which numerous ca.ses of cerebrospinal meningitis (meningococcal) had occurred rluring the previous winter. Probably
many men of these organizations still harbored meningococci
in their throat.s. The epidemic of influenza with its coughing
greatly increased the nunilx-r of the.se meningococcus carriers.
330
[>fo. 345
The cultural surveys of the hospital patients and barrack contacts (Table I) show an average meningococcus carrier rate
of nearly 13 per cent. From the wide distribution, as sho^vTi
Organization
Number of
meningococcus
pneumonia
cases
Number of
meningococcus meningi
Number of
meningococ
found wbile
patients in
hospital
Number of
meningococcus carriers
found in
survey of
barrack;
Total number of meningococcus carriers found
in each organization
131st Field
Artillery.
132dF.A.
5
1
3
3
No survey.
No survey
3
33
133d F.A.
2 (1 fatal).
5
No survey.
5
UOtli F. A.
3 (1 fatal).
12
No survey.
12
141st F. A.
5 (4 fatal).
4(1 fatal).
34
38
72
142d F. A.
2 (2 fatal) .
10
8
18
328th F. A.
1
1
No survey.
1
329tli F. A.
1 (fatal).
14
No survey.
14
330th F. A.
1
2
No survey.
2
114th Ammunition
Train.
310th A. T.
1 (fatal).
1
29
2
No survey.
29
2
114th
Trench
Mot. Bat.
61st Engineers.
Casuals . . .
1 (fatal) .
2 (1 fatal).
1 (fatal).
1 (fatal).
3
7
13
No survey.
No survey.
13
3
7
Total . . .
23(11 fatal).
9 (4 fatal).
125
59
184
in Table II, it was impossible to state definitely whether the
infections occurred after the patients were received into the
hospital or whether they had occurred in the barracks, but it
it probable from the high carrier rates in both places that the
influenza patients might well have acquired their secondary
infection in either location.
It would seem evident, therefore, that the meningococcus
was both endemically and epidemically distributed in the
rhinopharj-nges of the troops in Camp Coetquidon and that
this explained the relatively large number of cases of postinfluenzal pneumonia in which meningococci were isolated.
TECHNIQUE USED IN EXAMINATION OF MENINGOCOCCUS PNEUMONIA AND MENINGITIS CONTACTS
Swabs were taken from the posterior rhinopharyngeal wall
(curved wire swab "A" and tongue depressors "B" being
used) and immediately inoculated on a small area of a hemoIj-sed blood-agar plate. (Veal infusion agar -1-0.2 per cent to
phenolphthalein, or Ph. 7.8 was used; 3.0 c. c. of human, sheep,
or rabbit's blood, hemolysed with 10 c. c. of sterile distilled
water, were added to each 100 c. c. of melted agar at 50° C,
immediately before pouring plates). This inoculation was
then spread over the whole surface of the plate by means of a
sterile wire spreader (C), (either immediately or on return to
the hospital laboratory) and the plates incubated for from 18
to 24 hours at 37° C. They were then examined for suspicious
colonies with the naked eye or a 10-power hand-lens. Meningococcus colonies are round, transparent, light gray and not
umbilicated. Suspicious colonies were fished to hemolysed
blood agar or Loefiler coagulated serum slants and iucubated
over night. A gram-stained smear was then made from each
subculture.
Those containing gram-negative cocci were emulsified in
normal saline as follows :
1. Saline was added to the cultures with a pipette according
to the amount of growth (t. e., 2 to 3 c. c.) .
2. The growth was carefully washed off by means of a
dropping pipette (i. e., one fitted with a nipple) and transferred to a second tube.
3. Saline solution was added to these suspensions so that
all were distinctly and equally cloudy.
4. The emulsions were agglutinated with meningococcus
serum, the following technique being used : Five drops, or
TABLE HI
To the
1st
5 drops or 0.25
5 drops or 0.25
Previously
Making
tube.
c. c. of the
c. c. Rockefel
diluted to
the final
bacterial sus
ler Institute
1:25.
dilution
pension.
or N. Y. Board
of health polyvalent meningococcus serum.
1:50.
To the
2d
«
5 drops or 0.25
.<
«
tube.
c. c. Pasteur
type A meningococcus serum.
To the
3d
..
5 drops or 0.25
«
:
tube.
c. c. Pasteur
type B meningococcus serum.
To the
4th
..
5 drops or 0.25
.<
tube.
c. c. Pasteur
type C meningococcus serum.
To the
5th
<.
5 drops or 0.25
..
tube.
Gth
e. c. Pasteiir
t}'pe D meningococcus serum.
5 drops or 0.25
To the
Control.
tube.
c. c. normal
saline.
0.25 c. c. of the bacterial suspension and the same quantity of
various meningococcal type sera were placed in each of five
agglutination tubes as indicated in Table III.
The five tubes were then incubated at 37° C. preferably for
two hours in a water-bath or three hours in a dry incubator.
Lt. Col. M. H. Gordon's meningococcus type sera, I, II, III
and IV or the Eockefeller Institute normal, paranormal, and
intermediate type sera may be substituted for the Pasteur Institute type sera A, B, C and D.
When many cultures are to be agglutinated it will be found
more economical of time and material if onlv tubes 1 and 6
NOVEMBEH, 1919]
331
are used. If after two hours tliere is positive agglutination
with a polyvalent serum, the original suspension may then be
typed by agglutinating in tubes 2, 3, 4 and 5.
The men whose cultures gave positive agglutination with a
polyvalent serum were reported immediately as carriers, placed
under hospital or working quarantine (vide supra), and re
'..^
examined at three-day intervals until two successive negative
cultures were obtained.
APPARATUS
A. Ordinary hay wire was cut into six-inch lengths and
the distal half-inch was bent at an angle of 135° with the shaft.
Non-absorbent cotton was twisted around this distal curved
end. These were sterilized by dry heat in lots of 25 in metal
containers or glass jars, the tops of which were covered with
paper. In our opinion, this swab is more convenient than the
West tube swab not only on account of its greater simplicity of
preparation but from the fact tliat any one with a little practice
can swab the posterior rhinojjliaryngcal wall of an adult without touching the mouth structures.
B. It was found that requiring each man to use his own
mess spoon as a tongue depressor was often convenient.
C. To make spreaders six-inch lengths of hay wire were bent
as shown in the diagram. These were sterilized by dry heat in
lots of 25 in metal or glass containers.
THE OCCURRENCE OF THE PFEIFFER BACILLUS IN MEASLES
By Andrew Watson Sellards, JIajor, M. C, U. S. A.,
AND
Ernest Sturm, Second Lieutenant, S. C, U. S. A.
(From the Base Hospital, Camp Devens, Mass.)
Certain similarities between measles and influenza were
especial!}' noticeable when these disea.ses were prevalent during
the early part of last autumn. With the onset of influenza
at Camp Devens, ^lass., the symptoms in the earlier cases were
distinctly less fulminating than at the height of the epidemic.
The possibility of measles in the prc-eruptive stage required
consideration in establishing the diagnosis of the first group
of influenza patients admitted to the base hospital. The
acute onset of conjunctival and respiratory symptoms was accompanied by a pronounced leucopoenia. There are other
noteworthy similarities between the two diseases. Both arc
highly contagious and are frequently complicated by pneumonia in its various forms. The occurrence of the Pfeifl^cr
bacillus in a high proportion of patients has been reported in
measles as well as influenza. As we were engaged at this time
in the study of measles, it seemed advisable to investigate the
occurrence of PfcifTer and Pfeifi'cr-like organisms in measles
patients.
Summanj of Literature. — ^Thc literature contains fairly
numerous reports of the occurrence of B. influenza of PfeifTer
in cases of measles. Unfortunately a considerable number of
the reports fail to furnish the information upon which the
identification of the bacillus was based. In some, reliance
seems to have been placed upon microscopic examination of
smears stained by Gram's method ; in other instances typical
cultures were obtained upon blood-agar but no evidence was
furnished to show that haemoglobin was essential for successful
cultivation. Such results are open to doubt since other organisms may simulate closely the growth of B. influenza: on bloodagar. In the following review, as a rule, those papers will be
omitted in which pneumonia and a Pfeifl"cr bacillus infection
are reported as remote sequchv of measles.
The association of measles and the influenza bacillus was flrst
mentioned by Paltauf ' in 1899. He reports the occurrence of
B. influenza' in two cases of bronchopneumonia foUowiuK measles:
the details concerning the means of identification of the bacillus
are not stated.
Giarr& and Picchi ' were the first investigators to report the
occurrence of Pfeiffer-llke organisms in active Ciises of measles,
pure cultures being recovered readily from the conjunctival and
bronchial secretions. These authors raise the question of a possible specific efiologic r6lD of these organisms in measles.
Albrecht and Ghon ' in 1901 describe one case of bronchopneumonia developing three weeks after an attack of measles. At
autopsy the Influenza bacillus was isolated from the lung.
In the autopsy of 23 cases of measles Jehle ' reports the occurrence of the PfeifTer bacillus In the heart's blood In 15 and In the
lungs in 18 cases. This author regards the Influenza bacillus as
a common secondary Invader In the acute exanthemata.
SiisHwrin' in lOiil studiod measles patients clinically and at
autopsy; he recovered the PfeiiTer bacillus In 10 of 21 cases. The
positive cases were considered to be mixed infections of measles
and influenza.
Liob.scher* In autopsies of 11 ca.sea of meaalcs, recovered the
Pfelffer bacillus In 3 cases from the lungs; his work Is of especial
Interest In that two of three cases showed a pneumonia with the
Influenza bacillus present In pure culture.
333
[No. 345
Klienberger ' reports cultivation of " hsemopliilic " bacilli from
the conjunctiva: in 3 of 9 patients of measles during life, and in
one of two cases at autopsy a pure culture of " hsemophilic " bacilli
was obtained from the heart's blood.
Davis" examined uncomplicated cases of measles during the
stage of eruption. Cultures were taken from the sputum or from
throat swabs, a single examination being made in each case
Organisms indistinguishable from the Pfeiffer bacillus were isolated in 13 of 22 cases.
Pacchioni and Franchioni » obtained Pfeitfer-like organisms
readily from the mucous membrane of measles cases. Careful
blood cultures in 25 patients were negative for this organism in
all except one case; one positive culture was obtained shortly before death from a case complicated by bronchopneumonia. These
authors give serious consideration to the possibility that measles
may be caused by a Pfeiffer-like organism.
Reiss and Gins " report the cultivation of the influenza bacillus
from the blood 17 days before death from a case of postmeasles
bronchopneumonia.
Of especial interest are tho.-;e reports which record the
presence of the Pfeiffer bacillus in the uncomplicated cases of
measles during life. The bacillus has been found, as a rule,
only in the mucous membrane of the conjunctivee and in the
respiratory tract. Only rarely has it been recovered by blood
culture and then only in cases complicated by pneumonia. It
is noteworthy that Liebscher in 1903 reported the occurrence
of the Pfeiffer bacillus in pure culture in the lungs in two
fatal cases of pneumonia following measles.
EXPERIMENTAL WORK
The following examinations were conducted chiefly at Camp
Devens, Mass., and were commenced immediately after the
decline in the epidemic of influenza in September and October,
1918. The latter began on September 8, reached its maximum
8 days later and declined very rapidly during the next week.
In the remainder of September and October a few cases were
admitted practically every day ; by the first of November the
admissions for influenza had virtually ceased. Small foci of
the infection probably remained in camp throughout the
winter. A full account of the epidemic was reported by
Woolley." The measles parents were examined with the object
of determining the relative frequency of Pfeiffer or Pfeifferlike organisms and the period for which these organisms persisted after the subsidence of the symptoms of measles.
Numerous cultures of hffimoglobin requiring organisms were
isolated ; these strains were, superficially at least, identical with
B. influcnzce of Pfeiffer.
Technique. — The cases of measles were examined during the
stage of eruption, the first examination being made as a rule
within from 24 to 36 hours after the appearance of the rash; subsequent examinations were made at intervals of one to two weeks.
Only a single examination was made during the eruptive stage
in the cases which were negative. All of the patients showed the
usual respiratory symptoms but only two of the cases were complicated with a definite pneumonia. As a routine the sputum of
patients was examined, material being secured, as far as possible,
which had been coughed up from the trachea or bronchi. In the
hope of eliminating some of the commoner saprophytes, the
sputum was injected in quantities of 0.25 to 0.5 c. c. intraperitoneally into white mice according to the technique recommended
by the Rockefeller Hospital for the isolation of the pneumococcus.
The mice were sacrificed when they were markedly ill, usually
after about 10 to 12 hours, spontaneous deaths being for the most
part avoided. Cultures were made on blood-agar plates. Throughout this work human blood-agar has been employed — 10 per cent
blood in meat infusion agar with a reaction to phenolphthalein
equivalent to 0.1 per cent of normal acid. These plates were inoculated from the peritoneal exudate, from the heart's blood and from
any early pneumonic or ha^morrhagic patches in the lung.
The growth from the heart's blood and from the lung often
showed an almost pure culture of Pfeiffer-like organisms, i. e., a
small nonmotile Gram-negative bacillus (about 0.2 by 0.5 micron)
without capsule or spore formation, growing aerobically on
human blood-agar as minute discrete colonies without producing
hcemolysis. The need for haemoglobin was tested by substituting
TABLE I
Incidence of PFErFFES-LiKE Bacilli in Sputum of Measles
Patients
Nov. 12
" 12
" 12
" 12
" 12
" 12
" 26
" 26
" 26
" 26
" 26
" 26
" 28
" 28
" 28
" 30
" 30
" 30
" 30
" 30
" 30
Dec. 2
2
4
4
Period of observation
Negative
Positive
Negative
Positive
Negative
Positive
Negative
Positive
Negative
Positive
Positive 19,
or IH
10 to 14 days
liter eruption
Negative
Positive
Negative
Positive
Negative
Positive
Negative
Positive
Negative
20 to 25 Aaj3
after eruption
Negative
Negative
Positive
Negative
Positive
Negative
Positive 6,
or 24^
Positive 6
or 26^
40 days after
eruption
Negative
Negative
Negative
Negative
ascitic fluid for blood in the culture medium — 10 per cent of unhealed ascitic fluid, free from bile pigments, with a specific gravity
of 1.018. Blood serum was not employed on account of extremely
minute amounts of hfemoglobin which may sometimes sufiice for
the growth of the Pfeiffer bacillus. In testing the hjemoglobin
requirements of a given strain, blood and ascitic media were prepared from a common stock of agar. Heated blood-agar (chocolate-agar) was occasionally employed. Agar of the same composition as used for the fresh blood medium was mixed with human
blood (10 per cent). The mixture was maintained at a temperature of about 95° C. for approximately ten minutes.
Strains of a Pfeiffer-like organism were recovered from five
of the first six cases of measles that were examined. Seven
normal men on duty at the base hospital were tested in the
same way. Two of these men had had influenza 6 weeks before.
No organisms resembling the Pfeiffer bacillus were found;
these tests were repeated three and seven days later with nega
NOVEMBEB, 1919]
333
tive resiilts. The following table gives the incidence of the
Pfelffer-like organisms found in 25 additional cases of measles.
The cases in Table I are given in chronological order to show
that the positive results occurring on the first examination
♦ere distributed rather equally throughout the series.
Distribution of the Pfeiffer-like Organisms. — Examinations
were made for determining the extent to which the hivmoglobin
requiring organisms are distributed throughout the body in
cases of measles. Cultures for this purpose were made during
the first day of the rash from the conjunctivae, from morbillous
lesions of the skin, from the blood and in two cases from
Ijrmphatic glands.
Conjunctiva. — Inoculations from the inflamed conjunctiva; were made with a cotton swab on blood-agar plates. The
secretions showed comparatively few bacteria of any kind.
Fourteen cases were examined and Pfciffer-like cultures were
recovered from six; in two of these ca^es the organisms were
present in relatively large numbers in almost pure culture.
Skin Les'ion-s. — Small pieces of skin showing morbillous
lesions were excised and smeared on blood-agar. Eight cases
were examined but no hajmoglobin-roquiring organisms were
recovered.
Blood Cultures. — In view of the almost constantly negative
results of blood cultures for the Pfeiffer bacillus in influenza,
comparatively few examinations were made in the measles
cases. Meat infusion broth containing a little lakcd human
blood was inoculated with the patient's blood during the first
12 to 24 hours of the rash, from 1 to 5 c. c. of patient's blood
with 75 to 100 c. c. of broth being u.«ed. Large Erlenmeyer
flasks were employed as containers for the broth in order to
give a large surface area. After incubation for 24 to -18 hours,
subinoculations were maile from these flasks on ordinary bloodagar and on heated blood-agar plates. The results in seven
cases were negative. Six of these were uncomplicated. One
patient developed early pneumonic lesions; the cultures were
continued during the 2d, .3d and 4th day of tlie rash, but only a
non-ha'molytic streptococcus was recovered from the l)lood.
Lymphatic Glands. — In a rather large number of the infcctiou.s diseases the causative organisms can be recovered from
the lymphatic glands more readily than from the blood stream.
In measles there is at least a theoretical possibility that the
virus is disseminated by way of the lymphatic sy.«tem. In two
cases, a superficial gland was excised from the inguinal region
as soon as the rash had advanced to thi.s area. Smears from tlie
gland were made on blood-agar and on heated blood-agnr plates.
The results in one case were negative; in the other. "> or
colonies in all were obtained on the heated blood-agar, no
growth developing on the unheated media. Sub-cultures were
obtained either on heated or unheated blood media but only
with difiicult)'; no growth was obtained on ascitic agar. Even
on heated blood-agar the colonies were always much smaller
than the typical Pfeiffer colonies; sometimes growth (otild be
definitely demonstrated only by the microscopical examination
of a stained smear. In its morphology and staining reactions,
this organism corresponded to the Pfeiffer bacillus except that,
even in very young cultures on unheated blood-agar, numerous
forms were present which were from two to four times the
length of the typical Pfeiffer organism. After four subinoculations the strain died out.
CO.MPARISON OF PFEIFFER STRAINS FROM CASES
OF MEASLES AND OP INFLUENZA
These strains of organisms from the conjunctivic and the
sputum were propagated on human blood-agar, transfers being
made at intervals of four or five days. They were compared
with similar strains of the Pfeiffer organism isolated at autopsy from the lungs of influenza cases occurring during the
epidemic. Morphologically the strains from the two diseases
were almost identical. The cultures from the measles cases
showed little tendency to develop bizarre forms even on heated
blood-agar and then never in extreme degree. Davis ' has
reported the isolation of a strain of Pfeiffer bacillus possessing feeble haemolytic properties. Xo haemolysis was produced by our strains on human blood-agar or broth media
made of 5 per cent of blood in meat infusion broth just acid
to phcnolphthalein (0.1 per cent normal acid). Only very
scanty growth occurred in the unheated blood broth medium.
Fairly abundant growth was secured in liquid media by
partially laking the blood with two volumes of water.- Preliminary observations were carried out on the spectroscopic
changes occurring in cultures. L'ninoculated control flasks of
media showed typical absorption bands of o.xyha^nioglobin.
With whole blood slight growth occurred without any apparent
change in the absorption bands. With laked blood after
48 hours the cultures showed bands characteristic of methajmoglobin ; after 72 hours, in acidified samples a broad band
also appeared in the green. Cultures from measles cases produced changes more readily than those obtained from the
influenza patients, but these differences might readily be explained by a difference in the rate of growth.
The principal object of the comparison of the measles and
influenza strains consisted in an Httem])t to find some fundamental biological differences between tlie organisms obtained
from the.se two sources. Observations were conducted on the
reactions of agglutination and complement fixation, on tlic
resistance of the organisms to freezing and drying and on the
effect of bile and of sodium hydroxide. A comparison was
made of the local reaction of the two strains upon intracutaneous inoculation of rabbits; strains from measles cases
were also inoculated into monkeys and into some human
volunteers.
Immunity licaction.t. — Botli the agglutination test and the
complement fixations failed to show any constant differences
between tiie two strains of organisms; some of the measles
strains reacted with the serum of measles and influenza convalescents and also with normal individuals. In some instances
the serum of a measles convalescent fixed complement witii
strains of organisms obtained from either measles or influenza
patient^?. No evidence was ol)tained whidi possessed any significance regarding the etiology or diagnosis of measles. In some
experiments on phagocytosis, Pacchioni and Franchioiii ' re
334
[No. 345
port that the serum of measles patients possesses a high opsonic
index for Pfeiffer-like organisms.
For the agglutinations, a moderately heavy suspension of bacteria was prepared in physiological saline from a 4S-hour growth
on blood-agar. This suspension was mixed with an equal volume
of serum in dilutions varying from 1-10 to 1-100. The mixtures
were incubated at 37°C. for from 2 to 24 hours and at 55°C. for 12
hours. The majority of all the results were negative; only a comparatively few preparations showed well defined clumping.
The complement fixations were carried out with a sheep cell
rabbit serum hsemolytic system, two units of complement being
used. The antigen was prepared by digesting a saline suspension
of the bacteria at 37°C. for 5 to 6 days. After centrifugalization,
the opalescent supernatant fluid was titrated for its antigenic
power; one-half of the maximum quantity permitting complete
haemolysis was employed in the tests. The serum to be tested was
inactivated at 55°C. and 0.1 c. c. was employed; the total volume
of the final preparation was 2 c. c. One series of antigens was
prepared by alcoholic extraction of a saline suspension of bacteria
that had been allowed to autolyze for one week at 37°C. Since
these immunity reactions were essentially negative the results are
not recorded in detail.
The results of the agglutination tests conducted by Wollstein " indicate that the Pfeiffer-like bacilU can be subdivided
into smaller groups. Such evidence, unless very striking
differences are obtained, does not constitute proof of distinct
species. Accordingly, we did not carry the work on immunity reactions any farther. Some of the more general
biological characteristics of these two strains of Pfeiffer organisms liave been investigated in the search for evidence that
might indicate the existence of distinct species in the htemoglobinophilic group.
TABLE II
Showing Effect of FtaiEziNo on Pfeiffeb-Like Obqanisms
Growth on blood-agar afte
STRAINS FEOM MEASLES CASES
Slight
Heavv
Slight
Heavy
Heavy
None
Heavy
STRAINS FROM
INFLUENZA CASES
A
Heavy
Slight
Heavy
B
None
C
Heavy
Heavy
D
Slight
None
E
Heavv
P
Heavy
None
G
None
H
Heavy
"
Effect of Freezing.— Many of the Pfeiffer cultures were
found to be susceptible to even moderately low temperatures
whereas others were resistant. The measles and the influenza
strains did not fall into distinct groups. However, six of eight
cultures from measles cases in contrast to three of eight cultures from influenza patients were resistant to freezing.
Technique. — Emulsions of the Pfeiffer bacillus in physiological
salt solution were rapidly frozen and thawed 15 times, a freezing
mixture of ice and salt at about — 10° to — 12° C. being used. After
each 5 freezings, cultures were made on human blood-agar plates.
Table II gives a typical result.
Several repetitions of this experiment on these same cultures
showed that the behavior of the Individual strains was almost
constant. Some of the strains were not only unable to withstand alternate freezing and thawing but were destroyed by
continuous freezing at about — 10° C. maintained for from
two to three hours.
Effect of Drying. — These cultures of the Pfeiffer bacillus
succumbed rather readily to drying for a short period. Under
TABLE III
Showing Effect or Drying on Pfeiffeb-Like Organisms
Serial number
Growth on blood-agar
After i minutea
After. 8 minutes
STRAINS FROM MEASLES CASES
2
None
None
4
"
"
7
Alive
Alive
10
"
12
"
26
None
None
27
Alive
Alive
29
"•
"
STRAINS FROM INFLUENZA CASES
None
Alive
None
Alive
None
Alive
None
Alive
None
None
the conditions of the experiment, the measles strains survived
a little longer than those from influenza patients but the differences were not marked.
Technique. — A coarse coil of platinum wire was dipped in a
saline suspension of young cultures of the organism to be tested.
The moistened coil of wire, free from any gross droplets of the
emulsion, was suspended in a dessicator at room temperature for
periods of 4, 8 and 12 minutes. Cultures were then made on bloodagar. A characteristic result is given in Table 111, these results
being constant on two repetitions except in the case of one culture
(4) which was dead in one and alive in another of the two succeeding tests.
Action of Bile. — In contrast to their resistance to freezing
and drying, the measles strains seemed more susceptible to the
action of bile than the cultures obtained from influenza cases.
Technique. — Saline suspensions of 4S-hour cultures of the Pfeiffer organisms were mixed with an equal volume of varying dilutions of bile. The mixture was incubated for 1 hour at 37°C. in
a water-bath. Occasionally there was some macroscopic evidence
of clearing, but in order to obtain definite results, cultures were
made upon blood-agar. A similar technique was used in the later
November, 1919]
335
experiments in which bile salt and sodium hydroxide were substituted for bile. The dilutions given in the tables represent the
final strength after mixture with the bacterial emulsion.
The action of bile is illustrated in Table IV.
The difference in behavior of the two strains towards bile
appears at first to be very striking; moreover, the indiviilual
TABLE IV
Showing Growth on Blood-Ag.\k Afteb Exi-osire to Bile
Final dilution of bile
Serial number
STBAINS
FROM MEASLES CASES
1
None
None
None
Slight
2
"
Slight
"
4
'*
Heavy
7
•'
•'
10
"
•'
12
None
Slight
26
Slight
Heavy
27
•'
•'
29
"
Slight
STRAINS FROM INFLtTENZA CASES
B
Heavy
Slight
Heavy
Heavy
C
"
Heavy
"
D
Slight
Slight
Slight
Slisht
E
None
None
None
None
F
Heavy
Heavy
Heavy
Heavy
G
Slight
Slight
•'
H
Slight
Heavy
Heavy
cultures in four repetitions of this test behaved constantly in
this manner. ITowever, the total number of cultures tested
is small and even in moderate dilutions of 1 : 40 the difference
disappears altogether.
Action of Sodium Hydroxide. — The effect of sodium hydro.xide upon the cultures was rather variable, but the results
TABLE V
Showing Gbowtu o.n Blood-Agab After ExrosiEE to Sodium
Htdroxide
Serial
Final dilution of sodium hyilroxidc
number
N/8
N/10 N/M
N/60 1
N/100
I
itraiks from measles cases
1 None
None
Slight
Heavy
2
Slipht
*
None
Heavy
7
"
10
'
12
.«1i«ht
26
None
None
27
"
Slight
Heavy
29
None
Heavv
Sllfiht
Heavy
Slight
Heavy
STBAi:«8 FROM INFLtTENZA CASES
B
None
None
None
Slight
I leavy
C
"
None
SliKht
n
Slight
Heavy
E
"
'
Slight
p
"
None
"
G
Slight
Heavy
Heavy
H
None
Slight
Slight
in general were the reverse of those obtained with bile. The
following data in Table V are characteristic.
From Table V it will be seen that there is only a small rauge
of dilutions within which it is possible to demonstrate differences with sodium hydroxide ; moreover, with some strains of
organisms it is very difficult to obtain constant results under
apparently identical conditions.
Action of Bile Salts. — Whole bile contains not only the
biliary salts but an appreciable amount of alkali ; since bile and
the hydroxide act in a somewhat different manner on these
Pfeitl'er strains, it seemed desirable to ti-y the action of bile
salts alone. As in the case of other manifestations of the action
of bile, the effect of the purified salt was less striking than the
action of the whole product. Sodium taurocholate in 2.J per
cent concentration killed all cultures tested ; at 1 per cent the
majority of the cultures were killed, whereas with one-half
per cent about half of the measles and also lialf of the influenza
strains were killed ; at one-tenth per cent, all but 3 of IG strains
lived. Certain strains of the Pfeiffer bacillus are therefore
approximately as susceptible as the pneuniococcus to the purified bile salt.
Effects of Inoculation. — These cultures exhibited very little
virulence upon inoculation into the smaller laboratory animals.
Four cultures of measles strains and three of the influenza
strains were tested upon rabbits, guinea-pigs, and mice by
intraperitoneal inoculation. The rabbits and guinea-pigs
showed no symptoms ; occasionally the mice were killed in from
two to three days by the injection of the growth from one to
two blood-agar slants. A series of rabbits was inoculated
intracutaneously with the two strains of organisms. Seven
cultures from measles patients were tested ; in all cases well
marked oedema and inflammation developed during the first
24 hours, these symptoms persisting for from two to four days.
Of seven cultures from influenza cases, tested in a similar
manner, five showed virtually no reaction and two behaved
precisely like the cultures from measles cases. The influenza
cultures had been isolated approximately two months earlier
than those obtained from measles patients; the two influenza
strains producing inflammation were obtained earlier in the
epidemic than the five causing little or no reaction.
Two adult monkeys (Macacus rhe.fiis) were inoculated with
a mixture of eight strains obtained from the sputum and conjunctivsB of measles cases. These cultures had been isolateij
for periods varying from one to three weeks. The growth
from 48-hour cultures on blood-agar plates was suspended in
salt solution. This emulsion was thoroughly rubbed over the
mucous membranes of the eyes, nose, mouth and throat. In
one monkey the mucous membrane of the mouth was scarified
slightly on the right side ; on the left side 0.5 c. c. of the
bacterial suspension was injected under the mucous membrane.
The scarified mucous memlirane healed promptly and no local
lesion developed at the site of the inoculation under the mucous
membrane. Each of the.se animals also received intraperi toneally 2 c. c. of a moderately heavy saline suspension of these
cultures.
336
[No. 345
Daily temperatures and white counts were made upon both
monkeys. One remained entirely normal ; the other, after an
incubation period of six days developed definite malaise as
evidenced by the loss of strength and loss of appetite. This
animal had been under close observation for four months prior
to tliese injections and had remained entirely free from any
symptoms. During the period of malaise a suggestive drop
occurred in the leucocyte count, unaccompanied, however, by
any febrile reaction. The symptoms disappeared before the
normal white count was fully re-established. At frequent
intervals after inoculation, cultures were made from the
mucous membranes on blood-agar. PfeifEer-like organisms
were not recovered from either monkey. The temperature
and counts in the monkey which became ill were as follows:
INOCULATION OF MONKEY WITH PFEIFFER-LIKE STRAINS
OF ORGANISMS
Days after
inoculatioa
Temperature
White count
Room temperature
101.8
13,750
66°
1
100.8
25,250
63.5°
2
101.6
13,600
67°
3
100.2
23,800
77°
4
101.4
15.300
78.8°
5
100.4'
H,600
66°
6
101.2'
10,000
68°
7
101.0 =
10,800
68°
8
101.6 =
10.600
68°
9
101.2'
15,500
68.9°
10
102.6*
9,700
66°
11
102.0
11,100
68.9°
12
101.8
15,400
68°
13
101.6
16,000
68°
14
103.2
13,300
68.9°
15
102.5
15,300
68.9°
16
101.6
16,200
68.9°
17
102.0
17,300
68°
18
101.2
15,700
67°
19
100.6
16,400
68.9°
20
100.4
17,400
66°
^ Cyanosis, conjun
2 Deep cyanosis, ci
3 Marked improve
* Apparently norn
and loss of appetite,
ill.
'es clearing, appetite good.
A few inoculations of human volunteers were undertaken
with the Pfeiffer strains obtained from measles eases. A mixture of five strains was employed, three of which were obtained
from the sputum and two from the conjunctivae. These cultures had been under artificial cultivation approximately six
to eight weeks. All were easily killed by bile and all were
resistant to freezing.
For the protection of the individual, the precautionary
measures were taken, which have already been outlined for the
inoculation of volunteers with the virus of measles ; * these
precautions include observations for the exclusion of the
Pfeiffer bacillus. As an additional safe-guard for the first
inoculation, an individual was chosen who was immune to
measles and who had had influenza in the recent epidemic.
The mucous membrane of the eyes, nose and throat was inoculated with a saline emulsion of the five strains. During the
next two weeks cultures were made at three-day intervals on
blood-agar and mice were inoculated with sputum for the re
' Bull. Johns Hopkins Hosp., 1919, XXX, 257.
covery of the Pfeiffer organism. The cultures were negative
and the individual himself developed no symptoms.
Accordingly, a volunteer was inoculated who had had influenza recently but not measles. No symptoms appeared and
the cultures failed to colonize. Two additional volunteers
were inoculated, who as far as could be determined, had had
neither measles nor influenza. Both of these subjects remained
entirely free from symptoms; the white blood count and the
temperature did not vary beyond the normal limits, and the cultural examinations failed to show any evidence of colonization
of the inoculated organisms. Under natural conditions, the
Pfeiffer bacillus can readily establish itself in the mucous
membranes. Hence the failure to produce symptoms would
have possessed much more significance if successful colonization of the inoculated cultures had been obtained. These negative results are of some interest in view of the discussion regarding the occurrence of B. influenza in normal throats ; in
some instances, at least, it does not persist when heavily inoculated into healthy individuals.
Davis * found the Pfeiffer organism in a high percentage of
cases of pertussis. Under the more favorable circumstances
of an interepidemic period, this investigator reports the production of respiratory sjTuptoms with prolonged colonization
of the bacillus in man.
DISCUSSION
A comparison of dift'erent strains of the Pfeiffer bacillus
showed considerable variation, more especially as regards their
resistance to freezing and to the destructive action of bile.
The attempt to separate the cultures into two distinct groups
becomes very difficult during an epidemic on account of the opportunity for mixed and for cross infection. It is to be expected, for example, that a group of cultures obtained from
measles cases would contain some strains behaving like the
majority of those obtained from influenza. Such variations
wore numerous, but the individual strains were not consistent
in the series of tests that were employed. Thus, two of the
measles strains were susceptible to freezing. In this respect
they behaved like the influenza cultures ; yet these same strains
were resistant to drying and susceptible to the action of bile,
conforming in these tests to the majority of the other cultures from measles. The complete record of these strains that
were tested is shown in the following outline.
VARIATIONS IN PFEIFFER-LIKE ORGANISMS
Intracu
Tests employed
Freezing
Drying
Bile 1-10
NaOH N/20
taneous
tions
Serial number of
2
measles strains
4
4
None
resembling i n
7
26
26
17
fluenza cultures
29
29
Serial letter of in
A
fluenza strains
c
B
B
resembling
E
D
B
G
I
measles cultures
Our information concerning the Pfeiffer bacillus is as yet
extremely meagre; satisfactory methods have not yet been
XOVEMBEB, 1919]
JOHNS IIOPKIXS HOSPITAL BULLETIN
337
devised for performing tests for pathogenicity or for fermentation and immunity reautious. At present this bacillus is
identified by its size, the lauk of motility, its decolor ization by
Gram's stain and its multiplication only iu the presence of
haemoglobin.* The situation may be illustrated by comparison
with the very broad typhoid-colou group of organisms. As
regards B. coli and B. typliosiis these orgauisms are virtually
identical in their size, motility and staining characteristics.
Without either fermentation tests or immunity reactions it
would become a difficult problem to separate them into perfectly distinct species or even to determine the etiology of
typhoid fever.
In the absence of definite information it seems unwise to
attempt any final statements concerning B. in/lucitzw and its
possible etiologic role in the respiratory diseases in which it
is most commonly found. Certainly the general opinion at
present is decidely against the acceptance of the bacillus as the
specific etiologic agent of influenza. This opinion is held
largely because of the frequent failure to find the organism in
typical cases and because of its common occurrence iu other
respirator)' diseases. As in pneumonia it is conceivable that
various organisms might give rise to more or less definite
symptoms of influenza; the Pfeiffer-like bacilli, moreover, are
not more widely distributed in healthy individuals than is the
pneuniococcus. Some consider that B. influenza; is purely a
secondary invader in a variety of diseases initiated by other
agents; when the bacillus is found in pure culture in lesions
of the lungs, the natural explanation of a primary etiologic
action is set aside and a hypothetical virus is postulated.
However, there is good reason to believe that serious symptoms
may result when an infection with the Pfeiller bacillus has
become established ; its acceptance as a specific etiologic agent,
however, seems to us to be contingent upon some division of
these organisms such as the recognition of distinct species or
of virulent and avirulent varieties.
StJMWARY
1. The examination of a group of measles cases occurring
a few weeks after an epidemic of influenza showed tlie presence
of an organism indistinguishable from the Pfeifl"cr bacillus in
2.5 of 31 cases.
• Neisser " reports that the PfeifTer bacillus can he cultivated
Indefinitely on plain agar in " symbiosis " with ordinary micrococci.
2. This organism was obtained readily from the sputum and
with little difficulty from the conjunctiva;. A highly parasitic,
haunoglobin-requiring organism was obtained iu one of two
cases from an excised inguinal gland. The Pfeiller organism
was not obtained from the blood stream nor from the excised
skin lesions.
3. With the subsidence of tlie active symptoms of measles
these micro-organisms disappeared rather rapidly in about
three-fourths of the cases.
4. Cultures of the Pfeiller organism from cases of measles
failed to colonize when inoculated on the mucous membrane
of four healthy volunteers; two of these individuals supposedly
had not had either measles or influenza.
5. A comparison was made of the strains of the Pfeifler
bacillus isolated from measles and from influenza. The results
showed considerable variation iu the behavior of the individual
strains. It is theoretically possible that the haemoglobin requiring bacilli represent a group of micro-organisms containing distinct species.
6. The occurrence of the Pfeifl'er bacillus both in measles
and in influenza constitutes suggestive evidence against its
etiologic relationship in either disease. This evidence would
be materially strengthened provided the identity of the strains
from these two sources were accurately established.
7. The evidence which is available at present is not sufliciently complete to exclude the specific etiologic role of the
Pfeiller bacillus in some of the acute respiratory diseases.
LITERATURE
1. Paltauf, R.: Wien. klin. Wchnschr., 1899, XII, 576.
2. Giarre, C, and Picchi, L.: Clin, mod., 1900, VI, 178. Sperimentale. Arch, di biolog., 1903, LVII, 475.
3. Albrecht, H., and Ghon, A.: Ztschr. f. Heillc, Abt. f. palholog.
Anat, 1901, XXII, 29.
4. Jehle, L.: Ztschr. f. Heilk., Abt. f. Int. Med., 1901, XXII, 190.
. 5. Susswein, J.: Wien. klin Wchnschr., 1901, XIV, 1149.
6. Liebscher, C: Prag. med. Wchnschr., 1903, XXVIII, 85.
7. Klicnberger, C. : Deutsche med. Wchnschr., 1905, XXXI, 575.
8. Davis, D. J.: Jour. Infect. Dis., 1906, III, 1.
9. Paccbioni, D., and Franchioni, C: Jahrb. f. Kinderh. u.
physische Erzieh., 1908, LXVIII, 39.
10. Reiss, E., and Gins, H. A.: .Miinch. med. Wchnschr., 1911,
LVIII,' 2211.
11. Woolley, P. G.: Jour. Labty. and Clin. Med., 1919, IV, 330.
12. Wollstein, M.: Jour. Exper. Med., 1905, VII, 335.
13. Neiaser, M.: Deuteche med. Wchnschr., 1903, XXIX.462.
JOHNS HOrKINS HOSPITAL BULLETIN.
The Hospital Bulletin contains details of hospital and dispensary practice, abstracts of papers read and other proceedings
of the llcdical Society of the Hospital, reports of lectures, and other matters of general interest in connection with the work
of the Hospital. It is issued monthly. Volume XXX is in progre.«s. The subscription price is $3.00 per year.
(Foreign postage, 50 cents.) Price of cloth-bound volumes, $3.50 each.
A complete index to Vols. I-XVI of the Bulletin has been issued. Price 50 cents, bound in cloth.
338
[No. 345
THE REACTION OF THE LEUCOCYTES IN EPIDEMIC INFLUENZA
By Beverly Douglas
Duriug the epidemic of influenza occurring in the fall of
1918, the presence of a leucopenia in praeticall}' all the cases
was commented on by numerous observers. An opportunity
was afforded during the course of the epidemic in The Johns
Hopkins Hospital to make rather extensive and careful studies
of the blood, which it seems worth while to put on record.
The data can best be presented in the form of tables, with
notes appended thereto. .
1. General Course of the Leucocyte Curve in Uncomplicated
Epidemic Influenza. — It seemed that information of most
value about the general course of the leucocyte curve could be
obtained by compiling the averages of counts made in a number of cases on various days. The results of such compilations
are recorded in Table I and graphically represented in Chart 1.
The following points may be commented on :
f  T.. /
SffiHaiftffia
l-jJMiMM
Leucopenia is present, even on the day of onset of symptoms,
the count falling somewhat on the following day and then
gradually rising. One might almost imagine that there is
some initial shock which depresses the leucocytes and from
which they gradually escape during the subsequent days of the
disease. It is also noteworthy that the return to normal count
comes gradually, the average count still being subnormal on
the twenty-first day.
Table I also shows the reaction of the leucocytes in the cases
of influenza complicated by bronchopneumonia. These
counts bear out the impression obtained at the time of the
epidemic that a complicating bronchopneumonia, as a rule,
does not lead to leucocytosis. An attempt was made to see if
TABLE I.— AVERAGE LEUCOCYTE COUNTS COMPILED
FROM HISTORIES OF 250 EPIDEMIC INFLUENZA
AND SUSPECTED INFLUENZA PATIENTS
Epidemic of Oct.-Nov., 1918. J. H. H.
3 or more days before onset.
2 days before on
set.
Day before onset.
Day of onset
2d
3d
4th
5tli
6th
7th
Sth
9th
10th
llth
12th
13th
14th
15th
16th
17th
ISth
19th
20th
21st
22 days or more. .
Grand average . . .
25 »
6833
48
5323
41
5644
33
5838
18
5681
31
5412
13
6036
28
6203
14
6985
21
7050
17
7100
25
7340
25
7790
25
8350
23
7900
12
7560
15
8850
7
8370
2
5600
6
9030
5
8752
2
5230
436
6673
u.
4
13120
7
8130
5
7054
1
8800
1
8000
1
4850
7
8450
3
3127
1
2625
2
4705
1
6 =
5800
4250
°
4
5440
2
4
6700
6260
1
2
5760
3280
>
3
8550
i
5200
1
9450
3
6910
25
5040
7
3430
5
4580
5
4010
16^
4204
15
5408
15
5564
10
5850
11
8644
126
6745
1 Index number = miniber of counts averaged for that day.
- Onset of pneumonia.
» All except uncomplicated flu.
4
3656
4
4818
3
3880
10 =
4175
11
5396
11
5305
8
6492
8
8677
7
7530
4
8860
4
13960
5
9740
5
8432
4
7810
4
10860
2
9340
1
9800
4
7630
1
8120
174'
7066
the severity of the case from the clinical standpoint could be
correlated with the extent of the leucopenia. For this purpose the cases were divided into mild, moderate and severe.
XOTEIIBER, 1919]
339
Counts made on or before the fourth day after onset showed
in the mild cases an average of 5500, in the moderate, an
average of 5800, and in the severe, an average of 5400. The
lowest single count observed — one of 1900 cells, was in an
extremely mild case. It seems, therefore, that in a general
way, the extent of the leucopenia does not vary with the
scveritj- of the disease.
TABLE II.— SUPPLEMENTARY TABLE SHOWING HIGHEST
AND LOWEST COUNTS ON EACH DAY. (See No. 1)
I.NFLl'ENZA EPIOE.MIC OCT.-NOV., 1918. J. H. H.
3 or more days before
onset
2 days before onset. .
Day before onset ....
Day of onset
2d
3d
4th
5th
6th
7th
8th
9th
10th
11th
12th
13th
14th
loth
16th
17th
18th
19th
20th
21st
22d
10700
3440
10440
2500
11720
2640
12000
2240
12500
2520
10600
3000
10300
2400
10100
2120
11500
3260
12000
2640
12640
4720
14600
3100
10600
5200
16000
2500
13440
4000
10600
3320
30800
44S0
14600
6250
7000
4040
14600
6080
12500
7100
22480
6000
9200
7000
10000
4800
8800
8800
8000
8000
4850
4850
11980
5440
Kluc
broiicho
pneuin.
fatal
Too
Few.
4960
2000
2625
2625
4760
4650
6400
3400
10200
2460
14600
2600
3320
3240
18200
2200
noii-futal
4960
2640
6000
3800
5050
3140
6400
2675
13000
2440
13100
2075
18400
2320
31360
2360
11900
4650
14480
5760
24720
8160
11920
6120
10200
6300
9800
3640
13120
8640
10280
8400
9800
9800
8750
5080
8120
8120
2. In Table II, which should be studied in connection with
Table T, are presented the highest and lowest individual counts
encountered in the various cases on each day of the disease.
From this table, it is apparent that despite the general tendency
to a leucopenia, there may in some cases be a mndrrjii.' Icucocvtosis.
TABLE III.— AVERAGES OF PER CENT PMN. AND TOTAL
LEUCOCYTE COUNTS CO.MPILED FROM 250
INFLUENZA HISTORIES IN J. H. H.
Epidemic of Oct.-Nov., 1918
Day of iliscas
Av.
WUC
PMN- l)...vo(.lis<.,.se
Av.
WUC
Av.
PMS
Onset
2(1
3d
4th
5th
Gth
4'
5220
13
5575
6
7900
9
5675
2
7350
1
6600
3
6330
5
6456
4
9950
72%
66%
59%
53%
61%
62%
607o
56%
66%
11th
12th
13th
14th
15th
16th
17th
18th
19th
20th
3
6387
6
7843
3
8870
6
7930
11
7450
3
6560
4
8330
1
7400
11
8080
2
9870
45%
60%
57%
61%
62%
69%
62%
79%
73%
47%
7th
8th
9th
10th
' Small index number = number of counts averaged.
TABLE IV.— INFLUENZA. VARIATION OF PERCENTAGE OF
PMN. CELLS C. W. B. COUNTS (COUNTS AND
DIFFERENTIALS ON SAME DAYS)
Epidemic op Oct.-Nov., 1918. J. H. H.
WBC %PMX
WBC %P.MN
4000-4500
WBC %PMN
WBC %PMN
WBC %PMN
300O-S500
5000-6500
8000-8500
7000-7600
8000 40
4300 64
6040 «8
6080 65
7000 75
8100 51
4410 75
5120 6',l
6US0 66
7310 78
8160 S7
45110 78
6200 71)
6100 67
7400 78
8140 47
—
5440 A3
etoo isr
7400 79
Av. 4413 6B
6410 67
6100 80
Av. 8175 48.8
6480 61
6350 65
At. 7285 76
4600-5000
—
6320 81
SSOO-4000
SSOO 8<
3«I0 GU
4520 40
4620 60
4700 66
Av. 6296 63
6500-6000
6440 62
6480 68
6500 67
7500-8000
708U 66
7800 62
Av. 3600 51
6000 53
5760 75
6800 63
Av. 6283 84.7
7840 64
7910 k7t
Av. 46S6 40.5
68.<!0 66
SS80 icr
6500-7000
7l>60 62
6'.i00 63
6000 63
Av. 7810 56
6800 47 f
Av. 6844 64.6
eiOa 68
61>.'0 64
Av. 67S0 00.6
8000.4000
4000-6000
6000-6000
6000-7000
7000-8000
°v'."'' !*"• *'••
At. 4750 67.8
At. 6546 <8.7
At. 6404 61
AT. 75'.'4 06
8000-BSOO
0000-9500
10000 and above
SOnO SB
OlIOO 69
10000 88
80110 «l
0040 67
10500 71
MHO n
MOO 67
10600 67
8080 78
U200 68
10620 60
81«n 60
0480 70
10S80 60
8810 «8
ir5no 60
MOO 76
Av. 0184 68
11080 50
8440 66
^-^
060O-I0O00
At. 10970 62.8
At. 6180 M.t
None.
No dilTercntfala
8500-9000
on WBC above
8«tn 66
thia iwlnt.
8«sn 57
8090 «3
At. 8740 68.8
SOOODOOO
Booo-ionon
10OOO-I2O0O
0'*°'' [8882 84.6
•184 88.2
10096 82
340
[No. 345
3. Table III attempts to correlate the polymorphonuclear
leucocytes with the total count. In this relatively small number of eases, no significant relationship is made out.
4. Table IV shows the relationship of the polj-morphonuclears to the total count from another point of view — namely,
the total count rather than the day of the disease.
Condusions. — From these tabulations, the following general conclusions may be drawn :
Leucopenia is the rule in epidemic influenza, although a
few eases may show normal counts or a slight leucocytosis.
The leucopenia frequently is present on the first day of the
disease, after which it may become more marked for a few
days, with a subsequent gradual tendency to rise imtil the
normal mark is reached. In some cases the normal mark is
overshot during convalescence, and leucocytosis may be present.
There is no constant relation between the leucocyte count
and the severity of the disease.
The persistence of the leucopenia is the rule, even where
bronchopneumonia, fatal or non-fatal, supervenes.
Difl'erential counts show an absolute relative decrease in
polymorphonuclear cells, as well as during the stage of leucopenia, varying to some extent with the total count.
Acute non-influenzal respiratory infections, as a rule, are
accompanied by a leucocytosis.
A leucopenia is. therefore, a reliable diagnostic sign in
epidemic influenza.
BOOKS RECEIVED
American Pediatric Society. Transactions of the American
Pediatric Society. Thirtieth Session. Held at the Curtis
Hotel, Lenox, Mass., May 27, 28, and 29, 1918. Edited by
Oscar M. Schloss, M. D. 1918. 8°. 331 pages.
The Control of Hookworm Disease iy the Intensive Method. By
H. H. Howard, M. D. Publication No. 8. 1919. 8°. 189 pages.
The Rockefeller Foundation International Health Board, New
York City.
Manual of yeiiro-Surgeiy. Authorized by the Secretary of War
under Supervision of the Surgeon-General. Prepared under
the direction of the Neuro-Surgical Section of the Division of
Surgery, in collaboration with the Sections of Head Surgery,
General Surgery, Orthopedic Surgery, and Neuro-Psychiatry,
the Army Neuro-Surgical Laboratories, and the Instruction
Laboratory of the Army Medical Museum. 1919. 8°. 492
pages. Government Printing Office, Washington.
A Te.Tt-Book of Urology i7i Me7i. Women and Children. Including
Urinary and Sexual Infections. Urethroscopy and Cystoscopy.
By Victor Cox Pedersen, A. M., M. D., F. A. C. S. Illustrated
with 362 engravings, of which 152 are original, and 13
colored plates. 1919. 8°. 991 pages. Lea & Feblger, Philadelphia and New York.
Pulmonary Tuberculosis. By Maurice Fishberg, M. D. Second
edition, revised and enlarged. Illustrated with 100 engravings
and 25 plates. 1919. 8°. 744 pages. Lea & Febiger, Philadelphia and New York.
Roentgen Interpretation. A Manual for Students and Practitioners. By George W. Holmes. M. D., and Howard E. Ruggles,
M. D. Illustrated with 181 engravings. 1919. S°. 211 pages.
Lea & Febiger, Philadelphia and New York.
The Principles of Nursing. By Charlotte A. Brown, R. N. Illus- j
trated. 1919. 12°. 262 pages. Lea & Febiger, Philadelphia
and New York.
Pneumotorair Artificial, y Otras Intervenciones en la Tuberculosis
Pulmonar. Estudlo Critico y Cllnico. Por el Doctor Juan B.
Morelli. 2 volumes. 1918-1919. 8°. 1246 pages. Imprenta
Nacional, Montevideo.
iledical Report of the Durand Hospital of the John McCormick
Institute for Infectious Diseases. For the First Five Years,
March 12, 1913 to March 12, 1918. George H. Weaver, M. D.,
Physiciau-in-Charge. 1919. 4°. 32 pages. Chicago.
The following eight monographs :
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The Origin and Development of the LvTiiphatic S3'stem. By
Free Thrombi and Ball-Thrombi in the Heart. By J. H.
Hewitt, M. D. 82 pages. Price, $1.00.
Benzol as a Leucotoxin. By Laurence Sellixg, M. D. 60
pages. Price, $1.00.
Primary Carcinoma of the Liver. By JI. C. Wixteexitz,
M. D. 42 pages. Price 15 cents.
The Statistical Experience Data of The Johns Hopkins Hospital, Baltimore, Md., 1892-1911. By Frederick L.
Hoffman, LL.D., F.S.S. 161 pages. Price, $2.00.
Florence E. Sabin. 94 pages. Price, $3.00.
Venous Thrombosis During Myocardial Insufficiency.
Bv
Fr-ank J. Sladen, M. D., and Milton C. Winternitz.
M. D. Price, 75 cents.
Leukaemia of the Fowl: Spontaneous and Experimental.
By Harry C. ScmiEissER, M. D. Price. $2.00.
The Structure of the Normal Fibers of Purkinje in the
Adult Human Heart and Their Pathological Alteration
in Syphilitic Myocarditis. By 0. Van Der STRicm
aud T. Wingate Todd. Price, $2.00.
BALTIMORE, DECEMBER, 1919
==Contents==
Kenry Mills Hurd. The First Superintendent of The Jolins Hopkins Hospital. (Illustrated.)
«y Thomas S. Cillen 341
Bibliography of Henry Mills Hurd, M. 1)., 1.1.. D.
Prepared by Mix.me Wbioht Blogg, Librarian, The Jolins Hopkins Hospital 370
Index to Volume XXX of The Johns Hopkins Hospital Bulletin 373
HENRY MILLS HURD
THE FIRST SUPERINTENDENT OF THE JOHNS HOPKINS HOSPITAL
lU- Tho-m.vs S. Cullkn *
The sultjcft of this sketch, probablj' the best kiinwii hospital
superintendent in the United States, an expert on li()si)iUil
orfranization and management, professor of psyeliiatry, author
and editor, was a product of Michigan, a state that has
furni.shed many well-known figures in American medicine.
Sliortly after Dr. Hurd came to Baltimore a charming
sketch of his early life and of his manifold activities in Kalamazoo and Pontiac appeareil from the ])en of Dr. C. B. Burr,
his successor at the Eastern Michigan A.sylum at Pontiac.
This tribute appeared in the American .Jounwl of InxanUy,
• I have written this article at the request of Judge Henry D.
Harlan, president of the Roard of Trustees of the hospital, and
of Mr. George K. McGaw, one of the trustees of the hospital —
one of Dr. Hurd's warmest friends and the donor of a large
sum of money towards the erection of the Henry M. Hurd Library
Building which Is to be on the hospital grounds.
It was my good fortune to come to the hospital in 1891, just
two years after It opened. In my early years I viewed Dr. Hurd's
work from the immature standpoint of the junior intern, later
as a senior house offlcer, and for at least 15 years Dr. Hurd has
been one of my very best friends.
It has been a delight to browse through his early writings, to
digest the chief events of the hospital a« they were sketched by
him in the yearly reports, and to epitomize the results of his
labors since he retired from the active management of the hospital
In 1911. I had always looked upon Dr. Hurd as an Indefatigable
worker, but until now I have never had the slightest conception of
the tremendous amount he has accomplished and of how largely he
has been responsible for the phenomenal success of The Johns
Hopkins Hospital.
1809, Vol. 46, p. 303. As it cMiiiiof he impnixi'd u|h,ii I sli:i!I
give it in detail:
Henry M. Hurd, A. M., M. D., the recently appointed director
of The Johns Hopkins Hospital, Baltimore, and the subject of our
photogravure, was born May 3, 1843, at Union City, Branch Co.,
Michigan. His parents, Theodore C. and Ellen E. (Hammond)
Hurd, were of New England (Connecticut) stock. His father, a
pioneer physician, eamo to Micliigan in 1834; and. worn out by
laborious practice amid the hardships and privations of pioneer
life In a malarious country, died at the early age of 39, leaving
a wife and three little boys.
His mother remarried In 1848, and in 1854 the family removed
to Galesburg. 111. In 1858 he entered Knox College, where he
spent two years. Subsequently he devoted a year to teaching and
general study, and in 1861 entered the junior class of the T?nlversity of Michigan. He graduated from the university in 1863. and
In the same year began the study of medicine with his stepfather,
who was also a physician. He attended lectures at the Rush
Medical College. Chicago, and at the Cnlverslty of Michigan, and
graduated from the department of medicine and surgery of the
university in 1866. The year following graduation he spent in
New York In study and hospital work. Subse(|uently he removed
to Chicago, where he engaged In dispensary and general practice
for two years. It was during the time of his residence In Chicago,
In 1870. that ho received the appointment of assistant physician
to the Michigan Asylum for the Insane at Kalamazoo, and entered
that field of medical practice In which he has achieved so much
distinction. He served the asylum in the capacity of assistant
physician for eight years, at the end of which time he became
assistant superintendent. On the opening of the Eastern Michigan
Asylum at Pontiac In the fall of the same year he was appointed
Ita first superintendent, and occupied this position continuously
for 11 years. Possessing rare skill as an organizer, broad culture, literary attainments of a high order, a thorough medical
343
[No. 346
training and a long asylum and hospital experience, he brought
to the work of organizing the Eastern Michigan Asylum those
qualities which enabled him to place it at once among the progressive asylums of the country. He early identified himself with
the Association of Medical Superintendents, and was an earnest,
faithful and zealous member of this body.
During the period of his administration of affairs of the Eastern
Michigan Asylum he has seen the treatment of the insane
revolutionized. For the abolition of restraint, the employment of
the insane, the extension of the system of night-nursing, the development of the " cottage plan," and the introduction of home
comforts into the dull, unattractive institutional life of previous
years, he has been an ardent and enthusiastic advocate. To him,
perhaps, as much as to any other man among the present generation of alienists in this country Is due the rapid growth of progressive methods in the care of the insane, and the advanced position which American psycliiatry is taking. His mental culture,
which enabled him to grasp intricate problems in all their details,
his philanthropic instincts, his ready sympathies and his keen
insight into the needs of the insane, conjoined with the quick perception of the skilled physician, made him an ideal asylum superintendent. His personal presence was inspiring; he infused his
own spirit of tireless energy among his subordinates, he unified
his staff and his corps of employes, and could always rely upon
their thorough cooperation. In 1S81 he visited Europe for travel
and investigation in the special lines of work in which he was
engaged. The results of this trip were the subject of a special
communication to the joint Boards of Trustees of the Michigan
asylums, and were published in connection with the biennial report of the Eastern Michigan Asylum for 1882. His writings
upon the subject of mental medicine have been voluminous and
of a high order. Aside from the numerous papers published in
the American Journal of Insanity, as reference to its files for
the past 11 years will show, many of great merit have appeared
elsewhere.
Among his recent and most scholarly productions is his presidential address in 1889 before the alumni association of the medical department of the University of Michigan, on " The Mental
Hygiene of Physicians." His reports of the Eastern Michigan
Asylum are written in a masterly and finished style, and have
been warmly received and favorably noticed by the profession of
this and foreign countries. He was a vice-president of the Ninth
International Medical Congress, Is a member of the Michigan
State Medical Society and of the Detroit Academy of Medicine,
and is corresponding member of the Detroit Medical and Library
Association.
In June of the present year there came to him, without previous intimation, the tender of the position of director of The Johns
Hopkins Hospital. The offer came as a gratifying surprise, but
he hesitated to accept it. He was reluctant to relinquish the
work to which he had devoted his best years, to separate himself
from his. patients — may of whom had long been objects of his
care and solicitude — and from friends endeared to him by the
strongest ties. He hesitated to abandon the work in which he had
been so long and successfully engaged, and in which the prospects
for future usefulness opened wide and ever wider before him;
but considerations, paramount among which were the increased
opportunities for the education of his children, constrained him
to accept the position.
By mental endowments and education he is peculiarly well
fitted for the responsible and delicate duties of a hospital director. He is thoroughly deserving of his recent very great honor,
and will adorn the position to which he has been called; but as
we write these lines, the feeling returns with ever-increasing force,
that in the gain of The Johns Hopkins Hospital, the profession of
psychiatry sustains an irreparable loss, and the asylum system ot
Michigan is deprived of its most illustrious exponent.
When Dr. Hiird came to Baltimore to see Tlie Johns Hopkins Hospital and to meet the trustees of the hospital one of
the trustees from the Eastern Michigan Asylum at Pontiac
came with him with the intention of urging his superintendent
to decline the call. After he had met the trustees and had
visited the hospital he turned to Dr. Hurd and said : " My
object in coming with you was to see that you returned to
Slichigan, but I have changed my mind. If they offer you this
jiosition and j'ou do not accept it, you will make the mistake of
your life."
PAPERS ON PSYCHIATRY PUBLISHED BY
DR. HURD PRIOR TO HIS COMING
TO BALTIMORE
Amid his many a.sylum duties Dr. Hurd found time to do
much writing and, as intimated by Dr. Burr, contributed a
great deal to our knowledge of insanity. In 1880 he published
a paper on " Recent Judicial Decisions in Michigan Relative
to Insanity." This was followed in 1881 by " A Plea for
Systematic Therapeutical, Clinical and Statistical Study." In
this paper Dr. Hurd carefully analyzed the methods employed
in the various asylums and clearly pointed out where improvements might with much profit be inaugurated. On page 11 he
says :
Mucli of the present statistical information contained in the
published reports of the institutions for the insane is unsatisfactory. There are tables enough, but they lack uniformity, precision in statement and practical utility.
Their lack of uniformity is well illustrated by the varying number of tables given in different reports, taken at random from
a package before me.
In concluding this article Dr. Hurd says:
In this earnest plea for more systematic therapeutical, clinical
and statistical inquiries. I would not be understood as criticizing
the thorough work now done in connection with asylums. I have
merely attempted to point out the necessity for further progress,
and have suggested methods which would tend to increase the
efficiency ot asylum work.
In 1883 Dr. Hurd published papers on " Practical Suggestions Relative to the Treatment of Insanity " and " The
Treatment of Periodic Insanity."
At a sanitary convention held in Pontiac in January, 1883,
Dr. Hurd gave a most interesting address on " The Hereditary
Influence of Alcoholic Indulgence Upon the Production of
Insanity." His views as expressed 36 years ago t«lly so well
with our present conception of this most important subject
that I quote his conclusions :
In the foregoing paper I have endeavored to show that inebriety in parents is a frequent cause of insanity in their children,
because drunkenness produces a transient Insanity, even in a
healthy brain; chronic drunkenness produces organic brain diseases, bringing in their train impairment of the memory, inactivity of the reason, a weakening of the will, and a loss of the
natural affections; also moral perversions and vicious propensities, and finally, unmistakable diseases of the mind and nervous
system — all of which are capable of transmission to children.
THE JOHNS HOPKINS HOSPITAL BULLETIN. DECEMBER. 1919
PLATE XLI
Tli.-uil..r.-. iiKfil a
Charles. " 4
Henry. " 6
(Jalesliurs. 111.
10
1 ...,,a..ir
Henry.
Charles. " 8
Taken about 1853.
Galesburg. 111.
Il>iir> .\L 1 1 11 III
in lSti;i. agi'il 20.
.\nn Arbor. Mirli.
Henry M. Hurt!
in 1868. aged 2o.
Galesburg, III.
i'lrd. t
an : • \) Hurd
iiK'jil .7. .\prll. 1870.
UaleHburg, 111.
Hcnrv .M. Ihinl.
ag'-tl .n, in 1S74.
Chicago. 111.
THK KVOMTIO.N OF HEN'KY M. Ill KU.
These pictures were carefully treasured by Ur. Hurds mother. They were obtained surreptitiously and no one will be more
surprised to see them here than Ur. Hurd himself.
Decembeh, 1919]
JOHXS HOPKINS HOSPITAL BULLETIN
343
That the children of inebriate parents inherit diseases, such as
epilepsy, liysteria, chorea and idiocy, or if not actual diseases,
nervous systems which are abnormally responsive to every form
of disturbing influence and are easily disordered.
That between the ages of 20 and 45 insanity is liable to be
developed in the children of inebriates, and that insanity of this
type is recovered from imperfect^' or not at all.
And finally, that however much people may differ as to the
expediency of " prohibition," so-called, in the present state of public sentiment, there should be no difference of opinion among
thinking men as to the right and duty of the state to take
strenuous measures to prevent the transmission of an inebriate
heredity to children.
During 1S83 Dr. Hurd also puljli^ihoil a paper entitled
" Future Provisions for the Insane in Michi<ran." In this
article he sketched in a most interesting way tlie hai)hazard
manner in whic-ii insane patients were looked after in Michigan until the opening of the asylum for the insane at Kalamazoo. He spoke in no imcertain terras of tiie duty of the
state to care for the insane within her borders. The concluding paragraph in this article reveals very clearly the wise
statesmanship of Dr. Hurd :
I would reiterate the conviction that it is the duty of the state
to continue to care for her insane in the state asylums: that no
consideration of false economy should prevent her from doing
everything which can be done for the comfort and restoration of
every insane person. If he requires the restraint and seclusion of
an asylum for the dangerous insane, he should have it. If he
requires curative treatment in a hospital, or suffers from a form
of disease which calls for constant nursing, he should have that.
If his welfare will be promoted by giving him labor, the liberty
of home, and a manner of life nearly resembling that of a private
family, he should receive them. No money should be wasted upon
buildings, surroundings, or care. Sufficient, however, should be
expended to render each unfortunate as comfortable as his condition will permit. Anything less than this is unworthy a great
state like Michigan.
Dr. Hurd in 1883 also published " The ilinor Treatment
of Insane Patients." In 1886 he published an interesting
article on " Paranoia." During the year 1886 we find two
articles from his pen " The Relation of General Paresis and
Syphilitic Insanity" and "The Data of Recovery from Insanity." In 1887 "Gastric, Secretory and Other Crises in
General Paresis " and " The Colony System of Michigan "
appeared. In 1888 Dr. Hurd published an important article
on " The Religious Delusions of the Insane," also an article
on " Imbecility with Insanity." In 1880 he aUo contributed
a paper entitled " A Case of Inebriety with Insanity ; with
Remarks."
DR. HURD, thp: FIR.ST SUPERIXTKXDHXT of THK
JOHNS HOPKIXS HOSPITAL
Dr. Hurd vras appointed superintendent of The Johns
Hopkins Hospital in June, 1889, and assumed the duties of
the position on .\ugust 1, at which time President Oilman, who
had acted as director of the hospital since the preceding
February, and Dr. John S. Billings, who had been medical
advisor to the Board of Trustees for 12 years, terminated their
connection with the hospital. Dr. Hurd, as has already been
mentioned, was the first superintendent of the P^istern Michi
gan Asylum at Pontiac. Here he had taken charge of a brand
new institution, had worked out the details of its management
and had piloted its destiny most successfully for 11 years.
Here at tlie Hopkins he had a similar opportunity, differing only in that the patient.s were suffering from bodily
instead of mentiil ills. In this institution he was destined to
establish later the most harmonious relationship between the
hospital and The Johns Hopkins Medical School which opened
its doors in 1893. His wise council, liis broad vista and his
tact have in large measure been responsible for the continuous
cordial and intimate relations that have always existed between
the medical school and the hospital.
Dr. Burr in his tribute to Dr. Hurd said, " His reports of
the Eastern Michigan Asylum are written in a masterly and
finished style, and have been warmly received and favorably
noticed by the profession of tliis and foreign countries." The
same standard of excellence shown in the Michigan reports has
been maintained in the annual reports of The Johns Hopkins
Hospital. In fact, when the history of this institution is
written it will only be necessary to amplify what has already
been succinctly reported in the yearly record of the hospital.
The annual report has given the list of the trustees together
with their various committees, the consulting physicians, the
medical hoard, the house staff and the names of the physicians
connected with the out-patient department. Dr. Hurd then
briefly chronicled the important events occurring during the
year, referred in detail to the changes in the personnel of the
staff and pointed out where certain departments needed to
expand or where new departments should be created. It is
interesting to watch how a suggestion of his would bring forth
fruit. In one report he would advise the innovation, in the
next it would be briefly stated that tentative plans were under
way. The next report would probably say that the building
was under construction, and in the report of the following
year would be a detailed description of the building together
with splendid illustrations, and in addition there would be a
succinct rejrort of the addres.ses given at the dedication of the
building. A more detailed report of the proceedings would
usually be contained in the hospital Bulletin or form the
theme for an address.
The report of the Training School for Xurses has always
been given a prominent part in the superintendent's report
and since 1895 there has been a very full report of the colored
orphan a.sylum. Dr. Hurd has always made it a rule to make
acknowledgment of gifts tx) the hospital no matter how small
they have been, and since tlie ijcginning he has never failed
each year to thank the clergy who have held services in the
hospital on the Sabbath. The statistical tables relating to the
patients treated in the hospital and in the dispensary have
been most exact and very full.
The annual reports of The Johns Hopkins Hospital from
1889 to 1911 breathe the very atmosphere of Henry M. Hurd
and in no other way can the reader gain a better insight into
his make-up and into the tremendous amount of work this
splendid medical stati'sman has accomplished than by reading
these records.
344
[N"o. 346
A Synopsis of The Johns Hopkins Hospital Reports
From 1889 to 1911
No description of Dr. Hurd's work woiild be complete without a reference to that splendid Board of Trustees and that
rare medical staff with whom he was associated in the early
days of the hospital. I have accordingly had the first and
second pages of the first report reproduced. All who were
fortunate enough to have been connected with the hospital in
the early days will never forget that splendid, candid, wholesouled face of Miss Isabel Hampton. One never thought of
Mr. Emory without instantly associating him with Mr. Joseph
Hopkins, and everybody in the hospital, both young and old,
looked upon Miss Rachel Bonner as an elder sister.
For convenience I have divided the reports into the regular
calendar year, although, as a matter of fact, the hospital year
began February 1 and ended January 31.
1889
(May, 1889— January 31, 1890)
Dr. Hurd's first report begins as follows :
To the Trustees of The Johns Hopkins Hospital:
Gentlemen. — I present herewith a summary of the operations
of the hospital during the past seven and one-half months, or
since its opening in May last. It has seemed best, all things considered, to make this first report for the fractional year, so that
in future the hospital year may correspond with the fiscal year,
which runs from February 1 to January 31.
ORGANIZATION
The organization of The Johns Hopkins Hospital differs in
some essential features from that of other general hospitals in
the United States. The service is divided into three distinct
departments — medical, surgical and gynecological each under a
responsible chief with continuous service. The heads of these
departments are non-resident, but arrangements are made for
them to give as much time to the work of the hospital as the
necessities of patients demand.
Each department has a responsible resident physician who has
had a long and varied experience in a general hospital, and is
abundantly able to fill the place of the chief of the department
whenever he is absent from the hospital. Each resident physician
has a staff of assistants who give aid in case-taking, surgical
operations, clinical notes, examinations of urine, sputum, blood,
etc. — also in dispensary work generally. The resident and assistant resident physicians, surgeons and gynecologists, are resident
in the hospital.
The dispensary has a chief who directs and arranges the work
of the different departments, and each department in turn is
under the special direction and control of a responsible head,
who takes care of the work and has a continuous service. Each
head of a dispensary department has as many assistants as the
proper work of his department requires, whose medical work he
directs and controls.
The nursing work of the hospital is under the charge of the
superintendent of nurses, who also acts as the principal of the
training school. She has the responsibility of the management of
the nurses' home and the instruction of nurses. She selects
and accepts probationers, prescribes courses of study and arranges
duties. She supervises all nursing-work.
The purchase and delivery of provisions and the cooking, distribution and serving of food, are placed in the hands of a purveyor, who is made responsible for this branch of hospital work.
The care of rooms and buildings and the oversight of the work
of the laundry come upon the matron, who is charged with the
duty of purchasing bedding, dry goods, clothing, household and
laundry supplies. In addition to these offices there is a comptroller of accounts, who supervises the receipt of money and the
payment of bills; an apothecary, who purchases medicines and
prepares and delivers prescriptions; a supervisor of grounds, who
looks after all outside labor; and an engineer, who has the care
and oversight of the engines, boilers, filters, pumping apparatus,
machinery, warming and ventilating apparatus, water-tanks,
sewers, water-closets, lavatories, steam-cooking apparatus, water,
gas, electrical and steam distribution.
HISTORICAL
Upon the opening of the hospital in May, 1889, Dr. W. H. Welch
had been appointed pathologist. Dr. William Osier, physician-inchief, and Dr. William S. Halsted, acting surgeon and chief of the
dispensary; Dr. Henry A. Lafleur, resident physician, and Dr.
F. J. Brockway, resident surgeon; with Dr. H. A. Toulmin, assistant physician, and Dr. George E. Clarke, assistant surgeon.
Subsequently in June Dr. Howard A. Kelly was appointed
gynecologist and obstetrician, and Dr. Hunter Robb, resident
gynecologist. The value of the services of Dr. Billings in planning
and building the hospital cannot be too highly estimated. His
foresight as to the future of the hospital, his high ideals of hospital requirements, his familiarity with hospital work and his
versatility in adapting means to ends, have done much to bring
The Johns Hopkins Hospital to its present state qf excellence.
President Gilman's services as an organizer were of great value.
By an unusual occurrence of events it was possible for him to
bring the university idea into hospital management, and to give
to the inauguration of the hospital enterprise a breadth and
liberality which it might have lacked had it been exclusively
organized by a purely hospital officer.
COURSES OF MEDICAL INSTRUCTION
Beginning with January 6 of the present year [1890] courses
of postgraduate instruction in medicine, surgery and gynecology
have been inaugurated at the hospital. Daily lectures have been
given in the clinical amphitheatre, and clinics in medicine, surgery and gynecology have been given three times a week, at which
time the wealth of clinical cases afforded by the hospital and
dispensary have been utilized. Rare opportunities to study diseases have been afforded in the dispensary and the hospital wards;
and to witness surgical operations in the private operating rooms.
LABOR.i.TORIES
The work of the pathological laboratory, formerly carried on
by the university, was assumed by the hospital September 1, 1889.
No change, however, has been made in any of its arrangements
or courses of study, and the work of instruction and original
research has gone on as in former years. The pathological
material afforded by the hospital has proven unusually rich. It
has been most carefully and thoroughly studied by Professor
Welch and Drs. Councilman and Abbott.
The clinical laboratory has been in successful operation under
the direction of Professor Osier. Analyses of the blood have
been made carefully and systematically as a matter of routine,
both to determine its constitution and to ascertain the presence
of malarial or other organisms and parasites.
The hygienic laboratory has also been equipped and made
ready for practical work under the direction of Dr. Billings and
Dr. Abbott. Its work thus far has been confined to meteorological
observations, the study of ventilation, the analysis of groundair, and the bacteriological examination of water.
December, 1919]
345
THE TRUSTEES AND MEDICAL STAFF OF THE JOHNS HOPKINS HOSPITAL IN 1889.
These are facsimile pages .from the first annual report of the Hospital giving the Trustees, Consulting Physicians, Medical
Board and Hospital Staff at that time.
TRUSTEES.
1889-90.
President :
FRANCIS T. KING.
Tretuwer:
JOSEPH MERKEFIELD.
Secretary :
LEWIS N. HOPKINS
Member) oj Ihe Board :
Geoboe William Urown, Charles J. M. Gwinjj,
James Carev, Lewis N. Hopkins,
George W. Corner, Francis T. Kino,
William T. Dixon, .\lan P. Smith, M. D.,
Geoboe W. Dobbin, C. Morton Stewart,
Joseph P. Elliott, Francis White.
COMMITTEES.
Ezeculive CommiUee.
Geoboe W. Corner, Francis T. Kiko, ex offao,
George W. Dobbin, Alan P. Smith,
Francis White.
Finance CommiUee:
George W. Corker, Francis T. King, ez officio,
William T. Dixon, Francis White.
Building OommiUet:
George W. Corner, Fba-scis T. Kino, ez officio,
Georme W. Dobbin, Alan P. Smith,
Francis White.
CONSULTING PHYSICIANS.
Alan P. Smith, M. D., representing Hospital Trustees,
James Carey Thomas, M. D., reprenenlinj; Univereitj Trustees,
I. E. .\TKiNfiON, -M. D., T. S. Latimer, M. D.,
8. C. Chew, .M. D., F. T. Miles, M. D.,
F. Donaldson, M. D., O. W. Miltenberoer, M. D.,
W. T. Howard, .\I. D., L. McLane Tiffany, M. D.,
C. Johnston, M. D., W. C. Van Bibber, M. D.,
H. p. C. Wilson, M. D.
MEDICAL BOARD.
Alan P. Smith, M. D., representini; Hospital Trnstees,
James Carey Thomas, M. D., representing University Trustees,
W. S. Hai-'»ted, M. D., Howard A. Kelly, M. D.,
Henrt M. Hubd, M. D., William Osler, M. D.,
WiLUAJi H. Weix;h, M. D.
HOSPITAL STAFF.
Superintendent :
Henrt M. Hcrd, M. D.
Phyticiart : Resident Physician :
William Osler, M. D. Henry A. Laflecr, M. D.
Attislanl Resident Physieianf:
Harry Toulmin, M. D., D. Meredith Reese, M. D.
Surgeon: Resident Surgeon :
WiuJAM S. Halsted, M. D. F. J. Brockway, M. D.
Assistant Resident Surgeon :
Georoe E. Clarke, M. D.
Gynecologist and Obstetrician: Resident Oynecologisl :
Howard A. Kelly, M. D. Hunter Robb, M. D.
Assistant Resident Gynecologists:
W. W. Farr, M. D. a. L. Ghriskey, M. D.
Pathologist : Associate in Pathology :
William H. Welch, M. D. W. T. Councilman, M. D.
Assistant in Bacteriology and Hygiene:
Alexander C. Abbott, M. D.
OUT-PATIENT DEPARTMENT.
CAi>/ of the Dispensary :
William S. Halsted, M. D.
Department of General Medicine:
William Osler, M. D.
Department of Diseases of Children :
William Osler, M. D., and W. D. Booker, M. D.
Department of Nervous Diseases :
William Osler, M. D., and H. M. Thomas, M. D.
Department of General Surgery:
W. S. Halsted, M. D., assisted bv J. M. T. Finney, M. D.
Department of Genito- Urinary Diseases:
W. S. Halsted, M. D., and James Brown, M. D.
Department of Gynecology:
H. a. Kelly, M. D., assisted by Hunter Robb, M. D.
Department of Ophthalmology and Otology:
S. Theobald, M. D., and R. L. Randolph, M. D.
Department of Ixiryngology :
John N. Mackenzie, M. D.
Department of Dermatology:
R. B. MoRisoN, M. D.
Mibs Isabel A. Hampton, Superintendent of Nurses and Principal
of the Training School.
L Winder Emory, Purveyor.
Miss Rachel A. Bonner, Matron.
Stanley Hutchins, OcmplroUer of Accounts.
346
[No. 346
THE nurses' training SCHOOL
The Nurses' Training School was fonnally opened in
October, 1889. A full report of this momentous occasion is
given by Dr. Hurd in the first number of The Johns Hopkins Hospital Bulletin published on December 1 of that
year. After a short address by the president of the Board of
Trustees, Mr. Francis T. King, Miss Hampton spoke at length
on " The Aims of The Johns Hopkins Hospital Training
School for Nurses," and was followed by Dr. Hurd who took
as his theme " The Eelation of the Training School for Nurses
to The Johns Hopkins Hospital." I quote briefly from his
address on that occasion :
The beneficent work of The Johns Hopkins Hospital antedates
by many years its formal opening in May last. From its inception in the mind of its founder, and the subsequent elaboration
of the idea by the trustees so wisely chosen by him — during the
preparation of its plans and in the whole course of its erection —
from the first foundation stone to the last tile upon the roof, it
has constantly been fulfilling its mission. It has all along stimulated hospital construction to an unprecedented degree. From a
personal knowledge of hospitals east and west, I do not hesitate to
say that there is not a single hospital in this broad land which
has not felt the influence of its construction, either directly or
indirectly, or has not been energized by its example to make
more perfect provision for the care and treatment of sick people.
It has taught hospitals the practical application of the laws of
hygiene to heating, ventilation, house drainage, sewerage and
hospital construction in general. It has commanded attention to
the importance of sunlight and air space, and to the absolute
necessity of an abundant supply of pure air to each individual —
a supply properly tempered to meet the varying conditions of summer heat and winter cold. The cardinal principle of the hospital
has been to give the sick the most perfect hygienic surroundings
attainable in a city. It has so prepared the way for better provision for the comfort of the sick, whether rich or poor, that the
public now demand it. So great, in fact, has been the force of its
example for good, I do not hesitate to say that had the hospital
never received or treated a single patient, the work it has already
accomplished in showing the way to better hospital construction
would have fully justified the expenditure of every dollar it cost.
To-day we are assembled to witness the inauguration of one of
the departments of this hospital which we hope will influence in
a similar manner, even if not in an equal degree, training schools
for nurses throughout the country. Tliis school has been established in compliance with the instructions of the founder of the
hospital, in tlie following language: " I desire you to establish in
connection with the hospital a training school for female nurses.
This provision will secure the services of women competent to
care for the sick in the hospital wards, and will enable you to
benefit the whole community by supplying it with a class of trained
and experienced nurses." The Board of Trustees has carried into
effect this injunction in no grudging manner. No school in this
country has been more worthily housed or more fully equipped
for class-room and practical work and none has ever started out
with broader views or more comprehensive plans for the proper
training of nurses.
"What has the hospital a right to expect from the pupils of this
school?
1. They should have an adequate conception of the responsibilities assumed by the nurse when she enters the school. The
hands of a nurse are a physician's hands lengthened out to minister to the sick. Her presence at the bedside is a trained
vigilance supplementing and perfecting his watchful care; her
knowledge of the patient's condition an essential element in the
diagnosis of disease; her management of the patient, the practical side of medical science. If she fails to appreciate her duties
the physician fails in the same degree to bring aid to his patient.
2. The nurse should have an enthusiasm in the work of nursing. No one should assume the work without feeling it to be
of all occupations the one best suited to the tastes and capacity
of the individual. Nursing to be well done should be entered
upon with an " enthusiasm of humanity " which will lighten
every hardship, and render the nurse happy and +++++
CONTENTSed in her
chosen calling.
3. She should consider nursing a profession and view it as a
life work. It is not a trade, nor an occupation solely, nor a
means of support simply, but a vocation which brings into activity the best sentiments of the human heart and enlists the
finer sympathies of our better natures.
4. She should seek to fit herself to be a teacher of others. It
should be her ambition to learn the duties of her calling that
she may become competent to impart instruction. From this
school as from a center of knowledge should go forth graduates
to found similar schools throughout the land.
5. For her highest usefulness a nurse should have a capacity
for sustained mental effort. Having chosen her life work and
proven her fitness for it by a satisfactory period of probation,
she should pursue her vocation " without haste, without rest,"
steadily, persistently and courageously, with a mental equipoise
which keeps constantly in view a high ideal of excellence. The
sweetest rewards of earth come to earnest effort and faithful accomplishment in lines of philanthropic work. They are not
gained by fitful toil or half-hearted endeavor.
Lest there may be a misconception I ought to add that enthusiasm in work, devotion to duty, unresting fidelity to high ideals
of efficiency, keen humanitarian impulses and love of scientific
truth, cannot and must not be considered obligations peculiar to
nurses. The trustees and ofiicers of the hospital accept similar
obligations for themselves, and expect equal enthusiasm and devotion from all connected with the hospital in any responsible
capacity.
What, on the other hand, has the pupil in the training school
a right to expect from all who are connected with the hospital?
1. The pupil nurse has reason to expect, and should receive, the
respect, confidence and cooperation of every right-minded person.
2. She should enjoy every facility for securing instruction, and
an opportunity to obtain a higher training in every branch of
knowledge which promises to increase her efficiency and usefulness.
3. She should have proper hours for work, proper hours for
study and recreation, pleasant apartments, healthful surroundings, refining associations and every incentive to effort, and every
aid to accomplishment of her work.
Many hopes cluster about this training school. The work of
many years of patient labor spent in construction is over. The
scaffold has been swept away, and the completed edifice stands
before us. The work of the hospital cannot be complete until this
school is open and in successful operation. The poor of Baltimore
in their homes, suffering for lack of proper nursing and adequate
attention, look to this school for a solution of the problem of
district nursing among the poor. The homes of the wealthy
need no less the skilled nursing which this school aims to supply.
The trustees and officers of the hospital welcome the school and
bid it God-speed.
PUBLICATIONS
In the first annual report Dr. Hurd says :
There has been established, as an organ of the hospital, a
monthly publication known as The Joii.xs Hopki.ns Hospit.\l
Bulletin, which is to contain announcements, programs, reports
THE JOHNS HOPKINS HOSPITAL BULLETIN, DECEMBER, 1919
PLATE XLII
DK. HIC.NKV M. HCIM) WIIKN UK CAMK TO THK .KiHNS HOI'KIN>
IKlSl'ITAI. IN 1S89.
December, 1919]
347
of societies and minor medical contributions. The Bulletin has
met with much success and seems to have found a place in medical
literature. In addition to the Bi-llkti.\ a volume of Hospital
Reports is published in fasciculi which will constitute a volume of
about 500 pages during the year 1890. The first fasciculus contained 64 pages, and had the following list of articles: "On Fever
if Hepatic Origin. Particularly the Intermittent Pyrexia Associated with Gall-Stones," by Dr. Osier
Throujrli tlic medium of The Johns Hoi'kin.s Hospital
Bulletin tlic munorous activities of the hospital have been
duly chronirlcil and mtuiy important events have been recorded. The numerous discoveries in the various departments
have been brougrht to the notice of the medical world through
this journal. It has been a faithful mirror of The Johns
Hopkins Hospital and its establishment was one of the most
iniportjint moves ever made by the hospital. It has enabled the
institution to tell the civilized world promptly just what it has
accomplished. The Johns Hopkins Hosintal lie ports contain
the lengthy articles — those that are too extensive for a monthly
journal. They now comprise 18 volumes.
Dr. Hurd started both the Bi"LLETin and the Beports and
was editor of both from the initial issue until he relinquished
his position in 1911. He was the editor in every sense of the
word. Many of the articles which were rather crude in their
English con.'itruction were entirely recast by him. Any member of the staff wlm wandered into the superintendent's oflicc
late at night when all was quiet or on a Sunday afternoon
woidd find Dr. Hurd busily engaged in correcting galley
proofs for the IUlletin or for the Heporls.
Both of these publications possess a dignity and style rarely
noted in medical periodicals. The printing has been good,
the illustrations excellent and the text remarkably free from
typographical errors.
The Hopkins Rvlletin and the Reports are to be found in
medical libraries the world over. Dr. Hurd deserves the lion's
share of credit for the marked success of these publications.
societies
In the first report Dr. Third refers to the medical societies
of the hospital.
A flourishing hospital medical society has been established
under the direction of Dr. Welch, which meets bi-monthly and
is regularly attended by members of the hospital and dispensary
staff. At these meetings papers are read, patients are exhibited,
morbid pathological specimens are presented anil the results of
original investigations in the clinical, pathological and hygienic
laboratories are reported. These meetings have been of great
value, and the amount of work which has been done compares
most favorably with that accomplished by any other similar
society.
A Journal Club, composed of members of the hospital and dispensary staff, also meets bi-monthly. At these meetings the current literature in the various departments of medicine, surgery
and gynecology is presented in abstract by persons previously
appointed to report from these departments. This enables all
members of the staff to keep fully informed as to what Is being
accomplished by workers In every branch of medical science with
the least expenditure of time.
In November. 1890, a Historical Club was organized to hold
monthly meetings for the study of medicine in Its historical
aspects. These meetings have been well attended and have proven
interesting and profitable.
The Historical Club still continues. Scattered throughout
the various volumes of The Johns Hopkins Hospit.\l
Bulletin are many articles which were read at the Historical
Society. They are of much interest and value.
1890
(February 1, 1890— January 31, 1891)
In tlie report for the year ending January 31, 1891,
Dr. Hurd refers to the work of the hospital among the poor of
Baltimore and emphasizes the fact that care must be taken to
see that people who are financially able should not be given free
treatment :
The added experience of a year has demonstrated the necessity of the medical, surgical and gynecological work which this
hospital is doing among the poor of Baltimore. The free work
has constantly grown in importance and usefulness since the
opening of the hospital and hundreds of poor people have received
relief who could not have obtained it otherwise. This work has
been done cheerfully and ungrudgingly both among hospital and
dispensary patients. It is evident, however, that some persons
who apply for gratuitous advice and pi'escriptions in the dispensary, and free beds in the liospital are not objects of charity, and
should not receive the benefits of the institution.
In some of the New York hospitals the names of all persons
applying for relief, when any doubt exists as to the propriety of
granting it. are reported to the Charity Organization Society, and
a systematic investigation is made by an agent of this society.
After a careful review of the whole subject I am strongly of the
opinion that the time has come when an arrangement should be
made with the Charity Organization Society of Baltimore, whereby
all suspected cases may receive a prompt investigation. It demoralizes any man to receive as a gift what he is able to pay
for wholly or in part. Indiscriminate and haphazard charity
begets habits of improvidence and of wastefulness, if not of actual
vice among its recipients.
In addition to the evil effect upon the community of indiscriminate charity there is also danger of doing injustice to the profession of medicine, which numbers among its members so many
persons actively engaged in charitable work. Neither the hospital
nor dispensary should interfere with the sources of support of
these men by affording free medical or surgical treatment to
those who are able to pay for it.
In this connection mention may be made of the excellent provision which exists at this hospital for the accommodation of
private or pay patients— a provision which is not excelled in any
general hospital In tliis country.
Dr. Hurd in the report also refers to the Training ."School
for Nurses:
Each month demonstrates the value and necessity of the work
of the Training School for Nurses. The school Is developing a
new field of usefulness for the young women of Baltimore and
Maryland and Is growing in popular favor. The dignity and
Importance of the profession of nursing were never so well appreciated in this community as now.
From the early days of tlie hospital to the present it has
been a matter of frequent conmient that for intellectual refinement and for mental cajjacity few if any hospitals in America
have been as fortunate as The .Johns Hopkins Hospital in tlie
personnel of its Training School for Nurses.
348
[No. 346
1891
(February 1, 1891— January 31, 1892)
The report for the year ending January 31, 1892, contains
the names of the first class of nurses who graduated from the
training school. Among them are Mary E. Gross (Mrs.
John M. T. Finney), Georgie M. Nevins the superintendent of
Garfield Hospital, Washington, D. C., M. Adelaide Nutting
who later became superintendent of nurses in The Johns
Hopkins Hospital Training School and who is doing such
excellent work as professor in the Treachers' Training School
at Columbia University, New York. This list also contains
the name of Susan C. Eead (the late Mrs. William Sydney
Thayer).
1892
(February 1, 1892— January 31, 1893)
MEDICAL INSTRUCTION
In the report for the year ending January 31, 1893,
Dr. Hurd makes a most important announcement relative to
the opening of The Johns Hopkins Medical School.
By the endowment of the medical school through the generosity
of Miss Garrett and others, the university is now in a condition
to assume the responsibility of medical instruction, and commencing with October 1, 1893, both graduate and other work will
cease on the part of the hospital. It is gratifying, in the review
of the past three years, to notice that women have not in any
respect proven a disturbing element. They have pursued their
work under the same conditions as men, and have done faithful,
honest and successful work. Although the hospital ceases to
do any more medical teaching, the fact that the governing Idea
in its erection was the promotion of medical teaching cannot
be lost sight of. The construction of the wards, the location of
the laboratories, the arrangement of the dispensary and amphitheater, the divers systems of heating and ventilating, and the
facilities for their demonstration, all point to a preconceived
plan that the hospital should do its share in the work of practical instruction. It is confidently believed that no other hospital in the United States is better equipped to do medical teaching, or in its brief career has done more thorough and suggestive
work. The same faithful work will be continued by the same
men, under the direction of the university in future, as a part
of the curriculum of the medical school.
LYING-IN AND CHILDREN'S WARDS
The approaching opening of the medical school renders it important that no time be lost in arranging for the erection of
a lying-in ward, to provide for the proper instruction of medical
students and nurses. In many respects it seems most desirable
that this ward be situated adjacent to the hospital, so that nurses
may be readily provided, and yet far enough removed to render
it free from the stir and publicity of a large general hospital,
and a numerously attended out-patient department. This building
ought eventually to be built upon a well-approved plan, and should
furnish ample accommodations for women who are awaiting confinement, for parturient women, and for those who suffer from
any form of puerperal infection.
A children's ward, separate and distinct from other wards, must
be erected. Such a ward alone will give children the proper opportunity for comfort and recovery.
The children are now well provided for in the Harriet Lane
Home. After long years of waiting it is a pleasure to know
that in the near future the obstetrical department is to have
adequate and most satisfactory accommodations.
1893
(February 1, 1893— January 31, 1894)
In the report for the year ending January 31, 1894,
Dr. Hurd describes the colored ward:
The colored ward, of which mention was made In the last report,
has also been erected during the year and is now ready for the
reception of patients. It consists of two stories surmounted by
a halt story.
This addition to the hospital has been of great value as it
brings all the colored patients under one roof instead of
having them scattered in various portions of the institution.
Dr. Hurd then refers to important changes in the library.
The opening of the medical school, and the increased demand
for medical books on the part of medical students, have rendered
it desirable to pay special attention to the library of the hospital.
Miss Thies, who has received a careful training in the Enoch
Pratt Free Library, has accordingly been employed at the joint
expense of the university and hospital to catalogue and arrange
the collections which have grown rapidly during the year. It is
evident that by the close of another year the shelving will be
filled, and no more room will be available for future additions. It
consequently becomes important to know how increased accommodations can be secured.
In this connection it seems eminently proper to refer to the
great advantages which the medical officers of the hospital and
the students in our medical courses have derived from the
proximity of the library of the Surgeon General's Office. The
enlightened policy of this library, whereby valuable books of
reference otherwise unattainable are loaned to the hospital under
satisfactory guarantees against loss, cannot be too highly praised.
The medical officers of the hospital, and the instructors and students of the medical school, are under many obligations for the
uniform promptness and courtesy of those who have charge of
this unrivaled collection of books in meeting the frequent demands
made upon them.
THE WHITE ROSE FUND
By the generous act of Mrs. W. E. Woodyear, of Baltimore, the
" White Rose Fund " has been established and the sum of $5000
has been placed at the disposal of the trustees, the interest of
which is to be used for the comfort and happiness of sick children.
It was not proposed to endow a bed or to establish a charity, but
to use the income of the fund in such a way as to promote the
comfort and happiness of poor, sick children who occupy beds in
the public wards of the hospital.
It was the intention of the liberal donor to provide means by
which flowers, books, pictures, excursions, music and other means
of amusement could be afforded for the children in a more liberal
manner than would be practicable if these extra expenses were
paid out of the income of the hospital.
It is doubtful if any gift to the hospibil, no matter how
large, has yielded more downright satisfaction to the donor
than this gift has. Year after year Dr. Hurd has referred to
how much it has meant to the children and what added pleasures this fund has made possible. He has alw^ays been most
entluisiastic when speaking of it in report after report. It
reminds one of a thread of gold carried through from year to
year. Mrs. Woodyear gave this money in memory of her little
daughter, Eose Blanche Woodyear.
December, 1919]
JOHXS HOPKINS HOSPITAL BULLETIN
349
1894
(February 1. 1894— January 31, 1895)
In the year 1894 si'veral important advances were made.
Experience having shown that the work of the pathological
department was of great value and Importance to every other department, it was decided by the trustees, after a thorough consideration of the subject by the medical board, to organize this
department, and to give it an equal standing in the medical staff
by appointing a resident pathologist and an assistant resident
pathologist. In consequence of this action. Dr. Simon Flexner,
associate in pathology in the medical school, was appointed resident pathologist, and Dr. L. F. Barker, the associate In anatomy,
was appointed assistant resident pathologist.
As far as is known at present, this is the first instance where
similar officers have been appointed with staff standing in connection with any hospital in the United States.
OUT-PATIENT OBSTETRICAL SERVICE
This service has been placed under the immediate charge of
Dr. J. Whitridge Williams, the associate in obstetrics in The
Johns Hopkins Medical School, who has received the appointment
of assistant obstetrician to The Johns Hopkins Hospital. Dr.
G. W. Dobbin has been appointed an additional assistant in the
gynecological department to look after this work in a special
manner, both in the dispensary and in attending patients in their
homes. It is contemplated that poor patients expecting to be
confined, and unable to pay the expenses of a physician, shall
visit the dispensary to arrange for the services of the resident
obstetrician. In arranging for this service it is hoped to be able
to bring relief to patients who require the services of a physician,
and to furnish the attention of a skilled nurse during the first
24 hours following confinement. It Is expected that this service
will eventually grow into a branch of district nursing.
In this report Dr. Hurd refers to the resignation of Miss
Hampton.
Shortly after commencement exercises in June last, 1894. Miss
Hampton, who had been the superintendent of the training school
ever since its opening, tendered her resignation. Her services
to the school had been of great value, and her resignation and
relinquishment of all training school work must be regarded a
serious loss to trained nursing throughout the country.
Upon her resignation, Miss M. A. Nutting, who had been her
assistant for the previous two years, received the appointment
of acting superintendent. Subsequently, In December last, she
was appointed superintendent, and given leave of absence for
eight months from February first to visit other hospitals and
training schools in this country and Europe, to see their methods
and to perfect herself in nursing work.
THE COLORED ORPHAN ASYLUM
In Dr. Hurd's report for the year ending January 31. 189."),
we find the first report of the colored orphan asylum.
By the will of the founder of the hospital, the erection and
maintenance of a colored orphan asylum was enjoined, and provision was made for Its support out of the income of the hospital
fund.
A tract of land on Remington Avenue and King Street has been
purchased as a permanent site for The Johns Hopkins Colored
Orphan Asylum, and the children have been removed to their
new home.
A detailed report of the committee on the colori-d orphan
asvlum follows that of Dr. Hurd.
1895
(February 1, 1895— January 31, 1896)
In Dr. Hurd's report for the year ending January 31, 1896,
we find an account of an addition to the dispensary :
In accordance with the recommendation of the medical board,
the trustees erected, during the summer of 1895, In connection
with the dispensary four class-rooms for the accommodation of
classes from the medical school.
Dr. Hurd in this report also records the death of one of tlie
most picturesque members of the hospital family :
Upon the 16th day of October, 1895, Mr. L. Winder Emory, who
had discharged the duties of purveyor with conspicuous ability
and fidelity, died suddenly of angina pectoris. The vacancy thus
created was filled January 1. 1896. by the appointment of E. H.
Read, of Baltimore, who immediately entered upon the discharge
of his duties.
1896
(February 1, 1896— January 31, 1897)
THE CLINICAL LABOR.\.TORY
In the report for the year ending January 31, 1897,
Dr. Hurd refers to tlie new clinical laboratory :
By an unexpected gift of $10,000 from a generous donor, whose
name we are prohibited to mention, It has been practicable to
erect a large and convenient clinical laboratory for the use of
the hospital and medical school between the amphitheatre and
dispensary. This portion of the building, wliich was formerly one
story in height, has now been raised to three stories, and the
additional room furnishes ample accommodation for medical
classes.
iliss Nutting's report to the superintendent for the year
1896 announces the inauguration of the three-year course in
the Training School for Nurses.
The demand for information concerning the school remains
about as usual:
The number of written applications for
circulars 1143
Applicants formally considered 160
Accepted applicants 61
Among the acknowledgments for the year ending January
31, 1897, Dr. Hurd mentions ilr. Spence's gift of a reproduction of Tliorwaldseii's statue of Christ:
One of the most noteworthy and appropriate gifts which the
hospital has ever received Is a reproduction of Thorwaldsen's
celebrated statue of Christ, by Stein of Copenhagen, which has
been placed in the rotunda through the liberality of William
Wallace Spence • of Baltimore. A full account of the interesting
exercises at the unveiling of this statue, together with the addresses delivered on that occasion, was published in the Buixxrix
for January, 1897,
The superintendent's report for the year ending January 31,
1897, gives for the first time the " By-Laws, Rules and Regulations of The Jolins Hopkins Hospital." A perusal of this
18-page article gives a most illuminating idea of the inner
working of this hospital.
* The reader will be interested to know that Mr. Spence
rounded out his century — be died a short time after his 100th
birthday.
350
[No. 346
1897
(February 1, 1897— January 31, 1898)
In 1897 the first class of The Johns Hopkins Medical School
received their degrees from The Johns Hopkins University,
and the 12 students who stood highest in their class were
eligible for positions in the hospital. Dr. Hurd in his report
for the year ending January 31, 1898, says:
Beginning with the first of September, 1897, 12 members of the
graduating class of The Johns Hopkins Medical School are in
future to be appointed resident medical officers. These physicians
are divided Into three groups, and serve four months in each
department of hospital service, the service being determined by
lot. In this manner each resident medical officer secures four
months service in medicine, surgery and gynecology.
In addition to these resident medical officers, the resident
physician, surgeon and gynecologist each is supplied with a iirst
and second assistant, who are appointed from those who have
had previous hospital experience. The working of this plan has
thus far been satisfactory.
In accordance with this arrangement the following-named persons were appointed resident medical officers *: Drs. G. L. Hunner,
J. F. Mitchell, 0. B. Pancoast, L. P. Hamburger, Thomas R. Brown,
E. L. Opie, R. P. Strong, W. G. MacCallum, W. S. Davis, I. P.
Lyon, C. A. Penrose and Mary S. Packard.
The rotation system was abandoned after a few years.
* Taken as a whole this was the most remarkable group that
has ever graduated from The Johns Hopkins Medical School.
Several of them have international reputations.
Dr. Walter S. Davis died in September, 1898, and in the Annual
Report of the Hospital for that year Dr. Hurd paid a fitting tribute
to his worth.
Recently Dr. Clement Andariese Penrose, another member of
this group, died. He received his A. B. degree from The Johns
Hopkins University in 1893 and immediately entered the Medical
School. After his year as intern he located in Baltimore and in a
few years was recognized as one of the most promising of the
younger physicians.
In 1903 he served as Vice-Director and Surgeon of the Bahama
Expedition. His report of the medical conditions noted on the trip
is very interesting. The most valuable paper was that on Leprosy.
This paper graphically depicted the deplorable condition existing
in the Bahamas due to leprosy and to degeneracy resulting from
close intermarriage.
In the spring of 1917 he was appointed Chairman of the Baltimore Food Economy Commission and did much to further food
conservation.
In August 1917 he was commissioned major in the United States
Army and was sent by the surgeon general to make an exhaustive
study on army sanitation in the English and French armies.
General Gorgas in speaking of Dr. Penrose's report said: "This
report has been of great value to the Medical Department of the
United States Army."
After completing his work on sanitation he took charge of a
three-hundred bed hospital at Gondricourt, France. Here he
contracted a septic bronchitis which nearly caused his death at the
time. He partially recovered but was left with an impaired heart.
He returned to America late in December and for a time was
able to resume his practice. In March 1919 the infection again
became pronounced. He gradually lost ground and died early on
the morning of July 4, 1919.
Penrose was an excellent medical consultant, a man of rare
judgment, beloved by his patients and a loyal friend. His death
was a great loss to the citizens of Baltimore.
Dr. Kurd's report for this year also contains an account of
the addition to the gynecological operating room rendered
possible by the generosity of Dr. Howard A. Kelly, who gave
$5000 to assist in defraying the expenses.
In Dr. Hurd's report for this year scholarships and honorable mention in the Training School for Nurses are recorded
for the first time. |
Dr. Hurd says : '
The experience of another year has demonstrated the feasibility
and desirability of extending the course of training of nurses
from two to three years. The changes in the course of study
have enabled nurses to spend more time in learning the fundamental branches of their work, and the shortening of hours of
duty has enabled them to bring greater freshness and vigor of
mind to their studies and regular duties. The result has been
to improve the standard of nursing, and to give a greater state
of efficiency to the school than it has ever previously had.
1898
(February 1, 1898— January 31, 1899)
In his report for the year ending January 31, 1899, reference is made to an incident that cast a pall over the hospital
family. It is vividly remembered to this day :
It is my sad duty to report the death of Dr. L. E. Livingood
who had filled the position of assistant resident pathologist for
two years, and who had secured a leave of absence to go to
Europe for further study. He left his duties July 1 and was
drowned a few days after in the destruction of the ill-fated
steamer La Bourpoyne. He possessed unusual ability, great industry and a finely trained mind, a combination of qualities which
gave every promise of success as a teacher and research worker.
In his death the hospital and the medical school have experienced a severe loss.
The hospital lost another of its young medical men during
this year, Dr. Walter S. Davis died of Addison's disease on
September 27, 1898. In referring to him Dr. Hurd says:
Dr. Davis was full of energy and enthusiasm, and during his
medical course and his year of hospital residence showed himself thorough in his work, conscientious in the discharge of duties
and efficient and faithful in all he attempted to do. His teachers
and associates anticipated high success for him in his chosen
profession, and all lament his untimely death.
A glance through the list for this year of those who secured »
scholarships in nursing is particularly interesting. Among I
the names in the senior class is Elsie Lawler, our present '
superintendent of nurses. In the junior class the name of
Agnes Hartridge, one of the present assistant superintendents
of the hospital. The steady advancement of these two members of the training school for nurses is ample proof that
Miss Nutting made no mistake in her selection of her pupils
meriting scholarships.
1899
(February 1, 1899— January 31, 1900)
GEADUATES FILLING POSITIONS AS SUPERINTENDENTS OF TRAINING SCHOOLS FOR NURSES
One of the most interesting items in the report for the year
ending January 31, 1900, is a list of the graduates of the
December, 1919]
351
training school who are filling positions as superintendents of
training schools for nurses. This list contains the names of
24 graduates of The Johns Hopkins Training School who are
now themselves the heads of training schools. Nothing could
show more grapiiicaily how much the graduates of this school
are appreciated throughout the United States and Canada.
1900
(February 1. 1900— January 31, 1901)
In the report for the year ending January 31, 1901,
Dr. Hurd refers especially to Volumes VIII and IX of The
Johns Hopkins Ilospilal Reports:
The past year has been one of considerable activity in the publications of the hospital. Volume VIII of the Reports, containing
exhaustive studies by Dr. Osier and his staff in typhoid fever,
has recently been published, and Volume IX, which contains 38
elaborate articles prepared originally by his students to celebrate
the 25th anniversary of the doctorate of Professor W. H. Welch,
the pathologist of the hospital, was published in April last and
constitutes a volume of nearly 1100 pages. In point of e.\cellence
of matter and thorough presentation of scientific work the volume
is fully equal, if not superior, to any of similar character ever
published in this country.
In addition, the Billetix has been regularly published with
increasingly valuable contributions each month. Volume XI
which was completed with the December issue, contains 340 pages
and numerous illustrations.
1901
(February 1, 1901— January 31, 1902)
In the report for the year ending January 31, 19Qi2,
Dr. Hurd again refers to the great value of The Johns HopKixs IIosi'iT.4L BuLLETix and of the Reports. He says:
Volume X of The .Johns Hopkins Hospital Reports is in progress
and will be completed during the present summer. The Bulletin
of the hospital has been issued monthly during the year and
has now reached an annual volume of nearly 400 pages. It Is
gratifying to observe how extensively it is circulated and quoted
both in this country and in Europe. It is evident that this publication has made a permanent place for itself in medical literature and our publishers inform me that the series of volumes Is
already In active demand to supply libraries. The papers presented in it during the past 12 years form, in fact, a good commentary upon the advance of scientific medicine in America.
During the past year, it may be added, the volume of the BulLETi.N has furnished upward of 900 octavo pages of reading matter.
Dr. Hurd also mentions the suhstantial addition to the
public gynecological ward :
During the year. In order to furnish additional accommodations
for patients recovering from gynecological operations, and to
secure facilities for an examining room and laboratory in connection with this ward, Dr. Kelly, with great liberality, gave to the
hospital the sum of $10,000. This sum has been expended in building upon the north side of the public gynecological ward, a large
two-story annex which affords accommodations for 12 patients.
The superintendent also gave a complete list of the larger
donations made to the hospital from the time of its completion
ap to the end of 1901.
1902
(February 1, 1902— January 31. 1903)
From Miss Nutting's report to Dr. Hurd for the year ending
January 31, 1903, we learn of the esteem in which graduates
of the training school are held. This is shown by the large
number of requests for nurses to fill important positions in
other schools :
Letters requesting us to sena our graduates to fill positions as
follows:
Superintendents 26
Assistants 6
Head nurses 15
1903
(February 1, 1903— January 31, 1904)
Nearly every hospital board of trustees has its period of
anxiety and perplexity wondering just how it will meet its
financial obligations. The trustees of The Johns Hopkins
Hospital have been men of affairs — men possessing a broad
vision — and they have in every instance found their way out of
the dilemma. Early in 1904,* however, without a day's warning, their annual income was for the time being markedly
impaired. Dr. Hurd in his annual report published early in
1904 refers to this critical period in the liospital's career in
detail :
To the Board of Trustees of The Johns Hopkins Hospital:
Ge.ntlemen. — The close of the past year of the hospital has
been marked by the most serious calamity which has befallen
the hospital during its existence. On the morning of February 7,
almost before it had been possible to sum up the results of the
operations of the previous fiscal year, which closed February 1,
a general conflagration swept over the city of Baltimore and
proved most disastrous to the real and lease-hold property of
the hospital. During the fire 64 stores, warehouses and office
buildings, widely scattered in the business portion of the city,
representing an assessed valuation of more than a million and
a quarter dollars, were destroyed, entailing a loss of income
for at least two years of about $120,000. A portion of this loss
was made up by Insurance. In accordance, however, with the
policy of the hospital, an insurance liad not been secured against
a total loss, but merely for a sum which had been deemed sufficient to provide for rebuilding in case of partial destruction
by fire. The results, however, proved that such insurance was
wholly inadequate to repair the effects of a wide-spread calamity,
and a loss of capital funds of between $300,000 and $400,000
resulted.
For several weeks thereafter great anxiety was felt lest It should
become necessary to curtail seriously the work of the hospital
by closing wards and cutting down the staff of nurses and
employes. Through the liberality, however, of Mr. John D. Rockefeller, of New York, who liad familiarized himself thoroughly
with the work of the hospital. Its financial standing, and its loss
of income and capital, a half million dollars have been placed at
the disposal of the trustees to repair these losses and to enable
the work to go on without diminution. Never was assistance
more timely to the Institution. The magnitude of the work of
* As it often requires six months to assemble the data of the
preceding year the annual report appears about the middle of
the following year: hence the Baltimore fire of February, 1904,
was mentioned In the report for 1903.
353
[No. 346
the hospital and the need of increasing clinical facilities to meet
the growing demands of the medical school had hitherto consumed all its income and had left no available fund to meet the
unforeseen emergency of rebuilding its warehouses. Hence the
peculiarly timely character of the aid afforded by Mr. Rockefeller,
and the critical condition of the institution without such assistance. The thanks of the medical staff of the hospital and of
the officers of the medical school are due to him for his prompt
and generous recognition of the educational work of the hospital.
At a special meeting of the Board of Trustees of The Johns
Hopkins Hospital on Thursday, April 7, 1904, the following action
was unanimously taken in reference to the gift of Mr. Rockefeller:
" In view of the donation of $500,000 made to The Johns Hopkins Hospital by John D. Rockefeller:
" Resolved, That the Trustees of The Johns Hopkins Hospital
desire to express their grateful appreciation of the gift of Mr.
John D. Rockefeller to The Johns Hopkins Hospital, announced
to the trustees by his son, Mr. John D. Rockefeller, Jr., in a
letter to Dr. William Osier. This munificient donation will enable
the hospital to continue its works of charity, medical education,
medical research and the training of nurses; and the trustees
hope and believe that by a wise use of this donation they will be
able to expand and improve the great institution committed to
their custody."
The report for the year ending January 31, 1904, contains
the following sentence : " In the out-patient obstetrical department there were 385 cases treated, with no deaths." This
speaks volumes for the splendid work being done by tlie
obstetrical department.
This year brought another liberal donation to the hospital.
Through the liberality of Mr. Henry Phipps, of Pittsburgh, the
sum of $20,000 has been given to the trustees of the hospital to
increase the facilities of the out-patient department for the study
and treatment of tubercular patients. It was the wish of the
donor that one-half of this sum should be used to construct a
separate dispensary for tubercular patients so as to render it
possible to segregate these from other patients. It was his further wish that the remaining $10,000 should be so invested that
the income may serve to promote special work and investigation.
In this report Dr. Hurd quotes extensively from a splendid
paper by a member of the hospital staff. This article is
entitled " The Eolation of The Johns Hopkins Hospital to
Medical Education and the Promotion of Medical Knowledge." It gives a clear and concise view of the close connection between the work of the hospital and the medical school.
It takes up in succession :
1. Construction of the hospital.
2. Medical organization of the hospital.
3. Relation of the hospital to medical education.
4. Relation of the hospital to the advancement of medical
knowledge.
5. The treatment of patients.
6. The Training School for Nurses.
7. Relation of the medical school to the university and to
the hospital.
This paper should be read by all interested in medical
teaching and in hospital management.
In the report for the year ending January 31, 1904, we
find the first annual report of the x-ray department. Dr. F. H.
Baetjer has been in charge of this department from its incep
tion up to the present time. He has made an tmusual success
of this important branch of the work.
In the annual report for 1903 Dr. Hurd has made a splendid
innovation. He gives a complete list of the trustees of the
hospital from 1867 to the present. There is also a complete
list of the officers of The Johns Hopkins Hospital from 1889
to 1903. This list includes not only all the senior members of
the staff, but also every resident physician, resident surgeon,
resident gynecologist, resident obstetrician, resident pathologist, assistant resident physician, assistant resident surgeon,
assistant resident gynecologist, assistant resident obstetrician,
assistant resident pathologist, and every house medical officer.
It is in reality an up-to-date directory of every medical man
who is or has been connected with the hospital since its opening. It will be of the greatest value in succeeding years.
1904
{February 1. 1904— January 31, 1905)
Dr. Hurd in his report for this year refers to the new clinical
building.
The amphitheatre and surgical building, to which reference
was made in the last report, were completed and made ready for
occupancy in October. 1904. A full description was given in the
last report, and need not be repeated here.
The building has proven extremely useful, and has added very
much to the convenience of the surgeons in their operative work,
and has afforded needed facilities for those who are engaged in
teaching.
The basement of the building has been fitted up for a genitourinary clinic, under the charge of Dr. H. H. Young.
The new surgical building and clinical amphitheatre were formally opened on October 5, 1904. Appropriate addresses were
made by Henry D. Harlan, president of the Board of Trustees;
Dr. Lewis A. Stimson, of New York; Dr. T. Clifford Allbutt, of
Cambridge, England; Dr. A. Jacobi, of New York; and Dr. D. C.
Gilman, ex-president of The Johns Hopkins University. At the
unveiling of the tablet in memory of Dr. Jesse W. Lazear, addresses were made by Dr. James Carroll, of the United States
Army, and by Dr. William S. Thayer.
Dr. Hurd in this report also refers to the opening of the
Phipps Tuberculosis Dispensary.
The Phipps dispensary was opened with appropriate ceremonies
on the 21st of February of the present year. Short addresses
were made by Mr. Henry Phipps; Dr. William Osier; Dr. H. M.
Biggs, of New York City; and Dr. Henry Barton Jacobs, president of the Laennec Society, a society for the study of tuberculosis.
Mr. Phipps subsequently gave $5000 to be used for the purchase
of books and apparatus and for the endowment of the dispensary.
Under the arrangements which were made, the sum of $10,000
from Mr. Phipps's former donation was used in the construction of the Phipps dispensary, and the remaining $10,000 was
set aside as a permanent endowment.
1905
(February 1, 1905— January 31, 1906)
The effects of the fire were felt for a long period of time,
and in Dr. Hurd's report to the trustees for the year ending
December, 1919]
353
January 31, 1906, we find the following reference to the
financial stress that was still felt by the hosi)ital :
The work of the hospital during the past year has been attended with unusual cares and anxieties, due largely to the disturbed finances of tlie Institution, consequent upon a diminution
of Income. When the last report was presented, it was hoped
that, by speedy rebuilding, increased rentals from the buildings
which were erected might become available at an early day so
that the necessity of pinching economy might be removed. Unfortunately, however, the expense and delays of rebuilding, due
to the rush to erect a large number of buildings at the same time
in the burnt area, rendered it Impossible to regain the full income
of the hospital during any portion of the year, and we are forced
to conclude it with a large deficit. It is hoped that the coming
year will be more properous.
RESIGXATION OF DB. OSLER
The departure of Professor Osier wrenched the heart-strings
of each aiul all of the Hopkins family. Dr. llurd in his report
said:
In May last Dr. William Osier, who had filled the position of
physicianin-chief to the hospital since its opening in 1889, resigned to accept the position of professor of medicine at the
University of Oxford. This closed a most faithful, efficient and
active service on the part of Professor Osier, covering a period
of 16 years. During this time he had given himself untiringly
to the work of the hospital and had won reputation as one of the
most accomplished clinical teachers in America. Through his
energ>' and foresight the organization of the medical service of
the hospital was early perfected, and his long period of service
enabled him to fully develop the plans formed upon his coming
to the hospital. He was much beloved by his patients and by
the members of the medical staff. The trustees in liis departure
have lost an inspiring and a stimulating personality. It is gratifying to know that he is to return at stated intervals to Baltimore, in order to keep himself in touch with the work of the
hospital and of the medical school.
APPOINTMENTS OF DR. BARKER AND DR. THAYER
To fill the vacancy occasioned by the resignation of Dr. Osier,
Dr. Lewellys P. Barker, of the University of Chicago, once an
Intern and later a resident pathologist in the hospital, and for
several years a teacher in the medical school, was appointed physlclan-In-chlef, and Dr. William S. Thayer, for many years resident physician at the hospital, and former associate in medicine,
was appointed associate physician. Under the experienred guidance of these able men. It Is confidently felt that the medical
work of the hospital will continue with undiminished efficiency.
The ncconiniodation for children in the past had been totally
inadequate and through the cooperation of the trustees of the
Harriet l.rf»nc Home and those of the hospital it looked as if
ample facilities would be afforded.
Miss Helen Skipworth Wilmer, a graduate of The Johns
Hopkins Training School for Nurses, gave $30,000 in memory
of her father, and the trustees contemplated using this money
in erecting an additional building for the accommodation of
the ever-increasing number of pupil nurses.
Dr. Hurd in his report on these projects said :
By the will of the late Mrs. Harriet Lane Johnston, of Washington, a home for invalid children from the state of Maryland has
recently been established with an ample endowment, to be known
as the Harriet Lane Home for Invalid Children of Baltimore City.
After considerable thought upon the matter, the trustees of the
home deemed it wise to establish a working relation between the
proposed institution and some well-organized hospital. Accordingly, upon mature consideration on the part of the trustees of
The Johns Hopkins Hospital and of the Home for Invalid
children an arrangement has been made whereby the home will
be placed as a cliildren's hospital for medical and surgical cases
upon the grounds of The Johns Hopkins Hospital. The hospital
will provide a site for the building free of charge, furnish heat
and light, and assume the maintenance and nursing of the children
at a specified price. The home will remain under the charge of
the Board of Trustees as established by its founder, and an agreement has been made which will insure a wholly harmonious relation between tlie two institutions.
In December last Miss Helen Skipworth Wilmer of Baltimore,
offered to the hospital the sum of $30,000 to be used to erect a
memorial to her father, the late Skipworth Wilmer, Esquire, a
prominent citizen of Baltimore, and for a number of years a member of the Board of Trustees of The Johns Hopkins Hospital,
Mr. Wilmer, during his entire connection with the hospital, felt
a special interest in the education of nurses, and it seems peculiarly fitting that his daughter should thus desire to perpetuate
his memory. The trustees have accepted the gift, and propose
to erect in connection with the nurses' home an additional building to be used as dormitories for the nurses.
Strangers going to and from the hospital often linger to
examine the sun dial and in sunny weather to see how closely
their watches tally with the dial.
Mr. George K. McGaw, one of the trustees of the hospital, has
placed in the circle upon the terrace immediately in front of the
hospital entrance an ornamental bronze sun dial upon a pedestal,
after a novel design by Albert C. Crehore, of Yonkers, N. Y., and
so arranged as to tell the time during the entire day as well as
the time of sun-rise and sun-set throughout the year. This
dial from its original design and beautiful workmanship Is highly
ornamental to the grounds of the hospital.
Award at the Loiisiana Purchase Exposition
In 1904 the Maryland Commission of the Louisiana Purchase
Exposition made an appropriation of $700 to defray the expenses
of transporting and setting up an exhibit of The Johns Hopkins
Training School for Nurses at St. Louis.
The exhibit was duly Installed under the direction of Miss Ross,
and excited much Interest among those who visited the exposition.
The grand prize, consisting of a diploma and a bronze medal,
was awarded by the Board of Awards. Unfortunately, owing to
the high price of labor and tlie difficulties Incident to the transportation of the exhibit and fitting It up in St. Louis, an Indebtedness of about $350 was incurred, wlilch was assumed personally
by Mr. William A. Marburg, one of the members of the Maryland
commission and a trustee also of the hospital.
1906
(February 1, 1906— January 31, 1907)
The report for 1906 was made by Dr. Rupert Norton, who
had been appointed acting superintendent during the superintendent's absence. In his report to the trustees Dr. Nortf)n
says :
In the absence of Dr. Henry M. Hurd, superintendent, to whom
you have granted a year's leave of absence to date from November 1. 1906. I have the honor to submit the following report on
the work of the hospital during the year ending January 31, 1907.
354
[No. 346
Since the last report was presented the hospital has had a most
successful financial year, and it looks as though the coming years
would be free of many of those cares and anxieties which have
troubled the hospital in the past; the present year ends with a
small surplus to its credit.
Dr. Norton's report also chronicles the splendid Marburg
bequest.
Mr. William A. Marburg, Mr. Albert Marburg, Mr. Theodore
Marburg and the Misses Marburg gave to the hospital the sum of
flOO.OOO in memory of their brother the late Charles Marburg.
The money was expended in the erection of a four story private
ward called "The Marburg." This building has enabled the hospital to handle many more private patients than was heretofore
possible.
DR. HURD's vacation
Early in November, 1906 Dr. Hurd commenced his wellmerited year's leave of absence. He left for New York and
there boarded a steamer for Havana. After a short stay in
Cuba he journeyed to Mexico and remained there, visiting
various points of interest, until January.
In January he returned to Baltimore, and in a short time
left Boston for Europe accompanied by Mrs. Hurd, Miss Hurd
and Miss Anna Hurd. Their first stop was at the Azores.
They thoroughly enjoyed a visit to Gibraltar and to Algiers.
They visited in succession the chief cities of Italy and also
went to Sicily. After a stay at Lake Como they went to
Switzerland. Here Dr. Hurd left his family and journeyed to
England where he renewed many old acqtiaintanceships and
visited the asylums and hospitals. He greatly enjoyed an
extended tour through Scotland. Here also he was royally
treated.
Leaving Scotland Dr. Hurd rejoined his family in Holland
and attended the International Congress of Alienists in
Amsterdam.
He returned to America thoroughly rested and greatly
pleased with what he had seen during his happy year of leisure.
He resumed his hospital duties on November 1, 1907.
1907
(February 1, 1907— January 31, 1908)
In the report for the year ending January 31, 1908,
Dr. Hurd refers at length to the Training School for Nurses
and dwells especially on the los.s the hospital had sustained
through the resignation of Miss Nutting.
The training School for Nurses during the past year has been
called upon to part with its superintendent and principal, Miss
M. Adelaide Nutting, who had ably supervised its work since
1894, when she succeeded Miss Hampton, now Mrs. Robb, upon
the resignation of the latter
Miss Nutting, her immediate successor, graduated from the first
class of nurses trained by Mrs. Robb, and subsequently held important teaching positions in the school. Her connection with tlie
school in fact as pupil and teacher covered a period of about IS
years, and during this period she inaugurated many Improvements
in the methods of teaching which contributed much to the evolution of the school as we have it at present.
Hence, when Miss Nutting decided to accept the call to the
Chair of Institutional Management in Columbia University, it was
generally recognized that the training school had lost a most
valuable officer, whose place would be filled with great difficulty.
The best wishes of the trustees, officers and pupils of the hospital
and school for her success accompany her in her new field of
labor.
It is gratifying to be able to add that Miss Georgina C. Ross
has taken up the work which Miss Nutting laid down, and has
prosecuted it with intelligence and vigor. She, like Miss Nutting,
had been connected with the school tor many years. She was
trained here as a nurse, and after her graduation had filled many
positions in connection with the school. As acting superintendent
she has had charge of the school for several months, and has
discharged a difficult range of duties with discretion, faithfulness and efficiency.
THE DEPARTMENT OF SOCIAL SERVICE
Dr. Hurd in this report referred at length to the social
service department which had just been inaugurated.
It has long been evident that the work of the hospital, both
in its wards and in the various out-patient services, has been
incomplete by reason of the limitation of the sphere of physicians
and nurses, who, from the nature of their connection with patients,
necessarily confine themselves to the treatment and care of their
physical ailments only. When the care of the hospital is withdrawn and the patients return to their homes, they frequently
lose the benefit which they receive, because of bad social conditions, lack of proper food and improper hygienic surroundings.
With the hope of relieving many of these conditions and helping to render permanent the good received while under treatment,
the trustees of the hospital, largely through the initiative of Mr.
John M. Glenn, one of their number, for many years closely
identified with the public and private charities of Baltimore, have
established a department of social service under the special charge
of Miss Helen B. Pendleton, for many years a trusted and efficient agent of the Charity Organization Society of Baltimore. It
is her duty to look after those persons who need something more
than medical advice and prescriptions, and to bring them into
relation with such charitable agencies or philanthropic persons
as will enable them to improve their former unfavorable conditions of life. She has in her work the advice and council of Dr.
Charles P. Emerson, who has for several years organized and
directed a very extensive friendly visiting work among the poor
of East Baltimore, and the assistance and active cooperation of
a large number of friendly visitors from among the medical students of The Johns Hopkins University and other charitable
workers.
The work under Miss Pendleton is still in its infancy, having
been fully inaugurated only in September last, but its success
already has been gratifying and encouraging. A kindred but less
comprehensive work on the part of the officers of the hospital
and the medical students of the university, as before intimated,
had been carried on under Dr. Emerson's efficient and wise direction during the past five years.
1908
(February 1, 1908— January 31, 1909)
THE PHIPPS PSYCHIATRIC CLINIC
Dr. Hurd's report for the year ending January 31,
1909,
speaks of the Phipps Psychiatric Clinic.
The Phipps Psychiatric Clinic, which was given by Mr. Henry
Phipps last June, will soon be begun, and arrangements for the
conduct of this department upon the completion of the building
have been satisfactorily settled. The architect, Mr. Grosvenor
Attebury, of New York, has the working plans well under way.
December, 1919]
355
This is the most important gift that the hospital has receive!
since its original foundation, and one which will undoubtedly
add much to its usefulness. It is a matter of great satisfaction
that we have been able to secure Dr. Adolf Meyer, of New York,
as director, a man who in knowledge and experience ranks with
the first men in the United States and Europe in his special
calling.
The superintendent's report for the year ending January
;{1, 1909, contains three reports of exceptional merit — Report
of the Piiipps Dispen.-iary Nur.«e; Report of tlie Phipps Dispensary, and the First Annual Report of the Social Service
Department. Tlieso clearly show how nuuli the hospital is
doing for the welfare of the citizens of Baltimore in their own
homes.
1909
(February 1. 1909— January 31, 1910)
In the report for the year ending January 31, 1910, is a
splendid record of the work done hy the new social service
de|)artnu'nt.
To Dr. Hinry M. Hiird. Superintendent of The Johns Hopkins
Hospital:
Sir. — The second year of the social service department ending
February, 1910, shows a decided growth in the work. There are
now 980 cases recorded as compared with 414 in the preceding
year
That the hospital physicians recognize the usefulness of this
department is shown by the Increase in the number of cases referred to us from the wards. During the first year there were 4S
cases, this year there have been 123
Mabcakkt p. BitniiBKX,
In charge of
social service department.
1910
(February 1, 1910— January 31, 1911)
l>r. Iliird's report for the year ending January .^1, l!tll.
refers to the resignation of Miss Ross, the superintendent of
nur.«es and the ai)i)ointment of her .successor:
At the beginning of the fiscal year Miss Ross, in consequence
of ill health, resigned her position and Miss E. M. Lawler was
appointed superintendent of nurses and principal of the training
school in her place. Miss Ross had been connected with the
hospital since her graduation in 1894, and had served faithfully
in many capacities in nursing service. She devoted herself assiduously to her work, and her failure in health was much deplored
by all connected with the hospital. Her successor, Miss Lawler,
is also a graduate of the training school, and for a time was
assistant superintendent. Later she held responsible positions in
connection with hospitals at Toronto. Ontario, N'iagara Falls,
N. Y.. and Pittsburgh. Her training has been varied, her opportunities for acquiring familiarity with the duties of superintendent have been unusual, and she consequently comes to us an
expert teacher. She has now given nearly a year's faithful service to the hospital, and her success gives every prospect of
continued and Increasing usefulness.
rur. PROFESSOR OF r.SYClIl.VTHY
In this report Dr. Hurd also referred to the development
of the p.<ychiatrie department and to its director who had
recently joined The Johns Ilupkins Hospital staff:
The professor of psychiatry. Dr. Adolf Meyer, has been appointed psychiatrist to the hospital, and although the psychiatric
clinic is not ready for occupation. Dr. Meyer has been able to do
very effective work in connection with the hospital wards and
the out-patient department. It seems fortunate that prior to the
opening of tlie Phipps Psychiatric Clinic it has been possible to
utilize his services in connection with various charitable agencies
in Baltimore. Tliere is reason to anticipate wlien the clinic is
opened that these relations may be productive of great good by
promoting cooperation with the clinic on the part of many charitable organizations.
In the report for 1910 Dr. llurd gave a complete list of the
large gifts made from the ojicning of the hospital in 1889 up
to the end of 1910.
1911
(February 1. 1911— January 31, 1912)
THE RESUiNATIOX OF DR. HUKD
In the '2'M report of The Johns Hopkins Hospital for the
year ending January 31, 1912, on tlie ])age headed " Trustees "
we find : President, Henry D. Harlan ; vice-president, William
A. Marburg: treasurer, John C. Thomas; secretiiry, Henry
M. Hurd, M. D, On scanning the report still riirtlicr we rciul
[page 27] :
In May, 1911, Dr. Henry M. Hurd resigned from the superintendency of the hospital to become secretary of the board of Trustees, and Dr. Winiord H. Smitli, general medical superintendent
of Belle\Tie and Allied Hospitals, in New York, was appointed
his successor.
Dr. Hurd was the first superintendent of the hospital, and
held the office for 22 years. Dr. Hurd"s wise administration,
his higli ideals, liis example and his readiness at all times to
give of Ills knowledge to others, have contributed largely to the
general development of hospitals throughout the country.
The man of small calibre is ])rone to pick out as his successor one who has even less ability than he possesses — one
who by contrast will compare unfavorably with him. The
man of vision, on the other hand, is anxious to have the work
that he has carried on so successfully continue to broaden out
and will suggest for the post he is relinquishing the best
available man. Dr, Ilurd with Jiis u^ual good judgment of
men recommended the best man he could find. The wisdom
of his choice has been continually evident and it has ever
been a delight to sec how hapjiy and how proud Dr. Hurd
has been of the well-merited success of his successor, Dr. Winford II, Smith, Dr. Hurd's pride has been akin to that of
a father who views with the greatest satisfaction the splendid
achievemcnt.s of his son; the more he accomj)lishes and the
greater recognition his work receives the happier he is.
DR. liriM) I\ Ills {{KL.VTIOX TO Till'] IIOSi'IT.\L
.S'i'.\l-'i''
When The Johns iio|ikins Hospital opened there was no
me<lieal .school from wliich to draw hospital interns and they
consequently were continindly recruited from all parts of
the United States and Canada, This system had its advantages. Nearly every man came from a dilTerent school. The
men compared notes, tohl one another of the methods in
vogue in the school or hospital from which they had ( ome,
and thus each man scmn betame fairly familiar with what
was being done in a medical way all over the country.
356
[No. 346
Some of these iuteriis had had several years' training or by
instinct immediately dropped into line. There were others
of us who were young and immature and who needed careful
and persistent training. Dr. Hurd was a past master in
stimulating the house men to do their best. He did not mollycoddle them in the least. This good old state of Maryland
is celebrated for its Maryland or beaten biscuits and it is a
well-known fact that the more they are hammered in the making the better they are. Dr. Hurd with his keen perception
soon learned this fact and he applied the principle to good
purpose in his training of these men.* By a gentle but firm
hint here and a rather emphatic suggestion there he soon
transformed the raw recruit into a splendid house officer.
Some of the men in the beginning hardly knew just how to
take this discipline, but in a short time all thoroughly appre
* I had often heard of an interesting interview the superintendent had with an incoming group of interns and also vague
accounts of a very apt story related by the director on that occasion. I asked Dr. Hurd if he would mind repeating it. Here it is:
"THAT STORY"
" When the men who had been selected for the positions of
interns at The Johns Hopkins Hospital out of the first graduating
class of The Johns Hopkins Medical School came on duty, they
found an organization for their work which had already been
in successful operation for about eight years. They were bright
enterprising students who were peculiarly receptive to all new
ideas and much inclined to adopt them with little regard to their
bearing upon the former routine of hospital service. As all were
men of marked ability, some of the innovations which they wished
to inaugurate were improvements without doubt and made for
better service, but the general effect of their combined action
caused confusion and a lack of co-ordination in the different
departments. In fact, since the changes of hours of duty and
general methods of work caused so much trouble, it was felt that
some steps were needed to check a similar individualism on the
part of equally active and zealous young men who were to enter
hospital service in succeeding years. After the interns for the
coming year had been appointed I called them into my office for a
friendly talk about their duties and without referring to the
embarrassments of the past year I rehearsed the tale of the small
boy who while on his way to school trudging through the deep
snow was overtaken by a gentleman, in a fine turnout with a
dashing span of horses, who kindly asked him to ride with him.
The invitation was joyfully accepted and the boy was soon making
fine progress when the idea occurred to him that the driver of the
horses was not driving them properly. He knew that he could
drive them much better and suggested a transfer of the reins
to him in order that he might display his superior skill. To his
great surprise and discomfort his host stopped his sleigh and
gravely but decidedly Informed him that an invitation to ride
did not carry with it the privilege of driving and that he might
get out if he thought otherwise. I added that it gave the management of the hospital much pleasure to know that they were willing
to ride with us during the coming year and I felt sure that such
a journey together would be of great service to them and to the
hospital, but I deemed it my duty to say frankly that the management of the hospital must do the driving and would continue to
do so in future as it had in the past.
" The parable was promptly and correctly interpreted and there
was never any difficulty in this respect with the Interns at the
hospital. They have always been loyal and co-operative in
measures calculated to add to the efficiency of the hospital."
ciated the value of the standards set by the superintendent, and
they would, later on, view with amusement and pleasure the
probationary period of those w^ho came after them. One and
all soon came to realize that Dr. Hurd was their best friend.
Many a time when one of the interns was in deep water — when
illness occurred at home and he was called suddenly away,
some one would quietly slip up beside him, place his hand on
his shoulder and casually say " Can't I do something for you ? "
" Don't you need some money ? " — many a man has had his
load greatly lessened by this quiet, unostentatious friend.
A former student recently told me that toward the close of
his second year he had reached the end of his resources and was
preparing to leave the medical school and go to work.
Just after he had packed up and was arranging to leave
that night Dr. Hurd met him in the hall and said, " By-theway, I have been wanting to ask you how your father's estate
has turned out," and the young chap told him the facts.
Dr. Hurd took him into his private office, told him he must
under no circumstances give up his studies and insisted on
furnishing him with sufficient funds to see him through to the
end of the college year, and next year saw that it was possible
for him to continue his studies. This young man is now one
of the most promising investigators in this country. He told
me that he knew of at least five or six other students who had
also been helped out by the same genial superintendent.
Dr. Hurd did not hold himself aloof from the house staff,
but after the evening meal often dropped into the reading
room to have a chat with the men congregated there. Every
now and then an informal invitation came to dine with
Dr. Hurd, Mrs. Hurd and his daughters. These were red
letter occasions — events never to be forgotten.
Every one of the men who was connected with the hospital
during Dr. Hurd's time has a vivid recollection of that tall,
slender figure passing silently down the corridors with his
head bent slightly forward and apparently walking on air, his
tread was so light. He rarely was +++++
CONTENTS to mount the stairs
one step at a time, he invariably went up two at a time with
his arms outstretched as if he contemplated an aerial flight.
Celebrated men who are closely associated with large numbers of young men are often given a special name as a mark of
the esteem and affection in which they are held. When the
men of the hospital staff of 20 years ago gather together and
discuss old times they always refer to " Uncle Hank " with
the warmest regard.
The visitor to the hospital — the one who comes to stay a few
weeks or months — while impressed by the good work done in
the various departments and by the original articles published
by the hospital is more impressed by the spirit of cooperation
and good fellowship that exists in the hospital and medical
school. Dr. Hurd and the " Big Four " — Drs. Osier, Halsted,
Kelly and Welch — have in large measure been responsible for
this delightful atmosphere.
Many of the senior members of the hospital staff have been
geniuses and it is a well-known fact that geniuses frequently
become so engrossed in their individual subject that they are
temporarily totally oblivious to the fact that other people have
Decembeh, 1919]
357
to be considered and tliat these people have precisely the same
rights and privileges as they. A tactful, gentle but firm tug
emanating from the superintendent's office would awaken such
an individual from his revery. It was tiiis absolute fairness
on the part of Dr. Hurd that won for him the confidence and
affection of the senior staff. They knew that they would
always get a square deal.
Dr. Kurd's relations to the trustees have always been most
pleasant. The trustees in their selection of the first superintendent looked the field over for the most able hospital executive they could find, and, when they had selected Dr. Hurd
and he had accepted, they wisely abided by his mature judgment on all medical matters, and when he felt that it was wise
for him to relinquish the exacting duties as superintendent of
the hospital they insisted that he retain a connection with the
institution and made him secretary of the Board of Trustees.
As we look back, it does seem a pity that Dr. Hurd did not
have an assistant to relieve him of the many time-cousuming
and incidental details connected with his office. It was not
until the last few years of his life in the hospitiil that he was
relieved of these by the appointment of the late Dr. Rupert
Norton as assistant superintendent.
Dr. Hurd was an ideal superintendent. In addition to the
satisfactory administration of the hospital he was deeply
interested in the fundamental education of the medical student
and of the nurse. He was continually stimulating the house
officers to do their best and was ever mindful of the welfare of
the patient. He was no bureaucrat, but a man who had the
interest of all connected with him at heart.
ARTICLES PUBLISHED BY DR. HURD WHILE
SUPERINTENDENT OF THE JOHNS
HOPKINS HOSPITAL
Most men after caring for the many details of such a large
institution as The Johns Hopkins Hospital and editing the
Bulletin and Reports would find little or no time for other
labors; not so with Dr. Hurd. With the indomitable energy
which has always been so characteristic of him he kept right
on with his literary work, each year writing one or more
articles. His papers have in large measure been limited to
four main subjects — psychiatry, hospital management, medical
education and the education of the nurse.
In 1890 we find in the Maryland Medical Journal a paper
on " Periodicity in Melancholia." Dr. Hurd in the same year
was chairman of the Committee on Hospitals for the United
States and made his report at the National Conference of
Charities and Corrections held in Baltimore, May, 1890.
Immediately after reading this report he addressed the
assemblage on " The Relation of the General Hospital to the
Medical Profession." In this address he clearly outlined what
the general hospital should stand for. His ideas for that
period were so advanced that I quote them.
The mission of the general hospital may be summarized to
be: (1) To furnish metltcal treatment and proper nursing to the
sick poor, and especially to the homeless and friendless; (2) to
furnish similar treatment to those who are able and willing to
pay for It, and especially to those who are without families and
homes; (3) to provide aseptic operating rooms where antiseptic
surgery may be done with full confidence In Its results — this
confidence being based upon the knowledge that all scientific
requirements have been met by proper construction and thorough
manasement; (4) to provide Instruction in and full demonstrations of the most approved methods of treatment of the sick to
medical students and medical men; (5) to train capable, highminded, self-sacrificing women as nurses; and finally (6) to
advance medical study and increase medical knowledge.
It is evident that the old-time idea that the hospital is designed
for the destitute and homeless alone must be materially modified to meet the present exigencies of modern life. Many persons
in moderate circumstances live comfortably as long as they can
labor and produce, but, when ill, can procure skilled medical
attendance and proper nursing only at the cost of future debt
and a weary struggle to pay the obligations incurred. The expenses of living are constantly Increasing [1890] and the competition of modern life is intense, so that the majority of laboring
men, of necessity, spend their earnings as they receive them,
with little prospect of laying up a reserve for the traditional
" rainy day." Hence, whether it be considered a good policy or
not, provision must be made to care for many of tliese wageearners in public hospitals in the event of long continued or
serious illness. The same is true of the more wealthy classes.
Many of them cannot procure at home the constant medical care
and the thorough nursing required, and certain portions of the
public hospital must be set apart for them.
In the Transactions of the Medical and Chirurgical Faculty
of Maryland for 1891 appears a memoir to the late Richard
Gundry, a well-known asylum superintendent and later a
member of the Faculty of the College of Physicians and Surgeons of Baltimore. Dr. Gundry was an old and valued
friend of Dr. Hurd.
In the American Jo^umal of Insanity for 1892 Dr. Hurd
published an article on " Journal Clubs." In this paper he
spoke most enthusiastically of the value of such clubs and
pointed out how they should be conducted :
For the success of a journal club it is essential:
1. That the work be made obligatory. It will not do to rely
upon a zeal for study which may be cooled by other duties or by
social obligations. The work should be made a part al the regular routine of the Institution, and should not be pushed aside by
any trivial matter. The same rule which governs excuses from
any regular professional duty should govern all absences from
the journal club. No new man should be added to the staff who
does not Intend to devote himself as loyally to this as to any
other hospital or asylum duty. If outaiders are admitted — and
I should say the more the better— they should come Into the
work under the same conditions.
2. A definite hour which will be reasonably sure to be tree
from Interruption should be selected, and rigidly adhered to.
Such an hour ought not to be at the close of an exhausting day's
work.
3. The proceedings should be Informal, and free discussion
should be expected. The journal study should have the widest
possible range. French, German and Italian journals should all
bo laid under contribution.
4. The work should be thoroughly supervised by the superintendent or some person whom he may select. Whoever takes
charge of the club ought specially to prepare himself to sum up
each subject and to present Us practical bearings upon the better
study or the better treatment of Insanity. This will often Involve
358
[No. 346
study and extra exertion; but such mental effort is recreative,
and a grateful change from routine work.
The advantages of a journal club are manifold. A few of them
may be mentioned:
1. It develops a spirit of professional study among the members of the hospital or asylum staff. The spirit of investigation
and inquiry is easily lost unless special efforts are made to develop it. This is especially true where routine duties constantly
press themselves upon the attention. Unless a spirit of study
and inquiry is sedulously cultivated among the younger members of a medical staff, the zeal for professional advancement
speedily disappears.
2. It provides for the systematic acquisition of knowledge by
a division of labor; and the least possible waste of time on the
part of each person concerned. This is an age of cooperation in
literary work. Library and subject catalogues are undertaken
by associated laborers; and enterprises which would be impossible to an individual become practicable to the many. Witness
the success of H. H. Bancroft's gigantic historical enterprises.
The work which he has finished by the aid of collaborators would
have consumed 400 years of individual effort, had such a length
of years been granted to the head of the undertaking. It is in
keeping with the spirit of modern study to economize time and
effort by multiplying workers. Psychiatry and neurology are so
vast that each student cannot read the good, the bad and the
indifferent. The grain should be winnowed before it is gathered
into storehouses.
3. It supplies a common field of study where the members of
the staff may meet for contact of mind with mind. By means
of it, individual tastes and aptitudes for study may be utilized
for the common good. It gives a broader professional aspect to
asylum work by bringing each member of the staff into relation
with the whole field of psychiatry. It also effects the readier
training and more speedy assimilation of new members of the
staff. Young men come to asylum work fresh from medical schools
and hospitals with a keen zest for scientific work. This should
be utilized, and habits of regular study in lines of psychical
research should be acquired as speedily as practicable. The
journal club will also contribute materially to the unification of
a staff which may have been brought together from different
schools of medicine. This is too often neglected in large asylums.
In 1893 Dr. Hurd published an article on " Post-Febrile
Insanity." After discussing the subject in detail he recorded
three cases of this character that had occurred in The Johns
Hopkins Hospital, one after laparotomy for removal of diseased ovaries, one following pneumonia and a third during
convalescence from typhoid fever.
In 1893 we find an article entitled " The Relation of Hospitals to Medical Education." This appeared in the Boston
Medical and Surgical Journal, csxis, p. 1-41.
In the medical writings of a physician one rarely has the
opportunity of catching a glimpse of the personal charm or of
the depth of sympathy of the writer. On October 14, 1894, a
meeting was held in memory of the late George Huntington
Williams, professor of geology in The Johns Hopkins University. Dr. Hurd had known him since he was a boy and was
closely related to him by family ties. Dr. Kurd's tribute to
his deceased friend brought out ^dvidly that personal charm
and sympathy which has always so endeared him to those with
whom he has been closely associated.
In 1894 Dr. Hurd published a lengthy article on " Some
Mental Disorders of Childhood and Youth," and in the Bul
letin of the Ameri-can Academy of Medicine, 1895-6, an article
on " Laboratories and Hospital Work."
In the Maryland Medical Journal for 1896 we find a second
article on " Paranoia."
In the American Journal of Insanity for 1895-6, p. 477,
Dr. Hurd says :
It has been the custom of the Journal of Insanity during more
than half a century to publish full details of new Institutions
erected for the better care and treatment of the insane; hence
the recent opening of the new McLean Hospital at Waverly, near
Boston, calls for more than a passing notice.
Dr. Hurd then describes in a most interesting manner this
large institution for the care of the insane. He also gives
illustrations and plans of the various buildings. The paper
is a most complete one, occupying 26 pages.
On February 17, 1897, Dr. Hurd gave an address on " Hospital Organization and Management " before the Training
School for Nurses at the hospital of the University of Pennsylvania. This was published in the University Medical Magazine, ix, p. 488. It contains much of interest and I quote
some of the remarks made by Dr. Hurd on that occasion.
I cannot resist the temptation to say a word respecting the
improvements which have been made in hospital construction
during the past 30 years. These improvements I believe to be
largely due to the experience of the Crimean War in Europe and
of the Civil War in America. The first gave us training schools
for nurses and trained nurses, and the latter improved hospital
construction. These waves of progress from the East and West
crossed the ocean in turn and brought to the whole world better
facilities for the care of the sick and better methods of treatment.
The most noteworthy improvement in hospital construction
has been in the direction of better sites for buildings, which
are no longer crowded into narrow, dingy streets with unpleasant
surroundings, and amidst insalubrious and unsanitary conditions,
but are placed in open squares. In commanding situations, where
sunlight and fresh air can freely come upon their joyous and
health-giving missions.
The buildings themselves are more scattered, and sickness and
suffering are diluted by differentiation and segregation rather
than concentrated by piling one ward upon another. Hospital
wards also have been more conveniently arranged to do their
appointed work, and have had comforts and conveniences In the
way of service-rooms, tea-kitchens, rooms for the dangerously ill
and dying, and the like, which have contributed immeasurably
to the comfort of the sick. Special efforts have been made in
the construction of wards to provide for heating, ventilation, the
isolation of infectious, harmful, or offensive patients, and for all
sanitary needs. Laboratories for the investigation of disease have
also been built and fitted with instruments of precision for the
more accurate and scientific study of disease processes. Operating rooms have been planned and erected at lavish expense to
carry out as strictly as in a laboratory all the requirements of
antiseptic surgery. Disinfecting plants have been joined to every
hospital to destroy the germs of disease and to prevent the transmission of infection from one patient to another.
It is related that a surgeon-general of the United States Army,
now deceased, once stated that it was no part of the work of the
army medical corps to study disease or to engage in any work
of research, but rather to cure sick soldiers, forgetting that the
cure of sick soldiers is more promoted by the spirit which leads
to the study of disease than by the narrow view that the indi
December, 1919]
359
vidual soldier at morning sick-call alone should engross the attention of the army surgeon.
The best method of keeping the torch of knowledge lighted is
to pass it along from hand to hand. Hence I have little sympathy
with those who deplore the use of hospital wards as means of
Instruction. They should be used for the training of nurses and
for the instruction of medical students, and by their very use
for these purposes their efficiency for the cure of disease will be
augmented.
In a well-ordered hospital, as in a well-ordered state, there
should be an ultimate and final authority, a proper subdivision
of duty, and a tliorougli adjustment of all portions of a complex
and often cumbrous mechanism to its special uses. It is the
part of a Board of Trustees to establish the policy of the hospital, to give an impetus fo the machinery, to oil and readjust It
from time to time, to watch its operations, and to scrutinize its
results.
A friend of mine used to say that responsibility without power
is weakness. Responsibility and authority must go hand in hand.
If I were asked to indicate the best machinery for hospital
government. I should say a Board of Trustees to be sovereign
and responsible for the whole institution, a medical board to advise the trustees in all medical matters, a chief executive officer
to be known as director, secretary, or superintendent, whose duty
It should be to coordinate and supervise all qther departments,
a purveyor to look after food-supplies, a matron to supervise the
household and a superintendent of nurses to have charge of the
training school and the- nurses. Under these heads of departments there should be subordinate cliiefs of departments, like
the engineer, chief cook, laundry man. diet-school teacher, storekeeper and the like.
A word as to discipline. From the character of the work of a
hospital and the necessity of the development of kindly instincts
and humane methods of thought and action among all employes.
It is unwise to establish and enforce a semi-military discipline
or even one which would be practicable or advisable In a railway,
a large factory, a corporation, or other business enterprise. There
should be a rigid discipline and a strict accountability for the
performance or neglect of duty, hut this discipline should be sustaining in its nature and calculated to develop tlie individual.
Through Its kindly control the tlioughtless or untrained nurse
or employs should be lead to a higher level of conduct and feeling until her better nature becomes the governing power. To
many hospital employes the life becomes truly educational, and
the officer who does not strive to make it so fails of an important
duty. A wisely directed enthusiasm, a kindlinp of the moral
nature, a glimpse of a higher, broader, and more satisfying life
can thus be given to all wlio have to do with the sick in the
hospitals. Hospital work, when done with loving, eager enthusiasm, blesses the patient and the nurse alike. It should be
the aim of all to do charitable work in a charitable, kindly way.
1 have little patience with those who look upon the medical treatment of the sick In hospitals as a business matter only, and the
nursing of the sick as an avocation, a trade, a preparation for
getting a living, a matter of hours on duty to be endured as
patiently as possible for the relief which is afforded by getting
through with them. Vnless the care of the sick can bo glorified
by sympathy, kindly feeling, enthusiasm and personal Interest
It becomes drudgery and heartless routine. Hence the necessity
of developing the best Instincts of all wlio have to do with the
sick by a sustaining, fostering and kind discipline which regards
the individual and not the mass.
Much of the alleged lack of sympathy sometimes complained
of on the part of the hospital physicians, nurses and employes, I
believe to be due to overwork.
In 1897 Dr. Hurd and Dr. John B. Chapin, physician-inchicf and superintendent of the department for the insane of
the Pennsxlvimia Hospital of Phihidelphia, Pa., were asked by
the " Joint Select Committee to Investigate the Charities and
lleformatory Institutions in the District of Columi)ia " to
maJie a report on the hospitals of the District of Columbia.
This they did and their findings were embodied in a paper
presented to the committee on November 24, 1897. This
report embraced a full description of the Asylum and Almshouse Hospital: the Children's llospitjil; tiie Columbia Hospital for Women and Lying-in Asylum ; the Central Dispensary and Kmergency Hospital; the Freedman's Hospital;
the Garfield ilcmorial Hospital; the National Ilomieopathic
Hospital and the Home for Incurables. The report is an
exhaustive one. It points out the excellent features in each
institution, draws attention to the weak spots, and makes
numerous admirable recdnimcndations looking to the more
systematic and the better handling of patients in the District
of Columbia.
In the Albany Mfdiriil Annuls for February, 1898, we find
an article entitled " The Medical Service of Hospitals," and
in the Maryland Medical diiurnal for 1898-9 Dr. Hurd considers " The Non-Medical Treatment of Epilepsy."
At a meeting of the Gynecological and Obstetrical Society
of Baltimore, December 13, 1898, Dr. Hurd gave a paper on
" Post-Operative Insanities and Undetected Tendencies to
Mentiil Disease." This article appeared in the Amrricun
Journal of Olisfelrics, Vol. xxxix, 1899. It is interesting
to read Dr. Hurd's views on the subject. They are of much
importance to the laity as well as to the surgeon.
Post-operative insanity may be considered a complex affair,
comprising symptoms which may differ In cause, manifestation,
course and termination. There would seem. In fact, to be little
ground for the use of the term, were It not for the existence of
infectious processes accompanied by delirium or prolonged depression. In other words, if an operation is free from septic
infection in a case destitute of any tendency to insanity, tliere
can be no ground to think that tlie operation ;>('»• sr produces
mental disease or that the insanity is post-operative In the sense
that the operation bears a causative relation to the insanity.
There are disturbing factors, it is true, in connection with surgical operations, which may be competent to produce an Insanity,
and I will briefly refer to some of them; but the insanity wlilch
they produce can only he considered post-operative in point of
sequence rather than of causation. It is unquestionable that
the prolonged use of ana-stlietlcs like ether, chloroform, or nitrous
oxide has produced excitement, delirium, mental confusion, and
often prolonged mental alienation without the accompaniment of
any operation whatever. Instances are also not at all unr-ommon
wliore. following an operation, excitement has followed the local
application of Iodoform, the instillation of atropia or the administration of the salicylate of soda, and where, notwithstanding
the surgical operation, the symptoms of Insanity subsided wholly
upon the withdrawal of the intoxicating agent.
Similarly, we may have mental symptoms following an operation clearly ascrlbablo to shock, loss of blood, excessive exhaustion from the fatigue of a constrained and unnatural position,
long-continued vomiting from an anapsthetlc. or abstinence from
food owing to anorexia. There may also be a poisoning of the blood
and consequent interference with proper cerebration from defective action of the kidneys, due wholly to the withdrawal of water
by the mouth lest it may excite vomiting after an abdominal
operation; or the ang-sthetlc may have caused a transitory neph
360
[No. 346
ritis with accompanying loss of kidney function. These and
similar causes which are not surgical in character, but are necessarily an accompaniment of a surgical operation may produce
insanity which cannot in any manner be differentiated from
actual post-operative insanity due to infection.
In 1899 Dr. Hurd was president of the Medical Psychological Association. On that occasion he took as the theme for
his address " The Teaching of Psychiatry." That his interest
in the care of the insane never flagged is clearly shown by the
fact that from the first meeting of this association in 1879 up
to the time of his presidency in 1899 he had missed but two
annual meetings.
In this address he paid a touching tribute to an old friend :
While engaged in writing this address the crushing news comes
of the sudden death of Dr. Godding. It is difficult to realize that
our noble-hearted and cultivated associate has gone from earth.
He had a poet's soul, the charity of a saint and the heart of a
child. He loved poetry, literature, art and music; above all, he
loved his fellow-men.
In 1900 Dr. Hurd published a splendid article entitled
" Hospitals, Dispensaries and Nursing." At the end of tliis
paper he gave a list of the principal hospitals of the United
States that had been established during the last century.
In the Bulletin of the Iowa State Institution for 1901
appears a paper by Dr. Hurd entitled " Reception Hospitals
for Cases of Acute Insanity."
On November 21, 1901, Dr. Hurd delivered an address on
" Psychiatry in the Twentieth Century," at the opening of an
additional building at the New Jersey State Hospital at
Morris Plains. After paying a tribute to the late Miss
Dorothea L. Dix, whose work had been such a benefit to New
Jersey as well as to the entire country, he sketched the gradual
changes that had taken place in the treatment of the insane
in the United States. He then pointed out where improvements might with profit be made in the handling of mental
cases. The pith of his remarks is contained in his concluding
paragraph :
The future of psychiatry in America is bright with hope. The
era of foundation and construction is nearly over; institutions
have been evolved, developed and perfected; pathological institutes have been established and liberally equipped and supported;
trained men with broad learning and technical knowledge have
been raised up for special study, and an earnest spirit of investigation has been developed. We are on the threshold of new
discoveries and important improvements in the treatment of the
insane.
In 1908 Dr. Hurd addressed the graduating class of the
training school of the Garfield Hospital at Washington, D. C.
He took as his theme " The Educated Nurse and Her Future
Work." This paper was later published by the Friedenwald
Press in Baltimore. It should be carefully read by every
undergraduate and graduate nurse. It will also give to the lay
reader a very clear idea of what real nursing means — it portrays in no uncertain terms how much the medical profession
owes to the trained nurse.
Dr. Hurd gave a charming address on "The Duty and
Responsibility of the University in Medical Education," at
the gr-aduating exercises in the Yale Medical School on June
23, 1903. After briefly considering the subject of his discourse he said :
To discuss an educational question before university men suggests the appropriateness of the quotation from Confucius with
which an eminent scientist once prefaced an address made under
similar circumstances: "Avoid the appearance of evil: do not
stoop to tie your shoe in your neighbor's melon patch." A member of the teaching staff of one of the newest schools of medicine
ought to display a degree of modesty in the presence of medical
teachers whose thoughts and activities have been molded by the
traditions of one of the oldest medical schools in the United
States, the sixth in point of time of establishment, and should
hesitate above all to urge the duty and responsibility of a university in medical education.
Perhaps I may also plead in mitigation of my indiscretion a
degree of hereditary relationship to Yale in the fact that my
father graduated here in medicine in 18.30; my grandfather was
a student about 1795, but did not graduate; my great-grandfather
graduated in 1778; and my great-great-grandfather in 1739, and
may speak as one whose speech can be tolerated because of kin,
albeit remote.
In his remarks directed especially to the graduating class
he said :
In your chosen profession be students and productive workers
always. Do not look for speedy results and do not be discouraged
if the secrets of nature are not wrested from her jealous grasp
without a severe struggle. The foundations of our art are broad
and deep, and the superstructure should be erected slowly and
with care, by accurate observation of disease and painstaking
deductions. In your life as physicians be prepared for trials,
disappointments and adversities. Take for your motto the words
written by Sir Thomas Browne, that eminent physician, more
than two centuries ago: " In this virtuous voyage of thy life
hull not about like the Ark without the use of Rudder, Mast
or Sail and bound for no Port. Let not disappointment cause
Despondency nor difficulty Despair. Tliink not that you are sailing from Lima to Manillia, when you may fasten up the Rudder
and sleep before the Wind; but expect rough Seas, Flaws, and
contrary Blasts; and 'tis well if by many cross Tacks and Veerings
you arrive at the Port; for we sleep in Lyons Skins in our
Progress unto Virtue and we slide not but climb unto it."
Have a purpose and carry it out with fortitude. There can
be no more absorbing or inspiring career than is afforded by
the study of medicine at the present time. The scaffolding
reared by countless workers during thousands of years around
the fair temple of medicine, necessary for the building doubtless,
but concealing its proportions and too often defacing its beauties,
has been swept away, and for the first time it is permitted to
us to know something of the dimensions and architectural possibilities of the completed edifice. Can there be a nobler aspiration for any man than to assist in the completion of the work of
transforming the ancient art of healing into the science of
medicine?
In 1902 Dr. Hurd was the chairman of the Section on
Neurology and Psychiatry of the Medical and Chirurgical
Faculty of Maryland. At a meeting of the section held
November 14, 1903, he took for his subject "The Future
Policy of Maryland in the Care of Her Insane." When in
Michigan he did not hesitate to tell the state Just what her
duty was in the care of the insane. In Baltimore he spoke out
in the same fearless manner. He had carefully studied the
situation in Baltimore and in the various counties. Maryland
was far behind the times and at the meeting of the Medical
Decembeb, 1919]
361
and Chirurgical Faculty in 1897 a symposium on the state
care of the insane had been arranged. The papers read on
that occasion brought forth much resentment on tlie part of
the state authorities.
Dr. Hurd in his address in 1902 pointed out what had been
accomplished in the interim, but also stated in no uncertain
terms that in many places throughout tlie state the conditions
were still deplorable. He did not generalize as is so frequently
done, but was specific, mentioning the institutions at fault.
He then indicated how these appalling conditions should be
rectified.
A man who has the nerve and patriotism to come out boldly
and draw attention to the glaring faults in his own state and
at the same time to indicate the means by which these conditions can be ameliorated is without a doubt a most valuable
man in his community — he is a real citizen.
Dr. Hurd's concluding paragraph addressed to the medical
profession was peculiarly apt to the occasion :
Those who have read the recently published life of Pasteur
(every physician ought to read it) must have been impressed by
the fact that in the mind and life of this wonderful man scientific knowledge was Invariably regarded as the hand-maiden of
humanity. In the height of Pasteur's interest in the study of
ferments, which opened the way to our present antiseptic surgical methods, he turned aside from his chosen work for five
years to study the diseases of silk-worms, because of the sufferings of the people In certain portions of France consequent upon
the destruction of the silk industry. His subsequent studies In
puerperal fever, charbon. chicken cholera, plague and hydrophobia
were Inspired by a similar notion ; to use his own words, " To
give the heart its share In the progress of science." We may
not be able to imitate Pasteur in scientific achievement and In
broad and vivifying generalization from isolated scientific facts,
but we can Imitate his broad humanity and his desire to ameliorate the lot of the unfortunate. We can at present do no greater
service to humanity and the commonwealth than to use our professional Influence and personal effort to promote the hospital
treatment of acute cases of insanity and appropriate state care
for the insane poor of the chronic class.
All interested in the care of the insane should read this
article in full. It appeared in the Maryland Medknl Journal,
February, 1903.
Thanks to Dr. Hurd and his colleagues the disgraceful condition that then existed has long since been corrected. The
State Lunacy Commission, then more of an advisory board,
now has ample authority and at the present time Dr. Hurd is
the most valuable member of the commission.
In 1904 Dr. Hurd gave the address to the graduating class
of the Training School for Nurses at the Albany Hospital.
He took as his theme "Is Nursing a Profession?" This
paper was published in the Albany Medi<-al Anncds, September,
1904.
In his address at the graduating exercises of the Lakeside
Hospital School for Nurses in Cleveland, in 1906, his paper
was entitled " Shall Training .Schools for Nurses be Endowed ? " This is a theme that is engrossing the attention of
more than one institution.
In 1906 Dr. Hurd read a paper entitled " The Medical
Organization of General Hospitals." before the eighth annual
meeting of the Association of Hospital Superintendents. This
article was published in the National Hospital Pecord in
October of that year. At the annual meeting of the Canadian
Hospital Association, held in 1908, Dr. Hurd spoke on " The
Proper Length of the Period of Training for Nurses." This
paper was published in the American. Journal of Nursing in
June, 1908.
In May, 1908, Dr. Hurd gave a paper on '• Psychiatry as a
Part of Preventive Medicine." This was published in the
American Journal of Inmnity, 1908-9.
The object of preventive medicine being to lessen the burdens
of mankind by obviating preventable diseases. It is deemed appropriate at this time to inquire in what manner the experience of
those who are familiar with the problems of psychiatry may be
utilized to assist in this good work. It needs no elaborate demonstration to show the evils of insanity and the heavy public and
private burdens which it entails upon every community. Next
to alcoholism it is probably the most potent cause of pauperism
and dependence.
The article is a most instructive and important one. The
conclusions are particularly interesting:
The methods of rendering the teachings of psychiatry more
effective to prevent disease should be:
1. To instruct children in the schools the art of healthy and
useful living. Teaching should be more thorough and not restricted to fit one to get on in the world, but rather to inculcate
Ideals which will give him a conception of the prime importance
of self-control and moral rectitude. It should also include a
knowledge of the dangers of immorality and Intemperance.
2. To use the newspapers and the special reports of ofllcers of
institutions for the Insane and defective classes, to scatter broad
cast a knowledge of the laws of bodily and mental healtli, and
the best means of preventing the development of mental disorders.
3. To give a better recognition of psychiatry in the curriculum
of every medical school, so that physicians may become familiar
with the diagnosis and treatment of insanity. To this end psychopathic hospitals should be established to give clinical instruction, so that the family physician may recognize insanity, may
be able to scrutinize carefully the mental condition of neurotic
children and may give wise advice upon all educational problems.
In tlie Nursing Mirror for 1908-9, Dr. Hurd published an
important paper on " State Registration and the Education
of Nurses in the United States."
On November 30, 1910, a Health Conference was held in
Pittsburgh. On that occasion Dr. Hurd gave a short but most
practical paper on " Cooperation Among Hospitals." In this
address he emphasized the great value of cooperation. He
said :
Hospitals are often established by too zealous friends for these
medical men, or established hospitals fall under the dominion of
two rivals In the profession. Under the circumstances, cottperatlon between the two hospitals becomes difficult and often impossible. I know many cities where such bitter feelings have In the
past destroyed all hope of cooperation and where the friends of
able physicians or surgeons formed two armed camps. Even the
ladies become enlisted and fight under one or the other banner.
I am glad to say, however, that the days of bitter rivalry between
hospitals are passing away. The whole world is becoming more
tolerant and the odium mrdi'um Is following the course of the
odium Iheologicum. May Its departure be as speedy.
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[No. 346
In referring to the purchase of hospital supplies he mentioned a method that has given splendid results :
A very obvious form of cooperation is for all the hospitals of
the city to adopt a common standard of ordinary every-day supplies and to arrange for their purchase through a common purchasing agent.
In the city of New York recently also an attempt has been
made with very gratifying success to establish a hospital bureau,
which is a central supply bureau under a purchasing agent, whose
duty it is to make contracts for gauzes, cottons, surgical instruments, rubber goods, furniture, fixtures, bedding, blankets, linen
and the like. These supplies are purchased in large quantities
according to a definite standard of excellence and at the lowest
market prices. The saving of expense in the cost of supplies is
considerable, but the saving to the hospitals in the payment of
salaries to the officers to purchase is probably equally great. The
same is true of breadstuffs, fuel, machinery, etc. Every department of the New York hospitals has profited by the central bureau.
Hospital officers often do good in secret and the community
at large does not appreciate how much is done by the unpaid and
unselfish men and women who are managing our great hospitals.
The good work they do should be better known and this can only
be known by a wide publication of their work. They should not
put their candle under a bushel, but on a candlestick, that all
may see and cooperate in helping on their good work. There are
hundreds of men and women who long to do good, but who need
to be set at work. Tell the public what you are doing and do
not hesitate to ask for substantial support.
At the graduating exercises of the Nurses' Training School
of The Johns Hopkins Hospital on May 19, 1910, Dr. Hurd
gave a delightful address on " Florence Nightingale — a Force
in Medicine." He said :
I desire rather to speak of her career as a constructive philanthropist, as a sanitarian and as an organizer of nursing service
in city and country, of her statesmanlike grasp of the problems
of army nursing and of the influence of her life work upon the
medicine and surgery of the past half century.
In the course of his address he refers to the visits the late
Francis T. King, the late Mrs. Eobb, and Miss Nutting had
with Miss Nightingale. Dr. Hurd's address was most interesting from beginning to end. I shall quote a few paragraphs.
It is my task this afternoon to tell you in what manner she
has influenced the wonderful progress of medicine during the past
50 years.
1. First, and probably to a larger degree, she has wrought for
medical progress through her reform in nursing. She found it
an occupation and has made it a calling. From the very beginning of her career she insisted that any woman who engaged in
nursing should qualify herself as thoroughly for it as a man qualifies himself for any calling in which he expects to succeed. She
believed that the object of training was to teach not only what
was to be done, but how to do it. The physician or surgeon should
order whatever needs to be done for the patient's care, but the
training of the nurse should teach her how to do it to his order.
Training, also, should teach the symptoms of disease, so that the
nurse may know what certain symptoms indicate about any disease and whether the patient is worse or better when the symjptoms change. Telling the nurse what to do is not enough and
cannot be enough to make her work perfect.
2. In all her writings Miss Nightingale has constantly dwelt
upon the value of sanitation and obedience to the laws of health.
She speaks with endless iteration of the need of pure air, pure
water, efficient drainage, perfect cleanliness and sun-light in the
sick room
Her books in fact have been an immense influence in promoting the sanitation of the home and of the public and private
hospital. They furnished principles for the guidance of those
who would work out their own plans, when principles had once
been enunciated and detailed and specific plans for those to follow, who cannot plan for themselves. Her suggestions and directions for the care of patients in their own homes are invaluable
and have never been equaled by any other writer. She cries
aloud and spares not for good sanitation and for the care of the
patient. She may not always be in accord with present theories
of the bacterial origin of many diseases and may err in ascribing
measles and other infectious diseases to a lack of sanitation, but
her main thesis that bad air and all dirt are dangerous is unassailable
It may be called to mind that at this hospital its founder,
Johns Hopkins, made provision equally for the care of the sick,
the instruction of medical students and the training of nurses,
each duty being equally obligatory
3. One of Florence Nightingale's most important contributions
to medical progress is to be found in her " Notes on Matters
Affecting the Health Efficiency and Hospital Administration of
the British Army, Founded Chiefly on Experiences of the Late
War." This work in my opinion constitutes one of the most valuable contributions ever made to hospital organization and administration in time of war. Had the conclusions which she reached
been heeded in the Civil War in America or in the Boer War
in South Africa or in the Spanish-American War, hundreds of
thousands of lives might have been saved and millions of people
might not have mourned over a useless and needless sacriflce of
the flower of their young men. Her ability to analyze dry statistics and army returns and her rare power to draw correct conclusions from them seems remarkable.
Probably one of the most interesting articles that Dr. Hurd
ever penned was entitled " The Site of the Johns Hopkins
Hospital." This paper was read at The Johns Hopkins Hospital Historical Club in December, 1910, and published in the
Johns Hopkins Nurses Alumna Magazine, April, 1911.
A plat of the site of The Johns Hopkins Hospital which was
prepared to facilitate the sale of the property to the late Johns
Hopkins has recently come to light among the records of the
hospital and an examination of the survey has suggested to me
that it will be interesting to all persons connected with the hospital to see it and to learn something of its previous history.
The site of the hospital has been used for hospital purposes
for somewhat over 100 years. A general hospital was established
on this site in 1797 or in the early part of 1798. In an old
report it is spoken of as a beautiful site upon a hill, about a
mile from the city of Baltimore. When 1 came here 21 years
ago, the town extended but a little to the east of the hospital
and most of the neighboring streets have been opened since the
present site was selected.
Dr. Hurd then sketches the early history of Baltimore in a
most fascinating way and refers to the epidemic of yellow
fever that invaded Baltimore. In 1808 the old hospital was
leased to a firm of physicians, Drs. Sm}i;h and Mackenzie. In
1834 it was used as a lunatic asylum, later called The Maryland Hospital for the Insane.
From Dr. Hurd's paper we learn that at one time the town
of Joppa on the Gunpowder Eiver was larger than Baltimore
and that from this town there was a brisk trade in tobacco,
many ships sailing from Joppa to England. The old Joppa
December, 1919J
363
Road ran from Joppa through Baltimore to Auuapolis. It
crossed the present hospital ground a few feet north of the
present administration t)uilding. A house that faced on the
Joppa Road existed until a few weeks ago (June, 1919) and its
front foundation can still be seen on the south side of Monument Street between Bond and Caroline streets. It was
located direc'tly behind the moving picture parlor frequented
b)' colored people. This building was clearly visible from
Monument Street when the picture parlor was beijig constructed. Judging from the front of the house the Joppa
Road crossed the present Monument Street, going northward
and westward between Bond and Caroline streets. In 1836
land was bought bv the hospital on the north of tlie Joppa
Road and this once busy main thoroughfare was closed.
Johns Hopkins died the day before Christmas, 1S73. and early
In the following February the trustees organized for the first
time as a board and arranged to take over what property was
ready for them They made an effort to get competitive
plans, but finally gave it up and Dr. J. S. Billings, who is now
at the head of the New York Public Library, went abroad with
a set of plans which he submitted to all persons who were skilled
In hospital construction. In 1874 the original buildings had
been torn down, but it was not until 1S76 that Dr. Billings returned with his plans
The buildings were begun in 1877, but were erected no faster
than the trustees had the money to pay for them. They built
them wholly out of income and when money was not available
to continue the work they ceased building operations until more
money came Into the treasury. The result was a delay of full
12 years before the buildings were completed. The trustees were
bitterly attacked by the newspapers, especially in the columns
where the letters of the people appear, but they went on in their
own way and when the buildings were completed and opened in
1889, they had been constructed wholly out of income and the
capital fund of the hospital had been increased more than $100.000 during the process of building. Many hospitals are built
after a different plan and must contend with poverty and debt
for many years. The trustees of The Johns Hopkins Hospital
were more sensible. They knew that the hosi)ital was to last
for a long time and that there was no reason why they should
cripple It for all time In order that It might be opened a few
years sooner.
Dr. Ilurd then gave a short account of Johns Hopkins's life.
Accompanying the article is a picture of the old Maryland
Hospital ; the real estate plat of the present hospital area
showing the position of the original Maryland Hosjiital on
this ground and the location of the Joppa Road. The last
picture shows the site of the present liospital — a broad fence
around it, a tent on the site, and many men and horses, ready
to begin the excavation for the foundation of Tlie Joims
Hopkins Hospital. Every one interested in the institution
will be delighted witli Dr. llurd's article.
DR. IirRD. SKCRHTARY OF TTIK BO.\RI) OF
TRF.STFKS OF TIIF JOHNS
IIOPKIXS HOSPITAL
Shortly after Dr. Hurd relinquished his duties as su|)erin
tendent of the hosjiital lie moved "across town" to 1023
St Paul Street where he has since resided. His secretarial
duties have occupied much of his time, but he has nevertheless
always somehow made time for his literary work. The first
article from his pen after he became secretary was " Early
Days of The Jolms Hojikins Hospital and Medical School."
\ perusal of this splendid historical sketch gives one a graphic
jncture of the hospital in its formative days. To one who was
on the scene in those delightful days it brings back priceless
memories. In order that the reader may recall some of the
milestones I will quote sections of this sketch :
The late Johns Hopkins procured an act of incorporation of
his future hospital from the Maryland Legislature in 1867 and
named 12 able men, nearly all of them intimate and trusted
friends or relatives, to act as incorporators and trustees. Hoyond
deeding to this Board of Trustees a site for the institution,
which consisted of the buildings and grounds of the old Maryland Hospital for the Insane, founded in 1797, he had taken no
further steps towards Its erection at the time of his death in
December, 1873 The actual work of construction did not
begin until 1877, and the hospital was not opened until 1889.
The medical school, for wliich Mr. Hopkins made provision in
his will, when he made his hoquost to the university, was not
opened until 1893, 20 years subsequent to his death. These
delays and disappointments were due to financial difficulties,
for which the trustees of the university were in no way responsible
In August, 1889, when I came to Baltimore to assume charge
of the hospital as superintendent, I found four wards In commission, ri;.. a pay ward for men and women, two public wards
tor men and a public ward for women. An outpatient department liad also been opened under the charge of Dr. Halsted.
The pathological laboratory, under the charge of Dr. Welch with
a corps of assistants, had been operated as a branch of tlio university since 1886. although recently under the joint control of
the hospital and the university, owing to the financial difficulties
wliich hampered the university at that time.
Dr. W. H. Welch was in the full tide of his brilliant career as
a teacher, and had attracted to Baltimore such men as the late
Christian A. Herter and W. S. Halsted. of New York, W. T. Councilman, now of Harvard, A. C. Abbott now of the University of
Pennsylvania, F. P. Mall, later at Clark University and the University of Chicago, and many others of equal prominence, who
were all deeply engaged in medical research. Possessing encyclopedic knowledge, unusual geniality and largemindedness in his
relations with other men, and the gift of exposition, so essential
to the true teacher, he has been an active factor In the university
and hospital for many years. He is above all an investigator
with a judicial cast of mind and with the ability to stimulate
his associates and students to productive work, and the greater
ability to exercise a wise control over them.
Dr. W. S. Halsted was at the head of the surgical work of the
infant hospital which he had organized in accordance with the
newer teachings of Lord Lister, along the line of a better technique based upon the teachings of bacteriology. He possesses
the faculty of constructive work not alone in the principles of
surgery, but also in the details and minutla? of surgical technique.
He Is eminently thorough in all that he undertakes to do and
whatever principles of surgery lie has established have been
firmly founded upon experience as a surgeon, diligence as an
Investigator and experimental studies upon the lower animals.
He was then beginning to develop wliat was to become during
the next 20 years a school of surgery, not only In what was
accomplished, but also in the influence which he exerted upon
new men and the training which they received.
Dr. William Osier h.ul lately come from Philadelphia aa
physician-ln-chief of the hospital and had already attracted mucli
364
[No. 346
attention by reason of his unique personality, his versatility In
medicine and his literary facility. He was a master of English,
deeply versed in the history of medicine, an expert pathologist,
a well-trained diagnostician, filled with knowledge of practical
medicine, and a remarkable clinical teacher. He had unwearied
industry and a wonderful ability to utilize his gifts to accomplish beneficial results for medical science and for the world.
His call to Oxford in 1905 was a serious blow to the hospital.
It is remarkable that three such men as Welch, Halsted and
Osier should have been found to launch the hospital on its successful career, each possessing different powers and yet all
working harmoniously to supplement the activities of each other.
In October Dr. H. A. Kelly, came from Philadelphia to assume
his duties as gynecologist-in-chief of the hospital, and established
a public and private ward for surgical diseases of women. He
was and is a brilliant operator whose mechanical deftness and
manual skill have been the admiration, envy and despair of all
who have followed his work in the operating room. His ability
to devise new operations and to meet emergencies in surgery is
phenomenal. In addition to an extensive surgical work he early
became interested in the preparation of surgical books which
were clearly written and beautifully illustrated by the best medical artists procurable in this country or Europe. His interest in
art as applied to medicine and surgery has been an Important
contribution to the profession and has influenced widely medical
literature in America. Equally with Osier, Welch and Halsted,
he has trained students to do excellent work as operators and
teachers throughout the country.
All of these leaders were young men. the eldest not being more
than 40 years of age and many of them much younger. Gray
hairs thus far have not adorned the heads of most of those who
were interested in the development of the hospital, although it
must be acknowledged that some might have grown gray if they
had retained their original covering. All were wisely Interested
in the public welfare and used their influence in the city, state
and country at large to improve sanitation, to give better care
to the poor, earlier help to the tuberculous and to institute
healthier conditions of living eenerally
In the Journal of the American Medical Association, 1912,
Vol. lix, p. 1677, Dr. Hurd published a paper on "The
Proper Division of the Services of the Hospital."
In 1912 he was president of the fourteenth annual meeting
of the American Hospital Association. He took for his theme
on this occasion " Hospital Problems." This address appeared
in the International Hospital Record for that year.
In the Bulletin of the Medical and Chirurgical Faculty of
Maryland for 1912-3 he published an interesting paper entitled " Extracts from the Laws of Maryland and Virginia
Regarding the Early Care of the Insane."
Dr. Hurd's paper " Three-Quarters of a Century of Institutional Care of the Insane in the United States " appeared in
the American Journal of Insanity, 1912-3, Vol. Ixix, p. 469.
He divided the care of the insane during this period into four
stages :
1. The period of neglect.
2. The era of awakening.
3. The period of state care of the insane.
4. The period of scientific care.
After considering each of these stages in detail he took up :
Laws for commitment of the insane in every state ; the criminal
insane ; detention hospitals ; hospitals for the chronic insane ;
after-care of the insane; architectural changes and improve
ments ; scientific work ; biographies, et<:'. The article is a very
instructive one even for those who know little about psychiatry.
In the Modern Hospital for 1913 we find two articles from
Dr. Hurd's pen, " The Hospital as a Factor in Modern
Society " and " Hospitals and the Eeform of Medical Teaching."
During the year 1914 Dr. Hurd contributed eight papers to
the literature, " Some of the Writings of the Late Eugene
Fauntleroy Cordell " ; " Relation of the General Hospital to
the Training School for Nurses"; "Hospital Medical Statistics " ; " The Small Hospital a Factor in Medical Education"; "Mental Cases in General Hospitals"; "The
Human Side of Florence Nightingale " ; " Rupert Norton " ;
" State Registration of Nurses."
Dr. Cordell was the medical historian of the University of
Maryland and had published a most valuable history of medicine in Maryland. His book is a very interesting one and will
long remain the source of information relative to medical
events in this state.
Dr. Rupert Norton had been associated wUh Dr. Hurd for
several years. He remained assistant superintendent when
Dr. Winford H. Smith succeeded Dr. Hurd. In 1914
Dr. Norton developed typhoid fever and died.
Dr. Hurd in his article paid a well-deserved tribute to his
luimer associate.
A reference to Dr. Hurd's bibliography shows that he published no less tlian eight papers in 1915. Among them were
" The Early Years of The Johns Hopkins Hospital " ; " FortyFive Years Ago and Now "; " The Treatment of Mental Cases
in General Hospitals " ; " The General Government of State
Hospitals."
In 1916 Dr. Hurd in addition to a tremendous amount of
editorial work he had tmder way published sis papers. They
were " Some Sources of Friction in the Management of Hospitals"; "Another Source of Friction in Hospital Administration"; "Who Shall Manage the Training School for
Nurses?"; "The Advantages of the Budget System";
" Nathan Smith, Nathan R. Smith, and Alan P. Smith — a
Medical Family "; " Need of Segregation of Imbecile Women."
On March 12, 1917, Dr. Hurd read a paper on " Johns
Hopkins and Some of His Contemporaries " before the Historical Club. This was published in the July number of the
Bulletin for the same year. In his introductory remarks
Dr. Hurd says :
The primary object of our Historical Club, when it was founded,
was the study of medical history. To-night I have thought it
wise to speak of the life of one who was not directly connected
with the history of medicine, but who, because of the influence
which the university and hospital he established have had upon
medical education in this country, seems closely allied to medicine. I have also an additional reason for speaking briefly of his
personal history before this club, because as the years pass I find
that the career of Johns Hopkins becomes less familiar to the
present generation, and there is danger that he may become a
mythical personality. This is my reason for speaking of his
origin and personal characteristics and giving some account of his
career in Baltimore. I also wish to speak of his personal interest
THE JOHNS HOPKINS HOSPITAL BULLETIN. DECEMBER. 1919
PLATE XLIII
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December, 1919]
365
in the hospital and of the men he selected to carry out the
enterprises.
Dr. llurd then briefly sketched the life of the founder of
The Johns Hopkins Hospital and also gave a short account of
the original trustees of the hospital.
With a record of so much work done after resigning the
superintendency the reader will naturally ask why Dr. Hurd
did not remain at the helm. Physically, mentally and in every
way he was still in his heyday, but he felt that he had borne
the heat of the day long enough and that the running of the
hospital should now be placed in younger hands. One of the
trustees of the hospital who spent several weeks traveling with
Dr. Hurd some years after he had retired from the superintendency was so much surprised at his agility that he turned
to me and said, " I have never seen a man who can jump out
of bed, ."ay his prayers, shave and dress as quickly as Dr. Hurd
does, and he does not in any way curtail the length of his
prayers."
BOOKS WRITTEN BY DR. HURD
HospiT.\Ls, Dispensaries and Nursing
Edited hy John S. Billings, M. D., and Henry M. Hurd, M. D.
The International Congress of Charities, Correction and
Philanthropy was held in Chicago, June 12 to 17, 1893. Section 3 was devoted to the hospital care of the sick, training of
nurses, dispensary work and first aid to the injured. Dr. John
S. Billings was chairman and Dr. Henry M. Hurd secretary
of this section ; Miss Isabel A. Hampton was chairman of the
subsection on Nursing.
Many valuable papers were read in the section and it was
clearly evident that the addresses should be published, but the
necessary funds were lacking. Dr. Billings and Dr. Hurd
came to the rescue and at their own expense published and also
edited the large volume of over 700 pages. This splendid
publication is of much interest to Baltimorcans not only on
account of the many valuable papers, but also because Baltimoreans contributed in no small measure to the success of the
Congress.
Dr. Billings' chairmanship address was entitled " The Relations of Hospitals to Public Health." Miss Hampton took for
her theme " Educational Standards for Nurses," and Miss
L. L. Dock spoke on "The Relation of Training Schools to
Hospitals."
Dr. Hurd's address was on " The Relation of Hospitals to
Medical P^ducation." Mr. Henry C. Burdett, of London,
England, the Honorary Chairman of the Section, in discussing
Dr. Hurd's paper said :
I should like to say that I thlnlt it Is very Important that
wc should have a paper of this kind read this session. It is
important because it clearly lava down and hrings out clearly to
the non-tochnical mind the reason why the cost of administering hospitals tends steadily to increase, and what those who give
to hospitals really get back in return for their money. A man
is often amazed by the demands which are constantly made
for more and more money, especially for bulldlnKs, and I do
think that Dr. Hurd's paper will fulfill a very useful purpose,
and I hope it will be printed and widely circulated among
hospitals
Miss M. A. Boland, the dietitian of The Johns Hopkins
Hospital, gave an interesting address on " Hospital Dietaries."
Dr. Hurd gave a second paper " Description of The John.s
Hopkins Hospital." After briefly detailing the gift of Johns
Hopkins and speaking of the plans and building of the hospital, he described the institution in detail, giving numerous
illustrations and plans. The picture that will appeal most to
the older members of the faculty is the one of the isolation
ward, with the old boardwalk extending from the northern
exit of this building over to the steps of the pathological
building. One can even now vividly see those going from the
hospital to the laboratory in rainy weather, turning up their
coat collars and sprinting rapidly over to the i)athological
department.
The Congi-ess was honored by a paper " Sick Nursing and
Hcaltli Nursing " by Florence Nightingale, and by an address
by our own Cardinal Gibbons on " Work Done by Religious
Communities Devoted to the Relief of the Sick."
Too much credit cannot be given to Dr. Billings and to
Dr. Hurd not only for editing, but also for bearing the cost of
this volume which contiiins valuable articles from sjiecialists
in all parts of the world.
SVGGESTIONS TO HOSPITAL VISITORS
In 1895 Dr. John S. Billings and Dr. Hurd brought out a
small book entitled " Suggestions to Hospital and Asylum
Visitors."' The need for such a book was very evident and
S. Weir Mitchell prevailed upon these well-known hospital
authorities to "WTite it. Dr. Mitchell's introduction is so much
to the point that I quote it in full :
For several years I have been urging upon Professor Billings
the need for a small manual suited to the wants of hospital visitors. I have many times been asked by laymen who have to
manage eleemosynary institutions where they could learn liow
critically to inspect them with a reasonable chance of seeing
what is wrong and learning how to value what is praiseworthy.
It is useless to point the ln(iulrer to the greater works on hygiene.
These presuppose such knowledge as few possess who are not
educated physicians. There is needed a condensed statement of
ichat to see In a hospital and how to see it.
Every new domain of observation requires a peculiar ami individualized training. The acute microscoplst might be a dull
observer of the facts of disease which we call symptoms: the
clever artist may be a sad failure when called upon to see with
critical eyes the phenomena of the laboratory. How, then, can
we expect that quite untrained people should of a sudden become
useful observers in a field as new to them as Is a hospital?
Boards of managers are chosen out of the every-day life of
commerce and professions other than that of medicine. The
members are presumed to study results into which enter questions of cooking, dietetics, ventilation, medical and surgical
clpanllncsa, which Involves disinfection, and many other matters
exacting careful attention, and only to be thoroughly understood
after years of training. This little manual is meant to assist
untrained observers, yet even the most expert manager of a hospital or the ablest medical observer ought to find In it valuable
bints. This guide to the hospital visitor 1 have asked leave to
366
pSTo. 346
introduce. It lias cost an amount of care and thought out of
proportion to its size. While in manuscript it was critically
read by Professors J. M. DaCosta, J. William White, and myself,
and certain changes or additions were suggested. Finally, Dr.
Hurd, the accomplished director of The Johns Hopkins Hospital,
was kind enough to associate himself with Professor Billings
and to take the utmost interest in the work. Out of their joint
labor and the criticism of able physicians and nurses has come
at last the helpful little book which originated in my suggestion, and which I confidently commend to all who, being managers, trustees, or in any way connected with hospital work, are
not +++++
CONTENTSed to assume an official name and remain ignorant of
how honestly to fulfill the duties which should go with it.
S. Weie Mitchell, M. D.
It is doubtful if any small book of 43 pages was ever so
crammed full of iuformation and good advice. It should be
reprinted and be read by every hospital trustee and by all in
any way interested in hospitals. A perusal of its pages will
give the reader a very clear idea of the manifold details of
hospital management, will enable him to render valuable
advice without unjust criticism and will make the path of the
superintendent or director of the Jiospital a much smoother
one. In short, it will promote the maximum efficiency with
friction reduced to the minimum.
The copy of the book that fell into my hands contains a few
notes in Dr. Kurd's hand writing. These I venture to reproduce here without his knowledge or permission :
SUGGESTIONS FOR THE ORGANIZATION OF AUXILIARY BOARDS
OF VISITORS
1. Composed of men and women who are interested in humanitarian and philanthropic work.
2. They should be absolutely free from any partisan or political bias.
3. They should feel at liberty to make suggestions as to the
policy of the hospital, as to purchasing, administrative details,
etc. They should be +++++
CONTENTSed to present their \iews to the
governing body with whom must rest the responsibility of the
final decision.
4. They should seek to assist in all social service matters. The
officers of a hospital, as a rule, are not widely acquainted with
the possibilities of social help in the community or the sources
of aid. The Board of Visitors can do incalculable good by bringing the hospital into relation with all helping agencies.
5. Boards of Visitors should never lose sight of the fact that
they are privileged to assist in a most important public service.
The increasing wealth of the country and the growth of a leisure
class can only do harm if these become a source of personal
pleasure to those who have leisure and abundant means. If.
however, they use their good fortune for the public good, new
aspirations are aroused and new and most satisfying channels of
activity are found which dignify and ennoble the individual and
bless the community. Personal service to hospitals and similar
charities thus become not only a duty but a pleasure, and life is
enlarged and made purposeful by the performance of good work.
The Institutional Caee of the Insane in the United
States and Canada
At the 66th annual meeting of the American MedicoPsychological Association held in Washington, D. C, in May,
1910, Dr. Hurd gave an address entitled " A History of Institutional Care of the Insane in the United States and Canada."
This paper was published in the American Journal of Insanity,
1910-11, Vol. Ixvii, p. 587. In the course of his address
Dr. Hurd said :
The movement to write a history of the association and its
work had its origin at the Baltimore meeting in 1895, when Dr.
Powell, of Georgia, presented a very interesting outline of the
" rise and progress of a vast system of charities in the 15 commonwealths of the South," with detailed accounts of institutions
in Virginia, North Carolina and Georgia. It was evident from
the interest which was then excited that much had been done by
similar foundations in all the states of the Union, and from this
conviction grew the original resolutions subsequently presented
by Dr. J. W. Babcock, of Columbia, S. C. These resolutions were
considered and favorably acted upon, and a committee was appointed, but nothing seems to have come of it, although progress
has been reported from time to time, and an effort, has been
made to stir up a general sentiment in favor of completing the
work. For this and other reasons, although not aware of any
special personal fitness for the work, I did not feel at liberty to
decline the appointment made at the Cincinnati meeting, and
of which, by the way, I learned for the first time in June last at
Atlantic City. Since that time I have made an intermittent effort
to organize the work and to collect such material as I could find.
The full committee consisted of Dr. Henry M. Hurd, chairman; Dr. William F. Drewry, for the South; Dr. Richard
Dewey, for the West; Dr. Charles W. Pilgrim, for the middle
states ; Dr. G. Alder Blumer, for New England ; Dr. T. J. W.
Burgess, for British America.
The object of the present paper is to give some account of
the progress of the work and to say what needs to be done. I
hope, also, to stir up in the minds of the members of the association a feeling of responsibility for it, so that there may be cooperation in gathering the material and preparing it for publication
at the proper time. The difficulties in the task are very great.
Those who have been interested in the construction of the institutions for the insane in the United States have been largely
isolated workers, and their records are. consequently, widely
scattered throughout the different states of the Union
In his concluding paragraph Dr. Hurd says :
I have taken the liberty to embody the substance of this
paper in a resolution which I now offer to ascertain the will of
the association in the matter of the publication of the book. 1
shall be very glad to have it modified, revised, or in any way
changed so as to bring out more completely the wishes of the
association in this matter. I am not wedded to any theory of
publication, or any form of work. I am anxious that the work go
on with as much rapidity as possible. It is equally important,
however, that the work be done thoroughly, so that in future all
may know who in the past contributed to the success of an important philanthropic achievement.
Volumes I, II and III of this stupendous work appeared
from The Johns Hopkins Press in 1916 and Volume IV in
1917. These four volumes contain in all 2926 pages.
A glance at the preface to Volume I gives the reader a clear
idea of the tremendous amoimt of labor entailed in the preparation of these volumes. After taking up nearly three pages of
the preface in thanking various men for their cordial cooperation in furnishing data the editor says :
The obligations of the committee to the individual superintendents of nearly 200 institutions in the United States and
Canada are very great; in fact, without their cooperation it would
December, 1010]
367
hare been Impracticable to prepare any adequate history of the
movements in the various states and provinces.
It is evident from a careful study of all the material which
has come into the hands of the committee that a gradual evolution has occurred in the care of the insane in America during
the past halt-century, which bids fair to change materially the
discouraging views as to the hopelessness of their cure which
have prevailed for many years in the United States and Canada.
The movement towards the prompt treatment of curable cases
without the formality of legal commitment and under the same
conditions as in admission to a hospital for general bodily disease,
gives every hope that at an early day cases of recent attack may
be received everywhere promptly, and that greatly increased
numbers can be cured. Cases of a chronic nature are also now
much more satisfactorily dealt with in institutions on the cottage plan, with outlying colonies for the employment of patients,
and have a correspondingly better opportunity to attain selfsupport. These movements promise to make material changes
in future methods of caring for the insane.
Volume I i.-i historical in character. It gives a clear account
of the Association of Medical Superintendents of American
Institutions for the Insane from 1844 to 1803 and of the
American Medico-Psychological Association from 1803 to
1913. It then describes what the American Journal of Insanity has accomplished. Volume I was written by Dr. Hurd
and the reader can best obtain an idea of the wide range of
subjects considered in tiiis volume by glanriiis throuL''h its list.-;
of contents
I. Introduction 5
II. The Association of Medical Superintendents of American Institutions for the Insane, 18441893 11
III. The .\mcrican Medico-Psychological Association,
1893-191.3 53
IV. The American Journal of Insanity 75
Chapter II
I. Early and Colonial Care of the Insane 81
II. The Era of Awakening 93
Chapter III
I. Dorothea Lynde Dix and Her Work 101
Chapter IV
1. Evolution of Institutional Care in the United States.. 139
II. County Care of the Insane 144
III. Chronic and Incurable Insane 147
IV. The Colony System 156
V. State Care 163
VI. The Wisconsin System of County ("are 168
ClfAPTF;R V
I. Evolution of the Administration of Hospitals 179
II. Present Government of Institutions for the Insane .... 183
III. Methods of Investigation of Public Institutions 196
IV. Development of Hospital Architecture 204
Chapter VI
I. The Propositions 217
II. Reforms in Caring for the Insane 223
III. Medical Treatment of the Insane 230
IV. Non-Medical Treatment of the Insane 234
V. Employment for the Insane 242
VI. Asylum Periodicals 250
VII. Individual Treatment 254
VIII. Experimental Removals 256
IX. Origin of the Psychopathic Hospital in the United
States 258
X State Psychopathic Hospital at the ITnlversity of
Michigan 266
XI. Boston Psychopathic Hospital 276
XII. Research Work in Hospitals 281
Chapter VII
I. Training Schools for Nurses and the First School in
McLean Hospital 289
II. First Training Scliool for Attendants at the Buffalo
State Hospital (Asylum), 1883-1886 301
Chapter VIII
I. Private Care of the Insane 313
Chapter IX
I. Growth of the Law of Insanity 321
II. Commitment of the Insane 331
III. Conditions of Discharge 338
IV. Admission of Voluntary Patients 344
V. Care of the Criminal Insane 348
Chapter X
I. Immigration and the Care of the Insane 355
II. The Alien-Born in Relation to the Cost of State Care. . 362
Chapter XI
I. Insanity among the Negroes 371
II. Insanity among the North American Indians 381
III. Insanity among Indians in South Dakota 386
IV. The Chinese and Japanese Insane in the United
States 393
Chapter XII
I. Institutional Population 399
II. Census of the Insane 411
III. Feeble-Mindod in Institutions 421
Chapter XIII
I. Laws for the Commitment of tlie Insane in Canada. . . 427
II. Care of the Insane in Canada Previous to the Establishment of Provincial Institutions 446
III. Establishment of Provincial Institutions 454
IV. System of Care In the Provinces of Canada, and Gov
vernment and Inspection of Provincial Institutions. 458
V. The Contract System In the Province of Quebec 467
VI. Immigration and the Care of tlie Insane in Canada. . . . 472
VII. Census of the Insane In Canada 478
VIII. The Chinese and Japanese in Institutions in British
Columbia between the Years 1871 and 1913 480
IX. Dorothea L. Dix and Canadian Institutions 481
Volumes II and III and part of Volume IV are devoted to a
detailed description of tlie institutions for the care of the
insane in the United States and Canada. Volume HI also
includes the institutions in Hawaii and in the Philipi)incs.
Pictures of many of tlie institutions are given and often plan.s
of the buildings accompany them. In each article is a detniled
list of the medical personnel of the institution from its beginning to the time the volume appeared, so that the previous
activities of any man who has devoted his life to psychiatry
can be readily followed.
368
[No. 346
The latter half of Volume IV is devoted to biographies of
prominent psychiatrists in the United States and Canada.
The picture in Volume I that will interest Baltimoreans
most is that of the Maryland Hospital for the Insane as it
appeared in 1833. It faces on the old Joppa Road and in the
background is the present Church Home and Infirmary, then
the Washington Medical School. The site of the Old Maryland Hospital for the Insane is, as has been mentioned elsewhere, now occupied by The Johns Hopkins Hospital.
In Volume II is a splendid plate of the Sheppard and Enoch
Pratt Hospital. The frontispiece of Volume IV is a reproduction of a portrait of Miss Dorothea L. Dix, to whose pioneer
labors American psychiatry owes so much.
These volumes have brought forth much praise. Scien-ce
for July 28, 1916, in reviewing Volume I, which was written
in its entirety by Dr. Hurd, says :
This is one of the few worlcs in the English language in which
the history of a separate branch of medicine has been exhaustively treated Tlie present volume, although it professes
to deal only with the general history of institutional care of
the insane on this continent, is, in reality, an exhaustive history
of American psychiatry in all its phases, and is therefore likely
to remain the authoritative work on the subject for an indefinite
period
Dr. Hurd modestly regards this work as a source-book for the
historians of the future but it is undoubtedly a permanent history which may be extended, but will hardly be duplicated. The
chapters are complete in themselves, the book is well illustrated,
and the style is charming in its simplicity, sobriety and its traces
of delicate humor.
The American Journal of Insanity for October, 1916, in the
course of the review of Volumes I and II, says :
Too much praise cannot be given to the manner in which the
task imposed upon this Editorial Committee has been carried
out, and as one of the members of the committee. Dr. Burgess,
said at the meeting in New Orleans in April last, while all the
committee liave tried to help, the burden of the work has been
on Dr. Kurd's shoulders.
The Nation on February 8, 1917, says:
No survey of the treatment of American insane during the
last two centuries has before appeared; it is pleasant to find the
difficult task so well executed as in this volume.
The British Medical Journal for December 8, 1917, in
referring to the four volumes said :
Dr. Hurd is to be congratulated upon the success with which
he has carried out the collection and colligation of the numerous
interesting records contained in these volumes. Naturally they
will appeal most strongly to readers across the Atlantic; but
in their record and analysis of success and failure in attacking
a problem of great importance in all civilized communities —
namely, the care of the insane — they should find many readers
throughout the world.
In another foreign review we find the following tribute :
This monumental work, is, in the main, the product of the
veteran Dr. Hurd, emeritus professor of psychiatry in The Johns
Hopkins University, and formerly medical superintendent of the
Pontlac State Hospital, who is well known on this side of the
Atlantic as the most distinguished of American alienists. Dr. Hurd
has retired from active practice, but his abundant energy would
not suffer him to be idle, and he has employed his leisure wisely
and well In producing this great work, which will be a classic
from the day of publication.
It must be remembered that during the immense amount of
labor entailed in the preparation of these volumes Dr. Hurd
had been greatly troubled with his eyes and it was only his
indomitable will that continually spurred him on to the completion of these labors that were a fitting climax to his many
successful years of hospital directorship.
SUMMARY *
Dr. Hurd in addition to his other editorial duties has been
one of the editors of the American Journal of Insanity since
1897 and of the Modern Hospital since 1913.
He is a member of the Association of American Physicians ;
of the American Academy of Medicine, and was its president
in 1896 ; of the American Medico-Psychological Association,
of this he was secretary from 1892 to 1897 and president in
1898-9, he also edited three volumes of its proceedings; of the
American Anthropological Association ; of the American Hospital Association and its president in 1912. He is also a member of the American Public Health Association.
In 1895 Dr. Hurd was given the degree of LL. D. by his
alma mater, the University of Michigan.
On September 16, 1874, Dr. Hurd married Miss Mary Doolittle, of Utica, N. Y. They had three children, a son and two
daughters. The son died in childhood.
Mrs. Hurd was always greatly interested in her husband's
labors and ever manifested the same cordial relation to the
hospital interns and to the senior staff that Dr. Hurd did. A
year or two after they left the hospital Mrs. Hurd's health
began to fail and her death on March 14, 1913, was keenly felt
by the host of friends of the family.
Miss Eleanor and Miss Anna Hurd are the constant companions of their father and it is a delight to see the manner
in which they watch over his welfare and literally force him
to conserve his unbotmded energy.
Dr. Hurd is a Presbyterian. He has shown the same fidelity .
to his church that he has ever manifested in his professional
duties.
From the preceding pages of this article the reader will see
from what an intellectually sturdy stock he came and few men
have had such a long medical ancestry. Step by step he rose
until he was not only the first superintendent of a large asylum
in Michigan, but also a dominant figure in that commonwealth.
His fame as an administrator was not confined to his own
locality, but was widely known. It was for this reason that he
was later called to Baltimore.
All through his career he has been a thoroughly consistent
and industrious psychiatrist. He has published many valuable papers dealing with the study and treatment of the insane,
has for years been one of the editors of the American Journal
of Insanity and less than three years ago edited a monumental
work of four volumes on " The Institutional Care of the Insane
* This article together with " Random Recollections " by Dr.
Hurd will be issued in book form from The Johns Hopkins Press
In a few weeks.
%
THE JOHNS HOPKINS HOSPITAL BULLETIN, DECEMBER, 1919
PLATE XLIV
Decembeb, 1919]
369
in the United States and Canada." As mentioned before he
wTote Volume I and edited Volumes II, III and IV.
For years he has been a most valuable membur of the ilaryland State Lunacy Commission. A foreign journal speaks of
Dr. Hurd as " The most distinguished of American alienists."
It is clearly evident that in psychiatry he has reached the top
rung of the ladder.
The trustees of The Johns Hopkins Hospital manifested
rare discernment when they selected Dr. Hurd to become the
first superintendent of the hospital. It fairly blossomed under
his wise generalship until its fame spread far beyond the confines of this continent — until it was known in every civilized
land.
The Johxs Hopkins Hospital Bulletin and the Hospital Reports under his able editorship added greatly to the
prestige of the institution. As an expert in hospital organization and in hospital management he is recognized as tlie
leader in America. His advice in hospital and nursing problems is continually sought. His is invariably the final word
on these subjects.
His writings on hospital organization, hospital management, medical education and nursing are numerous and most
valuable and he has ever aimed to publish historical records in
order that they may not be lost — in order that they may be
preserved for future generations. Whatever he has undertaken
he has finished.
A prominent publisher who has come in contact with him
nearly every week for at least 25 years said to me recently
" Dr. Hurd is the most practical and business-like physician
that I have ever met " — and he meets an unusually large number. It is undoubtedly this practical bent, coupled with rare
discernment, a broad knowledge of men and a wide knowledge
of psychiatry and medicine that has enabled him to accomplish
.'io much apparently with so little effort.
From time to time brilliant statesmen advanced in years
have been spoken of as " grand old men." Dr. Hurd is the
grand old hospital statesman of America. Early in his career
he wanted to become a surgeon in the navy, but was disqualified
on account of his frail phjsical make-up. He would have
undoubtedly made his mark in government service, but what
a loss the asylums and hospitals of this country would have
sustained, and how much psychiatry and the profession of
medicine in general would have missed had he successfully
passed the physical requirements for the navy !
His has been a life well spent — a life full of labor for his
fellow man. In a memorial tribute to the late Dr. William
Whitney Godding, Dr. Hurd unconsciously gave a most vivid
description of himself. " You felt instinctively that you had
to do with one who knew no guile or self-seeking, but who
api)reciatcd it to be his duty to place his powers of mind and
heart unreservedly at the disposal of his associates or his
fellow men." But Dr. Hurd is not gone, he is still with us,
actively engaged in writing the historj- of The Johns Hopkins
Hospital. That he may long be spared to browse in the
Henry M. Hurd Library, which my friend George K. McGaw
is building as a mark of ajipreciation and esteem to our mutual
friend, the first superintendent of The Johns Hopkins Hospital, is our earnest prayer.
THE LATE GEORGE KEEN McGAW
For several months ilr. McGaw had been failing in health,
and in June he went to his summer home at Buena Vista.
The erection of the Henry JI. Hurd library was uppermost
in his mind, and the last thing he did on the morning he left
for the mountains was to turn over to Judge Harlan additional funds for the building. He was particularly anxious
that Dr. Hurd should not only see, but also have the opportunity of often enjoying the library bearing his name. My
account of Dr. Kurd's manifold activities was accordingly
promptly undertaken and as soon as it was completed, early
in July, Judge Harlan and I spent a delightful day with
Mr. McGaw and his family in the mountains. For fully two
hours Mr. McGaw listened with great interest to the recital
of tlie many tilings his friend had accomplished and again
expressed himself as so happy that the library plans were well
under way. That was the last time I saw tlmt whole-souled
and true friend. He had a fairly comfortable summer. He
died suddenly on the morning of September 9, 1919.
Dr. Ilurd and Mr. McGaw had known one another for many
years, as they both were prominent members of the First Presbyterian Church and Mr. McGaw was also one of the Trustees
of The Johns Hopkins Hospital.
In March, 1911, Mr. McGaw suggested a trip Soutli and a
few days later Dr. Hurd, Air. AIcGaw and myself left for an
extended trip, visiting Pinehurst, Columbia, Savannah,
Jacksonville, Knights Key, Havana, Key West and Miami.
It was on this trip that the lasting and intimate companionship and friendship was cemented between these two splendid
men, and since that time they liave been together week in and
week out. It was this close companionsliip that revealed to
Mr. ilcGaw Dr. Hurd's wonderful breadth of character, and
that prompted him to plan this tribute to his friend — a tribute
that will not only be a constant reminder of the first superintendent of The Johns Hopkins Hospital, but that will also be
of inestimable value to the succeeding generations of students
in The Johns Hopkins Medical School.
Dr. Hurd's estimate of his departed friend rings so true
and is so beautifully expressed in a recent letter to me that I
cannot help reproducing it here.
Seal Hakbou, Me., Sept. 13, 1919.
Dear Cullen : Many tlianks for your telegrams and your
thoughtfulness in sending them. I iiave been greatly shocked
by the unexpected death of the i)est of friends and I know of
no one who may occupy the vacant place in just the same way.
He was so noble in his ])lans and modest in carrying them out,
so that his own work might be minimized. I always felt him
to be a rare man. We all of us ought to be better men for
having known him. I have written to Mrs. McGaw, but I feel
that I could not in any way tell her properly how much I loved
him
Sincerely,
Henry M. Hurd
370
[No. 346
BIBLIOGRAPHY OF HENRY MILLS HURD, M. D., LL. I).
PREPARED BY
MINNIE WRIGHT BLOGG
LIBBAEIAN, THE JOHNS HOPKINS HOSPITAL
Recent judicial decisions in Michigan relative to insanity. Am. J.
Insan., Utica, N. Y., 18S0-81, xxxvli, 23-35.
1882
A plea for systematic therapeutical, clinical and statistical study.
Read before the Association of Medical Superintendents of
American Institutions for the Insane, at the annual meeting
in Toronto, June, 1881. Am. J. Insan., Utica, N. Y., 1881-82,
xxxviii, 16-31.
Practical suggestions relative to the treatment of insanity. Physician & Surg., Ann Arbor, Mich., 1882, iv, 385-399.
1883
Future provision for the insane in Michigan, n. p., 1883. 9 p. 8°
The treatment of periodic insanity. Am. J. Insan., Utica, N. Y.
1882-83, xxxix, 174-180.
Ducking in asylums. A refutation (letter). Am. J. Insan., Utica
N. Y., 1882-83, xxxix, 506-507.
The hereditary influence of alcoholic indulgence upon the production of insanity. A paper read at a sanitary convention held
at Pontiac, Michigan, January 31 and February 1, 1883. Re
printed from a Supplement to the Annual Report of the Secretary of the State Board of Health of Michigan, for the year
1883. Physician & Surg., Ann Arbor, Mich., 1883, v, 49-57.
1884
The minor treatment of insane patients; summarv. Am. J. Insan.,
Utica, N. Y., 1883-84, xl, 205-209.
Paranoia. Am. J. Insan.
1886
Utica, N. Y., 1885-86, xlii, 473-483.
1887
The relation of general paresis and syphilitic insanity.
Insan., Utica, N. Y., 1886-87, xliii, 1-18.
The data of recovery from insanity.
1886-87, xliii, 243-255.
Am. J. Insan., Utica, N. Y.,
The colony system of Michigan.
1887, xiv, 215-220.
Proc. Nat. Confer. Char., Bost.,
Gastric, secretory and other crises in general paresis. Am. J.
Insan., Utica, N. Y., 1887-88, xliv, 60-65.
The religious delusions of the insane. Am. J. Insan., Utica, N. Y.,
1887-88, xliv, 471-487.
Also: Tr. ix. Internat. M. Cong., Wash., 1887, v. 253-263.
Hurd, H. M. & Christian, E. A. The ultimate results in a case of
exsection of the head and upper third of the humerus. Ann.
Surg., St. Louis, 1888, vii, 431-434.
Imbecility with insanity.
261-269.
1889
Am. J. Insan.,
1890
Utica, N. Y., 1888-89, xlv,
First report of the superintendent of The Johns Hopkins Hospital
from May 15, 1889, to January 31, 1890. Bait., 1890, The
Johns Hopkins Press. 47 p. 8°.
Also: Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 77-89.
A case of inebriety with insanity; with remarks. Am. J. Insan.,
Utica, N. Y., 1889-90, xlvi, 61-70.
The relation of the Training School for Nurses to The Johns Hopkins Hospital. Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 7-8.
Periodicitv in melancholia.
269-270.
Maryland M. J., Bait., 1890, xxiii,
Proc. Nat. Confer. Char., Bost.,
Report of committee on hospitals.
1890, xvii, 155-156.
The relation of the general hospital to the medical profession.
Proc. Nat. Confer. Char., Bost., 1890, xvii, 156-162.
1891
Second report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1891. Bait, 1891, The
Johns Hopkins Press. 76 p. 8°.
Also: Johns Hopkins Hosp. Bull., Bait., 1891, ii, 124-132.
Memoir of Richard Gundry, M. D. Tr. M. & Chir. Fac. Maryland,
Bait., 1891, 178-183.
1892
Third report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1892. Bait., The Johns
Hopkins Press. 63 p. S°.
Also: Johns Hopkins Hosp. Bull., Bait., 1892, Hi, 97-102.
Journal clubs. Am. J. Insan., Utica, N. Y., 1891-92, xlviii, 372-375.
Post-febrile insanity. Maryland M. J., Bait., 1892, xxvii, 661-666.
Also: Am. J. Insan., Utica, N. Y., 1892-93, xlix, 26-34.
Fourth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1893. Bait., 1893. The
Johns Hopkins Press. 69 p. 8°.
The relation of hospitals to medical education. Boston M. & S. J.,
1893, cxxix, 141-143.
1894
Fifth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1894. Bait., 1894. The
Johns Hopkins Press. 69 p. 8°.
Hurd, H. M. & Billings, J. S. eds. Hospitals, dispensaries and
nursing. Papers and discussions in the International Congress of Charities. Correction and Philanthropy, section iii,
Chicago, June 12-17, 1893. Bait., 1894, Johns Hopkins Press.
733 p. S".
Internat. Cong.
The relation of hospitals to medical education.
In : Hospitals, Dispensaries and Nursing. . . .
Char, [etc.], 1893, Bait. & Lond., 1894, 98-105.
Description of the Johns Hopkins Hospital, Baltimore, Md.
I7i: Hospitals, Dispensaries and Nursing. . . . Internat. Cong.
Char, [etc.], 1893, Bait. & Lond.. 1894, 429-443.
George Huntington Williams. The minutes of a commemorative
meeting held in the Johns Hopkins University, October 14,
1894. Baltimore, 13 p. 8°.
Some mental disorders of childhood and youth. Boston M. & S. J.,
1894, cxxxi, 281-285.
Also: Baltimore, 1895, Friedenwald Co., 16 p. 8°.
1895
Sixth report of the superintendent! of The Johns Hopkins Hospital
for the year ending January 31, 1895. Bait., 1895. The Johns
Hopkins Press. 74 p. 8°.
Hurd. H. M. & Billings. J. S. Suggestions to hospital and asylum
visitors. With an introduction by S. Weir Mitchell. Phila.,
1895. J. B. Lippincott Co., 48 p., 8°.
The alienists of the past half century. Proc. Am. Med. Psychol.
Ass., 1894, Utica, N. Y., 1895, i, 167-171.
1S96
Seventh report of the superinter^dent of The Johns Hopkins Hospital for the year ending January 31, 1896. Bait., 1896. The
Johns Hopkins Press. 66 p. 8°.
Decembeb, 1919]
371
The new .McLean Hospital. .-Vm. J. Insan., Chicago, lS9o-6. lii, 477502.
Laboratories and hospital work. Bull. Am. Acad. M., Easton, Pa.,
1895-6, ii, 483-495.
Paranoia. .Maryland M. J.. Bait., 1896, xxxv, 1-4.
Also: [Abst.] Virginia M. Semi-Month., Richmond. 1896-7, i, 263.
Eighth report of the superintendent of The Johns Hopkins Hospital for the .vear ending January 31, 1897. Bait., 1897. The
Johns Hopkins Press. 88 p. 8°.
Hospital organization and management Address before the Training School for Nurses of the University of Pennsylvania,
February 17. 1897. Univ. M. Mag., Phila.. 1896-7. ix. 4SS-500.
Kurd, H. M., Burr, C. B. & Wise, P. M. Report of the committee on
statistical tables, to the American Medico-Psychological Association. .\m. J. Insan., Chicago, 1896-7, liii, 105-116.
Hurd, H. M. & Chapin. J. B. Report on the hospitals of the District
of Columbia. To the Joint Select Committee to investigate
the charities and reformatory institutions in the District of
Columbia. Washington, 1897.
1898
Ninth report of the superintendent of The Johns Hopkins Hospital
for the year ending January 31, 1898. Bait., 1898. The Johns
Hopkins Press. 91 p. S".
The medical service of hospitals. Albany M. Ann., 1898. xix. 137142.
The non-medical treatment of epilepsy. (Proc. Johns Hopkins
Hosp. Med. Soc, November 7, 1898). Johns Hopkins Hosp.
Bull., Bait., 1898. ix, 296-297.
Also: .Maryland M. J., Bait., 1898-9, xl, 53.
1899
Tenth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1899. Bait., 1899. The
Johns Hopkins Press. 92 p. 8°.
Post-operative insanities and undetected tendencies to mental
disease. Am. J. Obst., N. Y., 1899, xxxix, 331-335.
Presidential address. The teaching of psychiatry. Delivered at
the annual meeting of the American Medico-Psychological
Association at New York. May 23, 1899. Proc. Am. Med.
Psychol., Ass., 1899, vi, 79-92.
Also: Johns Hopkins Hosp. Bull., Bait, 1899, x, 205-209.
.4/so.- Am. J. Insan., Bait., 1899-1900, Ivl, 217-230.
1900
Eleventh report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1900. Bait, 1900. The
Johns Hopkins Press. 114 p. 8°.
.Memorial addresses in honor of William Whitney Godding, M. D.,
LL. D. Delivered before the Medical Society of the District of
Columbia, June 7, 1899. Nat. M. Rev., Wash., 1899-1900, Ix,
374-377.
Hospitals, dispensaries and nursing. (American philanthropy of
the nineteenth century). Char. Rev., N. Y., 1900, x, 298-305;
317-331,
Hospital construction from a medical standpoint. Brickbuilder,
Bost., 1900, Ix. 248.
1901
Twelfth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1901. Bait, 1901. The
Johns Hopkins Press. 114 p. 8°.
Reception hospitals for cases of acute insanitv. Bull. Iowa Inst,
Des Moines. 1901. lii. 3S-40.
1902
Thirteen! ii report of ihr .superintendent of The Johns Hopkins
Hospital for the year ending January 31, 1902. Bait., 1902.
The Johns Hopkins Press. 118 p. S\
The educated nurse and her future work. Address delivered at
the graduating exercises of the Training School of the Garfield Hospital, Washington, D. C: and similarly at the Training School of the Methodist Episcopal Hospital, Brooklyn,
N. Y. Baltimore [1902], Friedenwald Co.. 14 p. »'.
Psychiatry in the twentieth century. Address at the formal opening of the new hospital building at Morris Plains. New Jersey,
November 20, 1901. Albany M. Ann., 1902, xxiii, 125136.
1903
Fourteenth report of the superintendent of The Johns Hopkins
Hospital for the year ending January 31, 1903. Bait., 1903.
The Johns Hopkins Press. 110 p. 8".
The future policy of Maryland in the care of her insane. Maryland
M. J., Bait., 1903. xlvi, 45-54.
The duty and responsibility of the X'niversity in medical education.
Science. N. Y. & Lancaster. Pa., 1903, n. s., xviii, 65-76.
Also: Yale M. J., 1903-4, x, 1-17.
1904
Fifteenth report of the superintendent of The Johns Hopkins
Haspital for the year ending January 31, 1904. Bait, 1904.
The Johns Hopkins Press. 130 p. 8".
Is nursing a profession? Albany M. .Ann., 1904, xxv, 625-637.
1905
Sixteenth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31. 1905. Bait. 1905. The
Johns Hopkins Press. 133 p. 8°.
John Howard's observations on hospitals (1773-1790). (Proc. Johns
Hopkins Hosp. Med. Soc, October 23, 1905). Johns Hopkins
Hosp. Bull., Bait. 1905, xvi. 412-413.
Also: Tr. Ass. Hosp. Superintend.. 1905. vii, 157-166.
Response to Dr. Cheever's " Address of welcome." Tr. Ass. Hosp.
Superintend., 1905, vii, 50-52.
1906
Seventeenth report of the superintendent of The Johns Hopkins
Hospital for the year ending January 31, 1906. Bait., 1906.
The Johns Hopkins Press. 125 p. 8°.
Shall training schools for nurses be endowed? An address delivered before the Training School for Nurses of Lakeside Hospital, Cleveland, May 11, 1906. Am. J. Nursing, Phila., 1905-6,
vi. 843-853.
Also: Nat. Hosp. Rec. Detroit, 1906, x, 18-23.
Also: Brit J. Nursing [etc.], Lond., 1906, xxxvii, 225-227.
The medical organization of general hospitals. Tr. Am. Hosp, Ass.,
1906, vlii, 72-83.
Also: Nat. Hosp. Rec, Detroit, 1906, x. 14-16.
1908
Nineteenth report of the superintendent of The Johns Hopkins
Hospital for the year ending January 31, 1908. The Johns
Hopkins Press. 123 p. 8°.
The proper length of the period of training for nurses. Am. J.
Nursing. Phila., 1908, viii, 671-683.
How can psychiatry assist preventive medicine? (Editorial).
Am. J. Pub. Hyg., Boston, 1908, xviii, 273-278.
Psychiatry as a part of preventive medicine. Proc. Am. Med.Psychol. Ass., Bait., 1908, xv, 157-164.
Also: Am. J. Insan., Rait. 1908-9, Ixv, 17-24.
Also: N. Albany M. Herald. 1910, xxviil, 104108.
In memoriam. Daniel Coit Oilman, 1831-1908. Address. Johns
Hopkins Univ. Circ, Bait., 1908. xxvii. 20-23.
1909
Twentieth report of the superintendent of The Johns Hopkins
Hospital for the year ending January 31. 1909. Bait.. 1909.
The Johns Hopkins Press. 123 p. 8'.
State registration and the education of nurses In the I'nited States.
Nursing .Mirror. Lond.. 1908-9. n. s., vlll. 37-38: 53.
In memoriam. William Keith Brooks. 18481908. Address. Johns
Hopkins Univ. CIrc, Bait., 1909, xxvlli. 6-9.
1910
Twenty-first report of the superintendent of The Johns Hopkins
Hospital for the year ending January 31, 1910. Bait., 1910.
The Johns Hopkins Press. 123 p. 8'.
Co-operation among hospitals. A paper presented to the Pittsburgh Health Conference, November 30, 1910, as a part of
a symposium on " Co-operation."
373
[No. 346
Memorial services for Isabel Hampton Robb, who died April 15,
1910, at Cleveland, Ohio. Remarks. Johns Hopkins Hosp.
Bull., Bait, 1910, xxi, 251-252.
Florence Nightingale — a force in medicine. Address at the graduating exercises of the Nurses Training School of the Johns
Hopkins Hospital, May 19, 1910. Johns Hopkins Nurses
Alumna Mag., Bait., 1910, ix, 68-81.
1911
Twenty-second report of the superintendent of The Johns Hopkins
Hospital for the year ending January 31, 1911. Bait., 1911.
The Johns Hopkins Press. 109 p. 8°.
The medical service of a hospital. In: Hospital management, a
handbook for hospital trustees, superintendents [etc.]
(Aikens), Phila. & Lond., 1911, 97-107.
A history of Institutional care of the insane in the United States
and Canada. Am. J. Insan., Bait, 1910-11, Ixvii, 587-592.
Also: Proc. Am. Med.-Psychol. Ass., Bait, 1910, xvii, 4S3-488.
The site of the Johns Hopkins Hospital. A paper presented to the
Johns Hopkins Historical Club and repeated to the Teresians
in December, 1910. Johns Hopkins Nurses Alumns Mag.,
Bait, 1911, X, 5-20.
The proper relation of the superintendent to the trustees of a
hospital. Tr. Am. Hosp. Ass., 1910, Toronto, 1911, xil, 244-248.
1912
The proper division of the services of the hospital. Read in the
symposium on the relations of the hospital to the public in the
section on hospitals of the American Medical Association, at
the sixty-third annual session, held at Atlantic City, June,
1912. J. Am. M. Ass., Chicago, 1912, lix, 1677-1679.
[Hospital problems.] Presidential address at the fourteenth
annual conference of the American Hospital Association. In
ternat Hosp. Rec, Detroit, 1912, xvi, 9-11.
Also: Tr. Ass. Hosp. Superintend., 1912, xiv, 83-93.
Meeting in behalf of the Isabel Hampton Robb Memorial Fund.
Remarks. Johns Hopkins Nurses Alumnae Mag., Bait., 1912,
xi, 16-19.
1913
Three-quarters of a century of institutional care of the insane in
the United States. Am. J. Insan., Bait., 1912-13, Ixix, 469-481.
Extracts from the laws of Maryland and Virginia regarding the
early care of the insane. Bull. Med. & Chir. Fac. Maryland,
Bait, 1912-13, v, 85-88.
Early days of The Johns Hopkins Hospital and Medical School.
Johns Hopkins Alumni Mag., Bait., 1912-13, i, 105-114.
The hospital as a factor in modern society. (Editorial). Mod.
Hosp., St Louis, 1913, i, 33.
Hospitals and the reform of medical teaching. (Editorial). Mod.
Hosp., St. Louis, 1913, i, 182-183.
Review of " A History of Nursing." Johns Hopkins Nurses
Alumnae Mag., Bait, 1913, xii, 91-94.
1914
Hospital medical statistics. (Editorial). Mod. Hosp., St. Louis,
1914, ii, 44-45.
The small hospital a factor in medical education. (Editorial).
Mod. Hosp., St Louis, 1914, li, 104-105.
Mental cases in general hospitals. (Editorial). Mod. Hosp., St.
Louis, 1914, ii, 172.
The human side of Florence Nightingale. (Editorial). Mod. Hosp.,
St Louis, 1914, ii, 364.
State registration of nurses. Mod. Hosp., St. Louis, 1914, iii, 107;
137.
Dr. Rupert Norton. (Editorial). Mod. Hosp., St. Louis, 1914, Iii,
108-109.
Some of the writings of the late Eugene Pauntleroy Cordell. Bull.
Med. & Chir. Fac. Maryland, Bait, 1913-14, vi, 115-119.
Relation of the general hospital to the training school for nurses.
Boston M. & S. J., 1914, clxx, 333-337.
Twenty-fifth anniversary of The Johns Hopkins Hospital. 1889
1914. Address. Johns Hopkins Hosp. Bull., Bait, 1914, xxv,
355-359.
Presentation of tablets, portrait and medallion at the Hospital
October 7, 1914. Remarks. Johns Hopkins Hospital Bull.,
Bait, 1914, X.XV, 368-369.
Hurd, H. M., McCaw, W. D. [et a!.] Johns Hopkins Historical
Club. Special meeting. May 26, 1913, in memory of Dr. John
Shaw Billings. Johns Hopkins Hosp. Bull., Bait., 1914., xxv,
244-253.
1915
Hospital organization and management. Ref. Handb. Med. Sc,
N. Y., 3d ed., 1915, v, 299-311.
The treatment of mental cases in general hospitals. (Editorial).
Mod. Hosp., St. Louis, 1915, iv, 34-35.
The general government of state hospitals. Mod. Hosp., St. Louis,
1915, iv, 244-245.
Organization and administration of hospitals for the insane. (Editorial). Mod. Hosp., St. Louis, 1915, iv, 258.
Ought training schools for nurses to be endowed? (Editorial).
Johns Hopkins Nurses Alumnfe Mag., Bait, 1915, xiv, 2-3.
The early years of The Johns Hopkins Hospital. Johns Hopkins
Nurses Alumnae Mag., Bait., 1915, xiv, 76-89.
Forty-five years ago and now. An address before the Training
School for Nurses at the Sheppard and Enoch Pratt Hospital,
May 19, 1915. Johns Hopkins Nurses Alumns Mag., Bait.,
1915, xiv, 256-264.
The care of cases of mental disease in general hospitals. Tr. Am.
Hosp. Ass., 1915, xvii, 455-462.
Also: Mod. Hosp., St Louis, 1915, v, 33-35.
Hurd, H. M., Drewry, W. F. [et al.] The institutional care of the
insane in the United States and Canada. 3 v.. Bait., 1916, Johns
Hopkins Press. 8°.
Nathan Smith, Nathan R. Smith, and Alan P. Smith — a medical
family. Maryland M. J., Bait., 1916, lix, 56-59.
Also: Bull. Med. & Chir. Fac. Maryland, Bait, 1915-16, viii,
157-163.
Address on the occasion of the opening of the John Hubner Psychopathic Building at Springfield State Hospital, on June 9,
1915. Maryland Psychiat. Q., Bait, 1915-16, v., 29-32.
Need of segregation of imbecile women. Maryland Psychiat. Q.,
Bait, 1915-16, V, 64-67.
Report of committee on a history of " The Institutional Care of
the Insane in the United States and Canada." Am. J. Insan.,
Utica, N. Y., 1915-16, Ixxii, 176-177.
Some sources of friction in the management of hospitals. (Editorial). Mod. Hosp., St Louis, 1916, vi, 30-31.
Another source of friction In hospital administration. (Editorial).
Mod. Hosp., St Louis, 1916, vi, 112.
Who shall manage the training school for nurses? Mod. Hosp.,
St Louis, 1916, vi, 114-115.
Advantages of the budget system. (Editorial). Mod. Hosp., St.
Louis, 1916, vi, 186.
1917
Hurd, H. M., Drewry, W. F. [et at] The institutional care of the
insane in the United States and Canada. Vol. iv. Bait., 1917,
Johns Hopkins Press. 652 p., 8°.
Johns Hopkins and some of his contemporaries. Johns Hopkins
Hosp. Bull., Bait, 1917, xxviii, 225-229.
State hospitals and agricultural preparedness. (Editorial). Mod.
Hosp., St. Louis, 1917, ix, 24.
Burket, W. C. Bibliography of William H. Welch, M. D., LL. D.
With foreword by Henry M. Hurd. Bait, 1917, Johns Hopkins
Press. 47 p., 4°.
1919
A sketch of Dr. Lyman Spalding. Johns Hopkins Hosp. Bull.,
Bait, 1919, XXX, 125-129.
Also: Bull. Med. Library Ass., Bait, 1918-19, viii, 29-38.
I
December, 1919]
373
INDEX TO VOLUME XXX OF THE JOHNS HOPKINS HOSPITAL BULLETIN.
Abscess, postscarlatinal cervical, hiemorrhage into a. Ligation of
the common carotid. Recovery, 240.
Agglutination, phagocytosis and, in the serum in acute lobar
pneumonia; the specificity of these reactions and the regularity
of their occurrence, 167.
Anaesthesia and asepsis, reminiscences of two epochs, 273.
Antituberculosis measures, 49.
Asepsis, antesthesia and, reminiscences of two epochs, 273.
B. influciizw. the effect of different bloods on the growth of, 129.
Bacteria introduced into the upper air passages, the fate of, 317.
Barker, L. F., Osier as chief of the medical clinic, 1S9.
Barker, L. F. and Carter, D. W., Jr., Chronic pemphigus vegetans
of several years' duration, 302.
Benzine poisoning, with report of a chronic case, 309.
Blogg, SI. W., Bibliography of Howard A. Kelly, 293.
Blogg. M. W.. Bibliography of Sir William Osier, 219.
Blood sugar, studies on. IV. Effects upon the blood sugar of the
repeated ingestion of glucose, 306.
Bloomfleld, A. L., The fate of bacteria introduced into the upper
air passages, 317.
Bloomfleld, A. L., The relation of spontaneous nephritis of rabbits
to experimental lesions, 121.
Bloomfleld, A. L. and Harrop, G. A., Jr., Clinical observations on
epidemic influenza, 1.
Bloomfleld. A. L. and Mateer, J. G., Changes in skin sensitiveness
to tuberculin during epidemic influenza, 238.
Bloomfleld. A. L. and Waters, C. A., The correlation of X-ray findings and physical signs in the chest in uncomplicated epidemic
influenza. 252.
Boggs, T. R , Osier as a bibliophile, 216.
Books received, 139; 183; 256; 285; 315; 340.
Bridgman, E. W., Notes on the group of symptoms designated as
effort syndrome, 279.
Brown, T. R., Osier and the student, 200.
Brush, E. N., Osier's influence on other medical schools in Baltimore. His relation to the medical profession, 20S.
Brush. E. N.. Osier's literary style, 217.
Carter, D. W., Jr. and Barker, L. F., Chronic pemphigus vegetans
of several years' duration, 302.
Carter. E. P., RIchter, C. P. and Greene, C. H., A graphic applica
tion of the principle of the equilateral triangle for determining
^ the direction of the electrical axis of the heart in tlie human
electrocardiogram. 162.
Cerebral ventricles, fluoroscopy of the, 29.
Cerebrospinal fluids of cats, analysis of, with meningeal infections, 242.
Chatard. J. A., Osier and the Book and Journal Club, 211.
Chorea, an electromyographic study of, 35.
Clark, Admont H., The efl'cct of diet on the healing of wounds, 117.
Clark. Admont Halsey, In niemoriam, 272.
Clough, P. W., Phagocytosis and agglutination in the serum in
acute lobar pneumonia; the specificity of these reactions and
the regularity of their occurrence. 167.
Cobb. S., An electromyographic study of chorea, 35.
Colston. J. A. C. and Waters, C. A., The r61e of the Xray In the
diagnosis of longstanding renal tuberculosis, 268.
Councilman, W. T., Some of the early medical work of Sir William
Osier, 193.
Cross-Ptrlatlons. the development of. In the heart muscle of the
chick embryo. 176.
Crowe. S. J. and Thacker-Nevllle, W. S., Tlie influenza bacillus In
paranasal sinus Infections. 322.
Cull, S. T. W., Spina bifida with associated disturbances In a
human embryo 17 mm. long, 181.
CuUen, T. S., Dr. Henry M. Hurd, flrst superintondent of The
Johns Hopkins Hospital, 341.
Cullen, T. S., Dr. Howard A. Kelly, Professor of Gynecology in The
Johns Hopkins University and Gynecologist-in-Chief to The
Johns Hopkins Hospital, 287.
Dandy, W. E., Fluoroscopy of the cerebral ventricles, 29.
Davison, W. C. and Holm, M. L., Meningococcus pneumonia. I. The
occurrence of post-influenzal pneumonia In which the diplococcus
Introcellularis meningitidis was isolated. From observations at
Camp Coetquldon, A. E. F., France, 324.
Davison, W. C, Holm, M. L. and Emmons, R. V. B., Meningococcus
pneumonia. II. The epidemiology of postinfluenzal pneumonia
in which the diplococcus intracellularis meningitidis was Isolated, 329.
Diet, the effect of, on the healing of wounds, 117.
Digitalis, observations on the clinical pharmacology of, 131.
Douglas^ B., The reaction of the leucocytes in epidemic influenza,
338.
Effort syndrome, notes on the group of symptoms designated as,
279.
Electrocardiogram, human, a graphic application of the principle
of the equilateral triangle for determining the direction of the
electrical axis of the heart in the human electrocardiagram, 162.
Electromyographic study of cliorea, 35.
Emmons, R. V. B., Davison, W. C. and Holm, M. L., Meningococcus
pneumonia. II. The epidemiology of post-influenzal pneumonia
in which the diplococcus intracellularis meningitidis was isolated. 329.
Equilateral triangle, a grapliic application of the principle of the,
for determining the direction of the electrical axis of the heart
in the human electrocardiogram, 162.
Felton, L. D.. Analysis of cerebrospinal fluids of cats with meningeal infections, 242.
Fluoroscopy of the cerebral ventricles, 29.
Fry, Elizabeth — Quaker Reformer, 72.
Futclier, T. B.. Osier's Influence on the relation of medicine in
Canada and the I'nited States, 204.
Gastric mucosa, the occurrence of. In a case of Meckel's diverticulum producing Intestinal obstruction, 143.
Goetsch, E., The occurrence of gastric mucosa in a case of Meckel's
diverticulum producing Intestinal obstruction, 143.
Granules, degeneration, and vacuoles In the fibroblasts of chick
embryos cultivated in i i((0. 81.
Green, Horace, and his probang, 246.
Greene, C. H.. Carter. E. P. and RIchter. C. P.. A graphic application of the principle of the equilateral triangle for determining
the direction of the electrical axis of the heart In the human
electrocardiogram, 162.
Haden, R. L., Benzine poisoning, with report of a chronic case, 309.
Hiemorrhage Into a postscarlatinal cervical abscess. Ligation of
the common carotlrl. Recovery, 240.
Hamnian, L., Osier and the tuberculosis work of the hospital, 202.
Hamman, L. and Hlrschman, I. I., Studies on blood sugar. IV.
EITects upon the blood sugar of the repeated ingestion of glucose, 306.
Harrop, G. A.. Jr., The behavior of the blood toward oxygen In
influenzal Infections, in.
Harrop. G. A., Jr.. The production of tetany by the Intravenous
Infusion of sodium bicarbonate. Report of an adult caae, 62.
Harrop, B. A.. Jr., and Bloomfleld, A. L., Clinical observations on
epidemic Influenza, 1.
Hlrschman, I. I. and Hamman, L., Studies on blood sugar. IV.
Effect upon the blood sugar of the repeated ingestion of glucose.
306.
374
[No. 346
Holm, M. L. and Davison, W. C, Meningococcus pneumonia. I. Tlie
occurrence of post-influenzal pneumonia in wliicli the diplococcus introcellularis meningitidis was isolated. From observations at Camp Coetquldon, A. E. F., France. 324.
Holm, M. L., Davison, \V. C. and Emmons, R. V. B., Meningococcus
pneumonia. II. The epidemiology of post-influenzal pneumonia
in which the diplococcus intracellularis meningitidis was isolated, 329.
Howard, S. E., Bacteriological findings in epidemic influenza, 13.
Huck, J. G., Changes in the blood immediately following transfusion, 63.
Hurd, H. M., Some early reminiscences of William Osier, 213.
Hurd, Henry M., A sketch of Dr. Lyman Spalding, 125.
Hurd, Henry Mills, first superintendent of The Johns Hopkins
Hospital, 341.
Influenza bacillus in paranasal sinus infections, 322.
Influenza cases, fatal, comments on the pathology and bacteriology
of, as observed at Camp Devons, Mass., 104.
Influenza, epidemic, bacteriological findings in, 13.
Influenza, epidemic, changes in skin sensitiveness to tuberculin
during. 23S.
Influenza, epidemic, clinical observations on, 1.
Influenza, epidemic, the reaction of the leucocytes in, 33S.
Influenza, uncomplicated epidemic, the correlation of X-ray findings and physical signs in the chest in, 252.
Influenzal infections, the behavior of the blood toward oxygen in,
10.
Inoculation with blood from measles patients, insusceptibility of
man to, 257.
Inoculation with blood from measles patients, insusceptibility of
monkeys to, 57.
Intestinal obstruction, the occurrence of gastric mucosa In a case
of Meckel's diverticulum producing, 143.
Intravenous infusion of sodium bicarbonate, the production of
tetany by the, 62.
Jacobs, H. B., Osier as a citizen and his relation to the tuberculosis crusade in Maryland, 205.
Kelly, H. A., Osier as I knew him in Philadelphia and in the
Hopkins, 215.
Kelly, Dr. Howard A., Bibliography of, 293.
Kelly, Dr. Howard A., Professor of Gynecolog>- in The Johns
Hopkins University and Gynecologist-in-Chief to The Johns
Hopkins Hospital, 287.
Knox, J. H. M., Jr., Dr. George Peirce, 254.
Krause, A. K., Antituberculosis measures, 49.
Leucocytes, the reaction of the, in epidemic influenza, 338.
Lewis, M. R., The development of cross-striations in the heart
muscle of the chick embryo, 176.
Lewis, W. H., Degeneration granules and vacuoles in the fibroblasts of chick embryos cultivated in vitro. 81.
Lung architecture, stereoroentgenograms of the injected lung as
an aid to the study of the, 34.
McCrae, T., Osier and patient, 201.
MacCallum, W. G., In Memoriam— Admont Halsey Clark, 272.
MacCallum, W. G., Osier as a pathologist, 197.
Macht, D. I., A pharmacological appreciation of a Biblical reference to mass poisoning, II Kings, IV, 38-41, 38.
Manus meditationis, 184.
Mass poisoning, a pharmacological appreciation of a Biblical reference to, II Kings, IV, 38-41, 38.
Mateer, J. G. and Bloomfleld, A. L., Changes in skin sensitiveness
to tuberculin during epidemic influenza, 238.
Measles blood, the reaction of monkeys to the inoculation of, 311.
Measles patients, insusceptibility of man to inoculation with
blood from, 257.
Measles, the occurrence of the Pfeifter bacillus in, 331.
Meckel's diverticulum, the occurrence of gastric mucosa in a case
of, producing intestinal obstruction, 143.
Meningeal infections, analysis of cerebrospinal fluids of cats with
242.
Meningococcus pneumonia. I. The occurrence of post-influenzal
pneumonia in which the diplococcus intracellularis meningitidis
was isolated. From observations at Camp Coetquldon, A. E. F.,
France, 324.
Meningococcus pneumonia. II. The epidemiology of post-influenzal pneumonia in which the diplococcus intracellularis meningitidis was isolated. From observations at Camp Coetquldon,
A. E. F., France, 329.
Meyer, A. W. and Wynne, H. M. N., Some aspects of ovarian pregnancy, with report of a case. 92.
Miller, W. S., Granville Sharp Pattison, 98.
Miller, W. S., Horace Green and his probang, 246.
Miller, W. S., Stereoroentgenograms of the injected lung as an
aid to the study of the lung architecture, 34.
Nephritis, spontaneous, of rabbits, relation of, to experimental
lesions, 121.
Notes and news, 25.
Notes on new books: Carman, R. P. and Miller, A., The roentgen
diagnosis of diseases of the alimentary canal, 27; — Sellards,
A. W., The principles of acidosis and clinical methods for its
study, 136; — Strong. R. P. (chairman). Trench fever: report of
Commission Medical Research Committee, American Red Cross.
136;— Stokes, J. H., The third great plague, 136; — A''eddar, E. B.,
Syphilis and public health, 136; — Hartzell, M. B., Diseases of
the skin, 136; — Barjon, F., Radio-diagnosis of pleuro-pulmonary
affections, 136; — Prince, N. C, Roentgen technic, 136; — MacCurdy, J. T., War neuroses, 136; — Smithies, P., Quarterly
Medical Clinics. A series of consecutive clinical demonstrations
and lectures, 284; — Wenyon, C. M. and O'Connor, F. W., Human
intestinal protozoa in the near East, 284; — Lewis, T., The
soldier's heart and the effort syndrome, 284; — Wilson, R. M. and
Carroll, J. H., The nervous heart, 314; — Macleod, J. M. H., Burns
and their treatment, 314; — Von Hug-Hellmuth, H., A study of
the mental life of the child, 314; — Macleod, J. J. R., Physiology
and biochemistry in modern medicine, 314.
Noyes, M. C. Osier's influence on the library of the Medical and
Chirurgical Faculty of the State of Maryland, 212.
Osier and patient, 201.
Osier and the Book and Journal Club, 211.
Osier and the student, 200.
Osier and the tuberculosis work of the hospital, 202.
Osier as a bibliophile. 216.
Osier as a citizen and his relation to the tuberculosis crusade in
Maryland, 205.
Osier as a pathologist, 197.
Osier as chief of the medical clinic. 189.
Osier as I knew him in Philadelphia and in the Hopkins, 215.
Osier's influence in building up the Medical and Chirurgical
Faculty, 209.
Osier's influence on other medical schools in Baltimore. His
relation to the medical profession, 208.
Osier's influence on the library of the Medical and Chirurgical
Faculty of the State of Maryland, 212.
Osier's influence on the relation of medicine in Canada and the
United States, 204.
Osier's literary style, 217.
Osier, Sir William, bibliography of, 219. i
Osier, Sir William, some of the early medical work of, 193.
Osier, the teacher, 198.
Osier, William, some early reminiscences of, 213.
Ovum, single, twins, formation of, 235.
Paranasal sinus infections, the influenza bacillus in, 322.
Pattison, Granville Sharp, 98.
Dkckmhkk, ItM'Jj
373
Pelrce, Dr. George, 254.
I'empliigus vegetans, chronic, of several years' duration, 302.
I'feiffer bacillus in measles, the occurrence of the, 331.
Phagocytosis and agglutination in the serum in acute lobar pneumonia: the specificity of these reactions and the regularity of
their occurrence. 167.
Pharmacological appreciations of a Biblical reference to mass
poisoning, 11 Kings, IV, 38-41, 38.
Pneumonia, acute lobar, phagocytosis and agglutination in the
serum in; the specificity of these reactions and the regularity
of their occurrence, 107.
Pneumonia, meningococcus. 1. The occurrence of post-influenzal
pneumonia in which the diplococcus intracellularis meningitidis
was isolated, 324.
Pneumonia, meningococcus. II. The epidemiology of post-influenzal pneumonia in which the diplococcus intracellularis meningitidis was isolated, 329.
Pregnancy, ectopic, 15.
Pregnancy, ovarian, some aspects of, with report of a case, 92.
Proceedings of The Johns Hopkins Hospital Medical Society:
Bloomfield. A. L. and Harrop, G. A., Clinical observations on
epidemic influenza, 110: — Wolbach, S. B., Comments on the
pathology and bacteriology of fatal influenza cases, as observed
at Camp Devens, Massachusetts. 110; — Tliompson, W. G., A
functional re-education clinic: organization and methods, 110; —
MacCallum, \V. G., Malaria in the Federated Malay States. A
correction. 110.
Itichter. C. P., Carter, E. P. and Greene, C. H., A graphic application of the principle of the equilateral triangle for determining
the direction of the electrical axis of the heart in the human
electrocardiogram, 162.
Rivers, T. .M.. Haemorrhage into a postscarlatinal cervical abscess.
Ligation of the common carotid. Recovery, 240.
Rivers, T. M., The effect of different bloods on the growth of
B. influcnzir, 129.
Sellards, A. W., Insusceptibility of man to inoculation with blood
from measles patients, 257.
Sellards, A. W., The reaction of monkeys to the inoculation of
measles blood, 311.
Sellards, A. W. and Sturn, E., The occurrence of the Pfeiffer
bacillus In measles. 331.
Sellards, A. W., and Wentworth, J. A., Insusceptibility of monkeys
to inoculation with blood from measles patients, 57.
Singer, C, The manus meditationis, 184.
Skin sensitiveness, changes In, to tuberculin during epidemic
influenza, 238.
Smith, S., Reminiscences of two epochs — anaesthesia and asepsis,
273.
Spalding. Dr. Lyman, a sketch of, 125.
Spina bifida with associated disturbances in a human embryo
17 mm. long, 181.
Stereoroentgenograms of the injected lung as an aid to the study
of the lung architecture, 34.
Streeter, C. L.. Formation of single-ovum twins, 235.
Sturm, E. and Sellards. A. W., The occurrence of the Pfcifrer
bacillus In measles, 331.
Tetany, the production of, by the Intravenous infusion of sodium
bicarbonate. Report of an adult case, 62.
Thacker-Neville. W. S., and Crowe, S. J., The Influenza bacillus in
paranasal sinus infections, 322.
Thayer, W. S.. Osier, the teacher. 198.
Thomas, H. M., Elizabeth Fry- Quaker Reformer, 72.
Thomas, H. M.. Some memories of the development of the medical
school and of Osier's advent. IS.t.
Titles of papers appearing during the year, elsewlifre than In
the Bii-LETiN, by present and former members of the hospital
and medical school staff, 42.
Transfusion, changes in the blood immediately following, 63.
Tuberculosis, renal, the rdle of the X-ray in the diagnosis of longstanding, 268.
Ventricles, cerebral, fluoroscopy of the, 29.
Waters. C. A., and Bloomfield, A. L., The correlatiqn of X-ray
findings and physical signs in the chest in uncomplicated epidemic influenza, 252.
Waters, C. A., and Colston, J. A. C, The r61e of the X-ray in the
diagnosis of long-standing renal tuberculosis, 268.
Wedd. A. M., Observations on the clinical pharmacology of
digitalis, 131.
Wentworth, J. A., and Sellards. A. W., Insusceptibility of monkeys to inoculation with blood from measles patients, 57.
Wolbach, S. B., Comments on the pathology of fatal influenza
cases, as observed at Camp Devens, Mass., 104.
Woods. H., Influence in building up the Medical and Chirurgical
Faculty. 209.
Wynne, H. M. N., Ectopic pregnancy, 15.
Wynne, H. M. N., and Meyer, A. W., Some aspects of ovarian
pregnancy, with report of a case, 92.
X-ray findings and physical signs, the correlation of. in the chest
in uncomplicated epidemic influenza, 2.')2.
X-ray, the role of the. in tlic diagnosis of long-standing renal
tuberculosis, 268.
ILLUSTRATIONS
Two illustrations in a case of epidemic influenza — one showing
inside of mouth of patient, and the other spots found on mucosa
of check, 4.
Fluoroscopy of the cerebral ventricles, 31-32.
Stereoroentgenograms of an Injected lung, 35.
Electromyogranis used In study of chorea, 36.
Citrullus Colocynthis Arn, 39.
Ecballium Elaterium. 39.
Elizabeth Fry, 72.
Degeneration granules and vacuoles In libroblasts of chick embryos
cultivated in vitro, 91.
Gross specimens from a case of ovarian pregnancy. 96.
Granville Sharp Pattison, 98.
Nathaniel Chapman, 98.
Specimens of lungs from cases of Influenza, 108.
Specimens of kidneys showing relation of spontaneous nephritis
of rabbits to experimental lesions, 124.
Illustrations showing growth of strains of B. influcmw in human
blood meat infusion agar and rabbit blood meat infii^iion
agar, 130.
Electrocardiograms showing the eflect of digitalis on the heart
waves, 134.
Meckel's diverticulum, 144.
Magnified sections of muco.sa In a case of Meckel's diverticulum, 146.
eland tubules in .Vleckrl's diverticulum, 148.
L'mbllical polyp with central fistulous opening, remnant of
omphalomesenteric duct. In Meckel's diverticulum, 149.
Omphalomesenteric duct in form of an umbilical fistula In Meckel's
diverticulum. 151.
Umbilical polyp connected with Meckel's diverticulum and patent
omphelomesenteric duct with polypoid formation at umbilicus,
152.
Drawing Illustrating the fundamental principle of the equilateral
triangle for determining the direction of the electrical axis of
the heart In the human electrocardiogram, 162.
Drawings and electrocardiograms illustrating the principle of the
equilateral triangle for determining the direction of the electrical axis of the heart, 165-166.
Photographs and drawings in a case of development of cross
strlatlons in the heart muscle of the chick embryo, 178.
Spina bifida witli associated disturbances in a liuman embryo, 182.
Manus Meditationis (The Hand of Meditation), 184.
Sir William Osier in 1906. Painted by Sargent, 186.
Sir William Osier— the Saint, by Max Broedel, 192.
Sir Williarn Osier at a patient's bedside, 201.
Sir William Osier. Painted by Seymour Thomas, 206.
Bookplate of the Library of the Medical and Chirurgical Faculty
of the State of Maryland, purchased through the William Osier
Testimonial Fund for the Advancement of Medicine, 212.
Sir William Osier in 1901, 1902 and 1913, 214.
Dr. William S. Halsted, Sir William Osier and Dr. Howard A.
Kelly taken about 1900, 218.
Formation of single ovum twins, 236, 237, 238.
Horace Green, 246.
X-ray photographs of the chest in uncomplicated epidemic influenza, 252.
X-ray photographs of the kidney and ureter in a case of renal
tuberculosis, 270.
Dr. Admont Halsey Clark, 272.
Tablet in memory of Dr. Admont H. Clark, 272.
Dr. Stephen Smith, 273.
Dr. Howard A. Kelly, 288, 290.
Pemphigus vegetans, 302, 304.
Plate spreader and throat swab used in cases of meningococcus
pneumonia, 331.
Dr. Henry M. Hurd at various ages, 342, 346, 364, 369.
The Origin and Development of the Lymphatic System. By
Florence R. Sarin. 94 pages. Price, $2.00.

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Volume 30 (1919)

http://www.archive.org/details/johnshopkinsmedi30john

The Johns Hopkins Medical Journal 30 (1919)


http://www.archive.org/details/johnshopkinsmedi30john


THE JOHNS HOPKINS HOSPITAL BULLETIN


VOLUME XXX


BALTIMORE THE JOHNS FK)PKINS PRESS



BALTIMORE, UD., U. 6. A.


Entered as Second-Class Mntter at the Baltimore, Maryland. PoatofDee Acceptance for mailing at special rate of postace pn^viil.'d fnr in s.-rtinn llo.^. Art ..f Ortnht^r :i 1^17 Anthori^.^.i ..t, ,i.,k :i. ijjig.


Vol. XXX-No. 335]


BALTIMORE, JANUARY. 1919


Clinical Observations on Epidemic Influenza. (Illustratcil.) By Abtiiub Bi.oomkield and George A. Hakrop. Jr.

Tlie Beliavior of tlio Blood Toward Oxygen in Inlliicnziil In feetions. (Illiistratod.)

Bv (iEOBGK A. Harbop, Jr


Contents

Bacteriological Findings in Epideniie Inllneiiza. 1 By S. K. Howard, Jf. D 13

Ectopic Pregnancy. By H. M. X. Wynnk . . . l.O

1 Notes and News 25

10 I Notes on New Books 27



ECTOPIC PREGNANCY


By II. M. X

Hes'ideitl (li/necoloriisl. Thr

INCIDENCE In the 2t years from 18!t0 to l!tl(i inclusive, there iiavc Ijeen 303 patients with ectopic pregnancy in the tiynecological Service of The .Johns Ho])kins Hospital who were operated upon. There have been 22,fi88 patients admitted to the Gj-necological Service during the S'i years, of which 303 had extrauterine pregnancies, an incidence of l.:W.

Table Showino the Nimbeb ok Patients with ExTRAi'n':Ri.NE PREOXANCIE.S Each Year



^ *




1990


2


18«!


6


1902


8


1908


23


1014


14


1891


3


18(t7


1


1003


15


190U


23


1915


13


1892


4


1 898


8


1!X)4


23


IftlO


13


1010


13


isns


8


18it!t


7


HI05


23


I91I


16




I8»4


7


lOOO


10


1900


13


1912


11




1895


'


1901


10


1907


10


1913


11


Total


.103


Race— Negroes, 101; white, 202. Total, 303.

Of the.s(. 22.688 patients. i:.H2 were wliit.- and .">2:(i wer.' negroes. There were 202 eases of extrauterine pregnancy among the whites (1.16:^) and 101 among the negro» (l.'.il^).


Wynne.

Johns Ilopkins IlosjiHa]

AGE

(»f this .series of cases the age was rccnnlcil :>()() tunes. The youngest patient was a 1 ."i-ycar-old white girl, married .seven months previously to admission and never pregnant Ix'fore. .\n unruptured left tubal |)rcgi»Hncy was removed at operation. The oldest jjaticnt was a l.")-year-old ncgress, who had given birth to three full-term chihircn. .\t operation a fullterm litiiopedion. which iiad been in thf aiidomcn for four years was removed ( Kcjiorted by .1. (i. Clark, The .lohns Hopkins Hospital Bulletin. l«!i:. Vlll. and in Kelly's Operative Gynecology, Vol. 11). Of this series 182 (GH) occurred in the decade 24 to .5.3 years inclusive. Seven patietits were under 20 years and ten were over 10 years of age.

TAni.K Showixo Aokh ok 300 Patik.nth



MARITAL HISTORY

In a series of 284 there were 14 unmarried, two widows and nine twice married.


Table Showing Time of Admission Aftee


Marriage


Time


Number

of patients


Time


Number

of patients


Time


Number

of patients


Time


Number

of patients


married


married


married


married




yrs.



yrs.



yrs.



2 wks . . .



1


9


9


8


18


9


4 wks...



2


22


10


14


19


3


6 wks...



3


18


11


9


20


7


2 mo8. . .



4


13


12


17


21


6


4 mos. . .



5


I.i


13


11


22


2


5 mos. . .



6


12


14


8


23


3


7 mos . . .



7


21


1.5


9


20


1


8 mos . . .



8


13


16


6


27


1






17


8


Total


268


PREVIOUS PREGNANCIES

In the histories of 375 patients, the number of pregnancies prior to the ectopic pregnancy was recorded. In 57 (31^) there had been no previous pregnancy and of the 218 (79^) who had been pregnant before, 307 (95;?;), 75^ of the whole series, had given birth to full-term babies and 11 (5^), 4^ of the whole series, had had only miscarriages. Instrimiental deliveries had been performed on 19 patients (9;^ of those who had had full-term pregnancies). Histories of prolonged puerperia associated with chills, fever and abdominal pain were obtained from 38 patients (17.5^ of all patients previously pregnant) .


Table Showing Number of Previous Pregnancies


Number


Number of


Number of


Number of


Total


Number of


carriages


patients


children


patients



patients


1


65


1


77



57


2


25


2


32


1


67


3


8


3


27


2


42


4


5


4


21


3


22


5


2


5


17


4


22


6


2


6


14


o


16




7


8


6


16


Tola


1 107


8


2


7


13




9 .


2


8


8




10


3


9





11


1


10


3




12



11


1




13


1


12


1




14


2


13 14


1

1




Tota


1 207


15 16


1






Total 275


The interval between the last pregnancy and admission to the hospital for an ectopic pregnancy was noted in the his Table Showing the Interval Between the Last Pregnancy and Admission to the Hospital for Ectopic Pregnancy



"oS



•5Z



- »i



• a



»- n



aj S



fc. g



t- g



tM C



b. a


1


ft


1



i


It


1


it


1



B


z


B


z


B


S5


B


§.


E

Iz


mos.



mo:.



yrs.



yrs.



yrs.



3



9


5


3


23


9


5


15


3


4



10


1


4


22


10


8


16


1


5



11


2


5


13


11


4


17


1


6



12


20


6


20


12


6


18


1


7



18


15


7


19


13


1


19


2


8



2


36


8


5


14


1


Total


226


tories of 226 patients, the shortest interval being three months and the longest 19 years. The interval was between one and seven years iu 168 patients (74^).

PREVIOUS OPERATIONS

Forty-five patients had had operations prior to admission for ectopic pregnancy.

Dilatation and curettage had been performed on 15 patients for bleeding caused by the ectopic pregnancy; two of these operations were done in this hospital. One patient was curetted twice before admission for bleeding caused by the ectopic pregnancy.

Curettage was performed on 13 patients, from one to five years before their admission and simple dilatation of the cervix twice for sterility.

Incision of Bartholin gland abscess, five years before; one patient.

Pelvic puncture for inflammatory disease; three patients.

E.rplorafori/ laparotomy five years before; one patient.

Multiple myomectomy five years before; one patient.

Ovarian tumor removed; one patient.

Tu.nior removed and appendectomy; six years before; one patient.

Parovariancystectomy, right; suspension of uterus; appendectomy; two years before (Gyn. No. 16,409).

Suspension of tderus and appendectomy ; 18 months before (Gyn. No. 15,751).

Salpingo-oopliorectomy, left, and appendectomy; one and two years ago, for chronic pelvic inflammatory disease; two patients.

Salpingo-odphorectomy, right, and appendectomy ; one patient.

Appendectomy (only) ; three patients.

Appendectomy and nephropexy were done in another city on one patient for the symptoms caused by a right tubal pregnancy about six and eight weeks prior to admission to this hospital.

Five patients have been operated upon twice in this hospital for ectopic pregnancy.

Pelvic puncture, once.

Salpingectomy (alone), twice.

Salpingo-odphorectomy, twice.

COMPLAINT

The symptoms that patients complained of on admission were as follows :

Bleeding 93

Pain, general abdominal or not specified 99

Pain in lower abdomen 69

Pain in riglit lower quadrant of abdomen 33

Pain in left lower quadrant of abdomen 33

Pain in back 20

Pain designated as "bearing-down," 4 times: and as "cramplike," 4 times.

Tumor in abdomen 17

Tumor in right lower quadrant of abdomen 1

Tumor in left lower quadrant of abdomen 4

Swelling of abdomen 3

Tenderness of abdomen 4


January, 1919]


17


Pregnancy 2

.Miscarriage I

Amenorrhea 1

Dysmenorrhoea 2

Vomiting 9

Nausea 6

Diarrhoea 1

Pain on defecation 1

Dysuria 2

PoUakiuria 1

Fainting 1

From the foregoing list we see that the most i-oiumon causes for which these patients seek medical attention are pain, complained of by 254 (84;^) bleeding, complained of by 93 (31j^) and tumor, complained of by 28 patients (7^).

SYMPTOMS Onset (1) Acute without prodromal symptoms other

than bleeding or a missed period 14(> (48%)

(2) Acute with prodromal symptoms 72 (247c)

(3) Gradual without acute attacks 84 (28%)

Irregular bleeding 229 (76%)

Nausea 146 (48%,)

Vomiting 126 (42% )

Tumor 45 (15%)

Fainting 38 (137c)

Fever 29 (IO70)

Chills 12 (47c)

Weakness 87 (29% )

Defecation painful 28 (9% )

Urinary frequency 40 ( 13% )

Burning on voiding 27 (9% )

Pain on voiding 87 (29%)

Loss of weight 6 (2% )

Bad taste In mouth 3 ( 17c )

Patients believing themselves to be pregnant 11

Patients not suspecting pregnancy 3

Patients suspecting an abortion 1

Patients who had felt life 1

Patients having a sensation of fluid in the abdomen. ... 1 Patients who had passed complete casts of the uterus. . 2 Patients complaining of pain in the abdomen not otherwise qualified 131 (437o)

Pain, general abdominal 21 (7%)

Pain, limited to the lower abdomen 28 (9%)

Pain, limited to the lower left quadrant 43 (14% )

Pain, limited to the lower right quadrant 41 (137o)

Abdominal pain over pelvis, with pain in the epigastrium 2 Abdominal pain over pelvis, with pain In the umbilical

region 1

Abdominal pain over pelvis, with pain in the bladder. . . 1 Abdominal pain over pelvis, with pain in the rectum. ... 2 Abdominal pain over pelvis, with pain in the flanks. ... 2 Abdominal pain over pelvis, with pain In the thighs. ... 1

Abdominal pain over pelvis, with pain In the legs 2

Abdominal pain over pelvis, with pain in the right

shoulder 2

.\bdominal pain over pelvis, with pain in the chest 1

Patients complaining of backache 19

Patients complaining of headache 2

fowl. — The symptoms that a patient considers as sufliriently unusual to cause her to seek medical attention an' produced in the vast majority of cases by intraperitoneal bleeding. A history of abdominal pain was procured from


300 patients (yiW), the other three patients stated positively that there had been no abdominal pain or discomfort and they came to the clinic on account of irregular bleeding. In each of these three patients an unruptured tubal pregnancy was found at operation, but no evidence of any clot or free blood in the jicritoneal cavity.

The onset of the symptoms may be acute without other prodromal symptoms, although there is usually a history of a missed period or of irregular bleeding. In a second type there is an acute attack following prodromal symptoms, which the patient sometimes ascribes to her pregnancy. A third type of patient gives a history of gradual onset without an acute attack.

Recurring attacks of pain occurred in 102 cases (34^) ; seventeen patients complained especially of soreness and tenderness, ratlier than of definite pains. In several instances the pain was of several years' duration, generally with a recent exacerbation, but in each instance at operation some other condition, usually chronic pelvic inflammatorj- disease, was also present.

The pains seem rarely to radiate. Tlie character of the pain was described as violent, agonizing or severe in 90 cases, cramping in 41, colicky in four, bearing down in 14, laborlike in nine, shooting, cutting or sticking in si.\ and as dull or aching in 29.

Pain or irritation in the rectum and l)ladder occur after intraperitoneal hemorrliage, most often when clots have collected in the pelvis and adhesions have formed. Pain and vaginal bleeding often occur about the same time. Myssey (St. Paul Med. Jour.. ]!)14, XVI, 588) states that pain on defecation is almost pathognomonic of the condition, but in our experience, this symptom is also frequently present in cases of pelvic inflammatory disease.

MENSTRUAL HISTORY One hundred and three patients (34'ii) stated definitely that they had missed one or more periods; and 31 (10;^) said that their last period had been overdue for from one to five weeks, while 52 (IT"^) had noticed that the last period was abnormal in some other respect.



Number


Number


Number



of periods


ol


o( period!


ol



mined


patienta


mined


patients



1


42


7


1



2


14


8


2



<


14


9




4


2


lU


3



5


4


11


1



(t


U


Total


. .1U3 patients.



Increased frequency of menstruation 14

Constant bleeding since last period 60

No irregular bleeding 49

No irregular bleeding and no periods missed 18

Periods normally regular 210

Periods normally irregular 30


18


[No. 333


Last menstrual period :

Overdue 1 week 11

Overdue 2 weeks 1 1"

Overdue 3 weeks 2

Overdue 4 weeks 1

Overdue 5 weeks 1

Ahead of regular time 12

Shorter than usual 5

Longer than usual 2ii

Flow decreased 1^

Flow increased 9

Color abnormal 5

Xausea and vomiting occurred in a few cases, as in normally pregnant women and the patients with these symptoni> considered themselves pregnant. In the great majority, however, there was a history pointing to intraperitoneal hemorrhage before nausea or vomiting had occurred.

Abdominal masses were noticed by the patients in cases of advanced pregnancy and wliere a walled-otf hematocele was present.

Fainting occurred in some cases wliere there was profuse intraperitoneal hemorrhage.

Chills and fever were unusual .symptoms and always suggested the gravest complications.

Weakness is generally present in the more anaemic.

Loss of weight was noticed only in advanced tubal pregnancy, as also was the complaint of a bad taste in the mouth.

The notes in our histories as to whether the patient considered herself pregnant are very incomplete, and no conclusions can be drawn from them except that not all believed that they were pregnant.

SIGNS

In the following tabulation of physical signs, it is notable that many of the presumptive signs of intrauterine pregnancy are not present in the majority of this series of ectopic pregnancies. In the larger percentage of the cases in which the table gives " a softened and enlarged cervix or fundus " the notes Avere " slightly softened " or " slightly enlarged " and often there was a difference of opinion in those cases examined by two men. We believe that most cases of tubal pregnancy show no very definite gross changes in the cervix and uterine body, unless the foetus is living. In no case was a positive Hegar's sign recorded. Vaginal cyanosis was not marked in any case.

The usual aksence of definite muscle spasm or rigidity is in accordance with the signs of most pelvic diseases and, where present, there was invariably blood in the peritoneal cavity, not confined to the pelvis. Voluntary resistance to deep pressure was a very common sign.

Abdominal tenderness was frequently alj.sent in cases of pelvic hematocele ; in unruptured tubal pregnancy and in advanced cases, but in patients who had had a recent severe hemorrhage, the abdomen was generally exquisitely tender.

The figures recorded on pelvic tenderness are undoubtedly too low. Certainly in those patients that have been under my ob.servation, there is usually marked tenderness, and. especially when the pelvis is filled with recent clots, tliere is an


even greater degree of tenderness than is found in cases of pelvic abscess. I have seen two eases of unruptured tubal pregnancy in which firm bimanual compression of the mass elicited no tomplaint or discomfort, but they are very unusual.

Signs ox Physical Examination Shock (extreme) 15

Breasts:

Lactating 7

Colostrum present 46 (15%)

Abdomen:

Distention 90 (30%)

Free fluid 33 (10%)

Mass 72 (24%)

Tenderness, general 21 (7%)

Tenderness, limited to lower abdomen 71 (23%)

Tenderness, limited to lower right quadrant 52 (17%)

Tenderness, limited to lower left quadrant 39 (13%)

Muscle spasm 11 (4%)

Rigidity 17 (6%)

Pelvis:

Vaginal cyanosis 6 (2%)

Bloody discharge from vagina 85 (25%)

Cervix softened 85 (25%)

Cervix enlarged 48 (16%)

Fundus softened 15 (5%)

Fundus enlarged 86 (25%)

Mass, boggy 83 (24%)

Mass, firm 38 (12%)

Mass, cystic 40 (13%)

Blood clot crepitus 21 (7%)

Tenderness 146 (48%)

HEMOGLOBIN AND LEUCOCYTE COUNT

Unfortunately, hemoglobin determinations and leucocyte counts were not done in many of the cases. It is to be remembered that the lowest point of the hemoglobin curve is not obtained until from 48 to 72 hours after an acute hemorrhage (Dunn & AVynne, John Hopkixs Hospital Bulletin, XXIX, No. 323, January, 1918). On this account, the degree of ananiiia caused by the acute hemorrhage is not determined as a rule before operation. A high leucocyte count is usually found shortly after acute intrajieritoneal hemorrhage and cannot by itself be considered an indication of infection. In our small series of leucocyte counts, there were between 20,000 and 30,000 leucocytes in 8 cases (10^) and between 10,000 and 20,000 in 39 cases (-17.5^). Tliis observation agrees with those reported by other authors.



Hemoglobin


Before Operation


Per cent of

hemoglobin


Number of

patients


Per cent of

hemoglobin


Number

of patients


15

20-30 30-40 40-.')0 50-60


1 3 13

7 19


60-70 70-80 80-90 90-100


18

20

16

9


Total number of patients on whose blood hemoglobin determinations were done prior to operation, 106.


.I.\NIUHY, 1919]


19


LEfcocvTE Count Before Opebatio.n


W. B. c.


No. of patienta


\v. B. r.


No. of patienta


\V. B. C.


No. of patients


3.000

5,000-6,000

6,000-7 ,00t)

7,00ft-8.0OO

8,000-9,000

9,000-10.000


1

2

6

.;


10.000-11.000 11,000-12.000 12.00(UI3.00() 13.0<K»-14,00«1 14.000-l.i.llOO 15,000-16,000


12

I 8

4

t>


Ifi. 000-17. 000 W.OOO-IS.IMHI IS.OOO-lO.tKMt 20,000-21.000 22.000-23,000 30.000

3

1

1 5 2


Total number of patients on whom leucocyte counts were made before operation, 82.

TEMPERATURE AND PULSE

The temperature on ailnii^t^ion to tlie hospital was less tliaii 101° F. ill 164 (9H) of a series of 180 eonsci-utive adiiiissions for ectopic jrestiition and the pulse was loss tlian I'iO jH?r minute in the same number of patients. The majority sliowed .some increase in both ]iulse rate and temperature.

Temperatire axi> Pfi-.sK ON Akmissiox to the Hospital of 180

Co.NSEClTIVE PaTIE.NTS


Teraperalure


No. of patienta


Temperature


No. of patienta


Temperature


No. of patients


Did not reginter. . . 97.0-98.0 98.0-98.5 98. .5-99.0 99.0-99.5


1

.10 26 41


99.5-100 100.0-100.5 100.5-101 101.0-101.5 101.5-102


2!) 30 8 5 3


102.0-102.5 5 102.5-103 103.0-103.5 i 1 103.5-104 2


Pulae


No. of patienta


Pulie


No. of patienta


Pulae


No. of patients


60-70 70-80 80-90 90-100 100-110


4

9

46


110-120 120-130 130-140 140-l.iO


16 21 7 5


150-160 160-170 2 170-180 1 Could not be 1 counted


pre-operative diagnosis The pre-operativc diagnosis wa.s recorded on the history in 212 cases. The correct diagnosis was made on admission in !)8 cases (4G<) and confirmed on examination after the patients had l)een anu'sthetized for oi)erntion. Twelve additional ca.«es were diagnosed correctly oidy after the patients were under ana-sthesia, while a probable diagnosis of extrauterine pregnancy was made in five other ca.ses, one of whicii had a jwsterior vaginal coeliotomy performed before the laparotomy for confirmation of the diagnosis. In 28 othc i-ases the condition was suspected but not definitely diagnosc(l until some operative procedure had been performed. In <>!• ca.^es (•iS'i) the extrauterine pregnancy was not diagnosed, although in a number of these cases some other pathologiciil condition pre.«ent was diagnosed correctly. The diagnfiscs recorded were made by some member of the resident staff in the large majority of the ca.«es.

Table of Diaonosfs Before Opkratiox Extraulprinp pregnancy (on admission examination I . . . . 98 cases Extrauterine pregnancy (on examination under aniesthesis 12 cases


Extrauterine pregnancy (probable diagnosis)

Extrauterine pregnancy (after exploratory puncture) ....

Retained membranes of extrauterine pregnancy

Pelvic abscess or extrauterine pregnancy

Chronic pelvic inflammatory disease or extrauterine pregnancy

Appendix abscess or extrauterine pregnancy

Chronic appendicitis or extrauterine pregnancy

Cystoma of ovary or extrauterine pregnancy

Myoma uteri or extrauterine pregnancy

Calcified myoma or lithopedion

Flbro-cystoma

Ovarian cyst with twisted pedicle

Multilocular cystic ovary

Ovarian tumor

Ovarian tumor ( malignant )

Papillomatous cyst of ovary

Parovarian cyst

Myomata uteri

Myomata uteri with pregnancy

Myomata uteri, cystic, or sarcoma of uterus

Myomata uteri, cystic, or angioma of uterus

Myomata uteri with adherent dermoid cyst

Pelvic abscess

Pelvic abscess with general peritonitis

Pelvic abscess or appendix abscess

Chronic pelvic inflammatory disease

Subacute pelvic inflammatory disease

Acute pelvic inflammatory disease

Chronic appendicitis

General peritonitis

Retained membranes

Abortion, infected

Miscarriage due to retroposition of the uterus

Pregnancy

Retroposition of the uterus

Chronic pelvic inflammatory disease..

Tubo-ovarian abscess

Ovarian cyst

Submucous myoma, cystic

Ovarian tumor

Extrauterine pregnancy

Chronic pelvic inflammatory disease. .

Papillocystoma of ovaries "

Tuberculous pelvic inflammatory disease

Pelvic inflammatory disease with ovarian cyst. . " No diagnosis made "


4 cases 1 case

11 cases 6 cases

<! cases 1 case 1 case 1 case 1 case 1 case 1 case 1 case 1 case 1 case 1 case 1 case

1 case

5 cases

2 cases 1 case

1 case

1 case

11 cases

1 case

1 case 20 cases

2 cases

1 case

2 cases

1 case

2 cases 1 case 1 case

1 case

2 cases

1 case


1 case

! cases


We do not believe that the Hat-footed diagnosis of extrauterine pregnancy is as simple as many writers consider it. Ill making an estimate of the percentage of faulty dingiio.^es, we should al.<o include those cases diagno.'Jed as extrauterine pregnancy which, at operation, prove to be another condition. Ill this clinic the latter class of cases is nunierous. In jirivate jiractice among more intelligent patients, there sliould be a higher percentage of correct diagnoses made than in a free clinic. The classical case of an acute ruptured ectopic pregnancy is usually clear if a .satisfactory history can be olitained, but there are a great many cases in which the history points equally well to jielvic inflammatory disea.se. The latter ili.sease also gives .symptoms that not infrequently strongly suggest extrauterine pregnancy. Cases with unilateral intlammatory di.-^ea.se are .«een in this clinic fully as often as extrauterine pregnancies and may be very puzzling. Thi'


differential diagnosis in this class of cases is often difficult even when a careful history has been taken.

Very often there are other conditions present that make a positive diagnosis practically impossible. Another stumblingblock is encountered occasionally in patients who have had an early abortion with retained membranes and have a cystic ovary on one side. We have seen three cases of this cliaracter which were correctly diagnosed by one or more members of the staff, but which were considered to be unruptured extrauterine pregnancies by other members who examined the patients under equally favorable circumstances.

There are occasional cases in which the diagnosis is in doubt even after operation has been performed, as in the following :

Gyn. No. 22180. The patient was a white woman, age 33 ; she was admitted to the hospital May 16, 191G, complaining of "bowel trouble."

Married 18 years; three children, youngest six years of age. No miscarriages. Labors normal. Fever for two weeks beginning in the fourth week following the first labor ; otherwise the puerperia were normal.

Last menstrual period February. 1916; last preceding October, 1915. Miscarriage on January 1, 1916, after slight vaginal bleeding for the preceding week. A curettage was done by her family physician January 2 and the patient was told that " the afterbirth was perfect." No foetus was seen. A period normal, except slightly prolonged, began on February 7 and lasted seven days. On February 21 an appendectomy and a curettage were performed. The surgeon who operated said that the uterus, tubes and ovaries were normal at that time. No pain followed the operation until April 6, when she had a gradually increasing pain in the lower abdomen and back. This became quite severe, but lasted only one day. The abdomen felt sore for the following three days. She had no further abdominal pain until May 13 at 6 p. m., when she began to have pain in the left lower quadrant of the abdomen, similar to the previous attack. There had been slight vaginal bleeding for three days prior to this attack, during which the bleeding increased considerably. This attack of pain lasted 36 hours.

P. .E.— Pulse 100. Temperature 99.6°, May 15, 1916. W. B. C, 19,000. Hbg. 95;?;.

Abdominal tenderness marked in the left lower quadrant and less marked in the right lower quadrant. ^Moderate rigidity below the umbilicus. A firm, smooth mass can be felt about half way between the umbilicus and pubis.

Pelvic Examination. — A bloody vaginal discharge is present. Cervix slightly softened and slightly enlarged. The tumor described above seems to be the uterus. A moderately firm mass, which is tender, can be felt in the left fornix. Blood clot crepitus in the cul-de-sac.

Diagnosis. — Extrauterine pregnancy, left, probablv witli beginning tubal abortion.

February 17, 1916. — Operation. A pelvic puncture was performed and about three ounces of old black blood was evacuated from the pelvis. The patient was immediatelv


prepared for laparotomy. There was a considerable amount of old blood in the abdomen. The tubes were found densely adherent in the cul-de-sac, the fimbriated ends were open, both tubes were considerably enlarged and oedematous. No foetal or placental tissue could be found, nor was there any visible site of an ectopic pregnancy in either tube. The tubes were released from adhesions and a cigarette drain placed through the cul-de-sac. There was a good deal of fresh bleeding during the operation. The patient was discharged June 16 after a rather prolonged convalescence. At the time of discharge the uterus was still enlarged, but there were no pelvic masses or tenderness.

TREATMENT The treatment of our cases has been operative, either by the abdominal or vaginal routes. In several cases posterior vaginal coeliotomy has been performed for diagnosis. Pelvic puncture has been employed for pelvic hematocele in a number of cases, although in 60^ of these cases a laparotomy was performed immediately afterwards.

Table of Operatioxs

Vaginal (only ) 24 cases (S%)

Pelvic puncture (only) 16 cases

Pelvic puncture with laparotomy (for hemorrhage

following puncture, 4 ) 24 cases

Pelvic puncture with dilatation and curettage. ... 3 cases

Dilatation and curettage with laparotomy 5 cases

Vaginal salpingectomy 1 case

Exploratory above Poupart's ligament into sac ... 3 cases Laparotomy 279 cases (92%)

Abdominal incision of sac with drainage 5 cases

Removal of fcetus and placenta 6 cases

Salpingectomy (unilateral) 180 cases

Salpingectomy (bilateral ) 56 cases

Resection of one tube 1 case

Puncture of hematosalpinx 2 cases

Total extirpation of sac and CONTENTSs. 12 cases

Partial extirpation of sac 1 case

Oophorectomy (unilateral) 108 cases

Oophorectomy (bilateral) 24 cases

Resection of one ovary 11 cases

Ovarian cyst tapped 1 case

Hysterectomy 30 cases

Resection of uterine cornu 7 cases

Myomectomy 5 cases

Excision of accessory tube 1 case

Ligation of remaining tube 1 case

Excision of abscess sac 1 case

Suspension of uterus 10 cases

Excision of mesenteric cyst 1 case

Excision of umbilical hernia 1 case

Resection of omentum 1 case

Release of intestinal adhesions 5 cases

Suture of rectum 3 cases

Suture of sigmoid 1 case

Resection of ileum 3 cases

Lateral anastomosis 3 cases

Additional: Perineal repair G cases

Additional: Perineal repair with suture of rectal sphincter 2 cases



Laparotomy by tlie abdoniiual rout4j has beeu preferred in all cases except those in which there was a pelvic hematocele with symptoms and signs indicating infection. In such cases, pelvic puncture and drainage is usually a safer procedure, althougii a secondary laparotomy may be necessarj' later for continued pain.

The majority of our patients have entered the hospital after examination in the Out-Patient Department and have l)een operated upon on the day following admission, unless they were in serious condition at the time of admission, when immediate operation has been performed, with very satisfactory results. One patient whose case has been previously reported by Richardson ( JoHxs Hopkins Hospital Bulletin ) was in very extreme shock when admitted to the hospital and was treated expectantly. However, three days later, operation became imperative on account of marked abdominal distention and she died on the third day after the operation. Richardson thought this patient could have been operated upon the day following admission, when she had recovered somewhat from the primary shock and before serious distention had set in.

Whenever other pathological conditions demanding operation were present, they were included in the operative treatment, when the patient's condition justified a prolongation of the procedure.

Peritoneal Toilet. — In the majority of our cases the peritoneal cavity had been cleaned of blood and clot as well as possible. In 259 cases the peritoneal cavity was cleaned of blood and clot, and in eight cases no attempt was made to evacuate blood. We believe that the convalescence is more satisfactory when the blood is carefully removed.

Irrigation. — The peritoneal cavity was irrigated in 3^ cases, sterile normal salt solution being used in 35 ca.ses and sterile water in two cases. In recent years this practice has been discontinued.

The sac ha.s been irrigated following pelvic puncture in nine cases, but this procedure has been abandoned on account of the danger of breaking through the wall and filling the peritoneal cavity with the fluid, as occurred in one case and resulted in a general peritonitis. This patient recovered after a secondary operation for drainage of the abdomen.

Drainage. — Primary drainage has been used in 150 ca.«t glass tubes were employed twice and in the remainder gaui / usually in the form of a cigarette drain. The drains arc l)referably placed through the cul-de-sac into the vagina, rather than through the abdominal wall (38 cases were drained through the abdominal incision). At the present time drains are not employed unless there is .some evidence iif infection in the pelvis or a general ooze following the release of adhesions.

Stimulant.^. — Salt solution administered subcutancously \y depended upon for stimulation during operation and halieen employed in 5fi cases. Salt solution by rectum has been used in 13 cases and with equal parts of coffee in four rase.-. The peritoneal cavity was filled with salt solution In'fore


(losing the abdomen in 34 cases, but this procedure has been discontinued, as it seems to favor post-operative distention and generally increases the patient's discomfort, as well as spreading infection over the entire abdomen, if any should be present. In the case of one patient with very serious shock, an infusion of normal .^alt .solution was administered through the radial artery and resulted in gangrene of the hand. In a few cases drug stimulants have been used hypodemiically, strychnine in 16 cases, digitalis in three cases and brandy and ether in one case.

Transfusion of blood has not been used in any case included in this series. Very satisfactory results, however, have been reported by others who have used both direct and indirect transfusion, but sometimes there is no time to match the bloods of donor and recipient and a severe reaction following the transfusion may be fatal. The majority of these acutely ruptured cases can be stimulated sufliciently with subcutaneous infusions of large quantities of salt solution to tide them over the immediate shock. As all the.se patients are of ages most favorable for operative risk and as a rule have been in good health prior to the acute onset, they usually will recover if stimulated with salt solution for the first few hours.

Lichtenstein (Muench. Med. Wchnschr., 1915. LXII, 1597) reports eight cases treated by reinjection of the blood found in the patient's abdomen after defibrination and dilution with salt solution 3:2, a procedure open to criticism.

The intravenous injection of 7^ acacia in distilled water, filtered and sterilized by boiling, will probably prove to be of great value in those cases in which there is severe shock due to great loss of blood volume (Rous-Wilson, Jour. Am. Med. Assn., January 26, 1918). We have used this preparation in one case in which there was an abundant hemorrhage at operation and severe shock, with gratifying results.

There are, of course, patients in such serious shock when first seen that operation is contra-indicated. In these cases shock must be combated by some of the methods mentioned above, but as soon as the patient is in condition to stand operation, it should not be delayed.

The time consumed in operating is shown in the table for 255 cases.


Table Siiowixo the Dr


RATION ay


OrERATIONS






Number



Number


Timt


of


Time


ol


Time


ol



cues



C*Mt



cue*


mi».



An. Mill.



krf. ndi.



S


3


45


22


1 25


4


10


6


60


23


1 30


4


16


4


55


14


1 40


2


20


10



21


1 45


4


26


14


1 6


11


1 SO


2


30


21


1 10


17


1 65


2


35


29


1 16



2


2


40


23


1 20


8


2 10 2 26


2

1


Total, 256 operations.


All operations consuming less than 20 minutes were pelvic punctures only.


22


[No. 33.


Thirty operators performed 267 operations.

One operator performed 44 operations

One operator performed 35 operations

One operator performed 27 operations

One operator performed 21 operations

One operator performed 15 operations

Two operators performed 14 operations (each)

One operator performed 12 operations

One operator performed 11 operations

One operator performed 10 operations

One operator performed 9 operations

One operator performed 8 operations

Two operators performed 6 operations (eacli)

One operator performed 5 operations

Four operators performed 4 operations ( each )

One operator performed 3 operations

Six operators performed 2 operations (each)

Four operators performed 1 operation ( eacli )

Ancesthesia. — Iii the large majority of these cases, nitrous oxide followed by ether, administered by tiie open drop method, lias been used. Some patients have been given chloroform or ether only, and a few chloroform and ether.

Diagnosis at Operation

Ruptured with free blood in peritoneal cavity 100 -, .„^ .

Ruptured with encapsulated blood in peritoneal cavity 66 r Tubal abortion with free blood in peritoneal cavity ... 381 Tubal abortion with encapsulated blood in peritoneal I (19%)

cavity 13 J

Unruptured , 55 (20%)

Total 272

Interstitial pregnancy, right 2 '

Tubal pregnancy, right 135

Tubal pregnancy, left 131

Ovarian pregnancy, right 2 '


Total 270

' Wynne, J. H. H. Bull. XXIX, No. 324, February. 1918. - CuUen & McAll. Surg., Gyn. & Obst.. 1912; M.ver & Wynne, to be reported.

Advanced Extrauterine Pregnancy


In one case the pregnant tube was ruptured during the examination under ether. Active hemorrhage at time of operation occurred in 20 cases.

The peritoneum was noted as blood stained before bcinu opened in 43 cases.

The blood in the peritoneal cavity was designated as fluid in 66, clotted in 24 (infected, three) ; there were fluid and clots in 55 cases.

The opposite tube was noted to be normal in 15 cases.

The opposite ovary was noted to be normal in 12 case.s.

The appendix was described as normal in 31 cases.

The appendix was involved in the sac in 11 cases.

The appendix was adherent to a myoma in one case.

A CASE OF PREGNANCY IN A RUDIMENTARY HORN Gyn. No. 16T27. The patient was a white woman, age 30, admitted to the hospital June 9, 1910, complaining of vaginal l)leeding and pain the left .side of the abdomen. Married five vears; one child two years old. One miscarriage at two months, one year ago. Labor and puerperia normal. Last menstrual period January, 1910.

P. I. — The patient considered herself pregnant, but noticed that the uterus had not enlarged as rapidly as during her former pregnancy and that the enlargement was more on the left side than on the right. For a month she has noticed tenderness over the left side of the abdomen. At 6 a. m. on the morning of admission, she was awakened by pains in the pelvis, similar to labor pains and shortly after, passed blood and bits of tissue resembling placenta. There was slight bleeding afterwards, but the pain subsided. She was nauseated this morning.

Phi/gical Examination Under Ether. — On abdominal examination, a mass can be felt in the lower abdomen, which is rather soft and boggy and about the size of a large orange. The mass is movable and seems to be attached to the uterus.


Gyn. No.


Race


Age of patient


Date


Fre-operative diagnosis


Operation


Placenta


Result


Feetus




Years 114


B.


29


1890


Fibrocystoma.


Laparotomy.


Removed.


Died. Shock.


Dead. Male. Length 53 cm.


101


B.


28


1890


Abdominal pregnavicy (several mos. past term) .


Lai "•^'tomv

Removed.


Recovery.


Wt. 2800 grms. Male. Dead. Fully developed. Crown rump 30 cm.


1,705


W.


42


1893


Ectopic, two months past term.


Lapatpitomy.


Removed.


Died. General peritonitis.


Dead. Length. 42 cm.: wt., 4 lbs.


4,564


B.


45


1896


Calcified myoma or litliopedion four years past term.


Laparotomy. (Reported by


Removed. J. G.Clark).


Recovery.


Lithopedion. Weight, 43 lbs.


7,182


W.


34


1899


M u 1 1 i 1 c u 1 a r cystoma

ovarii. Ruptured tubal pregnancy,


Laparotomy.


Removed.


Recovery.


Dead. Length, 25 cm.


12.207


W.


41


1905


Laparotomy.


Removed.


Recovery.


Macerated. Weight, 12.')0






two months past term.





grms. Dead.


13.272


B.


28


1906



Laparotomy. Laparotomv.



Recovery. Recovery,


Full term, female. Living. Six months. 33 cm. long.


13,546


W.


35


1907


Extrauterine pregnancy.


Removed.






ruptured.






13.673


B.


30


1907



Laparotomy. Laparotomy.



Recovery. Recovery.



13,806


B.


33


1907


Abdominal pregnancy.


Removed.


Macerated remains of foetus.






(Reported by CuUen,


Surg., Gvn. cS:


b.st., 1915, X


X, 261.)



17,056


W.


35


1911



Laparotomy.


Removed.


Recovery.


Dead. Intraligamentary, rt. Weight, 6A lbs.


19,092


B.


22


1913


Extrauterine pregnancy, infected.


Laparotomy.


Removed.


Died. General peritonitis.


Macerated. Femur, 5.2 cm. Humerus, 4.8 cm.


21,494


B.


29


1915


Ovarian tumor, right.


Laparotomy.


Removed.


Recovery.


Dead. Weight, 1911 grms. 44.5 cm.


Januabt, 1919]


23


Pelvic Examination. — The vagina and cervix are normal. The fundus of the uterus is soft and boggy and, attached to it by a pedicle, is the mass described above.

Pre-Operative Diagnosis. — Extrauterine pregnancy or pregnancy in a rudimentary liorn.

Operation. — The mass was found to be a pregnancy in thi; rudimeutarj' left horn of a bicornat* uterus and was attached to the right side of the uterus by a small pedicle. The left tube was stretched over the pregnant horn and togetlier with the left ovary was so intimately associated with it as to necessitate their removal. The left horn was amputated close to the right side and there remained a practically normal uterus.

The patient was discharged on the 13th day after an uncomplicated convalescence.

Diagnosis. — Pregnancy in a rudimentary horn, left.

Pathological Xo. 15,150. — The specimen has been opened anteriorly in the operating-room and measures 7x8x5 centimeters. The walls measure 1.5 centimeter in thickness. Foetus of 4 to 5 months in unruptured membranes.


Patholooicai, Retobts

The tissues removed at operation have been studied histologically and the diagnosis has been verified. We are unable at the present time to give a thorough report on this interesting side of the disease.

The routine preparations, where the endometrium was examined, have been reported as follows:

Normal endometrium 13

Gland hypertrophy of the endometrium 5

Endometritis, chronic 5

Endometritis, acute 1

Decidual reaction of the endometrium 7

Cast of uterine cavity with decidual reaction 2

In addition to ectopic pregnancy the following diagnoses were made at or before operation :

Atrophy of the opposite tube 1

Hematosalpinx of the opposite tube 3

Hydrosalpinx of the opposite tube 16

Chronic salpingitis of the opposite tube 8

Pyosalplnx of the opposite tube 6

Tuboovarian abscess of opposite tube 1

Ovarian abscess •. 3

Chronic pelvic inflammatory disease 92

Cystic ovaries 13

Ovarian cyst, follicular 9

Ovarian cyst, corpus luteum 3

Parovarian cyst 1

Retroposition of the uterus 6

.Myomata uteri 17

.Membranous dysmenorrhoea 1

Mesenteric cyst 1

General peritonitis 1

Pre-operative rupture of abscess Into rectum 1

Post-operative adhesions 1

Bladder adhesions 1

Omental adhesions 14

Intestinal adhesions 19

Meckel's diverticulum 1


Umbilical hernia


2


Appendicitis, chronic


52


Appendicitis, sub-acute


5


Appendicitis, acute


2


Periappendicitis


7


Complications before operation : Pulmonary tuberculosis


2


Diabetes i


Insanity i


Arthritis deformans i


Chronic nephritis i


Ascaris lumbricoides i


Uncinaria Americana l


Post-operative Compucatioxs

The complications following operations have been as follows:

Acute bronchitis 2 cases with recovery.

Bronchopneumonia 2 cases with recovery.

Lobar pneumonia 2 cases with 1 death.

Fecal fistula, abdominal 2 cases with 1 death ")

Fecal fistula, vaginal 1 case with death. . . ll patient.

Urinary fistula, abdominal 1 case with death. . . J

Atonic ileus 1 case with recovery.

Peritonitis, general G cases with 5 deaths.

Infected drainage cavity with

collection of pus 3 cases with recovery.

Cystitis 2 cases.

Phlebitis (of left leg) 3 cases.

Tetanus 1 case with recovery.

(Reported by Casler at Southern Medical Association meeting in 1917.)

Gangrene of the hand following intraarterial (radial) salt infusion 1 case.

Mastitis, right 1 case.

Acute follicular tonsillitis 1 case.

Influenza 1 case.

Erysipelas (facial) 1 case.

Shock and antcmia have been omitted from this list, as accurate data for all cases are not available.


SuBSEQfE.XT Operations for Co.mplicatio.vs Abisino erom the Prim.\by Operatiom

Gyn. No. 2,612. Abdominal drainage for peritonitis following rupture of sac by Irrigation after pelvic puncture. Symptoms of peritonitis 11 days after operation. Recovery.

Gyn. No. 7,901. Exploratory laparotomy for localized poritonitta 36 hours after left salpingo-oophorectomy and vaginal drainage. Death on the sixth day from lobar pneumonia.

Gyn. No. 11,473. Pelvic puncture for drainage, 23 days after salpingo-oophorectomy. Recovery.

Gyn. No. 11,491. Dilatation of drainage tract and evacuation of pus 10 days after pelvic puncture. Recovery.

Gyn. No. 12,380. Rupture of abdominal incision 22 days after laparotomy. Recovery.

Gyn. No. 15,529. Right salpingo-oophorectomy and release of adhesions 1.J days after pelvic puncture and drainage of infected hematocele. Recovery.


34


[No. 335


Gyn.No. 17,251.


January 16, 1911, at the first operation, during hysterectomy, left salpingo-oophorectomy and release of adhesions, the rectum was torn. Abdominal fecal fistulae resulted.

April 29, 1911. Excision of- fistulous tracts, suture of rectum and bladder. Appendectomy. Failure.

September 18, 1911. The patient was readmitted to the hospital (Gyn. No. 17,804) for abdominal fecal fistula and a recto-vaginal fistula following her first operation.

September 30, 1911. Excision of abdominal fistula, resection of sigmoid, end-to-end anastomosis, suture of bladder. Shock.

October 5, 1911. Enterostomy for ileus.

October 6, 1911. Enterostomy for ileus. Death on the table.


CAUSE OP DEATH There have been 13 deaths in our scries of 303 cases and autopsies were performed on six of these.

Gyn.No. 114. (Autopsy No. 72.) Shock 12 hours after operation. This patient was in a very critical con


dition when operated upon. No anatomical cause of death was found at autopsy.

Gyn.No. 521. (Autopsy No. 181.) Died 24 hours after operation. The anatomical diagnosis at autopsy was: Acute general peritonitis (pure culture B. coli from bloody peritoneal fluid), perforation of appendix with circumscribed abscess.

Gyn.No. 1,795. (Autopsy No. 38S.) Died 10 days after operation. At autopsy an acute fibro-purulent peritonitis, chronic diffuse nephritis and gallstones were found.

Gyn.No. 7,901. (Autopsy No. 1562.) Death 6 days after operation, of lobar pneumonia.

Gyn. No. 10,678. (No autopsy.) Death 3 days after operation. On admission the hemoglobin was 15 per cent and on the day of death 10 per cent.

Gyn. No. 12,042. (No autopsy.) Death 9 hours after operation. This patient was operated on by the vaginal route and a large amount of clot and fiuid blood evacuated, followed by a gush of bright red blood. Laparotomy was immediately performed. Shock.


Table Showing Pbegnancies Since Operation


Character of operatit


No. of years since operation


of ciiildren and miscarriages since operation


1,636

1,710

2,805

4,120

6,482

8,441

9,740

9,746

10,258

10,544

11,215

11,244

11,592

11,830

11,834

12,236

12,268 12,398 14,167 15,309

15,644

15,955 17,428 18,744

19,781 20,777 21,017 21,082 21,483 22,303 22,445


Incision of sac with drainage

Enucleation of sac

Right salpingo-oophorectomy

Pelvic puncture with drainage

Right salpingectomy

Right salpingo-oophorectomy

Left salpingectomy

Right salpingo-oophorectomy

Left salpingectomy

Left salpingectomy with resection of right ovary

Right salpingo-oophorectomy

Pelvic puncture and exploratory laparotomy

Right salpingectomy

Pelvic puncture •

Left salpingo-oophorectomy

Right salpingo-oophorectomy

Right salpingectomy

Right salpingo-oophorectomy

Left salpingo-oophorectomy and resection of right ovary. . Left salpingo-oophorectomy

Right salpingo-oophorectomy

Left salpingo-oophorectomy

Right salpingectomy

Right salpingectomy

Right salpingectomy

Resection of right cornu

Right salpingectomy, resection of right ovary, myomectomy

Right salpingectomy

Right salpingectomy

Right oophorectomy

Left salpingo-oophorectomy


23 months 20 months

15 months

16 months


5 full-term children. 2 full-term children.

1 full-term child.

2 full-term children.

1 miscarriage at 2% months 4 years after operation.

2 full-term children, 1 miscarriage. 1 miscarriage.

5 miscarriages, the first 2 years after operation.

1 full-term child.

2 full-term children. 2 full-term children. 1 full-term child.

6 full-term children.

1 tubal pregnancy 8 years after operation.

1 full-term child.

2 miscarriages 10 and 8 years ago at 3 months;

1 full-term child 6 years ago.

1 miscarriage.

2 miscarriages.

1 full-term child.

1 full-term child 2 years after operation; 1 miscarriage 6 years after operation.

1 miscarriage and 1 full-term child 3 years after operation.

1 full-term child.

1 full-term child.

1 full-term child 14 months after operation; 1 fullterm child 32 months after operation.

8 months pregnant when heard from.

1 full-term child 1% years after operation.

1 full-term child 1 year after operation.

1 miscarriage (induced) 6 months after operation.

3 weeks from term when heard from.

1 full-term child IS months after operation. 1 full-term child 11 months after operation.


F^VE Patients Opekated on fob Second Ectopic Pregnancy in This Clinic


Second operation


4,147

9,781

13,776

15,771

16,230


Pelvic puncture in 1896

Right salpingo-oophorectomy in 1902

Left salpingectomy in 1907

Right salpingectomy in May, 1909

Right salpingo-oophorectomy in November, 1909


Right salpingectomy in 1904

Left salpingo-oophorectomy in 1905

Right salpingectomy in 1908

Left salpingectomy in November, 1909

Hysterectomy; left salpingo-oophorectomy in January, 1911


11,590 12,290 14,895 16,188

17,251


January, 1919]


25


These six fatalities were reported in Kelly's Operative

Gynecology, Vol. II.

Gyn. No. 12,830%. (No autopsy.) Death 4 hours after operation. The patient was in serious shock when operated upon. About 2 liters of free blood were evacuated from the abdomen.

Gyn. No. 15,314. (No autopsy.) Death 3 days after operation from shock. (Reported by E. H. Richardson.)

Gyn. No. 17,119. (No autopsy.) Death 2\i hours after operation. The patient was in good condition after the operation until 3 minutes before death. Probably embolus.

Gyn. No. 17,211. (.\utopsy No. 3489.) Death 8 days after operation. Anatomical diagnosis at autopsy: Acute general peritonitis.

Gyn. No. 17,251. (No autopsy.) Death S days after secondary operation tor fistula following primary operation. General peritonitis.

Gyn. No. 18,731. (No autop.sy.) Death 2Vi hours after operation. Shock. This patient had diabetes.

Gyn. No. 19.092. (Autopsy No. 38S4.) Death 12 days after operation. .\t autopsy acute general peritonitis and embolic pneumonia were found. At operation the sac containing foetal bones and infected material was ruptured.

Immediate Resvlts

Well 271 (89.4%)

Improved 19 (6.3%)

Died 13 (4.3%)

Ultijiate Results Letters were sent to the 290 patients who recovered from the operations for ectopic pregnancy. Answers to the fol


low-up letters were obtained from 118 patients and nine, who did not answer the letter, were later readmitted to this hospital. Of 120 patients, 100 have been well since operation, five have had poor health since operation, .seven report fair health and two no change in general health since operation. Four had good health for several months or years, and afterwards died, one of pulmonary tubenulosis, one of acute intestinal obstruction, one of post-operative pneumonia. In one ease the cause of death was not stated.

Of the series of 127 cases, there was no possiltility of future pregnancy in 33. Of the remaining 9G in whom there wa.s a possibility of future pregnancy 36 (38°) have since become pregnant one or more times; 61 pregnancies have resulted in •?7 full-term children ; two patients were pregnant almost at term when heard from. In 16 cases the pregnancy ended in miscarriages and six patients had a second extrauterine pregnane}'.

Opeuatioxs Subsequent to Operation fob Ectopic Pbeonaxct Post-operative ventral hernia has occurred in eight cases; four have been repaired in this hospital and one in another hospital, and three patients have not been submitted to another operation. One patient was operated upon for intestinal obstruction and one had a vaginal panhysterectomy performed in this hospital for carcinoma of the cervix. In all 14.5 patients have been followed on this point.

I wish to thank Dr. Howard A. Kelly for permission to publish this report.


NOTES AND NEWS


Dr. George Blumer is Chairman of the Medical Advisory Board, Yale University, New Haven, Conn.

Dr. Montague Boyd is Associate Professor of Surgery (Genitourinary), Emory University: Andrologist, Wesley Memorial Hospital and Visiting Genitourinary Surgeon, Grady Hospital, Atlanta, Ga. Government service: Captain. M. R. C, on duty in France.

Dr. Walter V. Brem is .Major .M. C, and Chief of the .Medical Service, U. S. Army Base Hospital, Camp Fremont, Cal.

Dr. Helen Smith Brown is Lecturer In Social Hygiene for the Commission on Training Camp .Activities, Washington. D. C.

Dr. S. W. Clausen is Instructor in Pediatrics, Washington University Medical School and Assistant Physician to the St. Louis Children's Hospital. He Is First Lieutenant, M. R. C, and is in active service.

Dr. Malvern B. Clopton is Major, M. R. C. He is a member of Washington University Hospital Unit No. 21, and is stationpd with General Hospital No. 12, B. E. F., Rouen, France.

Dr. Stanley Cobb is First Lieutenant. M. C, Division of Brain Surgery.

Dr. Sydney M. Cone Is Captain, M. R. C, and is stationed at the Alder Hey English Military Orthopedic Hospital. England.

Dr. Henry Wireman Cook is Associate Director of the Bureau of Medical Service, American Red Cross, Washington, D. C.


Dr. W. L. Cousins Is Surgeon-in-Chlcf of St. Barnabas Hospital, Portland, Me. Government service: Major, M. R. C, and Chief of the Surgical Staff U. S. Army Base Hospital, Camp Gordon, Ga.

Dr. J. Stalge Davis is Captain, M. C, U. S. Army, and is on active duty in Baltimore.

Dr. Ernest C. Dickson Is Associate Professor of Medicine, Iceland Stanford University School of Medicine. Government service: Captain, C. A. M. C, stationed In Basingstoke, England.

Dr. Richard N. Duffy Is Surgeon to the New Bern General Hospital, New Bern, N. C.

Dr. C. B. Dunn Is Chief of Staff, Southeastern Hospital for the Insane, Madison, Ind., and on the teaching staff King's Daughters Hospital, Madison, Ind.

Dr. Arthur B. Emmons Is Captain. M. R. C, and Is stationed In Evacuation Hospital No. 2, A. E. F., France.

Dr. W. L. Estes, Jr., la Director of St. Luke's Hospital, South Bethlehem, Pa. Government service: Captain, M. R. C, attached to Mobile Operating Unit No. 1. Section No. 1, A. E. F., France.

Dr. William W. Farr Is Captain, .Medical Corps, U. S. A., stationed at U. S. Base Hospital. Camp Shelby, Hattlesburg, Miss., with title of Chief of Subsection of Otolaryngology.

Dr. A. L. Fisher is Captain, M. C, and is In charge of the Surgical Service, U. S. Base Hospital No. 30, A. E. F.


26


[No. 335


Dr. J. M. T. Finney is Brigadier General, M. C, U. S. Army, and is Surgical Consultant, A. E. F., France.

Dr. Simon Flexner is Lieutenant Colonel, Medical Corps, U. S. A. He is on duty at the Rockefeller War Demonstration Hospital, New York City.

Dr. James R. Garber is Instructor in Obstetrics South Highlands Infirmary Training School for Nurses, Visiting Obstetrician to the Hillman Hospital, Attending Obstetrician to the Salvation Army Home, Birmingham, Ala., and Acting Secretary of the Southern Medical Association.

Dr. S. McPheeters Glasgow is Captain, M. C, and is stationed at Camp Zachary Taylor, Ky.

Dr. L. W. Gorham is Captain, M. R. C, and is stationed with I\ S. Base Hospital No. 33, Portsmouth, England.

Dr. F. F. Gundrum is Vice-President, California State Board of Health, and Consulting Physician, Sacramento County Hospital. Government service: Chairman Medical Advisory Board No. 7, Sacramento, Cal.

Dr. Louis Hamman is Acting Physician-in-Chief to The Johns Hopkins Hospital and Acting Professor of Medicine, Johns Hopkins University.

Dr. F. M. Hanes is connected with Base Hospital No. 65, A. E. F., France.

Dr. Henry Harris is Instructor in Medicine, University of California. Government service: Member of Medical Advisory Board, District No. 5, California.

Dr. R. F. Hegeman is Captain, M. R. C, and Is Assistant Chief of Base Hospital'No. 96.

Dr. Campbell P. Howard is Professor of Theory and Practice of Medicine and Clinical Medicine, State University of Iowa, and Physician to the University Hospital.

Dr. Henry T. Hutchins is Major, M. C, and is Surgeon-in-Chief, Evacuation Hospital No. 49, A. E. F.

Dr. J. Edwards Kerney is Visiting Urologist, Memorial Hospital, Pawtucket, R. I.; Visiting Urologist to Rhode Island State institutions; Associate Visiting Urologist to St. Joseph's Hospital, Providence, R. I.: and Surgeon in Urology to Rhode Island Hospital, O. P. D., Providence, R. I.

Dr. Clarence F. M. Leidy Is Captain, M. C, 62d Pioneer Infantry, Camp Wadsworth, S. C.

Dr. Hans Lisser is Instructor in Medicine, University of California Medical School, and Assistant Visiting Physician, University of California Hospital. Government service: Chief Examining Physician, Local Draft Board No. 4, Oakland, Cal.

Dr. Herbert M. Little has taken up again his work as Assistant Professor of Obstetrics and Lecturer in Gynecology, McGill University, after two years' duty overseas with the Canadian Army Medical Corps. He is also Assistant Attending Obstetrician, Montreal Maternity, and Assistant Attending Gynecologist, Montreal General Hospital.

Dr. David Russell Lyman is Medical Superintendent, Gaylord Farm Sanitarium, and Clinical Lecturer on Tuberculosis, Yale Medical School. He was for six months with the Rockefeller Commission for the Prevention of Tuberculosis in France, and with the Tuberculosis Bureau of the American Red Cross.

Dr. W. G. JlacCallum is Contract Surgeon, U. S. Army.

Dr. J. D. Madison is Captain, M. C, and is stationed in Milwaukee, Wis., as President of the Examining Board for Medical Officers' Training Camp, etc.

Dr. W. McK. Marriott is Professor of Pediatrics, Washington University Medical School, Physician-in-Chief to the St. Louis Children's Hospital, and Consulting Physician to the St. Louis City Hospital and the St. Louis Isolation Hospital.

Dr. Robert T. Miller is Lieutenant Colonel, M. C, Director U. S. Base Hospital No. 27, and Chief of Surgical Staff Mobile Hospital No. 1.


Dr. Ralph G. Mills, Assistant Resident Pathologist Johns Hopkins Hospital, is Professor and Head of Department of Pathology, ' Peking Union Medical College, Peking, China (absent on leave).

Dr. George R. Minot, Jr., is Assistant Professor of Medicine, Harvard Medical School; Associate in Medicine, Massachusetts General Hospital, and Assistant Consulting Physician to Collis P. Huntington Memorial Hospital of the Harvard Cancer Commission. Dr. Roger S. Morris is Forchheimer Professor of Medicine, Medical Department University of Cincinnati; Director of the Medical Division Cincinnati General Hospital, and Director of the Outdoor Dispensary. Government service: Major, M. C, on duty abroad.

Dr. W. Bean Moulton is Captain, M. R. C, and is stationed at Camp Greenleaf, Chickamauga Park, Ga.

Dr. C. D. Parfitt is Lecturer on Medicine, University of Toronto, and Advisor to the Tuberculosis Clinic, General Hospital, Toronto. Dr. Francis W. Peabody is Assistant Professor of Medicine, Harvard Medical School; Physician to the Peter Bent Brigham Hospital, and Consulting Physician to the Collis P. Huntington Memorial Hospital. Government service: Major, M. C, on active duty in France.

Dr. Louise Pearce is Associate in Pathology at the Rockefeller Institute for Medical Research, New York City.

Dr. Clement A. Penrose is Major, M. R. C, at present on inactive duty.

Dr. H. W. Plaggemeyer is Captain, M. C, and is on active duty in France.

Dr. Alexander Randall is Captain, M. R. C, and is stationed with the 6th Army Corps, France.

Dr. George K. Rhodes is First Lieutenant, Medical Corps, U. S. A., on duty at U. S. Base Hospital, Camp Meade, Md.

Dr. Hunter Robb is Major, M. R. C. He is stationed in the Medical Officers' Training Camp at Camp Greenleaf, Ga.

Dr. Peyton Rous is Associate Member, Rockefeller Institute for Medical Research, New York City, and Vice-Chairman, Division of Medicine and Related Sciences, National Research Council, Washington, D. C.

Dr. W. G. Sexton is First Lieutenant, M. C. He is on duty with U. S. Base Hospital No. 158, Camp Greenleaf, Ga.

Dr. W. F. Shallenberger is Associate Professor of Gynecology, Emory University; Visiting Gynecologist, Wesley Memorial Hospital; Visiting Gynecologist, Georgia Baptist Hospital, and Assistant Visiting Gynecologist, Grady Hospital, Atlanta, Ga.

Dr. Frank J. Sladen is Captain, M. C, and is Assistant Chief of Medical Service, U. S. Base Hospital, Camp Sherman, Ohio.

Dr. J. Morris Siemens is Major, M. R. C, and is Chief of the Surgical Service, U. S. Base Hospital No. 92, Cape Greene, N. C.

Dr. F. Janney Smith is Captain, M. C. He is Chairman, Cardiovascular Examining Board, and President, Certificate of Disability Board, 155th Depot Brigade, Camp Lee, Va.

Dr. Winford Smith is Colonel, Medical Department, U. S. A., and Chief of Bureau of Administration, Hospital Division, Surgeon General's Office, Washington. D. C.

Dr. Richard P. Strong is Major, M. C, and is stationed in France. Dr. Solomon Strouse is Assistant Professor of Medicine, Northwestern University; Attending Physician, Michael Reese Hospital; Director, Department of Medicine, Michael Reese Hospital Dispensary. Government service: Secretary and Member of Medical Advisory Board 3 J, Michael Reese Hospital.

Dr. Adrian Taylor, Assistant Resident Surgeon, The Johns Hopkins Hospital, is Professor of Surgery and Head of Department of Surgery, Union Medical College, Peking, China.

Dr. W. S. Thayer is Physician-in-Chief to The Johns Hopkins Hospital and Professor of Medicine, Johns Hopkins University. Government service: Brigadier General, M. C, U. S. Army, and Chief Medical Consultant, A. E. F., France.


Dr. Charles B. Thompson is Executive Secretary, Meulal Hygiene Society of Maryland: Psychiatrist at the Hebrew Hospital Dispensary, and Lecturer on Psychiatry to the Training School of the L'nion Protestant Infirmary.

Dr. Douglas Vanderhoof is Professor of Medicine in the Medical College of Virginia, Physician-in-Chief to the Virginia Hospital, Senior Attending Physician to the Memorial Hospital, and consulting Physician to the Johnston-Willis Sanatorium. Government service; Secretary Medical .-\dvisory Board No. 2. Richmond, Va.

Dr. Cecil \V. Vest is Captain. .M. C. and is stationed at Camp Meade, Md.

Dr. Carl \V. Waldron is Captain. C. A. M. C. O. C. The Canadian Unit. He is stationed at The Queen's Hospital, Frognel. Sidcup. Kent, England (for facial and jaw restorations).

Dr. Louis .M. Warfield is Major. M. C. and is Chief of the Medical Service, Jefferson Barracks. Mo.

Dr. S. Shelton Watkins is Lieutenant, M. C. U. S. Navy.

Dr. Ernest M. Watson is Instructor in I'rology. .Medical Department, University of Buffalo; Attending Urologist to Buffalo City Hospital, Municipal and Ernest Wende Hospital: Assistant Attending Urologist to Erie County Hospital, and Assistant in Clinical Urology, Buffalo General Hospital.

Dr. Charles W. Webb is Chief Surgeon to the Clifton Springs Sanitarium and Hospital. Clifton Springs, N. Y.

Dr. Harry 1. Wiel is Assistant in Medicine, University of California, and .Assisting Visiting Physician, San Francisco Hospital, San Francisco, Cal.

Dr. Gordon Wilson has taken up again his work in Baltimore after serving as Major, M. R. C. having been assigned to Camp .Meade as Tul>erculosis Specialist.


NOTES ON NEW BOOKS

The liuntgcn Diagnosis of Diseases of the Alimenlary Canal. By Ri'sstax D. C.vKMAN, M. D., and Auiebt Miixeb, M. D. (Philadel/ihia: W. B. Saunders Company. 1917.)

It Is quite refreshing to read such a splendid description of the various methods and means of diagnosis as are put forth by Carman and Miller.

After a description of apparatus, technic and interpretation they take up the different organs and the various manifestations of disease as evidenced by rcpntgon examination.

Of especial value is the liescription of the normal findings before each chapter on the various organs, thus giving the student a much clearer conception of the pathologic states as outlined later. The idea of giving classified lists of roentgenologic signs in various diseases is noteworthy and a splendid idea.

Among other things which make the book graphic and impressive is the fact that practically all cases shown have been verified by operation and noted in the text— also the references at the end of each chapter prove to be another great asset.

Altogether the book is of great value — easy to read and understand because of the clearness of the text — the various points are graphically portrayed by splendid illustrations, and every subject receives thorough consideration from all points of view. It is a book which should be read by every rrentgenologlst as well as all practitioners interested in the roentgenologic diagnosis of gastrointestinal conditions, as It Is undoubtedly by far the foremost publication on the subject to-day. E. H. G.


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Contents

Fluoroscopy of the Cerebral Ventricles. (Illustrated. t A Pliarmacological Appreciation of a BIhliral Reference to

By WAi.TtB E. Dandv J'J Mass Poisoning, 11 Kings IV, 3S-41. (Illustrated.)

Stereoroentgenogranis of tlie Injected Lung as an Aid to the B.v Uavid I. Maciit. A. B.. LL. B., M. D., F. S. .!.A. . 38 Study of the Lung Architecture. (Illustrated.)

By William Snow Miller 34 Titles of Papers Appearing Uurini; the Year. Elsewhere than in

An Electromyographic Study of Chorea. (Illustrated.) the Bulletin, by Present and Former Members of the Hos By Stanlet Cobb, M.D 35 pital and Medical School Staff 42


TITLES OF PAPERS APPEARING DURING THE YEAR. ELSEWHERE THAN IN THE BULLETIN, BY PRESENT AND FORMER MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF


Abel, J. J., and Pincoffs, M. C.

On the presence of albumoses in extracts of the posterior lobe of the hypophysis cerebri. — Utiid. Kockejeller Inst. M. Research, N. Y., 1918, x'xyiii, 193-203.

Atchley, D. W.

A study of eight cases of acute nephritis. — Arch. Int. ilcd.. Chicago, 1918, xxii. 370-408.

Renal action in acute nephritis. — Proc. Soc. Exper. Biol. A lied., X. Y., - 1917-18, XV, 85-88.

AUEB, J.

Generalized analgesia in cats after exposure to a war gas (CH3);S0,. — Proc. Exper. Biol, d Med., N. Y., 1918, xv, 104-106.

Localized pulmonary edema in cats after the inhalation of \yar gas I CH,)2S0,.— Ibid., 106-107.

AuEE, J., and Gates, F. L.

Experiments on the causation and amelioration of adrenalin in pulmonary edema. — Stud. Rocketeller Inst. M. Research, N. Y.. 1918, xxviii, 131-150.

AuER, J., and Kleixee, Isabel S.

Morphine hyperglycemia in dogs with experimental paucreatic deficiency. — J. Exper. M., Bait., 1918. xxvii, 49-03.

AuER, J., and Meltzer, S. J.

Lantern slide demonstration of the effect of magnesium sulphate upon tetanus. — Proc. Soc. Exper. Biol, d Med., N. Y., 191T-1S. xy. 36-37. The administration of epinephrin by intraspinal injections in acute or subchronic cases accompanied by a low blood pressure. — J. Am. M. .\ss., Chicago, 1918, Ixx, 70-71.

Baer, W. S.

Arthroplasty with the aid of animal membrane. — Am. J. Orthop. Surg.,

Host., 1918, xvi. 1-29: 94-115; 171-199.

Primary and delayed primary suture in the treatment of war fractures.

— Am. J. Orthop. Surg., Bost., 1918, xvi, 513-519.

Also: J. Am, M. Ass., Chicago, 1918, Ixx, 1530-1533.

Baetjer, F. H.

Differential diagnosis of bone tumors. — Am. J. Roentgenol., X. Y., 1918, y, 261-264.

Baetjer, W. A., and Miller, S. R.

Bence-Jones proteinuria : some observations on its occurrence, with particular reference to nephritis and hypertension. — J. Am. M. Ass., Chicago, 1918. Ixx, 137-139.

PoIIinosis or hay-fever : its specific treatment. — South. M. J. Birmingham, Ala., 1918, xi, 341-345.

Baetjer, W., Strong, R. P. let ah].

Report on progress of trench fever investigations. Trench Fever Commission of Medical Research Committee, American Reti Cross. — J. Am. M. Ass., Chicago, 1918. Ixx, 1597-1598.


Barker, L. F.

Heart murmurs. — Canada Lancet. Toronto, 1918, 11, 545-551. Endocrine functions and the digestive apparatus. — Med. d Surg., St. Louis, 1918, ii, 655-678.

The general diagnostic study by the internist. — -V. York M. J. [etc.], 1918, cvii. 489-493; 538-542; 577-582. Also: Med. Rec, N. Y., 1918, Nervous and mental symptoms in exophthalmic goiter. — J. Am. it. Ass., Chicago, 1918, Ixxi, 327-329.

The value of the classics as a part of the studies preparatory to medicine. — South. M. J., Birmingham. Ala., 1918. xi. 391-394. Address in Medicine. On the significance of " heart murmurs " that may be found on examination of candidates for military service. — Canad. M. Ass. J., Toronto. 1918, viii, 577-585.

Oral sepsis and the digestive apparatus. — South. M. J., Birmingham, -Ala., 1918. xi, 481-484. The first ten years of the National Committee for Mental Hygiene, with some comments on its future. — Ment. Hyg., Concord, N. H., 1918, ii. 557-581.

Barker, L. F., and Miller, S. R.

Perforating ulcer of the hard palate resembling tertiary syphilis. — J. Am. M. Ass., Chicago, 1918, Ixxi, 793-797.

Barker, L. P., and Rowntbee, L. G.

A report of a case of myrtol poisoning with comments upon the toxicity of eucalyptus oil and myrtoi in human beings and in animals. — Tr. Ass.

Am. Physicians, Phila., 1918, sxsiii.

Beall, K. H.

The diagnosis of nephritis. — Texas State J. M., Fort Worth. 1918, xiii. 349-351.

Berey, J. M.

Action of the gluteus maximus strain. — AZftonj/ if. Ann., 1918,

Blackfan, K. D.

Lead poisoning in children.


-Midland M. J., Birmingham. 191S, xvii.


Blackfan, K. D., and Maxcy, K. F.

The intraperitoneal injection of saline solution. — Am. J. Dis. Cliild., Chicago, 1918, xy, 19-28.

Block, E. B.

The relation of oral sepsis to the nervous system. — South. If. ./., Birmingham, Ala., 1918, xi, 606-609.

Bloodgood, J. C.

Some hernias that disqualify for military service, whether operated on or not. — J. Am. M. Ass., Chicago, 1918. Ixx. 515. A warning against operations for varicocele on applicants for enlistment, registrants for the selective draft and soldiers. — J. Am. M. Ass.. Chicago, 1918, Ixx, 409.

Medical preparedness and medical and surgical problems in this war. — Penn. M. J.. Athens, Pa., 1918. xxi. 389-394.

Medical preparedness in the great drive for democracy. — South. M. J., Birmingham, Alabama, 1918, xi, 51-56.


Aluo: Muruland M. J.. Unit.. T.HS. Ul. 1-0.

.ll»o; J. Florida it. Ast., St. Augustlue & .IiKksonvlllc, 1918. Iv, 2.-5 How the iniliisirliil surgodii <'iin host co-operate with the GoTornniPut

ilurlog the war.--NoM/fc. M. ./., BlrmlnKhain, Ala.. 1918. xl. 45:t-4ri4.

The liiiportiince of recocnlzlng the weakness or the obllteralinn of the

ronjolneil temlon In operations for Infrulnal hernia. — South. H. ./..

BlrmlDKhnm, Alabama. 191S. il. 3e«S(i9.

AKo: ">»f. il. Kr<-.. Omaha. Neb.. 1918. xilll. SOl-.W".

Soldiers illsableil In the war. (Letter). — South, il. J., BirinlDgham.

Alabama. 1918. xl. r,-2i;X , „ ,

Some principles Involvlne the treatment of Infeeteil wounds. — ./. J/.rf.

At: Georgia. Augusta. 1918. vlll, 9-i:i.

Bloomfield, a.

Typhoid bacterlemla during the course of miliary tuberculosis. — .liii. Kei: Tuberc, Bait.. 191S. 11. 28-35.

Brem. W. v.. Rolling. G. E. and Caspee. E. J.

Pandemic Influenza and seiondarj- pneumonia at Camp Fremont. Calif. —J. Am. il. .!»».. Chicago, 191S. Ixxl. 21.38-2144.

Bribgman, E. W., and Hibose, K.

The effect of diuretics on the general blood pressure in animals with constriction of the renal arteries. — Arch. Int. Ued., Chicago, 1918. xxi. 3.-1-.3.J3.

Brooks. B.. and Allison, N.

Arthroplasty: exp<TimentaI and clinical methods. — Am. ./. ()ilhiii>. Surg.. Boston. 1918, xvi, 83-93.

Brooks. B.. ScmMAciiER. H. W., and Wattenbero, J. E.

Intestinal obstruction: an experimental study. — Anil. Surg., I'hilii.. 1918. IXTll. 210-214.

Bbowx, T. R.

studies on some unusual tvpes of diarrhea. — ilcd. d Surg., St. I^ouis. 1918. II. 640-«4.".

BiSTixG. C. H., Martin. H. G.. and Loeveniiabt. A. S.

The mori'hologlcal changes In the tissues of the rabbit as a result of reduced oxidation.—^, i'j-pcr. J/., Bait., 1918. xxvii, 399-412.

BlBNS, J. E.

The diagnosis and treatment of urlnarr Ilthlasls. — llVst Virg. it. J., Huntington. 191s. xli. 280-291.

BfBNs, J. E.. and Hopkins, P. B.

A comparative study of the effects of thorium and other substances on the renal parenchyma when retained.— >/. Vrol., Bait.. 1918. 11. 145-1.')9.

BiBBOws. M. T.

A note on the mechanism of heart muscle contractions. — J. ilisaouri if. Atf.. St. liOUis. 1918. XT, 13S.

Why should autopsies be held? The argument to be used with relatives and friends. — Interstate it. J., Chicago, 1918. xxv. 700-763.

Burrows, M. T., and Neyjiann, C. A.

Studies on the metiiboilsm of cells In vitro. The toxicity of ilipeptiils for embryonic chicken cells. — i'ror. .S'oc. ICrpcr. Hiol. it iled., .N. Y., 1918. XV. 1.38139.

Camac, C. N. B.

Clinical report upon cases of lobar pneumonia treated with nnti Sieumococcus serum as observed at general hospital no. 6. Fort cFherson. Georgia. October. 1917. to May, 1918.— .4m.. J. M. Sc, Phila.. 1918. civi. 887-893.

Cameron. D. F.

Aqueous solutions of potassium and sodium iodlds as opaque mediums in roentgenography. Preliminary re|)ort. — /. .l»i. il. Asa., Chicago. 1918. Ixx. 754-7.—I.

Camebon, D. F.. and Gbandy. C. C.

Sodium ami potassium Iodlds In roentgenographv.--./. .4m. .1/. Ana., Chicago. 1918, Ixx. 1,'.I0-1.J17.

Campbei.l, C. M.

The r<^le of Instinct, emotion and personalllv in disorders of the heart.

With suggi-sllons for a clinical record. — ./. Am. il. .4»«., Chicago, 1918.

Ixil. 1021 1020.

A city school district and its subnormal children: with a discussion

of some soilal pmlilems lnv(dved and suggestions for constructive

work. — ilrnl. Iliig.. Concorii. .\. II.. 1918. li. 232-244.

A case of chlldhond conflicts with prominent reference to the urinary

system: with 8<ime general considerations on urinary symptoms In the

psyrhonru roses and psychoses. — I'fuchoanalut. Her., Wash., 1918. v.

269 290.

Carter, E. P.

F^irther observations on the aberrant electrocardiogram associated with sclerosis of the atrioventricular buniile branches and their tenninal arborizations, rilnical and histologic report of a case in which such aberrant complexes were obtained. — Arch. Int. iled.. Chicago. 1918. xxil. 331 3.'-,3.

Carter, E. P. and Wedd. A. M.

Report of a case of paroxysmal taehycarilia characterized by unusual control of the fost rhythm. — Arch. Int. iled., Chicago, 1918, xxil, 571!)80.

Casler. DeW. B.

Tetanus fnllnwlng laparotomy for ectopic pregnancy. Treatment hr subarachnoid injections of magnesium sulphate and anll-tetonlc serum — recovery —.Voiil A. il. ./,. Birmingham. Alo.. 1918, il, .-,12 ..n;.


ider.- /ii; Hod. frol. (Cabot), 8°, Phila. Jt .V. Y. St. Uiuls


Cailk. J. R.

Infectious of the bla

1918. 11. 80-131.

The treatment of undescended testicle. — Interstate il.

1918. xxv. 2S.'.-2S0.

The diagnosis of diseases of the central nervous system by means

of the cystctscopic appearance of the bladder. — Interstate il. J.,

St. lyouis. 1918, xxv. 102-104.

Remarks on kidney surgery. — South, il. ./., Birmingham. .Ma.. 1918.

xi. 299-305.

Caclk, J. R., and Greoitzer, H. C.

Occluded renal tuberculosis, nutune])hrectomy. — iled. d Sun/., St. Louis. 1918. ii. 4:.3-450.

Cecil, A. B.

An unique type of urethral obstrucllou.384.


^/. t rol. Bait.. 1918. 11. 379


Eiper. il.. Bait..


Chesxey. a. II.. and CtLij^N, G. E.

A note on the production of acid l)y pneuiiuic 1918. .\xvlil, 289-29i;.

Chesxey, A. M., and Moore, H. P.

A further study of cthylhvdrocui>rein toptochini In the treatment of acute lobar pneumonia. — Arch. Int. iled., Chicago, 1918, xxi, 059-081.

Churchman, J. W.

Melanosnrcoma of the rectum, with the report of a case. — .4m. J. il. Sc., Phila.. 1918. dr. 039-044.

Treatment of acute infections of the joint bv lavage and direct meditation.—./. .4m. .U. .4«».. Chicago. 1!>I8. Ixx. 1047-10.')0. Fibroma of the tongue with consiileratlon of other tumors of the tongue anouis, 1918. ii. 173-177.

A new incision for exposure of the lower abdomen and pelvis. — .liin. Surg., Phila., 1918, Ixvil, 180-182.

Clakk. a. H.. and Feltox, L. D.

A flltrable toxic product of the hemolytic streptococcus. — J. .4m. il. Ass., Chicago. 1918. Ixxl. 1048-1049.

Clark, J. G.

Medical teaching and research nftiT tli< 1918. Ixxvlii. 220-2.30.

The therapeutic use of radium in gyncci Chicago. 1918. xxvi, 019-024.

Clarke, T. W.

The baby that •


war.— tm. J. Obtt., S. Y.. ilogy. — Surg. Oynec. d Obst.,


ininot take milk.— trcd. Pcdint., X. Y.. 1918, xxxv, 193


Clausen. S. W.

a method for the estimation of potassium in blood. — .1. Biol. Chem..

Bait., 191.S. xxxvi. 479-484.

The effect of injections of pituitary solution on (he urinary output in

a case of diabi'tes Insipidus.- .4 m. ./. Dis. Child., Chicago. 1918. xvi.

195-204.

Clausen. S. W.. and Mo.senthal, H. O.

The malntinance diet In diabetes meliitus as determined by the nitrogen equilibrium.— .Irc/i. Int. iled.. Chicago. 1918. xxl. 269-281.

Clausen, S. W., Mosentiial, H. O., and Hii.i.eb, Alma.

The effect of diet on blood sugar in eliabetis meliitus. — Arrh. Int. ilrd.. Chicago, 1918, xxl, 93-108.

Cobb, S.

A note on the supposed relation of the sympathetic nerves to dccere hrate rigidllv. muscle tone, and tendon reflexes. — .Im. J. Physiol. Bait.. 1918, xlvl, 478-482.

Cole, R.

I'revenllon of pneumonia. — J. Am. il. Ass., Chicago. 1918. Ixxl. (',3.-i

0.39.

Pneumonia as a public health problem. — Kentucky il. J., 1918. xvi.

563-505.

Cole. R., and MacCallum, W. G.

Pneumonia ut a base hospital. 1140-1 l.'.O.

CoxE, S. M. a methoil


42-43.


if studying nerv<


(^hlcago. 1918, ixx.


Im. ./. Orlhnp. Surg., Bost., 1918. xvi.


Some of the results of work on the pathology of peripheral nerve

Injuries- Im. ./. Orthop. Surg., UnDt.. 1918. xvi. 319.322.

Surgliiil pathology of the peripheral nerves. -Ilrit. .1. Surg . Bristol.

-mal nervi's and war injured nerves rath, d llaclcrlol, xxil, 1051 II.


1917 IV,

lllstolnglcal observations on

with the neurokeratin slain.


Corner. G. W.. and Ht bni. F. H.

The non effect of corpus iuleum preparations on the ovulation cycle of the rat.— .4m. ./. I'hysiol., Bait., 1918. xlvl. 48.3486.

Cusiiiso, H.

A study of a series of wounds Involving the brain and Its enveloping

structures.- /Ir(». -1. Surg., Bristol. 1917-18, v. 5.1«.«84.

Notes on penetrating wounds of the brain. — Brit. il. J., Ixinil.. 1918. I.

221-220.

Dandy, W. E.

Extiniallon of the choroid plexus of the lateral ventricles In eommunl.nilng h^dnM ephalu". -.Inn. Surg.. Phila.. 1918. Ixvili. .-,09 .'.79. Ventriculogrnpbv folbiwlng the injection of air Into the cerebral ventricles— . I nil". Surg., Phila.. 1918. Ixvlii. 5-11.


Davis, E. G.

Duodeno urptei-al fistiilii of spcmtanpoiis oriRin : report of a case. — J. Am. M. Ass.. Chicago. lOls. Ixx. ;;7(! ::7s.

Urinary antisepsis: a stiul.v of tlie antisi'ptic properties and the renal excretion of compounds related to phenolsulphonephthalein : preliminary report.— .7. Am. M. A.1S., Chicago, lOlS. lx.\, 581-585.

Davis, E. G., and Hain, R. F.

Urinary antisepsis. The antiseptic properties of normal dog urine. — J. Viol. Bait., 1918. ii, ;'.0S)-320.

Davis, E. G., and Harrell, B. E.

.Acriflavine in the treatment of gonorrhoea — an experimental and clinical study. — J. Urol., Bait.. 1918, ii, 257-27G.

Davis, E. G., and White, E. C.

Urinary antisepsis, further studies of the antiseptic properties and the renal excretion of compounds related to phenolsulphonphthalein. — J. Urol, Bait., 1918, ii. 107-127.

Urinary antisepsis. The secretion of antiseptic urine following the Intravenous administration of acriflavine and proflavine ; preliminary report. — J. Urol, Bait.. 1918. ii. 299-^07.

Davis, E. G., White, E. C, and Rosex, R.

Urinary antisepsis. The secretion of antiseptic urine following the intravenous administration of an organo-mercury phthalein derivative.—,/. Urol, Bait.. 1918. ii. 277-297.

Davis, E. G., and Young, H. H.

The surgery of the douhle kidney. Report of a case of resection of upper segment for calculous pyonephrosis. — Surg., Giincc. d Obst., Chicago, 1918, xxvii. 1-l.S.

Davis, J. S.

The use of the pedunculated flap in reconstructive surgery. — .liiii. Surg., Phila., 1918. Ixviii, 221-230.

Davison, W. C.

The superiority of inoculations with mixed triple vaccine (B. typhosus. B. paratyphosus A. and B. paratyphosus B. ) over successive inoculations with the single vaccines, as shown by agglutinin curves in men and rabbits. — Arch. Int. Med., Chicago. 1918, xxi. 437-509.

Dawson, P. M.

I'nlversity ideals Pa.. 1918. n. s..


Sci€7ice, y. Y. and Lancaster.


-,r. Am. If. .Iss.. Chicago,


ilf. Ass.. Chicago. 1918. Ixxi. 63S-G39.


Dick, Gladys H., and Murray, Eleanor. The morphology of the inlluenza bacillus 1918, Ixxi, 1568.

Dickson, E. C.

Botulism ; a further report of cases occurring In the Pacific Coast

States. — Arch. Int. lied., Chicago. 1918. xxii. 483-495.

Botulism. A clinical and experimental study. — Monogr. Rockefeller

Inst. it. Research, X. Y.. 1918. no. 8.

Botulism.— Bh//. Canadian Army M. Corps. 1918. i. 85-87.

Al.w: Canad. M. .4.i.s-. ,/., 1918, vill, 903-909.

Dickson, E. C, and Burke, G. E.

Botulism : a method of isolating Bacillus Botullnus from infected materials. — J. Am. M. Ass., Chicago, 1918, Ixxi. 518-521.

Felton, L. D., and Clark, A. H.

A Bltrable toxic product of the hemolytic streptococcus. — •/. .Im. J/. Ass., Chicago, 1918, Ixxi, 1048-1049.

Flexner, S.

Control of meningitis. — .7.

Dr. p-ranklln P. Mall ; an appreciation. — Science. N. Y. & Lancaster,

Pa.. 1918, n. s., xlvli. 249-2.54.

Flexner, S., and Awoss, H. L.

The passage of neutralizing substance from the blood into the cerelirospinal fluid in actively immunized monkeys. — J. Exper. M.. Bait.. 1918, xxvlii. 11-17.

FLEXNER, S., Amoss, H. L., and Eberson, F.

Physiological stimulation of the choroid plexus and experimeutal poliomyelitis. — J. Exper. M., Bait., 1918, xxvii. 679-687.

Flournoy, H.

Notes sur 4 cas d'obsessions et impulsions a debut instantan^. — ( Coinmunication a la Soci^te Medicate de Gen&ve), Geneve, 1918. Kiludig. 24 pp. 8°.

l.'alcoi.iismt' et les enfants anormaux. — Extrait du xiii rapport de la Soriet*^ g^uevoise de patronage des Alleu^s. 1918, 16 pp. 8"^.

Ford, W. W.

I'tirther observations on the bacteria of the intestinal tract. — Tr. Ass. Am. Physicians, Phila.. 1918, xxxlli.

Fowler, H. A.

Anatomy, anomalies and injuries of the penis. — In: Mod. Urol (Cabot), 8°, Phila. & N. Y., 1918, I. 193-222.

FroNTZ, W. A.

Presentation of device facilitating the introduction of the cystoscope in certain difficult cases. — J. Urol, Bait.. 1918. ii. 39-41.

Froxtz, W. a., and Geraghty, J. T.

A study of primary hydronephrosis. — .7. Urol. Bait.. 1918. ii. 161-209.

Futcher, T. B.

Chronic hypertrophic pulmonary osteo-arthropathy following bronchiectasis. — Bull. Canad. Army Med. Corps. 1918, i. 38-40.

Career, J. R.

.\ iilea for prenatal care and the end-results of the h.vgiene of pregnancy.— Am. J. Obst., N. Y., 1918, Ixxviii. 506-575.


-.7. Indiana M.

Mod. Urol (Cabot). 8°, Phila. & X. Y.. Mod. Urol (Cabot). 8". Phila. & X. Y.. Radium. Pittsburgh. Pa.,


Phila.. 1917-lS. ngham, Ala.. 1918. xi.


locytic leukemia.


Gatch, W. D.

Some observations on the surgerV of the thyroid gland. Ass., Fort Wayne. 1918, xi, 13-17.

Geraghty, J. T.

Tumors of the bladder.

1918. ii. 187-244.

Tests of renal function

1918, Ii. 337-376.

The results of treatment of bladder tumor

1918. X, 77-85.

Geraghty, J. T., and Fbontz, W. A.

A study of primary hydronephrosis. — J. Urol, Bait.. 1918. ii. 101-209.

GiBBES, J. H.

Ilodgkin's disease; primary involvement of mediastinal glands with presentation of tumor mass over sternum. Blood-picture characteristic of well-advanced disease. Differential diagnosis. Etiology. Pathologic

anatomy. I'rognosis. Treatment. — Med. Clin *'

i. 1587-1594.

Oral sepsis an<l arthritis. — Sonth. M. ./.. Bii

489-492.

GiFFIN, H. Z.

Splenectomy following radium treatment fo Med. Rec, X. Y.. 1918, xciv, 1020-1023.

GiFFiN, H. Z., Sanford, a. H., and Szlapka, T. L.

Estimation of urobilin and urobilinogeu in the duodenal +++++ CONTENTSs. — Am. J, M. Sc. I'hila.. 1918, civ. 562-579.

GOETSCH, E.

-Vewer methods in the diagnosis of thyroid disorders : pathological and clinical. — .V. York State J. M., N. Y.. 1918, xvili. 239-207. Also: Clifton Med. Bull, Clifton Springs, 1918. 1-12.

GOLDBAOH, L. J.

Nasopharyngeal tibro-myxoma. undergoing sarcomatous changes. — Laryngoscope, St. Louis. 1918, xxyiii. 106-108.

GOODPASTURE, E. W.

An anatomical study of senescence iu dogs, with especial reference to the relation of cellular changes of age to tumors. — J. Med. Research, Bost., 1918. xxxviil. 127-190. Observations on mitochondria of tumors. — Ibid., 213-224.

Goodpa.sture, E. W., and Jacobson, V. C.

Occlusion of the entire inferior vena cava by hypernephronm. with thrombosis of the hepatic vein and its branches. — Arch. Int. M.. Chicago, 1918. xxii. 86-95.

GORHAM, L. W.

Xote on the diagnostic use of the X-ray in pneumonia, with especial reference to the position of the diaphragm. — .ilhany M. Ann., 1918. xxxix. 58-65.


.7. Physiol.


ulogy. — South. M. -/.. Birmingham.


eluding bands. —


Grey, E. G.

Observations on the postural activity of the sto Bait., 1918, xlv, 272-285.

Griffith, F. W.

Some of the common errors in gyne Ala.. 1918, xi. 40-42.

Gundrum, F. F.

Rat bite fever with report of two cases. — Calif. State J. M., San Fran..

1918, xvi, 16-18.

Nitro-benzol poisoning. — Calif. State J. M., San Fran.. 1918. xvi, 2o2

253.

Hain, R. F., and Davis, E. G.

Urinary antisepsis. The antiseptic properties of normal dog urine. — ,J. Urol. Bait.. 1918. ii. 309-320.

Halsted, W. S.

Dilation of the great arteries distal to partial

Proc. Nat. Acad. Si:. Bait.. 1918, iv, 204-210.

Cylindrical dilation of the common carotid artery following partial

occlusion of the innominate and ligation of the subclavian. — Tr. .im.

Surg. Ass.. Phila.. I'.US, xxxyi.

Ijetter to Dr. Keen. Communication on the subject of the Carrel Dakin treatment of wounds. In: Keen, \V. W. The treatment of war

wounds, Phila.. 2. ed.. 1918, 252-259.

Harrell, B. E., and Davis. E. G.

Acriflavine in the treatment of gonorrhoea — an experimeutal and clinical study. — •/. Urol Bait., 1918. ii. 257-276.

Harrop, G. a., and Mosexthal. H. 0.

The comparativi- food yalue of protein, fat and alcohol in diabetes mellitus as measur. d bv the nitro.cen equilibrium. — Arch. Int. .Med., Chicago. Iill8. xxii. 7.50-75S.

Hazex, H. H.

Syphilis and the war. — .4»i. ./. Syph., St. Louis. 191s

A more intensive form of arsphenamine therapy.

St. Louis. 1918, ii. 778-779.

More contract surgeons (Letter). — J. .\ni. M. Ass.

Ixx. 1184. „^„

Duties of the dermatologist. — J. Am. M. Ass.. Chicago. 1918. Ixx. 1989 1990.

Dermatology and the war. — Med. if- Surg., St. Louis, 1918. ii. 145-l,.l.

Hiller, Alma, Mosenthal, H. O., and Clausen, S. W. The effect of diet on blood sugar in diabetes mellitus. — Chicago, 1918, xxi, 93-108.


. 144 135. im. ./. Syph..

Chicago. 1918.


Arch. Int. Med..


Februabt, 1919]


45


Chi.ni:.!. 1!US. Ixxl.


Hl.NMAN, F.

Thi" nianagpiiicnt of siirKlcal risk: n review of 100 klilney iinil prostate 0[H>rations. auil 50 eases of enlnr^d prostate Dot operated iipou. — Call/. Stole J. M.. San Fran.. 1!>1S. xvl. 2tl-::i."i.

A niodlfleatlon of CltzmaDH's syringe for iMSterlor urethral Insilllatlons.^. Am. .U. .!»«.. Chicago. lOlS. \x\. l:;!>i.

His.MAN, F.. and Lissek H.

Srpbllls of the epliUil.rmls without Involvement of the testicle : Itcporl of cage.— .Im. .;. S„i>h.. St. Louis. 1018, II. 4»i.'>-471.

HlBSCIIFELDEB, A. D.

The leaching ni pharmacology. — ,/. Am Jl tiU'.l-tilL'.

HiRscHFELDER. A. D., and Caxtwei.i,, W.

KITiMts of sonic aminii acl.ls upon the e.\clse<l segments of Intestine. — J. Pharmntol. d f.'j-pcr. Thcrap.. Bait.. 1018. xl. ITS.

HrrzBOT, J. M.

The effect of spleneetomv on the normal Imllvhliial and In certain pathological eoDilltlons.—' .4nn. Hurg.. I'hlla.. 11118. Ixvll. .i4()-."in. Myeloma of the clavicle.— -Inn. b'urg., Thlla.. 1018. IxvUl. ICIM.

HoL.MES, J. B.

Keccnt work In anatomy, physiology and pathology of childhooil.- Am. ./. l>iH. Ihil.. ('hlcuga, IftlS. xv. L'78-308.


Hooker, D. R.

The veno-pre.


mechanism. — .liii. ./. I'hijHiol.. Bait.. lOlS. xlvl.


Hooker, D. R.. and Maciit. D. I.

Coueerning the action of the lodlile. bromide and nltnite Ions on the respiratory center. — ./. I'hnrmncol. A Expcr. Thcr<ii>.. 1018. xl. 113-G7.

HoPKixs, J. G., and Parker, Jilia T.

The effect of Injections of hemolytic streptococci on susceptible nnd insusceptible animals.—./. Exprr. J/.. Bait.. 1018. xxvU. 1-20.

Howard, C. P.

.Some of the medical lessons of the present war. — /. loira Sliitc U. .S'oc. Clinton. 1018. vlU. :t.-2.

Howard, C. P.. and I.ngvali>.sen-, T.

The mlm-ral metabolism of experimental s<urvy i<( thi- monkey. — L'vif. Iowa UonogrnphM, Studies In Med.. 1018. 1. 111).

Howard, C. P., and Steve.ns. F. A.

The Iron metabolism of hemochromatosis. — fiiir. loicii ilriHognipln-. Studies In Med.. 1018. 1. 1 IT.

Howell. W. H.

The coagulation of blood.— //nrrci; Lict.. lOli; IT. I'hila. & I,ond.. I'.Hs. JT2-:t2:t.

HowLAXD. J., and Marriott. W. M.

Ad.losls.— /'rnn. .1/. !.. Athens. I'a.. 101,8. xxl. 4i;0-4:!l!.

The Influence of a< Id phosphate on the elimination of ammonia hi I he

urini'.-.l rcA. Int. .Mrd.. Chicago. 1018. xxll. 4T7-48-.>.

Dbservatbms upon the calcium +++++ CONTENTS of the hlood In Infantile tetany

anil upon the effeil of treatment by calcium. — Quart. ./. .Med.. Oxford.

1018, xl. 280-tlO.

Hf.NXEB, G. L.

Anatomy, abnormalities. Injuries and diseases of the ureter. — In: .Mud.

I rol. (Cabotl. 8°. Phlla. & N. V., 1018. II. 24."i-:tll.

A rare type of bladder ulcer. Further notes, with a report of eighlicMi

cases. — /. .On. .1/. !»».. Chicago. 1018. \xx. 2();t 212.

Kluslve ulcer of the bladder. Further notes on a rare type of bladder

ulcer, with a reiiort of twenty-live cases. — Am. ./. Obxf., N. Y.. 101s.

ixxviii. :it4-:hi.-..

The etlologv of ureteral lalculus. — .S'lirtf. (Ifinrr. .{ olml.. Chicago. I'.ils. xxvll. 2.'>2-2Tn.

HtRWITZ, S. H.

The value of renal functional studies In the prognosis and Ireiiliinnt if nephritis.- f'liUf. State ./. U.. San Fran.. 1018, xvl. 28T-20:i.

HtRWITZ, S. H.. and Falconer, E. H.

The %nlue of Unehtgen rays and benxene In the treatment of poly cythemla vera. — /. Am. .M. Afn., Chicago. 1018. Ixx. 114:!lU.-i.

HtRwiT7, S. H.. Meyer, K. F.. and Tacssio, L.

Studies on the Mooil proteins. III. Alliumln-globulln rallo In anillnxli Immunity. — /. Infrrl. /ii«.. Chicago. I'.ils. xxll. 1-2T.

.Iack, W. D., and Balleiil, L. C.

The use of fascial transplants in war surgery. — -.Inii. Sinu . I'bll.i . 1018, IxvlU. 14.

Jaxe>vay, T. C. Richardson, H. B., and Park, E. A.

Kiperlmenis on the vasoconstrictor action of blood serum. — In/i fi;(. -Ved.. Chicago, 1018. xxl. .-.tl.'i-l!o:<.

Keidel, A.

rorasltologv anil serologv of syphilis. — .tin. ./. Suph.. St. I.<iuls. IOI>. II. 2Tii.2.sT. I No; South. .1/. ./., Birmingham. Ala.. 1018. xl. 2117 2T1.

Keidel, A., and Zim.mermann, E. L.

Tattooing and syphilis.— .tm. J. Spph.. St. Louis. 1018. I. 8.1. 00.

Keith, N. M.. and Thomson, W. W. D.

War nephritis, a clinical, functional, and pathological study. — (jiinri t. Sled., Oxford. 1018. xl. 220-200.


Kelly, H. A.

Fibroid tumors of the uterus treated with radium. — Charlotte |.V. f'.j

.U. ./.. 1018. Ixxvll. l.'i.-il.'lT.

Fibroid tumors and radium. — Virginia J/. Slonth.. Kichmouil. Va..

lOLs. xlv. IT,

Two hundn-d and ten fibroid tumors treated by radium. — 7'r. Am.

Olinrr. Soe.. rhila.. 1018. x||||.

The.Hlore Caldwell Janewav. 18T2-101T. — lloiton \l. Jt S. J.. 1018.

clxxlx. .-.'.iT-.-iO'l,

.loseph Trice. 18.-.:t-inil.— «o«foii, if. rf S. J.. 1018. dxxlx. 081-084.

.lohn llerr Miisser. 18.'i0-1012.— «osf. U. <t S. ./., 1018. clxxlx. 7T2.

lir. Kec nieillcal research. — Nciciicc. X. Y. & l.<incaster. Ta.. 1018.

n. s.. xlvli. 41!i.

Kempf, E. J.

Social and sexual behavior of monkeys with some comparable facts in human sexual behavior. — lAbstr.) Am. J. I rol.. .\. Y., 1018. xlv, 82-80.

Kino, J. T.

.\uscultation of pnlmonary apices in young men. — Mil. Surg.. Wash., lois. xlll. ou r,.-.

Knox, J. H. M.

.Vjnericas debt In Iranci. -.1 m. ./. /»i«. Child.. Chicago. 1018. xvl, 212

Kracse, a. K.

Itest.— .Im. Iter. Tuhrrc. Halt.. 1018. I. 080-082.

Klenientarv concepts of tuberculosis.— .4m. Urr. Tuberc.. Ball.. 1018.

il. o:t-Ti.

I'redlsposllliin. < IMltorial.l— Im. Rer. Tubere.. Bait.. 1018, II. 43-48.

Tobacco smoke and pulmonarv tuberculosis. (Kdltorlal.) — .4in. Ker.

Tnlnre.. Hall.. 1018. II. OO-lO.-i.

Autlliiberculosls measures.— .4m. Her. Tubere.. Bait.. 1018, II. 037-0.":;.

Fssays on tuberculosis :

1. Before the tiitiercle bacillus.

2. Before Itobert Koch.

(. Hubert Koch.

4. The tubercle bacillus.

.'•. Infection: Introdiulory considerations.

0. Sources of infection : Cornels theory of dust Infection.

T. Infeclioii by inhalation : Fliigge's theory of droplet Infection.

8. Infection by Ingestion: part one.

!i. Infection by ingeslion : part two: the lirst experiments.

10. Infection by Ingestion: I'urt three: The occurrence of iMVlne bacilli in man.

11. Infection: special characteristics of tuberculous infection.

— /. Outdoor l.i/e. N. Y.. 1018. xv. 1-0: 30-41: fl.->-73 : 80; 101 100: 120: 1201.17: 1031CO: 100.204.

— ./. Outdoor Lite. X. Y.. 1018. xv. 22ij-2:{0 : 24fl-2.'>0 : 20n-27.'i :

20."i-3OO.

^/. Oufrfooi- Life. X. Y.. 1018. xv, .{27-320: 342-344: :i03-:!fl7 :

374.

Lange, Linda B.

The complement Hxatlon test for tuberculosis.— Iwi. Iter. Tubere.. Bait.. 1018. II. .-.41 ..4.".

Lawrence. J. S.

.\ studv of the aerobic bacteria found In wounds received on the batllellelil o^ the Somme.— i/iJ. Surgeon, Wash.. 1018. xlll, 140-1.13.

Levy. R. L.

The effect of thvrold secretion on the excitability of the endings of the cardiac vagus. — .4rr)i. Int. Ued.. Chicago. 1018, xxl. 203-208.

Levy. R. L., and Alexander, H. L.

The predisposition of streptococcus carriers to the compllcatlonH of measles. Uesults of separation of carriers from non-carriers at a hniie hospital.^/. .Im. .1/. Axu., Chicago. 1018. Ixx. IN2T I8:io,

Lis.'iER. H.

Svphllls of Ibe lung.— Im. ./. il.'Se.. I'hila.. liils. civ. :i.-.0-380.

The prevention of congenital svphllls by aullluellc prenatal Iberapy. Cnli). state .1 . M.. .San Fran.. 1018. xvl, 384:t88,

A not 1 the use of corpus luteum to prevent the palurul breasts

of menstruation. — F,ndoerinolog)i . (llendale. Cal.. lois. II. 12 l.^i.

L18SER, H., and Hin.max, F.

Svphllls of ihc cpl.lldvmls without Involvement of the lesllde: Keport of case.— Im. ./. s,iph.. SI. Louis. 1018. II. 40.% 4T1.

LoEVEXHART, A. S., BiNTiNo, C. H., and Martin. H. O.

The morphological changes In the tissues of the rabbll as a result of reduced oxidation.- ./. Kxper. J/.. Bull., 1018. xxvll. 3011 412.

Lyman, D. R.

The control of the careless consumptive.— Ira. Iter. Tubere.. Bait.. 1018. II. 30-42.

Following up the discharged sanatorium palleiit.- Im Her. fulirre.. Ball.. 1018. 11. 01.-, (121.

MacCalli M, W. G.

I'albologv of the epidemic Hireptococcnl bronchopneumonia In lb.' army camps.—:/. Im. M. Am.. Chicago, 1018, Ixxl. 704-707.

MacCalli M, W. G., and Cole. R.

I'neumonia at a base hospital.-^/. .Im. M An,.. Chicago. 1018. In, 1140.I1.-.0.

McCli RE, W. B., and Sai er. L. W.

Observations regarding Ihi' loss of water vapor through the skin In Infants.- Irr/i. Int. Sled . Chicago. 1018. xxl. 428-430.

MiCrae, T.

Tuberculosis am


iddler. — .Im. He


Ball.. lOIM. II. 372


46


[No. 336


Macht, D. I.

Jewish food problems. — Jenish Forum, 1918, Nosi, l-U. A case of aspirin habit.— J/ed. Hec N. \. 1918. xciv, 't"- ,„,„.,„.,,

On the absorption of apomorphm and morphin through "uiji"-" channels.— Fcoc. 8oe. Exper. Biol. <C Med N Y., 191 --18, ^,y-,-^-- ' ,, On the comparative absorptive power for drugs of the bbuUler and urethra (male). — Proc. Soc. Exper. Biol. <C Med., N. \., lUli-lb. xv,

On the relation of the chemical structure of the opium alkaloids to their effect on smooth muscle and on the discoveiy of a new thHrapeutic a°ent as a consequence thereof. — Proc. Soc. Exper. Btol. d Med., >. 1.. 1§18. XV. 63-66. , ^ r ..t • 11 i,;,u On the relation between the chemical structure of the opium alkalouis. and their physiological action on smooth muscle with a pharm.iiological and therapeutic study of some benzyl esters : I. On the relation of the chemical structure of the opium alkaloids to their action on smooth muscle. II. A pharmacological and therapeutic study of some benzyl esters. — J. Pharmacol, d Eiper. Tlierap., Bait., 1918, xi, 389417 ' 419-446 .

On the absorption of drugs and poisons from the bladder and the urethra : I. Absorption of apomorphin and morphin. II. Absorption of various alkaloids, antiseptics, local anesthetics and salts. — J. L rol.. Bait, 1918, 11, 43-49 ; 211-226. ,, ., „ x- v ims

On parotitis as a complication of influenza. — Mca. Hec, .^. i.. iJis, xciv, 1117.

Macht, D. I., and Hooker, D. R.

Concerning the action of the iodide, bromide and nitrate ions on the respiratory center. — J. Pharmacol, d- Exper. Thernp.. Bait., l.ilS, si, 63-67.

Macht, D. I., Isaacs, S., and Gbeexberg, J. P.

On the influence of some opiates and antipyretics on the field of vision —Proc. Soc. Exper. Biol, d Med., N. Y.. 1917-18, xv. 4b-4S. On the influence of some antipyretics on the neuromuscular coordination test of •' tapping." — Proc. Soc. Exper. Biol, d Med., N. \., 191(18, XV, 61-62.


OS M. Soc, Topeka, 1918, Gynec. <f Obst., Chicago.


the presence of the meningococcus in the blood, birago, 1918, xxiii. 470-474.


Major, R. H.

Importance of focal infection in diseases of obi Herald, St. .Toseph. 1918, xxxvii, 159-163. Uremic ulceration of the intestine. — J. Kai xvlii, 136.

A study of the Krukenberg tumor. — Surg 1918, xxvii, 193-204.

Major, R. H., and Black, D. R.

A huge hemangioma of the liver associated with heniangiomata of the skull and bilateral cystic adrenals. — .Iwi. J. M. Sc. Thila., 1918, clvi, 469-483.

Marriott, W. M., and Howland, J.

The influence of acid phosphate on the elimin.ntion of ammonia in the urine. — Arch. Int. Med., Chicago, 1918, xxii, 477-482. Acidosis. — Penn. M. J., Athens, Pa., 1918, xxi, 429-436. Observations upon the calcium +++++ CONTENTS of the blood in infantile tetany and upon the effect of treatment by calcium. — Quart. J. Med., Oxford, 1918, xi. 289-319.

Marriott, W. M., and Sissos, W. R.

Variations in the lipoid ("tat") +++++ CONTENTS of the blood of infants under certain nutritional conditions. — ^iii. J. Dis. Child., Chicago, 1918, xvi, 75-82.

Marshall, H. W.

Structural deformities versus functional efficiencies as objects of treatments —BosfoH M. & 8. J., 1918, clxxviii, 708-712.

Revised ideas concerning toot defects and orthopedic footwear. — Boston M. d S. J., 1918, clxxviii, 428-432.

Maxcy, K. F.

Observations J. Infect. Di.

Maxcy, K. P., and Blackfax, K. D. The intraperitoneal injection of salin Chicago, 1918, xv, 19-28.

Mendenhall, Dorothy R.

Milk, the indispensable food for children. — T". S. Dept. I,abor. Children's Bureau. Care of Children Ser. No. 4, Bureau I'ubl., No. 3.i, Wash., Gov't I'rintlng Off., 1918.

Meyer, A.

Modern views and propositions on enforced treatment of mental diseases. — Maryland Psychiat. Q., Bait., 1918. vii. The mental hygiene movement.632-634.

Meter, A. W.

To Franklin Paine Mall. Ave Magister ! — Johns Hopkins Alumni May..

Bait., 1918, vi. 140.

Some observations on megacytes in lymphatic tissues. — Am. J. Anat.,

Bait.. 1918, xxiv, 91-104.

Studies on hemal nodes : VIII. The absence of hemal nodes in the

domestic pig. — Am. ./. Anat., Bait., 1918, xxiv, 109-120.

Miller, S. R., and Baetjeb, W. A.

Pollinosis or hay-fever: its specific treatment. — South. M. J., Biimiughani. Ala.. 1918. xi. 341-345.

Bence-.Tones proteinuria ; some observations on its occurrence, with particular reference to nephritis and hypertension. — J. .im. M. Ass.. Chicago, 1918, Ixx, 137-139.

Miller, S. R., and Barker, L. F.

Perforating ulcer of the hard palate resembling tertiary syphilis. — J. Am. M. Ass., Chicago, 1918, Ixxi, 793-707.

Miller, W. S.

A study of the nerves and ganglia of the lung in a case of pulmonary tuberculosis.— Am. Rev. Tuberc, Bait.. 1917-18, i, 123-139.


solution. — Am.


Vhild.,


-banad. M. Ass. J., Toronto, 1918, vlil.


Mills, C. W., and Hendersox, J. T.

The effect of pulmonary tuberculosis on renal function. — -4m. Aei;. Tuberc, Bait.. 1917-18, i, 573-597.

Mllls, C. W., and Forster, A. M.

The treatment of laryngeal tuberculosis by reflected condensed sunlight.— -Vat. Ass. Study d Prev. Tuberc, Tr., 1918, xiv.

Mills, R. G. . ,. , u h,

.lapanese medical literature. Review of current Pf^^'o^'cals by the staff of the research department. Severance t nion Medical College. Seoul. Korea.— Chino M. J., Shanghai, 1918, xxxu, 49-6o , 2o6--bi . An'^unSsuarcaseof double carcinoma with extreme resistance to one and death from the effects of the other.— C7mia M. J., Shanghai, 1918. xxxii.

Mills, R. G., Ludlow, A. I., and Vax Biskirk, J. D.

A simple method of water purification tor itinerant missions other travellers.— CftiJiO M. J., Shanghai. 1918, xxxu,, 13.-14o.

'^Pathologic hemorrhage. A group of cases illustrating this condition with a note on the early diagnosis of pernicious anemia.— Metf. tlni. X. Am., Phila., 1918, i, 1102-1124.

MixoT, G. R., and Loeb, R. F. „ , ,/ .

An attempt to prevent influenza at Harvard College.— Boston if. cCS. J., 1918, clxxix, 665-669.


ries and


-Surg.


' ""p^^mature separation of the .norm.allv implanted placenta. Oynec. Ob.it., Chicago, 1918, xxvi. 133-138.

Morris, R. S., and Friedlaxder, A. . ,. - i,- ,„

The significance of presystolic thrill in the examination of soldieis.— J. Am. M. Ass., Chicago, 1918, Ixxi, 3.o-3(i.

^"'RenaTJ'unf.^io^- as measured by the elimination of,^fl"^;^|- /"J^ ?nd nitrogen, and the specific gravity of the tivine. H- !«« ejie" -if, inS low and normal diets.— .Ircft. Int. Med. (^^^'^"SO. l^H-J^"- '-O^SO^,War nephritis, by P Ameiiille ..Transl. from the French by H. t. Mosenthal.— J^. Urol., Bait., 1918, ii, d1-106.

Mosexthal, H. O., and Clausex, S. W. • , k h, „»,„

The maintenance diet in diabetes mellitus as determined by the nltiogen eQuilihrium.— .liTji. Int. Med., Chicago, 1918. xxi, 269--S1.

MO.SEXTHAL, H. O., ClAUSEX, S. W and HiLLER ALMA

The effect of diet on blood sugar in diabetes mellitus.— lif/i. /»' Mca.. Chicago, 1918, xxi, 93-108.

MOSEXTHAL, H. 0., and Harrop, G. A. , , ^,. ,:,,„.„- „,pi

The comparative food value of protein, f«^-XV'^» ™h" ' 'l'-'"';** f"^'" litus as measured by the nitrogen equilibrium.— .liOi. Int. ilea., Chicago, 1918, xxii, 750-758.

Neymaxx, C. a., and Burrows, M. T. . . ^ ,- . ,

studies on the metabolism of cells i""", ,, The toxicity of dipept.d, for embryonic chicken cells.— Proc. Soc. Lxpc. Biol, d ilea., -n. i., 1918, XV, 138-139.


-Ann. Surg.. Phila.. 191S. Ixvii,


Nrsox, P. I.

Inflammatory tumors of the abdoinen.306-311.

Infantilism and other hypoplastic conditions of the uterus.—/. Am. M. Ass., Chicago, 1918, Ixxi. 1101-1107.

^'rhe^ pathological effects of Phthirus pubis.— Porasitoioffi/, London. 1918. X. 375-379. .^ , , j i oi c ., -ja^ jn".

The biology of Phthirus pubis.— Pai-asi<o7off!/, Lond., 1918, x, 3S3-4Uo.

NuTTixG, M. Adelaide. „„„,.,„„ vi„<,c*

War-time problems of the nursing profession. — lohns Hopkins .\uises Alumna: Mag., Bait., 1918, xvii, 93-100.

Opie. E. L., Baetjer, W. [et all. . ^. ,^ . „ ^^^

Report on progress of trench fever investigations. Trench lever Commission of Medical Research Committee, American Red Cross.— J. Am. M. Ass., Chicago, 1918. Ixx. 159i-lo98.

Opie, E. L., and Wobus, R. E.

Elephantiasis : report of a case.9S7.

OsLER, Sir W. ,„,„ • -^i -..

Typhoid spine.— B"». Canadian Army M. lorps l^l;^- i- 'S.;-'Graduated exercise in prognosis. — Lancet, ixinii., i.iis. i, -oi. The rimary examination for the F R. C. S. Eng. ; an appeal to the President of the Royal College of Surgeons.— Lancet, Lond.. 191S, i.

Medicine in America (Speech to University Extension Stiidents, summer meeting at Cambridge).- The Hospital, Lond., 1918, Ixiv, 43o.

The utility of artificial pneumothorax in the treatment of phthisis. — Canada Lancet, Toronto, 1918-19, Hi, 64- 1 2.

P\rk, E. a., Jaxeway, T. C, and Richabdsox, H. B.

Experiments on the vasoconstrictor action of blood serum.— 4rc/i. Int. Med.. Chicago, 1918, xxi, 565-603.

Patox, S. ,.,.,,,

Effects of low oxygen pressure on the personality ot the aviator. J Am. M. Ass., Chicago, 1918, Ixxi, 1399-1400.


Am. M. Ass.. Chicago. 1918. Ixx.


Februakt, 1919]


47


Peabody, F. W.

Ciinliuc ilfspnea.— Jm. J. J/. iV., Phlln.. 1918. civ. 100117.

Cardiac dyspnea. — Harvey Led., 1910-17. Phlla. 4 lA>nd.. lOlS, 24S •J71.

Peabody, F. W., Clovgu, H. A., Stubgis, C. C. {ft al.\ Effects of tbo Injection of eplnepbrln In soldiers with " irritable heart." rrelimlnary report. — J. Am. J/. Aat., Chicago, 1918, Ixxl, 1912-1913.

Peabce, Louise, and Bbowx, W. H.

Kxporiiiioutnl ir.vp;iutiiioiiii:isis : its application in chemotberapeiitkInvestlgations. — J. Exper. 11., Bait., 1918, IxviU, 109-147.

Pesbose, C. a.


Plaooemeyeb, H. W.

Kadicnl treatment for veslco-vaginal flstuln. — Grate Hasp. Bull.. Detroit. 191718. 11. 17-19.

QUINBY. W. C.

Anatomy and pbTsiolog; of the cidney. — In: Hod. fro/. (Cabot), 8°.

r-bila. & N. Y.. lins. 11. 312-3.-16.

Anutumv and phvslologv of the prost;ite and seminal vesicles. — In:

Mod. Int. (CalMiti. S . Phlla. Jt N. Y.. 1918. 1, 541-552.

The treatment of genital tuberculosis in the male. — J. Am. if. Ass..

Chicago. 1918. Ixxl. 1790-179G.

Richaedsox, E. H.

Note on saphenous varljt simulating a femoral hernia. — Ann. Surg.,

Phlla.. 1918. Iivll. 471-472.

Interpretation of lumbo-SJicral backache in women. — South, if. J.,

Birmlngliam. Ala.. 1918. xi. 139-144.

The effect of hysterectomy upon ovarian function. — Tr. Am. Oynec.

Soc, I'hila.. 1918. xliii.

Richardson, H. B., Jaxeway, T. C, and Pabk, E. A.

Experiments on the vasoconstrictor action of blood serum. — Arch. Int. Hcd., Chicago. 1918. xil. 565-003.

Roses, R., Davis, E. G., and White, E. C.

Urinary antisepsis. The secretion of antiseptic urine following the intravenous administration of an organo-mercury phthaleln derivative. — J. Crol., Bait.. 1918. II, 277-307.

Rocs, P.

Method for Intravenous Injection of guinea pigs. — ./. Exper. it.. Bait .

191, <(, xivll. 4.->9-462.

I'rinary slilcmsls. Hemosiderin granules In the urine as an aid In

the diagnosis, of pernicious anemia, hemochromatosis, and other dis

eases causing slilerosis of the kidney. — J. Exper. if.. Bait., 1918. xxvlil.

645-659.

Rovs, P.. and Olheb, J.

Experimental hemochromatosis 644.


Exper. if., Bait.. 1918, xxvlil, 02;


Rois, P.. and Robebtso.n, O. H.

Free antigen and antibody circulating together in large amounts (hemagglutinin and agglutinogen In the blood of transfused rabbits). — J. Exper. .1/.. Halt., r.iis. xxvli. 509-517.

Autobemagglutluutlun experimentally Induced by the repeated withdrawal of blood— J. Exper. J/., Ball., 1918. xxvll. 563-508.

Roi s. P., and Wilson, G. W.

hiuld substitutes for transfusion after hemorrhage; first communica tion. — J. Am. it. Aat., Chicago, 1918, Ixx, 219-222.

Rowxtree, L. G.

Syphilis in its medical its general, and its sociological aspects — Therap. Qai., Detroit, 15»1S, n. s., xxxTiti, 222-225.

Row-ntbee, L. G., and Bakker. L. F.

a report of a case of myrtol poisoning with comments upon the toxlcltv of eucalyptus oil and myrtol In human beings and In animals. — Tr. Alt. Am. Phyticiant, I'hila., 1918, xxxlli.

Rl'SIIMORE, S.

Progress In gynecology. — Boston if. <f S. J., 1918, clxxviil, 633-539.

Sabix, Fi.OBExrE R.

Franklin Paine Stall: a review of bis scientific achievement. — Science, N. Y. & Lancaster, Pa., 1918. n. s., xivll, 254-261.

Sampson. J. A.

The escape of foreign material from the uterine cavity into the nl.Tlii.veins.— .tm. J. Obst., N. Y., 1918, Ixxvlii, 161-175.

SeM-ards, a. W.

Viii. Ill- .lis. nrery and associated conditions. — ifed. Clin, X. Am.. Phlln.. 1141.

• if tropical sunlight with special reference to phot"

— J. Hcd. Research, Bost.. 1918. xxxvlll, 293-334.

•n of dilute sodium hydroxld on certain races of the pri, ,11,,,,, .„ , ,i.._v. .4m. .If. Ass.. Chicago. 1918. Ixxl. 1301-1.303. The treatment of amcrblc dysenterv with chaparro amargosa casli'ln nicholsonl. — J. Pharmacol, rf Exper. Therap., Bait, 1918. xl, 331.

Sellabds. a. W.. Spooseb, L. H., and Wyman. J. H.

Serum treatment of type I pneumonia. — J. Am. if. Ass., Chicago. 19I.K Ixxl. 1310 IMll.

Sharpe. W.

Diagnosis and treatment of brain Injuries with or without fracture of

the skull.— .4m. ./. Surg., X. Y.. inis. ixxll. 109-114.

The operativ., treatment of trifacial neuralgia. — Ann. Surg., Phlla..

19IS. Iivill. .".71-.T7S.

Kecent advances In neurological surgery and especially in the diagnos!"

and treatment of brain Injuries— CJiorfoMc (.V. CI If. J., Ixxvll. 2.T1


erlpheral facial


the time of labor. — Am. J. Obst..


Operative treatment In selected cases of chronic perl paralysis. — J. Am. it. Ans., Chicago. 1918. Ixx. 13541357. Recent advances In the surgery of the brain and spinal cord.— ./ourriar. I.ancct. .Minneapolis. 1918. xxxvlll, 313-318.

Fractures of the skull : the resulting intracranial pathology and the treatment.— .»/cd. rf Surg.. St. Ixiuis. Mo., 1918, 11. 319-333 Observations regarding neurological surgerv. and especially the diagnosis and treatjnent of brain injuries. — J. Tenn. if. Ass., .Nashville.

Observations regarding the iliagnosis and treatment of brain Injuries with or without a fracture of the skull. .l/iiiiir»«f<i I/.. I'MS. I. ;;n,-, SlMON, C. E.

A manual of clinical diagnosis by means of laboratory methods. — 9. ed.. Phlla. & Lond.. 1918. Lea & Feblger. 851. p. 80. The probable association of amino-aciduria with Bence- Jones |iroteinurla. — J. Am. it. Ass., Chicago, 1918, Ixx, 224.

SiSSOX, W. R.

A critical review of intestinal bacteriology in relation to certain diarrheas of infants.- f<o»(on if. rf ,S. J., 1918. clxxviil. 492-408.

Sissox, W. R., and Mabriott, W. M.

Variations in the lipoid ("fat") +++++ CONTENTS of the blood of Infants under certain nutritional conditions. — .4m. J. Dtt. Child.. Chicago, 1918 xvl 75-82.

Sladex, F. J., and Friedlandeb, A. [et al].

The epidemic of Influeniia at Camp Sherman, Ohio. — J. Am. i/. .4<r».. Chicago. 1918. Ixxl. 1052-1650.

Slemons, J. M.

The significance of fever 1918. Ixxvlii. 321-328. Analysis of the blood In 06sf.. N. Y.. 1918. Ixxvll.

S.MITII. W. H.

How nurses are meeting the present needs. — Im. ,/. Surging. Uorhester.

N. Y.. 1917-1918, xvlll. 979-989.

The civil hospital ami its duties in war time. lAbstr.l. — Trained

Xurse [etc.), N. Y.. 1918. Ix. 1315.

Medical aspects of the war. — Johns Hopkins Alumni Hag., Bait., 191S

vl, 348-307.

Some ospects of the nrognim of the medical department of the armv

and their effect on civil hospitals. — ifod. Hasp., St. Louis. 1918 xl

334-330.

Si'EBBY, J. A.

Results following operative treatment of pelvic inflammatory tilsea«e in the Standford University Clinic. — Calil. State J. .»., San Fran 1918 xvl, 388-390.


Stevens, A. R.. and Petebs, J. P., Jb.

A study lu war nephritis; a new condition associated with henior rhages in the bladiler wall and urinary symptoms: prellminarv report.^T/. Im. J/. Ass., Chicago. 1918. Ixx. 1760-1703.

Stboxo, R. p.

Etiidogy and method of tninsmlssion of trench fever. — Bull Arad dc it(d. Par., 1918. 3. s, Ixx.

Stboxo, R. P.. Swift, H. F. fef at].

Trench fever. Report of Commission Medical Research Committee. American Red Cross. [London], 1918. Ox/ord Vnirersity Press, 446.

Report on progress of trench fever Investigations. Trench Fever Commission of Medical Research Committee, .\merlcan Red Cross. — J 4m if. Ats., Chicago. 191S. ixx. 1597-159S.

Report on progress of trench fever Invesllgations of Trench Fever Commission of Medical Research Committee. American Red Cross. — ifrd ItuU. Par.. 191,s. I, 370-383.

Strovse, S.

.Juvenile diabetes in twins, (he Karell treatment of edema. The Importance of details In the treatment of angina pectoris. — .Ifrd. VUn. X. Am., Phila., 1917-18. I. 12411259.

Stbouse. S., and Bi.ocii, L.

Notes on the present epiilenilc of respinitorv disease. -./. .Im. Jf. .4»» Chicago. 1918. Ixxl. l.')08 1571.

Tiieoiiai.d. S.

Chief function of oblique tnuscles of the 1918. xil. 57.59.

VoKGTLix, C, and Mvkiis. C. N.

Phosphorus as an lnc|lcator of the vitamin


-iird .standard. Chic


+++++ CONTENTS of corn and


products. -/'Mil. Health Itep., Wash., 1918. xxzlll. 911-911 Wabfield, L. M.

vilhout acute onset. — J. Am. .If. Ass..


Chronic emiocardltis ' I91S. Ixxl. 970!iil. The eti..li>gy of nrlerlo III. 115<11i. I.<ictosurla : case pn-f ronsln it. J., 1917IS,


onset. clerosls.-^f. fall, rf fl(»i. .v., St. IjO\i\». 1917-18. nting unusual fentiiri's. cllnlrni n-porl. — Mis


Warfield. L. M.. and Smith. F. M.

Studies on Irritable heart; preliminary report. Chicago. 1918. Ixxl. 1815-1816.

Watson. E. M.

The development of the semlDit T(»IcIp(i In man.— xxlv. 305-435


wl.. 191 s bacilli ill


conslileralli.n of th<- methods for di'moiislrnilng tubercle the urin.-.— .4m. J. .W. Sr , Phlla.. lOIS elvl, 6.36-643. Xoten iin the recognition of certain le»ions of the male bladder. -.4nn Hurg.. Phlla., 1018. Ixvil. 06102.


The human seminal vesicles at birth, with observations on their fetal development. — Ann. Surg., Phila., 1918, Ixviii, 416-419. Also: Tr. . Hect. Oenito-Urin. Dts. Am. M. Ass., Chicago, 1918, Ixix. The essentials of success in prostatic surgery. — Canad. M. Ass. J., Toronto, 1918, viii, 327-332.

The place of Intraspinal therapy in urology. — J. Am. M. Ass., Chicago, 1918, Ixx, 296-300. ,

The developmental stages of the human seminal vesicles. — J. Urol,, Bait., 1918, ii, 129-139. '<

The structure of the verumontanum — a study of the origin and devel- • opment of its inherent glandular elements. — J. Urol., Bait., 1918, ii,(f 337-351. j;

Watts, S. H.

.\cute and subacute pancreatitis. Report of seven cases. — Ann. Surg., I'hila., 1918, Ixvii, 278-292.

The treatment of certain forms of subacute pancreatitis. — Surg., Oynec. d out., Chicago, 1918, xxvii, 286-288.

Weeb, C. W.

Surgical treatment of goiter. — N. York State J. il., N. Y., 1918, xviii, 272-278. Also: Clifton Med. Bull., Clifton Springs, 1918, 12-18.

Welch, W. H.

Letter to S. Adolphus Knopf, M. D. An introduction to " What the American soldier now fighting in France should know about tuberculosis," by S. Adolphus Knopf. — J. Outdoor Life, N. Y., 1918. xv. 14.

Whipple, G. H., and Cook, J. V.

Proteose intoxications and injury of body protein. IV. The metabolism of dogs with sterile abscess, pancreatitis, and pleuritis. V. The increase in non-protein nitrogen of the blood in acute inflammatory processes and acute intoxications. — J. Expcr. 11., Bait., 1918, xxviii, , 223-241 ; 243-252.

Whipple, G. H., and Van Slyke, D. D.

Proteose intoxications and injury of body protein. III. Toxic protein catabolism and its influence upon the non-protein nitrogen partition of the blood. — ./. Exper. M., Bait., 1918, xxviii, 213-221.

White, E. C, and Davis, E. G.

Urinary antisepsis. The secretion of antiseptic urine following the intravenous administration of acriflavine and proflavine preliminary report.—./. Urol., Bait., 1918, ii, 299-307.

White, E. C, Davis, E. G., and Rosen, R.

Urinary antisepsis. The secretion of antiseptic urine following the, intravenous administration of an organo-mercury phthalein derivative. — J. Urol, Bait., 1918, ii, 277-307.

Williams, J. W.

.\ consideration of some of the anatomical factors concerned in the production of deformed pelves. — Am. J. Obst., N. Y., 1918, ixxvii. 714758.


WOLFSOHN, J. M.

The predisposing factors of war psychoneuroses. — J. Am. M. Ass., Chicago, 1918. Ixx, 303-308. Also: Lancet, Lond., 1918. i, 177-180. The treatment of hysteria ; successful results of a rapid re-education methoi' — ./. Am. .U. Ass., Chicago, 1918, Ixxi, 2057-2062.

WOOIXEY, P. G.

Three cases which illustrate the consequences of coronary lesions. —

J. Lab. t£- Clin. M., St, Louis, 1917-18, iii, 192-198.

-Meningitis at Camp Greene. — ./. Lab. & Clin. M., St. Louis, 1917-18,

iii. 409-412.

Three cases of parietal aortic thrombosis. — J. Lab. <G Clin. Med.,

St. Louis, Mo., 1917-18. iii. ,-i39-347.

Convulsions. ( Editorial, i—-/. Lab. .£ Clin. M., St. Louis, 1917-18, iii,

719-720.

Yates, J. L.

Surgical methods in the treatment of malign affections of superficial lymphatic tissue. — Surg. Oimec. it Obst., Chicago, 1918, xxvii, 156-162. Observations of a Wisconsin medical officer in France. — Wisconsin M. J., Milwauliee, 1917-18, xvi, 476-477.

Young, H. H.

Cancer of the prostate. —

1918. i, 657-719.

Sarcoma of the prostate. 1918, i. 720-722.

Calculus disease of the prostate. — In: Mod. Urol. (Cabot), 8°, Phila. &

N. Y.. 1918, i, 723-724.

The employment of the high frequency current for the extraction of

calculi incarcerated in the lower end of the ureter. — J. Urol., Bait.,

1918, ii, 35-38.

A new operation for epispadias. — ./. Urol.. Bait.. 1918. ii, 237-251.

Recent progress in the treatment of cancer of the prostate, seminal

vesicles and bladder. — South. M. J., Birmingham, Ala., 1918, xi, 120 129.

Excision of vesical diverticula after intravesical invagination by

suction ; a new method. — Surg. Gynec. <t- Obst., Chicago, 1918, xxvi,

125-132.

Presentation of a radical operation for tuberculosis of the seminal

tract. — Surg. Oynec. A Obst.. Chicago. 1918. xxvi, 375-384.

Changes in trigone due to tuberculosis of kidney, ureter, and bladder.

Bridge formation and floating trigone. — Surg. Gynec. cC Obst., Chicago,

1918, xxvi, 608-615.

Young, H. H., and Davis, E. G.

The surgery of the double kidney. Report of a case of resection of upper segment for calculous pyonephrosis. — Surg. Gynec. d Obst., Chicago, 1918. xxvii, 1-13.

Zimmerman, E. L., and Keidel, A.

Tattooing and syphilis. — Am. J. Syph., St. Louis, 1918, i, 83-96.


2Iod. Urol. (Cabot), 8°, Phila. and N. Y. i; Mod. Urol. (Cabot), 8°, Phila. & N. Y.,


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Contents

Antituberculosis Measures. By Allen K. Kraisi: 49

Insusceptibility of Monkeys to Inoculation With HlooJ From Measll•^ Patients. (Illu>tiiitcd.> By Andrew Watson Sellards ami John A. Wentwortii S"

The Production of Tetany by the Intravenous Infusion of Sodium liicarbonate. Report of an Adult Case.

By George A. Harrop, Jr 6 Changes in the Blood Immediately Following Transfusion.

By John G. Huck, M. D. 03

Elizabeth Fry — Quaker Reformer. (Illustrated.!

Bv Henry M. Thomas 72


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[No. 337


Sixteen days after this injection, this animal was reinoculated with measles blood taken from a patient (C) wirhin from four to six hours after the rash had appeared. The blood was mixed with an equal part of 2 per cent sodimn citrate in physiological saline. Of this mixture 15 c. c. were injected intraperitoneally. On the following day, 24 hours later, another injection was made with blood taken from a patient (D) 12 hours after the appearance of the rash. This specimen of blood was diluted with an equal part of physiological saline and dcfibrinated ; 20 c. c. of this defibrinated mixture were injected intraperitoneally. After another interval of 24 hours a final injection was made with the blood of Patient E, taken not later than 12 hours after the rash had appeared. One part of blood was mixed with two parts of physiological saline and 20 c. c. of the defibrinated mixture were injected intraperitoneally. The efPect of these injections is given in Chart I. The temperature charts of these patients are also given. (Chart IV.)

Monkey II was kept under observation for 10 days. Blood for injection was taken from Patient B within from 6 to 12 hours after the first appearance of the rash. The specimen was mixed with an equal part of physiological saline and 20 c. c. of the defibrinated mixture were injected intraperitoneally. The white blood counts and temperature of this animal are given in Chart II. The temperature of the patient is recorded in Chart IV. Before injection this animal had a marked erythema o\ er the face and eyebrows ; a few macules were also present. This ra.sli faded during the first week of the incubation period, but increased somewhat 10 days after inoculation, mough its intensity was not so great as during


the period before injection. Since this time it has fluctuated considerably. At present, two months after the last injection, it is more marked than at any time during the incubation periods. Twelve days after the first injection of blood this monkey received injections of measles blood on three successive days ; these injections were exact duplicates of those just recorded for Monkey I, the same specimens of blood being used.

Monkey III. This animal, a young adult, was given a series of three injections simultaneously with Monkeys I and II. The same specimens of blood were employed though the details were different. The injection on the first day consisted of 8 c. c. of the mixture of citrated blood injected into the heart and 12 c. c. intraperitoneally. On the second and third days 30 c. c. of the defibrinated mixtures were given intraperitoneally. Tlie results in this monkey are recorded in Chart III.

REFERENCES

1. Hektoen: Jour. Infect. Dis., 1905, II, 238.

2. Anderson and Goldberger: Public Health Reports, 1911. XXVI, 847 and 887; Jour. Am. Med. Assn., 1911, LVII, 113, 476 and 971.

3. NicoUe and Conseil: Compt. Rend. Acad. Scien., 1911, CLIII, 1522.

4. Hektoen and Eggers: Jour. Am. Med. Assn., 1911, LVII, 1833.

5. Tunnicliff: Jour. Infect. Dis., 1912, XI, 474.

6. Lucas and Prizer: Jour. Med. Research, 1912, XXVI, 181.

7. Ricketts and Wilder; Jour. Am. Med. Assn., 1910, LIV, 463.

8. Tunnicliff: Jour. Infect. Dis., 1918, XXII, 462.

9. Plotz: Jour. Infect. Dis., 1915, XVII, 1.


THE PRODUCTION OF TETANY BY THE INTRAVENOUS INFUSION

OF SODIUM BICARBONATE

REPORT or A'm ADULT CASE

By George A. Hakrop, Jr.

(From the Medical Clinic of The Johns Hoiiki>is Hospital)


Many drugs and chemicals have been mentioned as causing tetany in adults. Following Frankl-Hochwart,' it has been customary to classify all these conditions in one group, as due to toxins or poisons. The clinical history of a patient with tetany which was produced, or at least precipitated, liy intravenous infusions of sodium bicarbonate follows :

L. H. Medical No. 39293. Colored. Aged 22. Domestic. Admitted, March 8, 1918. Died, March 18, 1918.

The family and past history were unimportant, except that the patient remembered no previous attacks which in any way suggested tetany, and the members of her family corroborated her statement.

Present Illness. — At 7.30 a. m. on the day of admission, before she had taken any food, she swallowed two 7%-grain tablets of bichloride of mercury, dissolved in a glass of water. Shortly afterward she vomited, and within an hour commenced to vomit


' Frankl-Hochwart: Die Tetanic der Erwachsenen, Leipzig, 1907.


blood. She was admitted to the hospital about noon. At this time she was vomiting dark colored material, and was very dull and drowsy.

Physical Examination. — Nothing abnormal was made out aside from tenderness and slight muscle spasm in the upper abdomen. The throat was red, but otherwise it showed nothing. All of the deep reflexes were normally active. No stigmata of rachitis could be found. Weight, 130 pounds. Mercury was recovered from the urine, feces, and vomitus.

Blood Examination. —W. B. C, 19,000. R. B. C. 5,624,000. Hemoglobin (Sahli), 90 per cent. Differential blood count normal. The Wassermann test was negative.

Course in the Hospital. — From the time of her admission the patient passed blood in her urine and stools. The usual energetic measures were taken to secure a large fluid intake and to eliminate the mercury.

On March 9 she became totally anuric and continued so until her death. On this day the plasma bicarbonate capacity (Van Slyke) was 45 volumes per cent, and the carbon dioxide tension of the alveolar air (Marriott) was 28 mm. of mercury. She was


March, 1919J


63


given 500 c.c. of a 5 per cent sodium bicarbonate solution intravenously.' No untoward effect was noted and she said that she felt more comfortable afterwards.

Twenty-four hours later (March 10). another intravenous infusion was given of 700 c.c. of a 5 per cent sodium bicarbonate solution, prepared as before. This made in all 60 grams of sodium bicarbonate given intravenously. A small amount given by mouth on March 9 had not been retained. About five minutes after this last infusion, which had been given slowly and had been apparently well taken, the patient's face suddenly grew pale, she commenced to have great inspiratory difficulty, and became very apprehensive. She complained of numbness and tingling of tlio fingers, and begged to have them rubbed. The hands assumed the typical obstetrical position, there was pedal spasm, and a first degree facial phenomenon (Chvostek's sign) was obtained. The pulse was accelerated to about 130, and the extremities became cold. There was no elevation of the blood-pressure. The acute attack lasted for about 15 minutes, after which the breathing became easier and she was less apprehensive. The main d'accouc/icur position was maintained for about two hours.

On March 11 a blood sample was taken for the calcium and phosphate determinations recorded below, and at the same time for a determination of the plasma bicarbonate capacity (Van Slyke), which was found to be 80 volumes per cent. This sample was taken about 20 hours after the original attack. On this day a second degree Chvostek's sign was obtained and Trousseau's phenomenon was easily elicited.

The further history of the case has no bearing on the present discussion, except that Trousseau's phenomenon was present until March 15, and Chvostek's sign was obtained the night before her death. March 18. Commencing on March 12 there was pitting edema of the lower legs, and on March 15 evidence of the accumulation of a moderate ascites. She became very anemic from the continued bleeding from the bowel, the hemoglobin (Sahli) on March 17 being only 20 per cent.


'This was prepared by boiling a sodium bicarbonate solution made up with freshly distilled water, and then reconverting the carbonate so formed back into the bicarbonate by passing a stream of carbon dioxide through the solution until it was no longer colored by a few drops of phenolphthalein.


The writer has been unable to find any clinical reports of tetany ocourring in adults followin-; the administration of sodium biiarbonato. Among the nuiny accidents following its use in the treatment of diabetic coma, the occurrence of convulsions, especially clonic in type, is frequently mentioned.' These convulsions have usually knl to a rapidly fatal termination, often in a few hours. Tetany, however, lias not been mentioned or identified as such, Ilowland and ilarrioic have observed tetany in young children following the therapeutic administration of sodium bicarbonate for acidosis and cite three cases.* During the period of tetany their patients showed a low calcium +++++ CONTENTS of the blood serum, a condition which they have shown to be pre.<ent during the active period of infantile tetany, particularly during or shortly after the occurrence of convulsions. The amount is usually tiien less than 7.0 mg. per 100 c. c. In the present case of adult tetany, analysis of the calcium +++++ CONTENTS of a blood serum samjile taken 20 hours after the original attack showed a value higher than 9.0 mg. per lOO c. c., iience about normal, and there was no marked accumulation of pliosphates (the phosphate +++++ CONTENTS of the blood serum was less than 6.0 mg. per 100 c. c.).* It shoidd be noted, however, that in this case there had been no actual convulsions. It seems clear that the condition here was associatetl with, if not directly precipit^ttod by, the suddenly increased alkalinity of the blood due to the sodium bicarbonate infusions.

In conclusion, it is desired to call attention to a danger, not too remote, attendant upon the intravenous u.se of sodium bicarbonate in conditions in which the renal excretory function is markedly impaired, and particularly when extreme oliguria or anuria is present.


'L. Blum: Ergeb. der inn. Med. u. Kinderh. 1913, XI, 480. " SjTuptomatologie und Therapie des Coma diabeticuni."

•Quart. Jour. Med., 1918, XL. 289.

'The calcium and phosphate determinations were kindly made by Dr. Howland and Dr. Marriott


CHANGES IN THE BLOOD IMMEDIATELY FOLLOWING TRANSFUSION

]?y John- G. Hick. M. D., Baltimore (From the Cliniral Laboratory of the Medical Department, The Johns Hopkins Univcrsilj/ and Hospital)


The ever-increasing use of transfusion as a therapeutic measure has stimulated interest to seek a clear explanation for the various changes that follow the introduction into one individual of the blood of another. Nevertheless, some of the simplest questions raised by this procedure remain still unanswered. For instance, although it is generally knowTi that after a transfusion the hemoglobin and the red corpuscle values are increased, the exact way in which the increase occurs is not understood. ^lany have assumed that the immediate effect is entirely mechanical, that is, that the blfjod of the recipient- is altered in direct proportion to the quantity of the blood introduced, just as though the two had been mixed in a vessel outside of the body; that, later, reactions on the


part of the blood-forming organs come into play, and these then take a part in detennining the succeeding changes. No doubt the mechanical and reactive effects are both important, but the relative importance of each is not clearly defined, and the decision has practical value, because the outcome may influence us to use either small transfusions frequently repeated or larger transfusions at longer interv'als.

Certain observations already at hand cast consideraiilc iloubt upon the view that the immediate effects of transfusion are purely mechanical and lead us at once to anticipate that these effects will be neither constant nor quantitative. T>am8on ' has shown how quickly and markedly the number of red cells in the circulation may be altered by the injection


64


[Xo. 337


of adrenalin. He is convinced by his experiments that the liver acts as a reservoir from which large numbers of red cells are poured into the circulation. No doubt other influences may act in the same prompt way upon this reservoir. Sellards and Baetjer,* from their experiments and a review of the entire subject, conclude that there is no constant nor quantitative response to the injection of foreign abnonnal elements into the blood. The object of the present study is to obtain detailed and exact infomiation upon the changes that occur in the blood elements immediately after transfusion.

METHODS

Transfusion was performed in each instance by a modification of the citrate method of Lewisohn, as described by Sydenstricker, Eivers and Mason." The details of the technique need not be repeated here. Especial care was taken in testing the donors to be'certain that the bloods were compatible. The amounts of blood given in different cases varied from 250 c. c. to 1250 c. c. Studies of the blood were made immediately before the injection, immediately after the injection, two hours, five hours and aboiit twenty-four hours later. These time intervals were followed rather closely in practically all of the cases. Each examination consisted of counts of the red cells and of the white cells, with a difEerential count of 300 white cells. Platelets were estimated in the smears and the hemoglobin was determined. Notes were also made on the moipliology of the blood cells. Counts were always made with the same instrmnents and by the same observer, with the same reagents ; and care was taken to draw the blood from the same part of the body, with uniform punctures.

The effect of transfusion was studied in seven cases of pernicious anemia, two cases of idiopathic purpura, four of benzol poisoning, five of secondary anemia and two of Banti's disease.

RESULTS

Eesponses to transfusion were so variable that it seems desirable to append the detailed protocols. A few of the niaiu points only will be summarized here.

Red Blood Cells. — In general, following the injection of blood, there was an immediate increase in the red cell count, the striking point being the marked increase in many cases apparently out of proportion to the quantity of blood introduced. Thus, in Case 2, the red coimt rose from 880,000 to 1,488,000 immediately after the injection of 500 c. c. ; and in Case 5, from 480,000 to 1,300,000, following the injection


of 650 c. c. Such remarkable changes indicate apparently a rapid redistribution of blood following an injection. In some cases the initial increase continued for several hours, usually falling, so that at the end of 24 hours the count had fallen to approximately where it was before transfusion. In other cases, however, there was a marked increase at the end of 24 hours. In several instances, after injection of blood, the count fell for a few hours and then rose slightly.

Hemoglobin. — The hemoglobin in most cases showed a uniform rise following transfusion, usually reaching its maximum at the end of 24 hours. In some cases the hemoglobin fell slightly after the initial rise. Changes in hemoglobin did not run parallel with changes in the red count, as may be seen best from the variations in the color indexes.

Leucocytes. — In practically every case following transfusion there was some increase in leucocytes. In several instances, however, they remained practically stationary or even fell. These relations do not seem to be constant in any particular type of case. The most striking change in the differential count is the increase in the polymorphonuclear neutrophiles, which was striking even in some cases where there was little change in the total leucocyte count. Occasionally a neutrophilic myelocyte was seen following transfusion, but they were not constant. In these cases no outpouring of nucleated red cells occurred, although in four instances a few were seen following transfusion, but not before. The numbers are so small, however, that this may have been accidental.

DISCUSSION

A general review of the immediate effect of transfusion upon the blood count in twenty cases does not reveal any constant changes following this procedure. The point of practical interest and importance seems to be that no exact mechanical effect can be demonstrated following the introduction of definite quantities of blood. Whereas, in a general way, it may be said that the introduction of blood raises the count, the effect is essentially a biological one involving the redistribution of blood in the body and its exact nature is not at present understood.

REFERENCES

1. Lamson: Jour. Pharmacol, and Exp. Therap.. 1915, VII, 169.

2. Sellards and Baetjer: Bull. Johns Hopkins Hosp.. 1918, XXIX, 135.

3. Sydenstricker, Mason and Rivers: Jour. A. M A., 1916, 117, 719.


M.VRCH, 1919J


65


BLOOD CHART— CASE 1 Patie-nts Name, Bbant; Wabd F; Age, 47; Medical No., 124 S33: Diagnosis, Per.nicious Anemia; Transfusion, 1250 c. c.


5-S1-I8

Before Transfusion

4.00 p. m.


P. M. N 143 47.e^< P. M. E 4 l.SSri

P. M. a

L. Lrm I 0.33%

S. Ljrm 146 48.e9<>

L. Mono 7 2.33%

Tnaa. 4 1.33%

K. Myelocytes

E. Myelocjtes

B. Myelocjtes

Mreloblasis I O.SS%

Smudtres 14 4.66%

Platelets Markedly decreased.

Nucleated R. B. C 2— Intermediate, 1

Normoblast. 1 Moderate anisocytosis. Moderate poikilocytoeis.

Basophilia Slightly diffused anc

punctate. No. Cells Counted and %. 300 99.91

lib 80%

R. B. C I 2.2SI.O00

W. B. C 3.200

C. 1 1.3

Condition of Patient No chill: no fever.

Blood Obtained Little fin^r left hand.


5-31-18


.31-18


5-31-18


8-1-18


After Transfusion





5.00 p. ni.


T.wt p. m.


10.00 p. m.


4.00 p. m.


n


ni


IV


^


lOfi 55.3%


141 47.095,


180 60.0%


227 75.6%


5 1.68%



5 1.60%



II


II



1 0.33%



4 1.33%



2 0.66%


113 37.8%


97 32.3%


S» SS.0%


40 1.13% 6 2.0%


8 2.66%


fl 3.09'r


3 1.0%


0.66%


4 1.33%



1 0.33%



II


8 2.60%


6 2.0%



6 2.0%


43 15.0%


5 1.68%


17 5.68%


Markedly decreased.


Markedly decreased.


Markedly dccreaflcd.




1-Megaloblast, 1


T) — Normoblasts, 5



Moderate anisocytosis.


Moderate anisocvtoeis.


Moderate anisocytosis.



Moderate poikilocytoeis.


Moderate poikiloc>'tosis.


Moderate poikilocytosis.


Moderate poikiloc.vtosis.


Slightly diffused and


Slightly diffused and


Slightly diffused and Slightly diffused and


punctate.


punctate.


punctate.




300 99.96


300 99.98


300 99.98


65%


65%


70%


70%


3,424,000


3,a12.000


2,960.000


2,688,000


4,200


3,340


S,W0


4.440



1.0


1.2


1.3


No chill: no fever.


Slight fever.


Slight fever.


Slight fever.


Third finger left hand.


Little flngcr left hand.


Third finger left hand.


Little finger left hand.


BLOOD CH.\RT— CASE 2 Patient's Name, Pa vuK ; Ward G; Age, 30; Medical No., 123834; Diagnosis, Pernicious Anemia; Transfusion, 500 c. c. 2d Transfusion


Date Time


3-26-18

Before Transfusion.

3.55 p. ni.


3-26-18

.\fter Transfusion

4.15 p. m.


3-26-18 6.15 p. m.


3-26-18 ).30 p. m.


3-2718 1.55 p. m.


P. M. N 1 187 62.3%

P. M. E 9 3.0%

P. M. B 1 0.33%

I. Lvm ! 8 2.66%

8. Lvm 68 22.8%

L. Mono 4 1.33%

Trans, 7 2.33%

N. Myrlocvtes 2.0%

E. MvelocVles

B. Mvclocvtes

MveloblasU 3 1.0%

Smudges 7 2.33%

Platelets Practically absent.

Nucleated R. B. C 1— Normoblast, 1

Marked anisocytosis. Marked poikiloc^'tosis. Bsjiophilia Slightly diffused.

N'o. CelU Counted and %. 300 99.98

Hb. 19%

R. B. C. 880.000

W. B. C. 3,800

C. 1 1.1

Condition of Patient .... No chill; no fever.

Blood Obtained Little Anger right hand.


16 5.33%


4 1.33%


3


L0%


10 3.33%


57 19.0%


^r, 5.0%


30


10.0%


45 15.0%


8 2.66%


10 3.33%


7


2.33% 2.0%


10 s.ssr/c


11 3.66%


1 0.33%


6


IS 5.0%


II



D





1 n.S3% 8 2.60%


2 0.60%


8


2.68%


2 0.68%


Moderatcl.y diminished.


Markedly diminished.


Moderately diminished.


Moderately diminished.


1 — Normoblast. 1


l-Normoblast, 1


.J-N


irmoblasts. 3



Marked anisocytosis.


Slight anisocytosis.


Marked


anisocvtosis.


Moderate anisocvtosis.


!l(oderate poikilocytosis.


Slight poikilocytosis.


Moderate


poikilocytosis.


Moderate poikiloc}'loai9.


Slightly diffused and


Slightly diffused.


Slightly


diffused.


Slightly diffused.


punctate.






300 99.94


300 99.95


300


99.99


300 99.92


25%


30%



30%


32%


1,488.000


1.512.000



1.410.1"!


1,688.000


4.300


8,700



5.4.^11


3,700


0.89


1.0



1.0


1.0


No chill; no fever.


Slight fever.



Fever.


No chill; no ferer.


Third Bngrcr right hand.


Little flngcr right hand.


Third finger right hand.


Little finger right hand


These cells are very I large in si7.e, the I majority with many lobed nuclei.


Patient's Name, Pavck; Ward G; Age, 30;


BLOOD rH.\RT— CASE 3 Medical No., 1L'S834; Diagnosis, Pebsiciocs Anemia; Transfusion, 500 c. c.


3-12-18

Before Transfusion

11.00 a. m.


312-18

After Transfusio

12.25 p. m.


3-12-18 .2.') p. ro.


3-1218 6.25 p. m.


3-13-18 11.00 a. n


P. M. X 194 54.6%

P. M. K n

P. M. B 1 0..'«%

I.. Lym » 1.68%

S. Lvm 80 26.8%

I.. Mono S 2.68%

Transitional 8 2.68%

N. MvelocTtes I n

K. Mvclocvtes ,

B. Myelocytes

Mvrlohlasts ; 2 0.68%

Smudges 2 0.80%

Platelets Moderately decreaaed.

Nucleated R, B. C. 6— Sormohlast, 4

I Intermediate, 1

I MegalohlasI, 1

Basophilia Moderately diffused am

punctate. Marked aniwocvtosis. Marked poikilocytosis. No. Cells Counted and %. 300 99.83

lib 10%

R. B. C 824.000

W. B. C 1,877

C. I I 0,83

Condition of Patient No chill; no fever.

Blood ObUined Little finger left hand.


10.0% 1.60% 1,60% 0.38%


2.0% atcly decreased.


Marked aninocytosls. Marked poikilocytosis. Slightly diffused and punctate.


O.XVfr

7.33% 0,80% 0.60%


30n 99.93

l.V^o

920,000

.1,040

0.83

No chill; no fever.

Third finger left hand.


M,rl:.-I nniaocTtosIs, Mark. I fiikllocytosis. I :<!•' 99.98

10% I (ca.noo

3,160 1.0


M;,rkc d animcytosls. MarkiMl poikilocvlosls.

ir«i 99.81

l.C.WI

I "

Krver.

Tliird finger left hand.


2.0% 14.0% .3.0% 2.33% 1.60%



Practicall.r abflent.

ThrMe seen larger in size'

and liirarre in shape. I l-lnlcnne<liatc, 1 Slightly diffused and

punctate. Marked anisocytosis. Markcfl poikilocytosis. .mo 99.96

15% 1,096,000 1.800 0.75 No rhill; no fever. I

Little finger left hand.


66


[No. 337


BLOOD CHART— CASE 4

Patient's Name, Alexander; Ward F; Age, 33; Medical No., 125655; Diagnosis, Pernicious Anemla; Transfusion, 750 c. c.

2d Transfusion


Date Time


6-29-18

Before Transfusion

11.00 a. m.


P. M. N

P. M. E

P. M. B

h. Lvm

S. L.vm

L. Mono

Transitional

N. Myelocytes

E. Myelocytes

B. Myelocytes

Myeloblasts

Smud,?es

Platelets

Nucleated R. B. C. . .


Basophilia

No. Cells Counted and %.

Hb

R. B. C

W. B. O

C. I

Condition of Patient

Blood Obtained


3 1.0%


Markedly diminished.


Marked anisocytosis. Marked poikilocvtosis. Slightly diffused and punctate.

300 99.92

44951

2,080,000

2,600


6-30-18 11.00 a. m


0.33% 43.0% 1.0%,


o.e


Markedly diminished. 1 — Normoblast, 1 Marked anisocytosis. Marked poikilocytosis. Slightly diffused and

punctate.

300 99.95


73.0% 2.66% 0.33%


20.6% 1.0% 0.66%


1 0.33%

i 1.33%

Markedly diminished.


Moderate anisocytosis.

Moderate poikilocytosis.

Slightly diffused.


Markedly diminished.


Moderate anisocytosis. Moderate poikilocytosis. Slightly diffused.


2,706.000 3,040


67.3% 1.66% 0.66% 0.33%

19.0% 4.0% 0.66% 2.33%




0.33% 11 3.66%

Practically absent.

4 — Megaloblast, 4 Marked anisocytosis. Slight poikilocytosis. Slightly diffused.

30O 99.93


No chill; no fever. Little finger right hand. Ft. transfused slowly in left arm.


A few pathol. lymphocytes seen in I, II, III.


Patient's Name, Bailet, Irwin;


BLOOD CHART— CASE 5 Ward M; Age, 30; Medical No., 121999; Diagnosis, Pernicious Anemia; Transfusion 650 c. c; 2d (1st Transfusion 12-15-17, 500 c. c; Washed Cells)


Date

Time

P. M. N

P. M. E

P. M. B

L. Lym

S. Lym

L. Mono

Transitional

N. Myelocytes

E. Myelocytes

B. Myelocytes

Myeloblasts

Smudges

Platelets

Nucleated R. B. C.


12-18-17

.\fter Transfusion

3.45 p. m.


12-18-17


12-18-17 8.45 p. m.


No. Cells Counted and %,

Hb

R. B. C

W. B.

C. I

Condition of Patient

Blood Obtained


— Megaloblasts, 2 Normoblasts, 3 Microcytes and macro cytes. Megalocytes. Slightly diffused and an

occasional punctate. .\nIsocytosis. Poikilocytosis.

300 99.91

Estimated (Sahli).

3%

480,000

6,080

0.37

No chill; no fever.

Little finger right hand.


Greatly decreased, large in size. 3 — Normoblast, 3

Microcytes and ' macro cytes. Megalocytes. Slightly diffused.


300 99.98

12% 1,360,000

5,640

0.47 No chill; slight fever. Third finger right hand.


12.3%

0.33%


Microcytes and macro cytes. Megalocytes. Slightly diffused.


0.71 Slight fever. Little finger right hand.


Microcytes and macro cytes. Megalocytes. Slightly diffused.


300

23% 1,324,000

6,000

0.84 Slight fever. Third finger right hand.


12-19-17 2.30 p. m.


89.0% 0.66% 0.33% 1.0% 8.0%



3 1.0%

Markedly decreased, not large in size.


Microcytes and macrocytes. Megalocytes.

Slightly diffused and punctate.

Marked anisocytosis.

Marked poikilocvtosis. 300 99.99


0.88 Slight fever. Little finger right hand.


Blood transfused in left arm slowly.


BLOOD CHART— CASE 6 Patient's Name, Ceockett; Ward G; Age, 65; Medical No., 120650; Diagnosis, Pernicious Anemia; Transfusion, 500 c. c.



10-22-17

Before Transfusion

11.45 a. m.

I


10-22-17

After Transfusion

12.40 p. m.

n


10-22-17 2.40 p. m.

m


10-22-17 5.40 p. m.

rv


10-23-17

11.45 a. m.

V




Remarks




P. M. N


108 36.0%

3 1.0%

1 0.33% 75 25.0% 79 26.3%

4 1.33% 4 1.33%

2 0.66%

24 8.6%

Normal; large in size.

8— Mieroblasts, 3

Normoblasts, 5

Many microcytes and

macrocytes.

Markedly diffused and

punctate. Marked anisocytosis. Marked poikilocytosis. 300 99.95 20% 1,176,000 5,000 0.90 No chill; no fever. Little finger left hand.


98 32.6% 1 0,33%!


60 20.0% 100 33.3%

1 0.33%, 3 1.0%

2 0.66%

35 ll'.6%

Normal; large in size.

18— Mieroblasts, 4

Normoblasts, 14

Many microcytes and

macrocytes.

Markedly diffused and

punctate. Marked anisocytosis. Marked poikilocytosis. 300 98.72 35% 1,432,000 6,320 1.2 No chill; no fever. Third finger left hand.


212 70.6%

2 0.66%


15 5.0% 53 17.6%

1 0.33%

3 1.0%

ii 4.66% Increased; large in size. 13— Mieroblasts, 3 Normoblasts, 9 Intermediate, 1 Few microcytes and macrocytes. Markedly diffused and

pimctate. Sliirht anisocytosis. Slight poikilocytosis. 300 99.85 34% 1.. '592,000 7,800 1.1 No rhill; no fever. Little finger left hand.


238 79.3%


ft 14 4.66% 32 10.6%

ft

3 1.0%

13 4.33% Increased; large in size. 5 — Mieroblasts, 1 Normoblasts, 3 Intermediate. 1 Few microcytes .-uid macrocytes. Markedly diffused and

punctate. Slight anisocytosis. Slight poikilocytosis. 300 99.89 32% 1,856,000 7,840 0.88 No chill; no fever. Third finger left hand.


108 36.0%

3 1.0%

4 1.33% 46 16.3% 77 25.6%

1 0.33%,

5 1.66%



1 0.33%

55 18.3%

Normal; large in size.

6— Mieroblasts. S

Normoblasts, 1

Intermediate, 2

Diffused and punctate.

Slight anisocj-tosis. Slight poikilocytosis. 300 99.85 31%, 1,368.000 8,200 1.1 No chill; no fever. Little finger left hand.



P. M. B



S. Lym


Nucleated R. B. C.



No. Cells Counted and %.



R. B. C

W. B. C

C. I

Condition of Patient




right arm, slowly, then rapidly.


March, 1919]


G7


Patiest's Name, White; Ward F; Age, 50;


BLOOD CHART— CASE 7 Medical No., 1226 IH, Diagnosis, Pebmcioi-s A.nemia; 2d Tbaxsfisiox, 600 c. c. (1st Transhsion. 2-3-18)



2-17.18 Before Transfusion


217-18 After Transfusion



2-1718


217 18


2-1818




Remark*


Time


10.45 «. m.

I


12.20 a. m.

n



2.20 p. m.

in


S.25 p. m. IV


10.4S a. in. V





140 46.9%


161 SS.OT'r


.>»


74.0%


246 82.0^0


21» 73.0%






3 1.0% 1)


1


0.38%




.< I.O^c

1 n.ss^'c






6 2.0%

'1 1
!!&


8 2.«8rt 84 28.0% 11 3.68%


I

6


O.SS% 16.8%

2.0%


4 \.3S% 27 O.IKT, 8 2.00%


2 0.66% .11 17.0% 4 1.3;i%





U Mono




! 8 2.as9e>



11 3.66% 4 1.33%


9

8


S.0% 2.68%


1 0.337e


i.6e7<>

.1 1.6870



N. MrelocytM



E. Mjeloc.vtes

"




1




1 0.33%


II 12 4.0%


17 5.68%


3


1.0%


5 1.88%


10 3.33%



Platelrts



Decreased slightly; some verj- large.


Norma


some Urge in


Markedly decreased. Some large in size.


Normal; some Urge In




2— NormobUsts.


5— Normoblast, 4


27—


Normoblast, 21


2— Nonnoblast. 1


8— Normoblast. 7





Intermediate, 1



Intermediate, 6


Intermediate, 1


Megaloblast. 1




SliKhtly diffused.


Diffused and punctate.


Slightl


V diffused and


Slightly diffused and Slightly diffused and




Slicht anisocvtosis.


Slight anisocvtosis.


punc


ate.


punctate.


punctate.




Slight poikilocj-tosis.


Slight poikilocjtosis.


Slight


anisoc.vtogis.


Moderate aniso^-tosis.


Moderate anisocvtosis.






Slight


poikiloc>'t06i9.


Moderate poikilocvtosis.


.M.Klt-ratc poikilocvtosis.




300 98.92


300 99.70


3(XI


99.92


300 99.97


300 99.97



Hb


S5% 1,288.000


44% 2,184.000



4870 2,64(1,000


48% 2.748.000


48% 2.448.000





W. B. C


3.720


2,760



2.400



3,560




1.4


1.0 No chill: no fever.


Severe


(I.S8 chill ; fever.


0.85 Fever.


1.0 No chill; no fever.





Blood ubuined


Little finger right hund.


Third finger right hand.


Little


finger right hand.


Third finger right hand.


Little finger right liand.


Blood transfused slowly in left arm.


BLOOD CHART— CASE 8 Patient's Name, Hopkins; Ward M; Age, 52; Medical No., 121133; Diagnosis, Banti's Disease; Transfusion, 400 c. (I.ST Transfusion, 500 c. c.) (Same Donor as 1st)



ll-*'-17


11-22-17

After Transfusion

11.43 a. m.

II


11-22-17

1.4.1 p. m.

Ill


11-22-17

5.45 p. m.

IV


11-2S-17

10.40 a. m. ' V




Before Transfusion 10.40a.m.


Remarks



I 1



P. M. F,. P. M. B.


Lym.

S. Lvm

U Mono

Transitional . . . N. Myelocyte* E. Myelocvtes . B. Myelocvtea . MyeloblaaU ...

Smudge*

PUteleU


Nucleated R. B. Basophilia


i.S% 1.66% 2.33% 2.33%! 6.33% 2.68% 4.33% 0.33%


38 12.8%

Increased; large in size.


99.87


Diffused.

Marked anisocvtosis. Marked poikilocytosis. 300 99.88


Diffused. .\nisocytosis. Poikilocvtosis. 300

81%

3,488,000 3,384.000

i 11,560 I 11,380

0.45 I 0.57

'Good; no fever; no chill. .No chill; no fever. Little finger right hand. Third finger right hand.


72.3% 5.0% 2.66% 1.68% 4.0% 1.66% 6.0%


20 6.69%

Increased ; markedly en Urged in size.


Diffused.

Marked anisocytosis. Marked poikilocytoeis. 300 99.94

40% 3,552,000 ll>,380 0.57 Slight fever. Little finger right hand.


83.0% 3.0%

2.sa%

1.33% 4.0% 0.66% 4.33%,


86.0% 2.3.1% 3.0%


1.0% 0.3.1% 4.60%


Greatlv increased.


Diffused.

Ani8oc>.t08is.

Poikilocytosis.


SOU


98.65


3.496.000

10.600

0.57

Slight fever.

Third finger right hand.


300 99.98

38%

4.352,000

10,049

0.44

No chill; no fever.

Little finger right hand.


Blood transfused In left arm, rapidly.


BLOOD CHART^CASE 9 Patibnt'8 Name, Thomas Hopkins; Ward M; Age, 52; Medical No., 121133; Diagnosis, Banti's Disease (?); Transfusion, 500 c. c.


Dale Time


11-917 rnre Transfusion 11.20 a. m.


11-9.17 ter Transfusion 1.35 p. m.


P. M. r.

P. M. B

L. Lym

S. l^

U Mono

Transltlnnal ... K. Myelocytes K. Myelocytes . B. Mvelocvtes . HyelohlasU ...

Smudges

Platelets


Nucleated R. B. C.


No. CelU Counted and %.


78,6% 3.0% l.SS% 2.33% 8.86% 0.69%


Increased markedly. Large in size.

2 — Normoblasts, 2 Macroc)-tcs aitd microeytes.

Diffused.

Marked anisocvtosis.

Marked poikilocytosis.

»nO 99.81

19%

2,890,000

9.940

.« 


73.3% 2.99% 2,0% 2,99% .1,99% 2,69%


14 469%

InfTcased markcdl.v. Large in size.

4— Normoblasts, 2 Microblasts, 2 Macrocytcs and micro cytei Diffused.

Markeil anisocvtosis.

Marked priikilocytosis.

300 99,gS

23%

2.68fl.flfl0

7,000

,44


Good; DO fever; no chill. iNo chill; no fever.


81,8% 2.88% 1.98% 1.38% 1,69% 5,0% 1.0%


17 S.<S%

Increased markedly. Large in <ize.

4— Normoblast*, 4 Macnvytes and microcytes.

Diffa«c<l,

Markcl anlaocytaria. Marked puikilocjtaris. 300 W.M

2»% 2,880.000 7,000 .41 Slight fever.


Rlood ObUined LiUle finger right hand. Little finger right hand. Little finger richt hand.


76.0% 1.60% 2.3.1% 3.00% .1.60% 1.3.1% 3.0%


Increased greatlv. Li

in size. 3— Normoblasts. MacTocytes and mlcro cyte*.

Diffused.

Marke<l anisocytosis. Marked poikilocytosis. 800 99.98

24% 8,416,000 8.120 .15 Slight fever.


,rhird finger right hand.


59.3% a 69% 0.60% 2.38% 890% 1.69% 7.69%


11.0% Large In size.


Diffused.

Marked anisocytosis. Marked poikiloc>.tosls 3110 99.

22% 2.840.000 9,000 ..19 No chill; no fever.


Little finger right hand.


del. cytcs.


These cells were seen

in slide n, Clamifled under

Trans. Seen in slide IV.

Classified under

Trans,


jPt, hsd no reaction

after transfusion

except fever of

lflO°,

Blood transfused In I left srm, rapidly.


G8


[No. 337


BLOOD CHART— CASE 10 Patient's Name, Petee Skafidos; Wakd F; Age, 24; Medical No., 120S04; Diagnosis, Echinococcus Cyst of Right Lung;

Transfusion, 500 c. c.



10-25-17

Before Transfusion

2.45 p. m.

I


10-25-17

After Transfusion

3.15 p. m.

n


10-25-17 5.30 p. m.

in


10-25-17

Before Operation

8.15 p. m.

IV


10-26-17

After Operation (18 hrs.)

3.30 p. m.

V




Remarks




p. M. N

P. M. E

P. M. B


228 7G.0% 5 1.66% 2 0.66% 8 2.66% 27 9.0% 5 1.66% 17 6.66%

's 2.66% Normal.


Diffused very little. 300 99.96 25%, 1,856,000 10.560 .69 Small hemoptysis and blood-streaked sputum. Little finger right hand.


227 75.6%,

1 0.33%

2 0.66%, 14 4.66%

16 5.33%,

3 1.0%

17 6.66%

!! '.'.

20 6.66%, Normal.


Diffused very little. 300 99.90 35% 2,184,000 12,640 .83 Small hemoptysis and blood-streaked sputum. Third finger right hand.


248 82.0% 1 0.33%, 1 0.33%, 10 3.33%, 18 6.0%, 6 2.0% 9 3.0%;

'9 3.6% Increased.


Diffused very little. 300 99.99 35%, 2,496,000 13,080 .73 Small hemoptysis and blood-streaked sputum. Little finger right hand.


247 82.3%,

3 1.0%

5 1.66%o 19 6.33%,

6 2.0% 14 4.66%,

'6 2.6% Increased slightly.

Diffused very little. 300 99.95 33%, 2,160,000 14,800 .78 Small hemoptysis and blood-streaked sputum. Third finger right hand.


251 83.6%,


. 2 0.66%,

5 1.66% 9 3.0%

6 2.0%, 10 6.33%

ii 3.66%, Increased slightly.

2 — Normoblasts, 2 Diffused very little. 300 99.91 32%, 2,776,000 20,120 .59 Fever. Some *' old " blood-streaked sputum. Little finger right hand.


Pt. died from hemorrhage on 10-31-17.


S. Lvm



L Mono




Cell seen in slide UI



classified here.




Nucleated R. B. C



No. Cells Ckjunted and %. Hb



R. B. C

W. B. C

C. I

Condition of Patient




left arm, somewhat rapidl.v.


BLOOD CHART— CASE 11 Patient's Name, Stlvia McMillian; Wabd O; Age, 26; Gyn. No., 122424; Diagnosis, Post-Operative; Transfusion, 300 c. c.



1-13-18

Before Transfusion

10.00 a. m.

I


1-13-18

After Transfusion

1.00 p. m.

n


1-13-18 3.00 p. m.

m


IV


V




Remarks





227 75.6%

1 0.33%


29 9.66%,

2 0.68% 12 4.0%

6 2.0%


1 0.33%


22 7.33%, Practically absent. 144— Normoblast, 144

Markedly diffuse; slightly

punctate. Moderate anisocytosis. Moderate poikilocytosis. 300 99.91 5%, 1,112,000 37,700 0.22 Fever. Little finger left hand.


126 42.0%,


3 1.0% 84 28.0% 6 2.0% 15 5.0% 42 14.0%


3 1.0% 21 7.0% Practically absent. 1329-Normoblasts, 1000 Intermediate, 329 Markedly diffuse; slightly punctate. Moderate anisocytosis. Jloderate poikilocj'tosis. 300 100.0 22% 1.216.000 26,360 0.91 Fever. Third finger left hand.


210 70.0%


3 1.0% 42 14.0% 3 1.0%, 6 2.0% 30 10.0%


3 1.0% 3 1.0% Moderately diminished. 849— Normoblasts, 809 Intermediates, 40 Markedly diffused; slight

punctate. Moderate anisocytosis. Moderate poikilocvtosis. 300 100. 19% 2.480,000 24,500 0.39 Fever. Little finger left hand.




To give transfusion rt. arm was used and had to cut


p. M. E

P. M. B




S. Lvm




p. m.







Nucleated R. B. C



No. Cells Counted and %. Hb



R. B. C

W. B. C

C. I

Condition of Patient





BLOOD CJHART— CASE 12 Patient's Name, Charles Thomas; Ward D; Age, 43; Surgical No., 121146; Diagnosis, Sinus Tract in Old Wound; Transfusion, 500 c. c.


Date Time


11-25-17

Before Ti'ansfusion

12.00 m.


11-2517 (er Transfusion 2.00 p. ni.


11-25-17 4.00 p. m


11-25-17 7.00 p. m.


11-26-17 12.15 p. m.


P. M. N

P. M. E

P. M. B

L. Lvm

S. Lym

L. Mono

Transitional

N. Myelocytes

E. Myelocytes

B. Myelocytes

M.veloblasts

Smudges

Platelets

Nucleated R. B. C. ..

Basophilia

No. Cells Counted and

Hb

R, B. C

W. B.

C. I

Condition of Patient . Blood Obtained


14 4.66%,

Normal.

Slight anisocytosis. Slight poikilocytosis.


300




42%

3,144,000

17,280

0.67

M chill; no fever.

.ittle finger right hand.


0.33%, 3.33%, 0.33%, 1.33%,


31 10.3%

Slightly increased. Slight anisocytosis. Slight poikilocytosis.


63%

3,296,000

14.640

0.82

Slight chill.

Third finger right hand.


30 10.0%

Slightly increased. Slight anisocytosis. Slight poikilocytosis. Diffused. 300 99.95

62% 3,696,000 12,160 0.72 \o rhill; no fever. Little finger right hand.


Greatly increased. Slight anisocytosis. Slight poikilocvtosis.

300




99.95

53%

3,656,000

14,5(X)

0.73

No chill; no fever.

Third finger right hand.


0.33% 2.33%, 3.0%


Greatly increased. Slight anisocytosis. Slight poikilocytosis.


300 99.91

52%, 4,288,000 11,620 0.61 No chill; no fever. Little finger right hand.


Pt. was operated on Sept. 20. 1917, for gastric ulcer. 50 c. c. blood injected when needle became clogged; interval of half hour before continuing.

Seen in slide I.

Classified under Trans.

Pt. was operated on again on Nov. 28, 1917. Found tubercles throughout abdominal cavity. Pt. died on Nov. 29, 1917.


March, 1919]


69


BLOOD CHART— CASE 13 Patient's N.\me, M. STRrzYKOwsKi; W.\rd G; Age. 14; Medical Xo., 120599; Diao.nosis, Typhoid Fe\'eb; Tbaxsfcsiox, 300 c. o.

(10-8-17 1st TR.\NSFnsioN, 400 c. c.)


10-11-17

After Transfusion

1.50 p. m.

n


Date 101117

Before Transfusion

Time 12 m.

I I

P. M. X 138 46.0%

P. M. E 4 1.33%

P. M. B P

L. Lvm S6 18.6%

S. Lvm 70 23.3%

U Jiono 3 0.66%

Transitional : 17 5.66%

N. Myelocytes

E. Myelocytes |

B. Myelocytes ,

Myeloblasts '

Smudges 13 4.83%

Platelets Decreased slightly; large Normal; large.

in size.

Nucleated R. B. C.

Basophilia Diffused.

.\nisocytosi8.

Poikilocrtosis. N'o. Cells Counted and %. 300 99.S8

Hb 33%

B. B. C 1,872,000

W. B. C 2,320

C. 1 0.91

Condition of Patient Slight fever.

Blood UbUineU Little finger left hand.


1011.17 3.15 p. m.


1011-17 5.15 p. m.


10-121 11.15 p.


65.0%


10.3% 21.6% 1.66% 2.33%


11.3%

is.e%

2.33% 2.83%


8 2.66%

Decreased; large in size. Large in size.


7.SS% 2.5.3% 2.33% 3.33%)


Diffused.

Slight anisooytosis. Slight poikilocvtoeis, 3i<0 99.82


Slight fever.

Third Bngcr left hand.


Diffused.

Slight anisoc}-toei& Slight poikilocytosis. 300 99.88

39% 2,168.000

5,200

0.93 Slight fever. Third finger left hand.


Diffused.

Slight anisoc.^iosis. Slight poikilocytosis. 300 99.87

40% 2,376,000

3,640

0.87 Fever. Second finger left hand.


Decreased; large in size.


Diffused.

Slight anisoc.vtoeis. Slight poikiloc^-tosis. 3U0 99.32

42% 2,352,000 3,240 0.91 Slight fever. Tliird finger left hand.


Blood transfused

left arm, v< 1 slowly.


BLOOD CHART— CASE 14 Patiext's Name, Marie Zahbodka; Ward G; Age, 29; Medical No., 120464; Diagxosis, Ttphoid Feveb; Transfusion, 250 c. c.


10-10-17

.\fter Transfusion 12.05 p. m.


Dale 1010-17

Before Transfusion

Time 11.00 a. m.

' I

P. M. N 9S 32.6%

P. M. E 2 0.6%

P. M. B

L. L»-m 46 15.3%

S. L.vm. 122 4a6%

U Mono 6 1.6%

Transitional 15 6.0%

N. Mrelorytes

E. Myeloc}-tes

B. Mvelocvtcs |

Mveloblaats

Smudges 12 4.0%

Platelets I..arge in size; decreased. Large in size

Nucleated R. B. C. None. None.

' Slight anisocytosis.

Slight Doikilocytosis.

Bcaophilia Diffused and punctate. Diffused.

Many cells seen. No. Cells Counted and %. 300 99.7

Hb. 30%

R. B. C I 2,128.000

W. B. C. 6,360

C. L 0.71

CondiUon o( Patient ....! Slight chill.

Blood Obuined 'Liule finger right band


10-1017 5.30 p. m.


10-lM 11.30 a.


13.3%

22.09<. 0.66% 9.6%


I Many cells seen.

38%

1.768,(100

7,440


99.89


51.3%


0.33% 20.6% 12.0%

1.0%

9.6%


I*arge

None.

Slight nnNoc.\-tosis.

Slight poikilocytosis.

Diffused; very few.

99.83


23.6% 10.0% 0.66% 7.0%


38.3% 10.3% 2.8% 9.8%


6.0% 14 4.6% 2 0.66%

size; decreased. r<arge in size; decreased. Slightly increased. None. None.

Slight anisoc.vtosis. Slight anisoc.vtoeis.

Slight poikilocytosis. Slight poikilocytosis.

Diffused and punctate; Diffused; few. few.

800 99.86 800 99.86

40% 39%

1,648,000 1,872,000

5,120 6,660


Chill. ' Fo

Third finger right hand. Third flngo


1.2


Fever.


1.0


38%

2,384,000

6,380

0.82

Slight feve


right hand. { Little finger right hand. : Little finger right hand.


Blood transfused in left arm— rapidly.


BLOOD CHART— CASE 15 Patient's Name. Baceb; Ward G; Age, 28; Medical No., 125383; Diagnosis, Benzol Poisoning; Transfusion, 600 c.


Date

Time


520-18

Before Transfusion

3.15 p. m.

I


5-2018

After Transfusion

4.10 p. m.

II


520-18 6.10 p. m.

m


5.2018

9.10 p. m. IV


5-21-18

3.16 p. m. V


Remsrks


P. M. N

P. M. E

P. M. B


60 16.6% 2 0.66%


230 76'.^°

5 1.0%

6 l-etfH,


1 0.13%


2 0.68%

3 1.0% PrartirallT absent. Slight anUocTtosis. Slight poikilocj-toris.

2— Normoblast, 1 Megaloblast, 1 Slightly diffused and punctate.

300 99.94

38%

l.9R4.nno

1.160 1.0 No chill: no ferer. Little finger left hand.


62 20.6%


8 2.66% 192 64.0% 20 6.66% 10 3.33%


2 0.66% 6 2.0% Practically absent. Slight ani«ooto»is. Slight poikilocytosis.


Slightly diffused and puncute

300 99.91

4.1%

1.768,000

2,640

1.2

No chill; no ferer.

Third finger left hand.


ft-. 81.6%

2 0.66%

n

n 1S7 62.3% in 3.83%


n



2 0.66%

4 1.83% Practically absent Slight aniwcylods. Slight poikilocytosis.


Slighily diiruacd and punctate.

300 t».«e

47%

2,240,000

1.38)

1.0

Slight fever.

Utile finger left band.


62 2n.69i


5 1.66% 220 73..1% 4 1.83% 4 1.83% (1


3 1.0% 2 0.66% Prarticallv absent. Slight ani.oK-vtnsis. Slight iK.ikil<<-yto<iis. 2— Normoblasts.

Slightly diffused s n d puncUte.

300 99.98

45%

2,796,000

1,280

0.83

Slight fevor.

Tliiril finger left hand.


47 l.'>.6% 3 1.0%

7 2.33% 218 72.6%

10 3.33% 8.0%

2 0.66%



1 0.33%

3 L0% Pnireically absent. Slight snisocylosis. Slight iKiikilocytosli.


Slightly diffused s n d puncUle.

ant 99.96

4.1%

2,.176,n00

2,000

0.96

No chill ; no fever.

Little finger left hsnd.







h. Mono.





V. Mrelorytes



r.. Mvplocytes



n. Mxlocrtes



MielnhlijU



Smudgm

rialelels

Nucleated R. B. C.

Buophilia

No. Oils Counted and %. Hh



R. B. C.

W. B. C

C. I



Tondition of Pittent

Blood Obuined


Pt. transfused slowly in right arm.


70


[No. 331


BLOOD CHART— CASE 16 Patient's Name, Chas. Webek; Waed F; Age, 17; Medical No., 122256; Diagnosis, Benzol Poisoning; Transfusion, 275 c. c.


p. M. N

p. M. E

p. M. B

L. Lym

S. Lj-rn

L. Mono

Transitional . . . N. Myelocytes E. Myelocytes . B. Myelocytes . Myeloblasts . . .

Smudges

Platelets

Nucleated R. B, Basophilia


Ifo. Cells Counted and *

Hb

R. B. C

W. B. C


1-11-18

Before Transfusion

10.00 a. m.


1-1-18

After Transfusion

11.30 a. ni.


1-1-18 4.30 p. m


20.0% 22.6% 1.07o 10.3%


Practically absent.


Slightly diffused. Slight anisocytosis. Slight poikilocytosis. 300 99.86

54% 2.648,000 2,400


Practically absent.


Practicallj' absent.


Slightly diffused.


Slightly diffused.


Slight anisocytosis.


Slight anisocytosis.


Slight poikilocytosis.


Slight poikilocytosis.


300 99.79


3WI 99.88


59%


57%


2,272.000


2,512,000


3,160


1,880


1.3


1.9


No chill ; no fever.


Slight fever.


Third finger right hand.


Little finger right hand.


Practically absent. "

Slightly diffused. .flight anisocytosis. Slight poikilocytosis. 300 99.92

67% 3,216,000 1,800 0.89 Slight fever. Third finger right hand.


Practically' absent.

300 99.84

Slightly diffused. Slight anisocytosis. Slight poikilocytosis.


54% 2,368,000 1,720


Blood transfused in left arm slowly.


BLOOD CHART— CASE 17 Patient's Name, Chas. Weber; Ward F; Age, 17; Medical No., 122256; Diagnosis, Benzol Poisoning; Third Transfusion, 300 c. c.



1-9-18

Before Transfusion

2.00 p. m.

I


1-9-18

After Ti'.insfiision

4.00 p. m.

n


1-9-18 6.00 p. m.

m


1-9-18

9.00 p. m.

IV


1-10-18

2.00 p. m.

V




Remarks




p. M. N

P. M. E

P. M. B


96 32.0% 1 0.33%


32 10,6% 115 . 38.3% 16 5.33% 28 9.33%

1 0.33%


II n

11 3.66% Practically absent; those seen large in size.


110 36.6% 1 0.33%

18 6.0% 129 43.0% 7 2.33% 28 9.33%,



1 0.33% 6 2.0%

Practically absent; those seen large in size.

Moderately diffused. Slight anisocytosis. Slight poikilocytosis. 300 99.92 42% 2,704,000 2,680 0.77 No chill; no fever. Third finger right hand.


111 37.0% 1 0.33%,

11 3.66% 127 42.3% U 3.66% 23 7.66%, 5 L66%


U 3.66% Practically absent; those seen large in size.

Moderately diffused. Slight anisocytosis. Slight poikilocytosis. 300 99.93 43% 2,752,000 2,080 0.79 Slight chill; slight fever. Little finger right hand.


90 30.0% 1 0.33%,


13 4.33%

162 54.0%

8 2.66%

18 6.0%

1 0.33% 1 0.33%


6 2.0% Practically absent.


Moderately diffused. Slight anisocytosis. Slight poikilocytosis. 300 99.98 40% 2,120,000 1,880 0.90 Slight fever. Third finger right hand.


90 30.0%, 3 1.0% 1 0.33%

17 5.66%, 130 43.3%

14 4.66%,

37 12.3%, 1 0.33%


7 2.33%, Practically absent.

1 — Normoblast. Moderately diffused. Slight anisocytosis. Slight poikilocrtosis. 300 ' 99.91 41% 2,296,000 1,840 0.93 No chill; no fever. Little finger right hand.


Many patho. lym. in


S. Lym


I, n, V. Nucleated R. B. C



No. Cells Counted and %.


Slight anisocj-tosis. Slight poikilocytosis. 300 " 99.88 39% 2,232,000 1,920 0.88 No chill; no fever. Little finger right hand.



R. B. C

W. B. C.

C. I

Condition of Patient




left arm slowly.


BLOOD CHART— CASE 18 Patient's Name, Ellen Foppino; Ward G; Age, 36; Medical No., 125109; Diagnosis, Benzol Poisoning; Transfusion, 750 c. c.



5-11-18

Before Transfusion

2.0O p. m.

I


5-11-18

.\fter Transfusion

3.45 p. m.

n


5-11-18 5.46 p. m.

m


5-11-18

8.45 p. m. IV


5-12-18

2.00 p. m.

V



Time


Remarks




P. M. N

P. M. E

P. M. B

L. Lym

S. Lym

L. Mono

Transitional . . N. Myelocytes E. Myelocytes B. Myelocytes MyelobLists . .

Smudges

Platelets


Nucleated R. B. C.


Basophilia

No. Cells Counted and %.

Hb

R. B. C

W. B. C

C. I

Condition of Patient . , . , Blood Obtained


36.0% 56.3% 4.0%


Practically absent.


Moderate anisocytosis. Moderate poikilocytosis. Slightly diffused. 300 99.96


Occasional ; those se&n large in size, bizarre in shape.


Moderate anisocytosis. Moderate poikilocytosis. Slightly diffused. 300 99.94

46% 2,856,000 640


Little finger left hand. Third finger left hand


Practically absent.


Moderate anisocytosis. Moderate poikilocytosis Slightly diffused.


Little finger left hand.


'ractically absent.


1 — Megaloblast. Moderate anisocytosis. Moderate poikilocytosis. Slightly diffused. 300 99.99

45% 2,464,000 800


Third finger left hand.


Practically absent.


Moderate anisocytosis. Moderate poikilocytosis. Slightly diffused.


Little finger left hand.


PL transfused slowly in right arnu


March, 1919]


71


Patient's Name, Stbombebger; Ward G;


BLOOD CHART— CASE 19 Age, 19; Medical No., 126431; Diagnosis, Idiopathic Purpura;


Transfusion, 700 c. c.


Date Time



5-12

IS



512

s


Before Triuisfusion


.\ft


er Transfusion



2.00 p


m.



3.10 p


m.



I




n



247



82.3%


233



77.6%


6



2.0%


6



2.0%


1



0.3S7c


2



0.66%






2



0.66%


SO



10.0%


SO



10.0^,^


4



1.33%


13



4.33%


8



2.68%


6



2.0%




1



O.SS%,



1




n.3S%


S



1.0%


8



2.66%



5


1218



8.M


p. in.

n'


230



7a 6%


7



2.33%


2



0.66%


SO



10.0%


14



4.66%


12



4.0%



1



0.33%


4



1.33%


Practically


absent.






Slight anisocytosis.


No poikilocytogis.


SISIS i.OO p. m.


P. M. E. P. M. B.


S. Lym

L. Mono

Transitional .... X. Myeloc>-tcs . E. Myelocytes .. B. Myelocytes . .

Myeloblasts

Smudges

Platelets

Nucleated R. B.


78.0% 1.33% 0.66%


Prnrt ically absent.


I.^lifrht anisoc>'to6)S. No poikilocytosis.




, ... 99.95

7S% 1 5.014.000

I 8.200

' 0.73

No chill; no fe\*er.

Little finger right hand.


Practically absent.


81%

5,120,(X»

12,r>(K)


Practically absent.


Slight anisocytods. No poikilocytosis.


.i.lK.OOO

12.600

('.S3

Slight fever.

Little finger right hand.


79.0% 1.33% 0.33%


13.6% 3.0% 1.66%


Practically absent.


Slight anisocytosis. No poikilocytosis.


81%

5.474.000

14,200



300 !

84% 5,616.I»K) 13,400 0.75 Slight fever. No chill: no fever.

Third finger right hand. Little finger right hand. Pt. transfused slowly

' in left arm.


BLOOD CHART— CASE 20 Patient's Name, Mary Stromuergeb; Ward G; Age, 19; Medical No., 126431; Diagnosis, Idiopathic Purpura;

1st Transfusion, 600 c. c.


Date

Time

P M. X

P. M. E

P. M. B

L. Lvm

L &.:::::

Transtitional .. N. Mvelocyles E. Mvelocvtes B. Mvrlocvtes Myeloblasu ..

Smudges

Platelets


4-29.18

Before Transfusion

12.30 p. m.


4.29-18

After Transfusion

1.55 p. ni.


4-29.18 >.5S p. m.


4-30-18 12.30 p. m.


65.3%

1.33%

22.0% 3.0% 4.0%


65.6% 0.66% 0.66% 2.33%

15.0% 2.66% 5.667e


2 7.33%

Practically absent; those Markedly diminished; seen large in size. those seen large in size

I and bizarre in shape.


Nucleated B. B. C. !»— Normoblast, 3 I

Marked ani!<ocytosis. |

Marke<l poikilocytosis. I

Basophilia Moderatelv diffused. Moderately diffused.

No, Cells Counted and %. ' 300 "300

lib I 40% 46%

R. B. C 3.492,000 3,9(10.000

W. B. C I 7.600 8,100

C. I I 0.66 0,58

Condition of Patient ....|No chill; no fever. No chill: no fever.

Blood Obuined iLittle finger left band. Tliird finger left hand.


Markcdlv Tliose 5C( size and shape.


85.0% 0.33% 0.33% 0.66%


4.66% diminished ; n large in bizarre in


.Slightly diffused.

300

49%

3,904.000

11.200

0.02

Severe chill.

Little finger left hand.


0.33% 8.33% 4.33% 8.0%


3 1.0%

Practic-ally absent; those' seen lar^c in size and bizarre in shape.


Slightly diffused.

sno

49%

3.912,000

11,680

0.62

Fever 103°.

Third finger left hand.


).66%

r.0%

1.33%

>.6e7o


Practically absent; seen large in size.


33% 33% those


Marked anisoc.vtosis. NLirkcd poikilocvtosis. Sliglitly diffused.


0.«f No chill: no fever. Little finger left hand.


Path. Lym. (Reider) Tu-o seen in I, one seen in V.


BLOOD CHART— CASE 21 Patient's Name, William Meyer; Ward F; Age, 52; Medical No., 121243; Diagnosis, Hypertension with Myocardial iNsumciENCY;

Control; No Transfusion


Date Time


11-30-17

Before Transfusion

2.20 p. m.


11.3017 r»cr Transfusion 4.30 p. m.


11-30.17 &30 p. m.


12-1-17 2.30 p. m.


P. M. B

U Lvm

S. Lvm

U llono

Transitions) ... N. Myelocytes E. Myelocyte* . B. Myelocyte* . M.velohlasts ...

Smudges

Platelets


Nucleated R. B. C

Basophilia

No. Cells Counted and %.


3.33% 17.0% 1.60% 3.60%


10 3.33%

Norma t

Vc anisocytosis. No poikilccyt'.sjs. 1 — Normoblast,


300 9».n

73% 4,384,000 7,300 0.84 No chill; no fever. Little Anger right hand.


S.0% 17.8% 2.83% 3.60%


Normal.

1 No anisocytosis.

j No poikilocytosis.


74% 4.376.000

7,.1B0

0.86 Vo chill; no fercr. Third finger right hand.


6.3S% ie.0% 3.0% 2.00%


Xormal.

No anisocytosis.

No poikilocytosU.


No chill; no fercr. Little finger right hand.


).0%

).66% )..'«% 5.66% r.0% J..33% 1.0%


Xormal.

No snisocytosis.

No poikilocytosis.


300 »B.»1

74%

4,392.000

7,240

0.86

No chill: no fever.

Third finger right hand.


73


[Xo. 33:


ELIZABETH FRY-QUAKER REFORMER'

By Henhy M. Thomas


111 speaking of Elizabeth Frj- to my friends I am struck with how little is kllo^vn about her, and yet one hundred years ago she was beginning in London a career that made her the most influential woman of her time, certainly in philanthropy and, I believe, in general.

To understand Elizabeth Fry and her struggles it is necessary to know something about Quakers, or the Society of Friends, to which sect she belonged.

Most of you know that the Society of Friends was founded by George Fox in 1647-48 as a protest against the formality and abuses which he believed had affected the Church at that time. He taught that true religion is a direct personal experience, and that there is in every man's soul something that responds to the truth as revealed in the Bible, which, when properly regarded and attended to, is a safe guide for conduct. This view led to a personal interpretation of the Bible and did away with creeds and the authority of priests or ministers. He and his followers " bore testimony," as they would say, against many customs and beliefs that they disapproved of. They took many of the injunctions of the Bible literally and felt it wrong to call any man master and to show more respect to one than to another, and they therefore refused to take off their hats before the great and keep them on before the lowly, said " thee " and " thou " to their equals and superiors as well as to those usually called inferiors, adopted a manner of dress which they did not change with the fashions, refused to take legal oaths, and many other such things. From the first they acknowledged the complete equality of women and gave them equal influence in the conduct of the Society.

George Fox was a powerful, persuasive preacher, and influenced many people particularly among the lowly, but not a few among the well-to-do and learned. Among these latter were William Penn, Eobert Barclay and John Gurney. John' Gurney, the ancestor of Elizabeth Fry, was put into prison with other Friends and remained there for three years because he would not take the oath of allegiance, his testimony being against taking any oath. All the Gurneys appear to have been prosperous, and were interested in woolen weaving and in banking.

John Gurney, Elizabeth Fry"s father, married Catherine Bell, the great granddaughter of Robert Barclay, the Quaker apologist, and so the Gurneys of Earlham could trace their ancestry on both sides through an unbroken line of influential Quakers to founders of the Society.

John Gurney had inherited quite a large property and had himself prospered. In 1786 he leased from Edward Bacon the estate of EarUiam in Norfolk near Norwich, and it is


^ Read before The Johns Hopkins Historical Society, Pel)nuiry 12, 1917.


from this estate which stayed in the Gurney family for nearly 100 years that the Gurneys of Earlham took their name.

Augustus Hare's book (The Gurneys of Earlham) is by far the most attractive account of this remarkable family. John Gurney and his wife had 13 children, 11 of whom grew up. Of these 11 there were seven daughters and four sons. Mrs. Gurney died when her youngest child was only a little over a year old, and tlie eldest, Catherine, who from that time took charge of the family, was only 17. Mr. Gurney and his wife were not strict Quakers, and although they conformed in some respects to the customs of the Society, they were very liberal in their manner of life and I have no doubt were the objects of deep concern to their plainer relatives and other members of the Society.

At the time of Mrs. Gurney's death, Elizabeth, the third daughter, was just 12, having been born on the 31st of May, 1780. There was one sister between Catherine and herseK and next to her came a boy, John, then four girls bom in three years, and three boys ending the flock. These 11 children, deprived of their mother, were drawn closely together and developed themselves and each other into a wonderfully united family. Catherine, who when still very young, was known as Mrs. Catherine Gurney, felt the chief responsibility of their bringing up, and with the help of the older girls guided them as l^est she could. The father interfered but little, requiring only that they go to Meeting on First Day at least once and sometimes twice. Even this slight conformity was resented by the young people and many are the disparaging remarks recorded in the journals of the children, for keeping of journals appeared to be one of the methods of education in this family, and, indeed, in general at that period. In " The Gurneys of Earlham " we find interesting abstracts from these journals and I wish that I might read you some of them. Indeed, I must read one note written by Louisa Gurney when 11 years' old, particularly as it refers to the subject of our study and gives us a glimpse of one phase of the family.

Aug. 14 (1796). Betsy is so ill, I look forward with the most

gloomy ideas concerning her A great many Friends came

to tea. I did all I could to please tliem. How charming it is to feel one is giving pleasure: though I can never say how

stupid they were to me After tea Kitty chose we should

work again; this was rather a tug to me, but I bore it pretty well, only Kitty did provoke me by making me give up something to Chenda, merely because she was the eldest; there is nothing I hate so much as this sort of partiality; it does provoke me so. We read a little Sacred History; I like the Old Testament amazingly.

The house at Earlham was very large and the Gurneys entertained freely, and as the girls grew older it must have been a most attractive place to visit. The seven girls dressed as gaily as possible, and were often seen in a band riding


THE JOHNS HOPKINS HOSPITAL BULLETIN, MARCH, 1919



msjs^


ELIZABETH, MRS, FRY. After the Portrait by George Richn


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73


over the country on their ponies, wearing scarlet ridinj; habits. The literary- and scientific youufr men of the neighborhood came to the house and tlicre was much discussion on the subjects of the day. particularly in relation to the philosophy of Rousseau, Voltaire and other free-thinking autliors of tliose times. Among this group there were only two young men who took a serious view of life — one the Baptist minister, the other a Roman Catholic chemist named Pitchford, and strangely enough it was this latter who was the one steadying influence to this flock of Quakers. Among this band Elizabeth was probably the gayest and in many ways the most attractive. She sang sweetly, danced beautifully, and was a remarkably independent character. From a very early age slie appears to have been delicate and to have suffered from marked nervous symptoms. She was dreadfully afraid of many things, particularly of the dark and of the water. She also kept a diarj-, but, unfortunately, when she read it over towards the end of her life she felt it wise to destroy all the early years. Judging from what she wrote later, it would have been a most valuable accomit of the feelings and experiences of a nervous child. She herself when 48 recorded her impressions of herself at an early age :

Dagenham. Eighth Month, 23d, 182S. My earliest recollections are. I should think, soon after I was two years old; my father at that time had two houses, one in Norwich, and one at Branierton. a sweet country place, situated on a Common, near a pretty village; here. I believe, many of my early tastes were formed, though we left it to reside at Earlham, when I was about five years. The impressions then received remain lively on my recollection; the delight in the beauty and wild scenery in parts of the Common, the trees, the flowers, and the little rills, that abounded on It, the farm houses, the village school, and the different poor people and their cottages: particularly a poor woman with one arm, whom we called one-armed Betsy; anotlier neighbor, Greengrass, and her strawberry beds around a little pond; our gardener, who lived near a large piece of water, and used to bring fish from it; here, I think, my love for the country, the beauties of nature, and attention to the poor, began. My mother was most dear to me, and the walks she took with me in the old-fashioned garden, are as fresh with me, as if only just passed; and her telling mo about Adam and Eve being driven out of Paradise; I always considered it must be just like our garden at Bramerton. I remember that my spirits were not strong; that I frequently cried if looked at, and used to say that my eyes were weak; but I remember much pleasure and little suffering, or particular tendency to naughtiness, up to this period. Fear about this time began to show itself, of people and things: I remember being so much afraid of a gun. that I gave up an expedition of pleasure with my father and mother, because there was a gun in the carriage. I was also exceedingly afraid of the dark, and suffered so acutely from being left alone without a light after I went to bed, that I believe my nervous system was injured in consequenre of it: also, I had so great a dread of bathing (to which I was at times obliged to submit) that at the first sight of the soa, when we were as a family going to stay by it, it would make me cry; indeed, fear wa.s so strong a principle in my mind, as greatly to mar the natural pleasure of childhood. I am now of opinion, that it would have been much more subdued, and great suffering spared, by its having been still more yielded to; by having a light left in my room; not being long left alone; and never forced to bathe; for I do not at all doubt that it partly arose from that


nervous susceptible constitution, that has at times, throughout my life, caused me such real and deep suffering. I know not what would have been the consequence, had I had any other than a most careful and wise mother, and judicious nurses, or had I been alarmed, as too many children are, by false threats of what might happen.

Even though treated so carefully by otliers her vivid imagination tormented her, and her early diaries must have contained many outpourings of her spirit. These are lost and we can only guess their character by her later struggles and the records of her sisters and friends.

John Pitchford records ' that she told him of being so impressed as a child by the story of Abraham and Isaac that she was afraid to go to fleeting for fear that her parents would be required to sacrifice her.

The state of her health secured her many privileges. She was allowed to sleep later than the other children and was usually excused from going to Meeting on Sundays — a much prized privilege. The meeting house in Xorwich was reached through Goat's Lane and the children always spoke of the meeting as " Goat's," and recorded in their journals their feelings with such remarks as " I stayed at home from Goat's which I was most glad of," "A long, dis(di.<gusting) meeting at Goat's," etc. (Louisa. 11 years.)

Mr. Gurney was "labored with" about liis indulgence of Elizabeth, and when she was older he required her to attend Meeting more regularly. There were no paid ministers among the Quakers and they depended for the " spoken word " upon certain of their members feeling called; that is, having a sense that they must either pray or preach. Certain members who spoke frequently and acceptably were acknowledged Ity the fleeting and designated as ministers, and certain of them traveled from Meeting to Meeting and were called Public Friends or Visiting Friends. It was to hear one of these that Elizabeth Gurney went when slie was 17 years old. Her diary, which has been presened from about this time, reads :

Sunday, Feb. 4th, 1798. This morning I went to Meeting, though but poorly, because I wished to hear an American Friend, named William Savory. Much passed there of a very interesting nature. I have had a faint light spread over my mind, at least I believe it is something of that kind, owing to having been mucii with, and heard much excellence from, one who appears to me a true Christian. It has caused me to feel a little religion. My imagination has been worked upon, and I fear all that I have felt will go off. I fear it now; though at first 1 was frightened, that a plain Quaker should have made so deep an Impression upon me; but how truly prejudiced in me to think that, because good came from a Quaker, I should be led away by enthusiasm and folly. But I hope I am now free from such fears. I wish the state of enthudiasm may last, for to-day I have felt that there Is a God; I have been devotional, and my mind has been led away from the follies that it is mostly wrapped up In. We have had much serious conversation; In short, what he said and what I felt, was like a refreshing shower, falling upon earth, that has been dried up for ages. It has not made me unhappy: I have felt ever since


Augustus Hare: Gurneys of Earlham. Vol. I, p. 47.


74


[Xo. 337


humble. I have longed for virtue. I hope to be truly virtuous; to let sophistry ily from my mind; not to he enthusiastic and foolish; but only to be so far religious as will lead to virtue. There seems nothing so little understood as religion.

A most interesting struggle had begun of which I can only give the bare outlines. She records two days following, on the 6th:

My mind has by degrees flown from religion. I rode to Norwich, and had a very serious ride there; but meeting, and being looked at, with apparent admiration, by some oflicers. brought on vanity; and I came home as full of the world, as I went to town full of heaven.

However defective the education of the Gurney children may have been; it had at least led to a remarkable independence of thought. Of all of them Elizabeth seems to have been the most independent, and she then and all through her life showed a ver}' clear insight into her thoughts and feelings. She records on Sunday, the 11th:

It is very different to this day week (a day never to be forgotten whilst memory lasts). I have been to Meeting tnis morning To-day I have all my old irreligious feelings: my object shall be to search, try to do right, and if I am mistaken, it is not my fault; but the state I am now in makes it difl5cult to act. What little religion I have felt has been owing to my giving way quietly and humbly to my feelings: but the more I reason upon it, the more I get into a labyrinth of uncertainty, and my mind is so much inclined to both scepticism and enthusiasm, that if I argue and doubt, I shall be a total sceptic; if. on the contrary, I give way to it. and as it were, wait for religion. I may be led away. But I hope that will not be the case; at all events, religion, true and uncorrupted, is of all comforts the greatest; it is the first stimulus to virtue; it is a support under every afiiiction. I am sure it is better to be so in an enthusiastic degree, than not to be so at all, for it is a delightful enthusiasm.

There are many other records of the struggle. She was so determined not to be carried away by her emotions that she got her father's consent to send her to London so that she might see for herself the attractions of the world and decide whetlier she could be +++++ CONTENTS in their enjoyment. Wliile in London she took music and dancing lessons, went to the plays and to the opera, and saw as much of gay society as her opportunities allowed. Her diarj' for March 26, 1798, reads :

This morning I went to Amelia Opie's and had a pleasant time. 1 called on Mrs. Siddons, who was not at home: then on Dr. Batty; then on Mrs. Twiss, who gave me some paint for the evening. I was painted a little, 1 had my hair dressed, and did look pretty for me. Mr. Opie, Amelia, and I, went to the Opera concert. I own, I do love grand company. The Prince of Wales was there: and I must say, I felt more pleasure in looking at him, than in seeing the rest of the company, or hearing the music. I did nothing but admire his Royal Highness; but I had a very pleasant evening indeed.

On the other side, William Saverj- was also in London and she went to Meeting to hear him preach and had some conversation with him, and when she returned after two months she began to feel pretty sure that she was going to turn into a plain Quaker. She regarded the change with great interest, but with not a little apprehension, as she knew what a trial it would be to her father as well as to the rest of the children.


In May, to distract her mind, her father proposed another visit to London, and she writes in her journal on the 24th :

I wrote to my father this morning. I must be most careful not to be led by others, for I know at this time I have so great a liking for plain Friends, that my affection being so much engaged, my mind may be also by them. I hope as I now find myself in so wavering a state, that I may judge without prejudice of Barclay's Apology.

It was about this time, when she was just 18, that she began her first independent philanthropic venture — the establishment of her school at Earlham for poor children. She had always fotmd it easy to do for others, and even before her religious awakening she had been her father^s instrument for the distribution of his charities. She took such a delight in doing for people and giving help that she recognized very clearly that she deserved no great praise for so doing.

Her development into a plain Quaker progressed deliberately and she took no step in that direction without much thought and travail of spirit, but she adopted one peculiarity after another in spite of the open opposition of her immediate family and often against what seemed to her the dictates of reason. She gave up dancing — a pleasure she delighted in — and singing, gradually changed the manner of her dress, and used thee and thou, the so-called singular form.

To counteract all this Mr. Gurney took her with some of the other children on trips, and she seems to have enjoyed what she saw, but the Quakers whom they met at various places interested her more. She on her part was the object of the deepest interest to the Friends, as indeed was natural.

At one time, when 19, she was appointed on a committee to in\-estigate the Ackworth School, and afterwards, wb.en the young people were encouraged to speak and nothing was said, she spoke. Of this she writes: "As it appeared to me it was delaying the meeting I took courage (as I thought it was more right than wrong to speak) : and said what I thought of the grammar and ciphering; I felt glad I had done it though i trembled at doing it not a little." She was then asked her opinion of other matters about the school. This seems to have been her first service on a committee of investigation.

During this visit she records on July 4, 1799 : " This morning we walked to York and saw its wonders. We .*aw the Friends' Retreat for crazy people which my father thought extravagantly kept." This institution had been founded in 1792 by Friends, under the guidance of William Tuke, and was the first place in England where the humane treatment of the insane was attempted. I have fotmd no other references to her having visited it again, but she was doubtless quite familiar with the ideas and methods carried out there, as the proper care of the insane was a common subject of discussion in the Society.

In America the Friends had long been interested in the subject. In 1709 the Philadelphia Monthly fleeting took steps towards the establishment of a hospital for the sick and the insane, but it was not until 1751 that the Pennsylvania


Mabch, 1919]


75


hospital wiis founded. This institution among other sick cared for patients "distempered in mind and deprived of their mental faculties." In 1813 the Philadelpliia Friends, stimulated by the success of the York Retreat, founded at Frankford a Friends' Asylum.

Upon returninjT to Earlliani, Elizabeth befjan to take a more active part in the ileetin<r, and in the fall of 1709 was appointed a representative. Her Sunday school for cliildren increased rapidly, and here she began to show her remarkable power over audiences. She paid great attention to the manner of reading (for she objected to the way the Bible was usually read), and it must have been here that she be^an lo develop the very remarkable style that was so effective throughout her life.

She was married when just 20 to Joseph ¥r\, the son of another prominent Quaker family. The Frys were also wellto-do and were in business in London. Unlike the Gurneys, they were the strict-est of plain Friends. You well imagine that this important step was not taken without due deliberation. Elizabeth felt that she had a distinct work, and like so many young women of to-day she was loath to give it up. The sisters helped in the decision by filling their diaries with hopes and prayers that Betsy might make no mistake. Joseph Frvs first proposal was refused, but thinking from the tone of a note that he might receive a different answer, he went back to Earlham. Augustus Hare, from whom I quote, gives a most amusing account of the outcome. Joseph Fry did not dare risk a second proposal so " he bought a very handsome gold watch and chain and laid them ujmu a white seat. .... * If Betsy take up that watch,' he said, ' it is a sign tiiat she accepts me, but if she does not take it up by a particular hour, it will show that I mu.«t leave Earlham.' The si.\ sisters concealed themselves in si.x laurel hushes, in different parts ol" the grounds, to watch." When Betsy first discovered the watch she retreated to the house, but the sisters kept up their vigil from the laurel bu.'shes. Just where Joseph Fry was tile account does not state, but continues: " Once again did the an.xious sisters see Bct«y emerge from the house, with more faltering steps this time, but still inwardly praying. and slowly, tremblingly, they saw her take up the watch, and the deed was done."

Upon going to London Elizabeth Frv' was thrown into quite new surroundings, and it is amusing to find that, altliDUgli she was considered austere and plain among the Gurneys, among the Frys she was looked upon as far too gay and too much given to worldly customs. Her children came rapidly, and by a most unusual circumstance in exactly the numlier and order as to se.x as her mother's, and as each one came it was given the name of the corresponding Gurney child. Her health was not good, and these first years were largely taken up in adapting her^lf to her new surroundings. She was always helping those in want when they came to her attention, but took no special part in public charities.


An interesting incident occurred shortly after her first child was born, and we find in her journal (A Memoir of the life of Elizabeth Fry, 1847, Vol. I. p. 108) the following:

Mildred's Court, Eleventh Month. 25th (1801). My cough has been so poorly that my husband called in Dr. Slmnis. I asked his advice about our little one being inoculated; he strongly recommended the cow-pox, and said that he would undertake the care of her if we liked: I think higlily of his judgment, and I believe it to be our duty to avoid evil, both bodily and mentally. So trifling a complaint as tlie cow-pox, being likely to prevent so dreadful a disease as the small-pox, at least it appears justifiable to try it; although the idea is not pleasant, it almost looks like taking too much on ourselves to give a child a disease. But 1 altogether was easy to do it. I felt a good deal about the operation, which was very little and easily performed. What a wonderful discovery it is if it really prevents the small-pox.

You may remember that the first vaccination with cow-pox was done by Jenner in 179G, just six years before this incident.

She became an ardent advocate of vaccination, and when, after the death of her father-in-law, in 1811, she moved to the large country place at Plashet, in the parish of East Ham, she herself vaccinated the cliildren of the parish, having been taught the method by Dr. Willan, an early and earnest exponent of the practice. She inspected the children from time to time to see that none were left unvaccinated. In these villages small-pox became practically extinct.

Elizabeth Frv- .^oon became the philanthropic Lady Bountiful of the parish, and there was nothing for the good of the people that she was not busy about. She saw that the sick and injured were visited, estiiblishcd a depot for the distribution of clothing, and in winter she had soup prepared at her house in such quantities as to supply hundreds. With the help of the clergyman and his wife she established a school in which 70 girls were taught.

From the first, after moving to London, Elizabeth Fry was iictive in the Society of Friends. She spoke more and more frequently in Meeting, and in 1811 her gift was formally acknowledged by the Meeting and she liecame a recommended minister.

The Frys ciitcrtainiMl Friends constantly, and it was not often that they did not have one of Elizaiictii Fry's brothers or sisters from Earlham staying with them. After moving to Pla.<het the hou-sehold became still more complicated, and there are many notes in her journal telling of the thought that she gave to her household, particularly to the proper treatment of servants.

Her first 10 children were liorn in K! years, and the last child six years aftenvards, Novemljer 1, 1822.

In 1813 she paid her first visit to Newgate Prison where she was much impressed by the misery of the women. There is nothing in her journal, however, that suggests that at that time she felt prison reform to be her great work, and it was not until three years later that she made her second visit, this time at the instigation of two of her brothers-in-law. The condition of this prison was most lamentable and some of the descriptions are hard lo briieve. Years before John


[No. 337


Howard had called attention to the prisons in England and had had laws passed by Parliament for their betterment, but these laws seem to have been at this time almost completely disregarded. The part of Newgate in which the women were confined was the worst part, and the conditions were those of utter squalor, misery and vice ; indeed, they were so terrible that the governor himself went there as rarely as possible, and it had for one of its titles " Hell above ground." All the women were herded together without any attempt at classification. There were many children among them, filthy and half-naked. It was in these discouraging surroundings that Elizabeth Fry and her companion requested to be left alone with the women. I doubt whether upon going there she had any plan formed in her mind, biit with her quick instinct she made the one appeal that was most likely to be effective. She spoke to the women of their children and showed them how their behavior was affecting them, and she suggested that, if they would co-operate with her, she would form a class to instruct the children, but that this must be with tlieir cO-operation and that they themselves were to select one of their number to be the teacher. The women immediately grasped at the plan and by the next visit they had chosen Mary Connor, a young prostitute convicted for stealing a watch, to be the school-mistress.

It was in these discouraging circumstances that the work began. The prison authorities were entirely skeptical as to the outcome, but allowed Elizabeth Fry and her associates to try it. The plan succeeded from the first and it was not long before numbers of the older women were clamoring to be allowed to attend the classes. Other ladies joined Elizabeth Fry and visited tlie prison daily, and it then became possible to extend the work to the older women. The women were divided into different groups, a monitor from among their number was chosen for each group, and occupation was provided for them as well as daily Bible readings and other instruction. A matron over the women prisoners was also introduced.

To do all this required a considerable sum of money which was provided by the committee, especially by Elizabeth Fry and her brothers. The visiting committee of ladies became later the British Ladies' Society for Promoting the Eeformation of Female Prisoners, with many branches throughout the kingdom.

The changes that followed these reforms on the women's side at Newgate were so marked and occurred so quickly that they attracted widespread attention, and two years after their inception, in 1818, Elizabeth Fry and her brother, Joseph John Gurney, visited many of the prisons in Scotland and the north of England. The notes (Notes on a Visit Made to Some of the Prisons in Scotland and the North of England in Company with Elizabeth Fry, etc., London, 1819) of this visit were published by ]\Ir. Gurney. The state of each prison they visited is recorded and at the end of the book he has brought together their ideas as to prison management. Later, Eliza


beth Fry published her views on this subject (Observations on the Visiting, Superintendence, and Government of Female Prisoners, London, 1827), and they can also be learned from the reports of various Parliamentary Commissions before which she gave testimony. In brief, she believed it essential that the women prisoners should be entirely separate from the men prisoners, that they should be under the direct care of only women, and should be visited by the men officers only in the presence of women; that the women prisoners should be classified, the tried from the untried, the more hardened ofllenders from those less so, etc. ; that they should be properly clothed, fed and warmed; that the uniform of each class should be difl'erent, and that prisoners should be graded according to behavior. She insisted upon the importance of instruction, particularly religious, and urged that the Bible be read to them daily and that it should always be within easy access. Useful occupation she regarded as of first importance, the occupation being so planned as to bring them some remuneration while in prison and to help them to earn their living when they were released. She did not feel that the lot of the prisoners should be made too easy, but she insisted that the first idea must be that of reformation. Solitary confinement she believed to be open to grave dangers, although she advocated strongly that each prisoner be alone at night. She earnestly opposed capital punishment in general, and especially when it was administered for trifling offences as it was at that time.

The importance of the supervision of prisoners upon their release was also insisted upon, and the ladies of the committee gave special attention to those women who were to be transported to the penal colonies in Australia. The condition of these women had been most deplorable and their residence in the colony a scandal. The committee was instrumental in providing work for the women to do during the voyage, matrons to have charge of them and proper methods for their recej)tion and care upon arrival.

Elizabeth Fry had the great satisfaction of seeing practically all of her suggestions adopted, and it was not long after she had begim her work for the prisoners that to her consternation she found herself famous. Few distinguished people visited London without accompanying her to her claSvS at Newgate. Her advice was asked by very many people; she appeared before committees of Parliament and many Societies. Her influence was little short of marvellous. Correspondence was established with philanthropic persons in various countries in Europe. She gave advice as to the niana,gement of prisons and the care of the insane. She had long correspondence with the philanthropic Venning brothers, John and Walter, who were living in St. Petersburg. It was through them that she sent advice as to the improvement of the lunatic asylum at St. Petersburg, in which the Dowager Empress had become interested and which she had taken under her special care. Elizabeth Fiy recommended east-iron window frames instead of the clumsy iron bars which had been used in the old institution. She also recommended that all except the


Mabch, 1919]


violent lunatics dine together at a table covered with a cloth and furnished with plates and spoons. Here, as cvenwhere, she felt the importance of the Bible, and the Xew Testament was introduced into this institution.

To show how closely Elizabeth Fn-'s suggestions were followed, I shall quote portions of a letter from Mr. Venning written after her death (Memoir, Vol. 1, p. 387) :

When I received a letter from your mother I always wrote It out in French and presented it in that language to the Empress, and when she had read it, it was very encouraging to see with what alacrity she ordered one of her secretaries to translate it into Russian, and then deliver it to me to be conveyed to the asylum, and entered into the journal there for immediate adoption. I remember, on one occasion, taking a list of rules, at least 14 in number, and the same day they were confirmed by the Empress; and these rules introduced the following important arrangements, viz.: The treating the inmates, as far as possible, as sane persons, both in conversation and manners towards them — to allow them as much liberty as possible — to engage ihem daily to take exercise in the open air — to allow them to wear their own clothes, and no uniform prison dress — also to breat up the inhuman system of permitting the promiscuous idle curiosity of the public, so that no one was allowed to see them without permission ; a room on entering the asylum was prepared for one at a time, on certain days to see their relations. The old cruel system drew forth many angry expressions from the poor lunatics, " Are we wild beasts to be gazed at? " . . . . Another important rule of your mother's was, most strictly to fulfil whatever you promise to any of the inmates, and above all, to exercise patience, gentleness, kindness and love towards them; therefor, to be exceedingly careful as to the character of the keepers you appoint. These are some of the pleasing results of your mother's work. The Dowager Empress on one occasion, conversing about your mother, said, " How much I should like to see that excellent woman, Madame Fry, in Russia."

Her health was never ver}- strong, but even when ill she could not restrain herself from trying to put right what she thought was wrong. On one occasion, in 1824, when resting at Brighton, she noticed the great number of beggars and how the charity was given indiscriminately, and seemed to be doing more harm than good. To meet this she organized the charitably disposed among the different religious denominations into the " Brighton District Society," which was, in effect, a charity organization society, and, so far as I know, the first one ever formed. After this slie was instrumental in establishing similar ones in many other places.

It was during this stay at Brighton, while she was suffering from frequent attacks of faintness at night, for the relief of which she was often taken to the window of lier room overlooking the sea. tliat her s_\-mpathy was aroused by the constant sight of tlie blockade man, or coast-guard, pacing the beach. She thought how lonely and isolated his life was and wondered how she could help him. She took the first opportunity of speaking to one of these men, but discovered that it was against orders for the men to speak to any stranger, as their duty was to prevent smuggling. To protect the man she gave him her card with the request that he give it to his superior oflHcer. Some days later she was much pleased to receive a visit from the naval lieutenant in charge of the sta


tion and he explained to her the nature of the service. Mrs. Frj' with her clear insight at once thought of a plan, probably the best, that might alleviate the hard lot of the coast-guards — .<lie established libraries containing tiie Bible and other books. The libraries became very popular and were distributed throughout England. Another national society was formed to look after tlie interest of this work. Official sanction was given and certain grants allowed. The report of tho committee in 1836 shows the magnitude to which the work had grown. This report ends as follows (Memoir, Vol. II, p. 229) :

The means thus so liberally afforded, have enabled the committee to provide and forw^ard to the coast, 198 libraries for the stations on shore, containing. .25,890 vols. 74 libraries for the districts on shore, containing. 12,880

48 libraries for the cruisers, containing 1,867

School books for the children of the crews of

stations 6,464

Pamphlets, tracts, etc 5,357 in No.

Making a total of 52,464 vols.

and thereby to afford a body of deserving and useful men and their wives and families (amounting to upwards of 21.000 persons) with the means of moral and religious instruction, as well as profitable amusement, most of whom, from their station in life, liave not the means of procuring such benefits from their own resources, and who. in many instances, are so far removed from places of public worship and schools, as to prevent the possibility of themselves or their families deriving advantage from either.

Mrs. Fry's interest in public institutions spread over the whole of England, Scotland and Ireland, and many branches of the British Ladies' Societj' were started in all of these countries. In 1835 she extended her influence to the Channel Islands and visited them again in the following year. The acts of Parliament pertaining to prisons did not apply to tliese islands, and their prisons were in a lamentable state. As usual, she was able to suggest many improvements in their management that could be and were carried out. Many of lier correspondents urged her to visit the Continent and give them the aid of her experience and personality. She felt it lier duty to comply with this call, and in 1838 she began her Visits of Gospel Love " to Europe. Siie made five such visits, and, as Friends would say, the way was wonderfully opened for her. Tliose in authority were nearly all more than anxious to have her visit their institutions to suggest improvements. Tlie various royal families received her most cordially

ind appeared to delight in her society. She must have made

a picturesque figure in such surroundings, dres.scd as she was in the simple elegance of the plain Friend whicii harmonized -o perfectly with her erect carriage, her dignified l)caring an<l lier earnest, sympathetic face. Her principles did not allow her to do many of the things that were considered neces.«ary in court, but this seems to have made no difference. Royalty in general seemed more pleased that she advi.sed them and prayed with them than if she had ki.«sed their hands. She ^uggested many things about the conduct of their prisons, asylums and hospitals, told them of her views as to the


[No. 337


religious state of their kingdoms, and when there was religious persecution — as was frequently the case — she pleaded for religious freedom. All this she was able to do with such wisdom and tact that her counsel was accepted in the spirit in which it was given and very frequently was acted upon.

She visited the Prussian Court twice, in 18-10, where she was received with peculiar consideration, and when the King of Prussia, Frederick William IV, visited England in 1843, to stand sponsor for the Prince of Wales (the late King Edward VII), he insisted, somewhat to the consternation of those who had charge of his entertainment, in spending much of his time with Elizabeth Fry. He requested that she dine with him at the Mansion House, went with her to visit Newgate Prison, and then took dinner with her and her family. He was heard to say, " She is the best friend I have in the world."

Little did Betsy Gurney think when, she renounced the pomps and follies of the world and adopted the customs of plain Quakers, that the path she had chosen was to lead her so often to the seats of the mighty !

Although Elizabeth Fry saw many things to criticize in her journeys to Europe, she also found things to commend and she met with many earnest workers for the amelioration of the distressed. It was during her first visit to Germany that she visited Pastor Fliedner's establishment at Kaiserwerth — • an establishment for the training of nurses, the first secular one that had ever been established. Fliedner had corresponded with Mrs. Fry, had visited her on two occasions and seems to have been much influenced by her example. Mrs. Fry, on her part, upon returning to England followed his example and established the first band of professional nurses in Great Britain. She herself could not take a very active part in it, but her sister, Mrs. Samuel Gurney, and some other ladies took the management of it. When not engaged in nursing, the " Nursing Sisters " resided at " The Home," in the city. They wore a plain but inconspicuous dress and were maintained and paid by the institution, but were not permitted to receive any money or gifts under any circumstances for their attendance in illness. The funds of the Society were small and were derived partly from subscriptions and partly from the liberality of those who were benefited.

The intimacy between Elizabeth Fry and the other members of the Earlham family never waned and she paid frequent visits to Norfolk. Her sisters for the most part difl'ered from her in religious matters, but this difference was never allowed to cause any break between them. Whenever there was illness, Elizabeth Fry, when possible, nursed the suft'erer in a peculiarly sympathetic, skillful manner. However strict she may have been with herself, she was more than lenient with everyone else and had a never-failing sympathy. This to some extent must have been due to the fact that she herself suffered frequently from bodily ills, particularly those most troublesome ones of a nervous nature, and she had a most unusual insight into such troubles.


In the Memoir " her daughters have included in the extracts from her Journal a number of notes which bear on her bodily state. These give some idea how, in her case, a peculiarly nervous, sensitive nature was controlled and directed and made most wonderfully effective by a firm religious belief. These extracts are probably only a few of many similar ones to be found in the original journal, but they are, I am afraid, too many to be included in this paper, and so I have been forced to select some which seem most interesting. I have already read you her own recollection of her childhood in which she speaks of her childish fears and nervousness. When she was 18, during her religious awakening, she shows in the following extract how she was struggling against her morbid fears :

Jan. 4, 1799. A plan, at least a duty, that I have felt for some time, I will now mention. I have been trying to overcome fear; my method has been to stay in the dark, and at night to go into those rooms not generally inhabited; there is a strange propensity in the human mind to fear in the dark, there Is a sort of dread of something supernatural: I tried to overcome that, by considering as far as I believed in ghosts, so far I must believe in a state after death, and it must confirm my belief in the Spirit of God; therefore if I try to act right, I have no need to fear the directions of Infinite Wisdom; I do not turn away such things as some do. I believe nothing impossible to God, and He may have used spirits as agents for purposes beyond our conceptions; I know they can only come when He pleases, therefore we need not fear them. But my most predominant fear is that of thieves; and I find that still more difficult to overcome, but faith would cure that also, for God can equally protect us from man as from spirit.

Before and after the birth of each child she usually suffered a period of depression, accompanied by great bodily weakness and a terrifying apprehension of death. After the birth of her second child, when 23, she writes :

Plashet, Fifth Month, 21st, 1803. I have long been prevented writing in my journal, by a severe attack of indisposition. It is difficult exactly to express what I have gone through, but it has been now and then a time of close trial; my feelings being such at times as to be doubtful as to whether life or death would be my portion. One night I was, I believe, very seriously ill; I never remember feeling so forcibly how hard a trial it was in prospect to part with life. Much as my mind, as well as body, was then tried in this emergency, still I felt forcibly an inward support, and it reminded me of that text of Scripture, " Can a woman forget her sucking child, yea they may forget; yet will I not forget thee." And then I told those around me, that I was so ill, I could almost forget my child, but I felt the existence of a power that could never forget. I have gone through much since, in various ways, from real bodily weakness, and also the trials of a nervous imagination: no one knows but those who have felt them, how hard they are to bear, for they lead the mind to look for trouble, and it requires much exertion not to be led away by them; nothing I believe allays them so much as the quieting influence of religion, and that leads us to endeavor after quietness under them, not looking beyond the present. But they are a regular bodily disorder, that I believe no mental


'Memoir of the Life of Elizabeth Fry. Edited by two of her daughters. London, 1847.


March, 1919]


79


exertion can cure or overcome, but we must endeavor not to give way to them.

Again six years later she records:

Seventli Month. 27th, 1S09. I am much better than I was, but I have believed, in these trying complaints to which I am liable, that the less I look outwardly for help the better; as I do not believe any doctor can do much for me. I feel the best satisfied when I simply endeavor to bear them patiently; I think I know myself, wliat is the best to take for them: they appear to be principally nervous, which I consider to be beyond the power of man either to understand or cure; but how often have I experienced true spiritual support and help, when I have endeavored patiently to wait on the source of good: and the mind being so nearly connected with the body, whatever tends to tranquillize it, really helps the complaint.

She often was pursued by the tlioujiht that possibly lier nervous depression might be due to a lack of faith, and an evidence that she was in some way untrue to her religious standards, although her intelligence told her that the condition was largely a physical one as is sliowTi by the following extract :

Plashet, Fourth Month, 30th, 1S14. None know but those who suffer from them the deep humiliations such disorders create, as those I have lately had; I mean great bodily weakness, accompanied by nervous lowness of spirits, and mucli mental fear. In the first place, how deeply do they try us, being in their own nature so painful: in the next, from the difficulty in doing strictly right in them, how far to endeavor to divert by cheerful amusement, or by taking such things as may soonest relieve them; and added to these, I think many are apt falsely to accuse themselves, and to mistake the painful restlessness and fear occasioned by them, for impatience and mistrust; I have sometimes a hope that this is not my case, thougli at others great fear arises, lest I should in any degree let go my hold, or be impatient after having so abundantly known the goodness, the loving-kindness of the Almighty. Oh, saith my soul, may He once more revive the spirit of His poor unworthy one. and breathe upon these dead bones, that they may live.

The neurotic disposition seems to have been an inherited tendency in this remarkable family, and Elizabeth Fry, when 53, wrote to one of her daughters, who was evidently suffering, the following helpful and encouraging letter:

(1833.) I feel in the first place, earnestly desirous that thou shouldst think as little as possible of thy nervous feelings. I luiow how extremely painful they are, but experience' has taught me. the less I think of them the better. It is most important to look upon them as much as possible like the toothache — that it must be endured while it lasts, but it is not dangerous in its nature. As for the discolored view, the imagination may at times give to things, nothing is more important than to set it down as a clear and fixed thing in the mind, that whilst this nervousness lasts it is not sound, and must not be believed or taken heed to. I would not have thee discouraged at this return of it. I believe I never had death brought home very closely. without being brought into a low nervous state, it is after all so awful: though I increasingly see. that this is real weakness, and that those who are believers In the Lord Jesus, however unworthy, need not fear it, as through Him its plague and sting will be done away. But it is folly in one sense to look ahead, we have enough to do to seek for help and grace for the present time to do our present day's work. When the day comes that we have to give up "this mortal life." we may and ought humbly to trust.


that through the unmerited mercy and love of our Lord, His grace will be found suflicient for us. I observe, for my great encouragement, that what we call nervousness often proves no common blessing, if made a right use of, and not given way to. It so wonderfully humbles, prevents the creature glorying, and makes willing to do anything to come to that peace, which quiets every storm. Thy uncles and aunts have nearly all been striking instances of this: and I believe, hard, very hard as it is to bear, it is a baptism to fit for a fulness of joy and glory rarely partaken of; but it in no common degree calls for patience. I always think both David and Paul largely partook of this sort of humbling experience. Therefore my dear .... if tried this way, possess thy soul in patience, and look upon it as a suitable, though bitter, medicine prescribed by the Physician of value to promote thy health and cure.

She always, wJiile engaged in her various philanthropic activities expended her strength most lavishly, and afterwards she usually had periods, often long ones, of great .suffering. Together with the physical weakness, the accompanying menXaI depression was often combined with the fear tliat she had received far too mucli personal adulation, and that she had ])erhaps put herself forward unduly. She was glad to use the power of her reputation and position in the furtherance of her ]irojects, but was very fearful that she might take to her.self — the instrument — the credit that was due to her Lord, and she at times looked upon her illnesses as corrective agencies.

As she was returning from her second visit to Germany, when 61, she WTites, in a letter to her husband and children, the following:

Cassel. Ninth Month. 26th. 1841. I have continued very far from well, with latterly a considerable stiffness in my limbs, so that I am obliged to be assisted to walk upstairs, and helped into the carriage, sometimes by one or two men. I might have had the same attack at home; but one thing is certain, we may fully trust in our Heavenly Father, who is constantly protecting us under the wing of His love, and who knows what is best for us, I have sometimes thought that after being so helped on my way, from the palace to the prison, it was likely that the poor instruments should need a little further refining and purifying, for our works are to be tried as by fire. I have very earnestly desired not to repine, or to be unwilling to drink the cup that may be given me to drink. We travel witli six horses to make the greatest speed home. I have a board in the carriage, tliat when your uncle and Anna are outside. I can quite rest and make a real sofa of It, when I need it, which I do for one or two stages In the day. Mary and Francois are very attentive and kind; indeed how differently am I cared for to many poor missionaries. I wish you to feel for me, but not to be too anxious about me; •ommil mo entirely to Him wuo only knows what is best for me. Ynur aunt lOlizabeih's Iflter wi.n very seasonable and acceptable. I wis!) her and all my children to know how it is with me. for I need their sympathy and prayers, at the same time that I feel the best help to be near, and the Power that says to the waves " So far shall ye go and no further." Often In my wakeful and at times distressing nights, a sweet peace comes over me to calm my troubled spirit. We hear from newspapers, that the poor Baptists In Copenhagen are to be released from prison, a small sum being paid by way of fine. What a comfort! and the poor Lutherans In Prussia say they are now so well off, that they do not wish us to ask for any more liberty for them from the King.

After this visit Mrs. Frj's health improved but slowly and, although far from well, she felt it her duty to go again to


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[No. 337


Fraufe in ]S43. Upon returning from this visit her health failed rapidly and she was practically an invalid from then until her death, although she was able to continue her correspondence and at times to take part in the various national societies she had founded.

Among the number of interesting references in the Memoir to this time I can only include the following :

One afternoon, when one or two members of her family were reading to her, she was unable to attend to a very interesting religious biography, saying, it was too touching to her — too aftecting. She added, after a pause, "How I feel for the poor when very ill, in a state like my own, for instance, when ' good ' ladies go to see them. ' Religious truths so strongly brought forward, often injudiciously.' "

As she became weaker her fear of death decreased and to one of the " Nursing Sisters " she thus expressed herself, " I am of the same mind as Paul, I can say, 'to me to live is Christ, but to die is gain.'"

Shortly before her death her daughters record a marked change in her dominant disposition:

There was another wonderful change. Her powerful understanding and great capacity had given her the habit of control — she was accustomed to power. During her long illness, this continued more or less to show Itself, and it was not always easy to distinguish how far her opinions about her own treatment and capabilities were well founded or not. This feature of her character had disappeared. The will seemed wholly broken, the inclination to resist, or even strongly to desire anything, passed away; and she was +++++ CONTENTS to leave little things and great to the direction of others. It was inexpressibly affecting to see her look of meek submission, to hear her plaintive answer, " Just as you like," to those about her.

These extracts that I have read show clearly how much Elizabeth Fry suffered throughout her life from her peculiar nervous organization. For two years before her death in 1845 she was an invalid, confined practically to her bed or chair. Exactly what organic trouble she had, I have been unable to determine, for her daughters speak only in very general terms of the symptoms. She became less and less able to take any active part in the various movements she had been instrumental in starting. She, however, attended Meeting whenever possible, often when she was too feeble to leave her wheelchair, and it is said that her mind remained remarkably clear in regard to her ministry, even when she found it very diflBcult to concentrate her attention on other subjects.

During the last months of her life she appears to have suffered intensely, and her strong will seems to have become passive, but her condition did not become acutely alarming until three days before her death when, I think, she must have had a thrombosis of the cerebral blood vessels. Slie gradually became unconscious and died October 12, 1845.

Elizabeth Fry's religious faith never wavered, nor did she ever regret having become a plain Quaker. She suffered


much for her principles, particularly from the fact that many of her sisters and brothers could not see as she did and that most of her children separated themselves from the Society. Her eldest son renounced his membership and others were disowned for marrjing out of Meeting. She believed most strongly that young people should be left free in their choice in marriage and encouraged her children in this by her svTnpathy and love. She felt as a minister of the Society of Friends that she could not go to their weddings, but she did attend the Meetings in which their names were taken from the list of members.

She was thrown much with earnest people of all denominations and had no trouble in uniting with them all. Her attitude to others was one of love and helpfulness, but of herself she was a severe critic. Although she felt it right for herself to confonn rigidly to the customs of Friends, she regarded it as a personal matter, and saw clearly that such conformity might be a stimibling block to others, particularly to the young. She had little patience with the empty forms of piety, whether in plain Quaker or in the most ritualistic of priests. Her religion was one of service and she truly followed George Fox's injunction, " That which Friends doe speake they must live in."

Augustus Hare (Gurneys of Earlham, Vol. II, p. 201) writes of her wonderful tenderness:

Mrs. Fry used pathetically to say at this time that she had been " undermined by excessive love," an expression touchingly significant of the secret spell of Elizabeth Pry — the spell which unlocked the hearts of kings to her, and caused the prisoners' chains to fall off at her approach. She had been no professional philanthropist, too much absorbed in humanity at large to care for the human item, but the public work had been, as it were, only the overflow of her woman's heart, the expression of the fulness that remained after children, grandchildren, brothers, friends, had been loved with an intensity which to her eyes seemed " excessive," almost sinful. This marvellous tenderness it was. thrilling in the tones of a voice whose natural music would have been almost sufficient to melt and convince, which had been the key to her influence and power — this, and her sweet humility of soul, her child-like, single-eyed devotedness.

This certainly accounts for the charm and appeal of her personality, but her effectiveness was due, I think, to the fact that she had a most remarkable faculty of grasping a situation and knowing, seemingly intuitively, what under the circumstances should be done to meet it. This is genius, and when genius is activated by Christian love what may it not do and who of us would not gladly follow ?

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Vol. XXX— No. 338]


Contents

DcKi'tieration tJranulcs and Vacuoles in the V'ibroblasts of Clii|>ital .M.Mli.al Society

Clinical Dliscivaf ions on Epideniie InlUiriiza [1)1!. .\. I.. Bloo.mkiki.h and Dr. (;. A. Harrop] ;— Comments on the Pathology and Bacteriology of Fatal Inlliienza Cases, as Observcil at Camp Devens. Massaclmsetts [Dr. S. B. WoLUAi ii] ; — .-\ Kiinctioiial lie-education Clinic: Organi/.ation and Methods (Dr. W. (i. Tho.mp.so\) ; — Malaria in the Federated .Malay States. A Coriection | Dr. W. (J. MacCallusi j.


DEGENERATION GRANULES AM) OF CHICK EMBRYOS C


VACUOLES IN THE Fir,HOBLASTS TILTIVATEI) IN VITRO


By Wahukx (From the llfpnrtmrnt of Anatomti.

l.NTKODrCTIO.N

Tlu' riirniiititiii ul' ;rriiiiuii'.s am! nT tluid vacuoli's within lin' lil>ri)l)la.tt.>< of ti.ssut'-fulturi'.s is of fn-qui'iit owurrcncc in |il)i.<iiia iinti in IxK-kcV .solutinn, witli or without tho ailditiun i>f othtT siihstaiiws. TIrtc arc other t\in'.>; of licfjciu'ratidii. Thi.>i vat-iioli/.utioii of the fytophLsni i.s one of the more coinnnin iiUMles of cell (lefieneratioii unil (K-iitli in tissiie-<-iilture.«. It liiis, however, reeeived very little eoiisiilenition, partly hecaiisi> the vacuoles have often lieeii eonfu.seil with fat ilr<i|is ami ])artly heeause iiivesti;:ators have heeii reaihinj; out in other tlireetion.*!.

I.icwis and Ix'wi.s ('!.")) eon.sidereil .somewhat hrietly tin fn"aniiles and vacuole.s H|i|)earin;; in the eell.s of eiiltiires. especially the ^rranule.** which .«tain with neutral red, Nile lilii. B extra, and lirilliant eresyl hlue 'ih. In the normal cell tli«'

raiiule.s were few in number, hut were plentiful in cells with

many vacuole,*. It wa.* al.«o noted that they accumulate ahout tho central liody (centrosphere) and are similar to the ;rraiiulcwithin the vacuoles. Xo relation.ship was founil between these in-anules and mitochondria.


H. Lewis The Johns Hopkitm Mcdiral S' hool)

'J'he aulliors al.sii (Icalt sipmcwii.it brictly witii the vacuoles found in the cytoplasm, recoj^niziiifj that they were si^nis of ilegeneration of the cylo))lasni and that there was a prof,Tt'i'-'*ive accimiulation in some types of defreneration until most of the cyto])lasm was useil up and only a framewurk remained. At first it was .sdiiicwhat dillicult to distin<;uish the vacuoles from tho fat ^.'lobule s|)aces in li.xi'd and staineil |)reparatioiis, but in the living cells no such ililliculty was encountereil. Small ihincinj,' oranules, varyinj,' in numiier from one to many, were seen within the vacuole; sometimes the ^franules were motionle.>Js and adherent to the wall of the vacuole. It was al.so ftuind that at times th(\v were colored jiale jfreeii with janus jfreen. With Nile blue B extra anil brilliiint cresyl blue 'ih the +++++ CONTENTSs of the vacuoles stained ])ink', and the jrrannles blue or purple. ('han;:es in the shape of the vacuoles and the formation of very unstable, thread-like processes exteiidin;: out from them were also ob.served. We were unable to trace any relation liotwoen mitochondria and vacuoles, although it wan often noted that the niitochondria chanfred from threads and rods to {.Tannics and vesicles, jiarallid with the increase in tin


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number of granules and vauuoles, and that in extreme vacuolization the mitochondria were lodged in the eytoplasmic framework between the vacuoles.

Maximo w ('IG) noted in plasma cultures of subcutaneous tissue of the adult rabbit, fixed with Zenker-formol, embedded in celloidin, cut into histological sections, and stained with cosin-azur, that the fibroblasts contain singular gi-anules which stain bright pink — i. e., are slightly acidophilic. At first these are minute and irregularly scattered in the cell body in small groups. The number of gi-anules varies, but increases with the age of the culture. " In old cultures vrithout cell proliferation all fibroblasts are often crowded full, up to the very end of their outgrowth, with large, round, closely packed

granules Besides the above granules the protoplasma

of many fibroblasts of the same preparation contains small and large vacuoles." In some vacuoles a large or small acidophilic granule of the same character was occasionally detected. ilaximow states that the impression produced is that the granules dissolve from the outside inward and form the vacuoles, and that the granules become permanent constituents which are transmitted to subsequent cell generations. He further finds that " the whole cell-body and its processes are then crowded full of spherical, occasionally very large, granules, so that but little is seen of the protoplasm itself." He regards this as an adaptation for life outside the organism. The vacuoles usually present are either scattered singly or joined in groups. " In the fibroblasts embedded in the masses of the old fibrin the majority of the large granules are substituted by vacuoles and the structure of the cell-body appears therefore coarsely foamy." These granules and vacuoles fomid by Maximow in the fixed and stained cultures of the subcutaneous tissue of the adult rabbit correspond to the granules and vacuoles previoush' described by Lewis and Lewis, and are probably similar to the ones considered more in detail in the present paper.

JIaximow concludes, from cultures fixed in Zenker-formol and stained ^vith iron hematoxylin after sectioning, that the above-described acidophilic granules represent the product of the direct transformation of the chondriosomes. He bases this view upon the very distinct pictures secured by the above method. He says : " The black chondrioconts change into round granules — the mitochondria, which increasing in size seem to transform themselves into the acidophilic granules." This theory regarding the derivation of the above-considered granules and vacuoles from mitochondria is probably cjuite incorrect. The two types of cytoplasmic inclusions have nothing to do with each other. Maximow's conchtsions are such as might be expected from the methods employed by him. He introduces the article under consideration by the statement that heretofore tissue-culture has lacked exact, authentic, systematic researches of a histological character, and that " we lack till now precise information concerning their microscopic structure, their correlation, and, above all, their origin from determined, well-knowTi elements of normal tissue." After this introduction he proceeds to show how cultures should be studied. What could bo more absurd than


to base practically all conclusions upon observations made on tissue-cultures that have not only been cut into sections, but have also been fixed in the same old mixtures that have so often led observers astray in normal tissues. The very thing we are trying not to do in tisstie-cultures is what ^Maximow seeks to introduce with his histological technique. The absurdity of depending ahuost entirely upon histological teclmique, section cutting, etc., ^\-ill, I think, be obvious to most American observers familiar with cultures. The greatest value of the tissue-culture method lies in the fact that it admits of a study of the living cell, and affords an opportunity actually to watch some of the changes which take place therein, both under the usual conditions of the culture and under various experimental conditions through the introduction of knowTi factors, such as vital stains, various chemical substances, drugs, poisons and other alterations of the mediimi. Maximow gives little or no attention to observations on the living cell, at least as far as one can judge from liis article. This is partly due, no doubt, to the fact that living cells are not so easily observed in plasma as in fluid media. I do not wish to undervalue the use of fixed and stained material, especially total mounts (we use them extensively) ; but the pictm-es found in fixed and stained material should be interpreted and controlled from extensive observations upon the living cells. The emphasis, in fact, should be laid on the study of the living cells, and this we have constantly done. It is, of course, more easily accomplished when fluid media are used and the culture grows out on the under surface of the cover-slip, than with the use of plasma. The fixed specimens are of great help in the construction uf illustrations, and some structures are more clearly revealed than in the living; but tmless they are to be seen also in the latter, their existence in the living cell, as seen in the fixed specimen, must always be open to question.

Maximow criticizes our methods very severely : "' In view of the imperfection of their methods (the preparations were made by vapors of osmie acid and examined in ioto, without making sections) their results are of but little importance." In the first place, osmic acid vapor, wdth the virtues of which Maximow is apparently not familiar, is a most excellent fixative for cultures in fluid media, far better than any of those employed by him — we have tested them all. It may not answer as well for plasma ctiltures, but with that we are not concerned. In the second place, there is little point in making sections of cells that are already flattened out on the coverslip, unless one wishes to trace their origin from the old piece ; for that purpose we have, of course, occasionally made sections.

Maximow also criticizes, as have others, the tise of Locke's solution. We have never claimed that this solution alone contained all the necessary food-stufEs, but with the addition of dextrose and bouillon or egg-yolk the need can be partially met. Just how complete a supply of food can be given in this manner has not yet been determined. Cultures have been kept alive for a month by washing and changing the medium every day or two, and possibly they might be carried on much lono-er. The cultures in plasma degenerate somewhat more slowlv, as a rule, than those in our solutions, but here also


April. liMOl


83


replantation is necessary for long continued growth. Burrows and Xeymann ('IT) believe that food materials for the growing cell^. in both i.-iotonic .<alt solutions and jilasma, come directly from tissue fragments in the explanted piece through disintegration caused by unfavorable environment. \Ve have long thought tliat some of tlie food elements might be sup])lied in this manner. The conditions, of course, are not normal either in ])lasnni or in Locke's solutiou, but tlu' first fibroblasts that grow out into the media show no al)normal cytologic chaugi^s. The conditions in these embryonic chick filirohlasts undoubtedly ditTer somewinit from those found in the aduh mammalian fibrol)lasts studied l)y Maximow.

Burrows and Xeynninn find that the cells in rilro " come to rest after a short ])eriod aiul .«how evidences of deterioration through vacuolization and failure to stain deeply." These authors evidently recognize that vacuolization is a sign of degeneration. We have not found that the process interferes with the staining of the c-ells unless they are ilead before fixation. A cell may be almost completely filled with vacuoles ami yet stain brilliantly with iron hematoxylin and a counter stain.

Luna ('IT) found small vesicles or vacuoles aj)pearing in the pigment cells of the retina, cultivated in ritro, and as their number seemed to increase with a corresponding decrease in the mitnchiuidria, he thought it probable that they were derived from the latter. Vesicles such as he pictures in his Fig. 7 correspond to the mitochondrial vesicles already figured and described by us in degenerating cells (1915). They do not correspond to the degeneration vacuoles described in the present paper.

M.\TERI.\I> A.NI) METHODS

Most of the observations were nnule on small explants from the leg& of G-, T-, and S-day chick embryos cidtivated in the usual manner in Ix)cke's solution plus 0.5 per cent dextrose. Such cultures show fibroblasts, clasmatocytes, and often ectodermal membranes and muscle-buds. The cultures of this special series usually rc^iched the maxinnim growth in about 48 hours. Some of them showed more or less degeneration at T2 hours, and at 0(! hours most of the cells were ccmipletelv degenerated an<l dead.

I wish to emi)hasi/.e liere tiiat the particular series of cultures (several hundred) used for these observations were made by an inexperienced a.ssistant and that the number of cultures showing granular and vacuolar degeneration was far in excess of that shown in any of our other series where such a mode of degeneration is not by any means the rule. Not only did most of the cultures show such degeneration, but the growth was usually below the average and sometimes there was no growth. I have not been able to analyze the factors responsible for this excessive amount of granular and vacuolar degeneration. The process is, however, essentially the same as that ob.served in other series except that in the latter case the cultures lived longer with normal appearing cells before degeneration liegan and that this particular type of degeneration was not so common.


The cessation of growth, of mitotic division, and degenerative changes, may depend luit so much on the exhaustion of the food supjdy as upon the accumulation of waste jjroducts in the medium. There was very little Huid in the small drops used in these cultures, and it is possible that it did not take very long for the accumulated waste |)roducts to exert injurious effects upon the cells.

Mitotic figures were found in some of lhe.<e cultures, often many in the same culture at the same time. Such dividing cells are found in the 24-, 48-, and T2-hour cultures. On the other hand, some cultures do not contain a single mitotic figure, and these are usually the ones which show degeneration changes, some even as early as the second day. We are still ])uzzled by the great differeiurs in the vitality of the cultures, ilue, perhaps, to unknown factors during the manipulations. This is more especially true when the method is used by an inexperienced worker. The rate and extent of growth are often equal to that seen in ])lasnui.

The living fibroblasts were observi'd over varying lengths of time in cultures of various ages, both with and without the use of vital stains and various other substances. The vital stains most frequently employed were neutral reil and janus black Xo. 2. The combination of these two stains proved the most satisfactory of all. We have, in the past, frequently used the combination of tun \ il;d stains, more especially neutral red and janus green. Tiie latter combination has been u.sed also liy Coghill ('15) on fresh amphibian material, and by Mrs. Lewis ('IT) on certain eggs and embryos. The neutral red is rapidly taken up by the vacuoles and certain granules of the fibroblasts, while the janus black No. 2 stains only the mitochondria a deej) blue-i)lack. Neutral red was used in strengths varying from 1-5000 to 1-800,000 in Locke's solution. For most of the observations I use 1-20,000 or 25,000. The janus black No. 2 was usually of the strength of 1 j)art of janus black No. 2 to 10,000 or 20,000 part,s of Locke's solution. Brilliant cresyl blue 2b and methylene blue (Ehrlich rect. or Ilarmer Lab.) were also used. These stain the same granules and vacuoles that take up the neutral re<l.

Until recently we contiinied to use osmic acid vapor as a fixative with excellent results. l.ately, however, the osmic acid in the market has not given satisfaction, and we therefore substituted Zenker's solution without the glacial acetic acid (2.5 per cent bichromic acid solution plus 5 per cent corrosive sublimate plus 1 per cent sulphate of sodium). This has given most excellent pre])arations when followed, as were the osmic acid specimens, with the iron hennitoxylin stain. The trover-slip with the attached growth is innnersed in the bichromate corrosive sublinnite mixture from i to 12 hours, washed and carried through the alcohols with a little TiUgol's solution. It must be borne in mind that fhe |)rocedure here used is suitable for cultures grown in Tiocke's .solution and not necessarily for jdasma cultures where the clot aits as a buffer through which the fixatives must penetrate. In cultures in Ijocke's soluiton the naked cells are exposed to the action of the fixative and the process is correspondingly rapid, reducing post-mortem changes to a minimnm. Comparatively few


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cultures were fixed, as we relied upon living material for our (onelusions. With the iron hematoxylin stain it was often impossible to disting-uish between small granular mitochondria and the degeneration granules, as both are stained black. The study of the living culture aids in the interpretation of the fixed material and vice versa. Some jioints would undoubtodlv liave been missed if only one method had been cniploycil.

DEGENERATION GRANULES AND VACUOLES Degeneration graniiles may be characterized brietiy as follows :

(1) They are rare or non-existent in tlic more normal, vigorous fibroblasts of the verj' young cultures.

(2) They vary in size from the ultramicroscopic grannies to ones larger than mitochondrial gi-anules.

(3) They increase in number with the age of the culture.

(4) Tliey tend to accumulate about the centriole or centrosphere.

(5) They are often moved about actively (by cytoplasmic currents), usually in paths from the periphery to the centriole or centrosphere, or vice versa.

(6) They take the neutral red stain with great avidity, also brilliant cresyl blue 2b and methylene blue (Ehrlich).

(T) They are not stained by jan\xs black Xo. 2 which stains the mitochondria.

(8) In fixed specimens stained witli iron hematoxylin many of these granttles are not distinguishable from mitochondria.

(9) They do not arise from the mitochondria.

(10) The degeneration vacuoles develop al)out tln'ni.

(11) Tliey are probably waste products.

(12) They accumulate under certain conditions in degenerating fibroblasts, and hence might be called degeneration granules.

The degeneration vacuoles show the following characteristics :

( 1 ) They are not found in tlie normal, vigorous fibroblasts of the cidtures.

(2) They are first apparent after there lias lieen a considerable accumulation of granules.

(3) They always seem to form about the granules and almost always contain one or more granules.

(4) "When first recognizable the vacuoles arc small and contain a relatively very large granule.

(5) They vary much in size.

(6) They tend to accumulate about the centriole or centrosphere.

(7) They often move in paths from the ju^ripbery to the centriole or centrosphere, or vice versa.

(8) They stain avidly with neutral red. l>ut not as deeplv as the granules; they also stain witli mctliylenc Idue and brilliant cresyl blue 2b.

(!>) They are not stained liy janns black Xo. 2.

(10) They often change shape in the living cell, all gradations from spheres to long thread-like channels being seen.

(11) They do not arise from the mitochondria.

(12) They are probably waste products.


(13) They accumulate under certain conditions in degenerating fibroblasts until the latter are often crowded full of them, and then as the cell dies they disappear and the dead cell has a moth-eaten appearance.

The granules and vacuoles especially considered here are most readily singled out from other cytoplasmic inclusions by their property of rapidly absorbing the neutral red dye. It is well known that neutral red stains certain granules in various types of cells in other animals, and the fact that they absorl> neutral red does not necessarily indicate that the granules are identical in composition : very likely they are not. We do not know whether the union of the dye with the granule is a physical or a chemical one. Such grantiles, however, probably have certain characters in common.

The determination of the presence of such granules in the normal, living embryo or animal is most easily aecomplisheil in small, more or less transparent forms that live in an aqueous environment. In embryos, such as the chick, it is more difiiciilt to ascertain with certainty if such granules are normal in any particular type of cell, such as the fibroblast. The mere act of isolating the fibroblast by separating it from the organism in teased preparations, in spreads, or in cultures, immediately alters the environment. Changes in the normal metabolic activity probably follow immediately, and the formation Qf such granules may result from the changed environment through alterations in the normal supply of gases, salts, carbohydrates, protein products or through the inadequate elimination of waste products from the immediate environment of the cell.

For the present, at least, we are micertain whether such granules actually exist in the fibroblasts under the normal conditions of the embryo. Occasionally one finds here and there, in cultures less than 24 hours old, fibroblasts entirely free from granules that take the neutral red stain. If these granules do exist normally they are probably small and few in number. Such filiroblasts exhibit a marked contrast to those found in many of the older cultures.

fiRAXULES IX THE TOUSG FIBROBLASTS

Tlu' liealthy vigorous fibroblasts of the young cultures are free from vacuoles and contain very few scattered granules that stain red with the neutral red. In the ordinary cultures there are usually to be fotmd, at the end of 24 hours — in the fibroblasts that have migrated from the explant, or other fibroblasts that have arisen from these by mitosis — scattered, clear, refractive g-rannles. They vary in number, often quite markedly, in difl'erent cultures and also in cells of the same culture. After 24 hours none of the fibroblasts are entirely free from such granules and many of them also contain small vacuoles with relatively large granules.

niSTRIBt'TIOX OF GE.VXILES IX THE HEALTHY FIBROBLAST.S

The comparatively few grantdes seen in the fibroblasts of the very young cultures are scattered through the cytoplasm without any definite arrangement, so far as I have been able to determine. Those in the body of the cell, however, a]iproacb


April. 1919]


85


to within varying distances of the edge of the much flattened cells. (Jriuiules are not uncommon in the lari;i'r iiroi-csscs, and here sometimes, since they may be nearly as larjje as tlic diameter of the i)rocess, they come close to tlie surface. It is not surprisinji that the granules are irregidarly and apiJarently indiscriminately scattered through the cytoplasm, as under the best conditions tlicy often move about, usually in a patJi from the periphery to the nucleus, or riVe cersu, and are tliu;! constantly changiutt ])osition. As we shall .^ee later, in tlu' fibroblasts of older cultures the granules and vacuoles come to have a very definite relation to the ccntriole, and their paths of movement are between the ccntriole and the ]icripliery, rather than between the nucleus and the periphery. The position of the ccntriole is dillicult to determine until there has been a considerable acciunulation of granules, but T think if it could be located in the younger, healthy tihrohlast.s wc should find that the granules were moving in jiaths between it and tlic j)eriphery. rather than between the nucleus and the ])eri|ilicry. Its close proximity to the nucleus makes it a])]>ear as thougii it were the nucleus that was the center for such activity.

IXCRKASK IN rilK XI .MBER .VXD SIZK OF THE GRAXfl.ES .\NI) VACUOLES

As the cultures get older there is a gradual increase in the number and size of the granules and vacuoles. In spite of great variations in the rate of accimiulation and the ultimate size of the granules and vacuoles in ditferent cultures, an accurate picture can be given of the more usual process found in the majority of cultures that undergo vacuolar degeneration.

As the granules increase in number it soon becomes noticeable that |)art of them accumulate at one side or at one end of the nucleus. In fixed material and in later stages this accumulation at the side of the nucleus is clearly seen to take ])lacc about the ccntriole or centrosphcre. It is rarely possible to recognize in the living cell, during the early stages of the accumulation of the granules, the ccntriole or centrioles at or near the center of the granular mass. Since, however, it is possible to do so in fixed material, and at later stages also in the living cell, I have not the slightest doubt but that this accimiulation of granules at one side or at one end of the nucleus always takes place about the ccntriole. This is a very interesting and im|)ortant ])oint. It is the centricde, then, ami not the nucleus that is most directly concerned in the accumulation or location of degeneration granules and vacuoles.

The ccntriole or the ap|iaratus surrounding it is the determining factor that in name manner governs, by its ju'culiar metabolic activity, the accnnndation of the granules and vacuoles about it. I shall speak of an accumulation of graindes about the ccntriole in these earlier stages, even though in the great majority of instances the centrifde was not positively recognized in the living material.

As the granules and small vacuoles increa.«e in nHnd)er, then, they accunndate nmre and more about the ccntriole. The nniss is den-^er at the center than at the iieriphery, and there arc always a few granules scattered through the cytoplasm. With the increase in number of the grannies the presence of snndl


vacuoles about many of them becomes more ajiparent. The granules also show more variation in size, in that nniny of them are larger than before. As the jjrocess goes on. the number and size of the vacuoles grailually increase, so tlial they form an ever-widening hah) about the centriule and centrosphcre. Most of the granules iieconie enclosed in vacuoles or show more and more distinctly their va<-uolar envelope. Vacuolization may continue until tiie entire cytoplasm i> crowded lull ol vacuoles except for the enlarging centrosphcre and a narrow peripheral nuirgin which usually renunns more or less clear. The cytoplasm in such highly vacuidized cells is reduced to a thin framework between the vacuoles, and to a dear, well-defined centrosphcre about the ccntriole tliat is entirely or almost entirely free of granules or vacuoles. I.,ong s])indle-shapcd fibroblasts, with the nucleus exten<ling nearly the full width of the cell, often have the ccntriole at one end of the nucieus, and the cytoplasm between the nucleus and that end of the cell may become ])acked with vacuoles lielore any appear in the other einl of the cell.

The rate of increase in the nundier of granules and vacuoles varies greatly in different cultures, ami also somewhat among the cells of a single culture. There is. however, usually more variation between different cultures than among the cells of the same culture. No two fibroblasts are ever exactly alike, even in the same culture: yet in sjiitc of this <lissimilarity among the individual cells tliere exists enough uniformity t^i give a peculiar character to each cidture. Since the rate of accumulation of tlie vncmiles :ni(l granules varies in different cultures, often quite niarkedly. one finds occasioindly in a "i-i-hour culture an accunnilation of vacuoles and granules as extensive as in the average 48- or even T2-hour culture. On the other liand, it sometimes hajipens that a 48- or a 7"<?-hour culture presents no greater accumulation of grainiles than the average 24-hour culture.

There are many other variations in the minilicr. size, inequality of size, etc., of the granules and vacuoles. It is the control ami production at will by enviroimiental alterations of such variations that will enable us to analyze more fully the processes that arc taking ]ilace. It <loes not seem beyond the realms of po,<sibility that some day we may be alile to jiroduce at will any desired variation.

The above conclusions in reganl to the increase in the number and size of the vacuoles and granules were not drawn from the continued observations of imiividual cells over long periods of time, but from shorter observations on thousands of cells in hundreds of cidtures. It would i)roiiably be possible so to rcgidate the comlitions of ob.servation that one conlil follow in a single cell this accumulation of granules and vacmdes from the condition foumi in the healthy fibroblasts, with few scattered graindes. to tin- completely viiciiolized cell, and r-vcn to the death of the cell.

Often during the observations, through the manipulation of the culture and the apfdication of neutral red and janns black Xo. 2, the c(dls were found to live hut an hour or so after the observations were begun. Such cells do not exhibit (hiring that hour or two anv niarkeil increase in the nnndicr of


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granules or vacuoles. Their death may ensue at any stage in the granular and vacuolar formation. Death may also take place at any stage in the cultures that are not thus manipulated. Several factors imdoubtedly contribute to the death of the cell, and sometimes one and sometimes another may predominate. In the highly vacuolated cells stained with neutral red the final death process is often quite rapid. The behavior of the colored vacuoles is quite striking; one after another, in rapid succession, they suddenly lose their color and flash out of siglit. When the process is complete, the cell has a peculiar, clear, unstained, moth-eaten appearance. Changes in the mitochondria and in the nucleus are also to be seen.

SIZE AXD SHAPE OF THE GRANULES

The granules vary iu size in the same cell. Some are barely visible with the highest powers, even with the neutral red stain; others are of considerable size and maj' measure onequarter or one-half the diameter of the nucleolus. The extreme minuteness of some of the granules indicates that other still smaller, ultramicroscopic ones are probably scattered tlirough the cytoplasm. Within certain limits it can be safely stated that the more healthy the cell the fewer and smaller are the granules. The granules undoubtedly increase iu size. One cannot actually see this increase, since the process is probably slow and the difficulty of following the same graiuile through any considerable length of time is too great.

Most of the granules are somewhat angular in outline, suggesting a crystalline formation. There is but a suggestion of this, however, since they are usually irregularly angiilar. I suppose an irregular angular mass might result from crystallization or from the accumulation of ultramicrosco[)ic particles. Such granules are difficult to distinguish, by their shape alone, in unstained cells, from the small gra:udar mitochondria (when the latter are present). In most healthv cells, however, the mitochondria are in the form of rods and threads which can be easily distinguished from the degeneration granules. In fixed specimens stained with iron hematoxylin it is likewise difficult or impossible to distinguish between granular mitochondria and degeneration granules. There is a method, however, by which the two types of granules can be distinguished in the living cell; i. e., the combination of neutral red and janus black No. 2, by which the granules are stained bright red and tlie mitochondria blue-black. Some of the special mitochondrial stains also enable one to distinguish the two types of granules in the fixed specimens ; on the other hand, certain fixatives, especially those containing acetic acid, destroy the mitochondria, but leave the granules miaffected.

Maximow noted that the griinules described by him were at first minute and irregularly scattered in the cytoplasm. This extreme minuteness of some of the granules is an important point, especially in relation to their possible origin from mitochondria, as alleged by some authors; for it would be logical to assume, if tliey do arise from mitochondria, that the latter first become reduced iu size to a minuteness which renders them invisible, and that this is followed by a change in constitution and a gradual increase in size. Mitochondria are


sometimes minute to the limits of visibility and yet retain the characteristic staining reaction with janus black No. 2. The most minute degeneration granules, on the otlier hand, exhibit the same characteristic coloring with neutral red seen in the larger granules. It is perhaps importtmt to note in this connection that those minute mitochondria are not always or usually found in fibroblasts that are just beginning to show the minute neutral red granules. It is only in the later stages of degeneration that the normal mitochondrial threads and rods tend to break up into granules.

THE RELATION OF GRANULE AND VACUOLE

It is not always possible to distinguish the granule from the small vacuole, as the granule may occupy practically all of the vacuole with only a thin rim of fluid. It may be that all the granules we are considering are included in vacuoles. The fact that granules are often irregular in outline would not nullify such a +++++ CONTENTSion, since vacuoles themselves are sometimes irregular. It is conceivable that even the smallest granule may be surroimded by a rim of fluid too thin for detection. In our present state of knowledge concerning these bodies it is of no particular consequence whether all granules lie within vacuoles or all vacuoles contain granules. Practically all vacuoles do contain granules, one or several, and it is vmcertain whether vacuoles exist that are entirely free from granules. We do not know why the vacuole should develop around the granule. It may be that minute vacuoles appear first and granules develop within them, or the granule may appear first and the vacuole develop about it. Since we arc not certain of the exact relations when the granules have attained visible sizje, the idtramicroscopic condition must necessarily be still more uncertain. The impression one gets from the study of uiunerous specimens is that many of the granules in the healthy cell are free from vacuoles, and that the latter subsequently develop about them. The granules in the smaller vacuoles often appear to be larger than those in the large ones. The larger vacuoles, however, usually contain several granules, with perhaps an aggregate of material equal to the larger granules of the smaller vacuoles.

In vacuoles of the same diameter containing solitiiry granules, the latter often vary in size. The amoimt of fluid in the larger vacuoles is much greater in proportion to the size of the gTanules than that in the smaller vacuoles.

Multij)le granules within vacuoles can be conceived of as arising in at least four ways: (1) By the coalescence of smaller vacuoles each with a single granule, the number of granules in the larger vacuole depending upon the number of smaller vacuoles which coalesce; (2) large granules may split up into small granules; (3) new granules may develop in vacuoles, by a process of crystallization, for example ; (4) granules free in the cytoplasm might be taken info the vacuole as it enlarges.

THE rOSITioX OF ORIGIN OF THE GRANULES AND VACUOLES

We have not been able to determine the position of origin of the granules and vacuoles. In the earlj' stages tliey are


APBIL, I'JIOJ


87


scattered, but as tlicy become more numerous, most of tlieiii are located in the immediate rejrion of the centriolc. Since they move about freely in the cytoplasm, either towards the centriole or away from it, one mifrht conclude tluit they form in the more i>eriplieral rej^ons of the cytoplasm and arc carried towards the centriole where they tend to accumulate, or that they arise near the centriole and arc carried outwards into the more peripheral rejiions of tiie cytoplasm. The ditliculties of the problem are increased by the fact that the smallest firanules are on the boundary of visibility, and from that one must conclude that they begin their existence in tlic cells as dustdikc jrraiiules invisible even with the hijflicst powers. Such •rranules in cyto])lasm would be unlikely to lie found in their position of orijrin when they attain the size of visibility. The fact that they accumulate about the centriole may indicate only that they are carried tiiere, as they form, l)y cyto])lasmic currents, if such currcntjj exist; and that tlie.^e currents tend, during degeneration, to flow more towards tlic centriole than away from it. Such a view receives some sujiport from tiie changes which oci-ur al)out the centriole. W'p have noted elsewhere that the centrosome increases in size during degeneration, and that about it a centrosphere develojis which gradually increases in size until it may become as large as the nucleus. The enlarging centrosphere is usually free or nearly free from granules and vacuoles, the latter surrounding it in a zone of varying thickness.

In cells with many vacuoles and a large centrospbcre, the latter is sometimes tilled with enormous numbers of the finest, du.«t-Iike granules which stain red with neutral red. What relation the.<e l)ear to the granules under discussion is not known, but very likely they represent a similar degeneration ]>ro<!uct. We have seen that the ordinary degeneration granules begin to form before the centrosphere apjiears; tlms they may arise independently of it.

TIIK MOVEiLEXTS OF TIIE ORAXILES .WD VACKH.ES

The granules and vacuoles exhibit a considerable amount of movement, ditfercnt from an<l more extended than the ordinary mit(H-hondrial movements. It is irregxdar, sometimes rapid and jerky, sonu-times slow and of varying speed. The distances traveled differ greatly; in general, the direction is from the region of the centriole or centrosphere to tiir |)eri[>hery, or lire \erxii. The amount of activity varies in ilifferent cultures and in cells of tiie same culture, and is apparently easily affectcfl liy environmental factors. Under certain conditions no movements r)f the granules are to l)c seen. Thes«' movements are probably not de|(cndi'nt upon the activity of the granules themselves, but upon either cytoplasmic currents in which the pa.ssive gramdes are carried or metabolic changes. It has not l)cen possible to .see cytoplasmiicurrents.

As statcfl aitovi', the movements of the granules are somewhat dilTerent in character from the mitochomlrial movements ; the amplitude is often greater and they are more lively. The movements are best followed in cells where the granules are stained red with neutral red and the mitochondria


blue with janus black No. 2. .\ red granule is sometimes seen passing along close to a blue-black mitocbondrium, .sometimes extending beyond the extremity of the mitocbondrium. Again the granules may pass back and fortli in paths that are some little distance from a mitocbondrium, and nniy cro.ss at varying angles above or below a mitocbondrium. Sometimes granules are detiected by the initocliondria as the latter are bent, or a])pear to l)e bent, i)y the tlowing granules. These appearances are such as to suggest that the granules arc located in a more fluid, streaming jiart of the cytoplasm, while the mitochondria arc in a less Huid part, tiie movements of which would be of a different ciiaracter, thus giving to tlic mitocbondrium and to the granule eacii its own peculiar tyjie of motion. On tiie otiicr iiand, tiie different types of motion may ijc due entirely to tile differences in I'cmijiosition of the mitochondria and of tiie granules, witii a resulting dill'ereiicc in tile inter-action tictween tlicin and tlie enclosing cyto|dasm.

niAMJKS IN IllK IDlfM OK THE VACUOLES

The viicuolfs Miry not only in size and jiosition. liut ai.so in sliape. In some ceils tiiey are constantly altering tlieir form such changes often occurring coincidently witii ciiange of position. Frequently many or almost every cell in a culture will show vacuoles tiiat are constantly ciianging iiotii form and position. -Vgaiii, viTy few if .uiy of tlic ceiis wiii siiow sucii changes.

The variations in siiajie wiiiili tiie vacuoles may assume arc quite remarkable. The usual form is spherical. Tiiis is the most staiiie condition and such vacuoles may remain unciianged for a long time. In contrast to this may iie found a complicated, tliread-like network of channels, very unstaliii' and constantly changing. Between tiiese two extremes a multiiilicity of forms occur in different ceils. The most common change is the sending outward from a \acuole of a long tiiread-like channel or process. Tiiis apparently cont^iins fluid similar to t.liat within tlie vacuole. These processes arc likewise constantly changing tiieir ])osition and length. The entire vacuole may iie converted into such a channel, wiiicii in rare instances may brancii and anastomose with other similar ciianneis to form a more or less comjdex network witii granules .scattered here and tliere witiiin the ciianneis. In such sjiecimcns the granules fre<|ucntly are larger than the diameter of tiie ciianncl and produce a distinct i»ulge in its wall. Tile granules are often oijscrved to sliift along tiie channel.

These vacuolar ciianneis are vi-ry unstaiiie and ciiange niucli more rapidly tiian tiie mitochondria. Many of tiiein are aiiout llie same size and siiape as tiie mitochondria, and at first may prove to be somewiiat confusing; but witii tlie use of neutral red and other vital dyes (methylene blue and brilliHul cre.syi lilue) tiicy can lie sliarply an<l clearly .separated from tiie mitochondria. Their ttehavior, too, is so difTerent tliat one soon comes to recognize that tiiey are entirely different. The vacuolar channels may change back into splitrical or oval vacuoles.


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I should suppose that these various changes iu the form, and ]ierha]is also in the position of the vacuoles, are dependent upon the metabolic activities, or upon the interchang-e of substances between the exterior and interior of the cell. The longprocesses and networks also suggest that there may be some relationship between vacuoles and the canalicular ai)]iaratus found in some other types of cells.

MITOCHONDRIA AND MITOCHONDRIAL VESICLES

Iu the vigorous, healthy fibroblast the mitochondria are usually scattered throughout the cell as long threads or rods, often branching or anastomosing and running in lines more or less parallel to the long axis of the cell; in others, radiating somewhat from the nucleus and centriole towards the periphery. As the granules and vacuoles increase in number the radial arrangement of the mitochondria about the centriole becomes more and more marked. In the earlier stages the mitochondria extend beyond the granular and vacuolar area into the clear cytoplasm. In some of the cultures the mitochondria come to lie in the cytoplasmic net between the vacuoles, and also partly in the clear peripheral regions at the ends of the cells. In such cells, even though the entire cytoplasm becomes packed with vacuoles and granules, the mitochondria may remain as short threads or rods until the cell is about to die.

Otlier cultures show fibroblasts in which the mitochondria midergo much more change. As the vacuoles and granules increase in number the mitochondria show more of a tendency to break u]) into short rods and granides, and these in turn may swell u]) into spherical bodies or vesicles of various sizes. The granules form very minute vesicles and the longer rods may form \esicles as largo as the neutral red vacuoles.

These changes apparently begin first in the mitochomlria lying immediately about the centrosphere and gTadually extend toward the periphery. They are usually preceded by changes in the mitochondria which give them an irregular appearance, and the longer threads seem to he broken up into short rods. The irreg-ularities of the mitochondria gradually become more marked and arc chiefly characterized by differences in the diameters of the various tlireads and of the different i)arts of the same thread or rod. These clianges are also accompanied by irregularities in the staining; that is, the mitochondria exhibit lighter and darker areas, especially w ith such stains as janus black Xo. 2. Under ordinary conditions of the culture, these changes in the mitochondria indicate degenerative changes in the cell. Similar changes can be brougiit about in a relatively short time in the long thread-like mitocliondria of Iiealthy fibroblasts by the use of potassium jiermanganatc. Witli a 1-20,000, 1-40,000, or 1-80,000 solution there takes place with varying degrees of rapidity, depending upon the strength of tho sohition, changes in the mitochondria similar to those observed in the more slowly degenerating cells of the cultures.

During these cliaiigcs both the thread and rod-like mitochondria and tile niitochoiulrial vesicles stain bluish witli janus l)l;ick Xo. 2. and ncxcr at any time do they take up tlie


neutral red. In fact, there is always a sharp distinction between the staining of the ntitochondria and the mitochondrial vesicles with janus black Xo. 2 and the staining ol' the degeneration vacuoles, the granules, and the processes of the vacuoles with neutral red. There are undoubtedly at times certain similarities between the two types of vacuoles when unstained, and in our earlier observations we were uncertain as to the relationship existing. For example, one often sees a small vacuole with a long mitoehondrium-like process that is continually changing in shape, size and position. Xow both the mitochondria and the neutral red vacuolar processes

I are subject to constant changes in form, size, and position.

I As mitochondria form vesicles the vesicular enlargement often takes place first at one end of the mitochondrium; the length of the unchanged narrow portion would vary, of course, with the length of the original mitochondrium and the size of the vesicle at the time of the observation. In unstained living cultures it might be impossible for the untrained eye to distinguish between such a changing mitochondrium and a neutral red vesicle with a mitochondrium-like process. With the application of a 1-10,000 solution of janus black No. 3 the mitochondria and the mitochondrial vesicles are stained bluish, whereas the neutral red vacuoles and granules remain unstained. If this stain is folloAved by a 1-25,000 solution ol' brilliant cresjd blue, it will be seen in a few minutes that the color in the mitochondria rapidly disappears, while the previously ixnstained vacuoles and granides take up the brilliant cresyl blue and appear bluish or violet in color. If, however, the janus black Xo. 2 is followed by neutral red ( 1-20,000 or 1-25,000), the blue color of the mitochondria and the mitochondrial vesicles is often increased in depth, while the previously imstained vacuoles and gi-anules take up varying amoimts of the neutral red dye. Then, too, the differences in the behavior of the two types of vacuoles when stained and followed with the application of potassium permanganate oichloroform indicate that we are dealing with two quite different things.

In some cells with almost complete vacuolization the mito- I chondria may show very little sign of degeneration or change, but apj)ear as rods and short threads in the cytoplasmic network between the vacuoles. In some of the long spindle cells \acuolization may be complete at one end of the cell and the mitochondria be more or less broken up into rods and granides ; while at the other end, the nucleus lying between the two parts, there may be almost complete absence of vacuoles and granules, and very little change in the long thread-like mitochondria. The degenerating end of such a cell seems to be always the end containing the centriole.

CHANGES IN THE REGION OF THE CENTRIOLE

As the cultures get older there is a gradual increase in the number and size of the granules and vacuoles. Parallel witii tliis increase very important changes take place in the region of the centriole. As the granules increase in number, they tend to accumulate about the centriole, which is located near one side or one end of the nucleus. This gradual accumulation


APKIL, lUlUj


8!)


of the granules, and later of the viuuolcs, about the eentriole gives a very characteristic picture, especially when tlic granules and vacuoles are stained with neutral red. One is often unable to recognize the centriole in the earlier stages in the living cell. In lixed material the centriole can usually l)c seen at the center of the mass of granules and vacuoles. Later, as these accumulate, the centriole becomes surrounded by a more or less dear area (the centrosphere) near the center of the mass of granules and vacuoles, and near one side or one end of the nucleus, with which it is more or less in contact. As the granules increase in number, the centrosphere increases in size, and at its center can usuallv be detected the double centriole. The centrosphere is usually entirely free from neutral red granules and vacuoles. It gradually increases and may eventually attain a diameter equal to, or even greater than, that of tiie nucleus. With its enlargement tiie granules and vacuoles api>ear to be pushed farther and fartb.cr away from tile centriole. The centrosphere usually presents a clear medullary zone immediately about the centriole or centrioks, and a much wider cortical zone, which often shows radiations. Occasionally one or two small neutral red granules appear td lie within the centrosphere. In some cultures which have been stained with neutral red the centrosphere .shows many very line, red, dust-like granules. Since this seems to occur only in c-ells that show somewhat advanced vacuolar degeneration, it may be that it is indicative of the beginning degeneration of the centrosphere.

We have already considered the radial arrangement of the mitochondria about the centriole and centrosphere; the i^ranules and vacuoles, lying between the mitochondria, also at times assume a more or less radial arrangement. We have considered also the movements of the granules and vacuoles which take place more or less in paths between the centriole or centrosphere and the perii)iiery. The accunudation of granules, vacuoles, and mitochondria about the centriole, and the accumulation or building up of an increased amount of what .«(H'ms to be a special type of cytoplasm about the centriole, would indicate that its activities are in some nninncr increased during the degeneration of the cells.

DISCUSSION

I venture to suggest that in due course of time it will lie found that the living part of the cell cannot be stained by any of the so-called vital dyes, since the combination of the dye with the living protoplasm would so upset the delicate molecidar constitution of the latter as to kill it : and because living ]>roto}>lasm is so eonstituteil that it cannot combiiu', either jihysically or chemically, with any other substances exce[)f such as are synthetically built up into itself. The corollary will be that till' so-raIle<l vital dyes stain only the non-living cytopla-smir inclusions, such as granules, vacuoles, secretion granules, food-glol»ules, mitochondria, etc.

One might well hesitate to ela.«s the mitochondria witli nonliving c.\-toplasmic inclusions, in view of the many claims tluii have been set forth as to tiie r«"ile of mitochondria in the transmission of hereditari- qualities, and above all as to their part


in the formation of various cell structures during histogenesis. They are supposed to form the coUagenic libers (Meves). myolibrils (Benda, Meves, Duesberg, Hoven and others), epidermal fibers (Firket and Uuesbcrg), neurofibrils (Uoven, Meves and G. Arnold), and .secretion granules (Grj-nfeltt, Bobeau, Kegaud and Marvis, Nicolas. Kegaud and Favre, Hoven and others) — a formidable list of authors imbued with the idea that the mitochondria po.s.scss magic qualities. I'owdry, in his recent excellent contribution, " The Mitochondrial Constituents of Protoplasm," states that " the radical claims concerning their role in histogenesis have forced the reinvestigation of the entire field." He is inclined to believe that the mitochondria are concerned, either directly or indirectly, witli nu>tabolism or with proto|)lasmic respiration. The mitochondria may well play an important role in the general metabolism of the cell, more especially in that particular part of the metabolism which is common to all cells, such as respiration, perhaps, as has been suggested by several authors (Kingsbury, Mayer, Kathery and Schaetler). The mitochondria niight jilay such a role in the general metabolism of the cell and still not be considered as a part of the living cytoplasm, any more than are the stored-up yolk-granules found in many eggs.

t'oghill suggests that during the i)rocess of digestion and assimilation of yolk in amphibian embryos certain end-products of the process segregate into what he calls alpha bodies and beta bodies, and that the former, proltably undergoing some chemical change, become free as mitochondria in the process of assimilation into protoplasm. AVlietluT this be true or not, more interesting still is the suggestion that the more toxic action of janus green (whicii st-siins the mitochondria), as compared with that of neutral red (which stains the bctn bodies), is due to the fact that tiie proces.«es leading up to tiie construction of protoplasm arc oi)structed i)y the reaction of tiiis stain ; whereas, only the residue, so to speak, of these processes is attacked liy tiie neutral red. If the mitochondria are concerned in tiie respiration of the cell, the action of jaiiu.green on the niitociiondria. for which it has a special alliiiity. might obstruct the rcs])iration to such an extent as to kill tiic cell. Coghill's suggestion as to the less toxic action of neutral red would apply to our conception tiiat neutral red stains only llie non-living matter, such as accumulated waste products or stored-up food-stuffs, or .some partially digested food-stuffs that are not iminediateiy essential to tiie ceil.

(Jranules witli a special affinity for neutral red iiavc been described in many iliffercnt types of cell in many different species of animals, and it will be interesting in tiiis connection to consider a few of the more striking cases. Fischel ('01) found in the living ectodermal cells of ampiiiiiian larva; many such granules. He considered tliem as living elenient.s, in conformity, perhajis, with the views of .\ltmann prevalent at that time. We know that tlie ectodermal cells of various vertelirates deposit witiiin themselves substances which are usually <-onsidered as non-living elements, and which in many ca.ses ultimately accumulate to such an extent as to finally transform the cell into a non-living scale. The fact that such


90


[Xo. 33S


deposits may serve a useful purpose in the organism does not invalidate the view that they are non-living inclusions.

The Clarks have described in the lymphatic endothelial cells of the tadpole's tail numerous gi-anules which take up the neutral red in the living. E. R. Clark has shown that the lymphatic endothelium is actively phagocytic, and since these cells possess the power of taking up particulate matter it may well be that they also take in ultra-microscopic particles and segregate them into granules that take up the neutral red. Whether these granules are of this nature, or whether they consist of waste products, is of course impossible to determine at present. Other phagocytic cells, such as the clasmatocytes and leucocytes, are especially rich in vacuoles and granules that have a great affinity for neutral red. The clasmatocytes are especially interesting in this connection, as they are abundant in most of our cultures. Certainly the vacuoles, and [irobably all the granules which stain so avidly with neutral red, are non-living inclusions, the granules for the most i)art being derived from cellular debris taken up by the cells.

It is well known that the partially digested dead +++++ CONTENTSs of the food vacuoles of protozoa stain with neutral red (Plato, Stole) and that disintegrating bacteria and cell debris in leucocytes stain in a similar manner (Plato, Arnold). Many eggs contain nmnerous granules and globules, probably foodstuffs, and perhaps accumulated waste products also, that stain with neutral red. The eggs of Cerebratulus, of the sanddollar, and of Lojthius piscatorius (M. R. Lewis), as also the amphibian egg (Coghill), have recently been studied with the aid of neutral red, and all were foimd to contain numerous neutral red-staining granules probably of the nature of storedup food-stuffs.

There are reasons for believing then that the granules and vacuoles considered here are non-living cytor()lasmic inclusions. Since the granules and vacuoles accumulate without noticeable enlargement of the cells, they must be formed in greater part from the cytojilasm rather than by the diffusion into the cell of substances and fluid from the outside ; moreover, thev are formed from the cytoplasm, ])resuniably as jiroducts of the metabolism of the living cell. Tliese products of metabolism may be divided into two classes — food products and waste or secretion products. The former are found most abundantly in egg and embryonic cells, and we should scarcely expect to iind cells cultivated in Ijocke's solution storing up food-stuff's. We are led, therefore, to accept the alternative theory, i. e., that the granules and vacuoles are accumulated waste products and that they are formed in part, at least, hy the breaking down of the cytoplasm. This process may be looked upon as a degeneration j)henomenon. since it ultimately leads to the death of the cell.

The altereil environmejit of the fibroblasts in the cultures pr<ibably sooner or later interferes in many ways with their normal metabolism, either from the absence of oxvgen, salts, or food-stuffs, or through the accumulation in the culture medium of waste products in suificient amount to prevent their normal elimination from the cells by osmosis. This altered environment M'itli its lack of certain essential salts, food-stutfs, and


perhaps of oxygen, would favor the breaking down of the cell protoplasm through starvation, and the accumulation of waste products. We have no method of determining whether the +++++ CONTENTSs of the vacuoles and granules are identical with the normal waste products excreted from the cell. An alteration in the composition of the waste products, however, might he expected to accompany the starvation of the cell.

Since the cells do not appear to increase in size as vacuolization spreads, we are more or less forced to conclude that part of the cytoplasm is broken down into granules and vacuoles. This process maj' use up most of the cytoplasm, leaving only a slender framework between the vacuoles. The enlarged centrnsphere usually remains intact and does not become vacuolated. The cytoplasmic framework is continuous with the centrosphere, radiating out from it in all directions.

The relationship of the gTanuoles and vacuoles, and likewise of the mitochondria, to the centriole and to the gradually enlarging centrosphere is not at all dear, if we attempt to explain it in physiological terms. The anatomic picture is plain enough, but why the granules and vacuoles should surround the centriole and centrosphere is miknown.

The centriole and its centrosphere have long been considered by many authors as the dynamic center of the cell, the focal point of the more active archoplasm of Boveri, the kinoplasni of Strasburger, the spongioplasm of Leydig, etc. This peculiar cytoplasm, which accumulates about the centriole during degeneration and which I have also seen much augmented in amount in giaait cells in certain cultures, seems to be different from the ordinary cytoplasm that occupies the bulk of the cell. Whetlier there is an actual increase in the amount of the stuff" forming the centrosphere or merely a concentration of already existing material about the centriole, is difficult to determine. There appears, however, to be an actual increase.

Conklin speaks of the spongioplasm of the egg of Crepidula as " the interalveolar or continuous substance within which are found enchylemnni, microsomes, mitochondria, as well as yolk, oil, and other inclusions." He finds that " large inclusions such as yolk spheres are forced out of regions where the spongioplasm concentrates." A somewhat similar phenomenon seems to take place about the enlarging centrosphere. where the vacuoles and granules are forced away hy the concentration or increase in the archoplasm or spongioplasm about the centriole in the degenerating fibroblasts. The framework of cytoplasm, which extends from the centrosphere to tlie peripheral layer in these highly vaciiolized fibroblasts, corresponds, perhaps, to the spongioplasmic framework in Crejiidula that remains throughout the entire cell and connects the nucleus and centrosphere of the resting stages to the peripheral layer after the centrifugal force has displaced the more fluid part of the cytoplasm, tiie yolk, and the other cytoplasmie inclusions. It is the spongioplasm that seems to be the living part of the cytoplasm, the ])art which determines the polaritx of the cell. In the normal fibroblast the cytoplasm, except for the mitochondria and a few granules, appears homogeneous. Does this a|)parent homogeneous cyto])lasm consist of two ])arts.


THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL. 1919 ' <« :.'•=.•;


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a sponorioi)la.«mic framework ami a more fluid enchvlemma y Or is it all H|)(iiijri(i|>la.-;mii- material. cxeeiJt for tlie iiKJusioiis above iiotinl 'i

The eauses of. or faetors eoiicemed in, the firadual enlar<,'emeiit of the eentrosphere are not known. It is well reeojjnized that in many ejijrs where food aceiimulations are eonsiderahlc tile attraction sphere is larjre. It is also larger in cells that are about ready to divide tluui in the restin<r cell. There is undoubtedly a relationship between the accumulation of foodstuffs in the eg-r and the size of the attraction sphere; and again, between the growth in size of cells which are destini'd to divide and the increase in the size of the attraction sphere.

Is the accumulation of granules and vacuoles about the centriole the factor that causes the enlargement of the eentrosphere?' Such an accumulation of granules and vacuoles would naturally alter the usual relation.ship of the centriole to the periphery of the cell, ujjsetting the metabolic balance in such a manner as to eaiise. perhaps, the building iip of the enlarged eentrosphere, since the metabolic activities which are centered in the centriole probai)ly de|)end upon a constant interchange of materials i>etween the centriole and periphery. The accimiulating waste products about the centriole in the form of granules and vacuoles would certainly tend to alter this.

BIBLIOGRAPHY

Burrows. M. T.. and C. .-V. Xey'raann: 1917. Studies on the metabolism of cells in vitro. Jour. Exp. Med., XXV.

Clark. E. L.. and E. R. Clark: 1919. On the reaction of certain colls in the tadpole's tail toward vital dyes. Anat. Rec.. XV.

Coghill. Ct. E. : 1915. Preliminary studies on the intercellular digestion and assimilation in amphibian embryos. Science. N. S., XLIII, 347.

Conklin. E. G.: 1917. Effects of centrifugal force on the structure and development of the eggs of Crepidula. Jour. Exp. Zool.. XXII.

Cowdry, E. V.: 1918. The mitochondrial constituents of protoplasm. Contributions to Embryology, VIII. Carnegie Institution of Washington, Pub. No. 271.

Fischel. A.: 1901. Untersuchungen liber vitale Farbung. Anat. Hefte, Bd. XVI. 417.

L^wis. .\I. K.: 1917. The effect of certain vital stains upon the development of the egg of Cerebratulus lacteus. Echinorachniu.s parma, and I..ophius piscatorius. Anat. Rec, XIII.

Lewis. .\l. R.. and \V. H. Lewis: 1915. Mitochondria and other cytoplasmic structures in tissue cultures. Am. Jour. Anat., XVII.

Luna, E. : 1917. Note citologlsche sull" epltello pigmentato della retina coltlvato " In vitro." Arch. Ital. di Anat. e dl Embr . XV.

.Maximow. Alexander: 1916. The cultivation of connective tissue of adult mammals in vitro. Russian .Archiv of Anat., Hist. and Embryology. I.

Plato, J.: 1900. feber die " vitale " Karbarkeit der Phagocyten des Menschen und einigen Saugethiere mit Neutralroth. Arch. f. mikr. Anat . LVI. 868.

Stole, A.: 1902. L'eber das Verhalten des Neutralrots ini lebendigen Protoplasma. Zeit. f. allg. Phys.. I. 209.

EXPLANATION OF FIGCRES

The figures are all drawn free hand from living cells stained with neutral red. and many of them with janus black No. 2 in


addition. The original drawings gave only vague outlines for the cells, as the author's attention was concentrated on the relations of granules, vacuoles, mitochondria, centriole. eentrosphere, and nucleus. Since then the borders of similar cells, both in living and fixed material, have been examined, and appropriate outlines added to the original cell drawings. Thus the greater number of the figures are composites. The edges of most of the fibroblasts present a peculiar scalloped condition, with slender processes of varying lengths extending from the points, much longer, as a rule, than those shown in the figures.

Figs. I, 2. 3, 4. and 5 are from 78-hour-old cultures; explants from the legs of 8-day chick embryos. Figs. 2 and 3 are from the same culture, the others are each from a different culture.

Fig. 1.— Healthy fibroblast with few granules. Figs. 2. 3, 4, and 5 show the gradual accumulation of granules about the centriole and the increasing radial arrangement of the mitochondria. In Fig. 5 are also seen many small vacuoles. Fig. 4 and 5 show small centrospheres.

Fig. 6. — A 74-hour-oId culture; explant from leg of 9-day chick, showing' increased number of vacuoles and granules about an enlarged eentrosphere. Mitochondria broken up into short rods.

Figs. 7 and S. — 54-hour-old cultures: explants from leg of 8-day chick. In Fig. 7 the centrospliere is at the side of the nucleus and the granules, vacuoles and mitochondria are arranged more or less symmetrically and radially about it. In Fig. 8 the eentrosphere is at one end of the nucleus. Very few granules or vacuoles are seen in the opposite end of the cell.

Figs. 9 and 10. — 7S-hour-ol(l cultures: explants from leg of 8-day chick. The eentrosphere either has not developed or is obscured by the crowded granules and vacuoles. The centriole was not seen, but its position in both cells is undoubtedly at the side of the nucleus.

Fig. 11. — A 78-hour-old culture; explant from leg of 8-day chick. Large eentrosphere surrounded by granules, vacuoles, and mitochondria. Wide cortical zone of eentrosphere shows radiations. The vacuoles in this cell were constantly sending out long processes.

Fig. 12. — A 4S-hour-old culture: explant from the leg of a 7-day chick. Cell crowded full of large vacuoles, except at the thin edge. Mitochondria broken up Into short rods which seem to lie in the cytoplasmic framework — eentrosphere obscure.

Fig. 13. — A 48-hour-old culture; explant from leg of 7-day chick. Very large eentrosphere surrounded by many large vacuoles. Radially arranged mitochondria, rather long rods and threads. No vacuoles or granules in the opposite end of the cell.

Fio. 14.— A 2-day-old culture: explant from leg of 7-day chick. Large eentrosphere: entire cell crowded with large vacuoles; mitochondria in form of short rods.

Fig. 15.— A 3-day-old culture: explant from leg of 7-day chick. The vacuoles showed much motion and were constantly sending out long processes or changing into channels, which are seen to anastomose at one end of the cell.

Fig. 16.— a 24-hour-old culture from the leg of a 7-day chick. The vacuoles and gianules showed considerable motion, and the vacuoles were constantly sending out processes and changing In form.

Fig. 17.— a 3-day-old culture from intestine of a 7-day chick. The mitochondria have all changed Into vesicles. Degeneration has progressed to such an extent that the vacuoles have begun to disappear.

Fic8. 18, 19, and 20.— 2-day-old cultures; explants from the legs of 7- and 8-day chicks; showing variations In the vacuoles, eentrosphere, etc. eentrosphere full of dust-like granules.

Fio. 21— A 3-day-old culture; explant from leg of 9-day chick. Mitochondria arc changing into vesicles.


92


[No. 338


SOME ASPECTS OF 0\ ARIAN PREGNANCY. WITH REPORT OF A CASE

By A. W. Meyer and H. M. X. AVyxxe

From the Department of Gyneeology of The Johns Hopkins Medical School, the Department of Embryology of the Carnegie Institiition.

and the Department of Anatomy of Stanford University


Although the first case of ovarian pregnancy under that heading in the Index Medicus is that of Kouwer ('97) (van Tnssenbroek, '99), careful scrutiny of the titles listed for the last decade reveals the fact that 5 cases of ovarian pregnancy were reported in 1908, 4 each in 1909 and 1910, 7 in 1911. 13 in 1912, 9 in 1913, 7 in 1914, 3 in 1915, 1 in 191G, and 5 in 1917. This makes a total of 58 cases apparently reported \vithin this decade. Since the reports on some of the cases were published in three different Journals, these were, of course, counted merely as one, and although the authenticity of four of the cases must be questioned on the basis of the titles alone, the series, nevertheless, is a large one in spite of these facts and of a marked decline in the number reported during the war. Since Norris ('09) stated that only 19 certain cases, a])proximately only one-third as many as all cases Usted in the last decade, were reported in the decade between 1899 and 1909, it would seem that ovarian pregnancy not only is receiving increasing attention, but that a change in attitude probably is in progress. Tliis conclusion would seem to be justified even though a careful examination of the descriptions of the cases reported in the decade between 1908 and 1917 would reduce somewhat the number listed.

Loekyer ('17) accepted as authentic only 22 cases of those reported between 1910 and 1917, but his review is only a partial one. Even so, it shows that there is a decided increase in the number of cases which have been regarded as genuine from decade to decade. The marked increase in the number of genuine cases re])orted in recent decades becomes still more evident if one recalls that Williams ('10) found only 13 positive cases up to 1906, whereas Norris found 19 positive cases in the single decade between 1899 and 1909. That is, ISTorris foimd more positive cases reported in this decade than had been reported in all previous medical history up to 1906. This surely is a significant fact.

The opinion that many, even if not all, cases of so-called hematocele, hematoma, apoplexy, blood cysts, and rupture of the ovaries, probably are nothing but cases of ovarian pregnancy in disguise, has been held by various investigators for some time. Hence, if hematocele of the ovaries repeats the history of hematosalpinx, it is not tmlikely that the near future will see a marked increase in the reported frequency of " a fact so curioiis and important in itself," as Granville aptly put it a century ago. This would seem to be true in spite of the fact reported by Norris and Mitchell ('08), that only a single case of ovarian pregnancy was found among 44 extra-uterine specimens and 58 hemorrhagic cysts contained in the collection of 1700 gynecological specimens at the hospital of the University of Pennsylvania. At any rate, a careful microscopic examination of all such eases would seem


to be indicated in the future in order to determine, if possible, which cases are, and which are not, conceptual in origin.

To-day it is no longer true, as stated by Freund and Thome ('06) and by Sencert and Arom as late as 1914, that authentic cases of ovarian pregnancy belong to the great rarities. Yet the fact that many of our states, as well as many large clinics, have not a single case on their records seems to suggest that the condition still is seldom recognized, a century after Granville observed his first case. Moreover, a nimaber of continental gynecologists and obstetricians, for a quarter of a century, have regarded the oceiu-rence of ovarian pregnancy as undoubted. Anderson ('17) stated that German writers began to report eases of ovarian pregnancy with some frequency after 1901, and Gilford ('01) also called attention to the fact that continental opinion long had accepted ovarian implantation not only as possible, but as proven. Gilfonl further referred to the often quoted opinion of Tait that ovarian pregnancy is as rare as " A blue lion or a swan with two necks," and in his article in 1899 also called attention to the opinion of Bland-Sutton, that ovarian pregnancy not only has no existence, but that it is impossible. These opinions are particularly interesting in view of the carefitl reports made by Granville (1830 and 1834), in connection with the two cases which he then and which others since have regarded a.< cases of undoubted ovarian pregnancy, in spite of the absence of microscopic examination. In view of this lack it is particularly fortunate that both of these reports of Granville are accompanied by splendid illustrations by Bauer, which also won his praise and admiration and which greatly strengthened his cases. It may be recalled in this connection that Werth ('01) accepted Granville's case recorded in 1820, but said nothing about his second more convincing instance reported in 1834.

Although there is as yet no agreement as to what constitutes an authentic case, a re\'iew of the literature justifies the growing and apparently well-founded belief that in the past too much emphasis has been laid on certain criteria wliich later experience has shown to be partly inapplicable. It is becoming clear that some cases, formerly excluded for reasons regarded as sufficient, with our present knowledge could no longer be rejected. Moreover, it does not seem at all improl>able that some cases listed as tubal really were orarian in origin. Xor must it be forgotten that not even the entire absence of remnants of the conceptus can positively exclude a case from the category of true ovarian pregnancy. In a number of cases in the literature, and also in the present case, the clinical history and gross anatomic findings suggest the conclusion drawn by Scott ('01) on a priori grounds alone, that the conceptus may be completely resorbed. It may, of course, also be aborted and disintegrate completely. That such an


April. l!il!t|


i:s8umptiuii is justified is indicated by the lysis of tlie emljiv" or fetus in a large number t)f eases of ovarian jtrejrnancy, and also by the very degenerated condition of some of the vesieles and of the surrounding ovarian stroma. The |)ossil)ility ol' such an occurrence is estal)lislied also by similar events in tlic uterine and tubal jiregnancies discussed elsewhere (Meyer. '19), and ])robal)ly is illustrated by such cases as those of Anning and Littlewood {'01 ). in which no mention is made (if an embryonic disc in a translucent conccptus the size of m

  • ' pea." Then, to be sure, there are the cases of unruiiturcil

ovarian ])regiinncies containing villi only, as well as the rare case, probaltly of double ovarian pregnancy, of Holland ('11 ). Although one cannot be certain that embryonic tissue was removed from the left ovary with the blood-clot which was forcibly c.\]ielled at the time of operation, it is not at all improbable that the small jdasmodial masses found in the Icli ovary were the only remnants of the concejitus. 1 realize fully that the conclusion that young concejjtuscs may be wholly dissolved is fraught with great uncertainty, but I am quite sure that it is justified by the facts, and that it therefore is in the direction of truth. It could oidy fail to be so if every ovum that beconu's implanted within the ovaries were al)orted or were removed by operation before lysis was possible.

One cannot rightly refuse to recognize the i)<)ssil)ility of tlie spontaneous disap])earance of an ovarian pregnancy. Sinee implantation in the ovary occurs under such al)normal conditions, it would .seem that for this reason alone the gn^at majority of .such implantations inevitably must succumb. This would .>;eem probable wholly aside from considerations regarding the development of the corpus luteum, although lack of, or interference with, the development of the latter also woulil .'ieem to condition early death of the conceptus if the results of the long series of experiments on rabbits by Frankel ('0.3-'10) are indicative of the role iilaycd by the ••orpus luteum in early imidantations in nian also. It surely is didicult. if not impo.ssible, to see liow implantation witbii: the (Jraalian follicle, and esj)ecially the later development ol the conceptus, can fail to interfere with the development of ii normal corpus luteum. Ca.^es in the literature, and also in tlie present case, did not reveal the presence of any well-pre.'<er\eil or even true luteal cells at the time the pregnancy was terminated. Although this fact does not presu|)pose an entire lack of developnu'ut of these cells in the earliest stages of tlu' implantations, it undoubtedly does im|)ly a defective development, which in it.*elf nniy have become responsible for tbi> death of the conceptus. \or should the jiossiide toxic eti'ect upon the conceptus of luteal lells be forgotten in this i-onnection.

I do not assnnu'. to j)e svire. that the eliiiieal symptoms mikI signs alone should suflice finally to group a s|)ecinien as truly ovarian, but when these arc indicative of the pre.«ence of an ectopic gestation, and when undouiitcd intra-uterine decidual changes are present, in the absence of abdominal pregmincy or tubal involvement and a normal corpus luteum. and the presence of a blood-dot within the ovary, there would seem to he little reason for doubting the authenticity of the ovarian implantation even in the absence of cnd)ryonic remmint.-.


Siiu-e i-hanges suggesting decidual reaction in the ii\ary ha\e l)eeu reported so seldom it is doubtful whether nnich emphasi^ can be laid on them. One seems justified in saying this in spite of the fact that the presence of decidua in the ovary formed the only anatomic evidence U])on which Kantorowic/ ('04) confidently classed his two rather atlvanced cases of ectopic pregnancy anumg the authentic. Moreover, if it be true, as stated by Webster ('04 ) that changes which cannot be distinguished from true decidual changes not infrequently occur in the ovary in connection with normal uterine pregnancies, then the ])rescnce of islands of decidual cells in an ovary surely cannot be regarded as indicative of ovarian pregnancy. 1 wonder, however, whether it woidd not be po.ssible to distinguish genuine decidual cells by modern histnchemical methods. In making this observation, 1 am fully aware that various criteria have been advanced from time to time by means of which to judge ovarian pregnancies, and that many of these have met with objection and have hence been nu>dified. Such modifications would seem to be inevitable as long as there is progress in the sulutinii nf mm unsettli'd question.

The absence of tlie iCtus in inanv of the recorded cases in itself demonstrates tlie entire inapplicability of the criterion addeil by .lacobsoii ('(I.S). .Moreover,' the histologiiappearance of the ovarian tissue around certain jiortions of the blood-clot in the present, ami also in some of the ca.ses in tinliterature, would seem to suggest that it may be very diflicull to find remnants of ovarian tissue at several points in a casi' of pregnancy which has ailvanced far. Hence, this criterion of Spiegelbcrg ('7S) cannot be regarded as necessarily crui-ial. Whenever the implantation is developed at the outer instead of at the inner margin of a follicle, as in the ca.^e of Banks ('12), early destruction, even if not early rupture, of the overlying ovarian stroma and cajisule would seem to be inevitable. Indeed, whenever the layer of ovarian stroma overlying the pliuiiita is thin, very early death of the fetus would seem to lie inevitalde from defective nutrition alone. On the other hand, when jdaccntal development occurs in the region of the follicle directed toward the body of the ovary, great destruction of the ovarian stroma woulil seem to be unavoidable, even if something akin to normal decidual formation actually took ]dace. In the case of Kngelking ('lU), f<ir exani])le, not a trace of an ovary was found in an ovarian pregnancy which had become interstitial. Kven without assuming the complete aidhenticity of this rather ecpiivocal case, it W(uild seem highly probable that the presence of ovarian tissue later in the pri'gnaiiey probably is determined very largely by the location of the fertilized follicle within, or by the e.\act location of the im|ilanta1ion upon the ovary.

Werth ('8T) is said to have collected 12 ca.srs. among which he regarded only that of Leopold ('S2) as authentic. Ix-opolil ('1)9) reported 14. (Jilford ('01), in a splendid succinct review of tlu' literature gave 28 cases. Hi of whi<h he regarded as nndoubteil and 12 as ]>robalile. Koclie {'02) accepted only 12 ca.<es. Filth {'02) accepted 21. Kantorowicz {'04), using the criteria of I.,eopold {'99), together with a microscopic examination as a basis, groujied the cases in the literature a


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certain, probable, and uncertain. He considered 17 as certain, 10 as probable, and 13 as uncertain. And to the 17 cases regarded as certain by him, Kantorowicz then added two of his own, basing his decision, however, mainly upon the presence of deeidua in the ovaries, thus making 19 cases regarded as authentic by him. Freund and Thome ('06) regarded 23 of all the cases reported up to that time as certain. Norris ami Jlitchell ('08) considered 16 as positive, 15 as probable and !) as fairly probable. Warbanoff ('09) collected 3-t cases and iSTorris ('09) regarded 19 of those contained in the literature of the previous decade as positive; but Williams ('10), from a critical review of the literature up to 1906, and upon tlic l)asis of the criteria of Spiegelberg, regarded only 13 as positive, 17 as highly probable, and 5 as probable. Mapes ('14) collected 30 cases, but wholly from secondary sources, and Lockyer ('17) 42, from the years 1910 to 1917. Of these eases Lockyer accepted 22 as authentic and 20 as questionable ami undecided from the evidence available to him.

This short summary suffices to show that there is as yet no consensus of opinion as to what constitutes an ovarian pregnancy. Although this fact finds its explanation partly in our lack of sufficient knowledge, it is due also to the meagerness of some of the reports. Besides, if complete disintegration and lysis of intraovilrian conceptusps can occur, then it must always remain a. question of opinion in the future wliether some of the cases so rejiorted really were or were not true ovarian jiregnancies. This must remain true no matter how thorouuh the microscopic examination, unless the clinical history or changes in the maternal organism can afford us crucial tests in such cases.

Anyone who reads far into the literature of ovarian pregnancy also nnist become aware of the fact that even very recently skepticism has been carried too far. Jacobson ('08), for example, placed the case of Ivouwer-van Tussenbroek (a ease which finally convinced Bland-Sutton) and that of Webster ('01) in the doubtful class! Furthermore, .Tacobson also insisted upon the presence of an cndiryo or fetus as absolutely essential.

It must be emphasized, however, that even a liberal attitude on the part of a reviewer would not justify him in accepting all cases reported as genuine upon the basis of the reports themselves, for they — especially the older ones — often are too meager to enable one to form a reliable opinion. This is illustrated also by such recent reports as those of (iarrard ('16), Martin ('17), Sweeney ('17), and of Mills ('17). Although it must he remembered that from the very nature of tilings it sometimes is impossible to make a report which in itself carries conviction, it is regrettable that in a niunber of relatively recent cases in which such a report apparently could have been made, this was not done. ^lills' case seems to have been an instance of ovarian implantation in a region other than the Graafian follicle, and hence recalls the first ease of Granville and the cases of Franz ('02), Norris ('09), Paucot et Debeyre ('13)?, and perhaps also that of Kouwer ('97) (van Tussenbroek, '99).

From evideiu'e contained in the literature, it is clear that further re|)orts of single cases are not needed for the purpose


of emphasizing the occurrence of ovarian pregnancy, yet such reports nevertheless may help in the determination of the relative frequency of this novel and sinister condition, and also throw further light upon its genesis and the finer relations of the implantations, as well as upon other matters. Moreover, since the cases which are accompanied by a careful histologic examination and wliich for this reason alone are wholly unequivocal from an anatomic standpoint still are relatively few, the report of an additional case would seem to be justified. The present specimen (Carnegie Collection, No. 1322) was donated by Wynne to the Department of Embryology of the Carnegie Institution of Washington, and the following clinical report furnished by him :

CLINICAL HISTORY

Gy.n. No. 22303. — The patient, an Italian woman of 37 years, was admitted to, the Gynecological Service of The .Johns Hopkins Hospital July 12. 1916, complaining of pain in the lower abdomen, nausea and vomiting.

Famil)/ History. — Negative.

Past History. — General health good. She has never had any serious illness. For the past five years following a labor she has had recurring mild attacks of pain in the abdomen without nausea or vomiting.

Menstrual History. — Always regular every month except when pregnant or lactating. Duration four to five days; painless, moderate flow. Last period ,Iune 25, 1916. Last preceding period March 16, 1916. No intermenstrual bleeding before present illness.

Marital. — Married IS years; seven children, oldest 16, youngest born IVa years ago (died. 1915). Has had three miscarriages. History of labors and puerperia vague.

Present Illness. — Began five days ago (July 7, 1916) with sudden pain in lower abdomen, nausea and vomiting. She has had marked dysuria and painful defecation. For 12 hours after onset there was rather profuse bleeding from the vagina and there has been a bloody vaginal discharge since.

(The patient does not understand English and her husband acted as interpreter. )

Physical Examination.— T. 101.6° F. P. 96. R. 20. W. B. C. 8400. Hbg. 46 per cent.

The patient lies in bed grunting with pain. The skin is pale. The lips and raucous membranes are quite pale. There is a systolic blow heard at the apex and increasing toward the base, being loudest over the pulmonic area.

A drop of clear fluid was expressed from the right breast.

The abdominal respiratory movements are limited, although she does not complain of pain on deep inspiration. The flanks bulge somewhat. There is no demonstrable movable dulness. There is tenderness all over the abdomen, most marked over the lower left quadrant. There is increased resistance over the lower abdomen, but no muscle spasm. No masses can be made out.

There is a profuse bloody vaginal discharge. The cervix is pushed up behind the symphysis by a soft, exquisitely tender mass, filling the cul-de-sac. No crepitus is made out. Rectal examination confirms the vaginal. The fundus of the uterus is not felt.

July 13. Ifiia. — Ether examination.

There is a dark, bloody discharge from the vagina. There is no vaginal cyanosis. The cervix is lacerated, firm, and normal in size. The fundus of the uterus is about normal in size and is in anteposition. A boggy mass fills the cul-de-sac and to the right of the uterus a fairly firm mass, the size of a small orange, which is somewhat movable, can be felt. Definite blood-clot crepitus can be felt on rectal examination.

Pre-Operative Diagnosis. — Extra-uterine pregnancy, ruptured.

Operation (Dr. W. R. Holmes, Resident Gynecologist). — A free midline Incision was made below the umbilicus. The peritoneum


Al-KIL. I'.IUtJ


95


was blood-stained. The abdomen contained 200 to 300 c. c. of dark fluid blood and clots, and a large clot filled the cul-de-sac. Active bleeding had ceased. The left tube and ovary were normal and free of adhesions. The ri,i;ht tube, which was quite normal in appearance, lay over a mass which had replaced the right ovary. This mass was roughly spherical. 5 to 6 cm. in diameter and semisolid in consistency. Over the surface there were six or eight nodular projections, about 1 cm. in diameter, .^t the top of one of these projections there was a very small opening, from which bloody fluid could be squeezed. The surface of this mass was white with spots of bluish-black discoloration.

The appendi.x was normal except at the lip. where it was adherent to a blood-clot.

The tumor was removed by clamping, tying, and cutting into the^ right iiifundibulo-pelvic ligament and the right utero-ovarian ligament. The right tube was not removed. The appendix was also removed and all blood and clots were cleaned out of the abdomen. The incision was closed without drainage. At the close of the operation, the uterus was curetted. The uterine cavity measured 7.5 cm. in length.

A subcutaneous salt solution infusion was started on the table and continued on the ward until 2000 c. c. had been absorbed.

The patient was in good condition at the end of the operation and made an uneventful recovery.

The urinr on admission contained red blood cells, white blood cells, no casts, acetone, a trace of albumin and no sugar. Several days after the operation it was negative, except for a faint trace of albumin.

August J, V.Hi't. — Discharged in good condition.

Oyn. Path.. \o. i^.?}'i". — Normal endometrium from curettage.

A letter from the patient dated February 12. 191S. said that she had remained in good health since the operation and had given birth to a full-term child January 29. 1918.

Several features in this cliuit-al history ikviTvo coninu'iit. First amoii<^ these is the menstrual a<;e as eoni|)ared witli the size of the chorionie vesiele. Since the eross-seetions of t!u' latter measure 15 x 18 mm. and since it and the amnion are degenerateil and devoid of an enihryo, it is evident that the latter must have <lied a jjood while before the time of o|)eriition. Hence, the menstrual period rei«)rted for June 25, l!)l(i. very evidently wa.s not the lii.it period before prejrnancy supervened, but the lirst jteriod which recurred after the death of the coiHej)tus. Consequently, tiiis prejrnmuy undoul)tedly dates from near April 13, the time of the first omitted period. Moreover, the conceptus must have died long enough before Jtine 25 to have niatie iidiiltition of the succeeding period impossible. It shoidd lie noted, however, that the original menstrual cycle n f) pure nil i/ was broken, for with the customary inter-menstruar period of 28 days, menstnuition normally would have fallen due on June 7 instead of .June 'i'>. Hence, the mainteimnce of the original cycle woidd have brought rufiture of this ovarian pregnancy, as indicated liy the symptoms, on July 7. in direct relation with the on.*et oi menstruation. Nor does it seem unlikely that the hyperemiii accompanying the return of menstruation on June 25, if sudi it really was, may have been jiartly responsii)le for the on.<el of a sufficiently large and persistent hemorrhage to cause tiie slight rujiture indicated by the symjitoms on July 7. It must also be rcmembere<l in this connection that cases of ovarian ()regiiancy have been reported in which menstruation was uninterrupted. But in the ca.«o of Chiene ('13), fi>r example, the death of the conceptus may have occurred .«o early that tli


succeeding period was not inhibited, and the same thing may be true of the case of Lea ('10).

Since the material from the curettage, done al ihc time of operation, showed the presence of a normal endometrium, the uterine deeidua as.sociated with this ])rcgnancy nnist have been shed some time jireviously. Such a conclusion also woulil seem justified iiy the condition of the conceptus. which apparently was unai)le to |)revent a return to the normal. Tinabsence of deeidua at the time of operation al.^o suggests thai what was re|)orted as a return of imrmal menstruation on June 25 may have iiecii licniorrhage accompanying the expulsion of the deeidua.

Since, in the present ca.-:c, the .iKiriunic vesicle was so degenerated and .<o completely isolated in a large clot, and especially since no well-iin|)lanted villi were found in the .sections and gross jiortions examined, it is not at all jirobahle that the hemorrhage that caused the rupture \va.< due to a contemporaneous invasion of the ve.-ssels by the fetal trophoblast, such as occurs in uterine and tubal im|ilantations, and as has been actually described also in ovarian implantations by Franz ('02) and by others. In the present, and in similar cases in the literature, it would strm that hemorrhage was made jiossihle also by degenerative changes in the highly va.«cular stroma of the ovary which ha<l been greatly com|ircssed and stretched by the proportituiately large blooddot, the organization of whieli would seem U> iiare been precluded by its size alone.

The fact that relatively few unruplured ovarian pregnancies are recorded suggests that the old tenet that rupture is le.>is likely the more advanced the jiregnancy becomi-s. probably is open to .serious doubt, as suggested by Hanks ('12), who bclievetl that the lubes can accommoilatc themselves more readily than the ovary. Hanks stated that in the majority of cases of ovarian jiregnancy rupture occurred in the lirst two or three weeks, and Caturani ('11) also cxjinwed doubts regarding the dictum that rupture of the ovary is lc.«s likely the more advanced the pregnancy. .No one will di'ny, 1 prc.sume, that the .symiitoms of rupture nniy have been totally absent, as rejiortcd in the ca.^es of .N'nrris ('OK) ami (Jrimsdale ('13), but this does not imjily that the ovarian stroma or the germinal cjiithcliuni still surrounded the lull-term i-onceptus. Such an occurrence would be possible only if tlu' ovarian stronni and the overlying germinal c|iithcliinn undi-rwent an astonishing hyperplasia. Although such a thing is conceivable it is decidedly significant that no one has reported any such finding or observed the presence of mitotic figures.

Insteail of undergoing hyperplasia the ovarian .stroma in this ca,«e is found invaded, stretched, compre.<.-<cd, anil degenerate, and the germinal epithelium is entirely absent. The fact that several observers have seen what they took for the fibrin layer of Xitabuch also shows that degenerative changes in the ovarian impbinlations may be extensive. Heur-e, it would seem to follow that the absence of symptoms of rupture merely nniy mean that the ovarian stroma and epithelium which ha|ipcned to overlie the fetal membranes gradually have died and degenerated before being forced apart by the expanding conceptus or the increasing hetnorrhage. That such


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a sequence of events is possible would seem to be undoubted, and merely distension of the ovarian stroma until it com])letely surrounded a full-term pregnancy ' is hardly conceivable ; whereas, the absence of pain upon the yielding of an exceedingly thin degenerate layer of ovarian stroma is quite conceivable.

That rupture may occur very early is exemplified also by the cases of Chiene ('13), Seedorff ('15), and especially by that of Aiming and Littlewood ('01) and of Holland ('11). In such curious instances as that of Grimsdale ('13) one can hardly assume that the ovarian tissue was preserved about the entire .•onceptus, and it is not at all unlikely that full-term ovarian ]iregnancies, which, according to WarbanofE, supplied a sur])risingly large percentage of all cases collected by him, will form a far smaller percentage in the statistics of the near future. Indeed, they already form a far smaller percentage of those reported up to the present, and the advances in diagnosis alone make it very imlikely that in the future many cases of ovarian pregnancy will advance far before being detected.

The present specimen, which had been hardened and cut before it came to my attention, is a firm, nodular, dark-colored mass, 26 X 16 X 11 cm., shown in Fig. 1. In the gross, it especially recalls the specimens of Freund and Thome, Giles ('14-'15), Jaschke ('15), and Lockyer's ('17) second case. The exterior is smooth though bosselated and formed by a rather injected layer which is extremely thin, showing tlie blood-clot beneath, aroimd the greater extent of the specimen. The surface layer is eroded over several small elevated areas in which the blood-clot imderneath is exposed. Hence, the capsule may have been ruptured in several or only in one ol' the areas as noted at the time of the operation. Xear the region of amjjutation through the mesovarium shown to the right in the figure and marked by the corrugations of the hemostat, the tissue overlying the clot becomes more opaque, thicker, and also more yellowish. Here it is studded with small cysts, the character of which in itself suggests ovarian tissue. The color of the area to the right also is suggestive, and the cysts later were foimd to contain a clear viscid fluid, so characteristic of cysts of the ovary. The location of the main portion of the ovarian stroma shows that implantation occurred near the mid-point of the free convex or posterior border of the ovary, and that the stroma forming the sides gradually was forced apart, not by the growing conceptus, except perhaps at the lieginning, but mainly by the liemorrhage itself.

The major ]iortion of the surface of the divided specimen shown in Fig. 2 is composed of blood-clot, the presence of which confirms the " blood-clot crepitus " spoken of in the history. This clot contains an empty vesicle, the wall of which is formed for the greater part of its extent by a thin fibrous layer, except near the proximal or lower portion in the figure, where a thicker portion of ovarian tissue hoods the clot. Approximately only about one-third of the ovarian stroma seems to be preserved.

Xear the exterior of the thicker portions of the latter, a small cvst with clear +++++ CONTENTS is fomid directlv beneath the


surface, as indicated in Fig. 4. The distal or upper portion in the figure shows the clot to contain an empty, smoothwalled, degenerate chorionic vesicle, such as is frequently seen in tubal clots.

Examination of the cut surface with the binocular microscope shows the presence of only a few isolated, degenerated, and some hydropic villi scattered through the clot. Examination of the chorionic vesicle shows the presence of only a few attached villi and that the amnion is fused to the chorion. Since the entire sjjecimen obtained at operation is still covered by a layer of ovarian tissue which is unbroken save in a few very small areas, it is e^ddent that we are dealing with a very good example of an undoubted ovarian pregnancy in spite of the absence of an embryo. The latter undoubtedly did not escape through the small rupture in the capsule, for the chorionic vesicle seems entirely intact. Although the absence of a corpus luteum in the opposite or left ovary was not especially mentioned, lack of comment would seem to suggest that none was present, for the ovary very evidently was examined. Hence, this implantation probably took place within the Graafian follicle itself, and not in some other area of the ovary.

Celloidin sections of the excised portion show that the bloodclot contains no fibrin and that it is composed of relatively fresh and fairly well-preserved blood in the region near the main body of the ovarian stroma. The latter is quite normal although decidedly vascular, and contains ova. The layer of the ovarian stroma which surrounds the clot becomes thinner and thinner the nearer the free border is approached. It also becomes more trabeculated, hemorrhagic and degenerate. No overlying layer of smooth muscle, as mentioned by Yoimg and Rhea ('11) and also by Kantorowicz, was seen. Some infiltration with pohauorphonuclear leucocytes is noticeable. Degenerate villi are scattered about in the blood and a few others are apparently still attached to the equally degenerate ovarian stroma. Trophoblast is absent on these, although some of the villi that lie isolated in the clot possess a very e\\dent epithelium and also are associated \\'ith a few small masses of very degenerate syncytium. Only a few degenerate nonvascular vilU are still seen on the chorion. Very little evidence of epithelial proliferation is present on these, despite the fact that the blood in which the vesicle is eml^edded is not very degenerate. This seems to suggest that the hemorrhage wliich caused the rupture of the ovary was comparatively recent, although the conceptus had been dead for some time. Some of the villi scattered about in the blood-clot are outlined by degenerate syncytium only, and nothing but small degenerate masses of the latter are seen on the chorionic membrane or lying about isolated in the degenerate blood foimd in other places. Nevertheless, the epithelium of the chorionic vesicle is thickened at several points. The amnion is fused -nith the chorion and both membranes are very degenerate and destroyed almost completely in several places. The surroimding ovarian tissue, which is markedly vascidar and degenerate, shows infiltration in jdaces, especially where it is stretched over the large clot. No fibrous layer bounds the implantation cavity, as in the case re]>orted by Seedorff. The ovarian stroma merely


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL, 1919



Fn;. 1. — External appearance of the reconstituted gross specimen (Carnegie Collection, No. 152'^). Natural size.


Fiu. 2. — Appearance of cross-section of specimen shown in Fig. 1. X 1.



Fin. 3. — Photograph of a section from a part of the specimen showing the clot largely surrounded by ovarian stroma and containing the empty vesicle. The arrow points to the portion near which degenerate masses of what may have been lutein cells aro found. X 2.


I"i(.. 4 l'liotopra|)h of a section t;il<in from the thick portion of the ovarian stroma near the mesovarlum, showing a well-developed Graafian follicle. X 3.


April, 1919]


97


is slightly i-ondenscil here ami thero. and in places contains areas of hyaline ilegeneratioii, tlie exact origin of which conld not be definitely determined. A few of these are found near tile thin bounding layer of the ovarian stroma, hut no lutein layer or even luteal cells could i)e recognized. Tiie only objects seen which might be regarded as ])ossibly luteal in origin arc two microscopic rhoniboidai areas which lie near a small depression upon tiie surface, indicated in Fig. 3. The.se areas, which were covered by a very thin layer of ovarian stroma only, were made up of parallel, ilegenerate, slightly separated cords consisting of a syncytium containing numerous rather pycnotic unequal-sized nuclei. No pigment was seen in these areas, and were it not for the arrangement of the syncytia! cords, one would not be reminded even remotely of a ])ossil)le luteal origin. Although the germinal epithelium was wholly absent in the areas examined, these questionable areas nevertheless may have had such an origin. In the absence of lutein cells the present ca.se corresponds to that of Freund and Thome luid others, and stands in marked contrast to the ca.se • if van Tussenbroek, Franz, Anning and Littlewood ('01 ) and Thompson ('0^). As in the tase of Seedorff, no decidua was jircsent and nothing suggestive of an attempt at decidual formation, as rejwrtcd by Franz, Webster ('04 and '07), and by Caturani and Kantomwicz, was seen in the jiortioiis examined.

In describing his ca.se, .Sccdorif declared that in some places "f c-ontact between the fetal and maternal tissues he could not discriminate between trophoblast and connective-ti.ssue cells which looked like decidual cells and lutein cells. It is interesting that Sudortf al.«o spoke of villi which were almost Idled with Langhans' cells, an observation which naturallv makes one wonder whether by any possibility these cmdd not have been Ilofbauer's cells.

The pre-served ovarian tissue which was found near the amputation stumji contained hemorrhagic follicles, as observed al.so by Mall and fuUen ('13). A Graafian follicle 3 mm. in section, shown in Fig. 4, protruded above the rest of the .-troma ajid was quite mature. The presence of this follicle might be taken as an evidence of the occurrence of ovulation during pregnancy, were it not for the fact that the pre'sence of so degenerate a conceptus shows that as far as any effect u|)oii the maternal organism was conc-erned, the pregnancy virtually had been terminated long before. That both ovulation and menstruation can and do return after the death of an ovarian conceptus, but before its removal from the ovary, is illustrated also by ca.ses in the literature, especially by that of Xorri^ ('09). One must assume, however, that few, if any, surviving fetal element.* can be present under these circumstances. This concliLsion also would seem to lie confirmed by the remarkable case of Sencert and .\ron ('14). These authors reported a case of ovarian pregnancy in which nothing but a portion of an umbilical cord ."> mm. long containing Wharton's jelly, two arteries and a vein, and what was regarded as a placenta, remained. The latter was said to be composed of a narrow layer of plasmodiuni and a much thicker layer of trabeculat..! syncytial trophoblast containing blood between the trabecula-.


Because of the singidar structure of this placenta and also because of the failure to find villi or any remnant of the membranes, the authors concluded that the chorionic vesicle therefore could not ha\e reached the villous sUige. How such a supposition can be reconciled with the survival of a portion of an umbilical cord entirely nornnd in structure, it is dilHcult to see. The ovary concerned was brown, of the size of a " large fresh walnut," and contained a tumor, apparently the socalled placenta, which was 2 cm. in diameter. Although these fetal remnants had brought about not only almost complete amenorrhea for two years and also atrophy of the ovary and uterus, ablation of the affected ovary was followed not onlv by a return of the menses, but by a normal pregnancy within .seven months.

A sec-ond instance of ovarian pregnancy of sjiecial interest was that of Giles. Xo fetus was found, although the jtregnancy was unrujitured, and Giles estimati'd that the conceptus had died in the third or fourth week. The operation was not done until five months after the onset of the pregnancy. What is particularly interesting in this case is that Giles s])eaks of the mucoid degeneration of the connective tissue of the villi. The latter were found to be large, much branched, and had ramified in the clot. Since Giles also spoke of one of the illustrations as showing a vascular state of some of the villi, it seems possible that this was a case of hydatiform degeneration, even though there were no signs of activity of the syncvtium. Since the fetal membranes were isolated in a bloodclot very much degenerated and the villi without a Langhans' layer, one scarcely could exi)cct to find much evidence of epithelial jiroliferation .so common (but not essential) in hydatiform degeneration. Giles estimated that four months had elapsed since death of the conccptu-s, and if this specimen really was a hydatiform degeneration, it is the first one observed in ovarian ])reginincy and hence of particular interest for this reason alone.

REFERENCES

Anderson, S.: 1917 Primary ovarian sestation. Intern. Clin., XXVII, ser. 2.

Anning, G. P.. and Harry Littlewood: 1901. Primary ovarian pregnancy willi rupture 14 days after last menstruation. Trans. Lond. Obst. Soc, XLIII: and Lancet. 1901. I.

Banks, A. G.: 1912. A case of ovarian prcRnancy. .Tour. Obst. and Gyn. Brit. Emp.. XXI.

Caturani. M.: 1914. Ovarian pregnancy with report of a case. Am. Jour. Ob.st.. XLI.X.

Chiene, G.: 191:!. A case of raptured very early primary ovarian pregnancy. Edin. .Med. Jour., N. S.. X.

Engelking, Ernst: 19i;{. Intraligamentar entwickelte Eierstockschwangerschafl. Eln Beitrag zur anatomlschen Dlagnoatlk vorgeschrlttener Falle. .Monatschr. f. Gcb. u. Gyn.. XXXVII.

Franz, K.: 1902. Teber Einbottung und Wachstum des Eies Im Elerstock. Beitr. z. Geb. u. (Jyn.. VI.

Fraenkel, L. : 1903. Die Function des Corpus luteum. Arch. f. Gyn., LXVIII.

Idem: 191ii. Noue experlmente zur Function des Corpus luteum. Arch. f. Gyn., XC.

Fiith. H.: 1902. Ueber Ovarialschwangcrscbaft. Beitr. z. Geb. u. Gyn., VI.


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Freund. H. W., u. R. Thome; 1906. Eierstockschwangerschat't. Arch. f. path. Anat., CLXXXIII.

Garrard, J. I.: 1916-17. A probable case of ovarian pregnancy. ,Tour. Med. Assn. Ga., VI.

Giles. A. E., and C. Lockyer: 1914-15. Case of ovarian pregnancy. Proc. Roy. Soc. Med. Lend.. VIII; Obst. and Gyn., Sect. 2-10.

Gilford, Hastings: 1901. Ovarian pregnancy. Brit. Med. Jour., II.

Idem: 1S99. Two further instances of extra-uterine (one tubal and one ovarian) gestation in which rupture occurred before the first month; operation. Lancet, I.

Granville, A. B.: 1820. A case of a human fetus found in th.^ ovarium of the size it usually acquires at the end of the fourth month. Philos. Trans. Roy. Soc. Lond., Ft. 1.

Idem: 1834. Graphic illustrations of abortion. J. Churchill. Lond.

Grimsdale, T. B.: 1913. Case of ovarian pregnancy with fulltime fetus. Jour. Obst. and Gyn. Brit. Emp., XXIII.

Holland. E.; 1911. A case of ovarian pregnancy; probably bilateral. Jour. Obst. and Gyn. Brit. Emp., XX.

Jaschke, R. T. ; 1915. Ovarialgraviditat mit wohlerhaltenem Embryo. Ztschr. f. Gebh. u. Gyn., LXXVIII.

Jacobson, S. D.: 1908. True primary ovarian pregnancy ; operation; recovery. Contributions to the Science of Medicine and Surgery, N. Y. Post-Grad. Med. Sch. and Hosp.

Kantorowicz, Ludwig: 1904. Eierstocksschwangerschaft. Samml. klin. Vortr.. Volkmann, N. F., Nr. 370, Gyn. 136, Leipzig.

Kouwer, B. J.: 1897. Ein geval van ovarlalzwangerschap (zwangerschap in ein Graafschen follikel ) Nederl. Tijdschr. v. Verlosk en Gynaec. Haarlem, VIII.

Lea, S. W. W. : 1910. A case of ovarian pregnancy with diffuse intraperitoneal hemorrhage. Jour. Obst. and Gyn. Brit. Emp., XVIII.

Leopold. G. : 1882. Ovarialschwangerschaft mit Lithopadionbildung von 35-jahriger Dauer. Arch. f. Gyn., XIX.

Idem: 1899. Beitrag zur Graviditas extrauterina. Arch. f. Gyn., LVIII.

Lockyer, C. : 1916-17. Two cases of primary ovarian pregnancy, with a review of the literature 1910-1917. Proc. Roy. Soc. Med. Lond., X; Sec. Obst. and Gyn.

Mall, F. P., and E. Cullen: 1913. An ovarian pregnancy located in the Graafian follicle. Surg., Gyn. and Obst., XVII.

Mapes, Chas. C: 1914. Ovarian gestation — being principally a review of the literature. Amer, Jour. Surg., XXVIII.

Martin, R. S.; 1917-18. Three interesting cases. Va. Med. SemiMonthly, XXII.


Mills, H. M.; 1917. Probable ovarian pregnancy. Am. Jour. Obst., LXXVI.

Meyer, A. W. : 1919. Uterine lysis, tubal and ovarian, and resorption of conceptuses. Biol. Bull., XXXIII.

Norris, C. C: 1909. Primary ovarian pregnancy and the report of a case combined with intra-uterine pregnancy. Surg., Gyn. and Obst., IX.

Norris, C. C, and C. B. Mitchell: 1908. Primary ovarian pregnancy with report of a case. Surg., Gyn. and Obst, VI.

Paucot, H., et A. Debeyre: 1913. Etude sur les grossesses ovarlennes jeune. Ann. de Gynec. et d'obst. 2s, t. 10.

Roche, J.: 1902. De la grossesse ovarienne. These de Lyon.

Scott, N. S. : 1901. Ovarian pregnancy; is it an explanation of ovarian hematomas? Am. Med.. II.

Seedorff, M.: 1915. Ein Fall von geborstener Ovarialgraviditat. Monatschr. f. Geb. u. Gyn., XLII.

Sencert, L., et M. Aron: 1914. De Tindependance qui existe entre le development du placenta et celui de I'embryon (t propos d' un cas de grossesse ovarienne.) Bibliog. anat., t. 24.

Spiegelberg, Otto: 1878. Zur Kasuistik der Ovarialschwangerschaft. Arch. f. Gyn., XIII.

Sweeney, Thompson: 1917. Ovarian pregnancy. Med. Rec, XCII; Am. Jour. Obst., LXXVI.

Tussenbroek, van, Catherine: 1899. Un cas de grossesse ovarienne (Grossesse dans un follicule de Graaf). Ann. de gyn. et d'obst., t. 52.

Thr same: 1899. Ovarialschwangerschaft (ein Fall von Schwangerschaft in einem Graafschen Follikel). Intern. Gynak. Kong. zu. Amsterdam; Centralbl. f. Gyn., XXIII.

Thompson, J. F. : 1902. Ovarian pregnancy, with report of a case. Trans. Am. Gyn. Soc, XXVII.

Warbanoff. Peter: 1909. Ein Beitrag zur Graviditas ovarica. Inaug. Dissert.. Miinchen.

Webster, J. C: 1904. Study of a specimen of ovarian pregnancy. Am. Jour. Obst., L.

Webster, J. C: 1907. A second specimen of ovarian pregnancy. Trans. Amer. Gyn. Soc, XXII.

Werth, R.: 1887. Beitrage zur Anatomie und operativen Behandlung der Extrauterinen Schwangerschaft. Stuttgart.

Werth. R.: 1901. Ovarialschwangerschaft. Handb. der Geb.. von Winckel, Bd. II. Th. 2, Wiesbaden.

Williams, J. W. : 1910. Ovarian pregnancy. Gynecology and abdominal surgery, Kelly-Noble, Phil, and Lond.

Idem: 1917. Obstetrics; A text-book for the use of students and practitioners, N. Y. and Lond.

Young. E. B., and L. J. Rhea: 1911'. Ovarian pregnancy. Report of a case. Bost. Med. and Surg. Jour.. CLXIV.


GRANVILLE SHARP PATTISON

By AVii.Li.VM .Sxdw iliLLEE, University of AViscoiisin


Gro.ss, in his biojiraplucal sketch uf Pattison, say,< :

It is no exaggeration to say that no anatomical teacher of his day, either in Europe or in this country, enjoyed a higher reputation; his forte as a teacher consisted in his knowledge of visceral and surgical anatomy, and in the application of this knowledge to the diagnosis and treatment of diseases and of accidents, and to operations.

Being a man ui' iiitunsc feeliiii;' and .-^tvoni; pn-juiHces he did not easily brook oppositimi. Because of tlic^e characteri.sties


'Read before The Johns Hopkins Hospital Historical Club. December 2, 1918.


tlie early years of his career were stuvniy and his reputation as a teacher was fully acquired only after many bitter controversies, one of which was so acrimonious that it was fought out on " the field of honor."

The year of Pattison's birth is usually given as IT!)], Imt he says in his " Refutation," addressed to Dr. Nathaniel Chajinian, of Philadelphia, under date of November 28, 1820, " 1 shall soon enter on the 28th year of my age " ; this ap]>areutly makes 1793 tlie more correct date. He died November 12. 18.52, after a short illness, of nlistrtictiim of the ductus eonimunis choledochus.


THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL. 1919



GRANVILLE SHARP PATTISON. Courtesy of Dr. J. M. H. Rowland.


THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL, 1919


PLATE VIII 7i V



NATHAMEL CHAPMAN. Courtesy of Dr. Howard A. Kelly.


April, 1919]


99


Granville Sharp Pattison was the youiijjest sou of John Pattisoii, of Kelvin Grove, Glasgow. Of iiis early eilueatioii we know nothing eseept the statement tiiat he was probaliiy edueated at the I'niversity of Glasgow. That he was a hanlworking student is shown by his being, when hut 18 years old. assistant to Allen Burns, and on the death of Burns, in 181:!. l)ec<)niing his suecessor to the Chair of Anatomy, I'hvsiology and Surgery in the Andersonian Institution, a recently organized medical school in Gla.'Jgow. Here he made quite a reputation as a lecturer, and had it not been for his naturally indolent nature and love of ea.se, would, no doubt, have attained in his later years preeminent re]iutation as an anatomist.

In Novend)er, 181S, charges were brought against him liy Dr. Ure. one of his colleagues, of having committed adultery with his wife, and a divorce was obtained by Dr. I' re on that ground. The divorce laws of Scotland were at that time iwpuliar; all divorce |)roeedures were brought in the consi.story court, which was an ecclesiastical organization. It was not newsisary that the parties charged with adultery liad ever seen each other ami the reputed paramour might not have ever existed. In any event, the accu.«ed ])aramour could not appear and defend himself. If the husbaiul obtained a divorce from his wife on the ground of improper conduct, he could immediately bring a .<econd action for damages and the accused party could then appear in court and endeavor t" disprn\r the charge.

This second action was never instituted by Dr. I'rc. .Vftcr the arrival of Pattison in this country. Dr. Ure attemjitcd \<y publish an octavo volume dealing with the case. One of liis witne.s.ses, however, having confessed that her declaration was false and that she had been induced to make her statements by means of threats and i)ribcs. Dr. Ure suppre.s.sed the volume, for he could not sustain his charges, and had he attempt^'d under the.<e circumstances to circulate the publication he would have subjected himself to criminal prosecution. This epi.sode was unfortunate for Pattison and it j)layed an im|)ortant role in the turbulent years which f(dlowed : for, although generally known to be luifounded, many venrs cla])sed before it ceased to be recalled.

In Glasgow the charge was generally discredited, for Dr. L r. did not poss<'ss an enviable reputation ; in fact, a statement is made that he barely escaped transportation to Botany Bay " for fraudulently stealing and destroying his father's will." In spite of this accu.<ation Dr. Ure retained his position in the .Vndersonian Institution. Pattison explains the situation in the following statement :

The Andersonian Institutinn of which Dr. I're is a member is an establishment of late date. The funcis which were ol)tain>(l for the erection of its buildings were procured by sul)scrlptioii : and as Dr. fre was very active, at the time when the niom-y was raised, in obtaining it. an(i gra<ite<l to the subscriber of t20 :i perpetual ticlcet of admission to one of the courses of his lectures, it has become a question, wliether the money was bestowed on him as an Individual, he granting personally an equivalent, or to the Corporation of the Institution.

When Dr. Cre. about six years asio. fraudulently stole his father s will for the purpose of defrauding his family, an attempt was niadi


to expell him from the institution: but as the Trustees, upon taking advice, learnt that his expulsion would involve them in a tedious liti!;ation. a litigation which would require to be carried on by money advanced by them as individuals, the attempt was abandoned.

IJejdying tu tliis. Dr. t'liapman shows that the institution was incorpordtctl on June !t, Kyti; when the buildings were ready for occu])ation he does not state, but he docs infer that Pattison was guilty of a misstatement in that he considered an in.stitution 21 years old as an " fstabli.shment of late date." The founder of this Institution was .lohu Anderson, a Scottish naturalist, who in his will provided I'or its establi.shment; he died January 13, 17!)6, and the incorixtration on .lune 9, 1790. was undoubtedly the first step in carrying out tiie iirovisions of the will. The mcclical dc|)artnicnt gave its (irst courses in 1799.

Dr. Chapman attempts to offset the stateinciit in regard to the will of Dr. Fre's father by saying:

.\'ot long before he came to this country. .Mr. Pattison was tried

for a felony, in stealing a body from the grave Mr. Pattison

merely escaped from want of evidence that he had taken the clothes of the deceased: the part of the offence most penal under the Scotch law.

In this instance Patti.son was in the lii>i nf cinnpany. for .Tohii Hunter. Sir .\stley Cooper and nearly every teacher of amitomy up ti> the ])as.<age of the "Anatomy Act" in ]S.i2. might with more or less justice be termed an " acquitted fellon."

The occasion of Pattison's coming to Pliiladclpbia was the e.xpectation of occtijiying the Chair of .\mitomy in the Medical Departnu'iit of the I'niversity of Peinisylvauia. nuide vacant by the death of Profes.sor Dorsey and temporarily lilled i)y Prof. Philip Syng Physick. That he was given to understand before leaving England tiiat the position was ojicn to him is certain, but that this was unofficial is also certain.

On Deceml)er 24. 1818, I'attison received a letter from his In-other, .lohu Pattison, who at that tiiue resided in Philadelphia, in which he .states that his legal adviser. Mr. Chauncy. agreed with him that there was an opportunity for a man of talent lo be appointed to the |)osition left vacant by the death of Dr. Dorsey. The fact that he was a foreigner was certainly against him. but he was " inclined to think tiiat the trustees will be more guidecl iiy talent, than l)y any otlier consideration." He advised that letters be obtained from Astley Cooper and others and " you had better say the extent of your museum. etc.. wiiich I know Mr. Bnrns considered invaluable."

liider date of April 20. 181!l. Dr. Dcwees. of Philadelphia, wrote Pattison a letter which eonlained the following statement :

I have, contrary to any right, taken the liberty to advise upon the subject. As far then as a firm belief that you would succeed (and that belief founded on pretty certain data) will offer an inducement lo pay us a visit, I have no hesitation to declare, that no question remains In my mind, that were you on the spot, your election would he certain. It Is unquestionably the opinion of two of the most intlucntial and best informed men here. Your visit should be as prompt as possible, that you might have the necessary time for the preparatory arrangements here. .My opportunities


100


[iS'o. 338


to judge of the sentiments of those, who have this gift in their power, will be best explained by your brother.

Acting on thi.s advice Pattison arranged his affairs as qiiickly as possible and sailed from Liver])ool for New York, where he landed Jnlv 6, and on the evening of Jnly 7. 181 '.i, reached Philadeljihia.

The two " most infiueutial and best-informed men " referred to above were Drs. Chapman and Physiok. Each of these denied having authorized the use of his name. ('ha])maii .states :

The trustees, after postponing the appointment for six months .... had publicly advertised that they would receive applications from any quarter. But we soon discovered our mistake — for at their first meeting which took place not many days afterwards, when all the testimonials of Mr. Pattison were submitted to them, so far from a favorable impression being made, these recommendations were treated contemptuously, as extravagant and hyperbolical — it being quite manifest, that no individual with halt the merit which they set forth, would sacrifice his actual possessions, to embark in so adventurous a scheme!

Chapman evidently forgot that Philadelphia and the country in general was peopled with those who had left the old countrv and settled in this country because they thought that tlu'\ had here an opportunity to improve their condition — that they were adventurers.

Shortly before sailing, while he was in London, Pattison Avas made a member of the Medicq-Chirurgieal Society of London and a Fellow of the Eoyal College of Surgeons. Had there been the stain on his character which was charged against him, it seems doubtful if these honors would have been bestowed on him. The " testimonials " were written by Prof. John Barclay and Dr. Thompson, of Edinburgh : Francis Jeffrey, editor of the Edinbvrgh Revieu' : James Wardrop and Astley Cooper, of London; the Eev. Dr. Love, of Glasgow, a celebrated clergj-man of the Kirk of Scotland : Sir James McGregor : Sir William Adams ; and others.

Just at this time there was a good deal of intrigue taking place in the faculty of the University of Pennsylvania, and in 1819 Philip Syng Physick,

Yielding up his own better judgment to the schemes of others, for perhaps the first time in his life, allowed himself to be transferred — for the act was not of his own choice — from the chair of Surgery, to that of Anatomy, from the place where he was emphatically at home, to one in which he was comparatively a stranger.

Pattison did not accept any appointment in tlie L'uiversity. though one was offered to him : he also declined a professorsliip in the Transylvania L^niversity at Lexington, Ky. Cha])man makes Pattison's declination of the call to Lexington appear in a false light and says :

The College, were, moreover, as I am told, justly indignant at the disrespectful manner in which they were treated, considering the only motive of Mr. Pattison, in procuring the appointment, was to have it published as an early recognition of his consequence in this country.

He also states that Dr. Caldwell was furnished witli all of Pattison's documents, and had a distinct miderstanding with


Pattison that if lie were elected he would accept. If such «ere the case, Dv. Caldwell would not fail to make mention of it in his " Autobiography," for such episodes as this are favorite themes in his narrative. A careful reading of Peter's " History of the Medical Department of Transylvania University " also fails to reveal a single reference to this incident. In 1820 Pattison was elected Professor of Surgery in the University of ilaryland, and he looked forward to leaving behind him all the intrigue and malevolence he had encountered at Philadelphia, fostered in a large degree by Dr. Xathaniel Chapman. This did not materialize, for One of the faculty, a Professor in the University of Pennsylvania! came to Baltimore immediately after my settlement in that City, apparently for the purpose of shutting me out from the hospitality of the citizens, by the most foul, the most malignant, the most false asperations against my character.

The animosity existing between Pattison and Dr. Chai)man. who seems to have been the moving spirit in the campaign against Pattison, soon reached an acute stage and Pattison issued a challenge to Dr. Chapman, which he did not accept. This led Pattison to go to Philadelphia, and on October 23. 1850, he put up in two jntblic places the following post:

To THE Pviu.ic Whereas Nathaniel Chapman, M. D., Professor of the Theory and Practice of Medicine in the University of Pennsylvania, etc. etc. has propagated scandalous and unfounded reports against my character; and Whereas when properly applied to. he has refused to give any explanation of his conduct, or the satisfaction which every gentleman has a right to demand, and which no one having any claim to that character can refuse, I am therefore compelled to the only step left me, and Post the said Dr. Nathaniel Chapman, as a liar, a coward and a scoundrel.

Granville Sh^vbp Pattison.

Following tlie European custom Pattison resolved to stay two days in Philadelphia ; but, he says :

My stay, however, was not long. left to my option I was

arrested at 11 o'clock A. M. of the day on which I had put up the post. Dr. Chapman denies all agency in the matter, be it so.

When the case came before the grand jury, all the correspondence in the case was furnished by Chapman, and Pattison says :

Perhaps he did this that I might be convicted, in order that an opportunity might be furnished him of displaying his (lenerosity and magnanimity, by applying " instantly in person to the Executive " for my " pardon."

In his letter refitsiug to meet Pattison, Chapman gives as his reason, " tlie character and conduct of Mr. Pattison, as well in relation to the causes which compelled him to leave Scotland, as to events which have subsequently happened." Xot satisfied with this, in Xovember, 1820, Chapman issued a pamjihlet in which he attempts to Justfy his conduct. To this Pattison replied in a like manner November 28, 1820. Pattison " had the good fortune and address to enlist the sympathy of his colleagues and a large part of the community in Baltimore in his behalf, and presenting his side of the case to a committee of prominent citizens, he was exonerated from all blame."


April. 1919]


101


This was iu)t Chapmiiirs first "affair"; hi- had soim- ycar^: ln't'oro i-halleii<.0(l Dr. Dewecs. In rogaril to this alTair ( liii|iiiiau says :

It happened fifteen or sixteen years ago: and if my conduct was reprehensible. I hope I have since atoned for it, by a friendship warm, cordial and sincere. What, however, will be thought of tln' nialiBnity of a man. who thus endeavors to disturb the hnpplnes> of families, by references of this nature! ! I

Patti.soii r('|ilyili;r to tliis does not |mt (liainnaii in :ni "•nviahle lijrlit :

I have not a " numerous family," I admit, and here I allow there is ii distinction. But did Dr. Chapman before he had a family, when he challenged Dr. Dewees. who had a numerous one. think this excused him?

The quarrel lietwoon Chapman anil I'attison was finally taken up hy General Thonuis Cadwalailer, Dr. t'haiimanV hrother-in-law, and four years after Pattison's arrival in thi> <Miuntry (IS'iS?) they met somewhere in Delaware. Cailwalader received the ball from Pattison's pistol in his " pistol iirm " which was disabled thereby durini; the remainder of lii> life. Pattison was uninjured, " but a ball i)assed tlu-oiii:]i the skirt of his coat near the waist."

In 1820 Pattison resigned his professorship at Baltimore and returned to England. Why he resigned a position whiib with liis professional services he states was bringing him ^10,000 a year is not clear; for, as a teacher, he had a successful record while in Baltimore, and the University ot Maryland enjoyed its greatest prosperity. On the one liand. is tile statement that he " led a very gay life " in Baltimore jind that his health was thereby impaired and that after he left it was doubtful whether he recovered; on the other hand. there is Pattison's flat denial and 'Hi additional years of activr life.

In July, 1827, Pattison was ap]>ointeil Professor of AnatoniN in the newly organized University of London. Before long Inbecame involved in difficulties, different from those at Philadelphia, but equally disastrous. Pattison was a Scotchman and had taught in Scotland and "America"; he had iiifroduced as a te.\t-bo(»k Fyfe's anatomy, written by a Scotchman : he had for his demonstrator a Mr. Bennett, an Englishman. who had conducted a school of anatomy in Paris which had. very properly, been refused credit at an English institution : he had iiicurrecl the displeasure of Wakley, editor of tlu' f.iincet, who supjjorted Bennett; hut chief of all he was a Scotchman. If any one doubts the attitude of London at thitime towards Scotchmen let him read Pichot's " Life ami Labors of Sir Charles Bell " and the " Lett^'rs of Sir Cbiirli Bell " by his brother Tieorgc.

Wakley began his attjick on Pattison by a sharp criticism of Fyfe's anatomy ; it must be acknowledged, however, that tln' criticism was justified. Wakley was a friend of the mclii jl students an<l supported them in most of their comjilaints ami. |)0ssibly, promptetl .<ome of them. That he was responsible fm many reforms in medical in.struction and medical i)racticcs ito his credit, and he deserves all the credit accorded to him. but he sometimes overshf>t bis mark; take, for e.\amj)le, bi


altitude towards Sir Charles Bell, Marsiiall Hall, and .itlu is who have left an honored name and life work.

On .luly 23, 1831, Pattison was dismissed from Hie Chair of Anatomy at the I'niversity of London. The events preceding and following his dismissal are full of interest. Clarke, in his " Autobiographical Recollections of the Medical Pr<ifession," says :

No matter what a mans talents and acquirements might be. he had little or no chance of advancement at a Hospital, except through family or money influence. .•\11 the prizes in the Profession were monopolized by those who could pay for them, or who were fortunate enough to have friends at Court. The apprentice of the Hospital Surgeon paid a very large premium for his inden tures, and. as a rule, it was understood, that he was to be placed on the Hospital staff as part return for his money outlay. This gave rise to a system of nepotism of the most objectionable character: Hospital Surgeons were selected, not from the ma.ss of the Profession, but from the private pupils and relations of the " staff," ....

To add to the dis+++++ CONTENTS prevailing, there had been (1S27) an unseemly quarrel at the great Hospital of St. Uartholomew's. in

which .Mr. .-Vbernethy did not bear an enviable part At this

time, too, the establishment of what was then called the " University of London " attracted increased attention to the system

of nepotism The announcement of the names of Professors

of this Institution startled the Profession by the fact that most, if not all but one of them, were "outsiders"; were not. in fact, connected with any of the large endowed Hospitals, but were all of high and deserved distinction.

The first iiaiiie on tlic list given by Clarke is that of Pattison.

In the is.suc of the Lancet for March .">, 1831, tiiere is a communication signed " A Senior Student of the London University" in which an attempt is made to show that Patfison is unworthy of his professorship and that Bennett shotdd have the position. Much of " Senior Student's " compl.-iint and most of the student dissatisfaction is based on the fa<t that Pattison attcmpte<l to enforce discijdine in his cla.ssroom. That Wakley had jirevious knowledge of wlnit was taking place in Patti.son's lecture room is shown by the following quotation from the above-mentioned communicafioii :

You are already, Sir, aware of the proceedings which were Instituted during the last session by a part of the medical students against one ot the lecturers upon anatomy, Mr. Pattison.

This communication was replied to by another student, who signs himself " Veritas," under date of March 7, 1831, and throws considerable light on the case. One of the charges brought against Patti.son in the original complaint was "that the defect in his articulation rendered him unfit for the chair." This charge was afterwards erased. It is interesting to note that this is identically the same charge brought by Wakley against Sir Charles Bell. " Veritas " says " a more inikind and unfeeling imputation could not have been made." Toward the clo.«c of his reply " Veritas " says:

Picture to yourself. Sir, an assembly of mere youths, many of whom have Just commenced their studies, met together to decide upon the ability or inability of a professor who was engaged in teaching anatomy before many of them had an existence. The very idea is preposterous.


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[No. 33b'


He goes ou to say that he has attended two sessions of Pattison's lectures and has always found them instructive and any one who pays attention to his lectures "cannot fail of reaping abundant store of anatomical knowledge."

As stated above, Pattison was dismissed July 23, 1831. Tlie resolutions passed by the Council show that they finally yielded to the student clamor ; but

In taking this step the Council feel it due to Professor Pattison to state, that nothing which has come to their knowledge, with respect to his conduct, has in any way tended to impeach either his general character, or professional skill and knowledge.

One member of the Cotmcil protested vigorously, but vainly, against Pattison's dismissal and enumerates eight reasons why he should not have been dismissed. In the seventh item the statement is made that the other professors testified to tlie excellency of Pattison's qualifications and that " many of them liad expressed their firm conviction to the Council, that the dissensions in the medical school did not ari.se out of any defect or misconduct of Professor Pattison." They evidently had in mind outside influences.

From this time mitil the end of the controversy in the Lancet the discussion was confined mainly to Wakley and Pattison, with now and then short communications from some of Wakley's friends. The final shot was fired by Pattison and his closing paragraph is exceedingly interesting reading:

In the letters of Drs. Turner and Thompson, and in your " strictures " on my Statement, the fact of my having been a successful teacher in the United States is treated with great contempt. " It does not follow " observes Dr. Turner, " that he could succeed in London because he was successful in America." The Americans, forsooth, are easily satisfied. It is very well for John Bull to say so. I should, however, have expected that you were too well informed as to the state of medical science in the United States, to have given currency to such a vulgar and unfounded prejudice. The Americans, I assert, are as far advanced and as enlightened in their medical opinions as any country in Europe: and I would further assert, without the fear of contradiction, that there may be numbered amongst the medical profession of that country, gentlemen who, tor extent and profundity of knowledge, and for capacity of conveying instruction, have no reason to fear comparison with the most eminent teachers in Europe. Let the improvements in medical and chirurgical science be reviewed for the last thirty years, and it will be found that America has furnished her full quota.

This defence of American medicine and American nuHJical men by one who had good reason for resentment shows Pattison to have been a man of more character than is generally acknowledged.

Shortly before Pattison was dismissed from the Chair of Anatomy Bennett died and the Committee of Education cif the University of Loudon looked about for a new jjrofesscir. They were fortunate in their selection, for they recummendcil Mr. Jonas Quain lur the |)rofessorshi|i and his In-nthei'. Mr. Eichard Quain. inr (lenioustrator, and ]ieace reigned fur the time being.

Pattison was not long withottt a professorship, for in lcS3v! he took up his duties as Professor of Anatomy in the Jefl'erson Medical College, in Philadelphia, where he met with innnediate success. He held advanced ideas as to the best wav in


which anatomy should be studied, as the following abstract from the annual announcement of the Jefferson ^ledieal College for the year 1832 shows :

Anatomy, the basis of all medical reasoning, can only be studied practicoUy during the term of the student's attendance on lectures. Should he neglect his opportunities for acquiring a complete knowledge of the science during the term passed by him at college, he must be +++++ CONTENTS to continue forever afterwards a mere driveller in his profession. Now, anatomy is not to be learnt by an attendance on lectures. Dissection, and dissection alone, can make a man an anatomist. The Professor of Anatomy, it is true, may, by animated and masterly demonstrations, do much to guide and assist the anatomical student in true prosecution of his studies, but it is in the dissecting room, with the dead body before him. by patient and assiduous dissections, that the student can alone acquire a knowledge of anatomy.

Pattison remained in Philadelphia tmtil 1841, when he joined in founding the iledical Department of the University of New York. Here he held for the remainder of his life the Professorship of General Descriptive and Surgical Anatomy.

With his return to this country, the strife and turmoil of his life very largely disappeared. He married a Scotch lady by the name of Sharp, who was possessed of some fortune. I have been ttnable to ascertain the date of their marriage, but it proved to be a very happy one, for Gross gives a pleasing pirtnre of their domestic life. He was social, ever ready to do a kind act, a lover of the beautiful in nature and art. He took an active interest in establishing the Grand Opera House in New York. He also was an enthusiastic disciple of Izaak "Walton.

Pattison was the atithor of " The Register and Library of iledical and Chirurgical Science." He edited with notes Burns' Surgical Anatomy of the Arteries of the Head and Neck, !Masse's Anatomical Atlas, and Cruveilhier's Anatomy : he \\'as one of the editors of the American Medical Recorder, a journal which contains many of his contributions to medical literature.

NOTES

Pattison's Exoneration. — All the facts concerning the divorce obtained by Dr. Ure were laid before the managers of the Andersonian Institution by James Burn. " Writer of the Signet." and Pattison was completely exonerated by them.

Pattison's Museum. — Cordell states that this " was extensively advertised in the medical journals and newspapers of the country." After he went to the University of Maryland he exerted a considerable influence in the councils of the University and he eventually induced the University to purchase it for $8000, and in 1S21 a new building (Practice Hall) was erected for its accommodation. It consisted " of upwards of 1000 selected morbid and healthy specimens, and in variety, excellence and number was far superior to any other in America." For some time it constituted the chief attraction for visitors to the University. Many of the preparations are still extant, but in a somewhat neglected condition.

Dr. Phj/sick's Transfer to Aiiatonu/. — Chapman made the statement to Pattison that he thought by transferring Dr. Physick to the Chair of Anatomy and by bringing Dr. Gibson from Baltimore to occupy the Chair of Surgery the changes " would operate beneficially in two ways. It would strengthen the University of Pennsylvania, and at the same time weaken that of Maryland." This was before Pattison received his call to Baltimore.


Apkil. 1!M!)J


io;i


Position Offered at the University of Pennsylvania. — The position offered Pattison at thr University of Pennsylvania was to bo shared with another, and he did not care to accept such an arrangement. He therefore besan to sive independent lectures on anatomy and surgery and he says that he had " a class of above one hundred and ninety students. " The hour of Pattison's lecture was fixed after consultation with Chapman and was one which Chapman assured Pattison would not conflict with any of the professors. When, however, ("liapnian learned that Pattison's lectures were popular with the students he changed the hour of his own lecture to that used by Pattison and thus prevented the students from attending Pattison's lecture.

Gibson-Putt ison Controversy. — Apparently no one in Philadelphia knew of the particular structure demonstrated by Pattison. Gibson, however, found in CoUes' Surgical Anatomy ' an unusually full and well-written account of those very parts, which Mr. Pattison had claimed as a discovery of his own." Like many another worker Pattison thought he had found something new. but as soon as he found he had been anticipated he withdrew all claims of discovery, only claiming that certain post-operative results were best explained by the presence of this structure (Colles' fascia).

Gibson's Chnnirteri.'itics. — " He was very vain in his personal appearance, and more so of his reputation as a surgeon and teacher of surgery. His style of lecturing was easy, agreeable, and instructive, but he never omitted an opportunity to set forth his own merits and to depreciate the ability of surgeons whom he disliked. He was especially vindictive against his leading rival in Philadelphia." In 1847 Cibson was in Europe and returned late in the fall with a wardrobe of broadly striped waistcoats and trousers to match. These he displayed to his class until the lot was exhausted, causing much merriment in the class-room and prolonged rounds of applause which he received as evidence of his personal popularity (Busey. l". P.. 1848). Dr. S. D. Gross says. "Gibson was not an amiable man. His ill temper often betrayed him Into unkind expressions, even in the lecture room."

During his last illness Gibson sent for Gross. " .\ly acquaintance with him was slight, and I was therefore not a little surprised when I received a message to visit him at his country residence. .\n old friend, to whom I mentioned the fact, exclaimed, ' Don't you know that lie has no friends in the medical profession of Philadelphia. "

Pattison's Hroiiue. — " What added interest to the speaker was a slight lisp and a Scotch accent, which never entirely forsook him. despite his efforts to overcome them in early life " (Gross).

Chnitmiin us n Teathrr. — " A cleft palate, with its consequent indistinct utterance, robbed him of every charm as a teacher, for which his vast experience, great learning, and qualities of heart and mind so well fitted him. The most careful attention, near and in front of him was necessary to catch the words as they were spoken, except by those who by long experience had become accustomed to his unfortunate and defective enunciation " (Busey. V. P.. 1848).

He (Chapman) "has seen several cases of hydrocephalus in girls about the age of puberty, caused by metastasis of action from the uterus to the brain."

Chapman believes " many cases that have a decided character of angina pectoris afterwards terminated in well-marked gout cases. -A gentleman long afflicted with this affection had gout induced In his extremities by the use of sinapisms, and the former affection was relieved: but. Improperly removing the sinapisms, the disease suddenly returned to Its place and Immediately killed him."

Epilepsy. " usually assigned to a certain state of the nervous system — a peculiar sensibility or irritability — It Is the temperament of genius and intellect — Julius Cspsar, Mahomet, Napoleon, etc." (From bound volume of MS. notes taken by .lames C. Hall (U. P., 1827 » of Chapman's lectures delivered In 1826.)


Pattison's Resignation from the University of .UuriiUind. — Pattison. in his " Statement of Facts in his connection with the I'niversity of London, " says that it was his intention to return to the States and deliver another course of lectures: instead of doing this he spent some time in Germany. I have tried to ascertain the date of nis resignation, but have been unsuccessful. This mlgtil help by showing that he resigned from the I'niversity of .Maryland to accept the position in the I'niversity of London.

Putti-ioii's iKtsiiniutioii Jrum the I'nirrr.iilii u) London. — The only medical man who was a member of the Council of the University ol London (Dr. Birkheck) supported Pattison and opposed .Mr. Bennett and the way in which Bennett was appointed. I do not think that Pattison. at the time he wrote his " Statement of Facts." realized the extent of Wakley's opposition and influence. Later he understood it better and gave it proper consideration.

Defense of Amrricuu .Mrdirim-. — Medicine in the I'nited States 1800 to 1830. Pattison, in the closing paragraph of his final communication made the statement that if the advances In medicine and surgery " be reviewed for the last thirty years, it will be found that America has furnished her full quota." 1 have had the curiosity to look up American medicine during this period and find abundant material to substantiate his aflirmation.

In Boston, there was .lohn Warren and J. C. Warren, eminent as anatomists and surgeons — the latter founder of the Massachusetts General Hospital: James Jackson in internal medicine and Jacob Bigelow. who published in 1820 his " American .Medical Botany " — his essay " On Self-Limited Diseases " did not appear until 1835. In New York, Wright Post and Valentine .Motl were doing pioneer work in surgery. In Philadelphia, there was Casper Wistar and W. E. Horner in anatomy: Philip Syng Physick in surgery; John C. Otto in clinical medicine (he was the first to describe hemophilia): J. K. .Mitchell in neurology: W. P. Dewees in obstetrics: Nathaniel Chapman in the theory and practice of medl cine. In Connecticut. Elisha North was introducing vaccination, recommending the use of the thermometer in fevers and in 1S17 established the first eye infirmary in the United States.

Nathan Smith was establishing medical schools in New England and furnishing the entire faculty: he was a pioneer operator for ovariotomy and. in 1824. published his essay on " Typhus Fever." now a medical classic.

In the West there were four men who have made a name in American medicine. Ephraim McDowell, B. W. Dudley, Wllllani Beaumont and Daniel Drake. .McDowell Is known the world over as the father of ovariotomy (Nathan Smith did not know of his operation when he operated in 1821). Dudley was famous in his day for his success in lithotomy. Beaumont, in 182.';, began those studies on digestion which he gave to the world in 1833. Drake was estal)lishin,< medical schools and publishing essays on niedlcal education in the Wrslrm .loiirnul of the .Urdirnl und Phii.siiul Sciences: at the same time he was preparing for his great work. " Diseases of the Interior Valley of North America."

Other names could be added to this list, but it is unnecessary. I consider the point raised by Pattison well proven.

Has the lurotid (Uund Ihrr liec, h:.rtiri)uled.'— The Professor of Surgery at the University of Pennsylvania (Dr. t;ibson) In a cUnic at the Philadelphia Alms House, open to students of the Jefferson and the University, referred slightingly to the claim of the Professor of Surgery at Jefferson (Dr. McClellan) that he had performed the operation (under a general attack on Sir Charles Bell who had made the same claim). He refers to Bell as a Cunvu.ihuik </i(' t more worthy of his gun than the Dipper (Dr. McClellan).

Pattison took up the challenge and made a reply which was brilliant for Its wit and sentiment and convincing with its weight of learning. In the same publication Pattison ridicules the story that he was so Ignorant of the subject that he mistook the omo hyofd muscle for the carotid artery and was about to llgate it


104


[Xo. 33S


when one of his students called his attention to the mistake and, being set right by his pupil, found the artery and tied It.

I have tried unsuccessfully to ascertain what were the relations between Chapman and Pattison after his return to Philadelphia as Professor of Anatomy at Jefferson. Dr. J. W. Holland, of Philadelphia, made Inquiries for me of a distant relative of Dr. Chapman and reported that " he does not know a living soul who could state what were Cliapman's relations to Pattison in later years." As nothing further appears in print, the animosities of earlier years seem to have died out and disappeared.

BIBLIOGRAPHY

Bell, John: Philip Syng Physick. Philadelphia, 1S61.

Busey, Samuel C: Personal reminiscences and recollections. Washington. 1895.

Chapman, Nathaniel: Correspondence between Mr. Granville Sharp Pattison and Dr. N. Chapman. Philadelphia, 1S20.

Idem : Case of divorce of Andrew Lire. M. D., vs. Catherine L're Philadelphia. 1S21.

Idejn : Correspondence between ilr. Granville Sharp Pattison and Dr. N. Chapman. 2d edition, with explanatory remarks. Philadelphia. 1821.

Clark. J. F. : Autobiographical recollections of the medical profession. London, 1874.

Cordell, E. F.: Historical sketch of the University of Maryland School of Medicine. Baltimore, 1891.


Gibson. William: Strictures on Mr. Pattlson's reply to certain oral and written' criticisms. Philadelphia, 1820.

Gross, Samuel D.: Autobiography, 2 vols. Philadelphia, 1887.

Henry, F. P.: History of medicine In Philadelphia. Philadelphia. 1897.

Lancet, The: London, 1830-31, 1831-32.

Pattison. G. S.: Experimental observations on the operation of lithotomy, with the description of a fascia of the prostate gland, which appears to explain anatomically the cause of urinal infiltrations and consequent death. Am. Med. Recorder, 1820, III.

Idem: An answer to a pamphlet entitled "Strictures on Mr. Pattlson's reply to certain oral and written criticisms, by W. Gibson. M. D." Philadelphia. 1820.

Idem: A refutation of certain Calumnies published in a pamphlet, entitled Correspondence between Mi. Granville Sharp Pattison and Dr. Nathaniel Chapman. Baltimore, 1820.

Idem : Final reply to the numerous slanders circulated by Nathaniel Chapman, M. D., Professor of the Institutes and Practice of Medicine in the University of Pennsylvania. Baltimore, 1821.

Idem : Professor Pattlson's statement of the facts of his connection with the University of London. London. 1831.

Idem: A lecture delivered in Jefferson Medical College, Philadelphia, on the evening of Tuesday, the 22d of January, 1833, on the question " Has the parotid gland ever been extirpated? " Published by the students of Jefferson Medical College. Philadelphia. 1833.


COMMENTS ON THE PATHOLOGY AND BACTERIOLOGY OF FATAL INFLUENZA CASES, AS OBSERVED AT CAMP DEVENS, MASS.


Bv S. BuKr WOLBACH, Bo.stou


Death from influenza means death from Imig eomi)lieiitions — pneumonia in some form. The pathological picture ol' the Itmgs as seen in a series of postmortems is a kaleidoscopic one. At first it was most difficult to correlate the various gross findings, and it also has been difficult to correlate the microscopic findings, and this part of the work is not yet completed. I have had the advantage of comparing my observations with those of Dr. Goodpasture at the Xaval Hospital at Chelsea, Mass., and again with a study of the series of cases we have had at the Peter Bent Brigham Hospital in Boston, and it now is possible to give a fair account of tlie probalile sequence of events and to explain tlie apparent great diiferences in the ])athology.

In a series sucli as is presented here two types of lungs staml out as strikingly characteristic findings in this disease. The first is encountered in those cases in which death has occurred within a few days after the onset of pulmonary signs. These cases yield lungs which are partially collap.sed, dark red, la.\. but meaty in consistency. Tlie pleural surfaces are often partly covered with a dusky red mottling, due to small extravasations of blood beneath the serous coat. There mav be a thin layer of dusky red fibrinous exudate u])on the pleural surfaces, particularly over the posterior borders. On sectimi these lungs are dark red and wet. They are dripping wet, and the fluid from some portions is a blood-tinged serous liquid and from others dark red and bloody. On close inspection the cut surfaces are usually found to be thickly sprinkled with air


vesicles of considerable size. The lung tissue as a whole, after the liquid has drained from it, is brownish-red in color, and somewhat translucent and friable. The mucosa of the bronchi is usually very dark red in color, and the bronc'hial lymph nodc^ are enlarged and deep red in color.

The other type of lung, which is found in patients that ha\ e lived for 10 days or more after the onset of the disease, whilr showing traces of the type of lesion just described, is characterized by a very extensive bronchitis, n'ith bronclio-pneumonia, discrete or confluent, and peri-bronchitis. These hmgs are more voluminous than the preceding, but they do not fill the chest cavity at postmortem. They are nodular, and the ]deural surfaces occasionally show a striking tracery, due ti> the injection of the stib-pleural lymphatics. Portions of the surfaces of the lungs may be covered with a thin layer of fibrinous exudate. On section the most prominent feature is the extensive injection of the bronchi, particularly the smaller imes, with a fibrino-purulent exudate. The injection of the lu'onchi may be so extensive and uniform as to produce geometrical patterns, which are very striking when the condition is accomijanied, as it usually is, by a marked infiltration of the inter-lobular septa. A casual inspection suffices to show that the smaller bronchi are distended, nsuallj' markedly dilated, and in eases of two weeks' duration spherical and cylindrical bruncliiectases are very common. The gross appearances of this type of lung are very much like those described by Dr. MacCallum in pneumonias after measles. The condition in fact


Ai-KiL. 1919]


105


is one of pan-bronchitis; peri-bronchitis with extensive infiltration of thf interlobular sopta : and organization in alvi-oli and bronchioles.

These two preduniinatiiig types on first consideration seem to represent ditTerent processes. 1 hope to show convincinglv that they simply represent difTeri'ut stages of the same process. Before I undertook tlie study of the Camp Devens cases I had .some experience with influenza pneumonias at the Peter Bent Brigham Hospital, and I have since quickly surveyed tlie material obtained there during the time I was at Camp Devens. The Brigham Hospital cases, on the whole, have been t|nit(' diflferent in their gross appearances. On the other hand, the cases at the Naval Hospital in Chelsea have been very similar to those at Camp Devens, and I think a cross-section of the study of one series of cases is very much like that of the other — to which Dr. Good|)asture agrees. There are many other interesting features of the i)athology of the lungs, such as tlic rapidity with which bronchiectasis occurs and the large number of case.s which develop interstitial emphysema, and of course the consequences of both of these conditions ; bronchieitatic abscesses and gangrene of lungs from the first, emjiiiysenia of the mediastinum and subcutaneous emphysema fnmi the second. Of this series of 2S postmortems, done between the 2d and 32d day of the disease, there were six that showed sulicutaneous emphysema: eleven showed emphysema of tlic mediastinum.

In comparing notes with other pathologists one is struck by the dillerenees in gross appearances of the lungs in dilferent localities. The .same is true in regard to the bacteriology. The table which accompanies this report shows the very higii percentage of pure liarillus injUienza: jmeumonias at Camp Devens : again, a similarity with the series at the Chelsea Na\;il Hos|)ital as reporteil i)y Keegan. However, in the Camj) Dcveii> series there were a few cases in which the hemolytic strejitocoecus and the pneumococcus were found, and the.se hnigs presented different gross apj)earances. In a cursory analysis of the Brigham Hospital cases auto])sied (about 30), I find a predominance of hemolytic streptococcus and pneumoco((ii> lungs. Without going into corroborative details at this time, I nniy say that in the gro.ss appearance of the lungs I have laid tniphasis ujion, li. iujiuenzte was the only organism wliirli could be cultivated and I iniliesitatingly associate these distinctive conditions with tiiat organism. In lungs .showing other types of solidification, other organisms were responsililc for the exudation characttrizing the pneumonias. The iicniulytic streptococcus, the staj)hylococcus and the pncumncoccn~. each produces its distinctive picture, the last often that i>\ lobar jtneunionia.

While the bacteriological evidence, based u|irin the assumption that B. iiiflttetizie is the cause of influenza, is very good in support of the stand that there is a distinctive lung lesion in these influenza [>neumonias, the histological sttiily has afforded very definite proof. Early in this study of tlic Camp Devens ca.ses. I recognized the fact, as have others, that a striking type of reaction was present, a condition of acute idveolar emphysema with the deposit of a hyaline fibrinoumaterial on the alveolar walls. The intervening alveoli af


compressed and filled with exudate, which in the early cases is largely serous or bloody, containing but little fibrin. It is this acute alveolar emphy.<ema, with the .-icrous and hemorrhagic exudate, that gives the characteristic gross appearance to the lungs in the early stage of the disease. In order to determine how eounnon this lesion is, I have gone over all of the Brigham Hospital autopsies on influenza cases, and find it to be constant. It may be nuisked by a jjueumococcus or streptococciis exudation or bv extensive hemorrhage, but its presence can always be determineil by the finding of the hyaline fibrin outlining greatly distended air spaces in the lungs. It is the one di,stinctive feature in the ]iathology of influenza i)neumonias. and its constant occurrence is indicative of the entity of the initial lung infection. The interjn-etation of this lesion was not ca.sy. The hyaline fibrin, because of its prominence and the jiixta])osition of cellular exudate, often simulates the outlines of alveoli. As a matter of fact, it outlines cavities filled with air, which may or may not completely fill groups of alveoli. Although alveolar walls in contact with tliis fibrin may be necrotic, tissue elements ])lay no part in its formation. .\ similar hyaline fil)rin was found in two cases of emphysema of the mediastinum where the mediastinal areolar tissues weninfected by ])neumococcus, secondary to ])neumococcus peri<arditis. The jihysical characteristics of this fibrin are determined by its contact with air, and an imiiortant factor is probably the mechanical com|)ression of strands of fibrin i)y air. What is the source of the exudation in the alveoli in these early jmeumonias! The exudation may be ])re.sent in alveoli ^vith intact walls, or walls showing very slight reaction, mainly evidenced by activity of the resjiiratory e])itheliuni. In all cases severe lesions were found in the finest bronchioles, and in the alveolar ducts. The latter show an exudation eompo.-icd mainly of polymorphonuclear leucocytes and small (pnintities of fibrin. The walls are filled with leucocytes, and are often necrotic in places. The intralobular bronchioh's show severe lesions of the mucosa, and it is often po.ssible to demonstrate the source of hemorrhages from cajiillaries. The obvious explanation, and indeed the only possible one from the material at hand, is tliat the major injury is to the bronchial system. and nniinly in the finest bronchioles and alveolar ducts. To secure the degree of cniphysenni ])re,sent it is necessary to assume a valve action of the exudate in the bronchi. Tbe character of the hyaline fibrin de])osit annmd air vesicles and upon the alveolar walls suggests a jiouring of exudation into the alveoli from the bronchioles and alveolar ducts, at a time when air is able to pass. Thus the patient is virtually blowing bubbles in his own lungs, into a medium of exudation relatively poor in fibrin.

The meibanism of interstitial eniiiby.senni formation is easily seen, where tbe greatly distended alveoli are in contact with the pleura of interlobular septa. In tlie.s' locations it is liossiblc to demonstrate ru])turc of the alveolar walls and the direct continuity of fibrinous strand.s, partially filling cleft* dis.sected by the air from alveoli to pleural or interlobular connective tissue. A series of gross .sections and microscopic sections from lungs with interstitial emphysema shows that the air finds the easiest route of exit from the lung in the con


106


[No. 338


iieetive tissue surrounding blood-vessels. It dissects altnig blood-vessels to the hylus of the luug and from there along the great vessels and bronchi into the mediastiuuni, over the j)ericardium into the anterior mediastinum, and upwards along tlie trachea into the tissues of the neck, whence it escapes into the subcutaneous tissues. This subcutaneous emphysema may appear very early, as will be seen by the accompanying chart. The earliest case was seven days from the first symptom, which means, of course, a shorter duration of the lung involvement. The majority of the cases were noted on or after the 10th day from the initial symptoms of the disease.

It must be l)orne in mind in considering the i)atliology of these lungs, that the lesions are not imiformly distributed, and therefore very extensive injury in portions of one or several lobes are compatible with life for a considerable period of time. The bronchial lesions apparently progress, and may extend throughout tlie whole of one or both lungs, producing the anatomical picture of the more chronic cases, that of a panbronchitis with bronchiectases and peri-bronchitis. During this period of extension in bronchi, a number of things may happen to the portions of the lungs first involved. They may become secondarily infected with pneumococcus or stre])tiicoecus, or the Gram-negative diplococcus called by English workers "Diplococcus mucosus." In rare instances Staphylococcus and Friedlander's bacillus have been encountered. Tlie fate of the tissue depends on the nature of the infectingorganism; as, for example, fibrinous exudation with the pneumococcus and abscess formation with the staphylococcus. In a number of instances these portions of the lungs, severely damaged at the onset, did not become secondarily infected ; at least, these lungs have shown only the influenza bacillus at the autopsy, and have undergone extensive organization resulting in cicatrices of large sizes. If we take a series of lungs which have shown only the influenza bacillus in cultures and in sections, we may still have all the stages described exclusive of those with secondary infection, and accordingly we must conclude that the reaction to the influenza bacillus is less intense in the later stages of lung involvement than in the earlier. This is shown best in comparing two lungs from the same ease, where in one lung, iisually the right, we find the severe damage of the early lesion with bronchiectasis ami peri-bronchitis, and in the other kuig a much less intense bronchial reaction, with much less marked peri-bronchitis, or none at all. The involvement of the pleura in lungs infectetl solely with tlie influenza bacillus is very slight. There are hemorrhages into the pleura and perhaps a thin layer of fibrin upon the surface. The amount of fluid in the ])leural cavities was always small, though blood-tinged. Empyema was found in cases secondarily infected with the streptococcus or pneumococcus. The involvement of the pleura may result from the extension of the inflammatory process along the interlobular septa and lymphatics, or, and this I believe is more commonly the case, from bronchiectatic cavities situated close to the pleural surface.

Gangrene of the lung was noted in one of the Camp Devens series in a case showing very extensive bronchiectases, witli bronchiectatic abscesses. Extensive necrosis of the hum- lias


been observed in a number of eases in this same series and at the Brigham Hospital — necrosis due to organisms other than the influenza bacillus.

Organization in the jiure B. infliienzce cases was a common end result. The organization of the exudate begins early, certainly before the 10th day of the disease, and a prominent factor in liringing about this result is, I believe, the plugging of the bronchi with exudation. In patients who had survived three weeks or more there Avere very complicated gross appearances, due to extensive cicatrization of large portions of the lung. The contraction of interlobular septa, due to the avascular organization of exudate, causes marked distortion of the lobules of the lung, and peculiar lines of retraction on the pleural surfaces.

It is not the purpose of the present report to include the whole pathology of influenza. There are a few interesting features in other organs which are worthy of emphasis, howover. Eight of the Camp Devens series showed waxy degeneration of the rectus muscles, and subsequent experience at the Brigham Hospital indicates that it was probably overlooked in some of the earlier postmortems done at Camp Devens. A number of these cases showed rupture and extensive hemorrhage into the rectus muscle. This lesion has been noted in other muscles ; for instance, the transversalis, the internal and external oblique muscles, the latissimus dorsi, the pectoralis major and the intercostal muscles. The testes occasionallv showed minute petechia, but on the whole no striking gross change was observed. Microscopically very striking changes were encountered in nearly every case, nameh', the cessation of activity in the seminiferous tubules; actual degenerative changes were frequently noted, and in late cases beginning fibrous tissue replacement of the degenerated tubules. This lesion of the testes seems to be wholly a toxic one, as there is very little cellular reaction. It is difficult to imderstand why such severe toxic lesions of the muscle and testes should occur, in the absence of effects attributable to toxins in other organs. For instance, the reaction of the spleen is very slight, the heart muscle rarely has shown any gross or microscopic lesion, and in general seems to escape entirely the toxic effect of the disease. Lesions of the adrenal, when extensive, such as hemorrhage, can be attributed to secondary infection, usually tlie hemolytic streptococcus. Minor acute lesions are constantly found in the cortex in influenza cases, but these lesions are similar to those found in manj^ infectious diseases — the disappearance of lipoid +++++ CONTENTS, and focal necrosis with mononuclear phagocytic cell reaction. The head was opened in 20 of these cases. Infection of the middle ears was found in 13. Infection of the sphenoidal sinus in 20, frontal sinus in seven, and of the ethmoidal cells in eight cases. The bacteriology of the sinuses is given in tlie chart. Three cases showed punctate hemorrhages in the cereliral cortex.

BACTERIOLOGY

I do not intend to discuss at length the bacteriology of the

epidemic. The table is a true account of the findings, and I

prefer to have individuals draw their own conclusions. The

opportunities for bacteriological work were particularly good.



THE JOHNS HOPKINS HOSPITAL REPORTS


VOLUME I. 423 pages. 99 plates.

VOLUME II. 570 pages, with 28 plates and figures.

VOLUME III. 766 pages, with 69 plates and figures.

VOLUME IV. 504 pages, 33 charts and illustrations.

VOLUME V. 480 pages, with 32 charts and illustrations.

Thf Maliirial Fevers of Baltimore. l'..v \V. S. Tii.\vi:n. M. 1

.T. Hewetson. M. D. A Study of some Ifatal Cases of Malaria. By Leweli.y

Studies in Typhoid Fever.

Bv WiLi.UJi OSLEE. M. D.. with additional papers liy C. Blcmer. M. P. 

Simon Flexnkh. JI. 1>.. W.vi.tek Keed, M. D.. and II. C. 1'ak.sc -

VOLUME VI. 414 pages, with 79 plates and figures.

VOLUME VII. 537 pages with illustrations.

VOLUME VIII. 562 pages with illustrations.

VOLUME IX. 1060 pages. 66 plates and 210 other illustrations.

Contributions to the Science of Medicine. Iie.licated by liis I'upils tn William IlENiiV Welch, on the twenty lifih


VOLUME X. 516 pages. 12 plates and 25 charts.

VOLUME XI. 555 pages, with 38 charts and illustrations.

VOLUME XII. 548 pages, 12 plates and other illustrations.

VOLUME XIII. 606 pages, with 6 plates, 201 figures, and 1 colored chart.

VOLUME XIV. 632 pages, with 97 figures.

Studies in Genito-Urinary Surgery.

The Treatment of Trostatic Hypertrophy by Conservative Perineal I'rostatectomv. An analysis of cases and results based on a detailed report nf 145 cases. "By HiMH II. YorNR. M. D. ,u t.

Recto T'ri'thril I'i-Jtiil-e 1 le^crintiivn "f New Procedures for their Trevnilinn iihI iiiir I'.v 111 .;ll II ^n^^,;. M. D.

The I'lih hi rn.i-i~ ,i!mI K;Hli.,il I'nir "f iicr.inoma of the Prostate. biMu;:

VOLUME XV. 542 pages, with 87 illustrations,

fwi-lve p,ipii-i on pneiuiuini.i. By liK.s. Cir.iT.tRD. Fabyan. Emeksox.

Mvi:sii\i,i. :MrCiiAE. STEiNER. IlbwAun and Hanes. V sfiii'ly of Uinrrhiea in Children. J. II. Mason Knox. Jr.. M.I)., and

El. WIN II. SCH.iItER. M. 11.

Skin Trini.-i'-hiiil.ition Bv .ImiN Staioe Davis. M.I).

rpidiMiiie (in-br.. spinal Meiiinu-itis and Serum Therapy at The .lohns Ilopkill-^ Ilosiiital. l!v Fi:ank .1. SLALEN. M. 1 1.

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Stndi.<s ill III.' i:xp.'rilii.-iil:il IT.. . In. l inn ..f Tuberculosis


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I till. Prostate Gland or of the

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il'iiations on White Rats. By


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v.-i. iii.r S..111111.11.-. ..! 1.1 r...tii ; I.

C.ii.lili.iii ..r tb.' |.Me» alliT .-lli'li

i;i:..k.:e Walker. M. 1 ). S(alpln._- A.ci.leiits. I'.v .limx Staige Davis. M. D. Db-itnii tion of the Inf.'rior Vena Cava with a Report of Eighteen Cases.

Bv .1. IlAl.I. I'LLASANrs. M. D. . .

IMivsi.doKbal and Pbanii.i.-..l..L-i<aI Studies on Cardiac Tonicity in Mam 

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VOLUME XVII. 586 pages with 21 plates and 136 figures. Free Thrombi and Ball Thrombi in the Heart. By .losBrn II. IlEwiT'r

Benzol as a Ijeucotoxin. P.y Lawrence Selling. M. D. Primarv Cariinoma of the Mvit. Bv Milton C. Winternitz. M. D. The Stati^tiial E\perii.n.e Hatii of Tb.' .Ti.biis lloiikins Hospital. Baltimore. Mil IS'lJ-lllll. By FllKl.KKl.K I,. II..,1MAN. LU D., F. g S.

The iirii.'iii ami I ii-\ .•loi.iii.nt "1 tli.' I.ympbatic System. By Florence It.

Th.- N'u.ri'i Tnbiris I.aterab-s ami the So-called GanRlion Dpticum Basale.

Bv la.wMili F. MA1...M:. M. D. Venous Tln-aiibosis 1 luring My. .cardial Insufficiency. P.y I.'rank .T. Si.aden.

M H .iml Milton c. Winternitz. M. D. lieiikiPinia of the Fowl ; Spontaneous and Experiiiienlal.

SCII.MEISSER. JI. I).

VOLUME XVIII. 445 pages with 124 figures.

Fasciculus I. .\ Stndv of a Toxic Substance of the Pancreas. By E. W.

M D . and (Jeorge Cl.vuk. JI. D. Old Aire ill Belation to Cell-oversrnwth ami Cai

I'ASTIRF :M D. ami <:. B. Wisi.ocki. JI. I). The Eff.-cl i'.r l!..lll..val of til.. S|ile,-n fpon Metabolism in Doss; Pn limiiiarv lieport. Bv .1. II. King. M. D. The FfFcct I'.f Kemoval of the Spleen I'pon Blood Transfusion. By .1. II.

King M II B M. Bernheim. M. D.. and A. T. .Tones. M. D. Studiesoii i'.uathvroid T.'tanv. Bv D. Wright Wilson. M. D.. Thornton

Stearns. M. D.. J. H. .Ianney. Jr.. M. D.. and JIadoe DeG. Thurlow.

Some' Observations on the Effect of Feeding Glands of Internal Secretion to Chicks. By M. C. Winternitz. M. D.


llAURV C.


By E. W. GooD


Spontaneous and Experimental Leuksemia in the Fowl. Bv 11. C.

SCHJIEISSEli. M. D.

Studies on the Relation of Fowl Typhoid to Leuksemia of the Fowl. By

M. C. Winternitz. M. D.. and H. C. Schmeisseb, M. D. Hyaline De,i:eiierati..n ..f tbi- Islands of Langerhans in Pancreatic Diabetes.

By M. C. WlNTLKNlTZ. .\I. D.

Generalizeil .Miliary riibir.ub.sis Resulting from I5xtension of a Tubercular Pericar.Iitis Int.. the Itigbt Auricle. By M. C. Winternitz. M. D.

Acute Suripurativr llypi.pbysitis as a Complication of Purulent Sphenoidal Sinusitis. Bv T. It. Bo.ais. M. D.. and iM. C. Winternitz. M. D.

A Case of Pulmonary .Moniliasis in the United States. Bv T. R. BoGGS. .M.D.. and M. C. Pincoffs. M. fl.

Gaucher's Disease (A Report of Two Cases in Infancy). By J. II. M. Knox. M. D.. II. R. Waul. .M. D.. and H. C. Schmelsser, il. D.

A Fatal Case of Multiple I'rimary Carcinomata. By E. D. Plass. M. D.

Congenital Obliteration of the Bile-ducts. By James B. Holmes. M. D.

Multiple Abscesses of the Brain in Infancy. By James B. Holmes, M. D.

Gastric Carcinoma in a Woman of Twenty-six Years. Bv R. G. HussEY,

.I. D.

Subdiaphragmatic Abscess with Rupture Into the Peritoneal Cavity Following Iniliiii'd Pneumothorax for Pulmonary Hsemorrhage. By' R. G. IlrssKv. M. II.

Heart Block Caused by Gumma of the Septum. Bv E. W. Bridge.man. -M. D.. and H. C. Schmeisser. M. D.

Analysis of Autopsy Records.

A. The .Johns Hopkins Hospital. I Table Showing Percentage of

Autopsies. I

B. Th.. City Hospitals. Bay View. iTable Showing Percentage of


on the Staff of the Department of Pathology.


"The .Mon.lay d (""linical Uepri'seii Donation.

Fasciculus II. The ROIe of the Autopsy in the Medicine of To-day. Bv M. C. Winternitz.

M. D. Exp.riin.-nt.il N.'i.liii.pathy in the Dog. Lesions I'rodnced by Injection

..I /;, Ijiniiiliisi plii'iin into the Renal Artery. By M. C. Winternitz.

-MI... ,111.1 WllllAM c. (JriNBY. M. D.

Mesaitiritis ,.r lb.. Pnliminary Artery. By M. C. Winternitz, M. D., and

II. C. Schmeisser. M. D. A Clinical and Pathological Study of Two Cases of Miliary Tuberculosis of

the Choroid. By Robert L. Randolph. M. D., and H. C. Schmeisser.

M. D. The l!bi..il-vess.-Is of the Heart Valves. Bv Siamioff I', v \ m. .Ii.nes. M. D. Equilibria in Pir.ipitin Keaitions. Bv Stanii.hi 1'.a\\i .I..\fs, M. D. Car.iii..ma ..f 111.' I'leura with ITvpertrophic ( ki . ,,;i 1 1 In ..jij 1 h v. Report of

a Case with a Des.ription of the IIist..l..::v ..1 th.- I'.oii.. Lesion. By

STANH..1.F P.AVNE-J.INFS. M. II.

The InteiT.lation of the Siiiviving Heart and Pancreas of the Dog in Sugar

Metabolism. P.y ADM..\r II. Clark. M. D. Congenital .\tri'sia of the I'^sopbagus with Tracheo-Esophageal Fistula

Associated with Fused Kidney. A Case Report and A Summary of the

Literature on Congenital Anomalies of the Esophagus. By E. D.

Plass. M. D. Ectopia Cordis, with a Report of a Case in a Fifteen-Month-Old Infant.

Bv Jami:s p.. Holmes. .M. D. Studies in th.' M.^ihanism of Absorption from the Colon. By Sami-el

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Carcinoma of the Uterus. Bv V. X. Leonard, M. D., and A. B. Davton.

JI. D. The Relationship in Typhoid Between Splenic Infarcts and Peritonitis

T'nassociated with Intestinal Perforation. By A. B. Dayton. M. D. Left Duodenal Hernia. Bv A. II Davl.n, M. D.

Hist..l..gi.:rl a^ K.l.i t .'.l t.. I 'In si..li .L-i. ii I an. I Chemical Differences in Certain -Mils, l.s ..f the Cat. Pv II IIA^s Billard. M. D. A Method of cb.arins Fr.iz.'n s.,li.ln^. I'.v H. Hays Billard. M. D. On the Occurrence ami Signiti.am-.' of Fat in the JIuscIe Fibers of the

Atrio-Ventri.'ular Svstem. P.y H. Hays Billarii. :M. D. Studies on the .M.^talmlism ..f C'lls in ritrn. 1. The Toxiiaty of a-Amino Acids for Einbyonii- Chiikeii Cells. By .Montrose T. Burrows. M. D..

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.M. D. The Oxvgen I'ressure Necessary for Tissue Activity. By Montrose T.

BiRROws. M. D. The Fiincti. iial Relation of Intercellular Substances in the Body to Certain Stru.tures in the Egg Cell and Unicellular Organisms. By

Montr. >si: T. ItcRKOws. M. D. Studies on th.' Gr.iwth of Cells iji ritro. The Cultivation of Bladder an. I

Proslat.. Tumors iiuisi.l,- the Bo.lv. Bv Montrose T. Bfrrows. M. D..

J. EnwAia. Ill iiNs. .M. Ii., ami Y..S111.1 SrziKL. M. D. The Stndv of a Small Dutl.reak ..f P.. Ii.. my. litis in an Apartment House,

Occurring in lb.' Coiirs.' of an Fi.i.l.iiii. ill a Large City. By Montrose

T Bliiiiows. M. D.. an. I I:i.»m:i.^ .\, I'akk. M. D. Papilloma of tbi. I.aivnx. i;rii..ii ..1 a Ca-.e Treated with Radium with

Resultant Chronic Diftiisi' I by n.i.lii is. By William C. Duffy. M. D. Analysis of Autopsy Records. Autopsy Statistics.

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The Effect of Diet on the Healing of Wounds. (Illustrated.) The Effect of Different Bloods on the Growth of //. Inftucn^n.

By Admoxt H. Clark. M. D 117 (Illustrated.)

Bv T. M. KivERS. M.D.. Haltimor.-. Md 129

The Relation of Spontaneous Nephritis of Rahbits to Experi- ".

^ , , ,1, » i J Observations on the Clinical Pharmacolofjv of DiKitalis. (Illus mental Lesions. (Illustrated. I •, fe. o v

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By Artiiub L. Br-ooMFiELD 121 ' „ .. . . ..

' By Alfred M. \\ EDO, M. D., Pittsburgh, I'a l.U

A Sketch of Dr. Lyman Spalding. N'otes on New Books 1;16

By Henry M. Hurd, M. U 123 Books Received 139


THE EFFECT OF DIET ON THE HEALING OF WOUNDS


By Admoxt (From the Pathological Laboratory of

The work uf lluojur and Whipple' on blood regeneration after anseniia .-jIiow.* that .;pecifie diets produce a very markcil effect. The rate of blood regeneration on a meat diet is very rapid, a matter of ilays or a few weeks ; whereas, on a diet rich in carbohydrate it is very slow, months being .sometimes required for coni])lete regeneration. Tliese results suggested the possibility that specific diets mi;,'ht influence the rate of wound healing and the following experiment.-; were accordingly underUikcn.

Carrel '• ' has studied the process of wound healing in both men and animals and has found that the curve representing thediminution in size of an aseptic wound while it is cicatrizing is regular and geometric. From Carrel's curves Du Xoiiy " has derived mathematical formula?, by means of which the area of a wound at any given date can be predicted. Ilis formula; arc :

S-S'

(1)

(VI




• The experiments reporte<l in this paper were carried out b.v Dr. Clark during the spring of 1918. Owing to Dr. Clark's death the results which they show are of a preliminary nature and represent incomplete work. I thought tliem. however, of sufficient interest to publish, hoping that they might suggest further work along the same line. — Janet Howell Cl,\rk.


II. Clark. M. D.

Thr Johns Hopkins i'niversitj/. Baltimore)

S represents the original area of the wouml. S' — area i days later.

T = time from first observation and — I'm ( 1 ). <' = time from .S" to S" .

i=constant coefficient which is ciiaracteristic of the womid and which varies with the size of the wound and the age of the jiatient. After calculating i from (1) S" can lie jiredicted with a remarkable degree of accuracy, any deviation from the calculated curve showing the |)resence of an infection.

In his e.\i>erinicntal work on animals'-' (dogs, guinea-pigs and cats), where the wounds were kept as sterile as possible. Carrel found the process of cicatrization ta be divided into four part.s:

(1) Quiescent I'l-riml. — During this period tlicrc is no contraction and the main characteristic of tiie period is its variable length, I-.") days.

(2) Period of Granulotis Contraction. — During this jieriod the wound contracts at a rate wiiich is jiroportional to tiie size of the wouiul.

(3) Period of ICiiidermizalinn. — Tiie epithelium iicgins to form and the process of healing may now continue by epidermization alone or by epidcrmization and contraction together.

(4) Cicatricial Piriml. — .\<Ut thr wound is healed the scar enlarges.


118


[Xo. 339


No previous work on the effect of specific diets on wound healiug has been reported.

EXPERIMENTAL METHOD

Twelve dogs as nearlj' the same age, size and general condition as possible were cliosen and three were put on each of the following diets :

(1) Mixed Diet. — 41 gm. of fat (lard or butter) and 107 gm. of lean meat (beef or liver) were boiled together, then mixed with 354 gm. of bread and run through a meat chopper. This was divided among three dogs.

(8) Carbohydrate Diet. — 500 gm. of bread moistened with water were divided among three dogs.

(3) Protein Diet. — 500 gm. of lean meat, either round of beef or liver, were boiled and divided among three dogs.

(4) Fat Diet.— 300 gm. of fat (equal parts of butter and lard) were boiled and groimd with 100 gm. of bread.

The dogs were fed on these diets for three days before the wouuds were made. Throughout the experiments the dogs were weighed and the weight was found to remain practicallv constant.

Preliminary experiments with various types of dressings showed that the wounds healed better and showed less tendency to infection when left entirely open with no dressing of anv' kind. The dogs were given ether anaesthesia, the backs were shaved and two circular skin flaps (one large and one small) were removed from each side of the back. The wounds were placed where the dog could not lick them and were left open. As soon as they were made, the size of the wounds was traced on a piece of transparent celluloid with a wax pencil and similar tracings were made at intervals of three or four days throughout the experiment. These areas were copied on heavy tracing paper and measured in square centimeters by means of an Amsler polar planimeter. If a wound showed marked infection the results were discarded.

A second set of wounds was made after the first had healed and finally a third set in which the dogs were interchanged in diets.


I. Effect of Diet on }Yound Healing. — The results for Sets 1 and II are averaged in Fig. 1. The large and small wounds are averaged together; the area given being the total wouml area on one dog (i. e., the area of two large and two small wounds). As there were three dogs on each diet in each set, each curve shows the average result on six dogs. Tlie diet seems to aiiect the length of the quiescent period. The \m>tein-fed dogs have no quiescent period, the contraction beginning at once. The carbohydrate dogs have a quiescent period of three days, those on the mixed diet, of four days, and the fat-fed dogs, of six days. After the sixth day the curves run parallel and the dates of final healing differ by the same amount as the lengths of the respective quiescent periods.

The diet, therefore, is a factor in determining the date of the beginning of Period II, the period of granulous contraction.


In Set III, four dogs which had been on a fat diet in Sets I and II were put on a protein diet. The results sho^^n in Fig. 2


c

V

r

10


"X \

« 



\ \



\\J


^






M t




\


\!^






r





\^


^





< u

n 5





\



!^


^^^^^^




HAYS


3


t


q


la


p

15


« 



Fig. 1.— Effect of Diet on Wound Healing.

Average results of Sets I and II.

C = carbohydrate diet.

P = protein diet.

M = mixed diet.

F = fat diet.

Abscissae = time in days; ordlnates :


wound area In sq. cm.


give the same result as Curve I, though not so markedly as might be washed. I believe that there should have been an


T P


\~ S


\


\ t


1

1 tj





\ 1






0




\


\









\


\,


\


^^->- T




SAYS o


3


t


1


1%


1*


l« 


3(


Fig. 2.— Effect of Change in Diet.

Curve F gives results for fat- fed dogs in Sets I and II.

Curve P gives results for same dogs fed on protein diet in Set III.

Abscissae = time in days: ordinates = wound area in sq. cm.


interval between the two sets of experiments during which tli dogs could be fed on the new diet. In this experiment Set 1 1 i


Mav, 1919]


119


was begun as soon as Set II was finished and the change in diet was simultaneous with tlie making of new wounds.


c



^





AHEA

Anr»

AMD


WOUND MOUND

St»K



X



c



\ ^


\







fc




\\v


^~.






r

H U





v


^


"~"-~

-.^




xn a, ?





K


\


S


^^^

->



<





\


\J



>^




HAYS

e


3


c


<?



f^


ir


Mi: T

IT


a/


Fig. 3. — Curve Showing Formation of Epithelium.


area of wound and scar.

area of wound.


Abscisss — time in da.vs: ordinates = wound area in sq. cm.

Ill Fig. 3, the pmgri-s.s of Period III. the period of epidermization, is shown, the dotted line indicating the area of the wound and the scar, the heavy line the wound area.

It is evident that the formation of the epithelium starts on the same day, irrespective of the diet and the size of the wound.



%







  • n


p. V..O Ik VtOUH




i


\


T^ *

1


X \



VL



XT





r.



1


V X




/


.-ATo;;







\


"



/





S




S


\ »A^a

-♦


"



lo


IT





Fio. 4. — Average Curve for Sets I ami II (all Diets).


area of wound and scar.

area of wound.


Abscissa- = lime in days: ordinates = wound area In sq. cm.

Contraction continues throughout Period III and tlie closing of the wound is due to a combination of the two factors, contraction and epidermization. The dotted curves giving tinarea of wound and .<car are parallel, showing that diet has no


effect on either the date of beginning of Period III or the course of epidermization. The difference between the two curves gives the area of the epithelium.

In Fig. 4 an average curve is given for all four diets (Sets I and II), showing the course of all four periods of wound healing. It shows that contraction continues all through the period of epidermization and even for live days after the wound is completely healed. At this point the formation of jiigment begins at the outside edge of the scar and as the pigmentation moves inward the scar rapidly enlarges until the pigmentation is complete, when it reaches a stationary state.

It would be interesting to compare this fourth period in animals with different degrees of pigmentation and determine the exact relationship l)etween the formation of pigment and the scar area. Carrel ' says that the expansion of the cicatrix after the wound is healed is less marked in man than in the 



^






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^


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Ir 1-^


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i;. 5. — Results of Sets I and II Averaged Separately for Large and Small Wounds.

Curve if = mixed diet.

Curve C = carbohydrate diet.

Curve P — protein diet.

Curve F = fat diet

Abscissa* = time in day.s; ordinates = wound area In sq. cm.


(log. If the expansion is conditioned by the formation of the ])igment this would naturally result.

II. Effect of Size of Wounds on Ckatriznlion. — Carrel' has already shown that tlie rate of contraction is proportional to the size of tlie wound, but tliat tbe rate decreases le.ss rapidly than the area, .«o that large and small wounds tend to become equal. Fig. 5 shows the results in Sets I and II averaged for large and small wounds separately for all four diets. In every case the curves siiow tiiat the rate of healing in large wounds is greater, so that tbe wounds heal in the .same length of time. The rate of healing as measured by the change in area per day is not, however, proportional to the size of the wound on any one day. For example, take


120


[No. 339


Fig. 5 (C). The area of the small wound is 2 sq. cm. on the fifth clay. At this time the rate of healing is .10 sq. cm. i)ev day. The area of the large wound is 2 sq. cm. on the teutli day when the rate of healing is .35 sq. cm. a day. However, if tlie rates throughout each set of curves are compared it will lie found that the ratio

rate of healing of large wounds rate of healing of small wounds on any given day is approximately equal to the ratio

original size of large wounds original size of small wounds

if the quiescent period is neglected (see Table I). So that, knowing the rate of healing of a wound of any given size, the rate of healing of a womid of any other size can be calculated. However, this probably would hold true only within certain limits of the original size. In these experiments the wounds are all relatively small.

TABLE I





Bo





Day


S, _ or


ginal size large wounds


Rate healing


Bi 1 , Rate healing ;i„x V='^i large wounds ^=



Sj original size small wounds


in square cm.






per day




M


.3-6



1.7


.04


.11


.07



fi-9




.16


.30


.27



9-12




.20


•33


.34



12-15




.13


.23


.22


P


3-6



1.7


.08


.13


.14



6-9




.16


.23


.27



9-12




.20


.40


.34



12-1.')




.l.T


.23


.25


C


3-6



1.8


.07


.12


.12



6-9




.20


.30


.36



9-12




.17


.32


.31



12-1.5




.17


.23


.31


F


3-6



1.7



.08




6-9




.36


.52


.61



9-12




.26


.33


.44



12-15




.10


.17


.17


The results for F are poor, but for the others are fairly good. If this fact has any general application and can be extended to the interpretation of womids of any size it would mean that the rate of contraction is governed by a variable factor depending on its age and a constant factor depending on the original size.

In comparing the curves for different diets in Fig. 5 it is seen that the effect of the diet on the length of the quiescent period is greater in the small than in the large wounds.

Xejtlier the diet nor the size of wounds has any effect on the time of beginning of Period III. The formation of the epithelium starts about the ninth or tenth day in every case. The amoimt of contraction subsequent to this depends on the size of the wound when the epidermization begins. The contraction and epidermization complete the healing together. The size of the sear when complete healing has taken jilace is about ihe same in every case, and equals approximately onequarter the size of the original wound.


DISCUSSION

In connection with these results it is interesting to consider the well-known fact that the ingestion of proteins produces a much greater increase in body metabolism than that of any other foodstuff's. In a recent monograph on the subject of the stimulating effects of nutrients, Benedict and Carpenter " have given a very complete report of this question. They find that while carbohydrates give a maximum increment to the metabolism of 25 per cent and fats 12 per cent, this increment occurs within two hours and the metabolism then returns rapidly to the base line. With proteins the increment reached a maximum of 25 per cent to 45 per cent and persisted for as long as 8 to 12 hours. This increase in metabolism, or excess energy given off by the body as a result of the ingestion of food, may be regarded as waste energy, but Benedict suggests that we may consider the extra heat developed under these conditions as a normal physiological stimulus to cellular activity. Practical experience with heavy muscular work on protein and carbohydrate diets points to this conclusion and the results reported here would certainly support the idea that proteins have a specific influence in stimulating the whole cellular system to greater activity.

CONCLUSIONS

The length of the quiescent period of wound healing is affected by the diet. It varies from zero in protein-fed dogs to six days in the fat-fed animals. This variation in the quiescent period is more marked in smaller wounds. As a consequence, the date of final healing differs by about five days for the protein- and fat-fed dogs.

When the second period, or period of contraction, has set in the rate of contraction is not affected by the diet. It is governed by a variable factor depending on the age of the wound and by a constant factor proportional to the original size —




^ = -^when Rj and /?„ = rates


if healing of large and small


wounds and S^ and .S\ = original areas of these wounds.

The beginning of Period III, the period of epidermization, is independent of the size of the wound and the diet. It is determined by the age of the wound. Contraction and epidermization continue together until the wovnid is entirely healed.

After the wound is healed the scar continues to contract until pigmentation sets in. During this latter process it enlarges and reaches a stationary state after pigmentation is complete.

REFERENCES

1. Hooper, C. W.. and G. H. Whipple; Amer. Jour. Physiol., 1918, XLV, 573, 576.

2. Carrel, A.: Jour. A. M. A., 1910, LV, 214S.

3. Carrel, A., and A. Hartman: Jour. Exp. Med., 1916, XXIV, 429.

4. Du Noiiy. P. L.: Jour. Exp. Med., 1916. XXIV, 451: 1917, XXV, 721.

5. Benedict, P. G., and T. M. Carpenter: Food Ingestion and Energy Transformation. Carnegie Inst., Wash., 1918.


May. I'Jlii]


121


THE RELATION OF SPONTANEOUS NEPHRITIS OF RABBITS TO

EXPERIMENTAL LESIONS*

By AuTiiiu L. Bloomkield {,From the Medical Clinic. The Johns Hopkins University and Hospital)

into the renal nrterv tliroujrh a fine needle. During the injection tlie kidney became mottled or blanched, but the normal color ])roni|)tly returned. Bleeding from the punctured artery was slight, and stopix-d when the kidney \va.< put back into the abdominal cavity. The wounds were closed with catgut and healed by first intention. In a few instances total or partial infarction of the kidney resulted from an arterial thrombus, but in most cases at autopsy the vessels were jiatent and there were no gross signs of circulatory disturbance.

After, two weeks a series of intravenous injections was begun with the organism previously used. The size of the dose and the interval between injections varied with the animal's reaction. The injections were regulated in such a way that the animals lost weight and seemed ill. In diilerent experiments from 1 to 19 re-inoculations were made over periods varying up to 15 months. Frequent urine examinations were made throughout the experiment, and in a few cases 'thallein tests were done.

Most of the animals died of cachexia and toxemia ; the remainder were sacrificed. Gross specimens were preserved, and blocks were fixed in formalin, embedded in paraffin, cut, and stained with hematoxylin and eosin.

Si.x strains of strejitococci were used : strains Q and Y were avirulent, long-chained green streptococci isolated from urine: strains T and S were hemolytic varieties obtained from septic infections and were highly virulent for rabbits; strains A and R, isolated from tiie throats of scarlet fever patients, were markedly hemolytic and virulent for rabbits. In the initial injections into the renal artery from 0.5 to 1.0 c. c. of a thick .saline suspension of organisms grown for 24 hours in meat infusion broth and killed by heating for half an hour at 60 to 70° was used. The charat'ter of the emulsion was such that most of the bacteria were filtered out by tiie kidney. This was controlled by microscopic examination of a few kidneys removed shortly after the injection. Living 24-hour cultures were employed in the intravenous reinjections.

EXPERIMENTS A single protocol of a typical experiment is givin m detail I in Table I ; the remainder are summarized in Table II.

Taiii.k I. — DhrTAii.Ki) Photocol of a Complete Exi-kkimknt No. 51. White male rabbit

March 1. 1916. Weight 1580 Km. Trine clear.

March 2. Left kidney exposed llirouKh lumbar Incision. It Is of normal size an'l consistency, but there are many shallow depressions on the surface, varying In size up to 2 mm. In diameter. Growth from 0.5 c. c. broth (24hour) of strain S (killed) Injected into renal artery. During injection, yellowish blotches appeared over entire kidney, except the lower pole and anterior surface.


During the past few years an extensive literature has accumulated, dealing with the experimental production of renal lesions. A variety of injurious agents has been employed, among which may be mentioneil cytotoxic sera,' cantliaridin,' foreign proteins,' uranium nitrate,' bichloride of mercury,' tartrates,' diphtheria toxin,' anesthetics," and a variety of bacteria, such as streptococci,' staphylococci," colon bacilli," Friedliinder bacilli," and others. Although lesions of various types have been obtained, many of them specific of the particular poison employed, it has not been possible adequately to reproduce a condition corresponding clinically or anatomically with advanced types of chronic nephritis in man. The work of Faber," who was able to produce arthritis in rabbits with great constancy by injecting streptococci intravenously .some time after a preliminary intra-articular sensitizing inoculation with the same organism, suggested the employment of a similar procedure in the attempt to produce experimental nephritis. It was thought that a preliminary injection of bacteria in relatively high concentration directly into the renal artery might sensitize the kidney in such a way that subsequent small repeated intravenous injections might result in renal lesions of a chronic type. Coulter and Pappenheimer" employed a somewhat similar method. Working with rabbits, they gave a series of intravenous injections of an extract of typhoid bacilli, and two weeks later injected the same material directly into the renal artery. To avoid possible confusion with " spontaneous lesions," attention was confined to the acute lesions, and the animals were killed after 48 hours. Scattered focal glomerular lesions, similar to tho.se described in bacterial endocarditis, were found. In the unsensitizcd animals these changes were either very slight or absent.

The following experiments are re|)orted because they represent an attempt to produce chronic renal disease by a method different from those previously used, and because it was possible accurately to control the significance of " spontaneous lesions " by direct inspection of the kidney at the beginning of the experiment, as well as by later examination at autopsy.


Healthy rabbits weighing from 1000 to 2500 gm. were used. After a preliminary urine examination,! the animal was anesthetized with ether and the left kiilney delivered through a lumbar incision. The vessels were stripped free of fat and connective ti.«suc and the bacterial suspension wa,< injected


• These experiments were carried out during the winter of 19151916, at the suggestion of and in collaboration w^lth Dr. Theodore Janeway. Publication has been unavoidably delayed.

f The urine was obtained by massaging the abdomen over the bladder.


122


[No. 339


March 3. Animal in good condition. Urine contains albumin, granular casts and a few R. B. C.

March 4. Urine clear.

March 6. Urine clear. Weight 1550 gm.

March 16. Growth from 1/20 c. c. 24-hour broth culture strain S (living) intravenously.

March 17. Urine clear. 1/20 c. c. (S) intravenously.

March 18. Looks sick. 1/10 c. c. (S) intravenously.

March 20. Urine clear. 1/10 c. c. (S) intravenously. 1490 gm,

March 22. Urine clear. 1/10 c. c. (S) intravenously. 1450 gm.

March 27. 1430 gm.

March 2S. 1/20 c. c. (S) intravenously.

March 30. 1350 gm.

April 5. Urine clear. 1390 gm.

April 8. Urine clear. 1/100 c. c. (S) intravenously. 1470 gm.

April 10. Urine clear. 1/100 c. c. (S) intravenously. 1490 gm.

April 11. 1450 gm.

April 12. 1/lOQ c. c. ( S ) intravenously.

April 17. 1/100 c. c. (S) intravenously.

April 19. 1400 gm.

April 22. 1/100 c. c. (S) intravenously.

April 24. 1350 gm.

April 25. 1/lOOc.c. (S) intravenously.

April 28. 1/lOOc.c. (S) intravenously. 1300 gm.

May 2. Urine clear. 1/100 c. c. (S) intravenously.

May 3. Urine clear.

May 6. 1/100 c. c. (S) intravenously. 1360 gm.

May 9. 1/100 e.c.(S) intravenously. 1320 gm.

May 11. 1/lOOc.c. (S) intravenously.

May 14. Urine clear. 1/100 c. c. (S) intravenously. 1300 gm.

May 15. Animal killed. Autopsy: General condition good. A few parasitic cysts of omentum. Heart and lungs normal.

Left kidney: Weight 5.0 gm. It is loosely adherent to region of scar without new formation of vessels. Capsule moderately thickened (post-operative), but strips freely. Same degree of surface pitting as seen at operation. Consistency seems normal. Cortex of normal width, markings distinct. Glomeruli appear as red dots. Intermediate zone separated from cortex by an irregular, grayish-yellow line about 1 mm. in thickness. Medulla rather pale. Microscopicallp: A good many small scattered areas of round-cell infiltration are seen. In some places there is a beginning fibrosis which causes the cortical depressions. The lesions are focal and interstitial. The glomeruli look normal. The vessels and tubules are normal except where Involved in the scars.

Right kidney: Weight 5.0 gm. Gross and histological examination similar to that of left; same degree of scarring. Renal vessels patent on both sides.

, RESULTS Apart from the " spontaneous nephritis " described below, no definite lesions were found. The glomerular, tubular, vascular and interstitial structures differed in no way from those of untreated controls. This result was unexpected in view of the direct and intensive injury, the constitutional reaction of the animals and the e\idence of at least transient renal irritation furnished by the appearance of albumin, casts or blood in the urine after some of the injections. Pappenheimer, Hyman and Zedman " studied rabbits' kidnej's removed at short intervals after the injection of streptococci into the renal artery. They found that the organisms were rapidly disposed of by leucocytic and fixed cell phagocytosis, with return of the glomerulus to normal. An overwhelming bacterial injury, on the other hand, led to immediate partial or complete disorgani


zation of the glomerulus by thrombotic or suppurative processes. This is possibly the explanation of the difficulty of producing experimentally a gradually progressive process such as that seen in the subacute or chronic glomerulonephritis of man. In our animals, despite repeated injections, the immediate injury was apparently promptly repaired without the initiation of an advancing lesion.

SPONTANEOUS NEPHRITIS

In connection with attempts to produce experimental nephritis, many writers refer to the difficulty of interpreting lesions which occur spontaneously in the kidneys of various animals, such as the rat," dog " and rabbit. Spontaneous rabbit nephritis has been recently described by Le Count and Jackson," who summarize the literature on the subject. Such lesions were found in many of our animals and correspond with those pictured in previous reports (Figs. 1-10).

Every grade of change from accumtilations of a few round cells between the tubules to extensive scars was seen in one or another of the specimens. On gross examination, the earliest forms of lesion appear on section as streaks about 1 mm. wide, slightly more yellowish than the normal kidney substance running from the base of the intermediate zone to the surface. At this stage there is no corresponding depression on the cortical surface, but the lesion is shown by a mottling of the kidney over it. With more advanced disease there are very slight depressions, and in extreme cases a coarse pitting which may affect the entire renal surface. These depressions vary in size from minute dents up to pits 2 or 3 mm. in diameter.

Microscopically, the earliest lesions appear as collections of a few round cells in the interstitial tissues between the tubules. The latter show granular degenerations and the cell boundaries and the nuclei become indistinct. Later the remains of the tubules may be seen between dense collections of round cells. The next stages show the presence of new connective tissue, wMch finally may take the form of scars which contract and distort the tissues. The tubules may be greatly dilated and contain detritus or casts. The glomeruli, as a rule, show relatively little apparent change, even when the intervening tissue has been largely destroyed. In some eases there is marked fibrosis about the capsule, htit the glomerular structure shows no definite alteration. Finally, the glomeruli may also disappear in the scar. The individual lesions may be large or small, they may be abundant or widely scattered, and they are located in cortex or in medulla. They are always distinctly focal, however, with normal intervening tissue, and are never diffuse, as in the contracted kidney of human nephritis. It seems probable that the lesion is a reaction to an injury which is not primarily interstitial.

In reviewing the reports on experimental rabbit nephritis, it is striking that many of the lesions described correspond in detail with these spontaneous lesions, thus raising the question of possible misinterpretation of the findings. An attempt was made in these experiments to control the significance of these lesions by careful inspection of the kidney for scars at


May, 1919]


123


the beginning of the experiment when the renal artery wa:injected, comparing its appearance with the later autopsy findings. It was also possible to compare the left kidney, which was directly treated with a large dose of bacteria, with the right, which was affected only by the smaller intravenous reinjections. These findings are summarized in Table III.

In all but four of the 16 animals the appearance of the kidney at the end of tlic experiment was exactly like that seen


at the preliminary operation. In these four animals, periods of 161, 25T, 352 and 4C0 days had elapsed since the beginning of the experiment, so that it is probable that the sliglit focal lesions which were similar to those seen in mitreated controls had developed spontaneously. The duration of the other 12 experiments varied from 8 to 74 days. In all of these animals in which tlic kidney had been smootli at the start no lesions were found later at autops}-, and where the kidney had


TABLE II.— SUMMARY OF RESULTS OF EXPERIMENTS


Brown (emile..


Brown male. Weight 251(


While mile. Weight 1420


Black male. Weight 1600


Brown hare. Weight 1990 gm.


Brown hare. Weight MM gm.


Dec. 8, 1915. Injection into left renal arter>' of growth from 5 c. c. of broth in 0.5 c. c. salt sol. of strain Y (killed).

Dec. 30, 1915-Mar. 13. 1917. Six intravenous injections of strain Y (living).


Dec. 13, 1915. Injection into left renal artery of growth from 5 c. c broth in 0.5 c. c. salt sol. of strain Y (killed). •

Dec. 24. 1915-Feb. 8, 1916. Six intravenous injections of strain Y (living).


Occasional trace of albumin in urine after injections. Condition goud except for lo^s of weight after injections.


.\ 1 b u m i n ir urine at times after the injections. Moderate loss of weight.


into left renal artery of growth from 1 c. c. broth in 0.5 c. c. salt sol. of strain Y (killed). Dec. 27, 1915-Jan, 28, 1916. Five intravenous injections of strain Y (living)

Dec. 14. 1915. Injection into left renal artery of growth from 5 c. c. broth in 0.5 c. c. salt sol. of strain Y (killed).

Dec. 27, 1915-.\ug. 29. 1916. Seven intravenous injections of strain V (living).

Dec. 22. 1915. Injection into left renal artery of growth frt)in 3 c. c. broth in 0.5 c. c. sail sol. of strain T (killed).

Jan. 5, 1916-Jan. 22 1916. Three intravcn ous injections o strain T (living).


Killed Mar. 13, 1917, 460 days from beginning of experiment. Both kidneys look normal except for few slight surface depress i o n s. Microscopi 

call]/: Glomeruli

normal; moderate spontaneous lesions iq. v.).

Killed Feb. 8. 1916, 61 days from beginning of experiment. Right kidney normal. Infarct of left except for lower pole. Microscopically: No lesions except the infarct.


Dec. 14. 1915. Injection [Steady loss of Died Jan. 20, 1916, 44 days from beginning of experiment. Both kidneya normal in g' r o 8 8 and microscopically.


Loss of weight Killed .\ug. 29, 1916.


after each ii jection. .\ftei sixth injcc tion, albumin and R. B. C, in urine (oi two days.


Steady loss of weight, bumin and casts in urine for five days after last injection.


Dec. 22. 1915. Injection into left renal artery of growth from 3 c. c. broth in 0.5 c.c. salt iol. of strain T

i (killed^

tJan. 5. 1919-Jan. 20.

I 1916. Four intravenous injections of strain T (living).

lUar. 2, 1916. Injection into left renal artery of growth from 0.5 c. c. broth culture in 0.5 c. c. Halt ftol. of Rtrain S (killed).

Mar. 16. 1916-May 14. 1916. 17 intravenouA injections of strain S (Hiring).

I

.Mar. 2. 1916. Injection into left renal arterv of .25 c. c. culture S (killed) in 0.5 c. c. •lalt sol. lar. 16. 1916~May 14. 1916. 17 intravenous intertions of strain S (living).


Stead;r loss ofloied Jan. 23. 1916. 32


weight, bumin after first Injection. Albumin, casts and R. B. C. for one day after fourth injection.


k-eight. Tran sicnt albuminu r i a following some Injections.


days from begin of experiment. IV-th kidneys show markr<l grade of sponlanpnu' Interstitial lc<<{on<^. Otherwise normal.


257 days from begi ning of experiment. Both kidneys normal in gross and microscopically, except for a very few lesions of spontaneous nephritis.


Died Jan, 22. 1916. 31 days from beginning of experiment. Both kidneys normal in


days from beginning of experiment. Both kidneys show marked h[Nintiineous interstitial lesions. Otherwise normal in grotis and microscopically.


Killed .May 15. 1916. days from beginni of experiment. B* kidneys show mo<l ate grsde of upontji ous inten«litinl sions. Otherwise n nial.


Steady Iom of Killed May 16. 1916. ~\


DescriptioD


Brown female. Mar. 20, 1916. Injection Steady loss of Weight 1250 I into left renal artery weight, gm. I of growth from .25

I c. c. broth in 0.5 c. c. [ , salt i^ol. of strain S

(killed). Apr. 4, 1916-May 4, 1916. 13 intravenous I injections of strain S I (living).


Brown female. Mar. 20. 1916. Injection Steady loss Weight 1020 into left renal artery weight, gm. of growth from .""

c. c. broth in 0.5 c. ' salt sol. of strain I (killed). I

I Apr. 4, 1916-Aug. 29, 1916. 15 intravenousj iivjcctions of strain SJ (living).


Brown female. Mar. 20, 1916. Injection Loss of weight Weight 1260 into left renal arter>- after injecgrn. uf growth from .25

' c. c. broth in 0.6 c.c. salt sol. of strain S t (killed).

Apr. 4, 1916-Mar. 7, I 1917. 16 intravenous injections of strain S (living).


JIale. Weight Mar. 25. 1916. Injection

1080 gm. into left renal artery

I of growth from 0.6

c. o. broth in 0.6 c. c.

salt sol. of strain R

(killed).

Apr. 8, 1916-June 15.

1916. 14 intravenous

' injections of strain R

(living).

Male. Weight Apr. 1, 1916. Injection 1090 gni. I into left renal artery

of growth from 0.6 c. c. broth in 0,5 c. c. salt sol. of strain R (killed). Apr. 15. 1916-May 19. 1916. 10 intravenous injections of strain H (living).

Apr. 1. 1916. Injection into left renal artery of growth from 0.5 c. c. broth in 0.5 c. c. salt sol. of strain R (killed).

Apr. 15. 1916-.Iunc 1. 1916. 12 IntravenouH injections of strain R

I (living).

Brown female. Dec. 9, 1916. Injection Weight 1550 into left rcnnl artery of growth from 6 c. c. broth in 0.5 c. c. salt sol. of strain (j (killed). Dec. 2*1. 1916. One intravenous injection of train () (living).


Male. Weight Apr. 27. 1916. Injection

1270 gro. i Into left rma! artery

of \ an agar fiUnt of

I hronchxAtptiruM in 0.5

I c. c. Hit sol.


lions.


i t h occasional albuminuria.


Steadv loss of


Steady loss of weight Developed a r tliritis of left hind leg.


Rapid emaeiatinn. Albumin and casta


'zr.


Killed May 15. 1916. 55 days from beginning of experiment. Both kidneys normal in every way.


Died Aug. 24. 1916, 161 days from beginning of experiment. Slight spontaneous lesions in both kidneys.


Died Mar. 7, 1917, 352 days fnmi beginning of experiment. Minimal degree of spontaneous lesion. Kid* neys otherwise normal


Died June 15, 1916, 71 days from beginning of experiment. Kidneys normal in every way.


Died May 19. 1916, 49 days from beginning of " experiment. Kidneys normal in gross and microscopically.


Died June 5. 1916, 66 days from beginning of experiment. Kldnej-s normal except for a few early spontaneous lewiuns.


Died Dec. 23. 1916. 14 days from beginning of experiment. Both kidneys normal in gross and microscopically.


Died Mav 5, 1916. eight days from beginning of experiment.

Extreme spontaneous Icitions.


124


[No. 339


been pitted at the start, focal interstitial lesions were found. Furthermore, in spite of the intensive direct treatment of the left kidney, in every case in which changes were present they were of equal extent in the two kidneys. It seems impossible to interpret these findings in any other way than that all these lesions were spontaneous and independent of the experimental procedure. The great frequency and variety of the changes, their apparent independence of any constant factor in the animal's condition, such as age, weight, etc., suggest that possibly many of the chronic interstitial lesions ascribed in the literature to experimental infection are really the effects of spontaneous nephritis.


CONCLUSIONS

1. An attemjjt was made to produce chronic nephritis in rabbits by intraveiaous injections of streptococci, following a direct injection into the renal artery.

2. Failure to produce chronic glomerular lesions was thought to be due to the means used by the kidney to dispose of injected organisms, which resulted in complete healing if the glomerulus survived the acute injury.

3. Chronic focal lesions were found in many animals.

4. Control examinations of the kidney at the beginning of the experiment, and comparison of differently treated right


TABLE I IL— SPONTANEOUS LESIONS

COMPARISON OF APPEARANCE OF LEFT KIDNEY AT OPERATION WITH LESIONS FOUND LATER AT AUTOPSV



Description


Appearance of left kidney at beginning

of experiment at operation


No.

days to autopsy


Lesions at autopsy


No


Description


Appearance of left kidney at beginning of experiment at operation


No.

days to autopsy


Lesions at autopsy


No


Right kidney


Left kidney


Right kidney


Left kidney


11



Normal size


460


Weight 8 gm. Looks


Weight 8 gm. Looks


63


White male.


Numerous mark

74


Weight 5 gm. Very


Weight 5 gm. Post

, ,


and appear


normal except for few

normal except f o r



Weight


edly depressed



many marked cortical


operative capsular



Weight 1560 gm.


ance ; surface



slight cortical depres

some thickening of



1450 gm.


scars over sur


depressions. Capsule


thickening. Similar



smooth.



sions. Capsule not


capsule (post-opera



face.



strips freely. Micro

lesions to those on





adherent. Micro

tive). Capsule strips






scopically: Man y


right and of same






scopically : Moderate


freely. A few slight






well-advanced lesions.


degree.






number of linear in

cortit-al depressions






with fibrosis, con






terstitial lesions, mod

(less than on right).






tracted scars, com






erately advanced. A


Microscopically:






pression and atrophy







few small, scatter

Same as right.






of glomeruli and tu






ed, round-cell infiltrations.







bules. Apart from these focal interstitial lesions, kidney is



14


Brown


X r m a 1 size


61


Weight 8.5 gm. Looks


Total infarct of kidney






normal.




male.


and appear


perfectly normal.


except for lower pole.


56


Brown


Nonnal.


55


Weight 4 gm. Normal


Weight 4 gm. Like



Weight


ance; surface



Capsule not adherent.


Microscopic sections



female.




in gross and micro

right except for post


25 lU gm.


smooth.



Microscopically : No


of lower pole show normal kidney.



W^eight 1250 gm.




scopically.


operative capsular thickening.


15


White male. Weight 1420 gm.


and appearance; surface smooth.


44


Weight 4.-1- gm.. Looks normal ; surface smooth. Capsule not adherent. Micro

Weight 4.-h gm. Some post-operative thickening o f capsule; strips freely. Micro

57


Brown female. Weight 1020 gm.


Surface perfectly- smooth.


161


Weight 5 gm. A very few very slight depresions on surface. Capsule strips freely. Microscopically : A few round-cell infil

Weight 5 gm. Same as right except for postoperative capsular thickening.






scopically: No lesions


scopically: No le



seen.







trations with beginning fibrosis.



16


Black male.


N o r m a 1 size


257


Weight 5.5 gm. Capsule


Weight 6.-r gm. Post Weight


and appear


strips freelv. A verv


operative capsular


59


Brown


.Surface perfect

352


Weight 5 gm. A very


Weight 5 gm. Same as



1660 gm.


ance; surface



few small '"' pits " on


thickening; strips



female.


ly smooth.



few scattered slight


right except for post



smooth.



surface; in general, is a smooth kidney. Microscopically: Two small round-cell accumulations with be

freely. No " pits " seen. Microscopically: One lesion seen in entire section, similar to right.



M" eight 1-360 gm.




beginning surface depressions. Microscopically : No abnor sections.


operative capsular thickening.






ginning fibrosis in entire section of the



63


Male.


Surface perfect

71


Weight 4.5 gm. Nor

Weight 5.5 gm. Like






cortex.




Weight 1030 gm.


ly smooth.



mal in gross and microscopically.


right except for postoperative capsular adhesions.


17


Brown hare.


Normal size


31


Weight 5.0 gm. Capsule


Weight 5.5 gm. Post Weight


and appear


strips freely. Surface


operative thickening


65


Male.


Surface perfect

49


Weight 5 gm. Normal


Weight 5.+ gm. Like



199U gm.


ance ; surface



smooth. Normal in


of capsule; strips free


Weight


ly smooth.



in gross and micro

right except for post



smooth.



gross and microscopically.


ly. Normal in gi-oss and microscopically.



1090 gm.




scopically.


operative capsular ad







66


Male.


Surface perfect

66


Weight 5 gm. Surface


Weight 5 gm. Like


19


Srown hare.


Kidnev showa


32


Weight 6.5 gm. Multi

Weight 7.5 gm. Post

Weight


ly smootli.



smooth and normal.


right except for post


Weight


multiple de


ple small depressions


operative thickening



1100 gm.




Microscopically : A


operative capsular



1650 gm.


pressed areas an surface. 1 to 1.6 mm. in diameter.



on surface, but capsule strips freely. Microscopically : Abundant, well -advanced.


of capsule; strips freely. Similar lesions to those on right and of same degree.






very few small, scattered, roimd-cell infiltrations


thickening.






scattered interstitial



12


Brown


Surface perfect

14


Weight 4.5 gm. Normal


Weight 4.5 -i- gm. Like






lesions, both in cortex




female.


ly smooth.



in gross and mici-o

right except for post





and medulla, with ex



Weight




scopically.


operative capsular






tensive round-cell in



1550 gm.





thickening.






filtration, fibrosis, and





compression and atro


77


Male.


Extreme pitting


S


Weight 6.0 gm. Ex

Weight 4.5 gm. Same






phy of tubules.




Weight 1270 gm.


of kidney surface.



treme pitting of kidney surface, but capsule strips freely.


kind and degree of lesions as on right.


51


White male. Weight

1580 gm.


Many small, depressed scars over kidney surface.


73


Weight 5 gm. Multiple small depressions on surface, but capsule strips freely. Microscopically : A good many small accumulations of round cells with beginning fibrosis. Kidney otherwise normal.


Weight 5 gm. Postoperative tli.kening of capsule; strips freely. Similar lesions to those on right and of same degree.






Microscopically : Tlie sections are shot with numerous contracted scars which distort the kidney structure. Areas of compressed o r dilated tubules containing casts. The most extreme grade of spontaneous lesion.



THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919




V


^:^^<'*'^* '--•-•




^<|V^


Fig. 1. — Earliest typ<' oi l. sum Shows beginning accumulation of round cells between the tubules.



Fig. 2. — Earliest type "l l. sum aii|» arini; :is ;i linear streak of round-cell infiltration.



Fig. 3. — Portion of Fig. 2. Higii pun^r. Siiuws round-cell Infiltration with beginning tubular changes.


Fig. 4. — Moderately advanced lesion.


THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919


.1. ' '^ ,


— Portion of Fig. 4. Higli power. Beginning scar witli slirunken and distorted tubules.




"t .' -SJ^^"^^,;^:^





Fig. 6. — Multiple small areas of scarring with normal intervening tissue. Well-advanced lesion.



.<?fiWH5«?^,



Fig. 7. — Same as Fig. 6. High power. Shows area of fibrosis with atrophied dilated tubules and fibrosis around a glomerulus.


Fig. S. — Very advanced lesion showing a linear scar with destruction of normal elements.


THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919


PLATE XIII



FiQ. 9. — Low power. Most advanced type of lesion, resulting in a scar.


m


Fio. 10.— Portion of KIg. 9. High power.


May, 1919]


135


and left kidneys sufr^est that all these lesions represented the " spontaneous nephritis of rahhits."

REFERENCES

1. Pearce, Richard M., and Elsenbrey, A. B.: A physiological study of experimental nephritis due to bacterial poisons and cytotoxic sera. Jour. Exp. Med., 1911, XIV, 306.

2. Opie. E. L.: Lymph formation and edema of the liver with experimental nephritis produced by cantharidin. Jour. Exp. Med., 1912, XVI, 831.

3. Longcope, Warficld T.: The production, of experimental nephritis by repeated proteld intoxication. Jour. Exp. Med., 1913, XVIII, 678.

4. Oliver, Jean: The histogenesis of chronic uranium nephritis, with especial reference to epithelial regeneration. Jour. Exp. Med., 1915. XXI, 42.5.

5. MacN'ider, William de B.: A study of acute mercuric chlorid intoxications in the dog, with especial reference to the kidney injury. Jour. Exp. Med.. 1918, XXVII. 413.

6. Underbill, Frank P.. Wells, H. Gideon, and Goldschmidt, Samuel: Tartrate nephritis. Jour. Exp. Med., 1913, XVIII, 322.

7. Frothinghani, Channing, Jr.: A glomerular and arterial lesion produced in rabbits' kidneys by diphtheria toxin. Jour. Med. Res.. 1914, XXX, 365.


8. MacNlder, Wm. de B.: A study of the naturally nephropathlc kidney of the dog rendered acutely nephropathic by uranium or by an anesthetic. Part 2. Jour. Med. Res., 1916, XXXIV, 199.

9. Le Count, E. R., and Jackson, Leila: The renal changes in rabbits inoculated with streptococci. Jour. Infec. Dis., 1914, XV. 389.

10. Major, Ralph H.: The production of kidney lesions with staphylococcus aureus toxins. Jour. Med. Res.. 1917, XXXV. 349.

11. Bailey. C. H : Chronic nephritis in rabbits by repeated intravenous injections of living colon bacilli. Jour. Exp. Med.,

1916. XXIII. 773.

12. Major, Ralph H.: The production of acute and chronic kidney lesions with bacillus mucosus capsulatus. Jour. Med. Res.,

1917, XXXII, 125.

13. Faber, Harold K.: Experimental arthritis in the rabbit. Jour. Exp. Med.. 1915, XXII, 615.

14. Coulter. C. B., and Pappenheimer, A. M.: Proc. New York Path. Soc. 1916, XVI, 80.

15. Pappenheimer, A. M., H>Tiian, H. T., and Zedman. F. D.: Proc. New York Path. Soc., 1916, XVI, 73.

16. Ophiils, W., and McCoy, George W.: Spontaneous nephritis in wild rats. Jour. Med. Res., 1912, XXVI, 249.

17. Winternitz, M. C, and Quinby, Wm. C: Experimental nephropathy in the dog. Jour. Urology, 1917, I, 139.


A SKpyrCH OF DR. LYMAN SPALDING '

By Henry M. IIukd, M. D.


Dr. Lyman Siial(lin<r wa.s iwrn at Cornish, X. 11., in 177"). His early education was ohtained at the Charlestown Academy, and later he was a student in the office of Dr. Nathan Smith, the eminent founder of medical schools, and the first of the name of the Smiths who later hecame distinguished in New England and Maryland. He afterwards visited the Harvard Medical School in 1794 ami attended two courses of lectures there, hut clid not receive his degree of M. D. until 1797. He returned to Cornish, N. H., the residence of Dr. Smith, an<l took charge of his jiractice during the hitter's ahsence in Euro|)e. He suK-iequently tauglit chemistry and materia medica witii Dr. Sniitli at the newly estahlished medical .school at Dartmouth College. N. H. He also hecame demonstrator of anatomy.

He soon removed to \Val|Mile, N. H., where he practised for a few months also. His residence there is mainly interesting hecauseof the fact that he purchased a set of Perkins Tractors, then much u.^cil ami highly prai.^ed for the treatment of disea.xes. These tractors were sold for -$30,00, with the c.xclnsivc right to u.«e them in |)ractice hoth in this country and in Europe. It was one of the common medical frauds which arc perpetrated on all nations ahout once in so often,

Dr, Spalding removed to Port.'^mouth, N. H., in 1797, and there had a succe.<sful career. He hecame a contract army surgeon, and had .«o much to do that ho relinquished his connection with Dartmouth College. He was a diligent student, and active in all matters i-onnected with medical co-o|)erHtioii.


'Read before The Johns Hopkins Hospital Historical Clvib, February 10. 1919.


He established a medical society, an anatomical museum, and originated and distributed .'Jo-called " Bills of Mortality," giving the causes of death of persons who died in Portsmouth from the years 1800-1 SI 3. He al.so essayed the growing of opium and lettuce in his garden for medicinal purposes.

In the "Life of Dr. Lyman Spalding " several interesting chapters are given on the introduction of vaccination into this country. Dr. Spalding, who was living at Portsmouth, wrote to Dr. Waterhouse, of Cambridge, who had received the Kiiie Po.x from Jenner in England and seems to have had the monopoly of the introduction of vaccination into this country. Waterhou.se was undoubtedly a man of ability and energy, but proi>ably lackwl money and felt the need of •.\|)Ioiting the new discovery for his own benefit. He, accordingly, writes to Dr. Sj)alding, in reply to his letter, asking for one-quarter of the amount received from Dr. Spalding's va<'ciinitions during the succeeding 14 months, insists that " the small sum of five dollars" be charged for each vaccimition, and ginirantees that the e.xclusive privilege will be granted upon these terms. He also nnikes carefid mention of the fact that he has .Tenner's matter direct from England. A long i-orrespondence took |)lace between Spalding and Waterhouse. Both parties seem to have been an.vious to make money from the introduction of vaccination, but Waterhouse appears in the most unfavorable light. After acceding to Spalding's proposition that he have e.xclusive control of vaccination in Portsmouth, ho shows great an.xiety that he, Spalding, should associate with him a Dr. Cutter and, later, Dr, Cutter's son, on the ground that the activity of these men would increase the number of vaccinations and thereby increase the profits to be


126


[No. 33"J


derived from the exclusive privilege of managing them. In one letter Spalding asks for the privilege for 12 months, and later suggests that he will pay 10 per cent of all the sinus which he receives for vaccination until such time as vaccination becomes public property. All that he received from Dr. Waterhouse seems to have been the exclusive privilege of vaccinating persons within the limits of Portsmouth, and a small piece of thread which had been dipped in the vaccine lymph. Later it seems that Spalding was to pay $130.00 for this piece of thread, and a certain proportion of the money which he received for the vaccinations. Owing to the fact that it soon became apparent that one patient could be vaccinated directly from the arm of another, the exclusive privilege of using the vaccine lymph was soon broken up.

This destruction of the monopoly was undoubtedly much hastened by the unsatisfactory character of the vaccination when the thread impregnated with lymph was used, and the great inferiority of this method to tlie method of vaccinating from arm to arm. The physicians had many failures. It is also interesting to note that Dr. Spalding, on two separate occasions, made observations upon patients who had been vaccinated and afterwards placed in smallpox hospitals, and freely exposed to the disease for a number of days without acquiring smallpox. Spalding also received a letter from Edward Jenner, the discoverer of vaccination, and subsequently a specimen of vaccine lymph directly from him.

Spalding issued at Portsmouth during the following 12 years bills of mortality— so-called— beginning in the year 1801. Copies of these bills were sent to John Adams, then President of the United States, and subsequently to Thomas Jefferson, Benjamin Waterhouse and Benjamin Bush. Waterhouse, with his usual critical spirit, made reply in the following letter :

Cambridge, March 18, 1802. Dear Sir: Your letter of the 11th mst. came duly to hand and I have endeavored to comply with your request, so far as to send you some matter on the point of a quill. As to the thread, it is full a month old, but was from a very perfect case and has been kept in a proper degree of temperature ever since. I am now so in the habit of taking the vaccine fluid from arm to arm, that I am not so constant in preserving it on the thread or otherwise. Considerable attention and patience are required in the first use of an old thread. It ought always to be moistened with the vapor of hot water.

You mention my not having answered your last letter. I have received no letter from you since you wrote to me in answer to one of mine. I received a printed bill of mortality, 5 or 6 weeks ago, but no written line whatever with it and I have had no letter from' you for 4, 5 or perhaps 6 months past.

I have just received "Observations on the Cow Pox" from Dr. Lettsom. I shall probably publish a second pamphlet in a month or so. being practical observations, etc. In the meantime I sent a few to the Medical " Repository " for their next number.

I am glad to find that you attend to the occurrences of Mortality. Excuse me for making a few remarks on the one you were so obliging to send to me. 1. Did APHTHAE kill the infant, or was it a symptom of another disorder, or in other words: was it sympathetic or IDIOPATHIC?

2dly. We very rarely see consumption in patients above 50 years of age, more rarely above sixty and very rarely indeed at 70.


There is a chronic cough and emaciation, and great expectoration in old people, but it is not the true Phthisis Pulmonalis.

3dly. Is not DEBAUCHERY rather a VAGUE term for a general Head? Does it mean Drunkeness exclusively?

4thly. I never yet saw a very young child with Epilepsy. There is a wide space indeed, between the convulsions of infants, and that truly wonderful disease, EPILEPSY.

5thly. Mortification: Was it in the bowels or the feet? As they are widely different in their cause. See Pott in the LATTER.

6thly. Death from SCROFULA is very uncommon. It predisposes to fatal diseases.

7thly. PAREGORIC: Does it mean that the Child was poisoned by that composition? If so, had it not better been by Opium as Paregoric means a Mitigator?

You will excuse these hasty observations that occurred on the perusal. They have not originated from a disposition to criticise but from a desire to have them free from every exception. Yours Steadily, B. WATERHOUSE.

In 1802 Spalding invented a galvanic battery, which gave rise to considerable corresjiondence, and which unquestionably was used extensively among his brother physicians. He had letters asking how to make similar batteries and also their exact therapeutic itses. He further devised a process for manufacturing oxygen for inhalation, and later invented a soda water fountain, which seems to have been quite extensively used. As he neglected to protect his invention by patents, as it appears in his biography some years later, patents were secured by other persons, and he was forbidden to use it without paying a royalty for his own invention. He was an active writer, especially upon anatomical and surgical subjects. His practice also extended in surgical line.s, and he performed operations for hernia, extraction of cataract and removal of necrosed bone. He continued his interest in vaccination, and received a second letter from Jenner, who acknowledged the reception of some interesting details concerning vaccination and the bills of mortality, for which he thanked him. In Jenner's letter an interesting detail is given concerning the good effect of vaccination in controlling cases of smallpox in Vienna. Prior to vaccination the annual average of such cases was 800. Four years subsequent to the introduction of vaccination, but two cases of smallpox occurred iii the city.

Dr. Spalding seems to have had a remarkable facility for friendship, and made warm friends in many parts of the country. One of his friends and subsequent correspondents was Bishop Philander Chase, a boyhood acquaintance, who subsequently became Bishop of Ohio, and later of Illinois and founder of Kenyon and Jubilee Colleges. Dr. Luther Jewett was another friend, a Vermont worthy who liad excelled in the practice of medicine, the practice of law. the gospel ministry and the editorship of an influential news])aper; four distinct branches of effort, in each of which he achieved marked success. He was also a warm friend of Dr. John C. Warren, of Boston; Dr. Alexander Eamsay, the famous anatomist from Scotland, and Dr. George Shattuck, of Boston. He wrote letters to John Bell, the distinguished Edinburgh surgeon, and also to Charles Bell, and as his thoughts turned very much to medicine abroad, he made every effort to get an opportunity to visit England and the continent to bettur fit


May. 1919J


12i


liimself to teach medicine. He sent a petition to the Secretary of State of the United States Government, asking that he be made a .«j)ec-ial messongcr to t-arry (li.<|mtehes to France, and received a courteous message to the elTcct that the services of no such messengers were nec(k'(l at that tinu'. He visited PhihHh'l|)liia in order to lit liinisidf hotter for his profession, and tlieri' saw tlie eminent Dr. I'liysick, and Drs. Wistar, Hush, Slii|)|)fii and Harton. lie writes tliat the school in Philadelphia had 3.")0 medical students and later, when in Xew York, he contrasts the ])o|)uhirity of I'iiiladelphia and tlie large nund)er of students witli tiie fact that New York had only about 100 medical students.

There is an interesting chapter in Spalding's life wiiich has been detailed at considerable length i)y his biograplier and deserves mention. In 1809 he became connected with the Fairfield .\cademy, located at Fairlield, aiwut 10 miles from Little Falls, N. Y. Fairfield .\cademy was one of a chain of academies whieli had been establisheil to promote edmation in tile state under the charge of the Board of Regents. The great demand for medical men to provide for the needs of an ever increasing emigration to the west at tliis time gave rise to many medical sdiools. In addition to the Xew England .schools founded by Ur. Xathan .Smith, there were schools at Pittsfield, Mass., and t'astleton, Vt., in addition to Harvard anil the schools in Philadelphia and Xew York. He was appointed lecturer at Fairfield .Academy in 1809, and lectured there for several years. The journey to Fairfield from Hoston wa.s a matter of three days and nights. He was made lecturer on chemistry and surgery during his first appointment, while Dr. George t". Shattuck, of Harvard, was made lecturer on medicine. The courses .seem to have been not simultaneous, but t-tindeni, as it were, Dr. Spalding lecturing on chemistry and surgery for si.\ weeks, and being followed by Dr. Shattuck, who lectured for tlie .same period on medicine, this making a term of three months. The success of tlie school was so great that it became nei-cssary to erect a new building, and ])ermi.ssion was aske<l of the legislature to establish a lottery to raise $.")000. Ix)tteries, it may i)e remarked, were at this time a popular method of raising money for educational and religious purposes. The Washington Monument in Baltiniori' was startetl ity a lottery, as also the University of Maryland, the First Presbyterian Church and St. Paul's Church. JIany <letails are given in the iiiography of S|ial<ling in reference to the lottery plan, and new light is thrown upon it by the suggestion in one of the letters that, if the Icg^islature granted the authority, the privilege of the lottery might lie disposed of to .xonie other parties at a discount. The success of the .school at Fairfield became .-io great as to e.xcite the cupidity of persons who were interested in the development of Hamilton .\cademy. at Clinton, X. Y.. into Hamilton ('(diege, and an effort to establish a siinilar medical school at Hamilton. The agitation finally brought an appropriation of $100,000 to Hamilton -Academy, and it l)ecanie Hamilton College, wiiile Fairfield was obliged to Im" satisfied with receiving $10,000 for the construction of a building and a <-harter giving the privilege to grant ilegrees, and thus to become an established medical .<chool.


The following letter, sent by Dr. S))alding to Dr. George Shattuck, of Boston, gives a very interesting idea of his conleption of the infiuencc of medical teaching, and its benefit to I he medical teacher:

Dear Sir: I can only say that I regret exceedingly the opinion of yourself and friends, that your avocations will not sulTer you to Wsit Fairfield once more. I acknowledge that, at present, the compensation is not adeqiiale lo the output and the loss of business, but. Sir. 1 do really believe that this school may be made second to none but Philadelphia. If not. I will join with you in resignation. What eflect has the Professorship already had on you? It has compelled you to pay close attention to your profession, to pass the wliole of CuUeu's " Nosology " in review, before you annually, and llureby qualifying yon for the practice of your profession more than any other way in which you could have spent your time. It is the high road to fame, and usefulness. I know that my sacrifices have been great. I know that yours must be. But, show mc the man who has risen to be a Prince of Physicians, while slumbering on the couch of idleness.

Soon after I came to Portsmouth. I resigned my office of Professor of Chemistry in Dartmouth, no doubt from the same motives that now influence you, with this addition, that my lectures there had to continue three months. I soon found myself slumbering on my oars and relaxing my pursuits. In fact, so far from Improving, I hardly kept pace with the others. A kind of indifference for science pervaded nie: Indignant I aroused. I went lo Hanover to see Ramsay, I went to Philadelphia, and I planned a voyage to Europe. This change, Sir, I consider the most happy circumstance in my wliole Professional career.

Admit tliat you resign your office. Man is an indolent animal. What inducement have you then, to labor incessantly? None! Your reputation is as liigh as that of your contemporaries. Then, wrapped in the lap of affluence and ease, you will slumber and sleep till old age creeps upon you. when you will find yourself outstripped in the race of usefulness and fame, your opinions so antiquated as to be regarded not, and yourself a mere old Granny!

Look at the Priaces, or rather. Fathers of Physic. Who have they been or who are they now? So far as my memory serves me; Teachers of Physic. Boerhaave, CuUen, Desault. lx>ok at Hush, Warren and Smitli. What has put them at the head of the profession? Notliing but their being compelled to labor, and annually to review their profession, and incorporate with their old slock all the new improvements. Show me a man in private practice who does this, annually. He is not to be found. But. your friends say that you can do this, yet stay at home. I acknowli'dge (his, but tell me honorably. Will you do it? No, Sir, you have no inducement. For a man to be pre-eminently great, there must be a great occasion. What made Washington Great? Opportunily. You are now on the same high road lo reputation that every Prince of Physicians has travelled. If you turn aside, you are lost forever. These in conjunction with those in my last letter are the reasons which ought lo inMuence you. You can have no doubt of my wishes on the sul)jecl. The time for the commencement of the lectures Is so near at hand, that no successor can be appointed in season for the next course. I therefore beseech you, on my account, if neither honor nor fame will move you, to deliver This One Course, and I will consent to any arrangement that you may then choose to make If nothing farther, as a mere matter of policy. I wish you to withhold your resignation till the meeting of the Trustees of tlie New Medical College and let us see what they win do for us.

Dr. Mann I knew had be<'n appointed a Hospital Surgeon, but 1 did not know that he had been made Surgeon General. He must be with the Army by this time, ami cannot be prepared for the ensuing course. 1 have no objection to this man, but must for want of room decline saying anything about your successor until I hear from you again. Your friend, Lyman Spalding.


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[No. 339


Sliattuck, after serving two terms as professor of medicine, relinquished the position, but Spalding, in 1813, was made president of the Fairfield College, and filled most of the chairs in 1814-1815 and 1816. The number of students seems to have varied between 50 and 70. Spalding seems to have done very faithful, conscientious work, for which he received somewhat irregular paj-, and often more pay in promises than in actual money. The school remained in active operation until 1839, when it went to pieces in consequence of squabbles among the faculties as to the division of fees from medical students. The fees seem to have been very small.

In 1814, Spalding went to New York to reside, and had an office on Broadway, for which he was to pay about $200 per year. His fees from his patients during the first year amounted to a little more than $1000. At this time, Spalding seems to have attempted to write a book entitled the " Institutes of Medicine " which, as far as I can learn, was never published in book fomi, but was circulated in pamphlets, each chapter furnishing a pamphlet. It was praised by Shattuck and Waterhouse, and the reception of a sample pamphlet was certainly acknowledged even by Dr. Caldwell, but the book seems to have made little impression.

The following letter is from Governor Plunier, of New Hampshire, a friend of Spalding's :

Epping, N. H., Oct. 24, 1818. Dear Sir: This weelc I received your letter with your "Reflections on Fever," and Report of the Trustees of the Free Schools, for which you will please accept my grateful acknowledgments. I have read your pamphlet with attention and pleasure, but it is on a subject with which I am not sufiiciently acquainted to decide with precision. You know the low state of the Faculty in New Hampshire. We have scarcely any who write on the subject of medicine, and of the great body of our country physicians but few who have any books to read. and what is worse they have little inclination to purchase books, to read those few that they have, or to investigate the complex and intricate subjects of their profession. These facts have long induced me to believe that, in many cases, the patient has more to apprehend from the ignorance of the physician, than from the disease, and that it is safer to trust to nature for a cure than to rely on the prescriptions of those whose knowledge is limited to a few hard technical terms. With us. the Gentlemen of the Faculty have made less progress than those of law and divinity: the latter, indeed, have much to do before they can attain real eminence.

In your profession I have long considered it a desideratum to have an able but simple work, accurately describing the nature and functions of the several parts of man in a state of health, the effect or changes diseases produce on each of those parts and of the remedies for those diseases.

I would purchase and read such a work with pleasure, and that pleasure would be enhanced if it was simple, plain and free, so far as the nature of the subject would admit, from abstruse technical terms, and of attachment to existing theories. Mystery is the enemy of improvement, and it is better suited to prolong the reign of ignorance and of error than to promote that of truth and science. And, the knowledge of things is vastly more important than that of words.

I really wish we had an accurate Journal kept in different sections of our Country of the actual state of the weather, the crops, the general diet and regimen of our citizens, the diseases most prevalent in each, their type, character and mode of treatment, etc., so as to exhibit the means by which health was preserved and lost and how far they depended on climate and modes of living.


Such a Society, I think, might be formed of Gentlemen living in various parts of our Country, with little expense and from whose reports much information could be obtained which would be useful to all, and particularly to Medical Characters. I would freely contribute to such an establishment.

But, I am wandering from the object of this letter, which was to thank you for your Pamphlets and to say, that if you or the Historical Society of N. Y., should need any of the few pamphlets we publish here, it will afford me pleasure to procure and transmit them. I remain with much esteem and respect. Yours, etc., William Plumer.

About 1817 Spalding began to agitate the preparation of a national pharmacopceia, notwithstanding the fact that several local pharmacopoeias already existed, the most extensive and authoritative one being that of Massachusetts. His motive in urging a national pharmacopoeia was due to his desire to secure uniformity, and also to discard local remedies which seem to have been used in different parts of the United States without any sufficient scientific authority. As an example of such local favorites may be mentioned Scutellaria or skullca]) as a remedy for hydrophobia. It was shown by Spalding that the authority for the use of this remedy was weUnigh universal. Numerous cures through its employment were reported, and in the literature its claims were overwhelming. We now know that it is worthless, and its elimination from the pharmacopceia was promptly made. The plan proposed by Spalding for the preparation of the pharmacopoeia was an excellent one, and has practically been followed for the last 100 years.

The pharmacopoeia was originated in a paper by Dr. Spalding, read before the medical society in the city of New York, in wliich he pointed out the difficulties attendant upon the present lack of uniformity in the preparation of drugs in the different states. As a result of the discussion which followed the reading of his paper, a committee was appointed, of which Dr. Spalding was chairman, to suggest measures for the preparation of a national pharmacopoeia. The country was divided into four districts, known as the nortliern, middle, southern and western. Through the medical societies of these regions, delegates were cliosen to meet at some central jioint in the district to discuss matters pertaining to the drugs to go into the pharmacopoeia, and to elect two delegates, each to go to Washington later to prepare the book for publication. The only two district conventions were those of New England, at Boston, and of the Middle States at Philadelphia, which met on June 1, 1819. The meeting in Philadelphia, although attended only by delegates from the middle district, had done valuable work in the discussion of remedies aud methods. The delegates chosen at the two district meetings met in a general convention in Washington on January 1, 1830, Dr. Spaldiii'jbeing one of the delegates. The two rough drafts from tlic district meetings were examined and discussed, and the prej):!ration of the pharmacopoeia was outliaied and plans made for its completion and adoption. A Committee of Publication was chosen, with Dr. Sjialding as chairman, which met in New York in June, 1820. The pharmacopoeia wa.s printed in English and Latin, and was immediately adopted as autlmritative throughout the covuitrv.


Mat, 1919]


129


About the same time Dr. Spalding also had, in addition to the pharmacopceia, a jdan for the establishment of what he ternieil a medical police to liave charge of all sanitary matters. The latter scheme, however, seems to have faded from public sight.

Dr. S])alding did not live long after the publication of the pharmacopoeia. In 1821, while walking in the city of New York, he was struck down by some building material whicli fell upon his head, and rendered him unconscious. Although he recovered apparently, he never enjoyed good health, and gradually went into a state of physical and mental decline. He gave up practice, sent his family to New England, and later rejoined them there. He died on October 31, 1831, a few days after he reached them.

It is evident that he was a man of unusual ability, being industrious, efficient, and with large powers of initiative. Imperfectly educated as he was, he had made himself an excellent physician, a remarkable surgeon and anatomist, an interesting and ins])iring medical teacher, and a member of the profession full of enthusiasm for its advancement and perfection. He wa.s denied the great desire of his life, the privilege of studying aiiroad, and doubtless liad lie been able to do so, and had returned to .\merica with tlie new ideas, his subsequent lal)ors might iiave resulted in great additions to the medical knowledge and resources of the country. The story of his life is a most inspiring one.

N(>T>:. — Since the above sketch was written and presented to the Historical Club, Dr. Kelly has placed in my hands a copy of tlie first edition of the Pharmacopoeia of the United States of America. It bears the following title page:


The

PH.\R.MACOPOEIA

of the

rXlTEn STATES OF AMERICA.

1820.


By the Authority of tlie Medical Societies and Colleges.


Printed by Wells and Lilly. For Charles Ewer. No. 51, Cornhill.


Dec. 1820.


It is bound in leather and is in excellent state of preservation. The name on the fly leaf cannot be deciphered definitely. It is in pencil and is dim in places. The inscription seems to be James Burbeck. 1827. It has undoubtedly belonged to a druggist or apothecary as it contains many recipes neatly interleaved In various portions of the book. There are also prescriptions for various diseases. The book contains an interesting Historical introduction explaining the object of the preparation of the National Pharmacopeia. There is also a Preface which gives full details as to the movements which led up to the preparation of the work. In the list of delegates orisinally selected to attend district conventions to prepare lists of medicines and to select local committees are to be found names eminent in the profession one hundred years ago, many of whom figured in medical literature. A good many of tlicm also were meiubers of the linal committee which prepared tlie National I'liarmacopeia.

From New York there were; llavid Ilosack, Samuel L. Mitchell. T. Romeyn 13eck. Lyman Spalding, John W. Francis and Valentine Mott. From Massachusetts; Jolin C. Warren. Jacob Uigelow, James Thaclier and George C. Sliattuck. From New Haven; Eli Ives and Nathan Smith. From Philadelphia; T. T. Hewson and Joseph Parrish. From Maryland; Nathaniel Potter, Elisha DeButts, Samuel Baker and Ennals Martin.


THE EFFECT OF DIFFERENT BLOODS ON THE GROWTH OF

B. INFLUENZAL'

P.y T. M. liivos. M.I)., Ballimorc :Md.


The growth of B. infiwnzx has been described as small dewdrop colonies invisible by direct light, but becoming larger when near colonies of other bacteria, as staphylococci, pneumocoeci and streptococci, this latter phenomenon being called obligate symbiosis. This is a correct description of the colonies as they appear on human blood agar.

In making routine throat cultures it was noticed that on certain days the colonies of B. influenzcB were large and easy to isolate, whereas on other days they were very small and often overlooked. The results from day to day differed so much tluit an explanation was sought. It was found that on tiie ilays when the colonies were large either cat or rabbit blood luid been used and human blood when thev were small or over


' From the Departments of Pediatrics and Patholog>', Johns Hopkins I'niversity.


looked. Tiiis led to the comparison of the effects of different bloods and sera on the growth of B. influenza:.

In three petri dishes respectively was placed 0.5 c. c. human. 0.5 c. c. cat and 0.5 c. c. rabbit blood. Then 10 c. c. of meat infusion agar were added at 40° C. from the same llask to each of the dislies. After liic agar had solidified, each plate was streaked with a broth siuspension of two strains of B. influenzcE. The growth on the raiiliit blood (Fig. 1) and cat blood agar was lu.vuriant. The colonies which were well separated became very large and slightly opaque, and when they were 48 hours old some were umbilicatod or checker-sluiiied. The growth on the human blood agar (Fig. 2) appeared very slowly and at the end of 48 hours was still seen with difTiculty.

Three other plates were made lus above and streaked wilii a broth suspension of B. influcnzw. In the center of ea<li plate there was also streaked a broth suspension of piicunio


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[No. 339


cocci. On the rabbit blood and the cat blood agar the colonies of B. influenza grew best at the edges where they were well separated. There was no tendency to be large.'it near colonies of pneumocoeci (Fig. 3). On the human blood agar the colonies of B. inftuenzm were just visible at the edges but grew large near pneumococcus colonies (Fig. 4). This has been repeated with six lots of meat infusion agar and each time the difference has been observe<;l.

B. influenzcE grows well on rabbit blood agar, cat blood agar and Averj' medium when 1 per cent of washed cells is added to the agar at 95° C. There is also no difficulty in growing the bacillus on " chocolate blood agar " even when human blood is used. If the " chocolate agar " is good there is no obligate symbiosis, but at times, when the medium is improperly made, this occurs. Very rarely does the symbiotic relationship appear on rabbit or cat blood agar.

It would seem that fresh human blood either has an inhibitory effect on the growth of B. inflii^nzce which pneumocoeci or other bacteria remove by their growth, or else it lacks something which is supplied in the neighborhood of other bacteria by the products of their metabolism. The fact that it grows well on Avery medium and on " chocolate human blood agar " makes it seem most likely that there is an inhibitory factor which is removed by heating or by the growth of other bacteria.

Two tubes each containing 0.5 c. c. of defibrinated human blood were inoculated respectively with api)roximately 100,000 influenza bacilli and "pneumocoeci. Two tubes of 0.5 c. c. defibrinated rabbit blood were likewise inoculated. A loopful from each was streaked on a separate rabbit blood agar plate 20 minutes later. There was a heavy growth (400-500 colonies) on all the plates except the one streaked from human blood and influenza bacilli which had only several colonies. After four hours' incubation a good growth was obtained from all except hiunan blood and influenza bacilli which was sterile. To be certain it was sterile an extra plate was streaked with one-tenth of the +++++ CONTENTSs of the tube. Still no growth was olitained. This precaution was taken because it had been observed that influenza bacilli' occur in chains and clmnps in liuman blood and serum whereas in smears from rabbit blood and serum they are found diffusely scattered. Clumping could account for a marked difl'erence in the number of colonies from a loopful, but not for a sterile plate from one-tenth the +++++ CONTENTSs of a tube.

Approximately 100,000 influenza bacilli were added to 0.5 c. c. meat infusion broth, 0.5 c. c. normal human serum, and 0.5 e. c. rabbit serum. The broth was used as a control. The tubes were incubated for two hours and a loopful from each was streaked on a blood agar plate. A heavy growth was obtained from the broth, less from the rabbit serum, and only a few colonies from the human serum. After 18 hours' incubation, the human serum was sterile while there was a heavy growth from the rabbit serum (Figs. 5, 6, 7, 8, 9).


- Uniformity of growth has been sought by using rabbit blood agar for plating and for each experiment the plates were all poured at the same time from one large flask of meat infusion agar.


Sera from four adults and one infant, some of whom had had influenza, others not, have been tried with several strains of influenza bacilli and all have shown a bactericidal effect. Sterile plates cease to be obtained at different points in the dilutions of the various sera when a constant number of bacilli are used for an inoculation. The same is true when one serum is used and the number of bacilli inoculated is varied. Normal human serum kills influenza bacilli rapidly, in many instances causing the death of thousands of bacteria in 20 minutes at room temperature. This bactericidal property is lost very rapidly upon dilution. Rabbit serum, also, is slightly bactericidal and, if a light inoculation is used, the midiluted normal serum may yield a sterile plate. There is no comparison, however, between the two sera. Guine'a-pig serum, too, is not very bactericidal for B. inflxienzce.

Inactivating himian serum at 54° C. for one-half hour markedly decreases its bactericidal properties for B. influenza. Normal rabbit and guinea-pig sera were tested at the same time with normal and inactivated human serum. Rabbit serum decreased the number of colonies at first, but this effect soon disappeared and at the end of 18 hours a heavy growth was obtained from the rabbit and guinea-pig sera. Even inactivated human serum kills in 12 to 18 hours.

Experiment Showing the Difference Between Normal and Inactivated Human Serum. The Count.s are Reported in Round Numbers for Convenience


Dilutions of normal and inactivated


Approximate inoculation

of each tube

with B. in fiuenza:


Number of colonies obtained at different times by

streaking a loopful from each tube

on a blood agar plate


liuman aerum


20 minutes


4 hours


18 hours


Serum


Locke's Solution


Normal


Inactivated


Normal


Inactivated


Normal


Inactivated


1.00 c.c. 0.75 c. c. 0.50 c.c. 0.25 c. c.


0.00 c. c. 0.25 c. c. 0.50 c.c. 0.75 c. c.


100,000 100,000 100,000 100,000


35 20 40 150


300 300 200 250





300 300 300 300






10

200

400


Attempts have been made to reactivate the inactivated human serum with rabbit and guinea-pig serum as they do not inhibit the growth of influenza bacilli to any great extent. This has been accomplished a number of times. It has been accomplished also with normal human serum. An objection might be raised to the use of normal human serum because it is in itself bactericidal. The experiment as shown in the table on page 131 .seems to show that it can be done.

During the epidemic of influenza last fall thousands of antemortem and post-mortem blood cultures were taken and very few positive results were reported for B. influenza, de.spite the fact that at autopsy they were as numerous in many of the lungs as pneumocoeci and hemolytic streptococci which were easily obtained in a large percentage of the post-mortem blood cultures. Positive blood cultures are at times obtained from patients with influenza endocarditis and from children with


PLATE XIV



F|... :.. -i.r.,.,;i, r.«.,ii,i,K ;. .u. .li.akinlfa rabbit blood Hg^r pUK »illi • loofiful of meat Infuaion broth which hxl been inoculateil with

ft .v»l-fr^--r n"-? nrihflf<»d 'wo hour".


THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919



•/ v.- • .#• V '.:•.•* . •




Fin. 8.— Growth obtniniil aa in KiK. R i-xccpt that incubation was for eJKhtccn houra iiiatcail oltwo.


Kiii.li.-firowth obialniMl iia in hit. 7 i-xep|.t that incubation una (or <'l([litcen houra inatcad of two (plate iaatiTik-).


May, 1919]


131


influenza meningitis, but these are the exception when compared with the patients who died during the epidemic and had influenza bacilli in the lungs at autopsy. B. infiuenza eitlu-r does not invade the blood stream, is promptly killed when it does, or, if alive, is not recovered by the present cultunil

EXfBRI.MK.NT Til SilOW Rl--\rTIVATl<).N OF THE I.VAITIVATEU HlMA.N SERf.M AMI Resix)RATION OK ITS Baotkkiciuai, Pkoperties. Thb Counts ark Rkpokted in Rocnd Nimbers for Convkniencb



Number of colonies obtained in streaking blood

agar plates witli a loopful from each

tube at different times


Smin.


,hr.


2 bra.


4bri.


7 hrs. U brs.


0.5 c. c. normal 100,000 human serum.

0.5 c. c. inacti- 100,000 vated human Derum.

0.4 c. c. inatti- lOO.OOO vated human serum +0.1 c. c. norma! human serum.

0.4 c. c. Locke's 100,000 solution 4- 0.1 c. c. normal human serum.


400

400

400 400



400

50 300



400

25 200



200


300



125


400






methods. As shown above, human serum and defibrinated blood are very bactericidal for the influenza bacillus in vitro as compared with other bloods used and also as compared with the pneumococcus. This bactericidal property is lost rapidly upon dilution, and laboratory strains have been grown in


100 c. c. of meat infusion broth with 10 c. c. human blood added even when very light inoculations have been made (le.>;s than 100 bacteria). Although conclusions cannot be drawn concerning hai>i)cnings in vivo by what occurs in vitro, may it not be possible that a combination of such factors accounts for so many negative blood cultures for H. inftuciiztp when they arc so abunilant in many lungs at autopsv?

CONCLUSIONS

1. B. infiuenzcE grows well and produces large, often o|)aquc, colonies, upon the projjcr medium.

2. B. infiuemm grows better on rabbit blood and cat blood agar than on human blood agar. Some of the discrepancies between the findings of various laboratories during the i'\ndemic may be explained possibly by the difference in the media used.

3. Obligate .symbiosis occurs more conmionly on liunum blood agar than on rabbit or cat blood agar and in part, at least, is due to the inhibitory effect of the blood which is removed by heating or by the growth of other bacteria.

4. Defibrinated hmiian blood and normal hujuan serum arc very bactericidal for the strains of influenza bacilli studied as compared with defibrinated rabbit blood, normal rabbit .serum and normal guinea-pig serum.

5. Inactivated human serum, although less bactericidal than normal serum, also kills in from 12 to 24 hours.

6. There is evidence that the marked bactericidal properties can be restored to inactivated human serum by a quantity of normal human serum which by itself is not bactericidal in the same lengtli of time. Keactivation can be accomplished by other normal sera.


OBSERVATIONS ON THE CLINICAL PHARMACOLOGY OF DIGITALIS


By Ai.FRKD M. Wedd, {From the Medical Clinic nf the Clcvelniitl

Although introduced into therapeutics by Withering in 1T85, digitalis received but little consideration from medical scientists until comparatively recent years, and the modem clinical knowledge of the drug may be said to date from the work of Jlackcnzie," reported in 1911.

The present communication is comjjiled from data on un.selected cardiac and caniiorenal patients admitted to the I'ity Hospital during the past year to whom digitalis was given, including 29 in who.se ca.ses electrocardiographic records were taken every 24 hours, or more frequently, during the period of administration of a standardized preparation of the drug.

I'rkparation and Dosaor The preparation was the tincture, two different lots being u.sed, each of which had been standardized by Prof. R. .\.


M. D., rittsburgh, Ta.

I'ity Hospital. Scrvi( e of Dr. K. P. Carter)

Hatcher, of ("ornell University. Digitalis dosage, referring to the tincture, in clinical practice is subject to rather wide variation; from a ihiily dose of 1 c. c. or less, used by some practitioners, tlirough the dose of from 4 to 6 c. c. recommended by ilackenzie, up to the massive doses of 15 to 25 c. c. in 2-1 hours (usually O.lKi c. c. \wt |)ound of body weight), advocated by Kggleston ' and recently studied ami indorsed by White and Morris.'

In this work it was desired to give enough of the drug to bring the ])atient pmnijitly under its influence, but to avoid such amounts as might by the early producti<in of toxic symptoms prevent us from following its jirogressive action. The daily dose us«'d was from 8 to 12 c. c, usually 10 c. r\, and this was continued until definite evidence of digitalis action was


'Mackenzie: Heart, 1911, XI, 273.


'Eggleston: Arch. Int. Med., 1915, XVI, 1.

' White and Morris: Arch. Int. Med., 1918, XXI, 740.


133


[No. 339


noted. The indications to discontinue the drug were alimentary disturbances, derangements of the cardiac mechanism or slowing of the pulse rate to a level beyond which it was deemed inadvisable to continue.

The cat unit of Tincture A was 1.11 c. c. and it was, acccjrdiiig to Professor Hatcher, a fairly good specimen. This ])re]iaration was given to five patients. The following are lirief details of these cases:

No. 320. Diagnosis, clironic myocarditis. Age, 16 years: body weiglit, 125 pounds. Total dose, 72 c. c. Rate wliile in bed slowed to 60.

No. 299. Diagnosis, chronic myocarditis. Age, 44 years; body weight, 140 pounds. Total dose, 115 c. c. No clinical effect.

No. 321. Diagnosis, chronic myocarditis and nephritis. Age, 48 years; body weight, 135 pounds. Total dose, 101 c. c. Rate, when up, reduced from 120 to 110. No toxic symptoms appeared.

No. 323. Diagnosis, chronic myocarditis and nephritis. Age, 52 years; body weight, 140 pounds. Total dose, 137 c. c. Pulse slowed from 120 to 60 after 119 c. c, then increased to 84 and remained at that rate. No toxic symptoms.

No. 332. Diagnosis, chronic myocarditis with atrial fibrillation, nephritis. Age, 45 years; body weight, 140 pounds. Total dose, 149 c. c. Fulse rate slowed to 56. No toxic symptoms.

These were the first cases studied and in tliree of them the drug was discontinued because it was feared that some unex])ected result might occur, since the dosage then far exceeded that usually given.

In the remaining work a second tincture was used, the cat unit of which was 0.85 c. c. The total dosage with this preparation showed considerable individual variation. In No. 368 nausea and vomiting occurred after 20 c. c, while in No. 374, 100 c. c. were given without the development of any toxic symptoms. Because of an oversight No. 304, a case of complete dissociation, received 280 c. c. during a period of 10 weeks without showing any clinical symptoms. In nine cases toxic sym])toms were produced by 40 c. c. or less; in seven lascs, by 40 to 60 c. c. ; six patients took from 95 td 100 c. c. The average total dose required for the production i>r toxic symptoms in 22 patients was 52 c. c.

No. 321 entered the hospital a second time six months after the first admission, with moderate decompensation, presenting a clinical picture similar to that when first seen. Digitalis was again given and nausea and vomiting occurred after 35 c. c. of the second tincture, whereas 100 c. c. of the first produced no clinical effect. The inefficiency of the first tincture was undoubtedly due to delayed absorption from tlic alimentary tract, as will be shown when the effect of digitalis on the T-wave is considered, but the cause of this is not known. It is evident, however, that biological standardization showiim' approximation to theoretical strength is no guarantee of the clinical efficiency of a given preparation of the drug. Individual power of absorption for a given tincture appeared to Iw quite uniform, so variation in toxic dosage is due to variatido in individual tolerance for the drug.

No constant relation between the amount of digitalis that could be given and the age or body weight of the patient or the condition cil' the nivocardium could be discovered.


Effect on Edema, Dyspnea and Cyanosis

That digitalis has no specific diuretic effect is now generally recognized. The decrease in edema depends on improvement in the circulation, and rest in bed alone is an important factor in bringing this about. In three purely cardiac cases the edema had almost entirely disappeared before any digitalis action was recorded. Its removal in cardio-renal cases was much more slowly accomplished. The value of determining the output of phenosulphonaphthalein before and after the administration of digitalis may be pointed out as a means of determining the relative cardiac and renal elements in the original clinical picture.

The alleviation of dyspnea was also seen to be an indirect digitalis effect, depending on improved pulmonary circulation, the rest, morphin and venesection, when used, affording the immediate relief, while more permanent removal of this distressing symptom came with improvement in the myocardium.

Cyanosis was a characteristic and persistent sign of myocardial involvement. In those cases in which true myocarditis was believed to be present, and especially in those whose electrocardiograms showed intraventricular or bundle branch block, even though free from edema and dyspnea on moderate exertion, the cyanosis was not influenced by any treatment.

The Effect on the Heart E.\te

It was formerly maintained that the function and the prinpipal action of digitalis was to slow the pulse. However, excessive slowing with the ordinary use of the drug usually occurs only in atrial fibrillation, and according to Cohn * reduction in rate is not constant, and to produce slowing is not a function of digitalis in therapeutic doses. In five cases of fibrillation the pulse rate was reduced to 55 or lower before or without the onset of toxic symptoms ; in one case it fell from 130 to 84 when nausea and vomiting occurred.

Eighteen cases with normal mechanism were studied ; in five the rate fell to 60 or lower ; in three there was no change : ill the remainder the reduction of the initial rate varied between 8 jier cent and 33 per cent, the average fall being about 20 per cent. Contrary to the statement of Sollman ' that fairly normal hearts are slowed by large doses, but that this is due to blocking of impulses from the atrium, the rate in six cases was reduced to 65 or lower before the onset of tdxic symptoms with an increase in the P-R interval varj'ing from 0.02 to 0.05 sec. as the only sign of block. In one case the rate after 10 c. c. had increased from 89 to 96 and after 20 I', c. nausea and vomiting occurred, the rate remaining at 96. In a number of cases after reaching a low level the rate increased as the point of toxicity was approached, c. g.. No. 323 ; rate after 119 c. c, 60, after 137 c. c, 84. This is comparable to the ex])erimental findings of Robinson and Wilson ° in which slowing continued until about three-fourths of the


  • Cohn: Jour. Amer. Med. Assn., 1915, LXIV. 463.

'^Sollman: Manual of Pharmacology, 1917, Philadelphia. "Robinson and Wilson; Jour. Pharni. and Exp. Therap., 191S, X, 491.


May, 191!) J


133


U'thal dose had been injected when acceleration set in and continued until fibrillation replaced the normal beat. Tiiis acceleration is due, accordinj; to Cushny, to increased irritability of the heart muiide rather than to any nerve influence.

It d(x\< not seem jKissiblc to form any definite conclu.«i(in alx)Ut the time factor in the slowinfr of the initial rate. Usually there was a jrradual fall of from four to ten beat.^^ daily. Other ajjents than difritalis, the rest in bed and the sedatives given, certainly contribute to the first sudilen lowering which occurs before there has been time for any specitic digitalis action. Thus, in Xo. 329, a case of fibrillation, an initial rate of HiS fell to 108 in 12 hours, during which 10 c. c. of the tincture had been given. Comparing this with other eases it does not seem reasonable to attribute this prompt reduction of 60 beats solely to digitalis. In general, there seemed to be a gradual ilecline in rate, which in the fil>rillation cases nearly always progres.<ed to a much lower level.

In each of 13 csises of atrial fibrillation examined while under the influence of digitalis, an increase in rate occurred following the administration of atropin (the dose usually given was 2 mg.). In all of these ca.<es in which the effect of atropin was studied both before antl after digitalis, the ma.ximuni rate after atropin in the digitalized heart was not equal to tiiat obtained before any digitalis was given ; in five of six eases this decrea.«e was exactly GO beats, and in one 72 beats. Atroj)in was given to 13 ca.ses witli normal mechanism lieforc and after the course of digitalis; in seven tliere was a decrease in the maximum e.<cape ranging from 4 to 32 beats; in Hiree there was an incrca.<e in the maximum of 3, 4 and 17 beats, res|)ectively ; three cases showed no escape after digitalis.

TllK KfFE( T (IN THK Hl.iiOl) rHKSSlKK

.Altiiough the digitalis ixidies profluce a characteristic rise of bifiod pressure in animals, the effect on the pressure in man is very variaiile. The subject has been recently reviewed and studied by Eggleston.' In 1(5 cases the blood pre.«sure was carefully followed: in 10 there was no appreciable change; in three the systolic increa.^ed without change in the diastolic: in two casi-s with high pressure the .systolic fell 3.") mm. and 30 mm., respectively, with a corresponding reduction in the diastolic of 10 mm. an<l 2.> mm.; in one the diastolic fell 2.J mm. while the systolic renniined unchanged. The conclusion is that the alteration in blood pressure is again an indirect digitalis effect which depends on the improvement in thi' circulation and is always in the direction of the optinuini pressure for the individual.

ToxK Kkkkcts The manifest-atir)ns regarded as evidences of digitalis toxicity were all included in the alimentary disturbances nr cardiac irregidarities. From 24 tf> 3(5 hours In-fore actual nausea and vomiting <wcurred, many |)atients complained "f general malaise, often headache or of some indefinite and indescribable sensation of discomfort and usuallv refused food.


Eggleston: Jour. Amor. Med. Assn.. 1917. LXIX. 951.


Considering 20 cases, nausea occurred in 12 and vomiting in six of these; diarrlnea was encountere<l five times. In nearly all eases these disturbances disai)])eare(i promptly after discontinuance of the drug. In Xo. 355 miu.<ea aiul diarrhum persisted for fo.ir days. This was the only instance of anything that might be regarded as evidence of the so-called cumulative action if digitalis. The central origin of the nausea and vomiting i>.-oduced by digitalis has been established by the work of Ilatchar and Eggleston." In six cases it was necessary to discontinuo the digitalis becau.se of the onset of serious cardiac irregularities unaccompanied by alimentarv symptoms.

DiGIT.VUS Irregil-vrities

Digitalis " coui)ling," a familiar sign of excessive digitalis dosage, appeared twice in the series. The occurrence of premature beat^ at irregular int^-rvals was frequently seen, usually at the time of otlier evidences of toxicity. These ])rcnniture beats, an expression of heightened irritai)ility of the ventricular muscle, always disa|)peared after atropin.

Sinus arrhytlunia <lue to digitalis occurred in two cases. In Xo. 334 (see Fig. ID) it disappeared |iromptIy after atropin, but returned and persisted, though gradually decreasing, for 10 days. In Xo. 37.J the arrhytlunia was not removed by atropin, although there was an escape of the pacennikcr (Fig. oD).

Production of " jiuisus altcrnans," dcscrilicil by Mackenzie and others was not encountered. In one ca.se in which that condition was originally present the alternation disappcareii under digitalis (Fig. 2). ."Similar results have been reported by Wimlle.*

In Xo. 342 after 25 c. c. of digitalis atrial tachycardia with irregular ventricular response and varying conduction time was present. .N'ornuii nirchanism was rcstoreij bv atropin (Fig. 3).

That com|)lcte atrioventricular dissociation may occur iluring the administration of digitalis is well known. Christian '" has reviewed some of the literature and reported ca.ses. Hoi)inson and Wilson ' have shown that in cats with the vagi intact complete dissociation constantly occurs when 7.") per cent of the mininnim lethal ilose has liecn given ;.with the vagi cut. the effect on conduction is not constant. In two cases transient complete di.ssociation occurred, beside the case of atrial tachycardia with high-gradi- block previously mentioned. The production of dissociation by action on the iidiibitory mechanism is illustrated in Fig. 4, which shows in sequence, prolongation of the I'-R interval, dropped beats and dissociation. In these cases of di.ssociation atrr>|iin restored the normal mechanisu) and this persisted during the hour under examination in the laboratory and was still present at examination 12 hours later. That "e.sca[)e" from vagus a<'tion on the con<luction system may occur is illustrated in Fig. 5; tlu- I'-H interval had


•Hatcher and Egglfston: Jour. I'harm. and Exp. Tlierap.. 1912. IV. 113. •Windle: Quart. Jour. Med., 1917, X. 274. "Christian: Arch. Int. Med.. 1915. XVI. 341.


134


[No. 339


lengthened from 0.12 to 0.22 sec, dropped beats were present and complete block was anticipated ; however, a record taken eight hours later showed the mechanism to be normal and the P-K interval 0.16 sec.

Changes in the Electrocabdijgram

Modification of the T-wave of the e^ jctrocardiogram by digitalis has been carefully studied 'jy Cohn and his coworkers." The following changes in tlie T-wave were observed in this study: Any degree of flattening of an upright or inverted wave until the isoelectric line was reached ; inversion of an upright wave ; reversion of an inverted wave ; the formation of a diphasic wave, either alone or in conjunction with any other change. The change in the wave continues throughout the administration of the drug so that its conformation varies from day to day with the amount given. Compare the T-waves in Figs. 1 and 3. These changes are attributed by Cohn to an alteration in the muscle balance, resulting in turn in an alteration of the relation of apex to base negativity. This action is for the most part on the myocardium itself. That the true digitalis effect may be masked by vagus stimulation is seen in the changes that frequently occur after atropin. The height or depth of a wave may be affected or reversal may occur, as in Fig. 3. These changes disappear with the action of atropin and the specific digitalis effect is again evident.

In every case the first definite digitalis effect was a change in the T-wave. This was found by Cohn in his cases and Robinson and Wilson ' in their experimental study observed the first change to be a flattening or inversion of T, which occurred with 25 per cent of the lethal dose.

A comparison of the T-wave changes produced by each of the tinctures used is interesting and points clearly to slow absorption of the first as the cause of its inefficiency. In No. 320 lowering of T, was observed after 16 c. c, definite inversion after 84: c. c. In the four remaining cases in which the first tincture was used an average of 34 c. c. was given before any definite change could be recognized. With the second tincture definite changes were recorded in most cases after 10 c. c. or less. In No. 371 Tj was lower after 5 c. c. ; in No. 368 Tj was definitely inverted after 10 c. c. Eecords were seldom taken between 10 and 20 c. c. and no attempt was made to establish the minimum amount that would produce a change.

From this small series in which large doses were used so that changes in more than one wave were recorded simultaneously it is not possible to say which T usually changed first, but it did appear that T. is most frequently affected and undergoes the greatest change.

The disappearance of the digitalis action may likewise be followed by changes in the T-wave which begin soon after the drug has been discontinued. The duration of the digitalis effect, as might be estimated by these changes, was not determined.

The alteration in tlic P-wave seen in some of these cases has been considered elsewhere." In nine cases, 30 per cent of


"Cohn, Fraser and Jamison: Jour. Exp. Med., 1915, XXI, 593. "Carter and Wedd: Arch. Int. Med., 1919, XXIII, 1.


the series, the P-wave was affected; in eight of these the change occurred only in the third lead, and in one in both the second and third leads (Figs. 1 and 5). In five cases an originally inverted P was rendered upright by digitalis and in three of these the return to the original form was followed after the drug was discontinued. In four of the cases of this group a temporary reversion occurred after atropin. In four cases an originally upright wave was inverted by digitalis and in three of these the wave was reversed by atropin and remained upright, whereas in the fourth the inverted wave was upright 12 hours after the discontinuance of digitalis. Satisfactory explanations for these observations are wanting. There may be a rearrangement of atrial muscle fibers, but the response to atropin in both groups indicates greater vagus influence than in the case of the T-wave. Concerning the limiting of the effect to the third lead, it may be noted that this lead represents primarily the left side of the heart, and all but two of these cases clinically showed marked enlargement to the left, and in six the electrocardiogram was of the type characteristic of left ventricular preponderance.

The occurrence of tlie U-wave as a component of tlie ventricular complex in the normal electrocardiogram is recognized. According to Lewis," it is not uncommon and is related to the early events of diastole. In the records of this laboratory it has seldom been seen. In one case (Fig. 6) a U summit appeared after 30 c. c. of digitalis had been given and continued throughout the remaining observations. It was not due to the appearance of a latent wave with a slower rate, for the rate when it was first seen was faster than the original, and it did not seem to be influenced by atropin. As the patient left the hospital, changes occurring after digitalis was discontinued could not be followed.

In his text Sollman states that, in man, a-v conduction is constantly impaired and that this is an early and positive sign of digitalis action, and Cohn and Fraser " found changes ' in 12 patients studied by them, including four who had no heart lesion. According to AVhite and Sattler " " this impairment of conduction is practically entirely due to increased vagus tone " and they report that in every instance after digitalis in which delay in conduction amounted to more than 0.05 sec. atropin reduced the P-R interval to less than its original value. In six of 21 cases in this series there was no appreciable change in the P-R interval. Measurements were made with calipers and a hand lens, but are believed to be sufficiently accurate for clinical purposes. In not one of five cases in which the conduction time was prolonged 0.05 sec. or more did atropin restore the original, and in two cases in which complete dissociation occurred the P-R interval in the normal mechanism after atropin was longer than in the original (Fig. 4). In the case with atrial tachycardia and high-grade block the P-E interval after atropin was the same as the original.


"Lewis: Clinical Electrocardiography, 1913, London. "Cohn and Fraser: Jour. Pharm. and Exp. Therap., 1913-14, V. 512. » White and Sattler: Jour. Exp. Med., 1916, XXIII, 613.


THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919

r



1


>»


1


t




I


R


f


[ [

[


I

i



>


Ui


V


f


THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1919


PLATE XVII


Fiii. 2 (Case 321). — A. on admission; B, after 102 c. c. of digitalis.


HBn^iji^^i*^iiP^N*jii^i'^i*iFVfci^*'*^wMi^^^




IKWl^lll




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^ ' ^ ' ^



mwii'liii mimitmiWjiMrmi] i owji^n "i





-- "f vv;-
::" / V - ^".f'--=


-f immm


- ' -H:5E-i


y^-mmAj'jm>^


Fig. 3 (Case 342). — A, on admission; B, after 12 c. c. of digitalis; C, after 25 c. c, atrial rate 216, ventricular rate 80; D. 30 min. after atropin; E. 1 hr. after atropin; F. 12 hrs. later.


Fig. 4 (Case 351). Lead II.— A. on admission; B, after 24 c. c. of digitalis; C, after 72 c. c. ; D, after 96 c. c. ; E, after atropin.


THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY. 1919


PLATE XVIII



rAiN>/VvV^'^i'N*s^/


/9


U¥«'w*'^*'^'w**^' " '***^* ^ ^ ^ W' * ***^ *» «>ii n »»»i^


'«M,^-^\V-*-**/-- s,,^^


TC


3> A. an.




HMMM V«y^MHMMM«<MMMM« 


-rff


Fig. 5 (Case 375).— .4. on admission; /}. aft. r nn c c of diK'iialis; C. 8 hrs. later: D. after 100 c. c. (a) ; after airopiu (b).


2)o.


I I


^t^mmmi p^^^




^^^-^^-A.



S,0m^*m^-Si


I I


^^,^,i0^f/m^Jf^^0^^


Kic. 7 (Case 354). Lead II.— .1. on admission: «, after 22 c. c. of digitalis: C. 19 lirs. later, after 29 c. c. (a) ; after atropin (b); /J. after 39 c. c. (a): after atropin (b).


fl a.


tr

y'*S/*V Xy*-V S,,r^V H.V<-v


atropin.


di»!iUiM.> 1 .1 p . .111. I HI II. 1. 1 later.


I


May, 101!) I


JOHNS HOPKINS HOSPITAL lULLETIN


135


Direct action on the conducting; tissue may be illustrated i)y Xo. 323: orijrinal P-R, 0.120; after digitalis, 0.213; altor atro])in, 0.163, and there was no escape of the pacemaker. In Xo. 27!) in which a lenirthening of 0.02 sec. occurred there was no shortening of conduction and no sinus escape after atropin. Also consider the I'-R intervals in Fig. 7. In otiior cases there was partial or complete reduction of the conduction time. The data ohtaincd tend to show that impairment of conduction by digitalis nuiy be due to either increased vagu-^ tone or to direct action on the conducting system, or to a combination of both, which is the usual mechanism in cases of pronounced action.

Definite ini|)airmcnt of conduction was certainly not an early evidence of digitalis action, but a gradually progressive one, and an appreciable change in it* time relation .seemed comparable to the finding of Robinson and Wilson, that prolongation of conduction time occurred after 50 per cent of the lethal dose had been given.

But few cases with an original conduction time of more than 0.18 sec. were studied. In Xo. 364, a referred patient, an original conduction time of 0.25 which had been increased to 0.29 by 12 c. c. of digitalis was restored completely by atropin. The possibility of escape from digitalis action on the conduction system has been mentioned (Fig. 5). Xo criterion was apparent by which a marked effect on conduction might be predicted and the conclusion reached is that of Cohn.* that any effect on conduction is a specific effect of the drug, a])art from any pre-e.xisting damage in the .system.

Action ix Fibrill.\tiox .vxd Flutter

There is sufficient satisfactory experimental evidence that digitalis produces its characteristic effects by acting centrallv in the medulla and locally on the heart muscle. The usual test for differentiating central and local action is the behavior after removal of vagus intluence, by section of the nerve or the use of atropin. That the various digitalis effects may l)e pro<luced in man through either mechanism alone or througli both simultaneously has been jiointed out when considerin": the specific digitalis actions.

In 1871 Traube showed that digitalis slowing was due to (itimulation of the vagus center and this has been confirmed by many experimenters since that time. Cushny " has demonstrated that in the perfused mannnalian heart, in certain rare cases with normal mechanism in man and specially in atrial fibrillation in man, digitalis may slow the pul.<e inde|)endently of the inhibitory mechanism. Robinson and Draper" have shown in atrial fibrillation in man that mechanical stimulation of the right vagus nerve usually cau.i^ed marke<l slowing or stoppage of the ventricular rhythm and state that the ventricular pauses were apparently due to blocking of .stimuli from the atria. Ilirshfelder" found that in dogs with artificially induced fibrillation the heart could be markedly slowed


"Cushny; Jour. Pharm. and Exp. Therap., 1918. XI, lO.S. "Robinson and Draper: Jour. Exp. Med.. 1911, XIV, 217. " Hirshfelder: Jour. Pharm. and Exp. Tlierap.. 1915, VI. 597


by digitalis and that tlie rapid arrhythmia promptly returned after paralysis of the vagi with atropin, and also that further .^lowing and com|)lete block could be i)roduced after the vagi liad been paralyzed, although the fibrillation continued. Commenting on this work, Cushny says: "But this is not the characteristic reaction in clinical fibrillation as he seems to suppose; the slowing in these cases is independent of tiie iidiibitory mechanism."

In all cases of fibrillation under the inllucnce of digitalis to which atro|)in was given an increase in ventricular rate occurred. Similar results have been reported by Cushny " and by Mackenzie. The atria are seen to continue in fibrillation, so there is no functioning pacemaker. Hence the increased ventricular rate must result from an increase in the number of impulses ])ermitted to pass through the conducting tissues, and such an increase brought about by atropin implies a former depression of conduction by vagus tone. Tinit digitalis produces more marked slowing by the direct action on the mu,«cle of the fibri Hating heart no one would attempt to deny, but that the vagus center in the medulla, the usual site of action of the drug, should be ignored because of an altered condition of the mycx-ardium which is less obvious. That the decrease in the ma.ximum rate under atropin of the digitalized heart which was observed in 100 per cent of the fibrillating hearts and in 76 per cent of those with normal mcchaiiisni nniy be tjiken as a measure of the local action of the drug is seemingly a possible interpretation.

From a compari.son of the reaction of the perfu.sed heart tfi digitalis with that of clinical fibrillation, Cushny concludes that the reaction so characteristic of fibrillation is due not to the fibrillation itself but to a more fundamental factor, malnutrition. Furthermore, it is conceivai)le that i)ecau.«e of the faulty circulation of the fibrillating heart an accumulation of cellular metal)olites may result, by virtue of an increased H-ion concentration in the jiroduction of a more highly glucosidolytic medium, and that because of increased destruction, there may result an increa.sed capacity for digitalis bodies. Similar action may jm.ssibly occur in other tissues also and may constitute the mechanism by which many individuals with .severe myocardial lesions can take large amounts nf digitalis before toxic symptoms a])])ear.

The action of digitalis in atrial fiulter, a condition similar to fibrillation, is both central and local (Figs. 7 and 8). In four cases of flutter examined the administration of atropin reduced the block to 2:1. Unfortunately atropin was not given after the change to fibrillation, but in Xo. 354 the normal mechanism jircsent after the last flutter record shows sinus cscajK' and partial n'ductidn of the conduction time.

.SUMMAKY

Careful observations on the action of tincture of digitalis have been made in many j)atients. It wa.s soon apparent that successive tinctures supplied to the hospital wards showed marked variation in their efficiency. Two biologically stand


" Cushny. Marrls and Silberg: Heart. 1912, IV, 33.


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[No. 339


ardized tinctures of approximately theoretical strength were studied and it appeared that the ineificiency of one was due to failure of prompt absorption from the alimentary canal, as was indicated by the larger amount necessary to produce a change in the T-wave, the earliest demonstrable digitalis effect.

Daily doses averaging 10 c. c. were given and continued imtil alimentary disturbances or abnormalities in the cardiac mechanism appeared. In no case was there any ill effect attributable to digitalis and there were no evidences of the so-called cumulative action. The toxic dosage showed marked individiial variation, from 20 c. c. to 100 c. c. The earliest signs of toxicity were slight nausea and premature beats. It is believed to be a perfectly safe procedure and one which will promptly bring about the expected benefits of digitalis to begin with an initial dose of 5 c. c. of tincture and to continue with 8 or 10 c. c. daily until signs of toxicity appear or until clinical improvement warrants discontinuing the drug.

The various changes in the electrocardiogram have been considered. Of these alteration in the T-wave was the earliest and most constant. Modifications of the P-wave in the third lead in about one-third of the cases is noteworthy. In one case digitalis appeared to be responsible for the appearance of a


U summit. Definite prolongation of the P-E interval, indicating increased conduction time, was seen in 80 per cent of the cases. In two cases complete dissociation occurred and in one atrial tachycardia with high-grade block, and in all these normal mechanism was promptly restored by atropin.

From a consideration of the effect of atropin on the pacemaker, the ventricular response and the conduction time, it is believed that in all cases the action of digitalis is both central, in the medulla, and local, in the myocardium, with relatively greater local action in atrial fibrillation. Exception is taken to the statement of Cushny that in fibrillation there is no digitalis action through the inhibitory mechanism, and it is suggested that the decrease of maximum rate after atropin of the digitalized heart may be taken as a measure of the local action of digitalis on the myocardium.

In the series studied were cases with all possible valvular defects, all grades of decompensation, renal lesions of varying degrees of soveritv', systolic blood pressures ranging from 90 mm. to 230 mm. and almost all of the recognized types of myocardial involvement, including cases of intraventricular block, bimdle branch block and complete dissociation, and there was not found any clinical entity which might be said to constitute a contraindication to the use of digitalis.


NOTES ON NEW BOOKS


The Principles of Acidosis and Clitiical Methods for Its Study. By Andrew Watsox Sellards, Associate In Harvard Medical School. {Harvard University Press. 1917.)

This work of some 111 pages exclusive of the bibliography deals with acidosis with a terseness of style and elimination of unnecessary detail which make it very interesting as well as valuable to the physician and student. There is careful consideration of the various theories concerning acidosis and the evidence in favor of each is thoroughly discussed.

The first three chapters are given to the consideration of the chemistry of acids &nd bases, their metabolism in the human body, and methods of diagnosing pathological alterations in the mechanism. Particular attention is paid to the exact importance of change in the alkalinity of the blood and the physiology of the kidney in adjusting its excretion to these changes. In the next chapter the reaction of the body to sodium bicarbonate in health and disease is taken up. The value of observing this reaction is brought out. In this chapter also a very valuable test for the changes in the alkalinity of the blood is described in full. .

Succeeding sections deal with the occurrence of acidosis and a definition of the condition. The determination of a definition is most timely, since there is considerable variance among writers as to the exact meaning of the term " acidosis." The part dealing with therapy is very suggestive, although no definite working guide is given. Nevertheless, from a discussion of cases and results sufficient data are given to enable the practitioner to make immediate use of the method described by the author.

By no means the least important part of the work is that contained in the appendix, in which necessary laboratory methods are described fully and clearly. Definite instructions for carrying out the author's test for acidosis are given explicitly. There is also a very helpful method described for determining the patient's tolerance for sodium bicarbonate.


A very important feature of the book is the discussion of the pathological processes in the acidosis of diabetes, nephritis, and Asiatic cholera, with a differentiation of the steps in each. It is perhaps to be regretted that the writer did not take up the more intricate problems of protein, carbohydrate, and fat metabolism with the relation of each to acidosis, or that other acetonurias were not considered in the same thorough manner. But what the book may lack in tliis respect it gains in being concise, containing no confusing details, and being available for any one wltn a rudimentary knowledge of biochemistry and physiology. It is an important contribution both from the standpoint of information contained and also from the suggestions made concerning other problems in tlie same field which offer rich opportunity for study.

H. M. W.

Trench Fever: Report of Commission Medical Research Committee, American Red Cross. Prepared for publication by Richard P. Strong. (Printed for the American Red Cross Society at the Oxford University Press ty Frederick Hall, Printer to the University, 191S.)

Members of Commission: Richard P. Strong, Major, M. R. C, Assistant Director Division Laboratories and Infectious Diseases. In charge Subdivision Infectious Diseases, A. E. F. Homer F. Swift, Major, M. R. C, Senior Medical Officer, No. 1 United States Army General Hospital. B. E. F. Eugene L. Opie, Major. M. R. C, Pathologist, United States Army Base Hospital No. 21, B. E. F. Ward J. Macneal, Captain, M. R. C. Head Department Bacteriology, Central Medical Department Laboratory, A. E. F. Walter Baetjer, Captain. M. R. C, in charge Clinical Laboratory, United States Army Base Hospital No. 18, A. E. F. A. M. Pappenheimer. Captain, M. R. C, Pathologist, No. 1. United States Army General Hospital. B. E. F. A. D. Peacock, Captain, R. A. M, C. (T.). 2d London Sanitary Co. (Entomologist). (Subsequently attached.)


May, IDli)]


137


David Rapport, first Lieutenant, M. C, National Guard, A. E. F.

Major Richard P. Strong, M. R. C, In liis report on trench fever, has given another proof of the brilliant work which the public is now learning to expect from the army medical corps: and the investigations he reports in regard to trench fever should rank with their model, the classic studies of Reed and his colleagues on the method of transmission of yellow fever. The fact that during 1916 and 1917 no other infectious disease caused so much sickness among the soldiers in France as did trench fever, and its great prevalence at Salonica, in Italy and in Mesopotamia, made it of primary importance. To ascertain the method of its transmission would enable the authorities to take proper preventive measures, and thus much could be done to minimize an enormous wastage among the fighting forces.

Accordingly. Dr. Strong, in October, 1917, was selected by the Medical Research Committee of the American Red Cross to take charge of the work ot a special Trench Fever Committee. From that time the committee conferred with the British Army and medical authorities, who were also studying the problem, with the result that in February, 1918, experiments on a group of 82 selected volunteers from the United States Army were commence<i. The work was carried on at a stationary hospital of the I3ritish Expeditionary Force in France, sufficiently near to the front line to insure the study of trench fever cases early in their course. As the spring offensive was expected in two months' time, Uie workers had only this short period to investigate the problem before them. There resulted a marvel of coordinated research, which required simultaneous experimentation along many closely associated lines, each modifying the others as the work proceeded. The clinical, bacteriological, serological, louse investigation, blood inoculation and other studies all contributed their part in completing the work, which was reported as it developed to the British Army medical officers, who were also at work on trench fever.

In all a total of 103 different human experiments were carried on in the study of trench fever and its cause, and in these the disease itself was produced experimentally 62 times in different ways. Too much cannot be said in praise of the soldiers of the United States Army who offered themselves so heroically in order to make possible this splendid medical study. The results of this masterly piece of work are best summarized in Dr. Strong's own words:

"The most Important facts which have been demonstrated by our investigations are:

"1. That trench fever is a specific, infectious disease: that it is not a modified form of typhoid or paratyphoid fever, and is not related, from an etiological standpoint, to these diseases.

"2. That the organism causing the disease is a resistant, filterable virus.

" 3. That the virus causing trench fever is present particularly in the plasma of the blood of trench fever cases, and that such plasma will produce the disease on inoculation Into healthy individuals.

" 4. That the disease Is transmitted naturally by the louse Prdivulus humanus. Linn., var. rorpohs. and that this Is the important and common means of transmission. That the louse may transmit the dieease by its bite alone, the usual manner of infection, or the disease may be produced artificially by scarifying the skin and rubbing in a small amount of the infected louse excrement.

" 5. That a man may be entirely free from lice at the time he develops trench fever, the louse that Infected him having left him some time previously as his host, and that the louse neea only remain upon the Individual for a short period of time In order to infect him.

" 6. That the virus of trench fever is also sometimes present in the urine of trench fever cases, and occasionally In the sputum.


and that the disease may be produced in man by the introduction of the virus in the urine or sputum through the scarified or otherwise abraded skin.

"7. That since the urine and sometimes the sputum of trench lever patients are infective, these should be sterilized in order to avoid the possibility of accidental infection from them.

" 8. That in order to prevent trench fever or limit its spread, and thus save manpower for the armies, greater efforts must be made to keep soldiers in general from infestation with lice.

"On account of the great importance of the matter, the following sanitary regulations are advised:

" Exceedingly great care should be taken to disinfect completely all patients as soon as practicable, and particularly upon their entering the hospital. Patients on entrance should be carefully bathed, and subsequently sponged with alcohol. Their clothing and blankets should be removed, and. whether or not lice or ova are found upon them, should be carefully sterilized by moist heat at a temperature not below 70° Centigrade for half an hour, since it is possible for the virus to be still present on the clothing. It should be borne in mind that a man with trench fever may be entirely free from lice at the time that he develops symptoms of the disease. Trench fever patients should at all times be carefully protected from louse Infestation, and inspection of them for lice should be made daily. They should be treated in separate wards. As the urine contains the virus and is infective, It should be sterilized durins the active stages of the disease. Sputum cups should be provided for patients, and any expectorated sputum and saliva from tliom sterilized. Officers should regard the systematic destruction of lice as one of the most urgent of their duties, and shotild exercise every effort to prevent louse infestation among soldiers and to see that any of them Infested with lice are promptly disinfected and their clothing sterilized."

He further discusses in some detail the nature of the experiments above referred to, with special reference to tlie transmission of the disease, and points out that tlie incubation period of trench fever, when studied experimentally, was shown to be from 14 to 38 days, depending on the dosage and other factors. No reliance, however, can be placed on a study of the apparent incubation period in uncontrolled cases, naturally produced anions the troops. The practical value of these incubation period studies lies In the fact that it may be from 10 to 23 days after the last bite by an infected louse before a man will develop trench fever. A man may be quite free from lice at the time of the outset of the symptoms of the disease, and. although a sufferer himself, he is of no danger to others, unless he is in a louse-infected community, so long as his urine and sputum are carefully sterilize<l.

The remainder of the book contains a careful and systematic detail of the numerous experiments which were the foundation of these conclusions. They enable the writer to examine the evidence and to decide upon the justice of tfie conclusions formulated by the commission. The work is most creditable to scientific medicine, and is a fresh example of what can be done by the association of a number of observers under the leadership of a competent and experienced head. Similar problems are existing throughout the world, and the need of equally coordinated investigations Is pressing.

G. H. W.

The Third Orrat Plague. By John H. Stokj^, M. D. Cloth $1.50. (Philadelphia: W. II. Saunders Company, 1!>1~.)

Stokes' essay Is a most timely one. This book is Intended primarily to enlighten the lay mind on the ever-Important topic of syphilis. It fulfills more than the author's purpose, for we believe any individual with medical training can profit by a thorough study of it.

The history, nature and course of syphilis; the blood test and treatment; the cure, hereditary aspects, transmission and hygiene


338


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of this ever-Increasing plague — so aptly termed — are sketched in a lively, virile, and Intelligible style, and best of all In a most understandable manner.

In the chapter on " Mental Attitudes in Their Relation to Syphilis," the moral and personal prophylaxis and the public effort against syphilis are approached and handled with a fairminded conception of what they entail. A very brief and unprejudiced expose of the pros and cons of this ever-burning problem are given with a circumspection and Judgment which entitle the author to a most respectful hearing.

The book, therefore, is decidedly illuminating; it answers so satisfactorily many of the every-day questions regarding the handling of this, one of our greatest and most serious medical liabilities. It is attractively presented; the style is easy and clear, and the author's attitude on the various moral, social and economic aspects of syphilis are very sane and commendable.

I. R. P.

Syphilis and Public Health. By Edvvabd B. Veddab, M. D. Cloth $2.25. (Philadelphia and New York: Lea and Febiger, lOlS.)

Following an introduction on the " Importance of Syphilis in Relation to Public Health," together with statistics of mortality, and after a discussion of syphilis as a sanitary problem, the book is divided into four chapters:

1. Prevalence.

2. Sources of Infection and Method of Transmission.

3. Personal Prophylaxis.

4. Public Health Measures.

An appendix is included describing the technic of the Wassermann test of the blood serum; and. In addition, several sections, including the " Control of Syphilis in the Army." " Methods Employed In Some Cities," etc.

This book is a real contribution to the literature of syphilis. Statistics are frequently a " necessary evil " and always open to criticism, but the value of figures in a book of this scope is essential, and therefore beyond the domain of a critical review.

Veddar's discussion of facts and of figures is supplemented by a splendid bibliography, especially on the methods of transmission. This latter chapter is worthy of careful reading. The presentation of the pros and cons of prophylaxis, as well as the discussion on the value of chemical methods of prevention, together with a history of the use of calomel ointment, are splendid features. The author's views on notification, treatment, and especially on the sociological aspects, are rational and worthy of commendation.

This handy volume is well written and well typed. We would recommend it most warmly to the notice of all individuals interested in the medical and (consequently) sociological field of syphilology.

I. R. P.

Diseases of the Skin., By Mllton B. Haktzell, M. D. Cloth $7.00. (Philadelphia: J. B. Lippincott Company, 1917.)

With the appearance of another text-book on dermatology, the reviewer naturally looks, among other things, for something new or for a different presentation of facts already known. Dr. Hartzell's book is, in this connection, both satisfying and disappointing.

The subject is handled by the author in the manner usually followed by the every-day text-book. Nothing new is suggested or proposed. One finds the invariable divisions of anatomy, symptomatology, general etiology, etc., followed by the customary division of the dermatoses, according to anatomic characters, hyperaemias, inflammations, hjemorrhages, new growths, neuroses, etc.

The size of the book is adequate, but it is neither a short resume for the student nor an encyclopedic reference treatise tor the specialist. Nevertheless, it should prove to be very profitable read


ing for the general practitioner who is not too deeply concerned with the finer distinctions of diagnosis, pathology and treatment. If considered in this light one finds the book sufficient, and although it presents nothing startling or new in the consideration of general etiology and treatment, it deserves credit for voicing the author's personal views on many subjects. It is unfortunate that the author, after attributing so much well-deserved credit to X-ray therapy, has not incorporated a brief section on this ever-increasing and important therapeutic agent, and also on radium therapy.

With the exception of several worthless colored plates, the photographs and plates are notably splendid; and the photomicrographs in particular — a genuine relief from the almost diagrammatic sketches in the older treatises — brook no criticism. The remarks on etiology and pathology are eminently concise, rational and clear; they are adequately stressed.

There are other outstanding features: the author has avoided much needless discussion; in tact, his somewhat didactic method of presentation is a real advantage; but it is questionable whether the omission of at least a selected bibliography enhances the value of the book. He has certainly done a service in clarifying our knowledge of some dermatoses usually relegated to an obscure grouping. The other brief chapter on sarcoids is ample proof.

It would lead too far to take up the various chapters in critical review. Although the discussion of syphilis appears to be rather scanty, and the pathology somewhat briefiy discussed, there are excellent chapters on ringworm and on carcinoma.

The few typographical errors will surely be remedied, together with correction of the spelling of some proper names. The book, therefore, should appeal primarily to the general practitioner; next, to the specialist for a brief review; and lastly, only to the student who, without delving too far, wishes to read and to learn.

I. R. P.

Radio Diagnosis of Pleuro-Pulmonary Affections. By F. Baejon, Medicin des Hopitaux de Lyon. Translated by James A. HoNEij, M. D., Assistant Professor of Medicine in charge of Radiography, Yale Medical School. (Yale University Press.)

This volume Is the second work published by the Yale University Press on the Williams Memorial Publication Fund — a gift made to Yale University by George C. F. Williams, M. D., a member of the class of 1S7S, Yale School of Medicine.

Although this translation is a little late in appearing, it arrives at a time when it is most needed. Nothing concerning the X-ray examination of the thorax as yet published has been so thorough as this book. The fluoroscopic examination at the expense of the plate method of study of lesions of the thorax might be mentioned as one of its few weak points.

Frequent reference to other French Investigators exclusive of all other nationalities is made and. although the book may have been intended only tor use by our French colleagues, it nevertheless must create a little embarrassment to other notables who have so earnestly tried — and, it may be added, not in vain — to elaborate this valuable asset to clinical diagnosis.

The book is divided into five parts with many chapters subdividing each part:

Part I. The Fluoroscopic Appearance of the Normal Chest Shadows when Viewed from All Different Angles.

Part II. The Study of the Pleur».

All the different pathological states of the pleurte are taken up somewhat in detail. Especially interesting is the dissertation on the influences in the production of the curve of Damoiseau. The second chapter deals with circumscribed and encysted pleurisy and is especially clear and well illustrated. The paragraphs dealing with pleurisy of the hilus region with case reports and illus


May, 1919]


139


trations is a genuine addition to tlie chapter. The pages devoted to pneumothorax are well illustrated, interesting and instructive.

Part III. Foreign Bodies in the Bronchi.

The metallic foreign bodies and foodstuffs are discussed in detail and the possibility of late and serious pulmonary complications resulting from failure to diagnose them is worthy of mention. The X-ray findings in acute and chronic bronchitis, bronchial stenosis and bronchial dilatation are also instructive. Tracheobronchial adenopathy is next studied and a very acceptable and descriptive explanation is given. The various groups of glands are discussed and the best means for observing them on the screen are pointed out. Emphasis is laid upon the fact that too litile attention is paid to the study of adenopathy. Illustrations and diaphragmatic drawings also help to complete this part of the work.

Part IV. The Lungs.

The first chapter deals with the fluoroscopic appearances in acute primary and secondary congestion, passive congestion and oedemas. Infarction, its appearance and differentiation from other pulmonary sliadows, is particularly clear.

The remaining chapters of Part IV, which are the longest of any, are given over to the study of acute infectious pulmonary processes, chronic pulmonary processes, pulmonary tuberculosis and lung tumors.

Pulmonary tuberculosis is considered under three distinct groups; (1. Pulmonary tuberculosis without clinical or stethoscopic signs. ( Latent forms. ) b. Pulmonary tuberculosis with positive clinical but negative, doubtful or very limited stethoscopic signs. (Early Forms. Period of incubation. Miliary.) c. Advanced pulmonary tuberculosis with evident clinical and stethoscopic signs. ( Chronic pulmonary tuberculosis with its many forms. )

Nothing new in the way of diagnosis is offered, but the appearance, development of complications and their appearance fluoroscoplcally is well pointed out and the total absence of fanaticism certainly adds materially to tliis greatly discussed topic, the X-ray diagnosis of pulmonary tuberculosis.

Lung tumors complete this part of the book and, aside from mentioning the good illustrations, little need be said.

Part V ends the l)ook and deals with the penetrating wounds of the thorax by war projectiles. A brief clinical and radiologic


entity Is given which proves interesting, but certainly not comprehensive enough from a clinical standpoint to be of any material aid to the surgeon or internist in determining the course of procedure in these grave cases. The points discussed in diagnosis and complications are interesting and instructive, but the problems in the localization and extraction of these projectiles are still unanswered. c. A. W.


liointgen Tahnic (Diaffiiostic). By Noknian C. Prime, M. D. St. Louis: C. T. ilosby i( Co.. UU7.)

This book of 140 pages deals principally with the technic employed In making X-ray plates of different parts of the body.

The descriptive technic is mainly good, but one cannot help feeling that some of the manufacturers of X-ray accessories have used undue influence in advocating their particular products.

In view of the increasing popularity of technicians for the performance of technical duties in an X-ray laboratory the book might have some usefulness in this phase of the work, but when this has been said, no further need for it can be found.

C. A. W.

ll'or Neuroses. By John T. M.mCihkv, M. D. With a preface by W. H. R. Ri\TERs, M. D. (Lond.). 132 pages. (Camhrirlgr: At The Universit)/ Press. H'lS.)

This book consists of observations originally published in the P.ii/chintrie BuUctiii of the New York State Hospitals, and records the author's conclusions after a brief visit to Great Britain in 1917.

The point of view adopted, with the emphasis on the conflict between the different instincts, that of self-preservation and that of loyalty to the group, and on the adaptive role played by the symptoms in the neuroses, is now so widely accepted as not to require special elaboration. The different groups of neuroses, those with predominance of anxiety symptoms, those with predominance of physical synii)toms, those where cardiac symptoms are specially in evidence, etc., are discussed in a clear and interesting manner. In special chapters the questions of etiolog>' and of treatment are succinctly dealt with.

C. M. C.


BOOKS RECEIVED


.Veir Jersey. Forty-First Annual Report of the Department of Health of the State of New Jersey, 1917. 1918. 8'. 381 pages. State Gazette Publishing Company. Printers. Trenton, N. J.

Persei-uiions of th'- <;riil;s in Turk-ii t<inrr the Beginning of the European ^\^nr. Translated from official Greek documents by Carroll N. Brown, Ph. D., and Theodore P. Ion. D. C. L. 1918. %'. 72 pages. Published for the American Hellenic Society by Oxford University Press, American Branch. New York City.

Miehigan State Board of Health. Forty-Fourth and Forty-Fifth Annual Reports of the Secretary of the State Board of Health of the State of Michigan for the years ending June 30, 1916. and June 30, 1917. 1917. 8 . 243 pages. Wynkoop Hallenbeck Crawford Company, Lansing, Mich.

Amputation Slumps. Their Care and After Treatment. By G. Martin Huggins, F. R. C. S. Oxford War Primers. 1918. 16 . 228 pages. Henry Frowde and Hodder & Stoughton, Oxford University Press. London.

Bipp Treatment of War Wounds. By Rutherford Morison. Oxford War Primers. 1918. 16°. 72 pages. Henry Frowde and Hodder & Stoughton, Oxford University Press, London.


Xursing Terhnir. By Mary C. Wheeler, R. N. 32 specially prepared illustrations under personal supervision of the author. 11918.] 16°. 265 pages. J. B. Lippincott Company, Philadelphia and London.

The Essentials of Materia Mediea and Therapeutiea for Xurses. By John Foote, M. D. Third edition, revised, enlarged and reset. Llppincotfs Nursing Manuals. 11918.] 8°. 310 pages. J. B. Lippincott Company, Philadelphia and London.

I nited States. Department of Commcree, Bureau of the Census. Sam L. Rogers Director. Deaf-mutes in the United States. Analysis of the Census of 1910, with Summary of State Laws Relative to the Deaf as of January 1, 1918. 4°. 221 pages. Government Printing Office. Washington.

The Indian Opi ration of Couehing for Catarart. Incorporating the Hunterian Lectures delivered l)efore the Royal College of Surgeons of England on February 19 and 21, 1917. By Robert Henry Elliot, M. D., B. S. (Lond.), Sc. D. (Edin.), F. R. C. S. (Eng. ). etc.. Lieut. Colonel I. M. S. (retired). With 4.1 illustrations. 1918. 8°. 94 pages. Paul B. Hoeber, New York.


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Diseases of the Male Urethra, Incluciing Impotence and Sterility. By Irvin S. Koll, B. S., M. D., F. A. C. S. Illustrated. 1918. 8°. 151 pages. W. B. Saunders Company, Philadelphia and London.

Clinical Diagnosis. A Manual of Laboratory Methods. By James Campbell Todd, Ph. B., M. D. Illustrated. Fourth edition, revised and reset. 191S. 12°. 687 pages. W. B. Saunders Company, Philadelphia and London.

International Clinics. A Quarterly of Illustrated Clinical Lectures and Especiplly Prepared Original Articles. By leading members of the medical profession throughout the world. Edited by H. R. M. Landis, M. D. Volume II. Twenty-eighth series, 1918. 8°. 286 pages. J. B. Lippincott Company, Philadelphia and London.

The Harvey Lectures. Delivered under the Auspices of the Harvey Society of New York, 1916-1917. By Prof. J. S. Haldane, Dr.

F. M. Allen, Dr. Paul A. Lewis, Prof. H. H. Donaldson, Prof.

E. V. McCollum, Prof. J. W. Jobling, Prof. John R. Murlin, Prof. F. W. Peabody, Prof. W. H. Howell. Series XII. 1918. 8°. 323 pages. J. B. Lippincott Company, Philadelphia and London.

The Hodgen Wire Cradle Extension Suspension Splint. The Exemplification of this Splint with Other Helpful Appliances in the Treatment of Fractures and Wounds of the Extremities and Its Application in Both Civil and War practice. By Frank

G. Nifong, M. D., F. A. C. S. With an Introduction by Harvey G. Mudd, M. D., F. A. C. S. With 124 illustrations. 1918. 8°. 162 pages. C. V. Mosby Company, St. Louis.

A Treatise on Cystoscopy and Urethroscopy. By Dr. Georges Luys. Translated and edited with additions by Abr. L. Wolbarst, M. D. With 217 figures in the text and 24 chromotypographic plates outside the text, including 76 drawings from original water colors. 1918. S°. 386 pages. C V. Mosby Company, St. Louis.

A Manual of Otology. By Gorham Bacon, A. B., F. A. C. S., assisted by Truman Laurance Saunders, A. B., M. D. Seventh edition, revised and enlarged. With 204 illustrations and two plates. 1918. 12°. 583 pages. Lea & Febiger, New York and Philadelphia.

Botulism. A clinical and Experimental Study. By Ernest C. Dickson, M. D. Monograph No. 8. 1918. 4°. 117 pages. Rockefeller Institute for Medical Research, New York.

University of Michigan. Transactions of the Clinical Society, October, 1916-October, 1917. Volume VIII. Edited by the Secretary-Treasurer. 1917. 8°. 146 pages. University Hospital, Ann Arbor, Michigan.

University of Michigan. Contributions from the Department of Obstetrics and Gynecology. Volume IV, 1915-1918. 4°. Ann Arbor, Michigan.

Neurological Clinics. Exercises in the Diagnosis of Diseases of the Nervous System Given at the Neurological Institute, New York, by the Staff of the First Division. Edited by Joseph Collins, M. D. 1918. 8°. 271 pages. Paul-B. Hoeber, New Y'ork.

Food Primer for the Home. Compiled by Lucy H. Glllett. 1918. 8°. 19 pages. Bureau of Food Supply, Association for Improving the Condition of the Poor, New York.

Clinical Disoj-ders of the Heart Beat. By Thomas Lewis. M. D.,

F. R. S., D. Sc, F. R. C. P. [Fourth edition.] 1918. 8\ 120 pages. Paul B. Hoeber, New York.

The Medical Clinics of Xorth America. Vol. 1. No. 6. May. 1918. 8°. W. B. Saunders Company, Philadelphia and London.


The Action of Muscles. Including Muscle Rest and Muscle Reeducation. By William Colin Mackenzie M. D., F. R. C. S., P. R. S. (Edin.). With 99 illustrations. 1918. S\ 267 pages. Paul B. Hoeber, New York.

Symptoms and Their Interpretation. By James Mackenzie, M. D., LL. D. [Aber. and Edin.] Third edition. 1918. 8°. 318 pages. Paul B. Hoeber, New York.

Naval Hygiene. By James Chambers Pryor, A. M., M. D. Published with approval of the Surgeon General, United States Navy and by permission of the Navy Department. With 153 illustrations. 1918. 12°. 507 pages. P. Blakiston's Son & Co., Philadelphia.

The Wassermann Test. By Charles F. Craig, A. M. (Hon.), M. D. (Yale). Published with authority of the Surgeon General, United States Army. Illustrated with colored plates, halftone plates, and 57 tables. 1918. 8°. 239 pages. C. V. Mosby Company, St. Louis.

Essentials of Dietetics. A Text-Book for Nurses. By Maude A. Perry, B. S. 1918. 12°. 159 pages. C. V. Mosby Company, St. Louis.

Concerning Some Headaches and Eye Disorders of Nasal Origin. By Greenfield Sluder, M. D. With 115 illustrations. 1918. 8°. 272 pages. C. V. Mosby Company, St. Louis.

War Surgery of the Abdomen. By Cuthbert Wallace, C. M. G., F. R. C. S. (Eng.), M. B., B. S. (Lond.). With 26 illustrations. 1918. 8°. 152 pages. P. Blakiston's Son & Co., Philadelphia.

La Suspension dans le Traitement des Fractures. Par P. Desfosses et Charles Robert. Preface de M. Pierre Duval. 1918. 12°. 172 pages. Masson et Cie, Paris.

Surgical Applied Anatomy. By Sir Frederick Treves, Bart., G. C. V. O., C. B., LL. D., F. R. C. S. (Eng.). Seventh edition, revised by Arthur Keith, M. D., LL. D. (Aber.), F. R. C. S. (Eng.), F. R. S., and W. Colin Mackenzie, M. D. (Melb.), F. R. C. S. (Edin.), F. R. S. E. Illustrated with 153 figures, including 74 in color. [1917.] 16°. 702 pages. Lea & Febiger. Philadelphia and New York.

A Text-Book of Physiology For Nurses. By William Gay Christian, M. D., and Charles C. Haskell, M. D. Illustrated. 1918. 12°. 168 pages. C. V. Mosby Company, St. Louis.

Surgical and War Nursing. By A. H. Barkley, M. D. (Hon.), M. C, P. A. C. S. With 79 illustrations. 1918. 12°. 208 pages. C. V. Mosby Company, St. Louis.

Hygiene for Nurses. By Nolie Mumey, M. D. With 75 illustrations. 1918. 12°. 160 pages. C. V. Mosby Company, St. Louis.

Nursing in Diseases of Children. By Carl G. Leo-Wolf. M. D. With 72 illustrations. 1918. 12°. 314 pages. C. V. Mosby Company, St. Louis.

Gymnastic Treatment for Joint and Muscle Disabilities. By Brevet Col. H. E. Deane, R. A. M. C. With preface by Temp. Colonel A. Carless, Army Medical Service, and by Brevet Lieut. Col. F. W. Mott, P. R. A. M. (T.). 1918. 12°. 146 pages. Henry Frowde and Hodder & Stoughton, London. (Oxford University Press, American Branch, New Y'ork.)

Contribution to the Pharmacology of Opium. 1915-1918. By Dr. David I Macht, Baltimore, 1918.

Metropolitan Asylums Board. Annual Report for the Y'ear 1917. (20th year of issue.) 1918. 8°. 57 pages. London.

Hygiene of the Eye. By Wm. Campbell Posey, A. B., M. D. 120 illustrations. 1918. 8°. 344 pages. J. B. Lippincott Company, Philadelphia and London.


May. 1919]


141


Neuropsychiatry and the War. A Bibliography with Abstracts, Prepared by Mabel Webster Brown, Edited by Frankwood E. Williams. M. D. 1918. S". 292 pages. War Work Conmiittee, The National Committee for Mental Hygiene, Inc., New York City.

The Medical Association of the Isthmian Canal Zone. Proceedings of the Medical Association of the Isthmian Canal Zone. Vol. X, Part I, January to June. 1917. 1918, 8'. 149 pages. Published by the Health Department, The Panama Canal. Panama Canal Press, Mount Hope, C. Z.

Public Health Reports. Issued weekly by the United States Public Health Service, containing information of the current prevalence of disease, the occurrence of epidemics, sanitary legislation, and related subjects. Vol. 32, Part I, January-June,

1917. 1918. S'. 1074 pages. Government Printing Office, Washington.

The Surgery of Oral Diseases and ilalformations. Their Diagnosis and Treatment. By George Van Ingen Brown, D. D. S., M. D., C. M.. F. A. C. S. Third edition, with 570 engravings and 20 plates, and a selected list of examination questions.

1918. 8°. 734 pages. Lea & Febiger, Philadelphia- and New York.

Anatomy of the Human Body. By Henry Gray. F. R. S. Twentieth edition, thoroughly revised and re-edited by Warren H. Lewis, B. S., M. D. Illustrated with 1247 engravings. 1918. 4°. 1396 pages. Lea & Febiger, Philadelphia and New York.

Oenilo-Urinary Diseases and Syphilis. By Henry H. Morton, M. D.. P. A. C. S. Fourth edition, revised and enlarged, with 330 illustrations and 36 full-page colored plates. 1918. 8'. S07 pages. C. V. Mosby Company, St. Louis.

Ah Introduction to the Mammalian Dentition. By T. Wingate Todd, M. B., Ch. B. (Mane), F. R. C. S. (Eng.), Captain, Canadian Army Medical Corps. With 100 illustrations. 191S. 8°. 290 pages. C. V. Mosby Company, St. Louis.

Radio-Diagnosis of Pleuro-Pulmonary .Iffertions. By F. Barjon. Translated by Jam&s A. Honeij, M. D. 1918. 8°. 183 paws. Yale University Press, New Haven; Humphrey Milford. London.

Dispensaries. Their Management and Development. A book for Administrators, Public Health Workers, and All Interested In Better Medical Service for the People. By Michael M. Davis, Jr., Ph. D., and Andrew R. Warner, M. D. 1918. 8'. 438 pages. Macmillan Company. New York.

The Diseases of Infaney and Childhood. Designed for the use of Students and Practitioners of Medicine. By Henry Koplik. M. D. Fourth edition, revised and enlarged, Illustrated with 239 engravings and 2.t plates in color and monochrome. 1918. 8'. 928 pages. Loa & Febiger, Philadelphia and New York.

Roentgen Diagnosis of Diseases of the Head. By Dr. Arthur Schiiller. Authorized translation by Fred F. Stocking, M. D., M. R. C. With a foreword by Ernest Sachs, M. D. Approved for publication by the Surgeon General of the United States Army. 1918. 8'. 305 pages. C. V. Mosby Company. St. Louis.

The Human Skeleton. An Interpretation. By Herbert Eugene Walter. With 175 Illustrations. 1918. 12'. 214 pages. Mac millan Company, New York.

Abstracts of War Surgery. An Abstract of the War Literature of General Surgery that has been Published since the Declaration of War in 1914. Prepared by the Division of Surgery. Surgeon General'.s Office. 1918. 8'. 434 pages, c V .Mn.-^hy Company, St. Louis.


Engliah, French, Italian. Medical Vocabulary. By Joseph Marie. 1918. 24." 112 pages. P. Blakiston's Son & Co., Philadelphia.

Text-Book of .Anatomy and Physiology for Nurses. By Diana Clifford Kimber and Carolyn E. Gray, B. So. (Columbia University), U. N. Fifth edition, revised. 1918. 8°. 527 pages. Macmillan Company, New York.

Vaccines and Sera, Their Clinical Value in Military and Civilian Practice. By A. Geoffrey Shera, B. A., M. D., B. C. (Cantab.). With an introduction by Sir Clifford Allbutt, K. C. B., M. D., F. R. S. 1918. 16'. 226 pages. Henry Frowde and Hodder & Stoughton, London.

Tumours. Innocent and Malignant. Their Clinical Characters and Appropriate Treatment. By Sir John Bland-Sutton LL. D., F. R. C. S. With 383 illustrations. Sixth edition. [1917.] 8'. 790 pages. Paul B. Hoeber, New York.

Stanford University. Medical Bulletin No. 5, 1917-1918.

The Newer Knowledge of Nutrition. The Use of Food for the

Preservation of Vitality and Health. By E. V. McCoUum.

Illustrated. 1918. 12'. 199 pages. Macmillan Company,

New York. College of Physicians. Transactions of the College of Physicians

of Philadelphia. Third series. Volume the Thirty-Ninth.

1917. S°. 518 pages. Philadelphia.

War Neuroses. By John T. MacCurdy, M. D. With a preface by W. H. R. Rivers, M. D. (London.) 1918. 8°. 132 pages. University Press, Cambridge.

lioyal College of Surgeons of England. Calendar of the Royal College of Surgeons of England. August 1, 1918. 407 pages. 8'. Taylor and Francis. London, England.

The Effect of Diet on Endurance. By Irving Fisher. 1918. 12°. , 55 pages. Yale University Press, New Haven; Humphrey Milford, Oxford University Press, London.

.1 Text-Book of Home Nursing. Modern Scientific Methods for the Care of the Sick. By Eveleen Harrison. Second edition, revised. 1918. 12°. 193 pages. Macmillan Company, New York.

Dietetics for Nurses. By Fairfax T. Proudflt. 1918. 8". 444 pages. Macmillan Company, New York.

Compendium of Histo-Pathologieal Teehnie. By Emma H. Adler.

1918. 12°. 92 pages. Paul B. Hoeber, New York.

Mental Diseases. A Handbook Dealing with Diagnosis and Classification. By Walter Vose Gulick, M. D. Illustrated. 1918. 8'. 142 pages. C. V. Mosby Company. St. Louis.

Equilibrium and Vertigo. By Isaac H. Jones, M. A., M. D. With an Analysis of Pathological Cases. By Lewis Fisher, M. D. Adopted as Standard for Medical Division, Signal Corps, Aviation Section, by Surgeon General and Chief Signal Ofllcer. United States Army. With 130 Illustrations. 1918. 8°. 444 pages. J. B. Llppincott Company, Philadelphia and London.

Physiology and Rioehemistry i7i Modern Medicine. By J. B. Macleod, M. B. Assisted by Roy G. Pearce. B. A., M. D., and by others. With 233 illustrations, including 11 plates In colors. 1918. 8'. 903 pages. C. V. Mosby Company, St. Louis.

The Rockefeller Foundation. International Health Board. Fourth Annual Report. January 1, 1917-December 31, 1917. (Publication No. 7.) January, 1918. 8\ 160 pages. New York.

Information for the Tuberculous. By F. W. WIttlch, A. M., M. D. 1918. 12°. 150 pages. C. V. Mosby Company. St. Louis.

Inited States. Department of Commerce. Bureau of the Census. Mortality Statistics, 1916. Seventeenth annual report. 1918. 4°. 543 pages. Government Printing Office, Washington.


142


[No. 339


THE JOHNS HOPKINS HOSPITAL REPORTS


VOLUME I. 423 pages, 99 plates.

VOLUME II. 570 pages, witli 28 plates and figures.

VOLUME III. "66 pages, with 69 plates and figures.

VOLUME IV. 604 pages, 33 charts and illustrations.

VOLUME V. 480 pages, with 32 charts and illustrations.

The Mal.nri.ll Fevers ot B.iltimore. By W. S. Thayer, M. D.. and

J. Hewetson. Jl. D. A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever.

. D.. with additional papers

D.. Walter Keed, .M. IL. ai

VOLUME VI. 414 pages, with 79 plates and figures.

VOLUME VII. 637 pages with illustrations.

VOLUME VIII. 552 pages with illustrations.

VOLUME IX. 1060 pages, 66 plates and 210 other illustrations. Contributions to the Science of Medicine.

Dedicated by his Pupils to William Henky Welch, on the twenty fifth anniversary ol his Doctorate. This volume contains 38 separate papers.

VOLUME X. 616 pages, 12 plates and 25 charts.

VOLUME XI. 555 pages, with 38 charts and illustrations,

VOLUME XII. 548 pages. 12 plates and other illustrations.

VOLUME XIII. 605 pages, with 6 plates, 201 figures, and 1 colored chart.

VOLUME XIV. 632 pages, with 97 figures.

Studies in Genito-Urinary Surgery.

The Treatment of Prostatic Hypertrophy by Conservative Perineal Prostatectomy. An analysis of cases and results based on a detailed report of 145 cases. By Hugh H. Young, M. D.

Recto-Urethral Fistula. Description of New Procedures for their Prevention and Cure. By Hugh H. Young. M. D.

The Early Diagnosis and Radical Cure of Carcinoma of the Prostate, being a study of 40 c:ises and presentation of a radical operation which was carried out in four cases. By Hugh H. Young, M. D.

VOLUME XV. 542 pages, with 87 illustrations.

Twelve papers on pneumonia By Drs. Chatard, Fabyan, Emefson,

Marshall, McCrae, Steiner, Howard and Hanes. A Study of Diarrhoea in Children. J. H. Mason Knox, Jr., M. D., and

Edwin H. Schorek. M. D. Skin Transplantation. By John Staige Davis. M. D. Epidemic Cerebrospinal Meningitis and Serum Therapy at The Ji.hns

Hopkins Hospital. By Frank J. Sladen. M. D.

VOLUME XVI. 670 pages with 151 figures.

Studies in the Experimental Production of Tuberculosis in the GenitoVrinary Organs. By Ceorge Walker. M. D.

The Effect on Breeding of the Removal of the Prostate Gland or ot the Vesicute Seminales. or of Both ; together with Observations on the Condition of the Testes after such Operations on White Rats. By George Walker. M. D.

Scalping Accidents. By John Staige Davis, M. D.

Obstruction of the Inferior Vena Cava with a Report of Eighteen Cases. By J. Hall Pleasants. M. D.

Physiological and Pharmacological Studies on Cardiac Tonicity in Mammals. By Percival Douglas Cameron. M. D.

VOLUME XVII. 586 pages with 21 plates and 136 figures.

Free Thrombi and Ball Thrombi in the Heart. By Joseph H. Hewitt.

M. D. Benzol as n Leucotoxin. By Lawrence Selling. M. D. Primary Carcinoma of the Liver. By Milton C. Winternitz, M. D The Statistical Experience Data of The Johns Hopkins Hospital, Baltimore,

Md.. 1802-1(111. By Frederick L. Hoffman. LL. D., F. S. S. The Origin and Development of the Lymphatic System. By Floreni:e R.

Sarin. M. D. The Nuclei Tuberis Laterales and the So-called Ganglion Opticum Hasale.

By Edward F. Malone. M. D. Venous Thrombosis During Myocardial Insufficiency. By Frank J. Sladen.

M. D.. and Milton C. Winternitz. M. D. Leuk.Tmia of the Fowl : Spontaneous and Experimental. By Harry C.

SCH5IEISSER. M. D.

VOLUME XVIII. 445 pages with 124 figures.

Fasciculus I. A Studv of a Toxic Substance of the Pancreas. By E. W. Goodpasture,

M."D.. and George Clark. M. D. Old Age in Relation to Cell-overgrowth and Cancer. By E. W. Goodpasture. M. D., and G. B. Wislocki. M. D. The Effect of Removal of the Spleen Upon Metabolism in Dogs : Pre liminarv Report. By J. H. King. M. D. The Effect ot Removal of the Spleen Upon Blood Transfusion. By J. H.

King. M. D.. B. M. Bernheim. M. D.. and A. T. Jones. M. D. Studies on Parathyroid Tetany. By D. Wright Wilson. M, D.. Thornton

Stearns, M. D., J. H. Jannet, Jr., M. D.. and Madge DeG. THCRrx)w,

M. D. Some Observations on the Effect of Feeding Glands of Internal Secretion

to Chicks. By M. C. Winternitz, M. D.


Spontaneous and Experimental Leukemia in the Fowl. By H. C.

Schmeisser. M. D. Studies on the Relation of Fowl Typhoid to Leukaemia of the Fowl. By

M. C. Winternitz. M. D.. and H. C. Schmeisser, M. D. Hyaline Degeneration of the Islands of Langerhans in Pancreatic Diabetes.

By M. C. Winternitz. M. D. Generalized Miliary Tuberculosis Resulting from Extension of a Tubercular

Pericarditis Into the Right Auricle. By M. C. Winternitz. M. D. Acute Suppurative Hypophysitis as a Complication of Purulent Sphenoidal

Sinusitis. By T. R. Boggs. M. D.. and M. C. Winternitz. M. D. A Case of Pulmonary Moniliasis in the United States. By T. R. BoGGS,

M. D.. and M. C. Pincoffs, M. D. Gaucher's Disease (A Report of Two Cases in Infancy). By J. H. M.

Knox. M. D.. H. R. Wahl. M. D.. and H. C. Schmeisser. M. D. A Fatal Case of Multiple Primary Carcinomata. By E. D. Plass. M. D. Congenital Obliteration of the Bile-ducts. By .Iames B. Holmes. M. D. Multiple Abscesses of the Brain in Infancy. By James B. Holmes. M. D. Gastric Carcinoma in a Woman of Twenty-six Years. By R. G. Hussey,

M. D. Subdiaphragmatic Abscess with Rupture Into the Peritoneal Cavity Following Induced Pneumothorax for Pulmonary Haemorrhage. By R. G.

Hussey. M. H. Heart Block Caused by Gumma of the Septum. By E. W. Bridgeman,

M. D.. and H. C. Schmeisser, M. D. Analysis of Autopsy Records.

A. The Johns Hopkins Hospital. (Table Showing Percentage of

Autopsies.)

B. The City Hospitals. Bay View. (Table Showing Percentage of

Autopsies. ) " The Monday Conferences."

Clinical Representatives on the Staff of the Department of Pathology. Donation.

Fasciculus II. The Role ot the Autopsy in the Medicine of To-day. By M. C. Winternitz.

M. D. Experimental Nephropathy in the Dog. Lesions Produced by Injection

of B. bronchisepticus into the Renal Artery. By M. C. Winternitz,

M. D.. and William C. Quiney. M. D. Mesarteritis of the Pulmonary Artery. By M. C. Winternitz, M. D.. and

H. C. Schmeisser, M. D. A Clinical and Pathological Study of Two Cases of Miliary Tuberculosis of

the Choroid. By Robert L. Randolph, M. D., and H. C. Schmeisser,

M. D. The Blood-vessels of the Heart Valves. By Stanhope Bayne-Jones. M. D. Equilibria in Precipitin Reactions. By Stanhope Bayne-Jones. M. D. Carcinoma of the Pleura with Hypertrophic Osteoarthropathy. Report of

a Case with a Description of the Histology of the Bone Lesion. By

Stanhope Batne-Jones. M. D. ,

The Interrelation ot the Surviving Heart and Pancreas of the Dog in Sugar

Metabolism. By .\dmont H. Clark. M. D. Congenital Atresia of the Esophagus with Tracheo-Esophageal Fistula

Associated with Fused Kidney. A Case Report and A Summary of the

Literature on Congenital Anomalies of the Esophagus. By E. D.

Plass. M. D. Ectopia Cordis, with a Report of a Case in a Fifteen-Month-Old Infant.

By James B. Holmes, M. D. Studies in the Mechanism of Absorption from the Colon. By Samuel,

Goldschmidt. M. D., and A. B. Dayton. M. D. Report of Two Fatal Cases Following Percy's Low Heat Treatment of

Carcinoma of the Utenis. Bv V. N. Leonard, M. D., and A. B. Dayton,

M. D. The Relationship in Tvphoid Between Splenic Infarcts and Peritonitis

Unassociated with Intestinal Perforation. By A. B. Dayton. M. D. Left Duodenal Hernia. By A. B. Dayton. M. D.

Histological as Related to Physiological and Chemical Differences in Certain Muscles of the Cat. By H. Hays Bullard, M. D. A Method of Clearing Frozen Sections. By H. Hays Bullard. M. D. On the Occurrence and Significance of Fat in the Muscle Fibers of the

Atrio-Ventricular System. By H. Hays Bullard. M. D. Studies on the Metabolism of Cells in vitro. 1. The Toxicity of o-Amino Acids for Embyonic Chicken Cells. By Montrose T. Burrows, M. p.,

and Clarence A. Neymann, M. D. The Significance of the Lunula of the Nail. By Montrose T. Burrows.

M. D. The Oxygen Pressure Necessary for Tissue Activity. By Montrose T.

Burrows. M. D. The Functional Relation of Intercellular Substances in the Body to Certain Structures in the Egg Cell and Unicellular Organisms. By

Montrose T. Burrows. M. D. Studies on the Growth of Cells in vitro. The Cultivation of Bladder and

Prostate Tumors Outside the Body. By Montrose T. Burrows. M. D..

J. Edward Burns. M. D.. and Yoshio Suzukl. M. D. The Studv of a Small Outbreak of Poliomyelitis in an .\partment House,

Occurring in the Course of an Epidemic in a Large City. By Montrose

T. Burrows. M. D.. and Edwards A. Park. M. D. Papilloma of the Larynx. Report of a Case Treated with Radium with

Resultant Chronic Diffuse Thyroiditis. By William C. Duffy. M. D. Analysis of .Autopsy Records. Auto'psv Statistics.

(n) Bay View.

(hi Johns Hopkins Hospital. Report of the Photographic Department. General Improvements.


Contents

The Occurrence of Gastric Mucosa in a Case of Meckel's Diver- Tlie Development of CroasStriations in the Heart Muscle of ticulum Producing Intestinal Obstruction. (Illustrated.) the Chick Kinbryo. (Illustrated.)

By Emu. Goetsch 143 By Margabkt Reed Lewis 176

A Graphic .Application of the Principle of the Equilateral

Triangle for Determining the Direction of the Electrical Spina Bitida with Associated Disturbances in a Human Axis of the Heart in the Human Electrocardiogram. Embryo 17 mm. Long. (Illustrated.)

(Illustrated.l p^. g j \Valli.s Ccll 181

By Edward Perkins Carter. Curt P. Richteb and

Carl H. Greexe I(!2

_, . . , . , i- . ^1 f . i T 1 The Manus Meditationis. (Illustrated.)

Phaeocytosis and Agglutination in the Serum in Acute Lulmr . „ „ ,_.

„ ' .If -c •. c Tu ij . J 41 By Charles Si.noer ... 184

Pneumonia: the Specificity of lhe.«e Reactions and the "

Regularity of Their Occurrence. By Paul \V. Clough 107 , Books Received 183


THE OCCURRENCE OF GASTRIC MUCOSA IN A CASE OF Mi:CKEL'S DIVERTICULUM PRODUCING INTESTINAL OBSTRUCTION

By K.Mii> (ioETScii (From thi- Departments of ffurgrry of The Peter Bent Brigham Hospital and The Harvard and Johns Hopkins Mrdiial Sihooli)


The occurrence in the human liody of ahcrrant glandular tissue, at times in place,* far removed from the motlier tis,«uo, is a subject not only of general medical interest and of special interest to the embrj-ologist, but also attract'* the attention of the pathologist and surgeon, who frequently meet with alinormalities arising from such aberrant tissue. The purpose of this report is to record such an in.«tance occurring in an interesting case of partial obstruction caused by Meckel's diverticulum in which, at operation, a striking variation was discovered in the mucous membrane of the distal half of the diverticulum. This area of mucous membrane at the tip of Meckel's diverticulum was differentiated strikingly from the pro.ximal mucosa by a sharp line of demarcation and by a difference in color, surface character and in thickness. On subsequent sectioning, this area of muco.sa proved to be of the preci.«e character of gastric (fundus) mucosa, containing the typical gastric glands (foveol.T gastricaj) composed of the two distinctive types of cells, the parietal and chief, each of which presented their characteristics of morphology and of staining reaction. It is desired further to explain the probable embryological origin of


tiiis ga.stric ti.ssue in Meckel's diverticulum with a view to throwing further light upon the occurrence of aberrant glandular tissue at the umbilicus and in the renuiins of the omphalomesenteric duct, as reported in the literature.

The ca-fe, Hospital No. (123, is that of a well-developed, single young man, lit years of age, and caterer by occupation. lie was born in Ireland and came to America four years previous to bis entrance into the Peter Bent Brigham Hospital on August 26, 191.3. He was admitted into the surgical clinic of Prof. Harvey Gushing, to whom I am indebted for the privilege of reporting this case. The young man complained of pain in the abdomen and vomiting. No information was obtained in regard to his family or past history which had any licaring on his present trouble except for the fact that six years previously, while he was in Ireland, he was operated upon for what he called a stomach abscess. The details of the condition for which he was operated upon he was unable to give. At that time the abdomen was explored at a point just below the umbilicus and drainage in.-^tituted. The abscess healed in a few weeks and the patient made a complete recov


144


[No. 340


ery. Except for this experience he had enjoyed exceptionally good health.

Without going into the details of his present illness suffice it to say that his symptoms began with headache 48 hours before admission to the hospital and were followed in about 36 hours by severe cramps in the abdomen, especially in the lower half and toward the right side. The day before coming to the hospital he suffered severely with vomiting and retching, the vomitus containing large quantities of bile. These symptoms persisted up to the time he came into the hospital. His appetite was poor during the two days of his illness, and his bowels moved once on the day previous to admission. During this same day the patient had a definite fever.

On admission to the hospital he appeared very ill. As a consequence of his excessive vomiting and retching his mouth was exceedingly dry, his tongue red and " beefy " and there was some bleeding of the gums. His temperature was 101.2°, pulse 92 to the minute and his leucocytes numbered 15,000 per c. mm. Examination of the abdomen showed no discernible irregularities, nor were any peristaltic waves seen. There was some fullness present, especially in the lower half. Eespiration was entirely costal in type. There was no marked general muscular rigidity, although there was increased tension of the abdominal muscles over the lower half of the abdomen. On deep palpation over McBurney's point slight tenderness could be elicited. Elsewhere there was no abnormal tenderness. On percussion, dulness could be demonstrated in the right lower abdomen and in the flanks. This dulness shifted with change of position of tlie patient and gave a splashing sound when the overlying abdominal wall was tapped while pressure was made in the flanks. There was evidence, then, of free fluid in the peritoneal cavity. The upper abdomen was markedly tympanitic. The evidence of former operation was present in an irregular scar just below the umbilicus, measuring about 1.5 cm. in transverse and 2 cm. in vertical diameter. Rectal examination revealed nothing abnormal. Without entering into further details of the examination it may be stated simply that the diagnosis appeared to be either intestinal obstruction or acute appendicitis with perforation. As the patient's general condition demanded immediate operation, abdominal exploration was advised and readily consented to.

The operation, done about one hour after the patient entered the hospital, was carried out through a right rectus incision. In the peritoneal cavity there was present a fairly large amount of free, serous fluid. Several moderately distended reddishlooking loops of small bowel were seen and also some collapsed grayish loops. Exploration was first made in the region of the appendix. Numerous adhesions resulting from the former abscess and operation had to be carefully separated. After considerable difficulty the appendix, which was coiled back on itself in U-shaped fashion and firmly adherent in the right iliac fossa, was freed and brought into view. It was unusually long, measuring 17-18 cm. in length, of uniform thickness and of fibrous consistency. There was evidence of a moderate chronic inflammation in this region ; the appendix, however, was not acutely inflamed. Appendectomy was done. The


condition of the appendix, I felt, could not be held responsible for the patient's present condition and furtlier exploration was made. At once a collapsed small intestine was seen low in the abdomen and pelvis, while numerous overlying, reddish, distended loops of small bowel were seen coming from above. After further seardi it was found that the division between distended and collapsed bowel was sharply demarcated by a thick, firm, pinkish-white cord, measuring 1.5 cm. in thickness and 6-7 cm. in length, attached at the distal end to the abdominal wall by means of adherent omentum at a point just below the imibilicus and connected at the proximal end with the terminal ileum at a distance proximal to the ileocecal valve, common for Meckel's diverticulum (cf. scliematic drawing. Fig. 1). Over this cord the loops of small intestine were draped like clothes on a line and had become obstructed. The distal end or tip of the diverticulum was attached to the abdominal wall at the site of the former abscess and operation. Without great difficulty, the distal end together with the adherent omentum was dissected free from the abdominal wall and the base of the diverticulum at its attachment to the ileum amputated and treated in the manner of an appendectomy. Further rapid search revealed no other abnormal findings, such as infection or seriously damaged loops of small intestine, whereupon closure of the abdominal wound was made without drainage. There were no disturbing symptoms following tlie operation and the patient made a rapid, complete recovery.

In view of the findings at operation it seems likely that the abdominal abscess for which the patient was operated uj>ou six years previously had its origin in a perforation at the tip of Meckel's diverticulum and that simple drainage of the abscess was done through a small incision just below the umbilicus, following wliich the abscess healed. The possible cause of the perforation will be considered later.

Upon further examination it was found that the diverticulum had a large lumen which at the point of attachment to the ileum measured about three-fourths of a centimeter in diameter. It did not have the appearance of acute inflammation. The diverticulum was then slit open in a longitudinal direction, whereupon a striking appearance was presented by the mucous membrane. The proximal three-fourths of the mucosa had a rather smooth, rolling, slightly folded surface. It was pale-pinkish in color and resembled in this respect the mucosa of the terminal ileum or first portion of the large bowel. The distal one-fourth of the mucosa was considerably thicker and was elevated above the surface of the proximal mucosa from which it was separated by a sharp line of transition. It had, furthermore, a sharp differentiation in color, in that it was of a deep red, cherry hue and its surface was thrown up into large folds, the surface of which again was irregular and granular in appearance. {Cf. drawing, Fig. 2, g. m.) There was a marked difference also in the thickness of the diverticular wall which, in its proximal portion, was of the thickness of the terminal ileum, while at the tip it was three to four times as thick as the latter. The muscular coat, on the whole, was rather thin, and externally there was a


THE JOHNS HOPKINS HOSPITAL BULLETIN, JUNE, 1919


PLATE XIX



Fill. 1- Meckel's <livrrti<'uluni, with adherent oiiieiituni.* iittjchetl to the anterior alMliiniinal vtall at a point just below the unibilii'us. ( Sehemal ir. ) The chn>ni<- Hbrous adhesions resulted from old abs<^?>s (urniation and jjubsequent operation.



Ki<


-Meokel>


inc Ihe thinner pnixinial inuttis;! t i. n appearance, and the thicker tlislal jp|H?arinK Kastrif nuiros.1 [ff. m.). V -harp line of transition (T.). At O "riientuin. (Natural size.)


'.I {..neilndinallv : ) rt'scniblinu' iUun lie of irntrnlar.


of adherent


- A


f^^;^



-*V




tofirraph -.ho\v^ tho strikinic «li(It left in the drawing (KifC. H. fflands in (he gastric niiic<>«a a


•e in thi< knew. U-twe*-!! tli' y a ^mall portion .*r the alM shown.




ftf


^'A


^y


^jf'-^.^ak^miM



the TiKht and the pi


, . • M,, Im.I.- I,.. Ill

Mill in -lain I The J

mal iiitesliniil niiicnsa on the lortuojily and depth of the


June, 1919]


145


serous peritoneal covering continuous with the serosa of the small bowel itself. At the tip there was a mass of adherent, corrugated-looking omentum which had probably become adherent tliere at the time of the former abscess and operation. Further examination at the time revealed no perforation nor evident defect in the mucosji at the tip of the diverticulum. The whole specimen was j)laced in 10 per cent formalin for subsequent study.

Frozen sections were made of the wall of tlie diverticulum BO as to include the transition line (cf. photomicrograph, Fig. 3) between the two types of mucous membrane and were then stained in lia.'mato.xylin and eosin. The proximal, thinner, mucosa (similar to that seen on the left in Fig. 3) resembled in structure that of the duodenum, or in many respects also tlie ascending and transverse colon ; whereas in the thicker. more irrt>gular. distal mucosa (on the right in Fig. 3), at the tip there were si^n deep glands which resembled in structure the fundus glands of tlie stomach and which were composed of two types of cells — the larger, less numerous, bright-red-staining eosinophilic parietal cells and the more numerous, smaller, indifferent-staining chief cells. In order to study in greater detail the two types of mucosa, paraffin sections were prepared. Several additional staining methods were used, namely, cresylecht-violett, the iron-ha-matoxylin method, the acid fuchsiii and the neutral gentian methods as recommended by Bensley and the mucicarmine method for the demonstration of mucus in the goblet cells and in the distal goblet zone in the surface columnar cells of the gastric mucosa.

I. Stkvctlre of the MrcosA Proxim.\l to the Transition Point (T) (cf. Fios. 2 and 3)

Sections were made at the line of demarcation or transition between the two adjoining types of mucosa. Fig. 3 represents a low-power photograph of an ordinary section stained in hsematoxylin and eosin and magnified 24 diameters. The photograph shows the sudden transition from the thinner proximal mucosa, on the left in the piiotograph, to the thicker, more irregular, distal mucosa on the right. The striking difference in the relative thickness of the two mucous membranes is well shofrn. A section of the proximal mucosa on the left when observed under the higher power and after staining in cresylecht-violett is seen to consist of a propria containing simple, unbranched, comparatively shallow tubular glands (cf. drawing. Fig. 4, of a similar section after iron-hiematoxylin). The mucous membrane has an irregular surface and forms papillar}- outgrowths between the openings or crypts of the glands. The lining epithelium is almost uniformly of the tall columnar variety, containing numerous goblet, mucous cells throughout the extent of the mucous membrane. These goblet cells in the neck and depth of the glands are so numerous as to form in places the majority of the cells lining the tubules. Here and there between the swollen goblet cells are seen thin, tall, irregularly compressed, columnar cells — probably discharged goblet cells. Their protoplasm is compact, non-granular and more deeply stained. The cells on the surface are of a low columnar, in places almost


cubical, type, with fewer goblet mucous cells tlian elsewhere in the glands. In sections doubly stained in iron-alum-hiematoxylin followed by mucicarmine (the strong stock solution of Mayer), as recommended by Bensley,* the goblet cells contrast strikingly on accomit of tiie brigiit red stiiin which their irregular, stringy or spongy +++++ CONTENTSs take, showing tlius tiie mucous character of the secretion of these cells. Afte'r staining in cresylecht-violett the mucous takes on a faintly purple tint as compared witii the remainder of the cell. Near the center of the cell is a denser, more deeply bluish stained zone of c}'toplasm separating the mucous section of the cell from the basal protoplasmic portion. The nuclei are large, rounded or oval, fairly clear and basally placed. They contain a moderate amount of chromatin and have each a densely stained purple nucleolus. Many of the nuclei, however, are elongated and flattened, due to pressure from adjoining cells; in tlie smaller cells they are basally placed, while in the discharged cells tliey have a more central location. The protoplasm of those cells lying between the goblet cells does not contain secretion granules.

Many of these appearances are seen as well in the sections stained after the iron-alum-ha»matoxylin method. Thus in the drawing (Fig. 4) the goblet cells appear unstained, being represented as clear spaces. There are no true villi of the small intestine type. In studying the section further in the oil immersion we find that the cells on the surface have a kind of striated cuticular Iwrder. The nuclei of the cells, which apparently rest upon a definite basement membrane, have the same character as those just described in the preceding paragraph. The protoplasm of the UM columnar cells between the goblet cells fails to show any granules which one would consider as the antecedents of fennent secretion.

The propria (Fig. 4) is a loose tissue, containing numerous .small blood-vessels and lymphatics, lymphoid cells and connective-tissue cells. In it are also a few smooth muscle fibers from the L. muscularis nuiscosce running upwards into the mucous membrane prolongations. In one area there is a definite aggregation of lymphoid ti-ssue with a germinating center; in fact, a lymphoid follicle with an outer denser. zone of small round cells in the center of which appears a clearer zone with larger cells and richer reticulum. Lymphoid tissue of this kind is seen also in the sections taken from this proximal portion of the mucosa.

The submuco.sa consists of a layer of loose connective tissue which contains blood-vessels and above which lies the L. muscvlaris mucosa (Fig. 4). Externally to this again there appears a thick tunica muscularis, consisting of a thick inner circular and an outer longitudinal layer, between which there lies a plexus of nerve tissue. A small portion only of this muscle coat appears in the lower right-hand comer of the drawing (Fig. 4).

Additional sections including both types of mucosa were made of the transition zone (T, Fig. 2) and .stained in hapmatoxylin and eosin, cresylecht-violett, iron-aluni-ha-matoxylin and in mucicarmine. In tlie mucosa just distal to the transition line (on the right in Fig. 3) the following changes


146


[No. 340


occur: The proximal duodenal or perhaps transverse-colon type of mucosa rather suddenly changes into a kind of transitional surface epithelium, consisting of two or more irregular cell rows and two different types of cells. The majority of these cells are of a taller t}'pe than those lining the intestinal mucosa, and the nuclei, which are irregularly oval or rounded, are more centrally placed and stain in ha?matoxylin a diffuse bluish-purple in which a darker pifrple centrosome is usually evident. These cells are often flattened and compressed, cylindrical, fusiform or dumb-bell shaped. Each surface cell has a marginal cuticular border and a distal clearer zone separated from the more proximal protoplasmic portion of the cell by a transverse denser cytoplasmic band. In the eresylecht-violett stain the distal clearer zone just described has a rather homogeneous structure and stains a very pale blue, as distinct from the denser blue proximal protoplasm. The nuclei stain a pale violet. In the mueicarmine the distal zone in many instances is stained bright red, showing the presence of mucus. In neither the eresylecht-violett nor in the iron-alum-hsematoxylin stained sections are any secretion granules apparent in these surface cells.

The cells of the second type in the surface mucosa are usually more deeply situated. These cells are rounded or hexagonal in shape and have a comparatively clear protoplasm. The nuclei are irregularly rounded or oval and deeply stained.

The propria is rich in lymphoid cells, blood capillaries and connective-tissue cells. Numerous mast-cells, so frequently seen in the normal stomach mucosa, are seen here also, and in their cytoplasm the characteristic large red granules, after staining in eresylecht-violett, can be recognized.

Numerous crypts or tubular prolongations are seen dipping down from the surface into the propria. These glands are highly tortuous, especially in their depths, and are lined by two kinds of cells. The majority of them, the chief cells, to use the terminology as applied to the gastric fundus mucosa, are low columnar or cuboidal in shape, with a darker-staining basal zone of protoplasm which has a slightly granular appearance. The lumen border of each cell is relatively clearer and the nucleus is rather large, irregularly rounded or oval, and basally placed. These cells after staining in eresylechtviolett are pale blue, with violet nuclei and bluish nucleoli. Secretion granules do not appear in this stain, but after the iron-alum-hajmatoxylin method, great numbers of black-stained zymogen secretion granules are seen, such as one finds typically in the chief cells of the gastric mucous membrane. A more detailed description of these cells is given later.

The cells of the second type found in these glands are considerably larger than the chief cell just mentioned. They do not, as a rule, touch the lumen of the tubule, as they have a parietal situation and f reqiiently lie between or upon the chief cells just mentioned. In the hfematoxylin-eosin preparation a cell of this type stains light red or pink in the eosin, as distinct from the chief cell. It has, further, a distinct cell definition and a round, usually centrally placed nucleus, rich in chromatin. Uniformly distributed in its protoplasm can be seen rather large, highly retractile, practically unstained


granules, suggesting in every way the appearance in the typical parietal cell of the stomach. In the cresylechi^violett these parietal cells contrast clearly with the chief cells by staining a faint pinkish-blue, while the latter are darker especially in their basal portions, which are dark blue. The secretion granules in such a preparation are of a violet color. The nuclei are well defined, large and vesicular, and contain relatively little chromatin. Many of the parietal cells are seen to communicate with the lumina of the tubules by a cleft between the neighboring chief cells. In the iron-alum-haematoxylin the parietal cells are clearly shown, and in their cytoplasm the secretion granules are seen to be uniformly distributed and stained black. Except for the columnar cells on or near the surface, the mueicarmine fails to show the presence of any mucussecreting cells in the neck, body or depths of the tubules. A further description of tliese glands as they occur in a section just beyond the transition line is given below (c/. Fig. 5). In the neck and body of a gland tubule the parietal cells are almost as numerous as the chief cells, while in the depths of the glands the smaller chief cells become more abundant. The appearance throughout in fact is that of gastric fundus mucosa, except perhaps for the greater tortuosity in the tubules than in the glands of the gastric fundus region (c/. Fig. 5).

Just below the mucosa there is a well-developed L. muscularis mucosce, which at one point just beyond the transition line runs upwards, as a papilla or indentation, into the mucous membrane and thereby suggests, together with the thickening in the outer muscle coat, the formation of a sphincter. Just beyond this point, furthermore, the mucous membrane assumes the exact appearance of the fundus mucous membrane and will be described in greater detail later.

The submucosa consists of a loose connective-tissue framework containing blood-vessels in great abundance.

The outer muscle coat is thick, and composed of muscle bundles, not in two definite layers as in the proximal intestinal portion of the section, but running in all directions and intertwining with one another. Numerous nerve fibers can be seen in the outer connective-tissue coat below the parietal covering and also between the muscle bundles. Here also scattered ganglion cells are seen.

II. Typical Gastric Fundus Mucosa From a Point Just

Distal to the Transition Line Described

Above (Fig. 5)

At a short distance beyond the transition line between the two types of mucosa the glands of a typical gastric fundus type just described for the transition zone are seen in great numbers. A more detailed description may here be given of the glands as revealed after staining with hematoxylin, eresylecht-violett, iron-aluni-h£ematoxylin, mu^picarmine, neutral gentian and acid fuchsin-niethyl-green. The appearance as revealed in the high-power magnification and in oil immersion need only be given here. Many of the findings in repetition of those described as occurring at the transition point are either omitted or only briefly mentioned. The drawing (Fig.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JUNE. 1919

A



^®»,.



^l« — ItiMttiiiic lit intNJfnitelv inan niA.-<l «lion ( • 7S) (5 niiira Ihirktma, ironlu-niatox.vllii nirlhiHl) taken from the ilJMtjil niiKfKii iit ii point ju*t l>ry<>nfl the lnin>.it>on iniic. X.ite the tvpif-al fhiiniitrr. of ira>lri<' funilti'. niwoia. the lull airfare ooliimnar relU at (.4), an<l the too charnrterislir t>Te< of rell». the . hief an<l parietal, in the ne.-k III), Ik.Iv (f| and Iwse (11) of the dee|> tortuou.i gland.


Km. Ii- Jlr;mnii[« "r m|Uuii'.I aTOw (.4, //. C, /(. Kilt. .'.I afliT hiKh.|>ower uil-innnerNion niaKniltnition, to Khiiw the rjiol.iKiiiil .luirarlerK of the i-<'llt. .. .iiipri.ini: the Klanil tnliiile. .V.>lr llie tall irfai-e. i-olunuiar. non 7.>tniHt<-riir -.•IIk. (.1) the larite r.lill ively i le:ir purli'l4il cHIh i-oiiliilnhiK nioilerale nuMilx'iv of liirve, Mark MalllinK. iii-iil<iphili<' (granule., a(i<l the ntorr nnlnenm.. 'nialhr. .lurkrr •hief r-ellv coiitajiiiiiir Iitrt;e ininilierM of

hiai'k otaininK. /> iteiiir Kranulea

airtrr<ifate<l aloiiie the lumen bor.ler> lit the ..lU III. <. /').


(FiK. 2. n (: • of llru thi» nertion with the simple tvi>e of rellii. the lymph foil de\eiope«l L, mu*rula


• diKMlenuni. .Note the n. the nunterfiuo jfohlet Kland., and the well


June, 1919]


147


5) illustrates the appearance of a tvpieal gland in moderate maguifit-ation, after irou-alum-ha>matox_vlin staining. Four areas squared in this lower power drawing (Fig. 5, A, B,C,D) are represented as seen in high-power oil iuiniersiou magnitication (Fig. 6, A, B, C,D).

Surface Epithelium. — Numerous crypts or depressions found in the mucous membrane resembling the typical gastric crypts represent the openings or communications through which the more deeply situated glands discharge their secretion into the lumen of the diverticulum. These crypts are lined by epithelium of the surface type, composed of tall, cylindrical cells in a single row or layer (Figs. 5 and 6, .4). The large nucleus of each cell witii a well-marked nucleolus is round or oval in shape and is usually centrally placed, but often is found above or below the center of the cell. It stains fairly densely by all methods, due to a fair abundance of chromatin. The protoplasm of these cells takes a pale blue stain in the cresylecht-violett and a gray in the luvmatoxylin and has a spongj" structure. Secretion fjranules are not seen in the protoplasm. In the distal one-fourth of many of the cells there is a clearer zone, in places grossly granular in appearance, having a cup shape and separated from the remainder of the cell protoplasm by a transverse cytoplasmic band. This is the mucuscontaining end or zone of the cell, which is not, however, a true goblet cell. True types of the latter were not seen at all in sections from this area. In the cresylecht-violett this mucus stains a pale blue and after mucicarmine a few of the cells on the surface showed this cup-shaped end, or theca, red stained and cither grossly granular or string}- in structure. Just below the surface in the cr}-pts the mucus-containing cells are more numerous than on the surface where they are very few in number. Many of the cells have, furthermore, an outer cuticular border.

Glands of the Gastric Fundus Type. — (Figs. 5 and 6, B, C, D.) Into the depths of the crypts empty the secreting glands, one or two, occasionally more, tubules to each cr}7)t. These glands are of the simple tubular variety and occasionally branched. The necks of the glands arc quite straight, but in the depths the glands are usually tortuous or convoluted, as indicated by the numerous tubules seen in cross-section in the deeper zone of the mucosa. The glands are in close contact with one another, with almost no intervening tissue of any kind. The propria forms the groundwork or supporting tissue for the glands, surrounds them evervTvhere and extends upward to the surface epithelium. Under the surface epithelium the propria contains a great many lymphoid cells uniformly and ditTusely scattered and fairly abundant. These lymphoid cells, together with numbers of mast-cells, a blood capillar}' network and some slips from the L. mu-scularis mucosa are also seen extending from the level of the latter upwards between the glands to the surface epithelium. A typical gland may be divided into three portions: the neck (Fig. 5, B), the body (Fig. 5, C) and the depth or base of the gland (Fig. 5, D). The neck of the gland consists of a rather straight tube with a ven- narrow lumen, lined by two types of cells. The first tj-pe is smaller, low columnar or almost cubi


cal in shape and stains bluish in hsvmatoxylin, with a darker basal zone and a clearer zone bordering on the lumen and containing numerous rather large, black-stiiining secretion granules. After the neutral gentian technique (Fig. T) these same cells are stained a violet, especially in the basal portion, and the secretion granules along the lumen border of tlie cell now stain a dark violet. In the acid fuchsin-methyl-green method (Fig. 8) these granules are faintly green or unstained. These are the characteristic chief cells as seen tyi)ically in the gastric fundus mucosa.

The second type of cell is larger, is irregularly rounded or oval, borders on the lumen or is slightly removed from it and covered in part by the neighboring chief cells. This cell is clearer, the protoplasm is stained uniformly pinkish in eosin, pale blue in cresylecht-violett, grayish in iron-htematoxylin, faintly orange in neutral gentian ( Fig. 7 ) and red in the acid fuchsin-methyl-green method (Fig. 8). Scattered uniformly through tlie protoplasm are definite, large, discrete secretion granules, black in the iron-h»matoxylin (Fig. 6, B, C, D), faintly orange in the neutral gentian (Fig. t) and red in the acid fuchsin methods (Fig. 8). The nuclei are large and vesicular, with relatively little chromatin, are centrally placed and contain a well-marked nucleolus. The cell outlines are sharp. These are the parietal cells, the second characteristic cell of the fundus mucosa of the stomach. The neutral gentian (a neutral combination of the acid orange G and the basic gentian violet) and the acid fuchsin-methyl-green methods were employed to demonstrate the specific staining affinities of the cells and granules of these fundus glands, to add additional evidence to that obtained from the iron-ha.'matoxylin method, that we are dealing with specific secreting gland cells of the true gastric fundus type. The zymogenic secretion granules of the chief cells, having a peculiar affinity for the gentian violet in the neutral gentian stain, are seen colored a dark violet, while the acidophilic granules of the parietal cells have a relatively slight iiftinity for the orange G and hence appear faintly orange. In the acid fuchsin-methyl-green method, the conditions are just reversed, for which rea.son this method was employed. We now find that the acidophilic granules of the parietal cells stain a brilliant red in the acid fuchsin, whereas the zymogenic secretion granules of the chief cells are faintly or not at all stained in the methyl-green. The absence of mitochondria, so well demonstrateil after osmic-bichromate fixation of the tissue and staining after the acid fuchsinmethyl-green method, is doubtless exi)lainable by the fact that the tissue in this case had remained for a long period of time in 10 per cent fonnalin. It would have been interesting to study the mitochondria in this tissue as well as the secretion granules, had it been possible to fix some of the original fresh tissue in some other fixing fluids, such as the well-known acetic-osmic-bichromate mixture. The findings described above are well illustrated in the beautiful drawings in color (Figs. 7 and 8) by Miss E. Norris.

Body aiul Depth of the Gland. — As one observes the gland tubules at greater depths one finds that the same two types of cells are found as described in the neck of the gland tubule.


148


[No. 340


Here, however, the larger or parietal cell has a truly parietal situation, that it lies removed from the lumen at the periphery of the tubules and communicates with the lumen of the tubules by a cleft between the chief cells. It also occurs oftener. The chief cells show the same characteristics described above. At the base of the cells and forming a kind of basement membrane, the membrana propria is evident. Secretion canaliculi in the parietal cells were not definitely seen, due probably to faulty fixation. We have here, then, a type of mucous membrane resembling in every particular, both as to structure and staining affinities, the characteristics of the fundus mucous membrane of the stomach.

A well-developed L. muscxdaris mucosce is seen, which here and there sends off small, thin prolongations into the overlying propria and between the glands. The submucosa has the usual structure of this layer in the intestinal tract.

The tunica muscuJaris is thick and composed of smooth muscle fibers intertwining with one another in various directions and not definitely demarcated into an outer and inner layer of longitudinal and circular direction. No definite nerve plexuses were recognized.

III. Section Taken From Proximal Part of Meckel's Diverticulum

The structure of the mucous membrane and wall of the diverticulum near to its intestinal attachment does not differ in any important detail from that described above as occurring just proximal to the line of transition (Fig. 4). It was thought that possibly the principal type of mucous membrane, that resembling transverse colon in structure, would assume at the proximal end of the diverticulum the character of ileal mucosa. This is not the case however, for the mucous membrane still resembles that of the transverse colon as described above. There is this difference, however: the mucous membrane is slightly thinner, the folds or plicae are lower and there is less IjTiiphoid tissue, both diffuse and in the form of follicles. There are more nerve fibers occurring in the submucosa, the tunica muscularis is thicker and more sharply demarcated into an inner circular and an outer longitudinal muscle coat, between which there are more nerve fibers recognizable. Inasmuch as the other findings are similar to those occurring more distally (Fig. 4), a further description need not be given here.

Thus, positive evidence has been advanced by the methods of finer cytological study, that the zone of aberrant glandular tissue in the tip of Meckel's diverticulum is identical in every respect with gastric fundus mucosa. It was thouglit desirable to make this detailed study of the histological character of this anomalous Meckel's diverticulum for three reasons: In the first place, to establish definitely the fact that we are dealing with a zone of aberrant, but typical, gastric mucosa. This was necessary in view of several reported cases of a somewhat similar nature in which the anomalous or aberrant tissue occurred at the umbilicus and was said to give the appearance of pyloric or simply gastric mucosa, although no histological


examination is reported. For purposes of argument in the explanation of these anomalies it was first of all necessary to advance definite proof that we were dealing with real gastric mucosa. This having been done I feel I have advanced good reasons for believing that the anomalous and aberrant glandular tissues occurring at the umbilicus, in obliterated vitelline cords, and, as in my own case, in Meckel's diverticulum, have a common origin, namely, from the remains of the omphalomesenteric duct. Cases in which pancreatic acini and Lieberkiihn's and Brunner's glands have occurred in Meckel's diverticulum have been reported and are given below. Undoubted cases of gastric mucosa, of pancreas and of Lieberkiihn's and Brunner's glandular tissue, occurring at the umbilicus in the form of polyps, depressions or fistulas, have been reported. Several cases are reviewed below in which such aberrant glandular tissue occurred in instances of umbilical fistulse which were connected with Meckel's diverticulum by a strand or cord. In one or two instances a patent Meckel's diverticulum connected with the umbilicus at which such glandular tissue was found. If we are forced to believe that certain fistulaj at the umbilicus, fibrous cords connecting with Meckel's diverticulum, and the latter itself represent the remains of the vitelline or omphalomesenteric duct, then it would naturally follow that all these anomalous glandular tissues have a common origin. With the discovery of gastric mucosa in Meckel's diverticulum, the chain of evidence of the common origin of these tissues is complete. Additional evidence is then afforded for believing that the umbilical anomalies arise from the omphalomesenteric duct, inasmuch as we know that Meckel's diverticuhmi represents the remains of the latter structure. A plausible explanation of the embryonic origin of these umbilical anomalies is thus afforded, a fact which is highly desirable in view of the many conflicting explanations with regard to the latter which have been advanced by authors writing on this subject. In the second place, it is interesting to speculate upon the manner in which true gastric mucosa comes to lie in Meckel's diverticulum, so far removed from the mother organ ; and in the third place, inflammations, ulcerations, and certain pathological new growths occurring at the umbilicus and in Meckel's diverticulum receive a rational explanation on an embryological basis.

In reviewing the literature in search for accounts of the occurrence of gastric mucosa elsewhere than in its normal location, I have found Chapter VII, pp. 144-158, of Dr. T. S. Cullen's ' excellent book on " The Umbilicus and Its Diseases " most helpful. A complete review is given in this chapter of the reported cases of gastric mucosa occurring at the umbilicus.* In the brief accoimt here to be given I have dra'mi f reelv from


  • The occurrence of intestinal mucosa at the umbilicus, in the

form of polypoid growths, with or without depressions or fistulfe, is relatively common as compared with the frequency with which gastric mucosa has been found in the same region. For a good review of the cases of umbilical polyps composed of intestinal mucosa the reader is referred to Cullen: "The Umbilicus and Its Diseases," Chapter VI, pp. 120-143. A complete bibliography on this subject is also given at the end of the chapter.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JUNE. 1919


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Fiii. 7. — DrawinfT of a Klaii'l tuhule (.'i niicra, neutral Ci'iitijii ttiiiii. uil iMiiiHToioiit fr.iiii ihc lip "f Mrckel's div<*rtit-itliim. rfim-spondink: tn tin- :iii>a ri*)ires<-n(i>(] in Kiff**. 5 aiKl fi. r anj D, I" wIm.w ihe rompItU' similarity in ttnirtntt' i)n<l Mainjni; atflnilv with the appi-annces tvpirally s*-«n in ffantrit- fumltiH iinuovi. Noti- (1) the rhiff o'IIh with ilicir zvni<>t.'i'ni< "M-rrclifn trriinnli's iili.nff thi- Iniiipn hor<)(-r «f tlif r^-IK ^.tainiil in the vi^lot: ;in<l (2) Ih.' pari.'tal (ills, Y.-.thvt and (l.artr and with larne. fjinily oranKP-fltained ffraniilf» MiitiercHl difTiiscly thn>iiKliout Ihe cyl'^plasm.




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Fin. 8. — Prawine of \hv Kliind lubiilcs in cross-wrtion (formalin, h niicra thickness, acid-fuclliln-niethvl-ifreen sliiiii. oil iinnursiolil from Ihe B-iini- ar.M as r.|)ri«,nliil in V\s. 7. The .hiif (ills iirc now scfii slain..! a taint Ki-c.'ii nnd the /.iiloKeni.- s.'.Ti'tion (rniniilfs ar.- Iiar.ll.v visible. The l.arietal .ells. liow. v.r, show their trial afflnilv for Ihe aii.1 fiichsin. and the laru-e irranules which the.v eonlain ar.> slain.sl a l.lilliani red. Note al-o an occii-si.iiial inast-eell in the inter-tubiilar conne.'tive tisnue.


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this review. Cullen (p. 145) classifies the lunbilical abnormalities in wliifh gastric mucosa was found into three tvpes, thus, for example :

I. An umbilical polyp attached to the umliilical depression by a short pedicle.

II. An umbilical polyp with a cystic cavity opening on the surface of the polyp.

III. An umbilical listula with or without a small projection. Fig. 9 will serve to illustrate the second type.

I. A most interesting example of the first type was described by Tillmanns" in 1882. In a boy, 13 years of age, there was found at the umbilicus a pedunculated tumor, the size of a walnut, bright red in color, without a central opening and covered with mucosa. After a meal had been eaten, the tumor would swell perceptibly, while the mucosa became redder and thicker. The secretion on the surface of the polyp had a tenacious mucoid character. Whenever the tumor was irritated the flow of secretion was increased so that at such times



Flo. 9. — A long umbilical polyp with a central fistulous opening, a remnant of the omptulomesenteric duct, (Schematic, after Cullen, p. 156.) This is an unusual t>-pe. the pol>-p being shorter and more KMile. A feu- instances are reported in which the lining mucofta was shown to be of gastric character. There is no connection between the umbilical polyp and the email inte.stine in this t^-pe of polyp.

2 to 3 c. c. of fluid could be collected in 15 minutes. The secretion was acid in reaction, digested albumen, and upon chemical examination was found to reseml)le normal gastric juice. Upon microscopic examination by Weigert the mucosa was found to have a structure similar to that of the pyloric region of the stomach. On account of its digestive action the secretion of the tumor had caused a maceration of the skin in the vicinity of the umbilicus. Histological examination of the mucosa of the tumor showed this to be similar in structure to pyloric mucous membrane. Tillmanns then explains the condition by showing schematically how a diverticulum of the stomach may be included in the umbilical cord as a prolapse of stomach wall through the umbilicus just as the ileum may do. This explanation will be considered again. No connection with the stomach or other organs was found.

Although the literature upon this subject is scanty, a few subsequent reports of ga.«tric mucosa occurring at the umbilicus were found. Thus, umbilical polypi with a covering of gastric mucosa have been desc-ribed by van Heukelom " (1888), Keichard" (1898), Strada " (1903), and Minelli" (1905).

In van Ileukolom's case, a child two and one-half years of age, a tumor the size of a hickory-nut was found in the umbilical depression. It was red in color and had a granular.


moist surface and was attached by a thin pedicle. The latter was divided and the tumor removed. On microscopic examination the tumor was seen to consist of an inner portion composed of muscle, connective tissue and vessels, luid an outer portion or cortex 2 mm. in thickness and consisting of a mucous membrane with long gland tubules, some interstitial connective tissue and some lymphoid tissue at the base of tlie glands. The latter resembled intestinal glands of tlie Lieberkiihn type. (Van Heukclom's explanation for tliis finding is given below.) Van Heukelom refers to 12 cases of this kind reported in the literature, his own being the 13th case. He feels that there doubtless are many more which have been reported under the diagnosis of " umbilical granuloma " and have not been examined further. Most of tliese granulomata when examined have been found to contain epithelium and glands of intestinal type. In these cases there is no mention made of gastric mucosa.

In a further study of the occurrence of gastric mucosa at the umbilicus and with particular reference to Tillmanns' case and his explanation of it, namely, that the gastric mucosa is derived from a gastric diverticulum, van Heukelom examined a number of human fetuses with this point in view. In one of his fetus cases he foimd a nodule of mucous membrane at the tip of Meckel's diverticulum constricted otf from the lumen of the latter. On microscopic examination this nodule was found to resemble the pyloric mucous menibriuic of this same fetus. The epithelium was very regular, composed of long cylindrical cells with refractile protoplasm and basally situated nuclei. There were no goblet cells. The mucous membrane of the diverticulum, on the other hand, and of the ileum itself was of an entirely different character, namely, intestinal in type. Van Heukelom att^Mupts to explain the origin of this heterotopic mucous membrane, a matter which we shall again consider. It is to be emphasized here that this piece of gastric mucosa was constricted off from the cavity of the diverticulum and in no way communicated with it.

Eeichard reports the case of a boy five years old who presented a tumor, the size of a hickory-nut, in the umbilical region, which had a small fistulous opening and from which a clear fluid escaped. There had been a " weeping navel " since birth. At operation the umbilicus was circum.scribed, the jjeritoneum was opened and a cystic, bluish, demarcated tumor was seen, from which a thin stalk ran upwards into the abdominal cavity. The stalk, which was very delicate and could not be followed, was divided. The tumor with the surrounding area of macerated skin was excised. Closure was made of the peritoBcum and abdominal wall and the patient made a good recovery.

The cavity of the tumor was lined with a mucous membrane which, when microscopically examined, was seen to resemble the gastric type. No further histological description 18 given and no statement is made as to whether it was clearly of pyloric or fundus character. Reichard is reminded of the case of Tillmanns, except that in his own case the condition had not gone on to evagination and prolapse of the tumor. He was inclined to believe in the theory of Tillmanns, namely.


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that this mucous ruembrane is derived from a diverticulum of the stomach, and that due to the rotation and further development of the stomach there is a twisting and later obliteration of the cord of communication with the stomach. Siegenbeek van Heukelom, as we shall see, is opposed to this view.

Strada reports the case of a young woman of 20 who had a tumor at the umbilicus covered with mucosa. On microscopic examination this mucosa was seen to consist of cylindrical epithelium and glands of the pyloric type.

Minelli describes an adenoma occurring at the umbilicus presenting a picture of gastric adenoma.

II. A case of the second type, namely, an umbilical polyp with a cystic cavity opening on the surface of the polyp, ha.s been described by Eoser" (1887) in a boy one and one-half years old. A bright red swelling was found at the umbilicus. Opening on the surface of this swelling, which, as stated, belongs to the second type, was a cystic cavity 1 cm. in diameter. The case was very much like that reported by Tillmanns. The secretion from the umbilicus digested the surrounding skin area, was acid in reaction and was responsible for a considerable induration and a red granulation-formation around the opening. The walls and mucous membrane of this cavity were excised. A secondary cauterization had to be done three weeks later on account of incomplete removal. A detailed description of the structure of the mucosa is not given, mention being simply made that the closely aggregated tubular glands, between which there was a good deal of muscle tissue, resembled in every way gastric mucosa. There is no mention made of a serosa nor as to whether the glands were of the fundus or the pyloric type. Eoser was inclined to accept the explanation of Tillmanns for this occurrence, namely, that a portion of gastric mucosa had been constricted off from the pyloric region at a time when the stomach had a vertical position and the pylorus was supposed to be nearer the umbilicus. It is hardly necessary to state, as will be explained in further detail below, that this assumption does not suffice, for it is well known that the pylorus in infants and very young children is in no such proximity to the umbilicus, inasmuch as the large liver sepalates the pylorus and the stomach from the anterior abdominal wall.

III. Fistulous tracts occurring at the umbilicus and containing gastric mucosa have been described by von Eosthorn " (1889), Weber (1898), Lindner"" (1898), Lexer" (1899) and Denuce' (1908). These belong to the third type of cases mentioned above.

Von Eosthorn reports the case of a boy seven years old who had an umbilical fistula. Its presence was first recognized when the cord dropped off. After this a red papule formed which secreted watery fluid and into which a sound could be introduced for a distance of 2 cm. There was a continuous flow of this secretion which amounted to 5 c. c. in 24 hours. It was acid in reaction, slowly digested albumen and did not positively contain free hydrochloric acid. The fistula was excised and the patient was wall in 10 days.


On microscopic examination of the tissues from the depths of the tmnor, gland lobules were found which reminded one of parotid gland, whereas the branched tubules resembled pyloric glands of the stomach. Von Eosthorn assumed that the acid reaction of the secretion was due to zymotic external influence which had altered the original alkaline reaction. Lieberkiilm's glands were also found in the fistula, von Eosthorn ofliers and accepts the explanation of Siegenbeek van Heukelom for the occurrence of his findings.

In Weber's case there was found in a boy three years old a small red tumor at the umbilicus from which a fistula led downwards for a short distance. From this fistula flowed a watery secretion which contained mucous shreds, but never intestinal or gastric +++++ CONTENTSs. The secretion amounted to half a wineglassful in 24 hours. At meal times the secretion was increased and then often accompanied by a colicky pain. A digestion ulcer had formed around the fistulous opening at the umbilicus which was one-half of a centimeter in diameter. This secretion was alkaline to litmus. Weber felt that the secretion of the tumor was increased during digestion probably by a reflex action through its nerve supply which he thought was doubtless the same as for the normal stomach, for, as we shall see, he felt that the tumor was derived from the stomach by a process of diverticulum-formation. This is iu keeping with Tillmanns' view.

The fistulous tract with the surrounding macerated skin was excised. After the peritoneum was opened a thin cord was found leading from the inner end of the tract to the under surface of the liver, but without attachment to either stomacii or intestine. A cystic bluish tumor was found at the umbilicus. The stalk was divided, the tumor extirpated as mentioned and closure was made, followed by recovery of the patient.

The cavity of the tumor was lined with a thick mucosa which was of the pyloric type. The columnar surface epithelium was seen to dip down to form glands which were made up of only one kind of cells. There were no chief and parietal cells as in the fundus region and no goblet cells, no villi and no glands or follicles of the Lieberkiihn type. There was an L. niuscularis mucosce and outside of this a longitudinal and circular muscle coat and a thick serosa. Weber felt that from the gross and microscopic appearances it was safe to assume that he was dealing with normal stomach mucosa from the pyloric region. He felt, also, that the cord passing to the under surface of the liver represented the remains of the umbilical vein. Weber was inclined to the view of Tillmanns, that this fistula and tumor represented a portion of the diverticular stalk from the pyloric region and had become constricted off at the umbilicus.

Lindner, iu the discussion of a case of extirpation of a persistent ductus omphalomesentericus reported by Korte in 1898, reports a ca.se of his own in which there was a small, reddish papule at the umbilicus in a boy three years old. For some weeks or even months there was a secretion from this fistula and around it there was a large area of digestion of the abdominal wall. A sound could be introduced into this fistula


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for a short distance. At operation a tumor was found, the size of a walnut, behind the umbilicus, wliich connected in no way witii tlie intestine. From the upper pole of the tumor there was a fine connective-tissue strand running to the under surface of the liver in the re>;ion of the incisura. There were no vessels palpable in tliis cord, which seemed to have no importance whatever. The tumor was excised and was found to be lined by mucous membrane of the pyloric type. Lindner states that ca.ses of this kind are extremely rare and dillicult of explanation. He refers to the cases reported by Tillmanns, but does not ajrree with Tillmanns' explanation of their occurrence. He states that there was no evidence in his case that the tumor had any connection with a diverticulum or former prolapse of the .<tomach. Lindner did not attempt to explain the oc-currence further.

Lexer's patient was a child one year old with a congenital umbilical fistula around which the skin was macerated. The fluid secreted bv the fistula was clear, tenacious and iicid in



Flo. 10. Persist*nre of the out«r end of the omphalomesenteric duct in the form of an umbilical flKtula attached to the small bowel by a (Ibroun cord. (Schematic, after CuUen, p. l.'>6.) This is the tj-pe of remnant of the omphalomesenteric duct described by Lexer. In the latter's rase, however, there was a blind fistula at the umbilicus leadinir downwanls a short distance and also a fistulous tract leadinf? from the small intestine through the fibrous cord or obliterated Meckel's diverticulum. The two fistulous tracts, however, did not communicate. The outer umbilical fistula was lineal by (gastric mucosa and the inner or proximal fistula by intestinal mucos;i.

reaction and chemically resemliled gastric juice, in that it readily digested egg albumen and fibrin. At operation the fistulous tract was found to have a cord of attachment, as thick as a lead pencil, to the convexity of the small bowel. The cord was amputated from the intestine and the fistulous tract excised. The child made a rapid recovery. The proximal or inner end of the cord, which was attached to the intestine, evidently represented Meckel's diverticulum (Fig. 10). The extirpated fistulous tract had a rather wide opening at the umbilicus and al.so at the intestinal end, although it was not completely patent throughout it.« whole extent. The external fistula was one and one-half centimeters in depth. The specimen was thus divided into two i)art.«. The proximal larger section, which communicat<'d freely with the bowel, had a mucous membrane very similar to that of the intestine and of the type generally found in Meckel's diverticulum. Lieberkiihn's glands with numerous goblet cells and individual lymph follicles characterized this mucosa. In the original, a plate of a low-power drawing is shown of the histological appearance which resembles my own case, the mucous membrane appearing very much like transverse colon in many respects. The appearance, as shown by section, of the external or umbili


cal portion of tliis fistula was very different. The mucous membrane was of tJie pyloric type, as similarly described by von Kosthorn and Lindner. The epithelium was tall and cylindrical and the protoplasm highly refractile. The nuclei were basally situated and there were no goblet cells. In the deptli there was to be seen a riclily developed zone of tubular glimds connected by numerous crypts with the lumen of the fistula. In general, then, the wliole structure of the mucous membrane resembled that of the pyloric region of the stomach. This structure was not as regular, however, as in the normal structure. In the original, a second plate is showi to illustrate this mucosa. External to the mucous membrane there are the usual muscular layers. For a short disUmce the luniina of the two segments overlapped one another, so that in a single section taken at this point one could see both types of mucous membrane: the intestinal, belonging to the proximal fistula or cavity, and the pyloric type, corresponding to the external or distal fistula. In the deptli there was only an imperfect cellular connection between these two types of mucous membrane. At this point tliere was a mixture of the two types of mucous membraJie and Ix'.xer believed that the outer fistula was formed originally, by a constricting process, from the original diverticulum of Meckel. The findiiig.s, as a whole, Lexer believes, allow of no other explanation than that there is a complete persistence of the ductus ompluilome.sentericus, whose outer portion, probably as a result of very early separation, is subjected to a different evolution of its mucous membrane than that portion of the fistulous tract which connected with the intestine, namely, Jlcckel's diverticulum.

In explanation of the similarity of the secretion from the outer portion with that of gjistric juice. Lexer was unable to give any satisfactory facts and referred to the rather unsatisfactory attempts at explanation by van Hcukelom and von Rosthorn. Lexer was more inclined to believe tliat tlu^se formations arose from rest* of the original omphalomesenteric duct and Meckel's diverticulum rather than from gastric diverticula, even though there was lacking the anatomical connection between the umbilicus and Meckel's diverticulum.

In order to feel that the gastric mucosa at the umbilicus was derived from the same mucosa or from the same structure* from which Meckel's diverticulum develops. Lexer said he would like to see a case in which there was a preservation of the connection between the gastric mucous memiirane at the umbilicus and a Meckel's diverticulum. My own case shows that even without such an anatx)niical connection gastric mucosa is found in Meckel's diverticulum and thus affords additional proof that the cases of gastric mucosa at the umbilicus have an origin similar to that of Meckel's diverticulum.

Denuce described in a boy 21 months old a congenital fistula at the umi)ilicus from which there was an abundant flow of secretion which was ordinarily colorless, sometimes slightly hemorrhagic, and which gave an acid reaction and upon chemical examination was found to be practically identical with gastric juice. There was digestive action on the skin around the umbilicus. The microscopic examination of the fluid revealed nothing of imjiortancc. Free hydrochloric acid was


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present. By means of a sterile pipette 3 c. c. of secretion were collected and examined chemically. The principal findings included demonstration of the presence of albumen, peptone and free hydrochloric acid. The fluid digested coagulated albumen. He concluded, then, that the secretion must be considered a kind of gastric juice. At the operation the fistulous tract was removed without necessitating the opening of the peritoneal cavity. The peritoneum was transparent and it was possible to see, a little to the left of the deeper attachments of the fistula, a cylindrical cord which, at its proximal or inner extremity, was connected with one of the intestinal loops (Fig. 11). It was at once recognized that this cord represented Meckel's diverticulum and connected at its distal extremity with the umbilicus. The diverticulum was then exposed and amputated at its base. The child made a good recovery.



Fig. 11. — An umbilical polj-p connected with Meckel's diverticulum by a fibrous cord. (Schematic, after Cullen, p. 121.) This is the type of remnant of the omphalomesenteric duct which was described in IJenuce's case. In the latter, however, the umbilical polyp had a central fistula which was lined by mucosa of the fundus tj-p'e. Remnants of practically the whole of the omphalomesenteric duct are present here. The outer end is represented by the umbilical polyp, the centrai portion by a fibrous cord and the inner end by Meckel's diverticulum. The latter had the usual intestinal type of mucosa.

The tissue removed was preserved in formalin. The specimen consisted of two parts : the outer fistulous part attached to the external surface of the peritoneum and the inner part or segment consisting of Meckel's diverticulum attached at its distal extremity to the inner peritoneal surface. A section from the outer fistulous part showed the mucous membrane to liave the characteristic structure of gastric mucosa of the fundus type. The surface cells were tall, cylindrical in type, and filled with mucus. In the connective tissue there were some fibroblasts, mast-cells and eosinophilic cells. The superficial tubules were continuous below with the true peptic glands. The latter were lined with clear cells containing zjaiiogen granules and a second type of cell, the parietal cells. These were very numerous in the depth of the culde-sacs, but less abundant in the deeper portions of the gland tubules. The eosinophilic cells and the mast-cells were also found in the deeper portions of the glandular zone. In the corium true lymphoid nodules with germinating centers were present. The muscular layer on the outside was very thick.

In brief, then, Denuce felt that he was deahng with a gastric heterotopy in the form of an isolated small cul-de-sac or fistula at the umbilicus, plainly and fully functioning. Before discussing further his own case he then refers to some previous observations on the development of our understanding of the


peculiar histology of congenital umbilical fistula of the socalled pseudo-pyloric type, which is extremely rare.

Finally, it may be well to refer briefly to the case described by Salzer "' (1904) of a patent diverticulum (Fig. 12), which in the free abdominal portion showed normal characters of the intestinal mucosa. In the prolapsed portion at the umbilicus, however, there were found glands resembling in structure the cardiac glands of the stomach. In the histological description of these glands he says the cells of the gland tubules are clear, finely granular, polygonal in shape and have a basal nucleus and some affinity for eosin.

In explanation thereof he suggests that, in the closure of the abdominal cavity, for some reason or other, there is a partial or complete cessation in the evolution of the vitelline duct and that thereby the entoderm is irritated or stimulated to



Fig. 12. — .\ patent omphalomesenteric duct with a polj-poid formation at the umbilicus. (.Schematic, after Cullen. p. 190.) This represents the type of case described by Salzer. The lumen is continuous through the umbilical polyp, through the persistent omphalomesenteric duct, and communicates with the small intestine.

a variable difl'erentiation, so that there is a development at one time of intestinal mucosa, at another time of gastric; again, there may be produced parotid gland or even pancreas. He says, furthermore, that these pathological pictures are always to be found at the distal end of the remnants of the \'itelline duct, in fact, just at that point where the incomplete involution of the vitelline duct is so apt to be found. There have been many different views in explanation of the origin of these aberrant tissues at the umbilicus, with particular reference to the occurrence of gastric mucosa. Before entering upon these, however, it will be helpful to review briefly the embryological evolution of the omphalomesenteric duct. In this way a clear conception can be had of the probable origin of a large number of anomalous conditions which one finds at times at the umbilicus and in its neighborhood.

The vitelline or omphalomesenteric duct represents in fetal life the communication between the intestine (ileum) and the yolk sac. The yolk sac in time develops into the umbilical vesicle. Ordinarily, at about the seventh week to the tenth week the yolk stalk, which connects between the ileum and the umbilical vesicle, separates from the intestine. The latter, which at first lies in part in the umbilical cord, retracts into the abdominal cavity and thereafter there is no further indication of the original connection between the intestine and the yolk sac. If the separation of the intestine from the yolk stalk is delayed or fails to


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occur at all, then various resultiug anomalies are found in the region of the umbilicus at the time of birth or even later in life. The slightest persistence of the vitelline duct is represented by a thin connective-tissue strand extending from the umbilicus to the ileum. This strand is of little interest aside from the fact that occasionally intestinal obstruction may be produced by it. The fullest degree of persistence of this structure is represented by complete patency of the duct, thus establishing a free communication between the umbilicus and the intestine. From a condition of this kind there develops the well-known type of congenital umbilical fecal listula, numerous cases of which liave been reported. Through such a listula a portion of the bowel wall or even a loop or more of small bowel may prolapse. Between these two extremes there are all possible transitions. The most common partial persistence of the vitelline duct is that of the well-known finger-like diverticulum of Meckel, which is usually entirely separated but may be connected with the umbilicus by a few fine strands of connective tissue. Such cases are also numerous. A diverticulum thus attached to the umbilicus may cause various types of fetal strangulations, torsions and obstruction. At other times, this duct connecting between the umbilicus and the intestine becomes obliterated at both the umbilical and the intestinal extremities with an intervening lumen lined by a cylindrical epithelium and containing more or less secretion. From a remnant of this kind arise the well-known cysts or entcrocystomata. Again, the duct may remain open at the umbilicus and become obliterated within the abdominal cavity. This type of persistence gives rise to umbilical fistulas, tumors and cysts. These may be opened externally at the time of the ligature of the umbilical cord or through umbilical inflammation. Again, there may be a nodule of mucous membrane with or without a lumen and constricted off from the tip of Meckel's diverticulum with which it thus has no communication. Both structures, however, evidently arise from a partial persistence of the original vitelline duct.

We might consider now the theories and views which liave been advanced to explain the occurrence of aberrant glandular tissue at the umbilicus and which concern particularly those cases of gastric mucosa reported above.

The first view was that of Tillmanns (1882), namely, that in the cases exhibiting gastric mucosa at the umbilicus in the form of a tumor or fistula we are dealing with remnants of gastric diverticula which have been preserved at the umbilicus, but which have severed their former connections with the motlier organ. This view was accepted by Reichard, Roser and Weber. The last, particularly, was a firm believer in this probable origin of the aberrant gastric tissue, and in his report in 1898 explains in detail the mechanism of this formation. As it was impossible for me to get Tillmanns' original article I have quoted largely from Weber's article which follows in general the views of Tillmanns. According to this view, then, there occurred in early fetal life a herniation of the stomach at the umbilicus, which herniation was still connected with the stomach by a kind of diverticulum and that this diverticulum was opened at the time of birth. The question which Weber


now puts to himself is this : How does a gastric diverticulum or herniation come to lie in the first portion of the umbilical cord? His explanation is as follows: In the youngest human embryos which had been examined up to his time, and which were from 14 to 18 days old, the intestine has not yet become a more or less closed tube, but communicates by a rather wide stalk with the yolk sac. Gradually the yolk sac develops into the umbilical vesicle, which is connected by means of the vitelline duct with the sub.sequent tubular intestine. The vitelline duct becomes a portion of the umbilical cord and later obliterates. The bowel retracts into the abdominal cavity and all connection with the umbilical cord disappears. Up to this point the presence of a portion of the intestine in the beginning of the umbilical cord is a physiological occurrence. If separation of the vitelline duct from the intestine is delayed, then traction within the umbilical cord is exerted upon the intestinal tract and the intestine remains as a normal +++++ CONTENTS of the first portion of the cord, thus producing an umbilical herniation with small intestine as its +++++ CONTENTSs. If this herniation remains it can be readily overlooked by the physician or the midwife, and at the time of ligature of the cord it may be opened so that a fistula may rise from which the child generally dies as a result of complicating peritonitis. On the other hand, such a hernia may be only a temporary occurrence and subsequently, after separation of the vitelline duct, the bowel may retract into the abdominal cavity. In a case of this kind a dilated ring persists at the umbilical opening and thus predisposes to a potential hernia. In this manner a diverticulum of the stomach might enter the umbilical opening, or even without assuming a delayed separation of the vitelline duct such a herniation is conceivable if one imagines the stomach held in application against the umbilical opening by the presence of adhesions.

The second question which Weber asks himself is this: Why is it that there is no tract or strand connecting with the stomach ; in other words, why is it that the prolapsed piece of mucous membrane appears as an anlage entirely separated from its point of origin ? He believes that there are processes of con.striction during the period of development which play a role if Tillmanns' theory is at all correct. Thus, if we assume that in an early developmental period there is an attachment between the first portion of the umbilical cord and the stomach, then, as a result of this, traction is exerted upon the stomach as against the traction of the mesentery. The stomach is drawn out into a diverticulum and the connection between the adherent portion and the stonuich proper is narrowed down to a very small duct. In addition to this, there are the subsequent changes of position to which the intestinal tract and the stomach are subjected in their further embryological development. Originally the stomach is formed as a fusiform dilatation of the otherwise uniform intestinal tract and has a vertical position. Its long axis becomes transverse and the pyloru.s comes to lie high on the right and the cardia moves to the left. The portion to the left then develops as the fundus. In addition there is also a torsion of the long axis, so that the left surface becomes anterior and the right


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posterior. The mesentery also makes these twists and must therefore alter its length and form, thus creating the bursa omentalis. If we now assume that abnormal adhesions have held tlie stomach wall in apposition with the region of the umbilicus, then this change in position can readily cause a narrowing of the duct-like connection between the umbilical herniation and the stomach, resulting in the formation of a twisted cord which in time obliterates and finally disappears entirely. Assuming these facts as a plausible hypothesis, Tillmanns and his adherents endeavor to explain the occurrence of gastric mucosa at the umbilicus as a form of ectopia ventriculi. Against this view van Heukelom takes a decided stand.

Van Heukelom, whose view was accepted by von Eosthorn, believes that these aberrant growths at the umbilicus represent remains of the vitelline duct and arise in a manner which he explains as follows : In the second month of fetal life the intestine still forms a loop which is to be found in the umbilical cord. The tip of this loop represents the point from which the ductus omphalomesentericus is constricted off. In the third month this intestinal loop retracts and then the intestine lies free in the abdominal cavity. If we now assume that this diverticulum or loop, for some reason or other, does not retract at its proper time on account of the tension of an unobliterated vitelhne duet, then the portion of the diverticuhim connecting with the intestine may be pulled away, and being thus entirely separated from the latter comes to lie isolated at the umbilicus. In this manner we have the beginning of our ectopia. If now this mucous membrane and musculature of the open diverticulum at the umbilicus continue to grow while the surrounding umbilical structures retract, then the former will evaginate and in this fashion, in time, a tumor forms, which is covered with mucous membrane. Van Heukelom refers to 12 cases of this kind which he has collected and gives reference to them, his own being the 13th. There are probably many more which have escaped notice because they are classified under umbilical granulomata without further report as to their histology. Many of these aberrant tumors at the umbilicus have been shown to contain intestinal glands and epithelium. In these 13 cases there is no mention made of gastric mucosa.

As already mentioned, van Heukelom described a case of his own of gastric mucosa occurring at the tip of Meckel's diverticulum and feels that there is a uniform origin for all the various aberrant tissues found at the umbilicus. There is a general consensus of opinion that these tissues are derived from the tractus intestinalis, but as to what part of the tract represents the mother organ there is a great difference of opinion. Van Heukelom, in the first place, answers what he considers the erroneous explanation of Tillmanns and Roser, namely, that umbilical gastric mucosa represents a portion constricted off from the early fetal stomach at a time when the stomach is supposed to lie in the vertical position, in close proximity to the umbilicus. Van Heukelom examined a series of fetuses with the purpose of determining the probability of such an occurrence. He concludes that it is impossible to


believe that gastric diverticula can thus be formed, for the reasons that the enormous liver occupies the space between the imibilicus and the deeper lying pylorus and relatively takes up more and more room, the younger the embryo. There is no connection between the pylorus and the umbilicus, but on the contrary there is always a wide separation between them. On the basis of his findings in one of his fetus cases, namely, of a portion of gastric mucous membrane at the tip of Meckel's diverticulum and separated from it, and the finding in Meckel's diverticulum itself of the usual intestinal epithelium, he constructs his theory for the explanation of these variations in histological differentiation.

Two questions, he says, now arise : Firstly, how can one explain the great difference between the epithelium of the distal portion separated from the diverticulum and that of the proximal portion of Meckel's diverticulum? And secondly, is it possible upon the basis of this observation to explain the origin of aberrant gastric ectopia at the umbilicus without resorting to the dangerous assumptions, such as those of Tillmanns and Roser ? In answer to the first question there are the f ollo%ving facts which are helpful : In very young embrj'os the intestinal tract is lined by a single layer of entodermal epithelium which is everywhere of uniform character. Later differentiation into gastric and intestinal epithelium appears and at the same time one recognizes folds and crypts which later become glands. Van Heukelom states further that the difference between stomach and intestinal epithelium occurs first at the time when the meconium or better when bile-stained material is found in the intestinal tube. Then for the first time one can differentiate the tall, regular epithelium from the intestinal epithelium, which is granular, low, shows a different kind of nuclei and contains many goblet cells. If we now remember that the portion of mucous membrane constricted off from Meckel's diverticulum was not in connection with the cavity of the diverticulum and therefore not in contact with the +++++ CONTENTSs of the intestinal tract and that this separated portion of mucous membrane corresponded in histological structure to that of the stomach, the thought arises that this differentiation in the types of mucous membrane is brought about by the influence of the intestinal +++++ CONTENTSs. It was van Heukelom's opinion that it is the influence of the bile which causes the differentiation into intestinal epithelium, and that the gastric mucosa and also this portion of mucosa separated from the diverticulum of Meckel, which do not come into contact with it, take on a different course of histological evolution. This explanation of van Heukelom can at once be considered as quite erroneous, for in the first place it is well known that the fetus swallows certain materials which must contain intestinal +++++ CONTENTSs and therefore bile. Van Heukelom assumes, however, that this swallowed portion is without the agent, which he feels acts upon the intestine differently than upon the stomach. In the second place, in my own case, the area of gastric mucosa occupied the distal third or fourth of Meckel's diverticulum, had a perfectly free communication with it and therefore the intestine and hence was subjected to the same influences as the intestinal mucosa. There could be no doubt about this point.


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One, therefore, need not assume, as van Heukelom did, that it was tlie total separation from the intestinal tract which caused this peculiar development of gastric mucosa.

Now as to the second question van Heukelom asks : Can the facts thus derived give a reasonable explanation for the ori^'in of aberrant tumors of gastric mucosa, such as Tillnianns, Roser and van Heukelom himself described? The latter felt that tliey could. He felt that Meckel's diverticulum might of course give origin to ectopia at the navel. The difficulty in the cases of Tillmaniis, Koser and van Heukelom lay in the fact that, whereas previous observers had derived the inti'stinal epithelium from Lieberkiilin's crypts, in the latter three cases the epithelium showed the character of pylorus. Van Heukelom e-xplains this variation by assuming that the ectopia at the umbilicus originated from the intestinal tract, inasmuch as in his own case the gastric mucous membrane was still attached to Meckel's diverticulum, which, as everyone grants, arises from intestine. The reason, then, for the variations in the initial ditferentiation into gastric and intestinal types of mucous membrane he explains by assuming that if the nmcous membrane preserved its communication with the intestinal tract up to and beyond the period of bile formation and was thus subjected to the influences of the latter, then intestinal epithelium developed; if, however, this aberrant epithelium became separated off from the intestinal tract before the secretion of bile appeared, it developed into gastric mucosa, and thus became morphologically identical with pyloric epithelium. Van Heukelom prefers this view to accepting the hypothesis of Tillmanns and Koser as to the origin of these tissues from gastric diverticula, which view has no anatomical basis and which a priori is doubtful. Here again my findings refute this view, for in my own case the gastric mucosa was developed in full connection and communication with Meckel's diverticulum and therefore in the presence of bile and its influences. Van Heukelom thus derives the intestinal ectopia at the navel from portions separated off from a true Meckel's diverticulum and as a consequence divides this umbilical ectopia into two groups: the first group which separated by constriction and became isolated very early, that is, before bile formation, and thus developed into gastric mucosa ; and the second group which became separated off at a later time. The former will thus contain pseudo-pyloric epithelium and later secrete an acid juice, the latter will show Lieberkiihn's crypts with goblet cells and secrete an alkaline fluid.

The third explanation for the origin of this aberrant tissue is that of Salzer (1901) and Kirnii.sson. According to this view, the following a.ssumption is made: At the time of the closure of the abdominal cavity, for some reason or other, there is a partial or complete cessation in evolution of the vitelline duct. As a result, the entoderm at the umbilicus is stimulated to manifold differentiation and, consequently, at one time we find a diverticulum of intestinal epithelium and at another time of gastric epithelium, and then again we may have the formation of parotid gland or pancreatic tissue. These pathological formations, according to Salzer, are always to be foum! at the distal end of the vitelline duct, at that point particularly


where the predisposing cause of the incomplete involution of the vitelline duct seems to be located. This cause may be in part local irritation or inflammation. In favor of the irritation or inflammatory view, these men pointed to the presence of lymphocytes, mast-cells and eosinophile cells in the mucosa. One need merely state, however, in refutation of this assumption that the finding of such cells is very common in the normal mucosa of the stomach and intestinal tract. There is the statement further that aberrant tissues are always to be found at the distal end of the vitelline duct, never at the proximal. With this assumption it would not be possible in my own case to explain the occurrence of gastric mucosa in Meckel's diverticulum, in a position certainly not subjected to irritative influences such as are supposed to be present at the umbilicus.

The fourth theory was that advanced by Albrecht and Fischl. According to this view these aberrant tissues arose from fetal inclusions or rests occurring at the time of the closure of the abdominal wall. This view is similar to that offered for the explanation of the occurrence of atypical tissues in various parts of the body. The misplaced rests from the junction points of the blastodermic layers are assumed to be the points of origin of these new tissues. It is thus assumed that these misplaced cells may retain their original powers of differentiation. This is the old teratological view for the origin of tumors and aberrant new growths. Here again one need not assume this view, for, in van Ileukelom's case in the fetus and in my own, the aberrant tissue was found in the former attached to Meckel's and in the latter within Jleckel's diverticulum, and thus probably was not the result of misplaced tissues at the umbilicus. In fact, in my own case the gastric mucosa was in direct continuity with the intestinal mucosa of the diverticulum. Salzer, however, admitted that in many cases in the closure of the umbilical ring there was a complete or partial persistence of the omphalomesenteric duct. Fischl felt that his theory explained more satisfactorily the fact that the abnormal formations of gastric, duodenal and pancreatic tissues are most often to be found in the distal extremity of the diverticulum than did those of Tillmanns and Salzer.

The fifth explanation offered by Lexer (18'.)9) and Denuce (1908), whose view is doubtless most nearly the correct one, assumes that these umbilical abnormalities represent the remains of the omphalomesenteric or vitelline duct. Lexer gives no real explanation for his peculiar finding of pseudopyloric glands in the case of the umbilical fistula which was attached to but did not communicate with .Me<'kcl's diverticulum ; but he leans toward the views of van Heukelom, that these tissues represent rests of Meckel's diverticulum rather than of gastric diverticula even in tiiose cases in which we find a mucous membrane with gastric structure and secretion, and in which there is no anatomical connection between the umbilicus and Meckel's diverticulum. He would like to see a specimen in which there is a connection between the umbilical gastric mucosa and Meckel's diverticulum in order to afford anatomical proof for his belief. Such a case is that described by Denuce, in which case the fistula at the umbilicus did not


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communicate with but was attached to Meckel's diverticulum. My own case completes the evidence, for in this case gastric mucosa is found at the tip of Meckel's diverticulum. Denuce, in spite of this latter view, cites the following facts : Originally the intestinal tract is lined throughout by a simple uniform entoderm. The differentiation into gastric and intestinal types is a later development. The cause of this differentiation in the epithelium is not clear. He suggests that isolation and occlusion of segments of a diverticulum from the intestinal tract are essential to the formation of gastric epithelium, and that there might be very early displacement in the original vitelline duct which gives rise to variations in subsequent differentiation. He is inclined to agree with van Heukelom that the occlusion of the segment is the initial cause for this variable differentiation, but he does not accept van Heukelom's view that the differentiation depends at all upon the action of the bile. He says this leads us into the domain of pure hypothesis. In other words, Denuce and Lexer lean to the view that these tissues arise from remains of the omphalomesenteric duct, namely, the intestinal tract, but offer no further explanation for the variations in subsequent differentiation. Denuce thinks that while occlusion and separation are probably responsible, the action of bile is not a factor. He gives no further explanation. Here again tliis view can be answered in a word, namely, that occlusion and separation are not necessary, for they surely were not present and could not be responsible for the variation in my own case. In a review of the cases reported in the literature of aberrant glandular tissue occurring in Meckel's diverticulum itself, I have been unable to find mention of the occurrence of gastric mucosa. In the search it became apparent, however, how often, relatively, pancreatic tissue has been found in the intestinal tract; in fact, cases were found in which pancreatic nodules occurred in the stomach, duodenum, jejunum, ileum and even in Meckel's diverticulum. There were no cases found in which pancreas was discovered below Meckel's diverticulum, a fact which will be considered again. Because of the relative frequency with which aberrant pancreas has been found in the intestinal tract, a brief review is given of these cases and finally a few others are also reported in which Lieberkiihn's* and Brunner s glands and pancreatic tissue were found in Meckel's diverticulum. There is one case also reported in which pancreas was found at the umbilicus. These cases are reviewed with the hope that they may throw some light upon our own case and in general upon the occurrence of gastric mucosa at the umbilicus and in Meckel's diverticulum. The case reports are reviewed in groups according to the location of the aberrant pancreatic tissue ; the first cases being those in which pancreatic tissue occurred in the stomach wall, then in the duodeum, jejunum, ileum, Meckel's diverticulum and at the umbilicus. In only a few instances are the histological descriptions complete and in many instances not really convincing enough to make one feel that the author was really dealing with true pancreatic tissue. On the whole, the explanations offered for these abnormal findings are rather unsatisfactory. Eeference, however, will be made to them in order to


complete our review of tlie theories which have been offered to explain these occurrences.

Klob " (1859) found a flat, circular swelling, of glandular appearance, inserted between the peritoneal and muscle coats, in the middle of the greater curvature of the stomach. Upon microscopic examination this glandular mass showed pancreatic structure throughout. No further description or measurements are given. Klob called this tissue " pancreas accessorium." In substantiation of the belief that he was dealing with an accessory pancreas, he refers to Leydig," who claims that in the land salamander in the wall of the jejunum and in pelobates in the wall of the stomach one can find isolated portions of the pancreas with excretory ducts.

Gegenbauer " (1863) similarly described an accessory pancreas occurring in the wall of the stomach, 2 cm. from the pyloric sphincter and near the lesser curvature. It consisted of a rounded, somewhat elevated, tumor mass 14 mm. in width and 6 mm. in thickness and covered everywhere by stomach mucous membrane. Upon microscopical examination the mass was found to he an acinous gland, resembling pancreas in structure. No further description is given. He found a small duct opening upon the surface.

Merkel " (1905) described two cases of pancreatic rests occurring in the submucosa of the stomach.

Wagner" (1863) described two cases of aberrant tissue occurring elsewhere than in the normal location. In one of these cases, which was very similar to Gegenbauer's case described above, the pancreatic tissue occurred in the wall of the stomach.

Hyrtl " (1860) mentions a rare occurrence of accessory pancreatic tissue behind the arteria and vena mesenterica superior and surrounding these vessels at their roots.

Bernard" (1858) described a second, smaller, pancreatic duct communicating with the main duct, oftentimes, however, emptying independently just below the main duct, in man, dog, cat and rabbit. Bernard has also described tubuloacinous glands in the wall of the duodenum, which are supposed to have the same physiological properties as the pancreas.

Klob" (1859), in a second case similar to the one he described above, found a mass in the posterior wall of the first portion of the jejunum, 4 cm. beyond the duodeno-jejunal turn. No duct was found. Upon microscopical examination the mass was found to consist of pancreatic tissue.

Merkl" (1905) described a pancreatic rest in the subserosa of the jejunum.

Zenker °' (1861) described a frequent variation called the "pancreas minus," a lobe of pancreatic tissue possessing a kind of attachment to the caput pancreatis and emptying usually into the ductus wirsungiajius:, often, however, 1 cm.1.5 cm. below the normal duct. Zenker records five eases, in three of which the accessory pancreas occurred in the wall of the small intestine. In the fourth case there were two accessory pancreases, one 16 cm. the other 48 cm. below the duodenum. The most curious was the fifth case : in this one there occurred, 54 cm. above the cecal valve, a finger-like, true diverticulum 5.5 cm. long, with a narrow, fatty mesentery, in the fat


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of which the accessory pancreas was found situated near tlic tip of the diverticulum. In a foot-note Zenker says:

Vielleicht bezleht sich eine alte von Meckel (Patholog. Anat. I Bd. S., 590) citirte Beobachtung von Schulze auf elnen gleichen Fall. Dieser (Acta, natur. curios. Tom. T. Obs. 226, p. 504, Ao. 1727) fand bei elneni Neugebornen an der Spitze eines wahren Darmdivertikels "cine driisenahnliche Warze." (Im oriprinal beisst es, cuius apicem glandulosa papilla quaedam quasi roronabat. ) Da dieselbe nicht welter beschrieben ist. lasst sich freilich dariiber nicht entscheiden. Vielleicht ist damit auch nur eine jener Ausstiilpungen gemeint, die sich bisweilen an der Spitze des Divertikels finden.

The location of the accessory pancreas in the bowel wall varies. It may be in the submucosa or between the serosa and muscularis. Zenker gives a general histological description, makes no mention of the zymogen granules or islands of Langerhans and states simply that the general structure was that of true pancreas. He was able to find a duct in all his cases. The largest accessory pancreas of this series had a diameter of 3.5 cm. The true pancreas in all cases was normal. He regards the occurrence of accessory pancreas as a developmental anomaly originating in the earliest anlage of the pancreas.

Zenker thinks these anomalies can be explained as follows: The usual pancreatic evagination is single, sometimes double. occasionally triple for the first anlage. These evaginations when multiple then develop into separate glandular bodies. In the further course of development, one becomes the main. true pancreas ; the remaining evagination, either above or below the pancreatic duct, is carried upwards or downwards by the further growth and elongation of the original straight intestine. If above, it comes to lie in the wall of the stomach; if below, it may occur either in the duodenum, jejunum, small intestine or even in Meckel's diverticulum. The last would be the lowest possibility, as Meckel's diverticulum lies at the transition line between the upper and the lower intestine. It is difficult to understand how the gastric anlage in our case could get below the embryologically possible position of the pancreas or how gastric mucosa normally above could get below the level of the pancreatic duct according to this explanation. Zenker could find no evidence of an effect of the accessory pancreas upon the digestion in these individuals.

Several cases are reported further of the occurrence of pancreatic rests in Meckel's diverticulum. Thus ilerkel (1905) demonstrated a pancreatic rest or anlage in the tip of Meckel's diverticulum.

Neumann" (18T0) found, in a child 10 months of age. a swelling the size of a ."mall bean attached to the tip of Meckel's diverticulum by a short pedicle. In its center was a lumen connected by a kind of duct with the lumen of the diverticulum. Upon histological examination, this body was said by Neumann to have gland alveoli resembling in appearance those of the pancreas. No further description is given. This case in many respects resembles the one of the hiunan fetus reported by van Heukelom. except that in this instance the nodule was completely con.stricted off from Meckel's diverticulum at its tip, .separated entirely from the lumen and Wii<


composed of gastric nmcosa. It is interesting to have two cases in many respects simulating one another, one case composed of pancreatic tissue, the other of gastric tissue.

Regarding this anomaly as a Meckel's diverticulum, and this in turn as coming from the ductus omphalomcsentericus, Neumann finds it difficult to see an association between tlie presence of the diverticulum and the occurrence of pancreas. Neumann suggests that the former may not have been a true Meckel's diverticulum, but rather a secondary formation due to mechanical pull of the evaginating glandular mass on the bowel wall. The location of the diverticulum and the subsequent report of a number of similar findings in true Meckel's diverticula would indicate th.it this evagination was probably also a true Meckel's diverticulum.

A good description, together with illustrations of a case in which an accessory pancreas was found at the tip of a Meckel's diverticulum, was given by Bize ' in 1904.

Albrecht' (1901) foiuid in the tip of Meckel's diverticulum a yellowish nodule, about the size of a pea, which resembled microscopically typical pancreatic tissue. In this case, contrary to many other cases described, the author fakes pains really to identify the new tissue formation. He mentions the occurrence of abundant zymogen granules in the cells, centroacinous cells, islands of Langerhans, ducts emptying into the lumen of the intestine, nerves and blood-vessels occurring in normal fashion. Five, possibly six, ca.«es of similar nature are reported in the literature, but without further discussion or description.

In regard to the origin and development of the.fe structures this author suggests that they are possibly :

1. Aberrant Pancreas. — He thinks this pos,<ibi]ify cannot be denied, for on the basis of comparative anatomy it has been shown by v. Kupffer that in the sturgeon pancreatic tissue has been found in the ductus cholcdochus. Others have demonstrated the occurrence of pancreas in the pajiilla minor. These probably represent isolated portions of the original anlage. It is questionable, however, according to this author, whether such rests would lie found as low down as the umbilicus. Furthermore, this conception does not explain why these rests, when found in the region of the lower ileum, occur regularly in the tip of Meckel's diverticulum.

2. Hestx of Glandular Formations Orii/itiatint/ from the Yolk Stalh- or Sac. — That such an origin might be possible is perhaps indicated by the findings of Graf Spec, who described in the yolk sac in the case of the human embryo numerous tubular glands with prismatic epithelium. Opposed to this view, however, is the fact that an analogy of the normal pancreas is impcssible, and furthermore that one would have to imagine that a comple metaplasia of an embryonic organ had taken place.

3. The Alaii.stic Formation. — There is no evidence for this view.

4. " Cdrro(ieneti^." — By exchwion, f.liis conception seems to be more probable as compared with those just mentioned. Whichever view one prefers, a number of interesting thoughts arise. In the first place, the same general developmental fac


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tors or influences must have been present which determined the formation of the normal pancreas, except for the causes of tlie greater growth and the topographical relationship of the normal pancreas. Thus at once we are forced to dismiss the belief that pancreas develops as a result of factors which are present only in the region of the duodenum, such as certain mechanical combinations or strictly localized hormones or similar tissue-stimulating substances. It would seem that, according to this author, the influences which can give rise to these aberrant pancreatic formations are not specific for the duodenum. In fact, the specific reasons for the occurrence of this aberrant pancreas must be sought for in the potentiality for pancreatic formation in the whole small intestinal portion of the original intestinal anlage, namely, the entoderm, certainly in that portion extending from the normal pancreas anlage down to the ductus omphalomesentericus. Perhaps the frequent location of the heterotopic pancreas in the tip of Meckel's diverticulum is consequent upon causative factors similar to those responsible for the formation of pancreas in both instances and sharply localized in the immediately contiguous bowel. These factors may be of a mechanical character.

In conclusion this author speculates upon the possible benefit this type of pancreas can have for its possessor. Since, at least in this present instance, the aberrant pancreas was capable of active normal secretion, it would seem to all appearances that there was a lessening of the danger to the patient of stagnation of the intestinal +++++ CONTENTSs with its consequent possible mechanical and infectious complications, Meckel's diverticulum in this instance being 25 cm. long.

Brunner,' as cited by Tschiknawerow, found in a case of invagination, in a child four and a half years old, a Meckel's diverticulum, 37 cm. above the ileocecal valve, which had at its blind tip a tumor measuring, in its various dimensions, 25 X 22 X 19 mm. Microscopic examination of the tumor showed it to be composed of two parts : one consisting of adipose tissue; the other composed of gland lobules, ducts and lymphoid nodules and resembling pancreas in structure.

Hedinger " (1906) demonstrated in the body of a 30-yearold man, dead of cardiac disease, a Meckel's diverticulum 5 cm. in length. In the wall at the tip of the diverticulum a granular, light yellow nodule of tissue was found measuring 2.5 cm. in length and .5 cm. in width. Microscopical examination showed this nodule to consist of typical pancreatic tissue with an occasional duct and with a second lobule resembling Brunner's glands in structure. He adds a review of the literature bearing upon similar findings and discusses the significance of them.

Nazari " (1909) reports the occurrence of aberrant pancreas in the tip of Meckel's diverticulum.

Tschiknawerow " described three cases of Meckel's diverticulum in which pathological tissue formation was found.

In Case I he described a spindle-celled sarcoma occurring in the diverticulum.

Case II was that of a man 25 years of age who had died of pneumonia. At the tip of and extending into the lumen of the diverticulum, which was 3 cm. long, there was found a small


body, 1 cm. in length. Near the surface of this enlargement glands of the Lieberkiihn type were found, while those in the depths resembled Brunner's glands both as to structure and as to position. The remaining mucosa of the diverticulum had the structure of intestine. The villi were well marked, lymph follicles occurred in areas, and everywhere typical Lieberkiihn's glands were present.

Case III was that of a woman of 55 years of age. At the tip of Meckel's diverticulum, which measured 7 cm. in length, there occurred a rather hard swelling which was found to consist of atypical Lieberkiihn's glands and to resemble pancreas to a certain extent.

Lecene " described an adenoma developing at the level of the free end of a Meckel's diverticulum.

A number of additional instances are reported of aberrant pancreas occurring in intestinal diverticula other than in the true diverticulum of Meckel. The aberrant tissue in the bowel wall is supposed by many to be the primary factor in the subsequent formation of these diverticula, which then enlarge by a secondary evagination of the bowel wall due to pressure within its lumen at a point probably weakened by the glandular mass. Whether this conception is correct or not remains an open question.

Nauwerk ™ ( 1893) reports the occurrence of a diverticulum 9 cm. in length, occurring 2-3 mm. above the ileocecal valve in which an accessory pancreas was found, covered on the outside by serosa and having an excretory duct. He explains the formation of the diverticulum by the mechanical pull of the accessory pancreas on the bowel wall. In addition to pancreatic acini a hyperplastic overgrowth of Lieberkiihn's glands was also found, and the impression was gained that numerous transitions occurred between these overgrown Lieberkiihn's glands and the true pancreatic lobules. Besides this diverticulum a true Meckel's diverticulum was also found, measuring 3 cm. in length and situated 80 cm. above the ileocecal valve.

Further examples of this condition are reported by Thompson,'" Hulst " and Albrecht and Arzt.

A case of pancreas occurring at the umbilicus was described by Wright." In a girl 12 years of age there was found a congenital umbilical fistula which, after breaking down twice following operation, healed as a result of complete extirpation of the fistulous tract in which a pancreas nodule was found.

Franchomme* (1893) has described in greater detail the anomalies which are apt to occur in the remains of the vitelline canal.

Discussion

It is seen, then, that the occurrence of aberrant glandular tissue, particularly gastric and pancreatic, may occur in the stomach, intestine, Meckel's diverticulum, in the obliterated cord connecting the latter with the umbilicus and at the umbilicus itself. These aberrant tissues have a great interest for embryologists in view of their possible explanation and to pathologists for this reason also, and furthermore for the reason that new growths and other pathological processes may rise from these aberrant tissues. To the surgeon, furthermore,


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because they may be the seat of inflammation, perforation, abscess formation and even subsequently of intestinal obstrui'tion. In jreneral. very few complete histological studies with the idea of absolutely determining the nature of these tissues under consideration have been reported. As a consequence, there has been considerable confusion in the past in certain instances as to the exact type of glandular tissue witii which one was dealing. The case reported in this present ])ublication offered, therefore, a good opportunity for positively identifying in the tip of Meckel's diverticulum an area of gastric mucosa of the fundus type. This was done beyond question, and therefore the facts can he used in clearing up or in refuting a number of theories wiiich have been offered in the past to explain the origin of these aberrant tissues and to furnish certain facts for a more probable theory as to tiieir origin.

Speaking in the first place of aberrant mucosa it may be recalled that several cases of gastric mucosa occurring at the umbilicus, in the form of polyps, depressions or fistulae, were reported by Tillmanns, Reichard, Roser, Weber, Lexer, Denuw and a few others. In one or two instances such a fistula was blind and was attached at its inner extremity to a librous cord or to Meckel's diverticulum itself. The latter in these instances had the structure of intestinal epitliclium. In one instance, namely, that of van Ileukelom, there was found in a human fetus a small nodule of gastric mucosa at tiie tip of Meckel's diverticulum which had become com})letely constricted off and separated from tiie lumen of the divertiiuluni, but was still attached to the latter.

In many of these cases the reports, in which histological examination was more or less incomplete or not made at all, are rather unsatisfactory. In only one instance, I may say, was there a very careful histological examination made, namely, by Denuce, who reported mucosa of the gastric fundus type occurring at the umbilicus. Aside from this there were no other cases in which gastric fundus mucosa was found or described. My own ca.<e, then, represents the only one in the literature in wliich a consideral)le area of mucosa at the tip of Meckel's diverticulum, communicating freely with it and in continuity with tiie remaining muco.sa of the diverticulum, was found to be of the gastric fundus type or even gastric at all.

In this manner, then, the link in the chain of evidence which goes to show that this aberrant gastric tissue arises from remnants of the omphalomesenteric duct is complete.

Several of the theories which have been advanced to explain the origin of this tissue are thus effectively answered in the negative. Thus. Tillmanns' theory, which had few adherents and which supposed that gastric mucosa occurring at the umbilicus is derived from gastric diverticula, becomes quite improbable. Van Heukelom had already quite effectivelv answered this theory.

The second theory is that of Siegenlieck van Heukelom, who believes that these aberrant growths at the umbilicus and at the tip of Meckel's diverticulum represent tiie remains of the vitelline duct. He, however, felt that the differentiation into gastric or intestinal epithelium depended upon whether or


not the mucosa in early fetal life had become differentiated before or after the influence of bile had become effective. This view is doubtless in part correct, but not altogether, for again my findings show that gastric mucosa may differentiate from the intestinal epithelium even under the same influences so far as concerns the action of the intestinal +++++ CONTENTSs. In other words, isolation of the mucosa very early in fetal life is not essential for the development of gastric mucosa.

The third explanation, namely, that of Salzer, that misplaced entoderm at the umbilicus is stimulated to a variable differentiation by irritation or inflammation and consequently may give rise to gastric, intestinal, or even pancreatic tissue, similarly does not fully explain, for again, as my case shows, gastric mucosa may develop in the absence of such irritative or inflammatory conditions.

The fourth theory, tiiat of Albrecht and Fischl, that these aberrant tissues arise from fetal inclusions or rests occurring at the umbilicus at the time of the closure of the abdominal wall, similarly does not suffice, for the occurrence of these tissues in the tip of Meckel's diverticulum can certainly occur without these factors being present.

The fifth explanation, which is doubtle-^s the most nearly correct, was practically accepted by Lexer and by Denuce. These authors assumed that these umbilical aijuormalities represent the remains of the omphalomesenteric or vitelline duct, although no very detailed facts have been offered to support this view. My own case would complete the evidence so far as gastric mucosa is concerned, for it shows in the first place that gastric mucosa can and does arise from the remains of the vitelline duct if one assumes, which is doubtless correct, that Meckel's diverticulum itself is the representative of such remains. One need assume no further factors nor circumstances, such as improi)able constrictions in tiie stomach or misplacements and irritations affcK-ting the entoderm, which are thus caused to undergo this peculiar differentiation. It becomes evident then how important this finding has been, because it has allowed us to answer effectively the previous views and to furnish indisputable evidence that the gastric mucosa as reported in previous cases occurring at the umliilicus has doubtless arisen from the omphalomesenteric duct. .\s to the ultimate influences which iiave caused this differentiation one cannot state definitely in the present condition of our knowledge concerning these processes.

The sixth and last explanation, practically that of Albrecht, is, so far as present evidence goes, the most nearly correct, and this holds for pancreatic tissue or gastric or in fact any of the glandular tissues of the intestinal tract, such as Brunner'a glands. According to this view the original entodemial lining of the intestinal tube and omphalomesenteric duct pos.sesse8 potentialities of development into any of the glandular structures in the adult intestine or of its acces-sory glands, and under the influence of certain circumstances, which we do not understand, groups of cells may retain one or the other potentiality and develop into a glandular tissue or organ very different from the surrounding glandular tissue and rescm


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bling the adult organ, such as stomach or pancreas, which may be far removed.

In view of his findings of aberrant pancreatic tissue at various points in the intestinal tract, Zenker felt that these anomalies represented pancreatic anlages, which in the further course of development were carried upwards or downwards by the further growth and elongation of the original straight intestine and which might come to lie hence in the stomach or in any part of the intestinal tract down to and including Meckel's diverticulum. If this assumption is made in the case of the pancreas, then one should assume the same, I think, in the case of the stomach, in which instance it seems quite impossible to believe that a gastric anlage could by such mechanism become displaced so far as to lie below the possible embryological position of the pancreas. One certainly could not apply this view to the occurrence of gastric mucosa at tlie umbilicus or in Meckel's diverticulum.

Finally, Albrecht's view as stated above is probably tlie correct one. If we accept this view of the imiform potentiality of the entoderm to develop into any of these glandular tissues, we can readily understand how cases of aberrant stomach, pancreas, Lieberkiihn's glands and Brunner's glands can occur anywhere in the intestinal tract as far down as Meckel's diverticulum. The intestine below Meckel's diverticulum which represents the hindgut doubtless has not these potentialities, as a consequence of which these aberrant structures have never been found below the level of Meckel's diverticulum.

To summarize then, I have reported a case of a young man, 19 years of age, who presented before operation symptoms and signs suggestive either of acute appendicitis or partial intestinal obstruction. On examination, among other things there was found just below the umbilicus a scar which had been produced by a former operation for an abscess. The nature of the abscess was not determinable. Upon subsequent operation it was found that the small bowel had become strangulated over a thick, fleshy cord consisting of Meckel's diverticulum and some adherent omentum which fastened the former to a point on the anterior abdominal wall just below the umbilicus. Excision of Meckel's diverticulum with the adherent omentum was done and the patient made an uneventful recovery.

Upon examination of the open diverticulum there was found in the distal third or fourth of the diverticulum an area of thickened, irregular, granular, dark red mucosa which was demarcated sharply from the proximal pale finer mucosa, which in turn was of intestinal character. Furthermore, upon careful histological examination this distal segment was found to consist of a mucosa definitely resembling in every particular that of the gastric fundus region. The glands were precisely of the fundus type and showed the characteristic zymogen granules of the chief cells and the eosinophilic granules of the parietal cells as characteristic in the glands of the stomach.

Upon a careful search of the literature it is found that a number of cases have been reported of the occurrence of gastric mucosa at the umbilicus in the form of polyps or fistula?.


Other aberrant tissues, such as pancreas, have been described along the intestinal tract and even in one instance in a nodule at the tip of Meckel's diverticulum and connected with its lumen. Another interesting case reported is that of van Heukelom in which a nodule of mucosa was foimd at the tip of Meckel's diverticulum, constricted off from it, not connected with the lumen, but attached by a fibrous cord. This mucosa proved to be of pyloric nature. My own case is the only one of which I am aware of gastric mucosa occurring in the wall of Meckel's diverticulum and in free communication with its lumen. Careful histological examination was made necessary because of the rather uncertain findings reported by previous authors and of the various theories which have been constructed to explain the occurrence of these aberrant tissues at the umbilicus.

The finding in my own case of gastric mucosa in Meckel's diverticulum, which it is agreed quite generally is a definite remains or persistence of the vitelline or omphalomesenteric duet, makes it appear certain that these al>errant tissues occurring at the umbilicus, in fibrous cords and in Meckel's diverticulum, have a uniform origin, namely, from the entoderm of the original intestinal tube or yolk stalk. It was very important to complete the evidence that these aberrant tissues may arise anywhere along the tract of the original omphalomesenteric duct in order to answer the various hypotheses which were previously advanced.

After a review of these hypotheses and in view of the evidence that I have brought forward, the best explanation for the occurrence of these structures is, that the original entodermal lining of the intestinal tube and omphalomesenteric duet possesses potentialities of development into any of the glandular structures of the adult intestinal tract or of its accessory glands, and under the influence of certain circumstances, which we do not understand, groups of cells may retain one or the other potentiality and develop into a glandular tissue very different from the surrounding glandular tissues and resembling the adult organ, such as stomach or pancreas, which may be far removed. The finding in my case of gastric mucosa in Meckel's diverticulum effectively answers the various theories that the gastric growths at the umbilicus may have arisen by constriction or separation from gastric diverticula in the early fetus, or that a differentiation in the mucosa or in these aberrant tissues is brought about by the presence or non-presence of the bile, or that irritations, inflammations or fetal inclusions at the point of union of the blastodermic layers are necessary. In fact, there is good evidence now, with the findings in my own case, for believing that these aberrant tissues arise from remains of the omphalomesenteric duct ; but as to the ultimate factors which cause this differentiation we cannot state in the present condition of our knowledge.

The finding of this gastric mucosa explains well the reasons for the finding of acid secretion with digestion at the umbilicus, in cases of umbilical polyps and fistula as reported in the literature, although cases in which gastric mucosa oc


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curred at the umbilicus had been reported before. Again, we have a good embryological basis for understanding certain adenomatous tumors and growths of an intestinal glandular nature occurring at the umbilicus, in oblitenxted intraabdominal umbilical cords and in Mecicers diverticulimi. In fact, in the caj?e reported it is interesting to speculate as to the condition for which the patient had been operated upon several years previously. It seems probable that there was at that time a perforation at the tip of Meckel's diverticulum, though none was found at the operation. As a consequence of this an abdominal abscess formed which was simply drained and whicli healed with the formation of adhesions between the tip of Meckel's diverticulum and the anterior abdominal wall. It is interesting to think also that this perforation at the tip of Meckel's diverticulum might well have been a perforative gastric ulcer, for so far as the structure of the mucosa went we were certainly dealing with the fundus type of mucous membrane. This perforation evidently healed subsequently. The case further illustrates the desirability of examining carefully all cases of Meckel's diverticulum for the possibility of occurrence of aberrant glandular tissues in the mucosa, both for embryological reasons imd also because of the importance of these structures in pathology and certain surgical conditions.

In conclusion, I wish to acknowledge my indebtedness to Mr. H. F. Aitken for the drawings in black and white, to Miss Ethel Norris for the two figures in colors, and to Dr. T. S. CuUen for the use of the drawings of the umbilical anomalies as illustrated by Mr. Max Brocdcl.

BIBLIOGRAPHY

1. Albrecht, E.: Ein Fall von Pankreasbildung In einem Meekel'schen Dlvertikel (Abstr. ). Munchen. med. Wchnschr., 1901, XLVIII, 2061; also. Sitzungsb. d. Gesellsch. f. Morphol. u. Physiol, in Munchen (1901), 1902, XVII. 52, cited by Tschikna.

2. Albrecht, H.. and Arzt. L.: Beltrage zur Frage der Gewebsverlrrung. (2) Ueber die Bildung von Darmdivertikeln mit dyatopischem Pankreas. Frankf. Ztschr. f. Path.. Wleb., 1910, IV, 167186.

3. Bize: Etude anatomo-cllnlque des pancreas accessolres situfis & I'eztr^mitg d'un dlvertlcule intestinal. Revue d'orthop., Paris, 1904, 2 b., V, 149159.

4. Bensley. R. R.: The structure of the glands of Brunner, The Decennial Publications. The University of Chicago Press, 1903. X.

5. Bernard, C: Legons de phys. exp^rim. Tome II, Schmidt's Jahrb., 1858, XCVII. 21.

6. Brunner, C: Ein Beitrag zur Chirurgle und pathologlschen Anatomie der Darmlnvaglnatlon. Beitr. z. kiln. Chir., 1895, XXV, 345.

7. Cullen, T. S.: The umbilicus and its diseases. W.B.Saunders Company, Philadelphia and London, 1916.

8. Denuc^. M.: FIstules pseudopylorlques cong6nitales de I'ombillc. Revue d'orthop«die. 1908, l.\. 1-29.

9. Franchomme. H.: Anomalies de r^-gresslon du canal vitellin; dlvertlcule de Meckel, flstules ombllicales. 4', Paris, ISg.!.

10. Gegenbauer, C: Ein Fall von Nebenpankreaa In der Magenwand. Arch. f. Anat., Physiol, u. wissensch. Med., Leipzig, 1863, 163-165.


11. Hedinger: (Fall von Mekelschem Dlvertikel mit Pankreasgewebe und Brunnerschen Driisen an der Spltze desselben.) Corr.-BI. f. schweiz. Aerzte. Basel. 1986, XXXVI, 395. 1. WIntersitzung DIenstag, den 3 Okt., 1905.

12. Hulst, J. P. L.; Ueber elnen in einem Darmdivertikel gelagerten Pankreaskelm mit sekundarer Invagination. Centralbl. f. allg. Path. u. path. Anat., Jena, 1909. XX. 12-15.

13. Hyrtl, J.; Handbuch der topograph ischen Anatomie und ihrer praktisch niediclnisch-cliirurgischen Anwendungen, 46, 1860, L, 667.

14. Klob, J.: Pancreas-Anomalien. Ztschr. d. k. k. Gesellsch. d. Aerzte zu Wien, 1S59, XV, 732.

15. Lecene, P.: Ad6nome d6velop6 au niveau de rextr6mlt6 libre d'un dlvertlcule de Meckel. Bull, et m#m. Soc. anat. de Par., 1912, LXXXVII, 63.

16. Lexer, E. : Magenschleimhaut im persistlrenden Dottergang. Arch. f. klin. Chir., 1899, LIX, 859-865.

17. Leydig, F. : Lchrhuch der Hlstologle des Menschen und der Thlere, 1857, 352, cited by Zenker.

17*. Lindner. M. H.: Discussion: Ein Fall von Extirpation des persistlrenden Ductus omphalo-mesentericus. Deutsche med. Wchnschr., 1S98. XXIV, 172v.

18. Merkel: Discussion: Abgesprengte Pankreasanlagen. Munchen. med. Wchnschr., 1905, LII, 337.

19. Minelli, S.: Adenoma Ombellicale a Struttura gastrlca. Gazz. med. ital., Torlna, 1905, LVI, 101-105.

20. Nauwerck, C: Ein Nebenpankreas. Beitr. z. path. Anat. u. z. allg. Path., Jena, 1892, XII, 29-32.

21. Nazari. A.: Pancreas aberrato in un diverticolo di Meckel. Bull. d. r. Accad. mod. di Roma, 1909, XXXV, 245-250.

22. Neumann. E.: Nebonpancreas und Darmdivertikel. Arch. d. Hellk., Leipzig, 1870, XI, 200.

23. Reichard, V. M.: Demonstratlonen zur Magen-Darmchirurgle. Zentralbl. f. Chir., 1898, XXV, 587-588.

24. Roser, W.: Zur Lehre von der umbilikalen Magencystenfistel. Zentralbl. f. Chir., 1887, XIV, 260.

24'. Salzer, H.: Ueber das offene Meckelsche Dlvertikel. WIen. klin. Wchnschr.. 1904. XVII. 614-617.

25. Strada, F. ; Adenoma congenlto ombelicale a tlpo gastrlco (Contributo alio studio dei tumor! congenitl dell 'ombelico). Sperimentale Archlv. dl Biol., 1903, LVII, 637-658, I pi.

26. Thomson, A.: Diverticula of the alimentary tract, with particular reference to those met with In the ileum resulting from an accessory pancreas and from tuberculosis. Tr. Med.-Chlr. Soc. Edinburgh, 1908, n. s. XXVII, 118-129, 2 pi.

27. TlUmanns, H.: Ueber angeborenen Prolaps von Magenschleimhaut durch don Nabelring (Ectopia ventricull) und iiber sonstige Geschwiilste und P'isleln des Nabels. Deutsche Ztschr. f. Chir., Leipzig, 1882-3, XVIII, 161-202.

28. Tschlknawerow, L.: Zur Kenntnis dor pathologlschen Gewebsbildungen In Meckel'schen Dlvertikel. Berl. kiln. Wchnschr., 1911. XLVIII, 1676-1679.

29. van Heukelom, S.: Die Genese der Ectopia ventricull am Nabel. Vlrchow's Arch., 1888, CXI, 475.

30. von Rosthorn, A.: Ein Beitrag zur Kenntnis der angeborenen Nabelflsteln, Wlen. kiln. Wchnschr., 1S89, II, 125; 154.

31. Wagner, E.; Accessorrlsches Pankreas In dor Magenwand. Arch. d. Hellk.. Leipzig, 1862, III, 283.

32. Weber, W.: Zur Kaaulstik der Ectopia Ventricull. Beltrftge z. klin. Chir.. 1898, XXII. 371-385.

33. Wright. J. H.: Aberrant pancreas in the region of the umbilicus. J. Boston Soc. Med. Sc, 1900-1, V, 497-498. 1 pi.

34. Zenker, F. A.: Nebenpancreas In der Darmwand. Arch. t. path. Anat. (etc.), Berlin, 1861, XXI, 369-376.


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[No. 340


A GRAPHIC APPLICATION OF THE PRINCIPLE OF THE EQUILATERAL TRIANGLE FOR DETERMINING THE DIRECTION OF THE ELECTRICAL AXIS OF THE HEART IN THE HUMAN ELECTROCARDIOGRAM

By Edward Perkins Carter, Cdrt P. Eichter and Carl H. Greene (From the Cardiographic Department of The Johns Hopkins Hospital and University)


In 1908 Einthoven ' first called attention to the fact that a definite relationship exists between the amplitude of the deflections of the electrocardiogram obtained from the three leads — right arm, left arm and left leg — and that when the amplitude of any two such derivations is known the third can be determined ; formulating his law, based upon this relationship, that


A year later, in a joint paper with Fahr and De Waart,' he expanded more fully the principle of the equilateral triangle and published tables, based upon trigonometrical formulae, which made it possible to determine, within a negligible factor of error, the direction of the electrical axis of the heart, the relative preponderance of either the right or the left ven


L.R.



Fig. 1. — After Einthoven. Illustrating the fundamental principle of the equilateral triangle. P^Q - E, p, — g, = c„ p, — 9, = e„ P, — a, = e« e, = c, + e,. The angle = + 55°.


under like conditions of electrical resistance and tension Lead III must equal Lead II minus Lead I.

In 1912, in an address before the Chelsea Clinical Society of London,' he furtlier developed his fundamental conception of the course of the excitation wave in the heart, based upon the analogy of the three leads employed to the sides of an equilateral triangle in which the direction of the axial current bears a definite and determinable relationship to the parallel plane of Lead I (E. A. and L. A.).


tricle and the shifting alteration of tlie axis of potential difference in the more bizarre forms of electrocardiograms so frequently met with.

The fundamental principles involved are briefly as follows: Assuming that the tliree leads usually employed — the right arm, the left arm and the left leg — represent the three sides of an equilateral triangle (see Fig. 1), we draw a line parallel to the line uniting the two ann leads at a level corresponding to the center of a circle enclosing tlie triangle, the right-hand


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end representing 0° and the left-hand ond 180°. At the center of this line is placed the point // representin<r the heart, the electrical axis of which is diagTanimatically illustrated by the arrow p-q. Rotation, then, counter-clockwise of the axis above this horizontal line represents a negative angle, whereajs rotation clockwise below tlie horizontal represents a positive anjrle. The normal electrical axis is illustrated by the direction of the arrow in the figure in which the angle a, tlie angle of deflection between the arrow p-q and the horizontal line corresponding to the plane of Lead I, measures in our figure +55°.

If upon this arrow indicating the direction of the axial current we mark off two points p and q, Einthoven has shown that the distjince between lines projected from these points: at right angles to any one of the three sides of the triangle, which correspond to the three leads, will represent the amplitude of the deflections for that lead, and that under all normal conditions the amplitude of i?,-f i?3 = 7?j. Furthermore, from the amplitude of these deflections we may determine the direction of the axis of potential difference in the heart and may calculate the angle a, thus determining in degrees the rotation of the electrical axis in the sagittiil plane and the accurate measurement of the angle formed in relation with the horizontal plane representing Lead I (R. A.-L. A.).

It should be clearly understood that the amplitude of any given deflection represents the difference in potential in the electrical axis existing in the heart at a given instant of time in relation to the lead employed, and that this amplitude will vary as the electrical axis alters its position in relation to this lead. Hence, it is evident that the amplitude of any given deflection may not represent the greatest difference of potential possible in that lead, and Einthoven insists that we must distinguish between what we may call the recorded difference of potential and the maximal possible deflection, which he designates as the " manifest potential difference " or the " manifest value.'"

This manifest value depends upon the maximal distance separating the two points between which the potential difference is developed and is only met with when the electrical axis and the lead employed lie in parallel planes. It can be calculated from the height of the recorded curves and can be expressed in absolute measure in millivolts by multiplying the deflection measured in millimeters by lO"* when the galvanometer string ha,s been standardized for the usual deflection. In determining the angle a, however, for all clinical purposes we may disregard this manifest value, though a tat)le giving the various determinations of this potential differeni c is incorporated in the last paper referred to above.

Einthoven's formulae are as follows: If we let p-q = E, representing the manifest value, Pi — 7i = ^i, Pz — <Ii'=^i e, =f^eo6a. (1)

f5 = £cos (a-60). (2)

«', = i?cos (120-O). (3)

e, = e,-e,. (4)


It is evident that under these conditions the potential difference present between the angles of the triangle must bear the following relationship e, : f, : e,. From these data when the angle a is unknown it can be determined from the relationship of any two of these potential differences from the following formula? :


ie —e

Losing r, and c. /fl. a = ' ^'•


Using c, and e., tg. a = Using Co and e, tg. a =


(5) (6) (7)


2e^ + c^ f,V3

We have stated above that under normal conditions this law that 62 = 6,-1-63 holds true. That clinically, however, we constantly meet with apparent exceptions to this statement is a matter of common observation. It must be kci)t in mind that while we are dealing theoretically with a fiat i)lanc we have actually to do with a very complicated muscle mass and it is the more remarkable that this seeming exception to this fundamcntjil law is apparent rather than real, and that it is due, as Einthoven has shown, to the phasic variation between similar peaks of the electrocardiogram.

In order to determine exactly the proportional amplitude of a given deflection in the three leads, especially in all instances showing conspicuous pliasic variation, we must know the exact time relationship of the deflection to the cardiac cycle in each of the three leads, ilanifestly, this can only be determined by simultaneous records of the heart sounds and the electrocardiogram, such as have been made by Falir,* or by the use of two galvanometers as employed by Williams.' Fortunately, this apparent exception to the simplicity of the fundamental principle involved does not invalidate the application of the formulae given above in all normal instances and may be corrected for as Einthoven has shown in the more obscure forms.

Using two galvanometers Williams (I. r.) has shown by the projection of vectors determined from the manifest value e, in conformity with the different leads, the essential nature of this phasic variation in homonymous peaks of the electrocardiogram, and has further demonstrated that the bizarre curves met with are due entirely to the manner in which the direction of potential difference is shifting within the heart, and that, although the peaks arc absolutely in phase in only a few instances, such absolute accuracy in the calculated values is not essential for. the majority of clinical records.

Based upon the principle of the equilateral triangle Pardee' has published a graphic method by which the negativity of the initial ventricular deflections determines within the limits of 60° the direction of tlie axis of potential difference. This i.s accomplished by dividing tlie circumference of the circle into six quadrants, into any one of which it can be shown, by the positivity or negativity of the recorded deflections, that the axis of potential difference must fall.

It is interesting to note how closely the angle, determined by means of the tables published by Einthoven, Fahr and De Waart, coincides with the results calculated bv the use of


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[No. 340


their formulas 5, 6 and 7 given above. These observers have further demonstrated that the angle varies with inspiration and expiration in different individuals from 12° to 36°, being always greater in inspiration than in expiration, the normal angle falling between +40° and + 90°.

In a true left ventricular preponderance the angle a has a value approaching —20°, falling between 0° and —40°, while with a right ventricular preponderance it has a value approximating +120°, falling between +90° and +150°. If we assimie that the electrical axis in these cases originally had a normal value, we must postulate a rotation of the direction of potential difference through an arc of from 70° to 140°. That this, however, implies a rotation of the anatomical axis of the heart throughout anything like the same extent is manifestly absurd, and the explanation for the rotation of the axis of potential difference must be sought in the shifting balance of the muscle mass and the ensuing relationship of the plane of the electrical axis to the Derivations I and III.

Figs. 2, 3 and 4 may serve to make this point clear. Fig. 2 illustrates the normal direction of the axis of potential difference. In this figure the excitation wave passes from base to apex within the heart and from apex to basal structures through the galvanometer, the deflections being upright in all three leads. In Fig. 3, the deflections are upright in Leads I and II, though the predominant deflection may be do'miward in Lead II, and downward in Lead III ; while in Fig. 4, the deflections are downward in Lead I, and upright in Leads II and III. The direction of the course of the difference in potential is indicated in each instance by the direction df the arrow.

In a paper upon the localization of the origin of the excitation wave in the human heart, Fahr and Weber ' have demonstrated the soundness of the principle involved in the use of the geometric figure and the facility with which one can graphically determine the measurement of the angle a and the direction of the axis of potential difference by plotting upon an angle of 60° the values, in tenths of a millivolt, of the two leads and projection from these values of right angle lines.

In the graphic method of plotting the angle a, illustrated by Fig. 5, we have made use of the principle of the equilateral triangle inscribed wdthin the circumference of a circle upon which are marked the degrees from 0° at the right to ± 180° at the left-hand end of the axis of the circle. Following Einthoven's original description rotation of the angle downwards and to the left, clockwise, constitutes a plus angle, whereas rotation upwards and to the left, counter-clockwise, constitutes a negative angle.*

The point marked by the intersection of the ordinate from the middle of the line representing Lead I and the horizontal axis of the circle represents the heart, and may further be regarded as the point p of the axis of potential difference, as illustrated in Ficr. 1.


  • This method of reading a positive or negative angle is at

variance with the accepted custom in vogue as given by Wentworth and Smith, " Plane Trigonometry," Chap. V, p. 77, 1914.


If from each side of our equilateral triangle we project ordinates, at a distance of 1 mm. apart, assigning to those on either side of the center of each base line, corresponding to the Leads I, II and III, their proper positive or negative sign determined by the projection of our arrow p-q, then the point of intersection of any two of these ordinates, representing the value of «!, e^ and e^ under their proper sign, must coincide with the point q in our diagram Fig. 1. A line from the center H to this point of intersection corresponds to the manifest potential difference E, and will give us the direction of- the axis of potential difference. By projection of this line to the circumference of the circle the angle a may be read off in degrees with its corresponding positive or negative value.

Utilizing the measurements of all three derivations in the terms of e^, e„ and e^, tmder their proper sign, we shall find that with the physiological electrocardiogram our point of intersection for all three leads coincides very closely, and that in those instances with a conspicuous phasic difference the point of intersection will vary slightly, depending upon the ordinates employed, thus suggesting in a graphic way the extent of this phasic variation.

In the instances suggesting a ventricular preponderance, the values e^ and e^ should be used, and whenever the initial ventricular deflections are definitely diphasic in character, their corrected value should be determined by deducting the lesser amplitude from the greater.

Figs. 6, 7 and 8 may serve to illustrate the method of application of the principles stated above for determining the axis of potential difference in the heart.

In Fig. 6, which represents a physiological electrocardiogram, i?i measures 9 mm., R^ 16 mm. and ^3 7 mm. in height. We may express these values in the terms of e, as e^=-\-9, e«=+16, and 63= +7, then ej^ej + fij. If we follow the ordinate +9 from the side corresponding to Lead I to the point where it meets the ordinate +16 from the side representing Lead II, we shall find that the ordinate +7 representing Lead III intersects this point (see the small circle in Fig. 5 in the lower right-hand quadrant) and a line from the center H projected through this point of intersection to the circumference of the circle gives the direction of the axis of potential difference and the value of the angle a as + 55° and approximately 30'. Determining the value of a for this electrocardiogram by Einthoven's formula 5 we get a value of + 55° and 53'.

In Fig. 7, the initial ventricular deflections have the following values: i?i=15 mm., jSi=— 1.5 mm., i?, = 4 mm., jSj = — 9 mm., i?3 = 1 mm., Sj = — 16 mm. We may ignore the values of S-^ and R^ as they approach each other so closely, and utilizing i?i and S^ (e, and 63) we repeat the steps outlined above and follow the ordinate + 15 representing the Lead I to the point intersected by the ordinate — 16 representing Lead III. A line from the center H through this point of intersection and projected to the circumference of our circle gives the value of the angle a as —34°. Determined by formula 6 the value is found to be —33° and 12' — an


June, 1919]


165


•K.A



X.A


•U.A


X.V..


Flo. 2. — lllutitmtin? the normal physiological dirrction of the axis of potentui difference in the heart. The arrows indicate the dirertiKii of the initial ventricular dellectlona in the three leads. See Fig. 6 and description in text.



Fio. 3.— IIlustratiiiK the direction of the axis of potential (Jiffercnce in left ventricular preponderance. See Fig. 7 and description in text.


Flo. 4. — IllustnitinK the direction of the axis of potential difference in ri(fht ventricular preponderance. See Via. 8 and description in text. Fiffs. 2, 3 and 4, modified after Pardee.




-i : : .






ii






m:



-L



1


• •!





r^'



1


! 1



1



electro. ar.liugrain. Tl.e iJ.Kli- a in..,..urM + .55" and approiimalel.r 30' bv plotting, and + i.i* and SS' by formula i.'


punilcmiiL-e. I lir titiKJi- a iii««Burcii — AA and i>nnie niinut>'< I'.t plotttlv, nd — 33' and 12' by fomiiilu ti.


Ittr prepondrmnce. The nnKJe a meiuiure« approximulciv -» 1'20" bv pliittInK, and exurllv -r I'JO by formula 0.


166


[No. 340


^^o_j:3o



Fig. 5.— Illustrating the graphic determination of the angle a by means of ordinatcs projected from each side, or base, of the triangle representing the three leads. The ordinates are drawn to scale 1 mm. apart. The small circles in the figure represent the points of intersection of the e values determined from Figs. 6, 7 and 8. The arrows projected to the circumference point to the plotted measurement of the angle a in degrees of these figures. Se3 description in text.


June, 1919]


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angle known to be associated with left ventricular preponderance.

In a similar way we may plot the values of Fig. 8, which after correction for tiie slightly dipliasic curves in Leads I and III are found to be as follows in the terms of e: e,= — 5 mm., «j= + 10 mm. Projecting our line from the center 11 through tliis point of intcrs:ection (see point in lower left-hand quadrant of Fig. 5) we find that the value of a falls between + 120° and +121°. Determined by formula 6 the value of the angle a for this figure is exactly +120°, an angle known to be associated with right ventricular preponderance.

The points of intersection of the ordinates as given above are marked by the small circles in Fig. 5, and the arrows indicate the projection of the axis p-q from the center H through these points of intersection to the circumference of the circle giving tlie direction of the axis of potential difference and the value of the angle o in degrees.

In addition we may determine graphically the true manifest value of the potential dilTerence. As Einthoven has shown {loc. cit., 1913), if the angle a = t)0° the manifest value E is equal to the deflection in Lead II, for this lead is then parallel to the electrical axis. If the angle a is equal to 0° or to ± 180°, E = e^. If the angle a=+120° or -60°, E = e,. Referring


again to the examples given above, in Fig. 6, £=16.2. In Fig. 7, J5:= i:.8. In Fig. 8, A'= 10.

It is then plain that this diagrammatic usage of the equilateral triangle is available for accurate det<>rminations of the direction of the axis of })otential dilTerence, the angle a and the manifest value H.

SU,M.\L\RY We have emphasized the value of the fundamental principle of the equilateral triangle as applied in the interpretation of clinical electrocardiograms, and have illustrated graphically a simple method of procedure by which the value of the angle a may be quickly found.

BIBLIOGRAPHY

1. Einthoven, W.: Pflug. Arch. f. die ges. Phys., 1908, CXXII, 55S.

2. Mem .• The Lancet, London, 1912, March 30, 853.

3. Einthoven, W.. Fahr, G., and De Waart, A.: Pflug. Arch. f. die ges. Phys., 1913, CL, 275.

4. Fahr, G.: Heart, 1912-13, IV, 147.

5. Williams, H. B.: Am. Jour. Phys., 1914, XXXV, 292.

6. Pardee, H. E. B.: Jour. Am. Med. Assoc., 1914, LXXII. No. 17, 1311.

7. Fahr. G., and Weber, A.: Deut Arch. f. klin. Med., 1915, CXVII. 361.


PHAGOCYTOSIS AND AGGLUTINATION IN THE SERUM IN ACUTE

LOBAR PNEUMONIA: THE SPECIFICITY OF THESE REACTIONS

AND THE REGULARITY OF THEIR OCCURRENCE

By Paul W. Clovoh (From the Medical Clinic of The Johns Hopkiyis Honpital)


In a previous article ' the writer reported the results of some observations in a .small series of cases on the activity of the serum developing, after crisis or lysis, in patients with acute lobar pneumonia. In agreement with the results obtained by most previous observers, it was found that the serum at this time usually developed a definite, though often feeble, protective power for mice, provided the test was made with the homologous strain of pneumococcus, isolated from the patient whose .scrum was being tested. This activity was not demonstrable in .«erum obtained during the active stage of the disease, either from patients who subsequently recovered or from those who died. It was further shown that, in a considerable percentage of the cases (six of 11 ca.ses), a definite phagocytic activity could be demonstrated in the serum from convalescent patients. It was especially emphasized that this phagocytic activity has a significance quite different from that of an increa.se in opsonic index, as determined by the Wright method. In the latter, one uses heterologous stock strains of pneumoi'wci of low virulence, which are at least moderately phagocytable in fresh normal serum. The strains studied by the writer, on the contrary, were (with one exception) of high virulence, and absolutely resistant to phagocytosis in fresh normal serum.


This phagocytic activity ran clo.«ely parallel with the protective power of the serum. It was entirely absent during the acute stage of the di.sea.se, and appeared only at or near crisis or lysis. It was not present in the serum of a fatal case. Like protective power it was manifested (with one exception) only toward the homologous strain of pneumococcus, and not toward those heterologous strains which were tested. It wa-s further siiown that in the two cases ti-sted as to this point, phagocytosis in riro ran ])arallcl to that in the testtube. In the peritoneal exudate of the protected mice, the pneumococci were ingested and dissolved within the leucocytes; whereas in the control mice receiving normal serum the organisms multiplied rapidly and remained exclusively extra-cellular.

In view of these facts, and of tiie ]mrt that jibagocytosis has been shown to play in the activity of jyotent immune serum,' the writer felt justified in concluding that jihagocytosis probably plays an imirortant role in the immunity developed in man at crisis.

The series of cases was too small, however, to demonstrate the regularity with which phagocytic activity develops. Furthermore, the strict limitation of the activity of each serum tested to the homologous strain of pneumococcus was sur


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prising, in view of the findings of Cole and Dochez that most strains can be classified in a small number of groups. It, therefore, seemed desirable to extend these observations over a larger series of cases, and to determine more definitely the exact specificity of the reaction.

The results previously reported by the writer ' were shortly confirmed by the independent observations of Lister ' in South Africa. Using a similar method, he also demonstrated in most of his cases definite phagocytic and agglutinative activity in the serum after crisis, when tested with the homologous organism. When these sera were tested with heterologous strains, pliagocytosis and agglutination occurred in some instances, but in others they did not. By trying crossed reactions with the cultures and (convalescent) serum obtained from 20 cases of pneumonia, he was able to classify the organisms into five definite groups. The individual strains in each group he found to be serologically identical; while strains in different groups had no serological relationship to each other. In a subsequent article," he reported further similar observations confirming the regularity and absolute specificity of the reaction, and added several new groups to his classification.*

The development of agglutinins in the serum of patients with lobar pneumonia has been noted by numerous observers. Bensangon and Griffon,' in 1900, reported positive findings in all but six of a series of 64 cases of pneumococcus infections of various types, of which 39 were lobar pneumonia. They obtained these results only by cultivation of the pneumococcus in concentrated serum from the patients, and failed to demonstrate any agglutinating activity when the serum was added to a broth culture of the organism. They found the activity most marked at crisis, and more effective toward the homologous strain than toward stock strains of pneumococci. Huber," using a similar method, obtained positive results in all of 10 cases of lobar pneumonia examined at or near crisis. Neufeld,' in connection with a study of the agglutinating action of immune serum, mentions the fact that in five out of about 15 cases of lobar pneumonia examined, the serum at crisis, when added to a culture of the pneumococcus, caused marked agglutination of the organisms. This occurred with serum dilutions of 1 in 4, or 1 in 8, but not in higher dilutions. Gargano and Fattori," in a series of 63 cases, reported that the development of agglutinating activity in the serum was " an almost constant phenomenon." The sera were all active in a dilution of 1 in 2, but none in a dilution over 1 in 10. They also found the homologous organism more readily agglutinable than heterologous strains. Jehle " also reported positive results in all of six cases examined. However, his findings differ radically from those of other observers, in that he found the seriun active in relatively high dilutions (1 in 20 to 1 in 80 and even 1 in 160) ; that the activity was well marked as early as the second or third day of the disease ; that it showed no tendency to increase as crisis approached ;


  • As the earlier literature dealing with the subject of phagocytosis is summarized in my former article,' it will not be discussed

here.


and that it disappeared entirely within from two to four days after crisis. More recently Chickering" has reported the demonstration of agglutinins in a 1 to 2 dilution of serum in 73.8 per cent of a series of 40 cases of lobar pneumonia. Most of the negative reactions were with serum from fatal cases. He found that the agglutinative activity developed only at or near crisis, and that it might be present only for a single day, or persist {in vivo) for several weeks. The agglutinating activity of the serum was strictly limited to organisms of the same type as that with which the patient was infected, but sometimes was more marked for the homologous strain than for a heterologous strain of the same type.

The method used by the writer was described in detail in the previous article,' hence only the essential points will be repeated here.

The cultures used were, with a few exceptions, those isolated in the routine study of the cases in the medical bacteriological laboratory of The Johns Hopkins Hospital, which have been reported by Mildred C. Clough," and by Sydenstricker and Sutton," and I am indebted to them for transfers of most of the strains.

Through the courtesy of Dr. E. I. Cole of the the Eockefeller Hospital, New York, who kindly furnished us immune serum for the purpose, it was possible to determine the type of each of the organisms isolated. The phagocytic activity of the Type I and Type II immune sera has been tested with most of the organisms studied, and in some of the later cases observations have also been made with Type III serum, and with serum corresponding to Avery's Subgroups 2A and 2B."'

The leucocyte suspension was obtained by adding a few

cubic centimeters of normal human blood to 1,5 per cent

sodium citrate solution, washing three times in 0.85 per cent

• salt solution, and pipetting off the leucocytic cream after the

last washing.

The bacterial suspension was prepared by carefully emulsifying a loop of growth in one or two drops of physiological salt solution. The suspension must be fairly dense to give the most clear-cut results.

Fresh serum obtained from the patient by any convenient method, usually venapuncture, was used in a majority of the cases, though it was found that in nearly all cases the activity of the serum persisted in vitro for several days at least. In some cases inactivated serum was also used.

Equal volumes of undiluted serum, bacterial suspension and leucocyte suspension were mixed and incubated in capillary pipettes at 37° C. The actual concentration of serum in the final mixture was, therefore, 1 in 3. The time of incubation varied from 15 minutes to two hours, depending on the strain of pneumococcus in question.

When a negative result was obtained, if possible, the test was modified by making the culture suspension directly in the serum to be tested, and by using defibrinated blood from the patient instead of a salt solution suspension of washed normal leucocytes. In this way the organisms were exposed to concentrated serum, instead of to a 1 in 3 dilution of serum. Corresponding control preparations were made, consisting of a


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suspension of the organism in normal serum and defibrinated normal blood. Five cases which gave negative reactions by the first method were tested by this method; tliree gave positive results.

Smears from the mi.vtures after incubation were made on slides and stained with Hastings' stain (polychrome methylene blue). Suitably prepared films are free from sediment, and both the bacteria and the protoplasm of the leucocytes are clearly stained. As a rule, the margins of the capsules are sharply outlined and the capsular material is diffusely stained a bright pink, in contrast with the bluish-black color of the organisms.

As in the previous work, counts of the ingested organisms were not made. Only gross differences were regarded as significant. The degree of phagocytosis was recorded as (0) absent (or not to exceed five pair in 50 cells) ; ( + ) definite (about 100 or more pair in 50 cells) ; ( + + ) strong ; and ( -F -f- -(- ) maximal. Degrees of phagocytosis less than ( -|- ) in the test preparations were regarded as inconclusive.

In practically every case the tests were subsequently repeated, different specimens of normal serum and leucocytes being used to guard against possible errors.

This metliod is very simple, but in order to obtain reliable results certain precautions must be observed :

(1) The leucocyte suspension must be active. Tliis can usually be determined by simple inspection of a fresh preparation under the high power. As pointed out by Xeufeld," if the majority of the leucocytes show numerous filiform pseudopodia, one can be fairly sure that they are active. It is advisable also to set up a preliminary test with a strain phagocytable in fresh normal serum (not one spontaneously phagocytable). If a very marked phagocytosis has occurred after 15 minutes' incubation, the leucocytes are suitable for use. Attempts to compensate for an inactive leucocyte suspension by prolonging the period of incut)ation give unreliable results. The best results are obtained with fresh leucocytes. Phagocytosis is usually less active in older suspensions.

(2) The bacterial suspension should be fairly dense, and must be homogeneous and free from clumps.

(3) In every case controls must he made with normal serum, of the same age and condition as the serum under investigation, and all tests without exception be discarded if any appreciable degree of phagocytosis is present in the controls.

(4) The time of incubation should, if necessari-, be adjusted for each individual strain, so that the test preparation will show as marked a degree of phagocytosis as possible without permitting any phagocytosis in the controls. For organisms of Types I, II and III, one hour is usually the optimum, though clear-cut positive results are often obtained after I'l to 30 minutes. If the results are negative or inconclusive bfcause the degree of phagocytosis in the test preparations is slight, convincingly positive results may sometimes be obtained by prolonging the period of incubation to two hours. Rarely is anything to be gained by a longer period of incubation.

For organisms of Type IV and .\typiral Type II. the period


of incubation should, as a rule, be shortened to 30 minutes, and in some cases to 15 minutes. If the incubation is too prolonged, there may be sufficient phagocytosis in the control preparation with normal serum to obscure the difference between these and the test preparations, a difference which would have been clear-cut after a shorter period of incubation. Too prolonged incubation may also obscure results, because it gives sufficient time for intracellular digestion of the ingested organisms, and because prolonged contiict with the organisms seems to injure the staining properties of the leucocytes.

(5) TJie films must be properly spread and stained. The leucocytes and the larger bacterial clumps, if agglutination has occurred, will be found along the margins of the film, at and near the terminal portion. If the film is too thick, so that the leucocytes are heaped up or not well flattened out, observations are difficult. The presence in a serum of isoagglutinins active on the red cells present in the leucocyte suspension does not interfere with phagocytosis, but it makes it difficult to secure even films.

Before considering the result« obtained with serum from convalescent patients, the behavior of the organisms in normal human scrum should be discussed. In no instance were strains of Types I, II (typical) or III, on isolation, phagocytable in fresh normal human serum under the conditions outlined above. They also rcmainwl rcsistjint to jthagocytosis for at least several months while under cultivation on artificial media. The medium used was 5 to 10 per cent human blood agar; transfers being made at intervals of a week or 10 days. One Type II strain became very slightly phagocytable after two months' cultivation, and a second after cultivation for about a year. Type I strains seemed more resistant Of three Type I strains followed for a long period, one became phagocytable in fresh nonnal scrum during tlie third year of cultivation on artificial media ; a second, during the fourth year; while a third, after four years' cultivation without intervening animal passage, is still not phagocyt«l)lc.

The behavior of Atypical Type II and Type IV strains was variable, but most of those observed were less resistant to phagocytosis than were organisms of the fixed types. The majority of the Atypical Type II strains, and some of the Type IV strains, on isolation (from patient* with pneumonia). were not phagocytable in fresh normal human scrum after an incubation of half an hour, though after longer periods a slight degree of phagocytosis was occasionally observed. This resistance to phagocytosis was frequently reduced after one to three weeks' cultivation, so that the organism became phagocytable in fresh normal serum. In some cases the original resistance could be restored by animal pa.ssage. Such strains, after Ix-coming phagocytable in frcsli normal serum, were not phagocytable in normal scnim which had been inactivated cither by heating or by preservation for several days in the ice "best, and they usually retained this degree of resistance to phagocytosis after many weeks, and several even after two to three years of cultivation on artificial media.

Other strains, even immediately after isolation, were phagocytable in fresh normal serum, though resistant to phagocy


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tosis in inactivated normal serum, even after considerable periods of cultivation. It was found that the phagocytic reaction of these organisms in inactivated homologous serum, either from an immune animal or from a convalescent patient, were nearly as clear-cut and just as specific as were those of the more resistant strains when tested in active serum. Two such cases (Nos. 40 and 41) are included in Table I. Such strains may possess a moderate virulence for rabbits and mice, and, as a rule, were not phagocytable in fresh normal rabbit serum.

In examining (in inactivated serum) these strains which are phagocytable in fresh normal human serum, it is, of course, imperative that the leucocyte suspension be very thoroughly washed in salt solution (at least three times) to remove as far as possible all traces of fresh serum. Absolutely complete removal is probably not possible, and, as might be expected, there was frequently a very slight degree of phagocytosis of these strains in the control preparations. This must be allowed for in interpreting the final results of tests made with these strains.

Finally, there is a group of Type IV organisms which are spontaneously phagocytable, i. e., they are phagocytable in inactivated normal serum or in salt solution. They are, of course, entirely unsuitable for use in phagocytic tests, although, since some of them show no agglutination in normal serum, the demonstration of agglutinative activity in the homologous serum might be possible. In the course of this work I have examined 13 such strains, all isolated from the sputum or blood of patients with lobar pneumonia. In four of the 13 strains, all isolated from sputum cultures, it was definitely shown that the organism isolated from the sputum was not the etiological agent in the disease, but was probably an ordinary saprophytic inhabitant of the mouth, since the serum of these patients in convalescence acquired the power of causing phagocytosis and agglutination of stock strains of a fixed type (in two cases typical Type II and in two cases Atypical Type II strains). In one case a second attempt was successful in isolating from the sputum the Atypical Type II strain for which the serum had developed phagocytic activity.

Of the remaining nine, five were obtained only from the sputum (four by culture, one by mouse inoculation). The patients all recovered, and no further evidence was obtained confirming or disproving the relationship of the organism in question to the pneumonia.

In four cases, however, the strains were obtained by blood culture from patients subsequently dying of the disease. In three of the cases there were 2000 or more colonies per cubic centimeter of blood. The pathogenicity of the organisms in these cases can scarcely be questioned.

Although the primary object of this study was to determine the phagocytic activity of the serum, note was also made as to the occurrence of agglutination in the preparations, and a rough estimate recorded of the degree of agglutination present. With ordinary care in emulsifying the growth, it was easy to obtain homogeneous suspensions entirely free from clumps, with virulent organisms of the fixed types. In a large number


of tests no agglutination of these organisms was ever observed in normal human serum even when undiluted. In the active (convalescent) sera, however, clumping was usually a striking feature of the preparations. The clumps varied in size from groups of a dozen pair up to masses occupying a large part of an oil-immersion field. Of course, no clumping was regarded as significant unless the suspension was perfectly homogeneous, and unless the control preparations with normal serum were entirely free from clumps. The agglutinated masses of pneumococci, however, differed strikingly in appearance from the masses occasionally met with in poorly prepared suspensions. In the former, the individual organisms were more widely separated, and presented an appearance such as might be produced if the capsular substance between the organisms had been greatly swollen in the process of agglutination. This appearance has been described by Neufeld,' Huber ' and others.

Equally clear-cut results were obtained with a majority of the Atypical Type II and with many of the Type IV organisms studied. With a number of cultures, however, which showed a sparse dry growth on blood agar, and in which the capsules either were small or were not demonstrable, it was difficult or impossible to secure satisfactory suspensions free from clumps. Some other strains acquired this characteristic after prolonged cultivation on artificial media. Such strains also occasionally showed some tendency to agglutinate non-specifically in normal or in heterologous serum, and they were, without exception, discarded. The majority of these organisms were spontaneously phagocytable, and probably were saprophytic inhabitants of the mouth.

The results of the tests made with the serum of patients with acute lobar pneumonia are tabulated individually in Table I and summarized in Table II. With a few exceptions noted in the table, the homologous strain of pneumococcus was used in the test : Of 33 cases in which serum obtained at or shortly after crisis or lysis was tested with the homologous strain, isolated from the same patient, 28, or 85 per cent, showed definite phagocytic activity, while five, or 15 per cent, were negative. Of these five negative cases, in three only a single specimen of serum was examined, and only in a 1 to 3 dilution. Tests in concentrated serimi (if tried) might have yielded postive results. Of five cases which gave a negative reaction on the first test in a 1 to 3 dilution of serum, three gave positive results when tried a second time in concentrated serum. To these 28 positive cases may be added six others (included in Table I) in which the infecting organism was not isolated, but in which the serum after recovery caused phagocytosis and agglutination of a stock strain of one of the fixed types (Type I, two cases; Type II, three cases; Type Atypical IIA, one case). Only three patients in the series (Nos. 13, 14 and 21) received serum treatment with Type I serum, and in the two cases (Nos. 13 and 14) giving positive reactions there did not seem to be any immediate association between the administration of the serum and the appearance of phagocytic activity in the patient's serum.

Of the 33 eases tested with the homologous strain of pneumococcus, 26, or 79 per cent, gave definitely positive agglu


June, 1919]


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tination reactions. The two sera which showed phagocytic but no agglutinative activity were among the three relatively feeble sera which were active only in full concentration. These figures correspond quite closely with those reported by Chickering" and obtained by a different method.

This phagocytic and agglutinative activity appeared with equal constancy after infection with pncumococci of Types I,

II and IV, and also in the only patient in the series with Type

III infection who recovered.*

Serum was also e.xamined from seven patients who later died of the disease, and the result was negative in six. The one case in which death occurred after serum activity developed will be discussed later.

In 18 of the 34 patients whose serum in convalescence was active in stimulating phagocytosis, tests were also made with serum obtained during the active stage of the disease. All were negative with three exceptions, and these three specimens were all obtained one day (or less) before the crisis. Of nine cases (eventually positive) tested 2-1 hours or less before the crisis, four were positive and five negative. Of nine cases tested about 24: hours after the crisis all were positive.

Very scanty data were obtained to indicate how long tlic activity of the scrum persists in the body. In one case it disappeared within 11 days, but it was usually present on discharge, from 10 days to three weeks after the crisis. In one case (No. 27) serum obtained two years later still showed slight phagocytic activity and fairly marked agglutinative activity for a stock Type II strain.

We may, therefore, conclude that the serum is inactive during the acute stage of the disease, and that phagocytic and agglutinative activity develop only at or near the crisis, occasionally appearing shortly before it, but often demonstrable only after recovery has definitely set in.

The only instance met with which seems to constitute an exception to this rule is No. 44, Table I. This patient was a man aged 61, alcoholic, with arteriosclerosis and hypertension. He was admitted to the hospital on the fifth day of the disease with signs of consolidation in the right upper lobe. On admission (fifth day), a Type IV pneumococcus was isolated from the sputum and also from the blood ( 1 colony per cubic centimenter of blood). On the 13th and 14th days the temperature fell by lysis, and it seemed probable that the patient would recover. However, the temperature did not reach normal. On the 16th day it again became markedly elevated, and a high remittent fever of the " septic " type persisted till death on the 21st day. A Type IV pneumococcus was again cultivated from the blood on the 18th day (2 colonies per cubic centimeter). All three strains were found to be serologically identical. On the 19th day the heart was found to be dilated, and a systolic murmur appeared


•The sera from two recent patients recovering rrom Type III empyema, not included in this series, showed well-marked phagocytic activity, but no agglutinative activity. This activity was present only In the fresh serum, and was limited to the homologous strain of pneumococcus.


at the apex. On this day the patient suffered a left hemiplegia. Nothing definite could be made out in the lungs or pleurae to explain the recrudescence of fever. No autopsy was obtained. While it was not certain tiiat the hemiplegia was not the result of a coincident cerebral hemorrhage, it was thought probable that a sepsis had developed, with an acute bacterial mitral endocarditis and a cerebral embolism.

The pneumococcus isolated from this patient was slightly phagocytable in fresh normal serum, but not in inactivated serum. The inactivated serum of the patient obtained on the fifth day caused no phagocytosis or agglutination of his organism, but a specimen obtained on the 13th day (during the remission), both in the fresh state and after inactivation, caused very marked phagocytosis and agglutination of this organism. A third specimen of serum obtained on tiie 18th day was equally active. This was two days after the recurrence of fever, and was after the reappearance of the organisms in the circulating blood. In this case, therefore, sepsis ai>parently ensued, despite the presence of phagocytic and agglutinative activity in the serum.

To determine the specificity of tlic reaction, a large number of crossed tests were made with the active post-critical .-ierum of each case, heterologous strains belonging to the same type and also strains of different types being employed. Table III shows results obtained with sera from patients recovering from Type I infections, and Table IV from infection with other types. In general, these data may be summarized as follows: A scrum which is active on the homologous strain, will, as a rule, cause phagocytosis and agglutination of any other strain of the same type, but is entirely inactive toward strains of any other type. This differs from the tentative conclusions previously reported by the writer. In the former series of cases, phagocytic activity, in the six sera in which it was demonstrable, was strictly limited to the homologous strain of pneumococcus, with the single exception of one serum, which was also active on one only of several lieterologous strains with which it wa.^ tested. In view of the findings in this present series the ex])lanation for the previous results probably is that only two of the organisms examined happened to belong to the same type.

The serum from patients recovering from Tyjic II iiifictidn showed no activity toward Atypical Type II strains (with the exception, possibly, of Xo. 27: Los., S.; Table IV). Serum from cases of Atypical Type II infwtions acted only on members of the corresponding suiigroup.

Case No. 14, Table I, illustrates well the sjjccificity of these reactions. This patient was admitted with a lobar pneumonia which was proven by si)utum and blood cultures to be due to an Atypical IIA infection. The serum shortly before crisis was inactive toward this organism, but shortly after crisis caused active phagocytosis and agglutination of it. Four days after crisis a second attack of pneumonia developed, a different lobe being involved, and a Type 1 strain was isolated from both blood and sputum. His serum at this time was inactive toward the Type I strain, though active toward the IIA strain. He had a second crisis on the eighth day, and after this crisis


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[No. 340


phagocytic and agglutinative activity for the Type I strain had also developed.

Serum from one of the three patients infected with a Type IV pneumococcus was active only on the homologous strain. That from a second case was equally active on the homologous strain and on one other Type IV strain from another case of pneumonia, serum from whicli could not be obtained for study. The third case also furnished a serum which was active in promoting phagocytosis, not only of the homologous strain, but also of one other Type IV strain, isolated from the spinal fluid of a case of pneumococcus meningitis. The demonstration, among a comparatively small number of Type IV strains examined, of two pair of serologically identical strains, is in conformity with the recent findings of Olmstead," and indicates the probability that further study will reveal new types among the pneumoeocci now included in Type IV.

The serum of this last case (No. 27; Los., S.; Table IV) also caused phagocytosis of typical Type II strains and, less actively, of several Atypical II strains as well. This patient's serum four days before lysis was inactive toward the homologous Type IV strain, but was not tested at this time as to its activity toward a Type II strain, as this anomalous behavior of the serum was not anticipated. This is the only instance in the series in which a serum showed phagocytic activity toward a strain of a type different from that which was isolated from the sputum (except for four cases in which spontaneously phagocytable mouth saprophytes were isolated from plate cultures). This might be explained either on the assumption that the patient had a double infection with a Type II and a Type IV organism, or that he had previously had a Type II infection, with persistence of the antibodies for Type II strains. The possibility of such a persistence of antibodies for a long period is demonstrated by the fact that a specimen of serum obtained from this patient two years later still showed slight phagocytic and well-marked agglutinative activity for Type II strains. The activity of this specimen of serum for the homologous Type IV strain could not be tested, as the strain had been lost.

The agglutinative activity of this serum was less specific than its phagocytic activity, in that it not only agglutinated those strains which it caused to be phagocyted, but several other Type IV strains as well. The agglutinative reactions of the Type IV strains, and of some of the Atypical II strains, as observed in these tests, were not as specific as were the phagocytic reactions.

A special effort was made to detect any possible quantitative serological differences between different strains belonging to Type I. In two sera (Nos. 1, T. A., and 5, M. M., Tables I and III), both of which were but feebly active, the homologous strain was somewhat more actively phagocyted than were the heterologous strains tested.* This is in accordance with the observations of Chickering " on agsrlutination in the serum


  • In two recent patients recovering from Type III empyema,

not included in this series, tlie piiagocytic activity of the serum was strictly limited to the homologous strain.


of convalescents. He reported that in several instances " the first organism to be agglutinated was the homologous strain, and only later was the stock strain agglutinated." Different strains may differ considerably in their phagocytability in the same serum. Thus, in one series of tests with stock Type I immune serum, strains S and R were phagocyted in 1 to 48 dilution ; strains V and B in 1 to 24 dilution ; while T and F were phagocyted only in a 1 to 12 dilution. When an active human serum was titrated in increasing dilutions with several different Type I strains, the highest titre was usually obtained with those strains which were most readily phagocytable in any Type I serum rather than with the homologous strain. Although such specific strain differences undoubtedly exist, they must be relatively slight, and it is not always possible to demonstrate them conclusively.

The activity of immune serum of the various types on most of the strains studied was also observed, and some of the results are recorded in Tables IV and V. The same complete specificity is observed here, except in the agglutinative action of Type II serimi on Atypical Type II strains. Type II serum in a concentration of 1 in 3 and with an incubation period of about 30 minutes caused agglutination of all the 25 Atj'pical II strains tested. However, Type II serum was much more specific in its phagocytic reactions toward these strains. With only two strains was any definite phagocytosis observed ; and this was much less active than was the phagocytosis of typical Type II strains.*

The Atypical Type II strains were actively phagocyted and agglutinated by an immune serum corresponding to the particular subgroup to which they belong, but were not affected by serum corresponding to the other subgroup or to any strain not belonging to their subgroup.

This test, therefore, offers an additional simple method for the differentiation of typical Type II and the various Atypical II strains, and has proved to be of practical value in the case of certain Atypical II strains, which were agglutinated macroscopically in Type II serum in dilutions of 1 in 32,- and even in 1 in 64, though somewhat more slowly that Tj-pical II strains.

The existence of other undescribed subgroups among the Atypical II strains is indicated by the fact that an immune serum prepared with a strain from a case of empyema, which did not fall into either Subgroup A or B, caused phagocytosis and agglutination of one other Atypical II strain.

As to the properties of the active substance which stimulates phagocytosis in these human sera, the observations previously reported by the writer have been confirmed. They are in the main thermostabile. In eight of nine cases tested, serum inactivated for 20 to 30 minutes at 56° C. retained its activity. When the lieating materially exceeded this, either in duration


• Several other Atypical II strains, after their resistance to phagocytosis had been lowered by cultivation on artificial media for a considerable period, also acquired a slight degree of phagocytability in T>-pe II serum. With the two exceptions noted, however, all strains when tested shortly after isolation were not phagocytable in Type II serum.


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TABLE I

PHAGOCYTIC AND AGGLUTINATIVE REACTIONS IN THE SERIM OF PATIENTS WITH LOBAR PNEUMONIA. TESTED WITH THE

HOMOLOGOUS STRAIN OF PNEUMOCOCCUS







Reault


Testa during meute itase


Tests during convalescence


Titre of

phagocytic

activity of

serum



No.


Name


Hospital number


Source of •train


Type


Ccri.18 L-lysis D-deatb


Day of

disease


Result


Daya before crisis, lyala.or death


Reault


Days

after

crisis or

lysis


Remarks



Phag.


Agren.


Phag.


Aggn.



1


T.. A.


3SS80


Sputum


I


L


21 !1 ..




+


,


4


1-1. -I





f»


•


18




t


v.. J.


3S430


Sputum


I


C


16


+'


+'


1


+



1 8


1-3,-11-6,0



3


R., C.


35482


Sputum


I


L


13




7 4




1 19


1-6, -^

1-12.0



4


S., J.


35517


Sputum


I


C


9



D


3


+'


+'



2

4

11


l-12,-(

Serum had become inactive 11 days after lysis.


s


M.. M.


35828


Sputum


I


L


6


c



4


+'



1


1-1, -t1-3,0



« 


P.. P.


35582


Sputum


I


C


6





1


+ '


+'


2


1-1. + 1-8,0



7


P., C.


35082


Sputum


I


L


11





8


+'


+*



1-3, -t1-6,0



8


li.,W.


35901


Sputum


I


L


10





8


+'


+»


4


1-3,-1


8


McK., C.


39702


Empyema


I


L


f





+*


-I-'


80(f)


1-3,+



10


R., J.


35902


Sputum


I



11





4


+


+•



1-3, -h



11


a., N.


35274


None obtained


(I)


C


6





+


+'


12


1-3,-1

Tested with stock Type I strain.


U


B..C.


35681


None obtained


(I)


L


12




6


+'


+*


1


1-3,-11-6,0


TestedwithstockTypel strain.


18


W., H.


37334


Blood, Sputum


I


C


7





+'


f»


10


l-S.-t


It


W., 0.


37&S0


Blood, Sputum


I


C


8




12


+'


+*



1-3, -h


1 1 A pneumonia. See No. S3.




<






IS


T.,C.


38870


Sputum


I


C


8





+


+'


1


1-3, -^


This (ollowcd 3 davs after a

Type 11 pneumonia. Not tested till 11 days after


1« 


B.,U.


35028


Sputum


I


L


6 11


1-1,0







16



Ivsis.


17


W., M.


35082


Sputum


I


L


7





2





2


1-1,0


Clinicallv broncho-pneumonia.


18


M., 8.


35594


Blood, Sputum



D


19





14






Pneumothorax following aspi

18


F., J.


35588


Blood


I


D


?





f






ration.


to


J. W.


35308


Sputum


I


D


9





B







21


J.


37409


Sputum


I


U


3





3







n


8.. F.


353 IS


Sputum


11


L


10






3

1


+'


+'


4


1-12,0



a


M.. T.


37419


Sputum


II


Lf


f





+'


+•


f


1-3,-1


u


D.,H.


39040


Ulood, Sputum


II


C


7





+'


-I-'





u


C, J.


35311


None obtained


(11)


C


9






+'


+'


11


1-3, -h


Tvpe IV from sputum 8 days after crisis. Tested with stock Tvpe [1.


M


T.. J.


35871


Sputum (IV)


(11)


L


9





+•


+'


1


1-3,-f


Phajfocvtiiole IV from sputum. Tested with stock Type 11.


17


L..S.


35681


Sputum (IV)


(II)


L


18





+'



1


1-S,-I

Tvpe IV from sputum. Tested with stock 11. See No. 41.


»


0.. E.


37279


Sputum


II


L


9






+


4


1-8,0


Not tested in concentrated serum.


18


W.. H.


39103


Sputum


III


C


3





+'


+



1-3, -h



30


C.,C.


35596


Sputum


III


D


7





4







31


H.,0.


37200


Sputum


IIA


C


7





+'


-I-'


S


i^,+



32


B, W.


37328


Sputum Blood, Sputum


IIA


C


7





+'


+'





33


W.. (;.


37556


IIA


C


7






+'


+'


6



See No. 14.


34


H., B.


37354


niood. Sputum


IIA


L


7





+*


+*





35


8..T.


37298



IIA


C


9





+'


+'


6


1-3,+



3« 


McC.. 0.


37468


(See remarlia)


IIA


C


8





+*


+'


3


1-3,+


Phagocytahle IV from sputum. Testeil with stock IIA.


37


J., H.


37074


Blood, Sputum


IIA


D


8





2







38


E.. R.


35806


Blood, Sputum


Atyp.II


C


10






7

1


+'


+'


6


1-6,0



88


D.. W.


37433


Sputum


Atyp.II


C


8 3


1-3,0


Not tested in concentrated


40


B..J.


35679


Sputum


IV


L


8





3


+'


-I-"


2


1-3,+



41


L.. 8.


35660


Sputum


IV


L


13





4


+'


-I-'


1


1-3,+


See No. 27.


41


W..H.


374U0


Sputum


IV


C


7





+'


+'


8


1-3,+



43


N.. A.


37810


Sputum


IV


L


8





+'


1





44


W.. J.


35627


Blood, Sputum


IV


D


21





18

8





1-3,+



4S


B.. W.


37335


Sputum


IV


L


8


+"


+»


3





6


1-3,0


Not tested in concentrated


4<


N.. H.


37285


Sputum


IV


D


8





'


"






TABLE II


SUMMARY OF PHAGOCYTIC REACTIONS IN THE


SERU


MOP


PATIENTS


WITH LOBAI


IPNE


UMONIA



Reacttona with serum from convalescent patients (lobar pneumonia). Cases tested with the homologous strain


Additional

cases tested

with stock

strains


Total positive

No.


Reactions of serum d

from patients whose

gave positive


ring acute stage, serum eventually reactions


Reactions of scrum from patients who subsequently died


Ko.


Poaltire


Negative


Pofitive


No.


PoaitiTt


1 NegatlTO


No.


PoaitlTC


Nagitir*


Type 1 1 IS

Type II 4


13

8 1 6

« 



2

2

i


IS S

s

8


U


3




8 2

1 '^


4


t



1


4


Type III 1 1



Type IV 6



Type Atyp. II 7




28-88%


6-lS%


6


34


IS


•8-17%


1 16-83' .


^


1-124%


7-874%





  • TheM thrM fpccfmena were obtsineU on the da/ before criiii.


174


[No. 340


or height of temperature, the activity was lessened or destroyed. The serum usually remained active in vitro for several weeks, though it gradually weakened in activity. In two cases, serum, which in the fresh state was feebly active, lost its activity after from two to four days. Nearly all the sera, however, remained active throughout the period during which they were under observation, which varied from a few days to four months.

If the serum had become inactive or feeble as a result of overheating, long preservation or dilution, the phagocytic activity could not be restored or increased by the addition of complement. The substance is, therefore, quite different from the active substances (opsonins) of fresli normal serum, and corresponds to the bacteriotropins as defined by Neufeld."

The active substance was present in the serum in relatively small amount. In a majority of the sera tested as to this point, no phagocytosis occurred if the concentration of serum in the mixture was less than 1 in 3. In a few cases it was active in a 1 in 6 dilution, and in one case in a 1 in 12 dilution.

These bacteriotropins, as well as the agglutinins, were precipitated from immune serum with the euglobulin, on the addition of 36 volumes per cent of saturated ammonium sulphate solution. The euglobulin fraction of the precipitate, redissolved in salt solution and freed from an excess of ammonium sulphate by dialysis, caused marked phagocytosis and agglutination. The pseudoglobulin fraction of the precipitate, obtained by the further addition of saturated ammonium sulphate solution to give a concentration of 44 volumes per cent, was likewise redissolved and diah'zed, and was found to be inactive, as was the dialyzed supernatant serum from which the globulins had been removed. In this respect, therefore, the bacteriotropins resemble most other antibodies which have been similarly studied.

These bacteriotropins are probably not identical with the agglutinins. In two sera in which definite phagocytic activity was demonstrable, no agglutination whatever occurred. As a rule, however, the agglutinative activity of the serum was


more marked, was usually present in higher dilution, and persisted longer in vitro than did the phagocytic activitj' of the serum. In one case agglutinative activity was observed to precede the development of phagocytic activity. However, the observations with reference to this point were not sufficient to determine which type of activity is usually the first to appear.


Of 33 cases of acute lobar pneumonia in which the phagocytic activity of the serum after crisis or lysis was tested with the homologous strain of pneumococcus, 28, or 85 per cent, gave definitely positive results. These results confirm and extend those previously reported by the writer.

In 26, or 79 per cent, of these cases agglutinative activity was also demonstrable.

In 18 cases in which definite phagocytic activity was demonstrable in the serum after recovery either for the homologous strain or for a stock strain of known type, tests were also made with serum obtained during the acute stage of the disease, and negative results were obtained in 15. The three sera which showed phagocytic activity were obtained 24 hours or less before crisis.

Serum was also examined from seven patients who subsequently died of the disease, and negative reactions were obtained in six. A positive reaction was obtained in one patient, who, after a short remission, died apparently of sepsis and endocarditis.

This phagocytic and agglutinative activity of the serum developed after the recovery from infection with pneumococci of all the recognized types. It was strictly limited to organisms of the same type as that with which the patient was infected, but, as a rule, was exerted equally well on the homologous strain and on heterologous strains of the same type. It is, therefore, specific as to type, but not specific as to strain, as the writer originally believed.

The agglutinative activity of the serum as observed in these tests paralleled closely the phagocytic activity. In the case


TABLE III PHAGOCYTIC AND AGGLUTINATIVE REACTIONS IN THE SERUM OF PATIENTS RECOVERING FROM TYPE I INFECTION,




TESTED WITH


HOMOLOGOUS AND HETEROLOGOUS


TYPE I STRAINS Strain of pneumococcus-Typc I


Serum


Type I (stock)


Type II (stock)


T., A.


v., J.


R., C.


S., J.


M., M.


p., p.


P., c.


M.,W.


McK.


R., J.


B.,H.


W.,M.


So.


Joh.


Fen.


McC.


Mt.


For.


Scrum, Type I (immune). Serum, Type Iliimmune)


+' +'

+

+ ! +3

+' +> +3 +>

+

+" +' +» += + +"



+» +'


U


+ S +3


+'

+= +'

+s +3 +3 +3


+ += + +


+ 3 +3


+ 3 +3



+ 3 +3


+ 3 +3



+3 +3


+3 +3




+3 +3



+3 +3



+3 +3 u


+3 +3


+2 +3

±

+ += +» +'

+2 +3


+3 +3

±

+ +'

+2 +3


+2 +3


+

+ = +3

+= +»

+3 +3



+ S +3


+

+ 3 +3 + ' +'


+' +'


+ 3 +3



Serum, V., J


+ 3 +3 + 3 +3 + 1 +3

+


43 +3 +S +3

+»


+: +' += +' +'


+ 3 +3

+ ' + =


'+="6'


+» +' +"

-r' +» + 11 + 2 +3 +3 +3 +3 +3 +! +8


+3

+ +=

+ 3 +3


+ +'

+ 2 +3 + 3 +3


+ 3 +3 + 3 43 + 3 +3


+=

+ 2 +3


+3 +3 +


+s + +' +1 +3


+2 + 2 +3 + » +»


+ 2 +3 +3 +3


Serum, S., J


+> +'






+ 3 +3


+ 2 +3

+3 +3


+ 3 +3 + 3 +3 + 3 +3


+2 +2 +3 +3 + +»



+1 +3






+3 +3 + 3 +3 + 3 +3 + +»






+ += + 2 +3






+ +'

+ +'




+ +'


+ +'


+ +»


+ +"


+ +=


+ +=


+ +'





+=



+»




+s +»


+2



+"


+'






ach column represents phagocytosis, ami the second a^'g^lutination.


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TABLE IV

P PATIENTS UECOVERINQ FROM IN AND WITH HETEROLOGOUS STRA


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176


[No. 340


of Atypical II and of Type IV strains it was not so sharply specific as was the phagocytic activity.

This phagocytic activity is entirely different from a possible rise in opsonic index, in that it brings about active phagocytosis of a virulent pneuniococcus, not at all phagocytable in normal human serum.

The active substances in the serum also differ from tlie opsonins of normal serum in that they are usually thermostabile ; they usually remain active for several weeks in serum preserved in vitro; and when their activity is lost, they cannot be reactivated by fresh normal serum (complement). Tliey are therefore qualitatively comparable with the bacteriotropins of potent immune serum.

In view of the facts: (1) That this activity of the serum develops in nearly all patients who recover, but only appears, as a rule, at or near crisis; (2) that it is limited to organisms of the same type as that with which the patient is infected; (3) that, as previously reported, the "phagocytic activity of the serum ran closely parallel with the protective power for mice, both in incidence, in time of appearance and in strict specificity as to the type of pneumococcus concerned"; and (4) that phagocytosis in the peritoneum of the protected mouse closely paralleled phagocytosis in the testtube; it seems probable that this factor plays an important part in bringing about recovery in man.

The part played by agglutination in immunity to the pneumococcus in animals has been emphasized by Bull, and in all probability it is also an important factor in human immunity.

That other factors are also concerned is indicated by the death of one patient from sepsis, despite the previous development of phagocytic and agglutinative activity in his serum ; and by the fact that in several instances pneumococci, which had been cultivated from the blood of patients dying of pneumonia, were phagocytable in normal serum or even spontaneously phagocytable in salt solution.

The clinical value of the test will not be great as a method either of diagnosis or of prognosis, since the reaction develops only when recovery sets in. In cases in which as a matter of scientific interest it is desirable to determine the type of organism concerned in a recent infection, the development of a positive reaction either with a stock pneumococcus of known type or with an homologous isolation, would furnish practically conclusive evidence that this organism was the etiological agent concerned in the disease.


REFERENCES

1. Clough, P. W. : The development of antibodies in the serum of patients recovering from acute lobar pneumonia. Bull. Johns Hopkins Hosp., Baltimore. 1913, XXIV, 295-306.

2. Neufeld, F., and Rimpau, W.: Weitere Mittheilungen iiber die Immunitat gegen Streptokokken und Pneumokokken. Ztschr. f. Hyg. u. Infectionskrankh., Leipzig, 1905, LI, 283-299.

3. Cole. R. I., and Dochez, A. R.: Report of studies on pneumonia. Trans. Assn. Am. Physicians, Philadelphia, 1913, XXVIII, 606-616.

4. Dochez, A. R., and Gillespie, L. J.: A biologic classification of pneumococci by means of Immunity reactions. J. Am. M. Ass., Chicago, 1913, LXI, 727-732.

5. Lister, F. S.: Specific serological reactions with pneumococci from different sources. Johannesb., 1914, W. E. Horter & Co. S. African Inst. Med. Research., Pub. No. 2.

6. Lister, F. S.: An experimental study of prophylactic inoculations against pneumococcal infection in the rabbit and in man. S. African Inst. Med. Research., Johannesb., 1916, No. 8, 1-57.

7. Bensangon, P., and Griffon, V.: Etude de la reaction agglutinante du serum dans les Infections exp^rimentales et humaines a pneumocoques. Ann. de I'lnst. Pasteur, Par., 1900, XIV, 449.

8. Huber, F. 0.: Ueber Agglutination der Pneumokokken. Centralbl. f. innere Med., Leipzig, 1902, XXJII, 417-421.

9. Neufeld, F. : Ueber die Agglutination der Pneumokokken und viber die Theorien der Agglutination. Ztschr. f. Hyg. u. Infectionskrankh., Leipzig, 1902, XL, 68.

10. Gargano, C. and Fattori, C: SuU' agglutinazione del dlplo cocco; contributo di fatti e di osservazioni. Riv. crit. di clin. med Firenze, 1903, IV, 177, 193, 209, 225.

11. Jehle, L. : Ueber Pneumokokken-Agglutination mit dem Blut serum pneumoniekranker Kinder. Wlen. kiln. Wchnschr., 1903 XVI, 917-919.

12. Chickering, H. T. : Agglutination phenomena in lobar pneumonia. J. Exper. M., Lancaster, Pa., 1914, XX, 599-613.

13. Clough, M. C: A study of the incidence of the types of pneumococci isolated from acute lobar pneumonia and other infections, and an analysis of the cases classified by types in regard to mortality, complications, associated diseases, bacteriemla, and leucocytosis. Bull. Johns Hopkins Hosp., Baltimore, 1917, XXVIII, 306-311.

14. Sydenstricker, V. P., and Sutton, A. C: An epidemiological study of lobar pneumonia. Bull. Johns Hopkins Hosp., Baltimore, 1917, XXVIII, 312-315.

15. Avery, O. T.: A further study of the biologic classification of pneumococci. J. Exper. M., Lancaster, Pa., 1915, XXII, 804.

16. Neufeld, F.: Bakteriotropine und Opsonine. In Handb. d. pathogen. Mikroorg. (Kolle and Wassermann), 2. Aufl., Jena, 1912, II. 401.

17. Olmstead (Miriam): A preliminary report on the classification of pneumococcus IV. Proc. Soc. Exper. Biol, and Med., New York, 1916, XIV, 29-31.

18. Bull, C. G.: The mechanism of the curative action of antipneumococcus serum. J. Exper. M., Lancaster, Pa., 1915, XXII, 457-464.


THE DEVELOPMENT OF CROSS-STRIATIONS IN THE HEART MUSCLE

OF THE CHICK EMBRYO

Bv Margaret Reed Lewis


The results obtained by different observers in regard to the development of the cross-striations in muscle-fibers differ so decidedly that one is forced to question whether any one of the views presents the entire story. Even though the discus


sion be confined to the development of this structure in one organ and to one form, as, for instance, the histogenesis of the myofibrils in the heart muscle of the chick embryo, it is found that, although the papers published are few in number.


JrxE. 1919]


177


they nevertheless differ fundamentally from each other. In an effort to determine, if possible, the reason for these differences, a careful cytological study of the development of the heart of the chick embryo was undertaken. For this purpose preparations of embryos varyinlnKi:i|>li "I H ' hi. K :mi.'i 48 lioiirs ini'iiliation. Tlii embo'O had 22 iti.vuluiiio. The lieiirl iiiu.*.i-le wu?. full of 4-niv.-striiitoil llbrils.


•


i 1 1 » il

II i\ J I

Km. S. — A niiiiiTu ilrauiiiK from Ihe heart of an eiiibivo in wliiili the tcneli M.mili' was just Kiii. fi.— Ciliiieni ilrawiliif "f a »nnill |.iirliim iif a few nliril« tn .hmv

i^Hii|ilFtr<l. The riuik-i mi-ii- lielow the kiirlarv uikI their pre~eri(e i. only ^liKhtl.v indicated. the different wiillh iif «liril» found in u given region •>! Ilie li.ad

Z.nker without aiili. uri.l pins a few ilr.ip, .,( i prr twit o»mic aiid. I'nstaiiied. Z^l^» No. S oc. nniM-le ..f a dii.k i-nil.ryo ..f 1.', wmiiU-s. and 2 mm. lelu.


Kl... 4.- A laii.rra .|ra»init nf a (.« •! in. ii.... were more fibriU pro*«nt lliaii are Khown m the dr. oc. and i mm. Ien>.


..i oi II,. M...,i .,1 the «mbr>o ..1 1 ..; J There

dliuji « 4ibove. MrtinefJ with lron-heniatuA>hu. jCciu No.


June, 1919]


179


fibrils upon fixation. Whether these fibrils became crossstriated, varicose, or smooth, or whether they were broad or narrow, depended entirely upon the treatment to which they had been subjected.

Stained preparations were much more ditticult to control. Many of tlie stains ditfused across the cross-striation ; in other eases, much of the substance of the cross-striation, but not of the fibril, was dissolved out in the process of dehydrating and staining. The unstained preparations were so satisfactory that little experimenting was done with stains. Fig. 4, however, is drawn from a preparation successfully stained with iron hematoxylin.

The embryo was occasionally mounted in a drop of Locke's solution and the fixing solution permitted to penetrate under the edge of the coverslip. By this means the formation of the fibril eould be observed under the microscope. In this way it was found possible to control the phenomenon and to produce various types of fibrils at will, thus showing that the form assumed is due to factors present during the fixation of some substance in the muscle tissue.

From the above it may be seen that by tlie use of Zenker's solution (without acid, and with the addition of a little osmic acid) and fixing with the muscle slightly extended, completely cross-striated fibrils are formed in the heart of the chick embryo at the early age of 10 myotomes. Many of the discrepancies of opinion shown by the above-mentioned writers were evidently due entirely to the lack of extension of the heart muscle, while others depended upon the fixing solution selected.

CROSS-STRIATIOXS

The simplest method of designating these cross-striations seemed to be the dark band, the light band and the gray band. When the wing muscle of the house fly was fixed side by side with the embryo heart, there was a marked resemblance between the pattern of the cross-striations of the two tissues. Text Fig. 1


Dark

LioKt

Dark


z J Q Q J z


m KroLvjLsels (nemurcLn.e. ^= ^arcou-c, SubstQ.rv.ce.


tvijool irx.e_




Tkxt Fio. 1. — A diaj^ammjitir re|)re^entAtion o( the pattern of the crowi-iitriati«ii» found In the heart mu«-le of the rhirk embrj'o of 10 domlten. The temis used to indicate the different partjt of the rross-striationa are placed opposite the part.

shows the manner in which the various terms used by other observers may be applied in these observations. The most pronounced part of the cross-striated pattern was the light band. This band was lighter than the cytoplasm and probably was composed of some substance which upon fixation did not become as dense as that of other portions of the cell. The dark band was much darker than any other structure of the cell and was probably quite dense. The gray band was practically the same as the cytoplasm. The dark band was never seen without the adjoining light band on each side. In certain rather round cells the fibrils could not be found, but the dark and light


bands wefe present and sometimes appeared to be scattered dark granules of uniform size, surrounded by a light area. From Congdou's figures it might be supposed that what was present in his material were not hexahedral compartments, but some such appearance as this. In his Fig. 2 the dark band, or granule, and the adjoining light bands are so spaced as to require little imagination to form them into such cross-striated fibrils.

Occasionally the cross-striations extended entirely across a cell without the presence of fibrils. These cross-striations were meager in depth and difficult to focus. The gray band was not noticeable as a special structure, but the regular space between the two light bands indicated its presence. The dark and light bands, however, were striking contrasts to other parts of the cell. Their appearance remained practically the same wherever found. The whole cross-striated fibril retained its characteristic appearance, whether widely spread out or only a narrow thread (Fig. 4).

The observations described above are based entirely upon fixed material. They show that the completely cross-striated fibrils can be demonstrated to be present at an age younger than that found by any other observer and also that they are already present at the time when these observers describe the presence of certain granules, threads, etc., from which tlie cross-striations are supposed to be derived later.

The presence of some substance which coagulates to form fibrils has been shown by Lewis (1919) to be characteristic of the smooth muscle, the heart muscle and the skeletal muscle. The same phenomenon is exhibited by these young embryos; t. e., fibrils form upon fixation in the smooth muscle of the amnion, in the heart muscle and in the skeletal muscle.

In all probability the cross-striations are laid down in the heart muscle-cell coiucidently with the diiferentiation of these cells to form the muscle layer around the heart. This substance coagulates to form fibrils. It increases in amount in the cells during the development of the heart, with the result that the cross-striations become clearer and clearer, and the number of fibrils which can be caused to fonu becomes greater. With the increase in depth of tliis material along the surface of the miscle-cell the pattern of the cross-striations becomes less readily distorted upon the formation of the fibrils. Since it can be demonstrated by one procedure that the fibrils are completely cross-striated from their first appearance it is logical to assume that other methods fail to preserve these structures in their early form. For this reason, it is not necessary to discuss which theory so far advocated as to the origin of these interesting bodies is correct.

LIVING HEART MUSCLE TISSUE Needless to state, the various aspects presented by the heart tissue as descril)ed above, including those observed by the several investigators mentioned, do not correspond to the appearance of the living tissue. This might readily be surmised if for no other rea.son than that one is dead and the other living. When preparations are made by the same method as that specified herein, except that in place of a fixing solution


180


[No. 340


a drop of Locke's solution is used, very thin living hearts are obtained and these continue to contract for an hour or longer. The most noticeable feature of such tissue is the complete lack of fibrils of any type.

The muscle-cells are not spread out into a flat layer as in the fixed preparations, but remain rather round or spindleshaped, and because of this it is very difficult to determine whether there are processes between the cells or not. Certainly, the cells do not appear to form a marked syncytium.

In these observations on the living heart several embryos with 11 myotomes were studied, and as many as six of each of the different ages of older embryos (12, 15, 18, 20 and 22 myotomes). The muscular tissue of the hearts of embryos of from 12 to 15 myotomes appeared to be essentially the same. In that of older embryos trabeculse began to appear. The cell walls were distinguishable in places. Sometimes only a single cell in a given field showed contraction. Again, all the cells of a given region took part in the same contraction. The continued movement of the cells made it difficult to trace their individual boundaries. The tissue of the heart of older embryos (from 15 to 22 myotomes) appears to be more syncytial in nature. No preparation of a living heart was obtained in which contraction did not occur. The movement of these muscle-cells takes place so rapidly that it is almost impossible to be certain of the actual occurrences during the phenomena. In none of .the hearts observed (about 50) was there any evidence of a slowing of the actual contraction. The rest periods became longer and longer, the number of contractions fewer and feebler, but the last contraction that took place was as rapid as any of the previous ones and in every case relaxation occurred after each contraction, even the last one. Rigor mortis was not observed.

MYOFIBRILS

No structure resembling the fibrils of the fixed preparation was present in the living heart muscle at any of the ages studied. In fact there were no long threads of any kind, not excepting the mitochondria. The latter did not extend farther than past the region of the nucleus, and were never seen to extend from one end of a cell to the other, or to pass from one cell to an adjoining cell. Certain preparations of pieces of the heart of four- to six-day embrj'os were used for comparison. No fibrils could be found even in this older heart muscle.

MITOCHONDRIA

The mitochondria were very abundant in the heart-muscle tissue of embryos of all stages up to four days' incubation. They exhibited active movement, bending, twisting and traveling in the cytoplasm. The most frequent forms were those of threads and rods. The longest filament, however, never extended the length of the cell. The long axis of a mitochondrium usually coincided with that of the cell. In round or only slightly spindle-shaped cells, the mitochondria seemed to lie in almost any direction. The outer cytoplasm of the cell was not invaded by these bodies.


When the heart of a 30- to 48-hour chick embryo was injected with Locke's solution, to which janus green has been added, and the preparation then mounted in a drop of the same solution, the mitochondria in the muscle-cells became stained. In such stained preparations the mitochondria appeared as bright blue threads, rods and granules. Certain portions of a mitochondrium occasionally stained more deeply than the remainder. There were no elongated blue threads, either smooth or varicose, extending the length of the cell.

NEUTRAL RED GRANULES

Preparations stained with neutral red in the same manner as that described above for janus green contained few small, red granules. When such a preparation was sealed with vaseline and kept under observation many red-stained bodies appeared in the cytoplasm. Similar bodies were observed in a few unstained preparations which had been kept under observation for a long time. The stained bodies were mostly in the form of round vacuoles, with one or more deeply stained granules; a few active pink filaments, with darker granules, were sometimes observed. Owing to their accumulation in such sealed preparations these neutral red vacuoles appear to resemble the neutral red bodies supposed by W. H. Lewis (1919) to represent waste products of the cell.

CROSS-STRIATIONS

The cross-striations are difficult to observe, either in the hearts of young embryos (11 to 18 myotomes), or in those of older ones (two days), without the most careful search. The most active cells contain the cross-striations as parallel bands of light and dark material. They extend only so far as the surface of the cell is in the plane of focus, becoming lost as soon as the vision penetrates below the surface. They may consist of only five or six parallel bands, or of as many as 10 or 12, again depending upon the plane of the surface. This is quite different from the fixed material, in which the cross-striated fibrils extend for long distances within the field of vision. In a few regions, such as along the side of the trabeculaj, the cross-striations can be readily distinguished. Here they are arranged in the characteristic pattern, i. e., dark band, light band, gray band, light band and dark band.

The cross-striations were most readily observed in the living heart by the aid of janus green. In such muscle tissue they appear frequently as a blue band with an adjoining light band. These were either close together or separated by a space where the gray band was indicated. The blue band was undoubtedly the dark band stained with janus green. In preparations which had been stained for some time the material between the two light bands (the gray band) also became slightly blue. In no instances were the cross-striations of the living material as marked as in the fixed preparations. This was largely due to the fact that they were never drawn into thicker bundles, i. e., fibrils, but remained spread out over the surface of the cell.


Jl NE, 1919]


181


SUMMARY

Thus it is st-eii that in the liviii-r irll cross-striations an |)rest'iit. hut not filirils. The cross-striations art- very tliin l)an<ls on tlie surface of the cell. They extend across the cell and are never in the narrow threads or lihrils. The fixation of the cell causes the formation of the surface layer into fihrils in which the cross-striations are drawn toj;ether into dee]ier bundles and thus hei-oine evident as shar])ly marked structures. In places where the pull on the surface of the cell is such that the latter is not coajrulated into (ihrils, the cro.ss-striations remain spread out as thin hands across the cell (Figs. 2 and 4).

The comjjlete cross-striations are present in the muscle of the heart of very younjr emhryos (10 myotomes) much earlier than was su|)posed hy other ob.servers.

The physifdojrists have endeavored without success to formulate a theory, based upon the myofibrils, to account for the contraction of the muscle-<'ells. It is not surprising that such a theory has not proved satisfactory, at least in regard to the heart muscle, since the structure u|)on which it was ba.sed is not a part of the living heart-muscle cell, hut only of the dead cell. In other words, a cell containing the structure upon which it was attempted to huihl the theory is not capable of undergoing contraction.

LITERATI-RE

Bruno. G. : 1918. La struttura del miocardio dell 'embrione di polio air inizio della sua funzione contrattile. Monitore Zool. Ital.. XXIX. 53.

Congdon, E. D.: 1918. The embryonic structure of avian heart muscle with some considerations regarding its earliest contraction. Anat. Rec. XV, 135.


Duesberg, J.: 1909. Ueber Chondriosomen und ihre Verwendung zu Myofibrillen beim Hiihnerembryo. Anat. Anz.. XXX IV. 123.

Idem: 1910. Les chondriosomes des cellules embryonnaires du poulet, et leur role dans la gen^se des myoflbrilles. .Arch. f. Zellforsch.. IV, 602.

Godlewski. E.: 1902. Die Entwickelung des Skelett- und Herzmuskelgewebes der Saugethiere. Arch. f. mikr. Anat.. LX, 111.

Heidenhain. M.: 1899. Beitriige zur .\ufklarung der wahren Wesens der faserformigen Differenzirungcn. .\nat. .Anz., XVI, 97.

Jordan, H. E., and Ferguson. J. S.: 1916. Textbook of Histology. New York, p. 95.

Kurkiewicz, T.: 1909. Zur Kenntnis der Histogenese der Herzmuskels der Wirbelthiere. Bull, intern, de I'acad. des sciences de Cracovie, p. 148.

Levi, G.: 1916. Migrazione di element! specifici dlfferenziati in colture di miocardio e di muscoli scheletricl. Arch, per le Scienze .Mediche. XL. 1.

Lewis. M. R.: 1919. .Muscular contraction in tissue cultures. Contributions to Embryology 35. Pub. 272. Carnegie Instit. Wash

Lewis, \V. H., and Lewis. .M. R.: 1917. Behavior of cross striated muscle in tissue cultures. .Amer. .lour, of Anat.. XXII. 169

Luna, E. : 1913. Sulla importanze dei condriosomi nella gene!-i delle mioflbrille. Arch. Zellforsch.. IX. 458.

Meves, F.: 1908. Die Chondriosomen als Trager erblichcr Anlagen. Arch. mikr. Anat., LXXII, 816.

Mlodowska. J.: 1908. Zur Histogenese der Skelcltniuskcln. Bull, intern, de I'acad. des sciences de Cracovie. p. 145.

Rouget. C. : 1863. .Memoire sur le d^veloppement embryonnaire des fibres musciilaires de la vie animale et du cii>ur. Jour, de la Physiol, de Brown Sequard. t. 6, p. 459.

Schlater, G.: 1907. Die Myofibrillen des embryonalen Hiihnerherzens. Arch. f. mikr. Anat., LXIX. 100.

Wieraan, H. L.: 1907. The relation between the cytoreticulum and the fibril bundles in the heart muscle of the chick. .Amer. Jour. Anat., VI, 191.


SPINA HIl IDA WITH ASSOCIATI

EMBRYO 17

Hy S. T. W TlieJoln,.^lIoi,l.-i

Human monsters at full term or in late fetal stages are .seen, sooner or later, hy almost every i)hysician. Similar anomalies in very young embryos, such as the one described herein, arc, however, not so well known. Dr. Mall ' estimates the frequency of full-tenu monsters as ."JO to every 5000 pregmmcics and gives a resume of the ])rotocols of 7."> specimens showing localiw*! anomalies (which he regards as the forerunners of monstx'r formation) found among 1000 specimens in the Carnegie Colle<'tion of Human Kmbryos. This particular embryo (N'o. 1961, Carnegie Collection) is, however, of especial interest in view of the fact that, although having a nu-nstrual age of only 79 days, it pn-sents ahnornuilities of brain, spinal cord, viscera and skeleton, generally suppo.sed to be characteristic


' Mall, F. P.: On the frequency of localized anomalies in human embryos and Infants at birth. Amer. Jour. Anat.. 1917. XXII. 49-72.


i) DISTruHANCES IN A HUMAN

MM. LONG

M.I.IS C'l 1,1,.

)/v Miilirnl Schoul

only of much oldir monsters. The cliiiiial history is hrielly asf.dlows:

Parents white. Mother 42 years of age; has had five pregnancies, two of which ended at term, one child living ( 14 years), the other dying of "inanition." The third, fourth and fifth pregnancies terminati'd In abortion, the last furnishing the specimen under discussion. The last menstrual period began on August 19, 1917, and lasted four days; abortion look place on Novemlier 6. As both parents were very anxious for another child the possibility of mechanical interference may be excluded. There Is no history o[ venereal disease. The only clinical symptoms which the woman presented were severe nausea and vomiting Immediately before and during the abortion.

The gross appearance of the specimen is shown in the figure on p. 182. reference to which will emibic the reader to under-tand better the following description. This is based upon ^1 i)reliminary c.vaniination with a binocular microscope, supple


182


[No. 340


iiieiiti'd by exaniiiiatiini under liiiiiuM- powers of serial sections tlirougli the cinbryo.

As seen in the \eiitral view, the enihryo is normal above the level of the eyes. The latter are synmietrieal, except that the left eye is placed slightly higher than the right. Microscopically, the lens of each eye is found to be hollow, the retina and choroid nuicb macerated, and pigment is scattin-ed throughout the vitreous. The e.xternal nares are represented by two pin-point depressions asymmetrically placed, and the lateral nasal processes are but feebly evidenced. The mouth is of normal width and in correct proportional position. It is gaping, however, and an enlarged tongue can be seen. The medial and lateral palatine processes are likewise visible. The ears show a well-marked helix, with no evidence of the original tubercles. There is a Tuint antitragus, and the primordium of the crus helicis can lie distinctly made out. Microscopically, the external auditory meatus and the Eustachian tube were



Spi.na Bii IDA wrrn A.s


!)CIATED DlSTUKHANCES I.X A HU.MAX EmiiKYO 17 .MM. Lo.NG.


traced in section, but nothing could be made of the labyrinth. Taken as a whole, the face represents a development considerably in advance of that noted in the oldest of the human embryos described by Rabl in his " Entwicklung des Geschichtes," which measured 14 mm. vertex-ljreech. and was estimated to be 36 or 37 daj's old. The face aaid ears, in comparison with other embryos in the Carnegie Collection, represent rather closely a stage of development corresponding to that of a normal embryo of the same length. Such embryos, according to the Mall curve, are about seven weeks old. From the degree of development of the head we may safely assume that 49 days is the maximum develofimental age of this specimen. The discrepancy between this and the menstrual age, namely, 30 days, undoubtedly represents the length of time the embryo remained in the uterus after its death.

The arm buds .show the transverse lines of division, and the contour lines of arm, forearm and hand. The hand pad .shows the rays for five fingers, but progress toward digitation is not marked. Except for this, the arms correspond to the normal. The legs are disproportionately .short for the general stage of development of the embryo, the foot pad showing practically no indi(ation of beginning digitation. Study of the sections


shows that the cartilaginous sbouldcr and pelvic girdle are normal, but there is some stunting of the tarsals, metatarsals and phalanges of the foot pads.

There is a small genital tubercle behind which the clt^acal membrane has disappeared, leaving the sinus patent. The tail bud has been absorbed until only a blunt coccygeal eminence remains. There is some slight indication of a urethral furrow, whereas, according to the tables of Keibel atid Elze, this should be *' fairly deep " in an embryo of 17 mm.

Practically the whole ventral wall of the abdomen has undergone pathological changes, sloughed or been torn away, leaving the abdominal +++++ CONTENTSs exposed. The viscera of thorax and abdomen show extreme maceration and histolysis, but their main outlines are well in evidence. In sections the alimentary canal may l)e readily made out : the mouth, pharynx, cesopliagus, stomach, duodenum and coils of gut can he followed throughout their length. The larynx, trachea, main bronchi and macerated portions of the lungs could also be followed through the sections. The heart has suffered in the general maceration, but one chamber for auricles and one for ventricles can be clearly made out. The bulbus and first part of the aorta were traced, iiut no vessel was found leading from the latter. The liver was in a state of extreme maceration, but masses of liver tissue could be traced in sections, and also some vascular attachments connected with them.

The mesonephros is fairly well preserved, and there are discrete masses of badly macerated tissue occupying the positions where the suprarenals should lie. No evidence of a liladder or any of the urogenital ducts can i)e found. The same is true of the spleen and pancreas. There is widespread destruction of . the vascular system; not even the main vessels can be traced with any sort of continuity.

From the dorsal aspect the most striking feature is the apparent failure of the medullary plate to close, a fact whicli was confirmed by microscopical examination. Caudad to the upper cervical region, and extending throughout the thoracic, luntbar and sacral regions, are two parallel rows of spinal ganglia on either side of the mid-sagittal plane, with discrete, scattered masses of nervous tissue between. Contrary to gross appearances, none of this tissue is naked, but all of it is covered by loose cellular tissue, undifferentiated and of irregular thickness. There is no trace of closure to form a cord. In the cephalic region as far back as the level of the eyes, closure seems to have taken place, and sections prove tliis to be the case, as the macerated remains of two cerebral hemispheres and a brain stem, covered with the same loose cellular tissue, are to be made out. The whole region, however, presents an irregular, bulging appearance indicative of an embryonic encephalocele. Meninges could not be found for the brain or other tissue of the central nervous system. In the region of the vertex there is a breach of continuity in tlie cranial vault, giving rise to an opening into the cranial cavity. This o])ening, upon a study of the sections, ajipears to be traumalic or the result of sloughing.

Twelve ribs and 30 verteVira' could be counted in sections, the latter with ditlicnltv, owint;- to the fusion and twisting


June, 1919]


183


of various centra. As determined from the sections, the vertebral axis shows the following points of interest : In the upper two-thirds of the back tliere is a deep cuneiform cavity, and exactly corresponding to this region is a very pronounced lordosis of the column. The middle of this region of lordosis marks a pivot point about which the posterior half of the vertebral column is twisted sharply to the right. In this way the ribs on the right side and the spinal ganglia are crowded together and appear in successive sections at the bottom of the depression. They are covered with loose cellular tissue. Tiic cavity is due to the lordosis. In the region of the sj-mmetrical depressions there is likewise a lordosis, and between these and the cavity the column is bent in the opposite sense — t. e., there is a slight kyphosis. The vertebra? show little or no evidence of neural processes, and of course no mcmbrana reuniens. Technically speaking, therefore, we have an eml)ryonic rachischisis and partial aniyelia. Owing to the maceration and poor staining, the details of the chondrocraniimi could not 1)C made out.

If due allowance is made for the extensive maceration, most of which probably occurred in xdero after the death of the embryo, we arc perhaps justified in asserting that the chief point of patliological attack lay in the axial skeleton and central nervous system below the brain. At any rate, it is here that we find its most important result*. There is some stunting of the arms and legs, but not sufficient to be of any great significance, except that, had the viscera been early and seriou.sly attacked, it is difTicuIt to see why greater nutritional damage did not effect the extremities; for in spite of the fart that its aliment is furnished by the mother, the embryo must of necessity possess a correlated metabolism of its own. There is nothing to indicate that the viscera did not develop in a fairly normal way: at least the state of maceration docs not suggest the contrary.


From the menstrual histories found among the records of the Carnegie Collection of embryos, it is more than probable that most of the pathological specimens are aborted witliin the first half of pregnancy, and, Uierefore, particularly if very young, their significance frequently escapes the notice of the j)ractitioner. It follows that, in those cases in which the pathological involvement is not sufficient to cause the death and expulsion of the embrj'o, the latter will sur\ive until the term or near term, and it is upon this limited group that tlie popular idea of the frequency of monsters is based. In the " Manual of Human Embryologj'," Dr. Mall has tabulated the comparative frequency of various types of monster formation at term and in aborted material, and finds a close parallelism between the two. The percentage of frequency of spina bifida is greater in the embr}o, however, than at birth, indicating that the mortality is greatest in this variety of monster. A more careful examination of abortion material in the future will probably reveal numerous specimens like the one here reported.

That the cause of such conditions exists early in pregnancy is splendidly shown in tlie specimen above described. As pointed out by Dr. JIall, the popular conception that mechanical influences have an important bearing upon the formation of monsters has been ovcrthrowni by recent chemical experiment*. The specific action of dilute salt solutions upon amphibian eggs, for instance, will produce spina bifida in a large proportion of the embryos. The trouble would seem to lie, therefore, not in the ovum iteelf. nor in the external mechanical influences acting upon it at a later date, such as amniotic bands which compress the imibilical cord, but rather in the impairment of nutrition associated with faulty implantation, or in the toxic influences arising from a diseased uterus.


BOOKS RECEIVED


United Statrs Army Xray Manual. Authorized by the Surgeon General of the Army. Prepared Under the Direction of the DivlBlon of Roentgenolog>-. 219 Illustrations, 1918. 12°. 506 pages. Paul B. Hoeber, New York.

United Btatet. Department of Commerce. Bureau of the Census. Financial Statistics of cities having a population of over 30,000. 1917. 4°. 373 pages. 1918. Government Printing Office, Waahlngton.

United (Stairs. Department of Commerce, Bureau of the Census. Birth Statistics for the registration area of the United States. 1916. Second annual report. 1918. 4'. 96 pages. Government Printing Offlce, Washington.

United States. Department of Commerce, Bureau of the Census. Financial Statistics of States. 1917. 4°. 129 pages. 1918. Government Printing Offlce, Washington.

Oxford Loose-Leaf Surgery. By Various Authors. Edited by F. F. Burghard, and Alien B. Kanavel. In Ave volumes. Over 1800 illustrations. Vol. I. 1918. 8'. 971 pages. Oxford University Press. London; American Branch, New York.


Practical Physiological Chemistry. A Book Designed for Use in Courses In Practical Physiological Chemistry in Schools of Medicine and of Science. By Philip B. Hawk, M. S.. Ph. D. Sixth edition, revised and enlarged. With two full-page plates of absorption spectra in colors, four additional full-page color plates and 18.S figures, of which 12 are in colors. 1918. 8°. 661 paRPs. P. Blaklston's Son & Co., Philadelphia.

The Hearts of Man. By R. M. Wilson, M. B. 1918. 12°. 182 pages. Henry Frowde and Hodder & Stoughton, London. Oxford Uni. verslty Press.

I nited Stales. War Department. Annual Report of the Surgeon General, U. S. Army, to the Secretary of War. For the Fiscal Year 1918. 8°. 735 pages. Government Printing Offlce, Washington.

fnited States. Treasury Department. Annual Report of the Surgeon General of the Public Health Service of the United States. For the Fiscal Year 1918. 8°. 373 pages. Government Printing Offlce, Washington.


184


[No. 340


THE MANUS MEDITATIONIS

By Charles Singer, Oxford


Man alone among animals knows that he must die, and civilized man alone among the races of men. Yet we moderns, with all the discoveries of science, all the complexity of our social system and all the wonders of past history crowding thick upon us, certainly ponder far less than our forefathers



upon our inevitable end. With the men of the Middle Ages it was far otherwise. Their present world was a small thing compared to ours and but a vestibule of the life to come. Mors jamia vita. It was upon the life after death that their thoughts were fixed and upon death as its portal. Death was their obsession, and there were whole classes of men whose current thoughts were of little but death and thereafter.


Every possible device was invoked to keep death ever before the mind.

But the physician spends his life in a contest which he must always lose at last and for which life is the forfeit. He, at least, hardly needs to be reminded of the temporary character of this life. Yet not so, thought our ancestors. They did not hesitate to insert a memento mori even in a medical work.

Among the means adopted to keep mortality before men's eyes was the manus meditationis, a method of illustrating, by a tale of the fingers, the thinness of the partition that separates the living from the dead. The manus meditationis that we here reproduce was inserted by some fourteenth century scribe in a very valuable and interesting collection of illustrated medical tracts now in the Bodleian Library. The phrases are written along the five fingers of the hand, a phrase for each phalanx and a terminal one for the nail. The phrases form rough but not unmusical verse.

TEXT Manus MEDrrAcioNES (sic!)

(1) Nescis quantum | Nescis quotiens | Quod deum offendisti

(2) Finis tuus amarus est | Uita tua breuis est | Uenisti in hunc

mundum cum peccato | Quod status tuus est miserabilis

(3) Nichil tecum afferes nisi quod fecisti | Uitam tuam non potes

prolongare | Mortem non potes evadere | Quod morieris

(4) Nescis quo deuenies | Nescis qualiter morieris | Nescis ubi

morieris | Quod hora mortis incerta est

(5) Cite obliuesceris | Quos relinquis parum facient pro te | Raro

facient pro te | Quod post banc uitam non est penetencia fructuosa

Meditari debes.

TRANSLATION In rendering a translation of this simple text we would call attention to the use of the word facient in line 5. Facere has sometimes in mediseval Latin the special sense of " to make a prayer," " to say a mass," or simply " to pray " — Orare est laborare.

The Hand of Meditation

(1) For that thou Itnowest not how greatly or how oft thou hast

offended God,

(2) For that thy end is bitter and thy life short, for that thou

earnest with sin into this world and thy condition is miserable,

(3) For that thy deeds alone thou canst take with thee, for that

thou canst nor prolong thy life nor escape death, for die thou must,

(4) For that thou knowest not whither thou goest nor place nor

time of thy deatli, for the hour of death is uncertain,

(5) For that soon forgotten thou wilt be, for that it is but little

and seldom that thy relicts will pray for thee, and for that after this life repentance availeth nought, Therefore meditate.


The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by the LORD BALTIMORE PRESS, Baltimore. Subscriptions. ?3.00 a vear (foreign postage, 50 cents), may be addressed to the pubUsherg, THE JOHNS HOPKIKS PRESS, BALTIMORE; single copies will be tent b» moil for flfty cents each. Single copies may also be procured from the BALTIMORE NEWS CO., Baltimore.


BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL

Entered ma Second-Class Matter it the Baltimore, Maryland, PostolHee Acceptanee (or mailing at special rate a( postage provided (or in Section 1103, Act o( October 3, 1917. Authorized on July 3, 1918.


Vol. XXX— No. 341]


BALTIMORE. JULY, I9I9


[Price, 50 Ce nts


CON

PAGE

Some Memories of t!ie Development of the Medical Scliool ami of Osier's .Ailvint. By Henky .M. Thomas ISo

Osier as Chief of a Medical Clinic.

By Lewellys F. Barker ISO

.Some of the Karly Medical Work of Sir William Osier.

By W. T. CoU.ncilman 103

Osier as a Pathologist.

By William (i. MacCali.tm 1!'7

Osier, the Teacher.

By W. S. Thayer lliS

Osier and the Student.

By Thomas R. Brow.n 200

Osier and Patient.

By Thomas McCbae 201


Osier and the Tuberculosis Work of the Hospital.

By Louis Hamman 202

Influence on the Relation of Medicine in Canada and the United States. By Thomas B. FrTciiEn 204


TENTS

PAGE

Dslcr as a Citizen and His Relation to the Tuberculosis Crusade ' in Maryland.

I By Henry Barton .Iacods 205

J Osier's Influence on Other Medical Schools in Baltimore. His 1 Relation to the Medical Profession.

By Edward X. Brush , 208

Inlluence in Building up the Medical and Cliirurgical Faculty.

' By Hiram Woods 200

Osier and the Book and .lournal Club.

' By J. A. Chatard 211

Osier's Influence on the Library of the Medical and Cliirurgical Faculty of the State of ilaryland.

By Marcia C. Xoves, Librarian 212

I Some Early Reminiscences of William Osier.

[ By He.nry M. Hurd 213

I Osier as I Knew Him in Philadelphia and in the Hopkins.

By Howard A. Kelly 21,">

Osier ns a Bibliophile.

By Thomas R. Boogs 210

Osier's Literary Style.

I By Edward X. Brush 217

Bibliography 210


SOME MEMORIES OF THE DEVELOPMENT OF THE MEDICAL SCHOOL AND OF OSLER'S ADVENT

By IIenuy M. Thomas


In thinking of tlic early days of The Jolins Hopkins University and IIosj)ital and the development of the nicdital school, my memories begin with the founder — Johns Hopkins. As a small boy lietween 10 and I'i I sat on the same beiu h with Johns Hopkins many Sunday mornings at the Friends' Meeting on P^utaw and Monument streets. I cannot remember that he ever spoke to me, and I remember him merely as a rather unkempt old gintlcninn. At that time he liad announced his intentions for his double bequest, had, in 186t^, incorporated the two institutions that were to Ijear his name, had niijiointed his trustees, and had lujught the site for the hospital. Calloway Cheston. the president of the university board : Francis T. King, president of the hospital board ; Francis White, James Carey Thooias. James Carey, and other trustees, were also


constant attendants at tiie meeting, and it is pleasjint now to think that in the congregation there were represented tlie founder, his trustees, and the rising generation which was to be benefited by tho bequest.*.

Johns Hopkins believed that his wealth had been given to him for a purpo.-^-, and, to use a Friendly form of speech, that he would bo " given to see how to dispose of it. He had asked atlvice freely and much had lieen volunteered, and many of his advisers have claimed that they suggested the objcct-s of his Ix-quests and the forms which they should take, but 1 like to think that the wise instructions that he gave to his trustees were finally determined in meeting. The most important of these for the development of the medical school was his direction in a letter to the hospital board, dated March 10, 1873,


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that iu all your arrangements in relation to this hospital you will bear constantly in mind that it is my wish and purpose that the institution shall ultimately form a part of the medical school of that university for which I have made ample provision by my will," so uniting forever the two bequests for the , furtherance of medical education.

Johus Hopkins died on December 24, 1873, and iu the early part of 1875 the trustees received the bequests and entered into active administration of the trusts. The first important decision of the university board was the wise and fortunate choice of Daniel C. Oilman as president of the university. He came to Baltimore May 1, 1875, and I can remember well the expectation and interest his coming aroused. He and his two daughters took apartments at the old ilt. Yernon Hotel, and for me a delightful friendship began.

Johns Hopkins chose his trustees well and left them untranuneled, and they in their turn gave President Oilman a free hand. They had already determined upon the establishment of a real university, which, as Oilman once said, was to supplement and not supplant existing institutions. In speaking of his first instructions which he received from the trustees, he says:

Often in private conversations and in official interviews, I was charged to hold up the highest standards, to think of nothing but the best which was possible under the limitations of the new establishment in a country where the idea of a university had not been generally understood.

Iu furtherance of these objects. President Oilman, in the summer of 1875, went abroad to visit the variotxs universities and to consult with the leaders in education. Medical education was much in his mind, particularly the establishment of the laboratories and courses of instruction in the fundamental sciences which would be best fitted for the preliminary training of medical students. The field was almost entirely unbroken, and young men not yet 30 were selected for its cultivation — Eowland in physics, Martin in biology, and Eemsen in chemistry. Rowland, although not then appointed to the chair of physics, had accompanied Oilman to Europe to aid him in the selection of physical apparatus and books. While on this journey he found time to publish some articles in the Philosophical Magazine which Oilman, with characteristic promptness and prophetic vision, dated from The Johns Hopkins University — the first university publications.

Oilman was inaugurated on February 22, 1876, and the university received students and began instruction in the fall of that year. Professor Huxley, who had taken much interest in the proposed biological department, and who had recommended a favorite pupil of his — H. Newell Martin — as its director, was in America and was asked to give an opening lecture. In this lecture he spoke of the importance of biological studies, and particularly their relation to a properly organized medical course. My father, who had selected me as the son most available upon whom to experiment with this new method of medical education, saw to it that I attended Oilman's inauguration and Huxley's opening lecture. I have no recollection of the inaugural exercises, but I do remember


hearing Huxley at the Academy of Music, principally, I think, on account of the storm of protest that followed. This protest was directed against the emi^hasis which the new university appeared to be giving to scientific research, especially in biology, even the study of which was thought at that time to be little less than impious, and was focused on the fact that Huxley, the great champion of science, had been asked to speak and that the lecture had not been ushered iu by prayer. I believe that Mr. King and my father, both devoted religious workers, were resi^onsible for this last circumstance. They certainly were astounded by the public reaction to this entirely consistent Quaker procedure.

Following the advice of Huxley and others the chemicalbiological course was designed, and was recommended to those students who intended to take up the study of medicine; indeed, it was also called the preliminary medical course. It was from the first the design of the university to establish the full medical course as soon as the hospital should be completed, and much thought was given to it. Martin and Eemsen were recognized as forming the nucleus of the medical faculty.

At the opening of the fourth academic year, September, 1879, Professor Acland,then Begins Professor of Medicine at Oxford, was expected- to give a- lecture embodying his advice as to the proper co-ordination between the university and hospital in the organization of an advanced medical school. Unfortunately, on account of illness, he was unable to deliver the address. His views, however, have been preserved in a letter to the university and hospital authorities. How surprised he would have- been had he been told that it was from this unborn medical school that his successor at Oxford was to be chosen !

In the early days the university was a small, compact body, made up, for the most part, of a young, active faculty, surI'ouuded by a group of advanced workers, called fellows, and other post-graduate students, and a few rather over-powered undergraduates. Every encouragement and opportunity was given to research and to prompt publication of work accomplished. There was the closest sympathy among all the departments, and everyone knew and sympathized with the work of the others. It was naturally around Martin that the idea of the medical school germinated, and a more inspiring teacher it would be hard to imagine. Besides the regular biological courses, he gave lectures to medical students and practitioners of the city, and graduates in medicine entered his laboratory for special work.

The emphasis which the university had put upon men in contrast to buildings had permitted it to function at once, and to strike a remarkable pace in a very short time. With the hospital it was different ; buildings were absolutely essential, and even though Johns Hopkins before his death had instructed his hospital trustees to begin work, time was necessarily consumed in the formation of plans, so that it was not until June of 1877 that these were adopted and the excavations were begim.

The choice by the hospital board, in 1876, of Dr. John S. Billings, surgeon of the United States Army, and librarian


I


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1919


PLATE XXIII


/;^



WILLIAM OSLER IN 1906.


I'.lliili'il li) S.i.|;iil.


1

I


JlLY. 1919]


JOHXS HOPKINS HOSPITAL BULLETIN


187


of the surgeon-general's office, as their medical adviser was most fortunate, both as to the construction of the liospital buildings and as to the future of tlie medical school. Dr. Billings was much in Baltimore, and his encyclopedic knowledge of things medical was always at the service of the university as well as the hospital. He supplemented Oilman, and made with him a remarkable team. He was attached to the university academic staff as a lecturer on the history of medicine and nmnicipal hygiene, although I do not think he gjue many lectures until after the opening of the hospital.

Among the physicians who were attracted to Martin's laboratory was Wni. T. Councilman, who began work in 1878, just after iiaving received his medical degree from the University of Maryland, and who, after his return from Europe in 1882. was made a fellow by courtesy, and was appointed associate in patiiology in 1884. He busied himself about medical problems, gave some courses in special subjects, and lectured at the University of Maryland on pathology.

In 18T9. Wm. H. Howell came from the Baltimore City College and entered the chemical-biological cour.«e and began a career which was to mean much to the university and medical School. He soon became a favorite pupil of ilartin's. and after receiving his bachelor's degree, he was made in quick succession a fellow, an assistant, and then, in 1885, an associate in biology, having received his Ph. D. the year before. He resigned from the university in 1889, to return again as professor of physiology at the opening of the medical school.

I. in my capacity as experimental animal, was entered in the university the same year, and I can well remember Howell as the model student and also on the football field where be made up for his light weight by the accuracy and neatness of his tackling.

I look back ujion my course at the university witli tlie greatest pleasure. To have been under such men as Martin, Renisen, and Hastings in physics, to have read Shakespeare with Sydney I^anier, and to have heard the lectures from the noted men who were constantly coming to the university, could not help being stimulating to a youth even though overoccupied with many athletic pursuits. It had been hoped by tho.se of us who took the preliminary medical course that at its completion the university would have started its medical school, but this was not to be. The buildings of the hospital were going up very slowly, and as there seemed no immediate prospect of their comiiletion, we were forced to go elsewhere for our medical in.Ktruction.

While at the University of Maryland. I attended Dr. Couik ilman's first lectures on pathologA'. and also took a course with him in the biological laboratory in the histology of the nervous system. We had excellent professors at the University of Maryland, but it was the old lecture system, the only laboratories being the dis.«ecting room and a newly established chemical laboratory. The students had practically no chance of getting close to patients, and I was graduated without ever having been instructed in physical diagnosis, and I received the prize in obstetrics without ever having seen a woman in labor I I took my medical degree in 188.5. By this time the


university was on the point of establishing its medical department. In the register for 1883-1884 it is announced that The medical department of the university is soon to be organized. Its plan is receiving the constant attention of the trustees, and it will be made known before the completion of The Johns Hopkins Hospital. The nucleus of a medical faculty has been instituted as follows: The president of the university: J. S. Billings, M. D., lecturer on hygiene: W. H. Welch, M. D., professor of pathology; Ira Itemsen, M. D., professor of chemistry; H. Newell Martin. M. D., professor of physiology."

In this somewhat casual way, the university announced the epoch-making facts that it had recognized pathology as a full university sul)ject, and had appointed Dr. Welch to fill the chair. The first was the natural development of the university idea in medicine, and the credit of the second has been claimed, in a friendly rivalry between the university and the hospital, both by Oilman and by Billings. However that may be, no other choice now seems conceivable.

Dr. Welch's appointment was the first one that had to do with practical medicine, and I remember my father's enthusiasm over it, for with it he felt that the university had made a wonderful beginning in medical teaching. What a wonderful beginning it was he was to learn later!

Welch gave his first course of lectures in Hopkins Hall in February and ilarcii, 188G, on microorganisms in disease. The hospital trustees allowed the university to furnish the autopsy house as a pathological laboratory, and so the first of the hospital buildings to be used was dedicated to the common purpose of the two trusts. Dr. Councilman had been appointed an a.ssociate in ])atlK)logy, and courses of instruction were started on November 1, 188(i. Halstead came from New York to work in the laboratory and Mall was apjiointed the first fellow. Other students gathered, most of them graduates in medicine, and when 1 returned from Europe at the end of the year I joined the grou]). Those early days have often been described, and it was, indeed, a rare privilege to have taken part in them. As the hospital was not yet opened, the institution had to depend ujwn other sources for its autopsy material. This was obtained for the most part from the City Hospital at Bay View. In the reorganization of this charity, The .Tohns Hopkins University had assumed the care of the insane, and my father. Dr. Councilman and I were appointed visiting physicians. Dr. Ct)uncilnian was also pathologist.

.\t this time everything seemed to point to the early opening of the full medical school. The buildings of the hospital were practically finislied, and there seemed to be no reason wliy they should not be shortly opened. The university authorities were completing their plans and Welch was on the spot. It was just at this time that financial calamity overtook the university. The Baltimore and Ohio lonmion stock, of which the university had nearly l.'j.OOO shares, dropped its dividend from 10 to 8 per cent in 188(i, to 4 per cent in 1887, and ceased paying the next year; the university was struggling for life and could not take on new obligations, so that the plans of the medical schocd were indefinitely suspended. The hospital income had not been affected as it was derived almost entirely


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[No. 341


from real estate, and there had been no inroads on the capital bj' the erection of the hospital buildings. It had, indeed, increased, and the hospital had now become the rich member of these organically joined twin bequests.

The time had come for the hospital to take up the work, but for it to begin to function, men had to be found to organize the various clinical departments. Above all, a physician-inchief had to be appointed and everything depended upon the choice. The question was anxiously discussed by the two boards of trustees and their advisers, and the little band of students in the jDathological laboratory discussed the question with critical, impotent anxiety. Now that adversity had fallen on the university, what hope was there that the unbroken series of phenomenal appointments could continue? Where could a clinician be found to match Oilman, Billings, Martin, Remsen, and Welch, and if found, would such a man come now that the opening of the medical school in the near future was less than probable ? We doubted, but we did not at that time know Dr. Osier and how impossible it would have been for him to have refused to add his strength to the endeavor to bring to fruition the long-nourished idea of a real university niedical school. He has given an account of his reaction to the proposal. In speaking of Billings' visit to him in Philadelphia, he says: "Without sitting down, he asked me abruptly, ' Will you take charge of the medical department of The Johns Hopkins Hospital ? ' Without a moment's hesitation I answered, ' Yes.' ' See Welch about the details ; we are to open very soon. I am very busy to-day ; good morning,' and he was off, having been in my room not more than a couple of minutes."

The appointment was made in the fall of 1888, and he was to begin his service at the opening of the hospital, which was announced for May, 1889. It soon became evident tliat although it was easy to announce the opening day, it was quite another thing to get the complicated mechanism of the hospital organized and ready to function. In this emergency the hospital appealed to the university and induced Oilman to assume the task. The work was colossal and the time was short, and it speaks volumes for the estimation in which Oilman's organizing ability was held that no one doubted the result.

The formal opening occurred on May 7, 1889, and Osier, with liis satellites, took his place as our guiding star. He brought Lafleur from ]\Iontreal, Scott and Toulmin from Philadelphia, and those of us who were able to do so joined the ever-increasing group.

The hospital annexed Welch with his already organized department of pathology-. Halsted was given charge of the surgical department and the organization of the dispensary, Kelly was brought in June from Philadelphia to take charge of gynaecology, and in August Dr. Hurd, as superintendent, took over from President Oilman the direction of the hospital.

The opening of the hospital was for the trustees, the faculty, and above all for us expectant, impatient medical novices, the beginning of the fulfillment of long-suppressed desires. For me the reality far surpassed the fantasy of my dreams. In the association that was to follow, which for my part was as close


as I could make it, Osier as a physician, teacher and friend, constantly raised my preconceived ideal. Memories of this time overwhelm me.

The dispensary was opened first and patients were admitted to the wards from it, and Osier, surrounded by a few of us, himself wrote the first dispensary history. Until the wards were full he was constantly in the dispensary, organizing the various subdepartments of medicine, for it was an unique feature of the system that the services were continuous, and that the various special departments were grouped under either medicine or surgery. As it was in the early days of the university, so it was with the hospital at the beginning. Workers formed a closely united body. All that happened was of interest to each of us. On the medical side Osier radiated by his example and personality constant stimuli to careful clinical work and investigation along all sorts of lines. He pointed out problems, encouraged everj-one in what he desired to do, and was more than liberal in his commendation of work done. His absolute generosity threw open his whole clinical material to the use of any one who had a problem. He urged and assisted in the publication of the results, and saw to it that the young men got the whole credit of the work when often it should have gone to himself. Is it to be wondered at that such a chief has such devoted followers ?

The Medical Society, the Journal Club, the Historical Club, and other associations, were organized in quick succession. Post-graduate courses were given, but the medical school of the university seemed as far from beginning as ever. The university trustees were not unmindful of the question, and some of them in spite of the depleted income, were constantly urging the establishment of the school. I have found among my father's papers the notes of an earnest appeal on the subject which he appears to have made to the Board of Trustees in May, 1890. Certain women, several of whom were daughters of trustees, who had from the first unsuccessfully sought admission for themselves and other women to the university, and who had been told that it was planned to admit women to the medical school when it should be established, collected money and offered $100,000 to the trustees on condition that it should be used to help the establishment of a medical school to which women should be admitted on the same terms as men. On October 29, 1890, the trustees made a minute accepting the gift, nath the proviso, however, that the university should not establish its medical school until an endowment of $500,000 had been secured, and that women who desired to enter should receive their preliminary education somewhere else. Miss Mary E. Garrett, who had contributed most of the original Women's Medical Fund, completed the endowment on December 23, 1892, by a gift of $306,977. Leading up to tliis gift there was a protracted three-sided discussion between Miss Garrett and her friends, the Medical Faculty and the Board of Trustees. The outlook for an agreement was often gloomy, and only one who was in a position to know, as I was, something of the ideas of all three parties to the negotiation, can realize on how many occasions the scheme came close to being abandoned. In this discussion, together with Welch and


.IlLV. 1919]


189


Martin. Osier was deeply concerned. He had become very restive uiuler the delay of the opening of the medical srhool, complained to me on one occasion of what he called the dry bones of post-graduate teaching, and even intimated that unless something were done he might be forced to go wIktc there were some real medical students.

The decision as insisted upon by Miss IJarrett. to lix permanently by the terms of the gift the conditions for admission to the medical school at an unprecedenteil standard, required no little courage, and although the results have abundantly justified it. it was then thought that it would greatly limit the number of students who would apply for admission. The first class of IT, including three women, entered in the fall of 1893. When, in the third year, they began to work in the hospital, first in the dispensary and then in the wards. Osier's genius as a medical teacher became more and more evident. He saw to it that the students came into the closest contact witli the patients in the dispensary, and he organized the hos|)ital wards so that the fourth-year students took an essential part in the management of the cases. Although this last liad been the intention since the inception of the hospital, and the main


building had been designed to house 20 senior students, its practical application met with opposition and presented difficulties, and it was Osier's insistence that threw open the wards to the students, a fact, the thought of which. 1 think, always gives him pleasure.

He did. indeed, put the students into the wards, but he did not leave them there. He stayed with them, and if ever medical students got clinical instruction on a university basis, they did. It is not given to me to speak of Osier as a teacher, for my chapter ends with the beginning of the medical school. For me, and for others similarly situated, wlio had been reared in the expectation of the new order in medical education, the coming of Osier ushered in the complete realization of longdeferred hopes. He set for us a difficult goal, and helped and cheered us on the way by his wise precepts, his kindly, friendly commendation, his vigorous leadership, and more tlian all. by simply being himself.

It is no fault of his that the finished product is no better, but what good there is in me as a teacher and a physician I owe to him, and on this, liis birthday. 1 lay it at his feet in grateful acknowledgment.


OSLER AS CHIEF OF A MEDICAL CLINIC


Bv Lewellys F. Barker


Internal medicine, like other branches of science, though making at all times some progress, is subject in its advance to fits and starts, the result of unusual concatenations of events. The ojiening of tlie medical clinic at The Johns Hopkins Hospital in 1889 was an opportunity for helping on the science and art of medicine that might amount to either much or little, \ depending upon its seizure. The time corresponded to the Hoodtide of natural science. Biology, physics and chemistry had participated in the great rise. Medicine, always quick to api)ly to its own service the results of investigations in tlie fmidameutal sciences, had responded by estal)lishing a whole series of special medical sciences (anatomy, histology, embryology, physiolog}', physiological chemistry, pharmacolog}', pathological anatomy and physiolog}-, bacteriology), to be studied and taught by men who gave up their lives exclusively to their promotion ; these sciences were to serve as a foundation upon which a great superstructure of clinical science and art might be built. The place to be filled, the professorship of medicine in The Johns Hopkins University, which carried with it the appointment as physician-in-chief to The Johns Hopkins Hospital, was in several ways unique, at least as far as medicine in America was concerned. For, in the first place, according to the will of Johns Hopkins, the well-endowed hospital was designed to be an integral part of the medical school of an endowed university, and funds were provided for salaries for the leaders of the clinics as well as for the chiefs of other university departnu^nts, one of the circumstances that, combined with others, led to the abandonment of the hitherto-prevailing " proprietary medical .schools " and to their replacement by medical schools organized as parts of great universities. In


the second ])lace, Tlie Jolins Hopkins University, through the action of its trustees, and of its first president, Daniel C. Oilman, had been organized, in all its departments, in the interests of original research as well as of competent instruction; with distinguished investigators in the arts department and with men like Jlartiu and Brooks in biology and physiology, Kowland in physics, Ecnisen in ciicmistry, and Welch in patholog}', it was clear that capacity for personal research and the power to stimulate others to engage in fruitful researches were regarded, along with ability to teach and to organize, as essential requirements of the occujiants of chairs in the university. .\nd, in the third place, the trustees of the hospital, in consultation with the president of the university, the professor of pathology, and Ur. John S. Billings of the surgeon-general's library, had planned and built (out of income from the endowment), a liosi)ital that, at the time of its completion, offered better facilities for the organization and conduct of clinical work than had heretofore been available in the United States. The ideals ihcrishcd in the university, the material cquii)mcnt at the hospitJil, the opportunities and possible rewards open to the clinical leaders who might be appointed, combined to provide unparalleled places for occupancy. If, then, for tbe.se positions clinical men could l)e found, wlio, by native ability and experience, would measure up to the extraordinary time and the unusual opportunities, success in the highest sense for the new institution would seem to be ensured. The chair of medicine is, by common consent, the most important clinical chair in a university medical school. For this professorship the university faculty recommended, and the trustees confirmed, the appointment of


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Dr. William Osier, then engaged in teaching medicine in the University of Pennsj'lvania and in consultation practice in Philadelphia. A member of a distinguished Canadian family, trained in medicine first in the University of Toronto and in McGill University in Montreal, and, later, as a graduate student, in the clinics and laboratories of England, France and Germany, interested and occupied in research and teaching in histology, physiology, pathology and parasitology as well as in internal medicine, and possessing personal qualities that even in youth marked him as a potential leader of men, the appointee entered upon his work with an enthusiasm that was stimulating, began to organize his department, selecting a group of young men as assistants, and soon set an example in practice, teaching and investigation that was contagious. The office and the man were suited to one another. The time, the place, and the person formed a happy conjuncture that was to mean much for internal medicine in America and in the world. Of the set of brief contributions here published concerning Professor Osier's work in Baltimore, those dealing mth his practice, his teaching, and his original inquiries are written by others; the part assigned to me is the preparation of a memorandum outlining the principles to which he, as the organizer of a medical clinic, persistently adhered, and the methods he employed in their practical application. He had vei7 definite ideas of what a medical clinic should be and he felt keenly the responsibility of seeing to it that the functions of the clinic were faithfully ijerformed. For him, the welfare of the patients who presented themselves in the clinic for diagnosis and treatment came first; next, came into consideration how undergraduate and graduate students could best be taught; and, finally, came solicitude that every opportunity for contributing to the advance of our knowledge of internal medicine should be eagerly seized. He took care to promote in every way possible the material, the scientific, and the moral interests of all who were associated with him in his work ; his personal advantage concerned him but little, though to anyone who aimed at such objects and achieved such purposes as he did, a modicum of profit and a maximum of honor and prestige were bound to accrue. The principles he fixed upon and the methods he used to illustrate them were manifoldly derived. In part they grew out of personal practical experience, in part they had their origin in other clinics in this country and in Europe. Men who were familiar with clinical work and clinicians in the larger centers of America, those who had " walked the hospitals " of London and Edinburgh, those who knew the laboratories and the clinical institutes of Austria, Germany and Holland, and those who had visited the clinics conducted by the best internists in Prance, had no difficulty in recognizing the sources of certain of the features of the organization of the medical service in Baltimore. Professor Osier's clinic synthesized diverse elements into a harmonious whole; it represented a new form, good in itself for its time, and yet plastic enough to admit of remoulding at later need. The limits of this article will permit of only brief comment upon the plan of organization and upon the way it was manasjed.


Where activities are complex, be they those of a factory, of a business office, of a scientific laboratory, or of a medical or surgical clinic, organization and management are two executive functions that must be properly exercised, if the work is to be successful. Organization involves: (1) An investigation of the conditions that exist and of the requirements of the whole situation; (2) the planning of a scheme that will meet the requirements, tliat will effectively and systematically correlate the activities of the working force, the materials, the equipment and the working space, so that the functions of the institution shall be competently, speedily and economically performed; and (3) the actual installation of the system as planned. Management, or the art of conducting an establishment after its organization has been devised and initiated, involves : ( 1 ) The attainment of the results that are aimed at ; (2) the overcoming of obstacles that are incident to the conditions under which the work has to be done; and (3) the application of knowledge and skill in the training of the staff, in the setting up and in the maintaining of standards, in the providing of suitable incentives, and in the establishing of right relationships between the leader and the led. The head of an institution, or of a department, who creates an organization that is adequate, and who manages it with skill, demonstrates his executive capacity.

On Professor Osier's appointment as physician-in-chief to The Johns Hopkins Hospital in 1888, he found certain conditions already exisflng that were to some extent determining, at least as far as the general organization of the institution was concerned. The buildings already completed included one for general administration, -nith a building on each side of it for private patients, a long row of public ward buildings behind, a building for a general out-patient department, a nurses' home, a pathological laboratory, a general kitchen and a laundry. In other words, a " general hospital," in which medical and surgical patients (free and pay) were to be received, distributed and treated, and in which, later on, medical students were to be taught, had been constructed on the pavilion system. There was no spatial concentration of the work of the single departments in separate institutes such as had already developed in some of the European centers, or, as was later adopted in the institutes built for psychiatry and pediatrics on the grounds of The Johns Hopkins Hospital ; on the contrary, to pass from some of his private patients in Ward B at the southwest corner of the grounds to some of his public-ward patients at the northeast corner, the internist and his staff were compelled to walk through corridors that extended along two sides of a square containing 14 acres ! As in most general hospitals, the functions of general superintendency, financing, accounting, nursing, purveying and housekeeping had been centralized, and with them the heads of the clinical departments had but little to do. But, thus relieved of much administrative detail, the head of the medical department, who was appointed permanently and had a continuous service, was to have a large degree of autonomy in the diagnosis and treatment of patients, in the selection of his staff, in the character and amount of his teachintr, and in the conduct of research. His staff was to con


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sist (1) of younger men who lived in tlie hospital and gave their whole time to the department, and (2) of s^enior associates who lived outside, giving part of tlieir time to the liospital and part to private practice. The chief of tlie medical service was to l)e ])aid a salary in order that he might make the work of the hospital and of the medical school his main occupation and interest, thougli he was permitted to supplement his income and clinical experience hy private consultations. The activities of the dilferent clinical departments were to be correlated partly by the general superintendent of the hospital, and partly by a medical advisory board that made reconiinondations to the trustees of the hospital. Wiien Professor Osier arrived, the buildings, and the general plan of organization already completed, had to be accepted as they were: the plans of his department had to be drawn so as to fit into them.

It was fortunate that The Johns Hopkins Medical Scliool was not opened until 1893 and that clinical instruction of undergraduates did not begin until 1895, for six years were thus available for perfecting the organization of tlie wards, the outpatient department, the laboratories, the staff, the records, the library, the hospital, the medical society, and the care of patients in the hospital before the function of teaching undergraduates was added. Courses for post-graduate students were, it is true, offered during this period, but the number of candidates was small and the work was not burdensome. With few patients at first, a small staff, and a limited amount of post-graduate instruction, lei.«ure was given for making plans (and for modifying them after small-scale trials in executing them), for instituting standards, for writing a text-book that concisely embodied the principles and practice of medicine and that was destined to have an unprecedented distrilnitiou among physicians and student.*, and. in general, for establishing traditions of the better sort in the clinic. With the organization thu.s far planned and installed before the students of the medical school entered upon their clinical work, it was a relatively ea.sy matter to expand it and to adapt it to the functions of undergraduate instruction when the time for this arrived.

^^'hen the definitive history of Professor Osier's work in Baltimore is written, many details of liis analysis of the functions of the clinic, of his applications of the principle of division of lalnir in the clinic, of his methods of selecting men, of as.signing them to appropriate t<isks. and of motivating them to high endeavor, and of the personal qualities through which he exerted that profound and lasting influence upon patients, students, assistants, and colleagues for which he is so widely kno«-n, must be recorded. The .scope of the present memorandum will permit mention of only a few of the more outstanding features of his organization and management, of those parts that made his clinic so successful a department of a university teaching hospital as it is known to have been.

One important element of success in the new clinic was the arrangement for a graded staff, particularly for a graded, whole-time, resident staff, among the members of which the responsihilties of the work were divided, not according to a so-called "military type," but rather in the manner of the


so-called " composite functional type " of organization. The professor of medicine (physieiau-in-chief to the hospital), though giving most of his time to the work of the clinic, lived outside the hospital, as did the associate professors who " visited " the wards, the out-patient department, and the laboratories. The resident physician, the assistant •resident physicians, and the medical internes lived in the hospital and were in close contact with the work always by day and as far as was necessar)- also by night. The resident staff of the clinic consisted of two parts: (1) A lower resident staff constituted by the medical internes appointed for a single year, usually on graduation with high standing from the medical school ; and (2) an upper resident staff made up of the resi<lent physician and several assistant resident physicians, usually men of exceptional promise, men who had already served as hospital internes and who were willing to enter upon a more or less prolonged resideat service, often of several years' duration, in order to secure the best possible training for the " higher walks " of internal medicine. This upper staff was chosen partly from the lower staff, partly, in order to prevent " inbreeding," from members of the resident staffs of hospitals in distant medical centers. The position of chief resident physician, which carried with it large responsibilities and opportunities, was a prize to be won only by men of exceptional ability, extensive experience, and favorable promise. Thus, those receiving it in Professor Osier's time, included Henry A. Lafleur (1889-1891). William S. Thayer (1891-1898)," Thomas B. Futeher (1898-1901), Thomas McCrae (1901-1904). and Rufus I. Cole (1904-190G). The careers of these men during their tenns of service and since illustrate on the one hand the wisdom of him who selected them, and on the other the growthpromoting influence of the duties and authority attached to the office. The assistant resident,*, even those who did not later become chief resident physicians, often continued in ofTice for several years. Such an ui)per resident staff, supported by internes and by senior students, besides forming a whole-time group of enthusiastic young internists for development under ideal conditions, afforded an excellent working force for carrying on the routine of the wards, laboratories, and out-patient department; this left the pliysician-in-chicf and his visiting associates largely free for planning, standardizing, supervising and controlling the practice in the clinic, for teaching, and for promoting original iii(|uiries. The historian bent on analyzing the conditions of achievement in Professor Osier's clinic will do well to consider carefully the significance of this upper resident staff.

A second characteristic feature of the medical clinic organized by Professor Osier was the introduction of more extensive and more systematic courses of instruction in the j)racticaltechnical methods of gathering data regarding disturbances of structure and function in the sick than had before been customary. The importance of careful hi story- taking and of accurate physical diagnosis had been, it is true, generally recognized : but the nnicbinery of instruction in these forms of fact-accumulation had been inadequate in the majority of medical clinics, and one of the first tasks of the new clinic con


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sisted in planning and installing a better organization for this purpose, and in seeing to it that the example set by all who participated in the practical work of diagnosis in the clinic was consistent with the methodological teaching. The most distinctive advance made in instruction in technique was, liowever^ the establishment of a systematic course in the application of the laboratory methods of chemistry, physics, and biology to the study of patients. Students in their third year of the medical school were not only taught the principles of these methods, but for two or three afternoons throughout the year were thoroughly drilled in the practical technique of these methods, so that, when the course had been completed, each student had attained to real skill in the use of all the more important ways of examining clinically the blood, the stomach juice, the feces, the urine, and the cerebrospinal fluid. No medical school has yet devised a perfect system of training, and the graduates of The Johns Hopkins Medical School, like those of other schools, doubtless exhibit certain special defects, but by common consent, they are well-trained in the methods of gathering clinical facts and especially in the technical procedures of the clinical laboratory. By many it is believed that, of the several contributions made by Professor Osier to the organization of the clinic, the development of the clinical laboratory and of the thorough education of students by competent instructors in clinical laboratory work before entering upon their duties in the medical wards is preponderant.

A third distinctive mark of the organization in Dr. Osier's clinic was the arrangement by which each student of the medical school became for a considerable period a member of the group that actually did the work of the diagnosis of disease and of the treatment of patients in the hospital. Thus each student in his third year, after having had instruction in history-taking and in the elements of physical diagnosis, assisted, under the supervision and control of instructors, in recording histories and in making physical examinations in the out-patient department. More important still, through the fourth year of the course, each third of the class acted successively for three months as " clinical clerks " in the stationary medical clinic, giving their whole time to the work of the medical wards. Thus the medical staff was reinforced during the entire school year by 30 student assistants, who, under the eye of the resident staff, took the histories of all new patients, assisted the internes in the making of the first physical examinations, made all the clinical laboratory tests on these patients, and accompanied their chief on morning rounds. At these rounds, the clinical clerk gave orally an epitome of the findings in the patient, watched the processes of control examinations used by the professor, and participated at the bedside in discussions of the pathological-physiological, pathological-anatomical, and etiological bearings of the case. He looked up recent articles on the subject and reported them at later ward rounds, followed the patient to the operating room if surgical procedures were indicated, watched the effects of the treatment employed in the ease of each patient directly assigned to him, and kept in touch with him during conva


lescence at his home after discharge from the hbspital, or in the event of a fatal issue attended the autopsy and the pathological-clinical conference that followed it. The fact that through all this he was regarded as an integral part of the working group of the clinic, the knowledge that tlie anamneses he registered and the results of laboratory tests he made became a part of the permanent records of the hospital, the feeling of responsibility he had when he realized that the diagnosis made and the treatment instituted were based in part upon data accumulated by him, the personal relationships established between student and professor at the hospital and on delightful Saturday nights at the professor's home at 1 West Franklin Street — all this combined to make the time of the clinical clerkship in Professor Osier's clinic a period of rich experience and of intense stimulation, never to be forgotten by any pupil who passed through it. Even in the more formal teaching of the clinic, it was Professor Osier's custom to permit the clinical clerk to have a share. Thus, at the main teaching event of the week, the crowded Saturday clinic in the amphitheater, where all the students of the third and fourth year, the whole resident staff, many of the visiting physicians of the hospital, physicians of the town and medical men from a distance were assembled, the clinical clerk gave a part of the clinic; he was always asked to tell the audience briefly (and from memory unaided by notes) the main points of the anamnesis of the patient and was called upon from time to time throughout the hour to report on laboratory tests and X-ray flndings, or to give his opinion of the significance of some datum. The pupil-teacher thus grew accustomed to facing a large audience and to thinking and speaking on his feet, an admirable preparation for some of the contingencies of later professional life. The student-assistantships in the out-patient department (in the third year) and the clinical-clerkships and all that they implied (in the fourth year) were, then, vital parts of the organization of The Johns Hopkins Medical Clinic.

Though the organization of the clinic in Baltimore presented, as we have seen, an interesting combination of novel features, no organization, no matter how well planned and installed, can function effectively without the skilful application of the art of management, and in the art of management the director of this clinic was to prove that he was a master. Thoroughly familiar himself with the principles, methods and problems of internal medicine, enthusiastic about, and for his time well trained in, the preclinical sciences that are fundamental, he possessed that personal experience in his subject and that superior ability that are always prerequisites to competence as a manager and to the command of the respect of those that are to lie managed. ' He understood human nature and loved it, despite its faults and its frailties ; no chief ever secured in greater measure the good-will and loyalty of his staff. Though he could be firm on occasion, he rarely found need to act as a strict disciplinarian. He was always cognizant of the good qualities of those about him, and though not blind to their defects he had learned that great lesson of suqcessful management that, for most subordinates, a word of apprecia


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1919


PLATE XXIV



tLlir '^'aint .IJnluit^ lluiphins Hnspital


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tion is of far greater value as a stimulus to good work than a volume of carping critiiism. He possessed to an extraordinary degree the capacity of making you feel tiiat lie was interested in you and in your personal welfare ; to come into contact with him mciuit, for most, the birth of a genuine affection for him. He had an orderly mind and manner; he lauded punctuality in a doctor and was always punctual himself. He seemed never to be in a hurry and yet he wasted no time, ilany a man recalling an interview that seemed leisurely when it occurred has been surprised, on analyzing it afterward, to find how brief it had been. He belonged to the first of the two groujis — tlic " larks " and the " owls " — into which men have been playfully divided. He retired early and was an early riser. At one time he lived for some months in tiie hospital and it is asserted that men learned to set their watches at 10 p. m. l>y the sound of his boots as they dropped on the floor outside his door. His more important work was done in the morning hours ; for him " great business must be wrought ere noon " ; private consultations were relegated to the later hours of the day. His power immediately to grasp the significaiup of situations, his ability to make quick decisions, his unfailing tact and discretion, together with his wide .sympathies and his lively sense of humor made it a pleasure to transact business with him. His ideals he kept ever before him and was ambitious to realize them, and these ideals and this ambition were alluring also to those whom he led. JIuch miglit be written, were there space, of the ways in which he overcame obstacles and met important emergencies, of the motives he appealed to when he desired to excite men to action or to


arrive at a decision, and, in general, of thos-c traits of character that act " directly by presence, and without means," or what is sometimes called " jiersonal magnetism." Many of the qualities that make for successful management, tliough easy enough to recognize when tliey exist, arc difficult of analysis and perplexing to tlie understanding. Some men are able to secure control without contest; whether they stand or walk or sit or wliatever thing they do," they can place men under their power. Of such character-control and of prestige-control Professor Osier had his full share. But, more importjint than these, he had grasped, as it were intuitively, tiie newer principles of association and of group organization. A man of many selves, he could enter into helpful association witli many different groups, letting his mind interact witii the other minds of each group for the purpose of arriving at ideas, feelings and impulses in common. Jlore than most he had learned how to live with other men, to discuss without antagonism, to secure co-operation by the subtle psychic process of reciprocal penetration. In this lay the secret of his co-ordinating power. He knew not only how to bring the various activities of his clinic into proper relation with one another, but also how to link the clinic with other departments of the university, with the medical profession, with the public near and far, and with national and international a.ssociations of different kinds. Through his power as an organizer and as a manager Professor Osier might, then, have trutlifully said, as did one of old, " I magnify mine office." And it is precisely capacity for sudi magnification of office that, along with ability to plan and to direct, is a distinguishing criterium of the superior executive.


SOME OF THE EARLY MEDICAL WORK OF SIR WILLIAM OSLER


Bv W. T. COUXCILMAX


William Osier, the son of the Rev. F. L. Osier, was bom in Tecumseh, Ontario, in 1849. He was one of a large family, and his ancestors were a vigorous, long-lived race. He graduated from Trinity College, Toronto, in 1S68, began the study of medicine in the University of Toronto, and after two years went to McGill University, Montreal, where he received the M. D. degree in 1872. From 1872 to 187 1 he studied abroad, working in the various London clinics, in the laboratory of University College, London, and in the laboratories and clinics of Berlin and Vienna. He came in contact with many eminent men, studied methods of work and of teaching, and the influence of this period of European study is seen in his after career. In 1873 he obtained the licentiate of the College of Physicians of London, in 1878 he was made a member of the college, and in 1884 was elected to the fellowship. In 1874 he returned to Montreal, was made lecturer on the institutes of medicine, and shortly afterwards was given the profes-sorship. Under the institutes of medicine were comprised the courses in physiologA- and pathologv', the latter limited to 20 lectures. At the end of 1874 he was made physician to the Small-pox Hospital, and in the following year, owing to the interest which he showed in comparative anatomy,


the professorship of helminthology, in the Veterinary School of the University, was taken into his already full hands. I shall discuss here only his early work, extending through the first four years of the Montreal period.

Beyond the bare facts, we know but little of his early education. In his various ^^Titings there are only scanty allusions to it save in the Toronto address, in which he mentions three men who were his early teachers and to whom he says he owes everything he has attained in life. These were the Rev. W. A. Johnson, of Weston, Ontario; Dr. James Bovell, of Trinity College, later professor of the institutes of medicine in Toronto University, and Prof. Robert Palmer Howard, of Montreal.

I have been able to learn but little of the Rev. W. A. Johnson, but it is evident that he was one of the many clergymen of the Church of England who have sought in various scientific pursuits a wider range of intellectual activity than is given by their profos,«ion.* I have gained this conception of the


• The Scottish Church has produced very few of these men, and they have been rare In America. However slnRular this may seem, the reasons are obvious. The clerKy of the rhurrli of England possessed a liberal education, and the taking of Orders


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Reverend Johnson from two passages in the early writings of Dr. Osier. In the first article jjublished by him (Canadian Diatomaceae, Canadian Naturalist, 18T0) when he was a student in Toronto, he thanks him for assistance in the use of books and microscopical apparatus. In this article there is an admirable description of the structure, mode of division and propagation of the diatom, which is evidently based upon observation. The mode of motion of the organisms is discussed and he is inclined to accept the hypothesis advocated by Professor SchuJtze, of Bonn. At the close he gives a list of 105 diatoms which he had collected and classified, giving also the localities where they were found and their frequency. He must have been for a long time interested in the subject and the organisms were collected over an extensive area. He gives credit to Mr. Johnson for having given him several of the specimens. He refers also to another clergj-man, tlie Rev. Mr. Eeade, who had invented a prism by the use of which the shell markings could be studied to better advantage, and wliich was loaned to him by Professor Bovell. The article shows familiarity with the microscope and capacity to use literature. The second reference to Mr. Johnson I have found in an article 12 years later (On Canadian Presh Water Polyzoa, Canadian Naturalist, 1882) which was read before the Natural History Society. There is here also an admirable description of the organisms with the differentiation of the species, but its main interest is in showing how early Osier — probably through the influence of Mr. Johnson — ^became interested in the study of nature. " In the sunmier of 1867, during a visit of my friend, the Eev. W. A. Jolmson, of Weston, I showed him the masses (the gelatinous aggregates of the Pectinatella magnifica of Leidy) and we agreed to subject them to examination by the microscope, not having any idea as to their real nature. Judge of our delight when we found the whole surface of the jelly was composed of a collection of tiny animals of surpassing beaut}', each of which thrust out to our view in the zoophyte trough a crescent-shaped crown of tentacles." A fool>note ppeaks of another clerg-jTuan, the Rev. Thomas Hincks, as the distinguished authority on British polyzoa.

His second teacher. Dr. James Bovell, seems to have been an interesting character. He was born in Barbados in ISIT, went to England in 1834, studied at Guy's Hospital, and took the medical degree in Glasgow in 1838. He then went to


did not demand any extensive preparation for the examinations. Most of them had an assured living in pleasant country surroundings, and the dogma was simple, fixed, and did not admit of controversy. Proselyting was not actively pursued In the English church, and the souls of their simple parishioners were not a serious care. They must have found little intellectual stimulus in the society of the country squires, and many of them were perforce driven into the study of botany and other branches of natural science. The Scottish church, on the other hand, demanded long and arduous preparation for the ministry, and most of its members did not have the background of a liberal education. Like the Scottish character, the church was a fierce, aggressive force, its dogma logical and uncompromising, and its defence and extension Involved a constant controversy, which left little time for the calm study of nature. In this country the conflicts of the sects give sufficient intellectual diversion.


Dublin, studied under Stokes and Graves for several years and after a severe attack of typhus fever, against the advice of his friends, who predicted a brilliant medical career, returned to Barbados. From there he went to Canada in 1848; took part in the establishment of the medical faculty of Trinity College, became Dean and Professor of the Institutes of Medicine, and also Professor of Natural Theology. After the disruption of this medical school he held a similar medical position in Toronto University. In 1870 he returned to the West Indies where he remained until his death. While there he took orders in the English Church and published a book on Natural Theologj'. He was regarded as an impractical, imiprovident man, was loved by his students and friends and took great delight in metaphysical discussions. Osier came tmder his influence in Trinity College, and in Toronto University, and he has dedicated to him the first pathological report of the Montreal General Hospital. It is not improbable that, through these two men and the atmosphere of liis home. Osier acquired the interest in biblical and ecclesiastical literature which was such a prominent characteristic of his later life.

The third of these men was Dr. Robert Palmer Howard, professor of medicine in McGill University, whom Osier speaks of as his second fatlier. He was a greatly respected teacher and practitioner of medicine and exerted a wide influence, btit he was not a prolific writer.

While in London, Osier published two articles from the laboratory of University College. The first, " On the Action of Atropia, Physostigma, and Curare on the Colorless Blood Corpuscles," was read before the Royal Microscopical Society in 1873, and published in its journal. Such a paper as this was rather utiusual at the meetings of the society which were mostly taken up with descriptions of microscopes, methods of preparation of microscopic objects, etc. The object of the investigation was to determine whether the antagonism between atropia and physostigma, which Fraser had shown to exist, could be demonstrated in the behavior of colorless corpuscles under the microscope, and the result was negative. It was interesting to find in the same volume with the paper of Dr. Osier a long, interesting and scathing review of Bastian's Beginnings of Life which had just appeared.

The second article, " An Account of Certain Organisms Found in the Liquor Sanguinis," was published in 1874, appearing in the Proceedings of the Royal Society. This forms one of the most important of Dr. Osier's contributions to medicine and demands a more detailed description in order to do justice to the originality shown in this article. From the massive literature on the subject four articles may be singled out, each of which was an important contribution to knowledge. In 1865, in the article of Max Schultze on the blood, certain bodies afterwards known as blood plates were for the first time adequately described; the second was the article by Osier, the third by Bizzozero in 1882, in which he gave a new method for their study and showed the part they played in thrombus fonnation, and the fotirth by J. H. Wright in 1910, who demonstrated their histogenesis. The name blood plates, given to the liodies by Bizzozero, has been adopted.


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It would be difficult to say who lirst saw and described tliciu. At this period the fresh uustaiiied blood was being actively examined by many witli a view to the discovery of microorganisms which might be the cause of infectious diseases. Zimmermann, in Rust's Magaziu f. d. gesannute Heilkunde in 1846, and again in Virchow's Archives, Vol. 18, I860, saw and described the bodies as small globules which he regarded as the elementary corpuscles from which the blood cells develop, but his description was very vague and he did not sharply separate tliem from other granules in tJie blood. The very remarkable article on the blood cells by Max Schultze conceals by its title " Ein Heizbare Objecttisch und seine Verwendung bei Untcrsuchxuigen des Blutes " (Arch. f. Mikro. Anatomic. Bd. I, 1865), tlie subject of the article much better than usually happens, in spite of the ingenuity which is often displayed in doing this. After a description of the varieties of the white corpuscles, the accuracy of which excites our admiration even now, he says " In the blood no constituent is without importance, and in conclusion I will call attention to a normal form constituent of the human blood which up to the present has been entirely neglected. I find in my blood and in the blood of numerous persons of different ages more or less abundant, irregular masses of colorless globules, the masses varjing in size according to the number of globules which compo.se them. The globules themselves are from one to two micra in diameter and also occur .separately in the blood. I have found three, four and even hundreds joined together, forming plaques of irregular size, 80 or more micra in diameter. These structures, on account of their irregular size and shape, give the impression of broken up tissue elements." *

This was the condition when young Osier was probably given the subject for investigation in the laboratory. He showed that these granular masses of Schultze were not present in the circulating blood, but were formed at the moment of examination by a rapid aggregation of the single bodies. He showed this by microscopic study of the blood, and also by the direct examination in salt solution of small clippings from the connective tissue of the rat in which he found the single bodies and not the ma-sses of them, within the small blood vessels. He also showed that the conception of their presence in the blood in aggregations was imtenable because the masses could not pass through the capillaries. He described the small bodies as exhibiting amccboid activity and .saw filaments form in connection with them, which were probably fibrin. The article is admirable, clear and concisely expressed, with full literature references. The next reference to the blood plates is in an article "Infectious Endocarditis" (Seguin's Arch., 1881), and here he anticipates Bizzozero's view of the part they play in thrombus formation. " In one case of mitral


• I have quoted from this article for one reason T)ecause It was used as a reference in the course of physiology given by Newell Martin in 1S7S, and the plate when I opened the volume appeared as a familiar friend. No one appreciated more than did Doctor Osier the Importance of familiarlzlnR students with the oriprinal sources of knowledge, and this was always done in Martin's laboratory.


stenosis a fresh vegetation when teased showed many closely packed spherules, some of which were larger than those met with in the ulcerative form. [These were the masses of micrococci.] I was greatly struck with the resemblajice which certain of these bodies, in tliis instance, bore to the individual elements of Schultze's granule ma,<ses — those peculiar, granular clumps common in the blood of some animals and of impoverished * persons." In 1882 there appeared a further article, " Ueber dcu dritten Formbestandteil des Blutes," in the Centrall)latt f. d. med. Wisscnsch., No. 30, in which he emphasized the part they played in the formation of thrombi and a final article " On the Third Corpuscle of the Blood, iledical News, 1883, a ratiicr popular presentation of the subject.

Osier returned to Montreal in 18'('4, bringing to his future work a remarkable equipment. He was 25 years old, possessed a vigorous healthy body, and a well-trained mind. His family was well and favorably known in the community, which gives no small advantage in a conservative society. He had received a valuable education, probably more valuable thougli different from that which men are now receiving. He had come into close contact with men of high ideals and good methods of work, he possessed the methods by which knowledge is obtained and had already made important contributions which gave him a reputation. He further had enthusiasm and the art of inspiring this in his students, native kindness of heart, a candid, open disposition, a great capacity not only for making friends, but for arousing the feeling of affection, and a fine sense of hiunor, never used to hurt, which made him a sought and delightful companion. He wTote well and easily, expressed himself simply and clearly, leaving no doubt as to the meaning, and the matter was well arranged. In spite of the number of these early articles, they all show care in preparation. He had also great capacity for work, and ambition, witii a definite end in view. For such a man there are always opportunities waiting, and Osier found them in ilontreal, as he would have found thcni anywhere, c\cn witli his friend Bovell in Nevis.

In the latter part of 18M, in addition to his position in the university, lie was made physician to the Small-pox Hospital, which gave him opiwrtunities for clinical study and an interest in the disease which he has always retained. With the salary which the position gave he purchased micro.scopes for teaching in the medical school. In 18T6 he published in the Canadian ^fcdical and Surgical Journal three articles on small-pox: (1) "The Initial Rashes of Small-pox"; (2) "On Hemorrhagic Small-pox"; (3) "A Form of Hemorrhagic Smallpox," which are valuable confriliutions to our knowledge of the di8ea.«e. They show accurate observation, good clinical judgment and a marked power of differentiation of conditions both clinical and pathological. He had studied skin diseases with Tilbury Fox in England, and the influence of these studies is shown here. It was an important work for him. for


•Osier did not usually use such ambiguous expressions: the presence of such masses in the blood might be regarded as one of the disadvantages of economic poverty.


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in the small-pox hospital he first acquired the power of close observation of skin lesions and the ability of differentiation and description which was afterwards such a marked feature in his clinical work.

A very interesting article appeared in the same journal in 1876, " On the Pathology of Miner's Lung." It is based upon the examination of the lungs of a coal-miner who died in the small-pox hospital, and in whom the condition was verj' marked, and several other cases showing various degrees of the same condition. It is a good piece of work, shows much originality, and is to be regarded as the best article in English on the disease, which was first described by Pearson in 1813. In this article for the first time the large mononuclear phagocj'tes were differentiated from the smaller corpuscles, and Osier showed that the large cells were those most actively concerned in the phagocytosis of the carbon. He says : " One most curious specimen was observed. On an elongated piece of carbon three cells were attached, one on either end and a third in the middle, so that the whole had a striking resemblance to a dumb-bell. I could hardly credit this at first, until by touching the top cover and causing the whole to roll over, I quite satisfied myself that the ends of the rods were completely embedded in the corpuscles and the middle portion entirely surrounded by another." His description of the position of the carbon in the lungs and its relation to the lymphatics is accurate. He gives a figure of a microscopic piece of coal which was found and which showed the scalariform tissue of ferns, thus proving its origin, and another piece with two holes representing the dotted cells of firwood. In conclusion, there is an experimental study of the effect of foreign bodies in the tissue made by the injection of India ink into the axillae and lungs of kittens.

The study of the blood plates gave him a familiarity with blood examination which he utilized in the study of anaemia, and there are several papers on this in 1877. The first of these, " A Case of Progressive Pernicious Anaemia," was published in association with Dr., Gardner in the Canadian Medical and Surgical Journal. It is probable that Osier -nTote the paper and was responsible for the blood examination, and the description of the autopsy, which showed the usual conditions found in the disease. It is a good type of medical paper, the descriptions of the blood and of the marrow changes are accurate, and the relation between the blood changes and the marrow, wliich had been described by Cohnheim in the same year, is confirmed. An abstract of this article, with detailed measurements of the various blood cells " Ueber die Beschaffenheit des Blutes und Knochenmarkes in d. progressiven pernicioser Anamie" was published in the Centralblatt f. d. med. Wissensch., 1877, No. 15, and a second article in the same journal on the study of a second case. Another article on the same subject, in which he was associated with Dr. Bell, appeared in the Transactions of the Canadian Medical Association, and here he gives Addison the credit for having first recognized and described the disease under the name of idiopathic ansemia. There is a final article in the following year, " Entwickelung von Blutkorperchen im Knochenmark


bei pernicioser Anamie," Centralblatt f. d. med. Wissensch., 1878, in which he confirms Neimiann's results of the study of blood formation in the marrow.

During this period also he wrote a number of articles on comparative pathology, the first on " Verminous Bronchitis in Dogs, with Description of a New Parasite " was published in the Veterinarian, London, 1877. He found this parasite in the bronchi in an epidemic among dogs in Montreal. He gives an accurate description of the parasite, and the points of differentiation. It has been accepted as an original description and credited to him, the name Filaria osleri being one of its synonyms. The only mistake he made was in classing the organism among the strongyli and not the filarise, the main difference being that the strongylus is oviparous and the parasite described by him produces living embryos. The lobular pneumonia which he found, associated with the presence of the parasites in the bronchi, he referred to the inhalation of inflammatory products produced by them. The paper closes with a discussion of the mode of infection which he thought was by the direct inhalation of the dried embryos and it would have been more valuable had he subjected this theory to experimental test. There is also a paper on Trichina spiralis (Canadian Journal of Medical Sciences, 1876) which gives a good description of the disease and the life history of the organism, but which does not add anything new, and there are a number of other articles which appeared at intervals up to the time he left Montreal for Philadelphia. In the last article, " An Investigation Into the Pork Supply of Montreal," wliich was conducted in association with one of his students in the veterinary school, A. W. Clement, who was afterwards well known in tlie early days of the pathological laboratory of the Johns Hopkins, he speaks of having made 900 autopsies in Montreal, in four of which trichinffi were found.

There are two interesting addresses in the period. The first was to the graduating class in medicine in 1875. It was probably the habit of the faculty to place the burden of such an address upon the youngest member. Eeading over this address, one is conscious that Osier had very little interest in it. Probably he looked over other addresses given on similar occasions and they must have been a very poor lot. He gives the usual good advice to the students, telling them to keep up their reading, to observe patients well, and even at this early period introduces Sir Thomas Browne, but he does not use him effectively. It seems by far the worst thing he ever published ; there is no trace of humor in it, and no indication of the remarkable power he showed in his later addresses.

The second address is of a totally different character. It represents much more work and care in preparation, as though Osier had concluded that giving addresses was to be part of his future work and that they should be good. There are a number of quotations, many of them apt, the usual good advice to students, and some really inspiring sentiments, well expressed. For instance, " You will have moments when the way appears rugged, and the outlook dark, but never fear; others have succeeded in tlie face of the same difficulties, and with patience and perseverance you will do so too. Banish the future. Live


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only for the hour and its allotted work. Think not of the amount to be accomplished, the diflBculties to be overcome, or the cud to be attained, but set earnestly at the little task at your elbow, letting that be sutlicieut for the day, for surely our plain duty is ' not to see what dimly lies at a distance, but to do what lies clearly at hand.' " It is difficult to give a student better advice than this. Of the family physician he says " But while the soldier and the statesman win honor and fame, the family physician will draw to himself the love and gratitude of manifold hearts; he will have no enemies, martial or political; and his labors, if directed by a wise and prudent skill, will be for the welfare and benefit of all."

From 1872 to 1878 was a great period in medicine; it just preceded the bacteriological era in whicli the nature of infection was established; Pasteur had completed his studies on fermentation and the silk-worm disease and was in the midst of his revolutionarj- work on anthrax ; Koch, an obscure countr)' physician, was beginning his studies on bacteria and


developing the methods which made their scientific study possible; Virchow was at the height of his fame; Cohnheim and Weigert had begun in Breslau and in Lcipsic their remarkable work; a new university in Strasburg had just been established which became famed through its products ; physiology, in England and under Ludwig in Leipsic, had taken a new life; Lister in England was in the midst of the work which revolutionized surgery; the modern medical clinic was slowly being established, and medicine was becoming scientific, its procedures based upon knowledge and not conjecture; new ideals and methods in medical teaching were being everywhere introduced; America was feeling the enormous stimulus of the promise given in the estiiblishment of The Johns Hopkins Tlniversity. Osier was under the stimulus of all the new life. He^ could easily have become a great scientist, but he chose the path which led to the formation of the great clinician which he became ; a worthy associate of the great men wlio have made English medicine famous.


OSLER AS A PATHOLOGIST

Bv William G. MacCallim


The statement may be safely ventured that no clinician in English-sjwaking countries has had at his command such a wide and detailed knowledge of morbid anatomy as Osier. There may be different opinions as to the reasons for his greatness as a teacher, as a man among men and in other ways, but hardly more than one opinion as to the foundation of his greatness as a clinician.

In the two small volumes of Pathological Reports printed at the McGill Universitj', in a complete collection of reprints of his papers beginning in 1877, and in the first edition of his Practice of Medicine, the development of his knowledge of pathological anatomy may be clearly traced. Throughout there is no diminution in his keen enthusiasm and little change in the character of his interests, but there is an extraordinary advance in the clarity of his ideas keeping pace with the discoveries of the European and other workers in the field of patholog)'.

During a period of more than 40 years — years that have witnessed the most phenomenal advances in medicine — his attention was very largely devoted to these studies which were constantly maintained as the basis of his more purely clinical work.

Osier's training lay not iti chemistrj- — the growth of i)acteriology found him a spectator and experimental metiiods seem to have had little attraction for him. Nor did he attempt any protracted researches in patholog)' for its own .<ake. Instead his interest was and has always been in the observation of rather gross and striking anatomical alterations usually on account of the sjTnptoms which they produced and not with the aim of investigating their minute details or their ultimate causes. In all this he has shown himself critical and sane and quite unwilling to pursue what seemed a fantastic theory tinless convinced by definite proofs. He was skeptical of the


malarial organisms of Laveran for a time until he became familiar with them himself and demonstrated them in this country. He would not believe that the micrococci found in acute endocarditis were anything more than accidental invaders until he had convinced himself by actual studies of the valves.

But in his early days he did not wait for others to unearth new facts. He pressed ahead alone in the investigation of une.xplained phenoniciia and was perhaps the first to see clearly the blood platelet which he described in 1874 as the third corpuscle of the blood.

He was early in the field with his studies of the bone-marrow in pernicious aiin?mia and evidently recognized megaloblasts and other cells at a time when such recognition must have been very difficult.

But from the beginning he appears to have been more readily interested in the physical aspects of morbid anatomy, especially in so far as there could be traced a chain of events. In the first volmne of the McGill reports he describes a case of idiopathic hypertrophy of the heart, the topogra])hy and effects of various aneurysms, cases of phthisis, pneumonia, cancer, ulcer of the duodenum, typhoid fever with perforation, incarceration of the ileum, etc. In the second volume is found a series of similar miscellaneous cases. Some of the.se were remarkable as, for cxam])lc, the instance of aneurysm of the hepatic artery. It is to be noted that even in his discussion of these cases he showed that the special literature of foreign countries was quite at his commnnd. He met with a case of hypertrophic cirrhosis of the liver — the first in his experience — and while he was studying it there appenrcd Hanot's thesis, the importance of which in relation to his own case he recognized at once. From this period at McGill University where he performed a great many postmortem examinationa


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and supervised them in tlie hands of students he acquired much of his familiarity with morbid anatomy. It is his spirit of serious research which has remained to inspire the splendid work in pathologj' carried on ever since in that school and his preparations formed the foundation of their magnificent museum of pathological anatomy.

Osier was impressed from the beginning with the usefulness of considering together a group or series of similar cases. There is something statistical about this plan, but since no two cases of any disease are precisely alike in all details, much light comes from the study of a series. This method may be traced through the work of his later years and in that of all of his pupils. It is apparent in all the papers of his Philadelphia and Baltimore periods and reveals his careful method of preserving minute notes on all he saw, for some of the recent studies refer back to cases encountered in the Montreal days.

Comprehensive papers on endocarditis, tuberculous pleurisy, peritonitis, pericarditis and abdominal tumors, followed and later similar analyses of long series of cases of typhoid fever, meningitis, erythema multiforme, Addison's disease, myxoedema, splenic anaemia, malaria and many other conditions. In these there is a sustained and constant interest in the pathological anatomical changes, but rather in their relation to the general history and symptomatologj' of the disease than for their own sake. The details of the causes and development of the lesions are discussed only briefly, but an important outcome of such studies was in several instances the more definite outlining of disease entities from the recognition of the repeated occurrence of the same group of symptoms and pathological alterations.

This has long been the first great step in the study of disease and it is for this reason that many of the great names in medicine are associated with the diseases in which they have been the first to discern the constancy of the association of several features. The ability to see these relations and to connect a group of phenomena with a common cause is given to few. It is only less difficult than to discover the hidden cause of disease.

On the other hand, with diseases well recognized by everyone. Osier's interest in new manifestations and new combinations of symptoms or lesions has been unfailing. After the long period of observation and study of typhoid fever in which he associated with himself all the men on his staff he analyzed


the disease from every point of view. However, in these studies only the grosser anatomical changes are considered and there was no special advance in the knowledge of the bacteriology or immunity reactions of the disease.

Syphilis has always claimed much of his attention and interest, although he has written little on it except in the form of test-book articles and papers concerning aneurysms. Nevertheless, the multifarious manifestations of this disease have formed a prominent subject in his teaching and he believed that there was much in tlie statement that he who knew all of syphilis knew nearly all of medicine.

In his later years he worked no longer at actual dissections and no longer studied the details of pathological anatomy with the microscope, but he never slipped into that state of confidence in unaided clinical diagnosis which would allow him to remain away from the autopsy room. Instead he came there not only to follow minutely the dissection of cases from his own hospital service, but to learn what he could from those belonging to the surgical and other services. His presence was an inspiration that led us to great efforts toward careful work, and his long experience and unfailing memory, which enabled him to recall the conditions found in a whole series of similar cases, gave us a background upon which the case under investigation stood out.

The pathological anatomy of his text-book is of this quality and it is for that reason that the students in pathology are told to read it. No one has written more systematically, or more concisely of the changes underlying the manifestations of disease ; no one has recognized more clearly the boundary line between the known and the imknown or sifted more judiciously and unerringly the truth from error. His long habit of considering each disease on the basis of knowledge gained from the analysis of a large series of cases has allowed him to estimate justly the relative frequency and importance of each feature and to state them in the most helpful and orderly sequence. This clearness of vision with regard to the actual natural history of disease, always referring to a well-remembered series of cases, helped to make his teaching a memorable delight to his students. His actual contributions to our knowledge of pathology are many and important, but even more valuable to the science of medicine in general is his example, in that he has built his clinical medicine solidly on a foundation of pathological anatomy.


OSLER, THE TEACHER

By W. S. Thater


Observe, record, tabulate, communicate.

Use your five senses. The art of the practice of medicine is to be learned only by experience; 'tis not an inheritance; it cannot be revealed. Learn to see, learn to hear, learn to feel, learn to smell, and know that by practice alone can you become expert. Medicine is learned by the bedside and not in the classroom. Let not your conceptions of the manifestations of disease come from words heard in the lecture room or read from the book. See, and then reason and compare and control.


But see first. No two eyes see the same thing. No two mirrors give forth the same refiection. Let the word be your slave and not your master.

Live in the ward. Do not waste the hours of daylight in listening to that which you may read by night. But when you have seen, read. And when you can, read the original descriptions of the masters who, with crude methods of study, saw so clearly.

Eecord that which vou have seen; make a note at the time;


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do uot wait. " The flighty purpose never is o'ertook, unless the deed go with it."

Memory plays strange pranks with facts. The rotks and fissures and gullies of the mountain-side melt quickly into the smooth, blue outlines of the distant panorama. Viewed through the perspective of memory, an unrecorded observation, the vital details long since lost, easily changes its countenance and sinks obediently into the frame fashioned by tlie fancy of the moment.

Always note and record the unusual. Keep and compare your observations. Communicate or publish short rxoU^s on anything that is striking or new. Do not wast€ your time in compilations, but when your observations are sufficient, do not let tliem die with you. Study them, tabulate tiiem, seek the points of contact which may reveal tlie underlying law. Some tilings caji be learned only by statistical comparison. If you have the good fortune to command a large clinic, remember that one of your chief duties is the tabulation and analysis of the carefully recorded experience.

The collection and study of your own observations is much, but he who works in his own small compartment leads, after all, a restricted and circumscribed life. Go out among your fellows, and learn of tliem. The good observer is not limited to the large hospital. The modest country doctor may furnisli you the vital link in your chain, and the simple rural practitioner is often a very wise man.

Respect your colleagues. Know that there is no more highminded body of men than the medical profession. Do not judge your confreres by the reports of patients, well meaning, perhaps, but often strangely and sadly misrepresenting. Xcvcr let your tongue say a slighting word of a colleague. It is not for you to judge. Let not your ear hear the sound of your voice raised in unkind criticism or ridicule or condemnation of a brother physician. If you do, j'ou can never again meet that man face to face. Wait. Try to believe the best. Time will generally show that the words you might liave spoken would have Iwen unjust, would have injured a good man, and lost you a friend, and then — silence is a powerful wcaimn.

When you have made and recorded the unusual or original observation, or when you iiave accomplished a piece of researdi in laboratory or ward, do not be satisfied with a verbal communication at a medical societ}-. Publish it. Place it on permanent record as a short, concise note. Such communications are always of value.

Mix with your colleagues; learn to know them. But in your relations with the profession and with the public, in everything that pertains to medicine, consider the virtues of taciturnity. Look out. Speak only when you have something to say. Commit yourself only when you can and must. And when you speak, assert only that of which you know. Beware of words — they are dangerous things. They change color like the chameleon, and they return like a boomerang. Do you know the story of the young physician, about to enter ])ractice, who was sent by his father to his old friend, Sir William Stokes, for advice ? A pleasant conversation, and, at the door


way, a last word : " Charley, don't say too much." Then, at the gate, a voice: "Charley, come back a minute: I'm very fond of you, my boy ; don't do too much."

" Don't do too much." Keniember how much you do not know. Do not pour strange medicines into your patients. Our greatest assistance is given by simple physical and mental means, and by the careful employment of such drugs as have been adequately studied, with regard to the action of which we have real information. Do not rashly use every new product of which the peripatetic siren sings. C-onsidcr what surprising reactions may occur in the laboratory from the careless mi.xing of unknown substances. Be as considerate of your patient and yourself as you are of the test-tube.

Familiarize yourself with tlie work of others and never fail to give credit to the precursor. Let every student have full recognition for his work. Never hide the work of others under your own name. Sliould your assistant make an important observation, let him publish it. Through your students and your disciples will come your greatest honor.

Be prompt at your appointments; that is always possible. Many are alwa)'s late at a consultation; few miss a train. There is no excuse for tardiness.

Live a simple and a temperate life, that you may give all your powers to your profession. Medicine is a jcahius mistress ; she will be satisfied with no less.

Save the fleeting minute; do not stop by the way. Leani gracefully to dodge the bore. Strike first and quickly, and before he has rec-overed from the blow, be gone; 'tis the only way

If you can practice consistently all this, .... and then, if you can bring into corridor and ward a light, springing step, a kindly glance, a bright word to every one you meet, arm passed within arm or thrown over the shoulder of the happy student or colleague; a quick, droll, epigrammatic question, observation or appellation that puts the patient at his ease or brings a pleased blush to the face of tlie nurse; an apprehension that grasps in a minute the kernel of the situation, and a memory teeming with instances and examples that throw light on the question ; an unusual power of succinct statement and picturesque expression, exercised quietly, modestly and wholely without sensation ; if you can bring into the lecture room an air of perfect simplicity and directness, and, behind it all, have an every-ready store of the most apt and sometimes surprising interjections that so light up and emphasize that which you are setting forth tliat no one in tlie room can forget it; if you can enter the sick-room with a song and an epigram, an air of gaiety, an atmosphere that lifts the invalid instantly out of his ills, that produces in the waiting hypochondriac so pleasing a confusion of thought that the written list of questions and complaints, carefully compiled and treasured for the moment of the visit, is almost invariably forgotten ; if the joy of your visit can make half a ward forget tlie symptoms that it fancied were important, until you are gone; if you can truly love your fellow, and, having said evil of no man, lie loved by all; if you can select a wife with a heart as big as your own.


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whose generous welcome makes your tea-table a Mecca ; . . . . if you can do all this, you may begin to be to others the teacher that " the cliief " is to us !

An eye whose magic wakes the hidden springs Of slumbering fancy in the weary mind, A tongue that dances with the ready word That lilce an arrow seeks its chosen goal, And piercing all the barriers of care, Opens the way to warming rays of hope. A presence like the freshening breeze that as


It passes, sweeps the poisoned cloud aside.

An ear that 'mid the discords of the day

Swings to the basic harmonies of life.

A heart whose alchemy transforms the dross

Of dull suspicion to the gold of love.

A spirit like the fragrance of some flower

That lingers round the spot that this has graced.

To tell us that although the rose be plucked

And spread its perfume throughout distant halls.

The vestige of its sweetness quickens still

The conscience of the precinct where it bloomed.


OSLER AND THE STUDENT

By Thomas E. Beowx


In a lay sermon delivered before the Yale students a few years ago in which Dr. Osier offered them " A way of life " — " a path in which the wayfaring man cannot err, a life in daytight compartments, the main business of which is not to see dimly at a distance, but to do what lies clearly at hand," and which had been the starting point of his life-habit — he began with two words which show more plainly than many pages could his real relation to the student — for these two words were " fellow students." In these words lay the real reason for his unique and lasting influence upon all who studied with him, for he, with his vast experience, his wonderful insight, his profound knowledge, his poetic vision, his deep sympathy, was still always at heart the student, always studying, always delving more deeply into the mysteries of health and of disease, giving always, yet always ready to receive, teaching, yet ever ready to learn.

To those privileged to be his students in the early days of the medical school — a truly golden age to each and every one of the small, though ever growing group, he preached, as he lived, a glorious philosophy of life, a joy in work, doing the day's tasks, " living for the day and for the day's work," with a wonderful belief in his fellowmen, never losing faith becau.se some had failed him, giving without stint his best to everyone with no thought that some might prove unworthy of the trust. He felt with Goethe that "the classical is health, and the romantic disease," and he strove for the one with the Greek love of perfection, while for the other he had the passion of the truly adventurous .spirit sailing on uncharted seas. To us who were his students in the early days of The Johns Hopkins Medical School, his memory is so vivid, so fresh, that it seems but as of yesterday when he worked and played in our midst, and we have but to close our eyes to see him in fancy, almost as clearly as we saw him in fact in the late 90's, the great teacher and the great student in his manifold relations to his students. Now we see him riding to the hospital in the Monument Street car, and to the group about him prophecying with keen yet ever kindly vision the ills — physical, mental and spiritual of the derelicts en route to the dispensary, here in the wards demonstrating the complex psychology of Giles de la Tourette's disease, as exemplified by a poor bit of .sodden humanity whose coprolalia but exemplified — in a way a bit embarrassing at times it is true — the symptom-complex he was discussing, or in an alcove ofP the ward playing with little


Theophilia as she was emerging from the night of cretinism into the day of normal happy childhood imder his skillful guidance; now in the class-room of the dispensary — for he loved the polyclinic, and believed in its wonderful potentiality as a teaching factor — with one deft touch solving a case of great complexity, or bringing from his vast storehouse of knowledge the one last link needed in a disease-picture hitherto poorly understood, listening, suggesting, directing, teaching, guiding both student and patient, and all the while filling countless scraps of paper with the names of one of the three great teachers of his youth ; now in the clinical laboratory studying a blood specimen, and suggesting to the student some line of original investigation which might, perhaps, light into flame the doi-mant investigator and research worker ; now in the autopsy room studying in death the puzzles that he had helped to unravel during life ; now walking through the wards and corridors of the hospital with a smile or an epigram for every doctor and nurse who pasfsed, a kindly word, and his ever-stimulatiHg psycliotherapy — encouragement, optimism, hope — to every patient he saw ; in his myriad activities always making each student feel that he also was but a student of health and of disease, of men and of morals, and yet such a student as to fire our minds, our souls and our bodies to renewed efforts so that we might, in some measure at lerast, prove worthy of this fraternity. To us who were privileged to be his students — his fellow students in those days, he was — and still is — always our inspiration and always our model. In him the fire burned so brightly that no dross nor tinsel could survive its pure flame, and he was ever " our cloud by day, our pillar of fire by night." With Bossuet he taught that " le bon sens est le genie de I'humanite," and he gave to us " a golden age which never rusts, a spring which never fades, eternal youth." Always true to himself and to others, he made us think daily of words of his beloved Plato " Whence has the progress of cities and nations arisen if not from remarkable individuals coming into the world we know not how and from causes over which we have no control ? "

Is not the greatest tragedy of growing older the loss of our illusions — the discovery sooner or later that so many of the gods of our youth, Jove-like Olympians of those days when our world was young and pregnant with possibilities, have, after all, but feet of clay? But with "the chief" this could


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never be. The more we learned, the more wonderful his boundless knowledge seemed ; the wider our vision, the more limitless his appeared.

Everyone who has ever been his student is. as it were, still studying with him, or peripatetiiiilly following his footsteps as he journeys through life, always teaching some new lesson of niedieine or of living. Every honor that has befallen him has enriched us and made us prouder of our brotherhood ; every step upward or onward of his has made our paths easier and


the heights seem not so far away. We have rejoiced in his happiness and in his honors, and perhaps he has been helped in his sorrows by the knowledge that they are ours as well, for he has shown us how work could be made play, and how the real could be made ideal. Because of him our lives have been better, our successes more real, our failures less hard to bear, for through the tangled skein that sj)ells life each of us knows that in him be bus, and will always have, a teacher, a friend, and a true fellow student to tiic end of the ciiaptcr.


OSLER AND PATIENT

Bv TllcMAS ilcCliAE


111 all tile relations of physician to patients there are two sides — the strictly medical and the personal. Some have a blind spot for the latter, but taking the profession as a whole these are in the minority. No one could work in close association with .Sir William Osier without realizing that both sides were well developed in him. There was always the desire to do the best for the |>atient in a medical way, but the personal aspect was never forgotten. Patients were patients and not cases. Interest in the personal side was much in evidence and it was the exceptinn for his patients to fail in a])])reciating this. There was always a great charity for the weakness of human nature ami there were neither unkind nor hasty judgments. We know how often in bis addresses he has em])hasi/ed tlie imjK)rtanc-e of this quality.

To the writer was given the opjjortunity of knowing the relation of Sir William Osier to the patient botii by |)ersonal e.xperience and by the oltservation of others. The former came by my having an attack of typhoid fever while a Iwnse orticer in The Johns Hopkins Hospital, .\fter the pas.sage of years it is didicult to estimate in detail one's feelings towards bis physician, but the main impression

left on my mind after a long interval is tiiat <>f alisohitc contidenec. His visits were usually short, but when he hail gone there was a feeling that everything was all right. The visit was nearly always marked by some cheering saying or amusing quip.

One in<ident comes to memory with regard to the impression made by him on a patient many years ago; it is also an exani|)le of curious coincidence. Hack in the eighties one of my father's friends was stricken with a malady of which I heard some of the <letaiis dis<-u8.<ed without realizing that they were to \tc remembered. The patient had .\ddison's disea.se with an unusual degree of pigmentation which attracted great



attention ami was naturally commented on by liis friends. I remenii>ered hearing that lie iiad gone to the United States to consult a ]iliysiciaii and had come back R'alizing tliat he could not recover. These matters had apparently been comidetely forgotten, but were recalled when 'i't years later the friend who acconipanietl the patient on the journey said to me: "1 wonder if you could bcl]) me to identify tiie physician wiiom .Mr. .\ consulted in I'iiilail('l|iiiiii. Ills nanic made little iiiiprc»icin nil nic at tin' time." This seemed ratlicr a (lillicult undertaking, but 1 asked wliat lie remembered of the visit. He gave the following details: " The examiinition was very thorough ; he strippeil ilr. .\ and went over him from head to foot. He said very little. (.\t this iKiint the thought of Sir Wililam came to my mind.) When Mr. .\ asked liim as to the outlook, he i^aid, 

Do you think you have enougli of the

grace of (Jod to nnike a clergyman,' or something like tliat. .\t any rate Mr. .\ uiKlerstood the meaning which wMs iiiirmicd ami commented with approval on the way in which it was conveyed." .Nftcrwards I asked Sir William if he was the physician, and found I hat he was and that be rcmcmliered the patient very well. This brings up aiiolber of bis characteristics with regard to patient.s — the marvellous nu'mory which he has of the details regarding nnuiy of them. On oneiK-casion a physician brought a patient to consult him. The ]>bysician began to give the bistfiry when Sir William said : " I -saw Mr. — before with so and .-^o " — mentioning the diagnosis. Both the physician and the patient denied this until Sir William showinl them the notes of the jtrevious visit. It seems almost impossible to miagine that both should have fr)rgotten the consultation, but such was the case. On nuuiy occasions patients came back to the clinic after an interval of years and Sir William could give the details of the bistorv at once.


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In oue of his essays, which gives the title to a book, "Aequanimitas,"' he dwells on the importance of not permitting one's poise to be disturbed or allowing the expression to show what would be better concealed. He practised this in his daily work and many who came in contact with him never realized how much anxiety he often felt, but rarely displayed over patients. This was particularly true if it was a case in which a diagnosis had not been made and in which, therefore, the best treatment was a question of doubt. One such instance comes to mind of a young man with typhoid fever and severe hemorrhages. In this case, of course, we were suspicious of perforation. Sir William made a special trip to the hospital at my request to try and settle this point. The decision was that there was no positive evidence of perforation and exploration was delayed, but the signs of general peritonitis next day showed our error. I remember well his words on the fallibility of human judgment and of the sorrow that one felt when he had judged wrongly.

His influence over patients was marked and especially over those unfortunates whose nervous systems had suffered. As a general rule he did not spend a great deal of time over them in the hospital. However, the results came; in many cases no doubt, largely by faith in him. It has been said by .some that Sir William was not particularly interested in jDsychotherapy, but one might say that he did not need to be — he practised it, not always consciously, perhaps, but always effectively. He had extraordinary patience with querulous patients and it was very rarely that he ever became irritated with them. With the jiatient who was ready to fight and be disagreeable he never argued : " Glad to see you come and glad to see you go " was a favorite answer.

Many interviews with jiatients come to memory. In one the center of the stage was occupied by a nervous woman, to whom something had been said in a very kindly way of the need of self-control. With the tears flowing freely and a handkerchief in active use she said : " Oh, Dr. Osier you misjudge me cruelly." He, standing at the foot of her bed, replied with a serious tone to his voice and a twinkle in his eye : " Madam, I learned early in life never to judge any woman and tliat rule I have strictly kept. Therefore, I cannot have misjudged you. Good morning " — and he was away before she could frame a reply. Later in the day the brunt of his hasty exit fell on me. In a large private ward service it was not possible for him to spend a long time with each patient. To his house officers it was always a source of interest and a good lesson to observe


how he could get into and out of a patient's room without giving a chance for the flood-gates of talk to open. Many patients would lament that they had not been able to tell him this or that. But with this he had a remarkable ability in discerning when the patient needed a special interview and he was always ready to give it.

There was one subject on which he would never listen to a patient, and that wa.s when something was said which reflected on another physician. When the patient began any such statements he showed his displeasure at once and if this was not enough a very sharp rebuke followed. In fact this was about the only thing whicli made him lose patience and was the rare occasion of his showing sternness. The talkative patient was a trial to him — and of whom is this not true ? He used to have a very characteristic look when he escaped and I can remember his delight, after a particularly trying interview of the kind, when I quoted to him from " Kim " : " The husbands of the talkative will have a great reward hereafter." However, he was rarely caught twice by the same person.

Of one class of his patients a word may be said — the doctors. He was consulted by many of the profession and especially in the latter years in Baltimore. This had grown to be a heavy burden, but one which he carried willingly. He never spared himself or thought of his own convenience when something was to be dime for a physician or a member of a physician's family.

Of the attitude of patients towards Sir William much might be said. Perhaps the most striking characteristic was absolute confidence. There was the certainty that there would be no failure from lack of skill or interest on his part. His cheerfulness had much to do with this and the ability to give the desire to fight to those who had lost courage and hope. He was always careful in giving an opinion to put matters simply, so that the chance of misunderstanding would be as slight as possible. In the consideration of what a patient should do he always had in mind what he could do. It was a good lesson to observe the care which he took to avoid saying anything in the hearing of a patient which might cause disturbance or increase anxiety. This was especially marked when the outlook was being discussed and seemed unfavorable. He never forgot to be sure that the patient was not within hearing. In all the giving of advice he was sparing of words and might be described as one of those " who have not the infirmity, but the virtue of taciturnity, and speak not out of the abundance, but the well-weighed thoughts of their hearts.


OSLER AND THE TUBERCULOSIS WORK OF THE HOSPITAL


Bv LoLis Hammax


Dr. Osier's interests were so universal that I fear I run grave risk of contradiction in saying that he showed a particular interest in tuberculosis. I came in contact very intimately with his enthusiasm for tuberculosis study and perhaps for this reason I exaggerate the position it held for him. Certainly


he never tired of reiterating to students the imi)ortiUice of a thorough knowledge of the two great infectious diseases, tuberculosis and syphilis. From the beginning of his career as physician-in-chief to this hospital he studied the tuberculous patients with minute care. The first patient admitted to his


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medical service on Maj' 16, 1889, was suffering from tuberculous peritonitis and one of the first clinical papers he published was upon this aspect of tuberculous disease. In 1903 I undertook at his request a study of all the cases of serous membrane tuberculosis that liad been in tlie hospital up to that date and I noted that many of the histories have copious notes dictated by him.

That this interest in tuberculosis extended beyond the details of clinical observation is shown by the establishment in 1898 of a special fund for the study of tuberculosis, the initiative for its inuujriiration and much of the money coming from Dr. Osier liimself. Dr. Charles D. Parfitt was appointed to conduct the work and a laboratory was equi])ped to afford him suitable opportunity for investigation. Unfortunately after an active year, which gave promise of substantial contributions to the study of tuberculosis, Dr. Parfitt was taken ill and the work was abandoned to be resumed some years later in the laboratory of the Phipps dispensary.

A further evidence of Dr. Osier's unfailing interest in tuberculosis, and his zeal for the dissemination of tuberculosis knowledge amongst the students, is the foundation of the Tjaennec Society in 1900. This was tlie first society in this country and, as far as I know, the first in the world to devote \Uii\f to the study of tuberculosis. I remember clearly the first meeting of the society held in the fall of 1900 in the basement under Ward G. Dr. Osier presided, outlining the aims of the society and explaining the appropriateness of its name; a review of Laennec's life and work followed. Since this date the society has continued to liold regular meetings and it has proved itself an important and stimulating center of tuberculosis interest in the hospital. Unfortunately, there are no records of the early meetings of the society, but I rememlier Dr. Osier's unfailing attendance at all the meetings and his brilliant and stimulating discussions.

Shortly after the establishment of the Laennec Society Dr. Osier with liis peculiar prescience of coming events inaugurated the home visiting of tuberculous patients registering in the dispensary. At first this work was undertaken by medical students. Blanche N. Epler, Adelaide Dutcher and Elizabeth H. Blauvelt successively giving it their service. The study of Miss Dutcher reported before the Laennec Society and published in The Piiiladelphia iledical Journal, December 1, 1900, is, I believe, tlie first contril)ution in this countrj' to lay the proper emphasis ujwn the importance of the jiome in the spread of tulK-rculosis. From this modest beginning grew the .subsequent study and care and supervision of tuberculous patients in the dispensary. Dr. Osier soon enlisted the interest of Mr. Victor Bloede in the work and through his generous support a nurse was employed to visit and instruct patients in their homes. At the same time under liis guidance the first steps were taken towards establishing a special clinic for the tuberculous. .Although no separate rooms were available for this purpose, all tuberculous patients were put under the care of Dr. Hennan Bruelle for detailed study and advice.

It would give a very incomplete impression of Dr. Osier's tuberculosis interests to omit reference to his activities outside


of the hospital. He was always deeply concerned about the social ap])lications of medical knowledge and he played a prominent part in furthering and directing the awakening interest in the control of tuberculosis as a disease of the ma.<ses. For instance, he took a very active interest in tiie Tuberculosis Exposition held in January, 190-1, under the auspices of the State Board of Health, the first exposition of the kind held in this country. Umler his infiuence a remarkable collection of books on tuberculosis were displayed, illustrating the development of our knowledge of the disea.<e from Hippocrates to modem times. Before the collection was dis]wrsed Dr. Osier reviewed it with the medical students, illuminating eacli epoch with his surprising knowledge of the historical aspects of the subject.

In 1903 Mr. Henry Phipps learned of the work Dr. Osier was trying to do with such modest equipment and generously sent $10,000 to support his endeavors. The check came quite unexpectedly and was the means for Dr. Osier to plan at once to materialize one of his dreams. With great enthusiasm he began to develop a special department for the study of tuberculosis and the care of tuberculous patients. Mr. Phipps' additional gift of over $20,000 made it possible to remodel the old stable standing between the dispensary and pathological department buildings into a two-story structure with four rooms on each floor. The building was formally opened at a special meeting of the Laennec Society on February 21, 190."), and the first patients were received on the first of March of the .same year.

Dr. Osier left the liospital the year the tul)erculosis dispensary was opened, but his interest in the dc])artment never ceased. Messages of encouragement and ai)i)reciation came at irregular intervals. Whenever an article ajipearcd by a member of the staff, usually the first and always the dearest recognition was a postal or a brief note da-slicd off in his characti'ristic way. As the dispen.«ary gradually grew into a recognized place in the medical clinic, at every turn of fortune there came his clieering congratulation. It is impossible for me to look back upon tho.se years without the deepest emotion. I do not know if Dr. Osier ever appreciated what these crisp, kin<lly messages flashed from abroad really meant for us, nor am I able adequately to express all we felt. Certainly this much is true, tijey were always the brightest ray of encouragement to our work, the most comforting reward that made us forget the long dreary hours of labor and the discouragement and doubt that often assailed us.

Since the first few years the tuherc\iIosis dispensary iias grown steadily in im])ortance. Further gifts from Mr. Phipps allowed the hospital to adcl to the building in 190S, dnul)ling its capacity. Ilecently the generosity of .Mr. Kenneth Dows has further improved the building and lias jiut the research department of the dispensary upon a sound footing. The tuberculosis clinic is a ver\' different department now from the modest dispensary arrangements of a physician without a room to work in and with no other equipment but his st<'thoscopc. But this is the fruit that has gro\m from tliat tiny seed of interest and enthusiasm planted by Dr. Osier many years ago.


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INFLUENCE ON THE RELATION OF MEDICINE IN CANADA AND THE UNITED STATES

By Thomas B. Futcher


Sir William Osier has done more than any other member of our profession to bring about cordial and intimate relationships between its members in the United States and Canada. A Canadian by birth, a graduate of McGill University, Canada's most distinguished medical representative, and a man with a most magnetic personality and great breadth of spnpathies and interests, it is only natural that he should have exerted a most potent influence in encouraging close associations between the members of the profession in the two countries. Particularly was this the case after his call to Philadelphia in 188i, and to Baltimore in 1889. While this bond has naturally been more intimate between internists, his influence indirectly brought about a closer contact between the members of the other specialties.

Altliough Osier was graduated in medicine from ilcGill University, he was born at Teciunseh, Ontario, on July 13, 1849, and was educated at Trinity College, Toronto. Various members of his family, leaders in their respective professions, have resided in the latter city. As his reputation grew, it was only natural that his influence on the profession in the two older provinces of Canada should have been very great.

After his graduation from McGill in 1872, he sjjent the ue.xt two years in research work abroad, at University College, London, and at Berlin and Vienna, where he formed associations with such men as E. A. Schiifer, Virchow, Nothnagel and others. While abroad, he published in 1873 his researches on the blood platelets in which he established their corpuscular character. Upon his return to Montreal in 1874, he was appointed professor of the institutes of medicine, at McGill University, a position he filled until 1884. During this period, he was brought into intimate association with his old teacher, Robert Palmer Howard, who was professor of medicine and dean of the medical faculty, and with those able clinicians, Ross and MacDonnell. His natural bent for research and investigation, had been further stimulated by his experiences abroad. A full appreciation of the importance of the microscope in medical research led, upon his return, to its more extensive adoption in the laboratories of McGill. While there, Osier laid the foundation of his keenness as a clinician, through his recognizing the great importance of following the fatal cases to the autopsy room, performing many of the necropsies himself. These investigations resulted in the publication of numerous important contributions to medical literature. Among these may be mentioned his paper in which mycotic aneurisms in association with ulcerative endocarditis were described for the first time, and his account of the ball-valve thrombus at the mitral orifice, which also was the first recorded case.

He was very much interested in comparative pathology, and performed many autopsies on lower animals with that keen veterinarian, Clements, who later went to Baltimore, where he died an untimely death from myocardial disease.


Many of Osier's students of this period are scattered througliout Canada and the United States, and they look back with 2ileasure and profit to the training and stimulus they received under him at McGill. One of the powerful influences he possesses was manifested, even in these early years, through his readiness to report interesting observations before local medical societies and provincial medical associations, and to encourage others to do likewise.

Osier's contributions to medical literature while at McGill, and his papers read before medical societies in the United States, naturally attracted a great deal of attention, and, when in 1884 the University of Pennsylvania was seeking the best trained man to fill the chair of professor of clinical medicine, Osier was its choice. While in Philadelphia he was brought into close association with such men as Weir Mitchell, William Pepper, Tyson, Musser, Keen, Wilson and others. His influence on medicine in the United States was very marked even during this Philadelphia sojourn from 1884 to 1889. He was one of the original members of the Association of American Physicians, which was organized in 1886 with Francis A. Delafield as its first president. He always took an active interest in the annual meetings of the association, contributing nimierous original papers and entering into the discussions. He was himself its president in 1895.

While at the University of Pennsylvania, Osier's contributions to medical literature were nimierous and important. Much of his material for his monograph on the " Cerebral Palsies of Children," published in 1889, was gathered during this period. His experience at Blockley, that wonderful storehouse of clinical and pathological material, provided him with a mass of data later freely utilized in the preparation of his text-book.

In 1889, as the construction of The Johns Hopkins Hospital was nearing completion, the trustees of the university and hospital, seeking the best man to fill the chair of professor of medicine in the university, and the position as physician-inchief to the hospital, at once thought of Osier, who was then considered the most brilliant clinician available. The offer was tendered and accepted, and he was on duty when the first patient was admitted to the hospital on May 10, 1889.

It was during his period of residence in Baltimore from 1889 to 1905 that Osier's influence on medicine in the United States and Canada was chiefly exerted. In making appointments to his hospital staff, graduates of medical schools in both the United States and Canada shared the privilege of working under him. Owing to his close affiliations with teachers in the Canadian medical schools, it was only natural that these men should be appealed to from time to time to supply assistants for its interne staff. His first resident physician was Lafleur, of McGill, who during his tenure collaborated with Councilman in the publication of their important monograph on amoebic dysentery. Lafleur, as have other assistants, returned


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to Canada and carried with him to McGill and the Montreal General Hospital the stimulus and methods acquired while under Osier. Hewetson, also of McGill, soon followed Lafleur as an assistant. The unfortunate development of tuberculosis prevented him from pursuing what promised to be a brilliant career. Thayer, of Harvard, who now holds the chair in medicine on the whole-time basis, succeeded Lafleur as resident physician and served until 1901.

J. E. Graham, who was for many years professor of medicine at Toronto University, an excellent clinician and a man much beloved by his students, was a close personal friend of Osier. Through him several Toronto University graduates became assistants of the latter. Among these may be mentioned. Barker, Parsons, Thomas McCrae, the late John McCrae — the immortal composer of " In Flanders' Fields, Gwvn, and the writer. It may be of interest to note that all these, with one exception, were previously resident physicians during the summer months at the Robert Garrett Hospital for Children at Mt. Airy, Md., which was under the direction of Dr. Walter B. Piatt. Barker, later succeeded Osier, as professor of medicine. The writer, and Thomas McCrae, in turn succeeded Thayer as resident physicians. W. G. MacCalluni, now the professor of pathology at Johns Hopkins, although a medical graduate of this university, but a graduate in the aca'Hemic department of the University of Toronto, was, after graduation, an assistant on Osier's staff. Mention is made of these various Canadians to point out how Osier acted as a magnet to draw them from across the border to Baltimore, and to emphasize the fact that they have, through their "chief," indirectly constituted an important link helping to keep up intimatfi associations between the profession on both sides of the line.

Following Tliomas McCrae, the resident physicians, with the exception of B. A. Cohoe, a medical graduate of Toronto University, who served from June to Septeniher, 1908, have all been graduates of The Johns Hopkins Medical School. They have been in succession, Rufus I. Cole, Charles P. Emerson, Thomas R. Boggs, Frank J. Sladen, Paul W. Clough and the present occupant, Arthur L. Bloomfield. Cole was the only one of these who served as resident physician during Osier's occupancy of the chair of medicine, although Emerson and Boggs were assistant resident physicians under him before he left for Oxford, in 1905. Osier's ideals and influence have


been disseminated by this group of resident physi(Jians in tlie various fields in which their activities have been ca.st.

The first edition of Osier's " Principles and Practice of Medicine " appeared in 1892. This, and the subsequent seven editions, have been the standard text-book in medicine used by students and practitioners in both the United States and Canada. The influence of this work, with the fascinating and practical way in which the various diseases were treated, has been very great on the professions of both countries. The same can be said for the two editions of " Jlodern Medicine," of which he was chief editor, Thomas McCrae being associated with him.

Throughout Osier's professorship at Johns Hopkins, courses to post-graduates were given yearly. The medical school was not opened until 1893, and under-graduatc instruction in medicine consequently did not begin until 1895, so that, up to that year, post-graduate instruction was the only teaching conducted in the medical wards. Osier's ward clinics and clinical lectures were attended by physicians from all parts of the United States and Canada. Members of the profession rubbed shoulders, gained invaluable clinical experience, and formed professional ties and friendships which have continued ever since.

Although domiciled in the United States, the Canadian profession always felt that it had a personal claim on Osier. His trips to Canada to see his family in Toronto, to consult with physicians, to read papers before societies in various parts of the Dominion, and often to spend his vacation on the lower St. Lawrence, enabled him to keep in close touch with the profession of his native land and to exert a strong influence on its members north of the border.

Almost as important a sphere of influence as The Johns Hopkins Hospital was Osier's home at 1 West Franklin Street, where physicians from both sides of the line were always welcome, and where they were ever made to feel at home by the " chief " and his gracious wife, now Lady Osier.

In 1905 Osier was called to Oxford to occupy the chair of Regius Professor of Jledicine in that university. His interest in the medical profession of both countries has not a whit abated. The home of Sir William and Lady Osier, at 13 Norham Gardens, has been almost a daily rendezvous for the khakiclad medical officers of the American and Canadian Expeditionary Forces during the last two years of the world's war.


OSLER AS A CITIZEN AND HIS RELATION TO THE TUBERCULOSIS

CRUSADE IN MARYLAND

]',v lIiNRY Barton Jacobs


Though Osier like Nathan Smith, Austin Flint and Marion Sims and the philosophers of old is essentially a peripatetic, a medical nomad, yet wherever his feet may take him. there he establishes and identifies himself, interests himself in local conditions and undertakes the responsibilities of citizenship.

In the course of his wanderings Baltimore has had the privilege and the profit of halting his onward steps for fully


sixteen years. Here he came in the vigor of his promising 40 years, trained and ready, not to say anxious, to jump into the life of his new surroundings. Many paths there are which lead to useful citizenship — Osier cho.se one peculiarly his own, and followed it consistently and unfailingly, guided only by the unswerving conviction that whatever he might do to advance and improve conditions in the profession to which he was


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allied, in that way alone could he be of the greatest benefit, not only to those immediately under his tutelage or care, but to the city and to the nation at large. In his final address on leaving Baltimore he says " I have lived my life in my beloved

profession I have never departed from my ambition to

be first of all a servant to my brethren."

The advancement and improvement of medicine and service to his fellows, therefore, is the primary path of his endeavor. The wayside results of such a course pursued with intensity, with kindness, with sympathy, with laughter and joke, with good fellowship and hospitality, also with hard study and thought and work, diligently and persistently, year by year, are quite unusual, and lead as is only natural to wide friendships, extraordinary and general influence, both with individuals and with peoples.

Scarcely had he arrived in Baltimore in the spring of 1889 when he was asked by the officers of the State ]\Iedical Association, the old Medical and Chirurgical Faculty of Maryland, to deliver the oration at the annual meeting of the society to be held in April of that year. This invitation he accepted, choosing for his topic " The License to Practice." At this period it should be recalled there were in Baltimore no less than four or five medical schools with two-year courses of study for a degree to practice, and this degree the only license required. The argument Dr. Osier made in his address was so cogent, so direct, so illustrative of the evil conditions existing that immediate steps were taken by the leaders of the medical profession of the city and state to liave prepared a legislative Bill for the appointment of medical examiners whose duty it should be to examine candidates, and to issue to the successful ones licenses to practice. This was Dr. Osier's first effort in Maryland toward the advancement and improvement of medicine, and coincidently his first pronounced effort in good citizenship. As a farther resultant the University of Maryland decided to lengthen its course of medical study and to raise its standard. Moreover, the seed was growing so fast that in February, 1890, a meeting of representatives of all the medical schools of Baltimore decided to request delegates, from the medical schools of the country, to meet in JSTashville with the idea of raising the standard of medical schools all over the United States. At this conference an agreement was reached for a three-year course and other reforms.

The Legislature of 1890 passed the Bill for the appointment of a board of medical examiners, a bill which looked to the betterment of medical practice in Maryland and to the general elimination of the numerous quacks and charlatans who had been permitted to carry on their trade in the state. Unfortunately Governor Jackson did not give his approval, and so two years had to go by before its final adoption by a new Legislature, and the signature of Governor Brown. This was but the beginning of Dr. Osier's eiforts for better state and municipal laws.

The almost unrestricted prevalence of typhoid fever in the United States, particularly in Baltimore, was a source of deep aggravation to him, and called for the use of all his


powers of voice and pen to bring light into the darkness, that rational legislative measures might be inaugurated to restrict its incidence.

Baltimore at this time was without a general system for tlie disposal of its sewage. Backyard privy vaults were nearly universal. Dr. Osier was strongly of the belief that typlioid fever would be greatly reduced with the introduction of a proper and adequate sewerage system and a pure water supply. Xote how vividly and forcefully he spoke at the meeting of the Maryland Public Health Association held on November 13, 1897, upon the subject of mortality from typhoid fever as related to these important city improvements :

The penalties of cruel neglect have been paid for 1896; the dole of victims for 1897 is nearly complete, the sacrifices will number again above 200. We cannot save the predestined ones of 1898, but what of the succeeding years? From which families shall the victims be selected? Who can say? This we can predict — they will be of the fairest of our sons and of our daughters; they will not be of the very young, or of the very old, but the youth in its bloom, the man in the early years of his vigor, the girl just wakening into full life, the young woman just joying in the happiness of her home. These will be offered to our Minotaur, these will be made to pass through the fire of the accursed Moloch. This, to our shame, we do with full knowledge, with an easy complacency that only long years of sinning can give.

Such writing as tliis is not only convincing, but is intensely moving, and must have played no small part in securing the desired end which happily came before he was to leave our city, a boon and a convenience to every member of the community, not to speak of the assthetics of the new order when street and sidewalk gutters were no longer redolent with the morning's dishwashings.

Whatever gives promise of adding to the stock of medical knowledge immediately arouses Dr. Osier's enthusiasm. Early he became interested in the amcebic theory of malaria. Well do I remember his coming to the Massachusetts General Hospital in Boston to demonstrate amoebae in blood corJ)uscles to Dr. Fred. Shattuck, then the young medical attendant to that hospital. This must have been in 1887 or 1888. No effort of his for good citizenship, or for the advancement of medicine was more remunerative than the stimulus he gave in this country to the solving of the problem of the causation, cure and prevention of malaria, a disease which had so sorely afflicted the people of states south of Mason and Dixon's line. Baltimore became the prime center for its study outside France and Italy, and Thayer's book written in The Johns Hopkins Hospital from Osier's clinic marks a salutary epoch in the history of this mosquito-borne infection.

Never was it out of Dr. Osier's mind that a better educated and more widely read medical profession made for better living conditions of the people, greater civic comfort and diminished suffering and death, so in all ways possible he encouraged students and practitioners alike to greater learning. To this end he insisted upon greater comradeship and larger attendance upon medical societies where experiences could be interchanged and interesting cases seen and discussed; he also insisted upon enlarged librarj' facilities, and adequate


^


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1919


PLATE XXV 1



si,i:it. I'.AiiT.

Wllllnm lh<' K..WI.T, Ciilllniimo roiBi-liMir I I lore In I'lill hliii tliii!' mill wlii-n I hiiiii The I'liiinti'rri'li |iri'»4'ntiii<'nl iif the niiin. I fcrl hlH IM'I. I hi-iir hiK nrriiva whir. Mnkc III thi' liKiii'l.v Kiiriiiinii- no ili'iiiiir, Nnr nil II nniiiliiiillon liiy n linn

With which II II if Mivrnn liirilK Iipbiiii,

lli-nry Ihi- Kowlrr wim flmt Kiniifmr.

Ani'li'iiliix wii» A|Milli>» rhnwn mm.

I'.iil til ihiil oiiii hi' ni'ViT li'hl hU Imw,

.Ni.r illil lli-iihii.".iii» iiiiih 111 fiirci- hl« ni'l :

lliith siM-riis hiith Imiiirhil HkIit wmi.

Ills ninci'il wiinl?! 'iriil.-hl In Ihi'lr i|iinrry gn.

Ail hi'iirm lire hnMi-ii li.v hli mi>»hi'K yi't.


Il.\»ii. I,. (iii.iii:iisi.i:»:vK


f


July, 1919]


207


supplies of current medical magazines and standard books. Under liis inspiration and leadership the old state society of Maryland took on a new life, and its I'bnuy so long nuiuKlering on it*; shelves sprang into usefulness. To him more than to any single man does the medical profession of Maryland owe its present faculty building with its large and growing library — a library in Mhich he took no less interest than in his own. To this extent, then, we must think of him as contributing enormously to the welfare of the community through an enlightened profession influencing public opinion in matters pertaining to health, sanitation, and general hygiene.

Xot less than his trenchant writing and speaking was Dr. Osier's own personality of influence upon men and the community; so strikingly straightforward, so genial, even convivial, so playful in youthful spirit, so enthusiastic in helpfulness and sympathy, so painstaking and so wise, he .^oon had both patients and acquaintances alike in an attitude of devotion, almost. I might say, of adoration. And although he took no otticial part in the civic affairs of the city, he gained through his association in the medical profession, by reason of his acknowledged eminence in that profession, and through his friends and acquaintances, a leadership in the affairs of the city and state which was most powerful and beneficent even though it was exercised in an indirect way.

From the moment when Koch discovered the germ of tuberculosis in 1882, Dr. Osier has never lost interest in this disease. He dwelt upon it in his teaching and he insisted that his students should be familiar with it. When in 1892 the use of tuberculin was thougiit to be specific, he was among the first in this countrv' in giving it a thorough trial in the wards of the hospital. For greater encouragement to the study of the disease, which so long has been such a fatal enemy of mankind, he suggested and carried out the establishment of a society whose single purpose sliould be the consideration of the history and the various phases, clinical and pathological, of tuberculosis, and this .society he named, after the great French student of tuberculosis and discoverer of the stethoscope — The Laentiec.

On November 14, 1899, Dr. Osier read an important paper on the " Home Treatment of Pulmonary Tuberuclosis," at the semi-annual meeting of the faculty at Westminster, and on the same day and in the same place Dr. Charles S. Millet of E. Bridgewater, Mass., described his outdoor sleeping porches for tuberculous patients. This was the first public discussion of the value of unlimited night air in the cure of consum])tion and marks a new epoch in the metiiod of treatment. Incidentally I may remark that at this same meeting mention was first made by Dr. Joseph E. Gichner of the need and desirability of a State Sanatorium in Maryland.

On April 19, 1901, at the invitation of Dr. Osier, Dr. Lawrence F. Flick of Philadelphia came to Baltimore and before the Clinical Society delivered an address on the " Registration of Tuberculosis," saying that Philadelphia and Xcw York had already inaugurated such a provision. Dr. Osier urged that Maryland should do likewise, as in this way the location of cases could lie known to the health authorities


and such steps be taken as would be of advantage to the patient and to the community.

By tlie end of the year 19111 there had arisen great interest in the tuberculosis movement, and it was proiui.scd that the Legislature of January, 19(i2, sliould pass new and vital laws which should be of benefit to the whole people. To this end a big meeting in McCoy Hall was proposed under the auspices of the Maryland I'uljlic Health .Association, the Medical and Chirurgicul Faculty of Maryland and the Laennec Society. Dr. Osier's "fiery "' speech thrilled the audience:

Mr. Chairman and my long suffering, patient, inert fellowcitizens: .... now what is our condition in this city, and what are we doing for the 10.000 consumptives who are living today in our midst? We are doing, Mr. Mayor and fellow<itizens, not one solitary thing that a modern civilized community should do. Through the kindness of a couple of ladies — God bless them! — I have been enabled in the past three or four years to have two of the medical students of The Johns Hopkins University visit every case of pulmonary consumption that has applied for admission to the dispensary of our hospital, and I tell you now that the story those students brought back is a disgrace to us as a city of 500,000 inhabitants. It is a story of dire desolation, want and helplessness, and of hopeless imbecility in everything that should be in our civic relation to the care of this disease.

He then argues for registration, disinfection after death or removal, a State Sanatorium for curable cases and a hospital for advanced cases, a sewerage system and a hospital for contagious diseases. This address and others made tiie same evening had an effect, to \rit : The Legislature of 1902 created a Tuberculosis Commission, the Governor naming Dr. Thayer as its chairman.

All that is progressive or worth while in the Tuberculosis Crusade in Maryland followed thereafter; the commission with its advi.'iors taking the initiative in beneficial measures. At Dr. John S. Fulton's suggestion the commi.ssion decided upon a tuljerculosis exposition in January, 1904, which should show graphically and practically the general incidence of tuberculosis, its methods of prevention and cure, its jetiology and pathology, it.s relations to social and economic problems, and a history of its study from the time of Hippocrates. Such an exposition for any single di.sease had never before been attempted. I^ectures and demonstrations were given and the attendance not only from Baltimore but from the counties and from outside the state was remarkable. The public was inten.sely interested and the exposition "demonstrated that it is both expedient and practicable to admit the general public to free participation in the scientific knowledge of tuberculosis." (Editorial, Md. Med. Jour.)

Dr. Osier was the moving spirit in this most successful undertaking and it was he who invited the distinguished speakers who were heard. As a result of this exposition, the Legislature of 1904 passed laws requiring:

(1) Registration of tuberculosis in Marjland, and

(2) Providing means and measures to be administered by the State Board of Health for the domestic prophylaxis of consumptives.

Growing out of this exposition, too, was the formation, fol


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[No. 341


lowing the suggestion of Dr. S. A. Knopf, of the National Association for the Study and Prevention of Tuberculosis. In this enterprise Dr. Osier had a leading part. In its organization he was made vice-president, and since his residence in England has been continued one of the two honorary vicepresidents, Mr. Eoosevelt being the second.

In December, 190-4, the Maryland Association for the Prevention and Cure of Tuberculosis was formed and again to this local movement Dr. Osier lent his interest and enthusiasm. His last effort for the tuberculosis cause in Baltimore was to induce Mr. Phipps to give the sum of $10,000 for a Tuberculosis Dispensary at The Johns Hopkins Hospital. This was opened with addresses on February 21, 1905, Mr. Phipps being present.


In reviewing thus briefly the activities of Sir William Osier during his sixteen years in Baltimore, I realize how inadequately I have been able to convey any idea of his great work and influence, or the universal esteem, love and honor in which he was held not only by the people of ilaryland, but by the country at large. I cannot believe that any man ever left our shores for a new work elsewhere more deeply and sincerely missed by a larger army of friends. His address of farewell delivered before the Medical and Chirurgical Faculty of Maryland April 27, 1905 on " Unity, Peace and Concord" typifies his attitude to all his fellows both professional and lay. In closing he sums up this relationship in the one word which he leaves as his benediction — Charity — and the greatest of all is Charity.


OSLER'S INFLUENCE ON OTHER MEDICAL SCHOOLS IN BALTIMORE

HIS KELATION TO THE MEDICAL PROFESSION

Bv Edwaed K". Brush


To estimate correctly Osier's influence upon other medical schools and upon professional thought and conduct would require an inquiry into the methods of medical teaching in vogue more than a quarter of a century ago, and into the social and professional relations of the physicians of the city and state toward each other.

At about the time of Osier's arrival in Baltimore to assume the duties of physician-in-chief to The Johns Hopkins Hospitiil there was a movement on foot to improve and enlarge the medical cui-riculum. The University of Maryland in 18S9 announced that after 1891 a compulsory three-year course would be required in the medical department with a preliminary examination in English.

In March, 1890, a call was issued by the medical staff of The Johns Hopkins Hospital, and the medical faculties of the University of Maryland, The College of Physicians and Surgeons, The Baltimore Medical College, The Baltimore University and the Woman's Medical College for the organization of a medical college association with a view to the cooperation of all medical teaching bodies in bringing about a three-year graded ccurse, written and oral examinations, a preliminary examination in English and laboratory instruction in chemistry, histology and pathology.

At the meeting of the Medical and Chirurgical Faculty in 1889 the annual address was given by Dr. Osier, who took for his theme " The License to Practice," and undoubtedly this address gave an impetus to a movement, already receiving support, for higher medical education and a better qualified student body.

My own connection with medical teaching in Baltimore did not begin imtil eight years subsequent to this date, but I realized before that period, and have had oceasior. to know since, the great interest which Osier took in promoting reforms in medical teaching not only here, but in the country at large, the great and lasting influence of his advice, and above all, his example as a teacher.


Trained as he had been as a laboratory man, realizing to the fullest extent the results which flowed from his laboratory studies and tlieir bearing upon the practical work of the hospital ward and the consulting room, as well as in the lecture hall, he urged the establishment of laboratories.

Thoroughly equipped laboratories, in charge of men thoroughly equipped as teachers and investigators, is the most pressing want to-day in the medical schools of this country.

The hospital was, from his point of view, a college — a place of teaching, the most essential part of the machinery of a medical school.

The systematic use of the resources of the hospital which he inaugurated and which he urged upon other communities and described in detail in his address before the New York Academy of Medicine in 1903 found in the minds of the more progressive teachers of the Baltimore schools a ready acceptance.

For those working in my own special field, it is gratifying to believe that it was a few words spoken in his farewell address at the university, February 22, 1905, which gave an impetus that resulted in the establishment of a psychiatric clinic at the hospital.

From his address at the dedication of the Wistar Institute of Anatomy and Biology of the University of Pennsylvania, 1894, I take the following:

What, after all. is education but a subtle, slowly effected change, due to the action upon us of the externals; of the written record of great minds of all ages, of the beautiful and harmonious surroundings of nature and art, and of the lives good or ill of our fellows — these alone educate us, these alone mould the developing minds.

The whole career of Osier in Baltimore, his life here as a teacher, hospital physician, consultant and citizen was devoted to the better teaching of medicine, to better ideals in education; and from his life, from his example, proceeded influences which not only moulded developing minds, but stimulated all


Jii.Y, 1919J


209


who had a real ambition, to teach and, in teaching, to learn also, and develop.

To emphasize sufficiently his influence upon medical education is most difficult. One of his constant pleas for other schools was for larger clinical advantages, and better use of those alread)' provided. In 1897 in his address on Internal Medicine as a Vocation, before the New York Academy of Medicine, lie says :

To-day the serious problem confronts the professors in many of our schools — how to teach practical medicine to large classes; how to give them protracted and systematic ward instruction? I know of no teacher in the country who controls enough clinical material for the instruction of classes, say of 200 men, during the third and fourth year.

Never a controversialist, none the less did he bear a large share in the controversies of 30 or more years ago, which preceded and eventually brought about the changes in the methods of medical education which have taken place since that time. His influence was exerted not in argument or controversy, but in the force of e.xamplc, by the way in which he lived his ideals and induced others to share them with him.

He studied " to be quiet " and do his " own business," " to walk honestly toward them that are without " and one of his chief pleasures was " to work among [us] as a friend sharing actively in [our] manifold labors."

Some years ago I had occasion to apply to him a quotation from the presidential address of the late Dr. Charles M. Ellis before the Medical and Chirurgical Faculty in 1898. These words seem to me particularly appropriate to Dr. Osier :

Many [doctors] by reason of natural endowments and acquired fitness elevate their lives to a professional plane on which it is possible for an Intellectual life to develop; and on which it does develop, not only to individual sufficiency, but to public usefulness and a public influence, that on the one hand meets and supplies public emergencies and, on the other, largely directs and controls public thought and movement.

These words from what I know of tlic intimate and friendly relations between the two men may well have been brought to the mind of Dr. Ellis by his knowledge not only of the intellectual life of Dr. Osier, but by his appreciation of the controlling influence of his mind upon public tliought and movement, particularly in professional circles.

Ver}' early in his residence in Baltimore, notwithstanding that he " studied to be quiet," he became a by no means unimportant factor in the social life of Baltimore physicians.

He so regulated his work that he always had a certain


amoimt of time to give to his friends in social converse, or in conference over the more serious things of their everyday lives and work.

Ho appreciated the difficulties and perplexities wiiich surrounded the lives of many of his professional brethren and many a burden has been made lighter, many dark hours brightened, by his wise and thoughtful advice and his cheering optimism.

More than one doctor laboring amid discouragement and the indifference of open opposition of his fellow-citizens, whose lives he was manfully trying to make more tolerable, whose surroiuidings he was endeavoring to make more healthful, has found to his surprise that Osier had learned of what he supposed was unknown beyond the bounds of his own community, and has received from him words of ciieer and commendation, which were a powerful incentive to renewed effort, just when all the uses of the world appeared to him "weary, stale, flat and unprofitable."'

His farewell address " Unity, Peace and Concord " is an eloquent recital of his consuming eagerness to be " a servant " to his brethren to do all in his " power to help them."

He strove always to live in unity, peace and concord with his fellows. He strove with none — not that none were worth the strife, but because of a deep conviction of the hatefulness of strife. Those wortli the strife he won by other and gentler means, and bound them to him by the everla.<ting chains of friendship.

In 1881 there was formed in Baltimore the Baltimore Monthly Medical Reunion. It met at the home of members in turn and around the dinner table and at the fireside many friendships were made and consolidated. Very soon after coming to Baltimore, Dr. Osier became a member of the Reunion and always when he was present at the monthly gatlicrings, as with The ^fcGregor, where Osier sat was " the head of the table," the center of conversation, the focus of wit and wisdom.

As in the past, so in the future in all that makes for truth and righteousness, in all that holds forth liigh ideals, in all that encourages culture and all tlie virtues of the Christian gentleman and the ideal physician the name of Osier will bo one to conjure with. From time to time, as on the present occasion, his friends for many years, let us hope, will send him greetings across the .«ca. He has given us the master word and with that in our hearts all things are possible. Have we not seen it exemplified in his life and character?


INFLUENCE IN BUILDING UP THE MEDICAL AND CHIRURGICAL

FACULTY


Bv Ilnt.vM Woods


" Influence in Building Up the Medical and Chirurgical Faculty " is a theme one might approach from numerous paths. So great was Dr. Osier's influence, in so many directions did it work, so broad was his conception of the possibilities for good in the organization, so keen his appreciation


of the obstacles to progress, some traditional, some personal, that the many-sided subject is bound to appeal to his friends in difl'erent ways. Adequate organization of the library ; revelation to the younger man of what the library even in those days afforded; provision for the purchase of new books — these


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[No. 341


are themes which have been selected for special review and will be presented by others. I shall try to give some idea of his work from another standpoint — that of personal influence. Yet, with the selection of this special topic, I am aware that I shall speak from my own personal impressions and memory and may fail utterly to express the feelings of another just as indebted to Dr. Osier as am I.

I have asked myself. What were Dr. Osier's basic thoughts and principle in his work for, and devotion to, the State Medical Society? He held the most influential position medicine in Baltimore could give ; he had at command greater powers than any one medical man had ever possessed in the city ; his teaching and organization duties in the new medical school were exacting enough to take all his time, and yet he went to work on the state society in a way which soon gathered recruits happy to work under — not his direction — but his mind and heart. What led him to do it? I think he felt that the biggest medical foundation Baltimore liad ever had ought to benefit the existing profession. He thought there should be a high valuation of the profession itself ; realization of the obligation of self-improvement; a breaking-down of the " middle wall of partition " between those, who, by a connection -with the new school, seemed to possess an advantage, more or less adventitious, and those who foimd, or thought they did, a definite obstacle to practice in the new Foundation. He felt the meaning of " Unity." He told us of this — at least in words — only on the eve of his departure. And yet he had told us about it previously in a better way. Go over the papers he lirouglit to the faculty meetings and the smaller gatherings of the local society and you will, if I mistake not, see that he presented the problems of disease, cause, prevention and cure, as the same for tlie hard-worked country doctor, with little time to read, and the man with hospital and laboratory advantages, plus trained nurses and competent assistants. But here the roads parted, in a sense. The practitioner brought his experiences and difiiculties. Modern methods of investigation were not at his command. Dr. Osier felt that the man with greater advantages should, in the first place, qualify himself to luiderstand the point of view of his less fortunately placed colleag-ue, and then, from his greater advantages, make up the deficiency.

Sometimes a chance thing makes a life-iong impression, and such an occurrence has come back to me time and again. At a society meeting typhoid fever was the topic. I believe I am quoting accurately : " Typhoid fever, the monster that destroys the best of our sons and claims the fairest of our daughters ; are we to let it continue or stop it ? " And then followed a clear, scientific and yet almost a domestic demonstration of preventive measures which coiild be taken home and taught to those who did not know, but who, if they knew, might save their own and others' lives. This, I believe, was Dr. Osier's motive force : aim to realize the other man's point of views and his needs, and to reach these needs if he could. But if such was the self-imposed task, success could come from no wiser-than-thou attitude. There had to be a comradeship ; not the assumed, patronizing variety, but the sort that cements


tlie minds and hearts of men earnest after the same thing — knowledge. How many of us have met him browsing around in tlie library, and soon foxmd ourselves just talking? Yet from that talk we afterwards found we had gleaned a great deal. It was from one such talk that I took away definite impressions about the evils of narrow specialism. Again, after we got to know him laetter, we would sometimes find him in deep conversation with a beginner in medicine, or a man we hardly knew, and we shied off. It was perfectly clear what he was doing. But the comradeship was the real thing; there was nothing professorial about it. This comradeship extended beyond the confines of men who were active students for their own good or those who needed prodding. It went after and reached those > who had something to give, and who did not know how to give it; maybe they did not know they had it. There are matters of importance to the faculty and profession, bearing others' names, which would never have come into being without William Osier's realization of their importance and pointing out the way to achievement. I cannot speak more definitely; but men familiar with the faculty's history will know. This comradeship went farther. It reached those who for one reason or another had met nith little or no success. It made them feel that in spite of what miight be termed failure, honesty of purpose gave standing to a man in medicine and brouglit him into unity with his brotliers upon wliom fortune had smiled more kindly.

Work for the library, teaching its value by precept and example, demonstrating the unity of the medical profession and the spirit of comradeship soon won the esteem, confidence and affection of men throughout our state. This feeling wa.*^, possibly, best expressed in a telegram sent to Dr. Osier's mother in April, 1905, when he was about to leave Baltimore. The telegram was sent Ijy vote of the faculty at its annual meeting and signed by the president, Samuel T. Earle. It reads :

The greetings of the Medical and Chirurgical Faculty ot Maryland to Mrs. Osier, asking her to share their sentiments in taking leave of William Osier, congratulating Mrs. Osier first on the distinguished career of her son, but most on the innate qualities which have endeared him to his associates in Maryland.

A few days later the following reply was received : Mrs. Osier, who is unable from her great age to write, asked me to express her heartfelt thanks to you for the very kind telegram of greeting sent through you from the Medical and Chirurgical Faculty of Maryland, and to say that the receipt of the message gave her the greatest pleasure, more especially in the expression of affection and appreciation called forth by the personal qualities of her son, since these are, in her eyes, more precious than all his honors.

She knows that it must be hard for him to sever his connection with such kind confrrrrs. and she is sure that the friendships he has made during his residence in the States will be among his most cherished memories. I am, sir, yours sincerely,

jEiA.NNETTE OSLEB.

One w^ho had thrown his heart and soul into an enterprise would be keenly disappointed if his work fell through in later years. There seems no danger of this wliile there survive the men who came under Dr. Osier's leadership. The funds


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obtained through his influence, and others, which have come since, because of tiie spirit he put into the organization, are keeping the faculty up to date. But these material things, important as they are, would fail in tlieir purpose, unless something else lived and permeated tlie faculty's life. I mean tlie mental attitude wliich I have tried to present. It is interesting to go over a book in a public library even if one owns a copy himself. The latter he feels free to mark, but it demands a certain amoimt of bad taste to mark passages in a book which does not belong to you. However, this bad taste does exist here and there and sometimes it may not be without its advantages. It shows the other fellow's thought. Recently I picked up " Aequanimitas " at the library and opened by chance at the delightful es.say " Teacher and Student." That a library-worn book like this should open right there is not witliout significance. It means that there are youngsters coming on now who are getting from the printed page some of the things others got from personal intercourse. This passage is marked with a heavy lead pencil :

The measure of value of a nation to the world is neither the bushel nor the barrel, but mind: — wheat and pork, though useful and necessary, are but dross in comparison with those intellectual products which alone are imperishable.

In " Unity, Peace and Concord," written in 190.3, 13 years after the essay to which allusion has been made. Dr. Osier speaks of " the petition in the Litany in which we pray tliat to the nations may be given unity, peace and concord." Then follows this, which I do not attempt to summarize:

Century after century from the altars of Christendom this most beautiful of all prayers has arisen from lips of men and


women, from the loyal souls who have refused to recognize its hopelessness, with the war-drums ever sounding in their ears. The desire for unity, the wish for peace, the lonKing for concord, deeply implanted in the human heart, have stirred the most powerful emotions of the race, and have been responsible for some of its noblest actions. It is but a sentiment, you may say, but is not the world ruled by feeling and by passion? .... As with the nations at large, so with the nation in particular; as with people, so with individuals, and as with our profession, so with its members, this fine old prayer for unity, peace and concord, if in our hearts as well as on our lips, may help us to realize its aspirations.

Now, 14 years later, wirli tlic world still "refusing" to recognize its "hopelessness" and struggling toward the realization of permanent unity, peace and concord, these words seem almost prophetic. From the " nations at large " through successive steps, this great principle of unity, peace and concord reaches the medical profession and " individual " doctor. His comprehension and use of it will depend on his relative valuation of the "barrel and bushel" and "mind." Dr. Osier's method of upbuilding the faculty differed from others' in that he aimed to inerea.*e the individual's receptivity for what the faculty had to offer. So long as the faculty sees its responsibility to offer only the best; so long as its members appreciate the nature of wliat is offered and remember tliat profit is a question of their own liearts and minds, there will be no danger of deterioration ; but both are neccs.<ary. While we are congratulating Dr. Osier and gratefully acknowledging our debt to him, let us not forget what his cxam]de tiiught; for it is only thus that we can keep what lie had .so large a share in giving us.


OSLER AND THE BOOK AND JOURNAL CLUB


Bv J. A. Ch.vtard


Of all the varied activities and interests that occupied Sir William Osier, while in Baltimore, possibly none appealed to him personally, luid to the little group of supporters that lie gathered about him in the early days of 189G, more than the idea of getting together a few of the men of the profession at periodic times for the discussion of old books on medical sul)jects and the presentation of papers on the historical side of medicine. At the seme time the members, by their interest in the work and by the voluntary sul)scri])tions olTered, helped much in the improvement of the library of the Medical and Chirurgical Faculty by the purclia.-ie of new books and journals.

In these early 90's the faculty was in a quiescent mood with few regular meetings at which, for the most part, only routine busine.<s was transacted. For lack of funds the librar}' was much neglected and the book and journal files were far from complete. This Dr. Osier saw and at once put his great store of knowledge and earnestness, at the disposal of the members of the faculty, with the result that the Book and Journal Club was .soon in a flourishing condition.

Those of us who went to the early meetings can still remember the enthusiasm of Dr. Osier in his presentation of rare old


historical medical subjects or in the enlightening discussion that he gave following someone else's ])aper. After some time he would then sliow some of the fine old Iwoks illustrating the talk, tho.«c books not infrequently coming from liis own medical library.

But for one man's enthusiasm and zeal we might have missed so many interesting tiilks on the " Hippocratic Writings," the " Plague of 1G30 in Milan," " Haney as an Embryologist," " Some Diseases Bearing the Names of Saints," "The Resurrectionists of London and Edinburgh," "The Books of Vesalius," Assyrian Medicine," and last but not least, our old friend Sir Thomas Browne. These and so many other historical subjects he was instrumental in bringing before us. leading us on to browse among the old masters and find there the very things we may be looking for to-day.

During his presidency, the Book and Journal Club collected over five thousand dollars by voluntary subscrijjtion and in addition to paying for the binding of many journals, we were able to pun-base annnally about 2T0 books and subscribe to 56 journals. To tho.<e of us who know how crippled the


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[No. 341


finances of the faculty were at that time, and how little was available for the library fund, this money from the Book and Journal Club was a treasure indeed.

To the older members of the faculty his work and zeal for their interests was of wonderful help and assistance, and liis close association with them will always be looked back on with the deepest and most lasting pleasure. To the younger, some of whom are now among the older members of the faculty who knew him at that time and worshipped from afar,


his example should be a help to be better students and workers. To the youngest members of the faculty, who, alas, knew him not, it becomes a duty to emulate his efforts in historical study and so join in the company of those who can find that all is not dry and musty in the old discolored books upon our shelves. It is only by thus fostering and helping along a search for old tniths that the newer ones assume a more crystalline appearance and we are better able to value them in the light of advancing thought.


OSLER'S INFLUENCE ON THE LIBRARY OF THE MEDICAL AND CHIRURGICAL FACULTY OF THE STATE OF MARYLAND

By Ma]:cia C. Noyes, Librarian


Associations of Dr. Osier are so interwoven with the library of the Medical and Chirurgical Faculty that what we have become is, in reality, but an expression of what we felt he would have us be.

The name of Osier is writ large in the history of the library from the time of his first connection with it in 1890 ; and the impression made by his character on the lives of those with whom he came in contact has been a powerful influence for the betterment of medicine in ilaryland and in the upbuilding of the state society and its library.

Dr. Osier was elected a member of our Library Committee in 1892 in which year the committee reported difficulties, financial and otherwise, in the management of this " most valued and noble inheritance." Although never serving as chairman, that he lent himself to the surmounting of these difficulties we know, and what was accomplished between 1893 and 1905, his tenure of office on the Library Committee, is given, in part, herewith.* From a collection of n few thousand old books in 1892 it grew to 14,590 volumes in 1905, and has grown steadily ever since.

The library, which dates from 1830, had been partially revived in 1881 and was housed in rooms in the basement of the old ]\Iaryland Historical Society in 1885; but it was Dr. Osier's interest which brought about its renaissance and the purchase of and its removal to the home at 847 N. Eutaw Street (Hamilton Terrace) in 1895. After a year without proper supervision it was owing to Dr. Osier, who personally saw to it, that the Library Committee employed a trained worker and the present


LIBRARY OF THE MEDICAL -aJ^D . .CHIRURGICAL FACULTY

OF THE ST T^ ^ ^'^^.rt^^OF MARYLAND



PURCHASED THROUGH T" IF

WILLIAM OSLER

TESTIMONIAL^FUND ,, :

FOR THE ADVANCEMENT OF MEDICINE


  • When abroad for his annual outing, Dr. Osier always had the

needs of our Library in mind, and we owe many of its greatest treasures to hisi interest. Some of these were a direct gift from him, and others selected for purchase on the Frick Fund.


librarian took charge. To him we owe the founding of the Charles Frick section of the library, in 1896, which was made possible by the generosity of Messrs. William F. and Frank Frick; and the establishment of the Book and Journal Club at about the same time. These funds gave the Library a definite income for the first time in its history.

Dr. Osier was president of the Faculty in 1896-1897, and in his presidential address, April, 1897, in outlining the purpose of, the Book and Journal Club, and of the Frick memorial said : " I envy Charles Frick the good fortune to go down to the future generations in this Faculty with his name linked to an important section of our library. Posthumously and by proxy, as it were, tlnis to carry on, though dead, the work lie was interested in while living, is the nearest approach a man can make to rheating the great enemy, and in Charles Frick's case it is in a measure a (•(impensation for the untimeliness of Ills taking off." He also spoke of the approaching centennial as follows : '" We ' :in try in the centennial year to obtain 1 proper endowment for the Faculty hom our friendj among the citizens. We shall need a larger hall, more in keeping with the rank and work of the profession of this city — quarters as complete as our brethren enjoy in Piiiladelphia and New York. And an endowment yielding a few thousand dollars annually is absolutely essential for the proper development of the library." At the centennial of the Faculty in 1899 he gave the first thousand dollars toward such an endowment fund; and it may safely be said that it was principally due to his influence that the Charles M. Ellis bequest was made in 1910.

It was because of the widespread desire to honor Dr. Osier that the present home of the library, at 1211 Cathedral Street, became a fact in 1909 ; and because of a further expression of



July, 1919]


, JOHNS HOPKINS HOSPITAL BULLETIN


213


this desire that the Osier Testimonial Fiind for tlie purchase, in his name, of books on medicine was presented to us in 1917. It is singularly fitting that his name should be linked for all time witli that of the Medical and Cliirurgical Faculty and its librar}', for he delighted so keenly in the phrasing of the old title — the chirurgical, so hard for the uninitated to pronounce — and in the usage of the word faculty instead of society. The development of the library, to its fullest extent, interested him beyond measure, for he was not only a lover, but a user of books, and he insisted that his students should learn the art. The familiar slip bearing his reference was presented almost daily by some one of them, and our reading room on Saturday afternoons became a rendezvous for students and physicians who thought to meet him there to seek his advice. In those days, the pausing of a hansom at the door, if followed immediately by a cheery whistle, presaged his advent to the initiated. Hardly a Saturday passed without Dr. Osier coming to scan the shelves containing the new journals and to browse among the books to be found in the Charles Frick Reading Room.

Akin to his interest in books is his interest in medical libraries in general, and he was intimately familiar with and always a welcome guest at the library of the Surgeon General's Office, the College of Physicians of Philadelphia, the New York Academy of Medicine, the Boston Medical Library and the library at McGill University, as well as the libraries in Baltimore and manv of the smaller medical libraries elsewhere.


some of which he fostered. He was not only familiar with tlie books in tliese collections, but he knew intimately the catalogers and workers who do not usually come in contact with the readers, as well as the librarians in charge.

This interest found expression in the founding, in conjunction with Dr. George M. Gould, of Philadelphia, of the Medical Library Association in 1898. Owing to his generosity our library was a member from the beginning, and has become an influence in the medical world because of this membership and our connection with the exchange of the association.

No one man has so left his imprint on the libraries of two continents as has Sir William Osier, and a quotation from his address "Books and ^fen " delivered in 1901 at tlie opening of the new building of the Boston Medical Library, at 8 The Fenway, simis up wliat his example has meant to this library and Faculty:

It Is hard for me to speak of the value of libraries in terms which would not seem exaggerated. Books have been my delight these thirty years, and from them I have received incalculable

benefits For the teacher and the worker a great library

such as this is indispensable. They must know the world's best

work and know it at once For the general practitioner

a well-used library Is one of the few correctives of the premature senility which is so apt to overtake him. Self-centered, selftaught, he leads a solitary life, and unless his everyday experience is controlled by careful reading or by the attrition of a medical society it soon ceases to be of the slightest value and becomes a mere accretion of isolated facts, without correlation.


SOME EARLY REMINISCENCES OF WILLIAM OSLER


Bv IIexry M. Hurd


In September, 1883, while on a vacation trip with a friend. I stopped at Kingston, Ontario, and found my.«clf in a busy throng of physicians in attendance upon the Canadian Medical Association in annual session there. The physicians were diligent in their attendance upon the meetings of the as.sociation, proud of their mutual calling and eager to advance it. The secretary- of the organization, and one of the leading spirits, was Dr. Osier, a resident of Montreal, a young man of 34 years, who then, as always, appeared younger. He knew in person every physician present and was easily the guiding force in the association. He participated freely in the discussions which followed the reading of papers and did not hesitate to express his mind freely and frankly on all important questions. In the meetings there were the usual differences of opinion between the rank and file of the profession and the members of the medical examining board and verbal encounters sometimes took place between many men of different minds. Osier spoke boldly and without reserve and had an opinion upon all matters, but never seemed to excite ill feeling or lasting resentment on the part of those who differed with him. He was an excellent secretary and carefully watched the progress of the special work of the meetings. He was spare in figure, with a sharp, piercing eye, and although of sallow complexion, was vigorous and in excellent health. He


was neatly and quietly, but carefully dressed and in manner and bearing displayed the characteristics which I later learned to recognize and appreciate as peculiar to him. One circumstance in the meeting attracted my attention in a special way ; a prominent member read a paper entitled " The Conduct of Medical Men Towards Each Otlier and Towards Each Others' Patients," which displayed great wrong-headedness and perversity of feeling in reference to the relations of pliysicians to each other in the matter of consultations over very ill patients. He held tliat a physician was justified, when called in consultation, in getting control of his brother practitioner's patient and concluded by saying: "Take all the ca.ses you can get and keep them if you can without reference to the rights of any other attending physician," He also deemed it justifiable to report one's cases of operations or extraordinary cures in tlie newspapers and inquired, "Why should not medical men report their cases as well as a lawyer his speeches or a clergyman his sermons? " When he had concluded reading his paper he was called sharply to order by several members and referred to the Code of Ethics which existed in Canada to govern the relations of physicians t/> each other. Whereupon the offender announced that he had never seen any such code and that it had no meaning to him. Dr. Osier sprang to his feet and drew from his pocket a pamphlet copy of the Code of


21-1


[No. 341


Ethics wiiich he waved about his head and in a loud, clear voice announced that he took great pleasure in supplying a copy to his innocent and untutored friend and was glad to learn that he had " sinned unwittingly through ignorance."

In 1889, when I came to Baltimore, I found Dr. Osier in temporary charge of The Johns Hopkins Hospital, which had been open in part for a few weeks. He lived at the hospital and guided its work in company with Dr. Halsted and such members of the early staff as Lafleur, Brockway, Clarke and others. I remember on my first visit while walking along Broadway in company with Osier and President Gilman, the day being very hot, the latter, as usual, had an umbrella which he used to protect himself against the rays of the sun. He invited Osier to walk with him, who declined saying, " The chill of nearly 40 Canadian winters is still in my veins and I do not need any such shelter."

He was a delightful companion with children and took much pleasure in conversing with them and even mystifying them by detailing remarkable personal experiences and sometimes tragedies. Once he invited two young girls to a luncheon at his house on Monument Street, where his niece, now Mrs. Abbott, kept house for him. He came late to luncheon and explained his delay by the fact that he had been caught in a down-pour of rain when crossing Monument Square which had produced a flood sweeping him off his feet; that he had escaped only after vigorous swimming and had barely saved himself by grasping the shaft of the Washington Monument with both arms. A more harrowing tale was that of the loss of a young friend by falling from his row-boat into the St. Lawrence Eiver. He explained that he might have rescued her had he not resolved never to act hastily and without due consideration. He had accordingly tossed up a coin to determine what his action should be. It fell adversely and he rowed ashore alone weeping bitterly ! Fancy the difficulty of duly impressing high moral precepts upon the young in tlie light of such a confusing example. Children delighted in his presence and were charmed by him, but \evy naturally were always uncertain as to the logical nature of his conclusions and equally puzzled by his apparent indifference to conventional conceptions of duty and obligation. There was also in his attitude towards pupil nurses a similar light-hearted irresponsibility which marked some portion of two addresses to nurses to which reference is made later. It is possible, however, to perceive that under the cloak of these apparent trivialities there lurked a seriousness of purpose and a keen desire to point a painful moral in a kindly way. AYitli children, however, it was simply an expression of his ample imagination and of his desire to please and puzzle them. Even older people were sometimes at a loss to follow his moods and strange fancies. He was invariably cheerful, hopeful, and optimistic even under circumstances of discouragement and doubt. I remember on one occasion one of his colleagues, mystified by his imperturbability in a trying emergency said, " Osier drop your mask, let us know what you actually think of the situation," but no one ever did gain that knowledge.


Osier's habits of work, while he resided at The Johns Hopkins Hospital, were exemplary and somewhat unusual for a man of literary taste. Such men are usually inclined to turn night into day, but he rose promptly at 7 a. m., took his bath and breakfast and was ready for work at 8 o'clock. He seemed to have a faculty for setting his mental machinery in motion immediately and accomplished effective work -svithout delay. Wlien his secretary came he generally began to dictate and by practice acquired great faciUty in terse and vigorous expression. This quality also was undoubtedly assisted by his familiarity with King James's version of the Bible, the Prayer Book, and Sir Thomas Browne. His method of the preparation of the Principles of Medicine was worthy of being followed by other writers. He gathered the literature of any subject which he had on hand by judicious foraging in his library and elsewhere. The volumes thus collected were piled four square generally, open at the page to be consulted upon the table, as long as room sufficed and later upon the floor until movement about the room was much restricted. I remember that when after seven months of strenuous labor he completed the first draft of his treatise on medicine I chanced to look into his room and found that it contained an immense heap of books piled as high as the table like an ancient sacrificial altar. The first draft was carefully revised wdth no great amount of change in sentences and forms of expression. Such changes as were made, however, did not destroy the crisp, breezy style or the epigrammatic form of expression which has always been characteristic of his literary work. The book contained many personal references which gave peculiar satisfaction to his friends l)y reason of the goodnatured personal touches he frequently gave to the cherished beliefs and traditions which he did not share. I remember in speaking of the use of turpentine in typhoid fever, he said, " The routine administration of turpentine in typhoid fever is a useless practice for the perpetuation of which, in this generation, H. C. Wood is largely responsible." This somewhat pointed condemnation of a generally recognized method of treatment at that time brought forth a vigorous rejoinder from Dr. Wood in a medical journal, but fortunately there was no loss of friendship on the part of either Osier or Wood.

Osier was also \ery scrupulous in fulfilling his duties in attendance upon the meetings of medical societies. When once informed by a student that he did not attend the meeting of a medical society because he was not sure that he could get anything out of it he replied, " Do you think I go for what I can get out of it or for what I can put into it ? " Those who knew him felt a deep impression that in all activities in medical societies and in behalf of his students he labored solely to inspire them with a love of work for its own sake and for what he felt to be its final effect upon their growth and development.

This fact was brought out in his relations to the Training School for Nurses, established at the hospital in October, 1889, which were of an ideal character. He had a warm friendship for Miss Hampton, the organizer of the school and its first principal, and also for Miss Nutting, her successor. He gave


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1919


PLATE XXVI



Xi<


Taken in 19(i1.


Takkn in 191;



T.VKKN IN 1902.


Taken in I'JIS.


JrLY. 1919]


215


mueii assistance in tlio way of advice and in teaching and was waimly interested in its success. He gave two graduating addresses also, one entitled, " Nurse and Patient,"' and the other, " Doctor and Nurse." He was appreciative of the work of nurses and touched lightly and gracefully upon the mutual relations of the nurse to her co-worker, the doctor, and to the object of her care, the patient. There was, however, a suspicion of an attitude of reserve towards trainetl nurses as a class a.s may be inferred by the quotations which preceded these addresses when published. One, for example, had this significant motto, from the Psalms of David, " I said I will take heed to my ways that I offend not in my tongue. I will keep my mouth as it were with a bridle. The other quotation


was from Sir Thomas Brownie, Think not silence the wisdom of fools, but if rightly timeil the honor of wise men who have not the infinnity, but the virtue, of taciturnity and speak not out of the almndance, but the well-weighed thought!* of their hearts. Such silence may be eloquence and speak thy worth above the ])ower of words."

Osier in fact seemed always appreciative and helpful while at tlie same time he had an air of detachment as one who was endeavoring to sec whither the movement for the education of nurses would ultimately lead. In the end I am sure that he learned to understand and appreciate the work of the training school and felt the great importance of it to physicians and to the advance of the science of medicine.


OSLER AS I KNEW HLM IN PHILADELPHIA AND IN THE HOPKINS


Bv Howard A. Kelly


I find myself wondering, in these days of pleasant retrospection, now that our much loved friend Sir William Osier is so splendidly rounding out his seventh decade, whether, of all his friends here, I may not claim the credit of having known him first.

I was living in Philadelphia up in the big mill district of Kensington, culling a surgical out of a large general practice, and at the same time keeping in close touch with things at the University of Pennsylvania, for eight years my college, when it became manifest that some fresh and stirring blood had entered the college life.

The university, with so many eminent men camping on her very doorstep in Philadelphia, and with that tendency to nepotism, a form of paternal pride seen in all successful institutions, had, as we younger men thought, driven John Guiteras of brilliant promise in general medicine, away from her doors to protect Pepper from rivalry, and now, not without great hesitation as we understood, she had actually broken her shackles, throwni traditions to the winds and inillcd William Osier down from McGill in Montreal.

Fresh invigorating currents of life and new activities in our stereotyped medical teachings began at once to manifest themselves, and every sturdy expectant youngster in short order lined himself up a.s a satellite to the new star. Osier breezes were felt everywhere in the old conservative medical center, and yet it was not without some difficulties that he securely established himself. Weir Mitchell, who had rea.«!on in his later days to cultivate kindlier feelings towards the university than in his young nianhcwd, was from the first Osier's devoted and intimate friend, and one by one the faculty was won to appreciate him, perhaps including even Pepper too, though I am not so sure. My own life touched Osier's in the Kensington mill district in northeast Philadelphia. A.side from anatomy and chemistry, I got most of my real medical education while a resident in the Episcopal Hospital and next in the homes of the Kensington folk. Wood's physiological therapeutics, and Still^'s didactic lectures on medicine seemed


deadly to me, and worst of all was Tyson's pathologj- elucidated by Formad's quizzes. So it remained to get the education at the bedside, and here Osier came to my aid. It was more than a Sabl)ath day's journey in those days to go to Kensington from the heart of the city; it was an hour in the street car, and a long drive over bad, very bad, Philadelphia streets, but Osier came and Agnew came with their lamps in their hands to illuminate a few of the problems in the vast domain in which all medical graduates are jiresumed to be experts.

I think the first patient that Osier saw w^as .suffering from anorexia nenom, a condition wliich I had never seen before, and of which I was ignorant. He stayed to dine in Norris Square, and was particularly interested in my collection of old medical books.

Then he was whisked away to Kaltimore, and then after a year's time, I followed at his behest, glad to have a more concentrated field of work.

Here I can add nothing, for his record is knowni and read of all men, and what a blessing he, and Welch, and Halsted, and Hurd proved to he in this community. I leave others to appreciate Osier's skill as a medical man, and his love of the classics. I always think of him first of all as one who brought order out of the chaos in the medical profession of this city, a great task effected by his kindly jier-^onality, his insight into human nature, and the genuine affection he ever felt for all men who were even half way good.

It was a .settled ])olicy of Osier's life never to speak ill of any one but always lo find the good, and in that way he converted the hostile cam]) of Baltimore into a kindly family of cooperating doctors.

Jleflicine here had fangs in the old days. Osier and Welch more than any others drew them : and so made possiide medical progress.

I want to lay claim to the gift of prophetic insight (a role I doubt not in which many of my colleagues have anticipated me) ; I had said from the first that Osier was bound for London, and in the old days I longed to be ready to go with


216


[No. 341


him when he went. The outcome has exceeded, I think, all our anticipations, and who but he would have maintained unabated the same interest in all his old friends, and who else could have turned the ocean into a highway, and his new position.


detached as it is from any vast clinical facilities, into a veritable medical Mecca for all our American medical world. That many lustra may still be added to the kindly years of Lady and Sir William Osier is the wish of many hearts.


OSLER AS A BIBLIOPHILE


By Thomas

Adequate treatment of this important side of Dr. Osiers activities would far transcend the present writei-'s abilities and the space allotted to this article. But it may be of some value to discuss briefly Dr. Osier's interest in old books as reflected in his informal talks with the students.

In looking back it seems to the writer that tlie interest in the early editions was a development of the fundamental value he placed in the study of the history and evolution of the science and art of medicine, and that it was in connection with his studies of the fathers of medicine in all times and countries that he began that collection of first and rare editions which has now reached such remarkable proportions.

WTien the plan of collecting the works of the founders of British Medicine was first originated is unknown to the ^\Titer, but it had already reached a large degree of perfection at the time when the class of 1901 began to make the Saturday evening visits to the old house at No. 1 West Franklin Street.

Most of us will ever retain the delightful recollection of those informal gatherings about tlie big table in the diningroom, when after the discussion of the week's work in the wards was finished, " the chief " would bring out some of the books from the special shelves devoted to the masters of medicine and show us the first editions, tell us the story of their discovery and acquisition, point out the notable passages, and give the salient facts in the author's life history. For many of us this was the beginning of our knowledge of the histoi7 of medicine and of our own feeble attempts to follow in his steps as collectors.

How reverently we handled and admired the rare little volumes, of Linacre's grammar, or the spurious first edition of the Eeligio, or Digby's Animadversions, with their choice bindings by Riviere or Zaehnsdorff. How thrilled by the story of the discovery of such a treasure on a York bookstall, bound in with an Almanack and bought for half a crown. With what delight we turned the pages of the tall copy of the Pseudoxia Epidemica and dipped into the grave Sir Thomas's discussion of the verity of the pictures of God, or the popular idea " that elephants have no knees." A beautiful Aldine from Mead's own library brought out the story of that great collector and his testamentary instruction that his library be sold so that others might have some of the pleasures of acquisition wliich he had so much enjoyed. We were given a glimpse into the special lore of the bibliophile, and learned something of the work of the pioneer printers and of the great presses of a later


R. BOGGS

date. We learned a little of the fonts of type and the watermarks of papers, as well as the characteristics of the bindings peculiar to certain periods. The nature of book auctions was disclosed to us and we became familiar with the magic names of Sotheby and Quaritch, until some of us found the perusal of a good catalogue as exciting as a detective story. Still more important, we heard about the more famous collections of medical works, and began to project personal visits to the Bodleian, the Royal College of Physicians and the Bibliotheque Nationale.

But best of all and doubtless the ultimate object of all was the gradual acquisition of an epitome of the history of medicine wliich has kept us interested ever since those days.

Moreover, it was not merely the cultural value of a knowledge of the beginnings of the profession, but the constant lesson of the individual worker's triumph over handicaps of isolation, poverty, ridicule or personal peril, to add some contribution to the sum of knowledge, and the reiteration of the theme that the painstaking and observant physician, even though removed from the centers of learning and wide opportunity, has in the past contributed fundamentally to the advancement of knowledge, and may hope to do so in the future.

Again, Dr. Osier stimulated in us an interest in the medical writers of the early days of our own country and showed how much might be found by the investigation of the early journals and books, and tlois has led to the substantial contributions by his associates and pupils to the history of medicine in the colonies, the United States and Canada.

In conclusion, another side of Dr. Osier's bibliophilic activity must be noted, that is, his generous interest in the medical libraries of the country. He was not satisfied to acquire rare and interesting volumes for himself, but was constantly giving such books to the various professional libraries with which he had been associated; thus, McGill, Boston, The College of Physicians in Philadelphia and our own Maryland Faculty and Johns Hopkins have repeatedly received valuable acquisitions from him or from others whom he had induced to give rare volumes or even whole collections.

We are happy to know how vastly " the chief's " collection has grown since he removed to the University of Oxford, so that it is now one of the very best in existence. The catalogue, bibliographic, biographic and literary, of this great collection of the epoch-making works of science occupies most of his leisure, and will form another great contribution to the literature of medicine, second only to the immortal Practice.


I


July, 1919]


217


There are in connection with the task which has been assigned to me many very pleasant aspects. To make a critical analysis, to present a clear picture of Dr. Osier's literary style demands, however, more time and space than are at my disposal and above all more ability as a literar}' critic than I am endowed with.

In reading Dr. Osier's contributions to the literature of medicine, as well as his occasional addresses and essays, I am tempted to linger here and there, to point out the clarity of expression, the simplicity and beautj* of diction and quote passage after passage in illustration of my thesis. Sucli a course would simplify the task before me because these quotations would show the author's style better than any powers of description or any ability of analysis I possess.

In his purely scientific work, as for example, in "The Principles and Practice of Medicine," the author's method and his grasp of his subject are admirable. He follows the advice of the friend of Cervantes when the author of Don Quixote was in a quandary over the preparation of his preface, " Nothing but pure nature is your business ; her you must consult, and the closer you can imitate, your picture is the better."

In my student days some one placed in my hands a copy of Watson's Practice.* While it was not recommended as a text-l)ook to follow as an exponent of the then recognized principles of medical thought and practice, I found it one of the easiest works to read and one from which I obtained much of lasting value. Commenting upon this fact to my preceptor I was told that I had fallen upon a book which possessed, something not common in medical treatises, a good style.

The same is true of Osier's writings upon the strictly scientific aspect of medicine. Unity, order, clarity of description and ease of diction abound throughout his text-book and his various monographs. A master of his subject, liaving made the nature of disease his business, he imparts his information in such a manner that the reader at no time finds it difficult, because of ambiguous phra.«eology or doubtful expression, to grasp his meaning. ITis thoughts are "linked with the wants of his readers," and by the invisible chains which bind mind to mind, he and his reader become one.

The reader finrls that he has a message to imjjart, a principle to establish, a rule of conduct to promulgate, and that be has done so in a logical, attractive manner which compels attention ; and that to my mind is the test and measure of good writing.

Another view of Osier as an author is revealed in his occasional addres-ses and essays. In the two volumes l)efore me — " Aequanimitas and Other Addresses " and " An .\labama Student and Other Biographical Addresses " — Osier's style in all its directness, strength and grace is shown in full measure.

In these volumes, as in other addresses not therein con


• Lectures on the Principles and Practice of Physic. By ThomaB Watson. M. D.. etc.. London. 1843.


OSLER'S LITERARY STYLE

By Edward N. Brush

taincd, notably his farewell to his professional associates and friends in Maryland under the title " Unity, Peace and Concord," Osier exemplifies ButTon's dictum : " The style is the man himself."

Sir Thomas Watson in his memorial of Latham, whose " Lectures on Clinical Jledicine " are examples of the best English style, says : " His letters are treasures of good sense, of lively and epigrammatic comments on men and things and of shrewd and weighty reflections, wise advice and affectionate greetings"; and this can be with great trutli applied to the addresses and essays of Dr. Osier. Lively, epigrammatic, shrewd, weighty and affectionate are all terms which well suit my purpose, which reveal the man through his writing. " Talent alone cannot make a writer," says Emerson, " there must be a man behind the book, a personality which by birth and quality is pledged to the doctrines there set forth."

With Byron one "hates an author that's all author." In Osier's case the author is all man, and the man reflects himself in his work. It is an easy task for those who liave had the pleasure and advantage of intimate association with him to invoke his presence when reading his addresses, as for example, " Internal Medicine as a Vocation," " Medicine in the Nineteenth Century," " The Hospital as a College " and " The Master Word in Medicine."

What, if any, are the secrets of Osier's style ; upon what does it depend? The answer, I think, is simply a love for and thorough mastery of good literature and a message to convey full of high ideals. One William Harrison, writing in 1577, speaks of " an excellent vein of \<Titing not bcforetinie regarded " which had become manifest in England. This he intimates is tlie result not only of a knowledge on the part of WTiters of their own tongue, but of an acquaintance with the Latin and Greek apd often with French and Spanish.

This excellent vein of writing soon became the glory of the Elizabethan age. The development of higher ideals in English national life was rapidly followed, as well as fostered, by the great authors of tlic age of England's literary glory. Style, literarj' excellence, came to be recognized as desirable, and reached its highest manifestation. Back of it all, however, were the ideals which fostered and gave material for the expression of literary style. There was an atmosphere of a great elevation of ideals, public and private, and at the same time tangible objects of national ambition and glory. England was " contending in the cause of the world as well as her own " and there was an outburst of genius which found its counterpart in a smaller degree many years later when England was contending again the world-ambition of Napoleon.

Will a similar development follow the world's war out of which we are just emerging?

When a man who has ideals and honesty of purpose and has filled his mind with the productions of the master spirits of the ages feels the call to write or speak, a beauty of literary style almost inevitablv results.


218


[No. 341


What were the Pierian springs from which Osier drank, from which he attained, as has been said of him, " a breadth of learning and a knowledge of general literature that astound one ? "

I would place first the English Bible. How often either by direct quotation or paraphrase does one find in his addresses and essays sentences and phrases from this well-spring of good English.

Of a liberal knowledge of the classics abundant evidence is found and a ready ability to take text, and illustration as well, from mythology.

With the masters of the English tongue from the early dawn of English literature till the present he has clearly dwelt on terms of greatest intimacy.

That half hour devoted every day to commujiion with the minds of the past finds lessons reflected in writing, but never with any indication of servile copying. Osier's style is his own.

The last page of Aequanimitas has a list of books which Osier has called a Bed-side Library for Medical Student*. This is: 1. Old and Xew Testament; 2. Shakespeare; 3. Montaigne; 4. Plutai ch's Lives ; 5. Marcus Aurelius ; 6. Epictetus; 7. Eeligio Medici; 8. Don Quixote; 9. Emerson; 10. Oliver Wendell Holmes — Breakfast-Table Series.

John Brown, of Edinburgh (Horae Subsecivae, p. 400), gives a list which he commends to the medical student. These are " Shakespeare, Cervantes, Milton, Dryden, Pope, Cowper, Montaigne, Addison, Defoe, Goldsmith, Fielding, Scott, Lamb, Macaulay, Jeffrey, Sydney Smith, Helps and Thackeray." Brown's list has nearly twice as many names as that given by Osier, but in solid worth the shorter list outweights the longer.

Dr. Osier's list fulfills in brief compass the requirements of a liberal education and presents to the reader examples of the best in literature.

Reference has already been made to the fact that Dr. Osier is reflected in his writings, that in the words of Taine " behind the docmnent there was a man."

In this instance that man had for years exercised, as I have tried to show elsewhere, a singular and powerful influence on medical education, hospital methods and in binding together for harmonious action the members of his profession.

He had encouraged the study of medical history and biography and found time in the midst of duties, which might well have availed as an excuse from further intellectual labors, to contribute in large measure to these subjects.

Always, with no false note, his cry has been for scientific righteousness. He has had ideals and, as an idealist, he has done what he has himself said other idealists have often done, "gradually moulded to their will conditions the most adverse and hopeless."


All of this and much more is reflected in the text of Osier's writing, presented often in epigrammatic form, reinforced by text and example from many sources, enlivened by a humor that is irresistible.

No medical contributor to general literature since Holmes has possessed the saving sense of humor to the degree shown in Osier's writings and no one could have used it with greater discrimination or more certain effect.

Often when apparently writing in a most humorous vein he has been the most serious in his meaning, and how often and with what delicate touch does he expose some of our human faults and foibles. I yield to the temptation to quote here an illustration of that to which I have just referred. " Curious, odd compounds are these fellow-creatures, at whose mercy you will be ; full of fads and eccentricities, of whims and fancies ; but the more closely we study their little foibles of one sort and another in the inner life which we see, the more surely is the conviction borne in upon us of the likeness of their weaknesses to our own. The similarity would be intolerable if a happy egotism did not often render us forgetful of it. Hence the need of an infinite patience and an ever-tender charity toward these fellow creatures; have they not to exercise the same toward us ? "

To Osier's stylo may be applied part of his own estimate of some of the older writers. Burton, Browne and Fuller : " A rare quaintness, a love of odd conceits and the faculty of apt illustration."

In his writings he reminds us of what he has said of Browne, " The ehann of high thoughts clad in beautiful language may win some readers to a love of good literature ; but beyond this is a still greater advantage .... the Eeligio is full of the counsels of perfection."

So, too, is there with Osier a charm of high thoughts clad in beautiful language and always the " counsels of perfection."

Osier's literary work is yet unfinished, the three score years and ten which he has attained have but ripened his judgment and enlarged his field of vision. He has seen many of his ideals become realities. The stress of the great world war has pressed heavily upon him and brought to him a great sorrow. The iron has entered into his soul. His future work will bear the stamp of all these.

He has made his own estimate of the " princes of the blood " in literature from our profession. He places Sir Thomas Browne, Holmes and John Bro^^^l, of Edinburgh, in a group high in the circle.

Osier possesses many things in common with these three in literary style and in literary excellence, and deserves a place in the same exalted iVllowship.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1919


PLATE XXVII




fTtf^j^


I


July, 1919]


219


BIELlOGRArHY


Sir William Osier's bibliography covers a period of 49 years (18T0-1919). The 730 titles include both books and articles. Many of these are in the library of The Johns Hopkins Hospital and have added value as being personal gifts from tlie author.

1870 On Canadian diatomaces. Canad. Naturalist. Montreal. 1S70, n. s., V, 142-151.

In his: Published Mem. & Communicat.. Montreal, 1882, S".

(Collect, repr., 1872-1882, i. no. 1.]

1873

Action of certain reagents — atropia, physostigma and curare — on the colorless blood-corpuscles. Quart. J. Micr. Sc, Lond.,

1873. n. s.. xiii. 307-.'?09.

In his: Published Mem. & Communicat., Montreal, 1882, 8'. [Collect, repr. 1872-1882, I, no. 2.]

1874

An account of certain organisms occurring in the liquor sanguinis. (Rep. bv J. B. Sanderson.] Proc. Roy. Soc. Lond.,

1874. xxii. 391-398.

In his: Collect, repr., 1872-82, i, no. 3.

1875

Valedictory address to the graduates in medicine and surgery. McGill University. Canada M. & S. J.. Montreal, 1874-75, iii, 433-438. In his: Published Mem. & Communicat.. Montreal, 1882, 8°. [Collect, repr, 1872-82. i, no. 4.]

1876

Introductory remarks to, and synopsis of, practical course on Inatltutes of medicine. Canada M. & S. J., Montreal, 1875-76, iv. 202-207.

On the pathology of miner's lung. Canada M. & S, J., Montreal. 1875-76. iv. 145-168. In his: Collect, repr, 1872-82. 1. no. 7.

Case of scarlatina millaris. Canada M. & S. J., Montreal, 1875-76, Iv, 49-54. In his: Collect, repr., 1872-82, i, no. 5.

On the histology of leucocythemia. Canada M. & S. J.. Montreal, 1875-76. Iv, 439-477. In his: Collect, repr. 1872-82, 1. no. 6.

Clinical notes on small-pox. I. The initial rashes. II. Htemorrhagic small-pox. III. A form of hjpmorrhagic small-pox. Montreal. 187fi. Gazette P't'g House. 35 p., 8°. Also: Canada M. & S. J., Montreal. 1876-77, v, 241; 2S9. In his: Published .Mf-m. & Communicat., Montreal, 1882. [Collect repr, 1872-82, 1, nos. 8, 9. 10.]

Trichina spiralis. Extract from a lecture on "Animal parasites and their relation to public health." being one of the Somervllle lectures of the Natural history society. Canad. J. M. Sc. Toronto, 1876. I. 134-13.->.

1877 Introductory lecture on the opening of the forty-fifth session of the medical faculty. McOlll T'nlverslty. Oct. 1, 1877. Montreal, IS77. Dawson Bros.. 19 p., 8°. Also: Canada M. & S. J.. Montreal, 1877-78, vl, 193-210. In his: Published .Mem. & Communicat. Montreal, 1882, 8'. [Collect repr. 1872-82, I. no. 14.)

Verminous bronchitis in dogs; read before the Montreal Veterinary Medical Association, March 29. Veterinarian. Lend., 1877, I, 387-397. In his: Published Mem. & Communicat, Montreal. 1882, 8'. (Collect, repr. 1872-82. 1, no. 12.]

Beschaffenheit des Rlutes und Knochenmarkes bcl pernlcioser Anamie. Centralbl. f. d. med. Wissenscb., Berl.. 1877, xv, 498. /» his: Published Mem. & Communicat, Montreal. 1882, 8". [Collect repr. 1872-82. i, no. 18.)


Osier, W., and Bell, J.: Case of progressive pernicious aniemia. Clinical report, by John Bell. Pathological report, with remarks, by William Osier Montreal, 1877, Lovell Print. & Publ. Co., 12 p., 12°. In his: Collect repr, 1872-82, i, no. 16. Osier, W., and Gardner, W.: Case of progressive pernicious aniemla (idiopathic of Addison). Canada M. & S. J., Montreal, 1876-77, v, 385-404. In his: Collect, repr, 1872-82, 1, no. 15.

Osier. W., and Gardner, \V.: Ueber die BeschafTenlieit des Blutes und Knoclionmarkes in der progressiven perniciosen Anamie. Centralbl. f. d. med. Wissenscli., Berl., 1877, xv, 258-260. In his: Published Mem. & Communicat, Montreal, 1882, 8°. [Collect repr. 1872-82, i, no. 17. J

1878

On the pathology of the so-called pig-typhoid. London. 1878, Bailli^re, Tindall & Cox, 20 p., 8°. Vet. J. & Ann. Comp. Path.. I>ond.. 1878, vi, 385-402. In his: Publislied Mem. & Communicat, Montreal, 1882. [Collect, repr., 1S72-S2, i, no. 20. |

Over-strain of the heart, as illustrated by a case of hypertrophy, dilatation and fatty degeneration of the heart, consequent upon prolonged muscular exertion. Montreal, 1878, Gazette P't'g House. 13 p., 8°.

Also: Canada M. & S. J., Montreal, 1877-78, vi, 385-395.

In his: Published Mem. & Communicat, Montreal, 1882, 8°.

[Collect repr. 1872-S2, i, no. 19.)

Phthisical cavities in left lung; gangrene of pulmonary tissue about one of them. Canada M. & S. J., Montreal, 18'77-78, vi, 114. Also: Montreal Gen. Hosp. Rep. (1876-77), 1878, i, 37.

Pleura. Small fibroid thickenings on visceral layer. Canada M.

& S. J.. Montreal. 1S77-7S. vi. 115-116. Also: Montreal Gen. Hosp. Rep. (1876-77), 1878, i, 40-41. Fracture of 1st and 2d ribs near vertebra>, from direct violence;

deep abscess of the neck; obliteration of subclavian artery;

empyema. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, 1,

11-12.

Necrosis of tibia. Ulcerative endocarditis, pyaemic pneumonia.

Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, 1, 12-13. Necrosis of femur, pya-niic pnounionia; abscesses in superficial

muscles; pustular eruption on skin. Montreal Gen. Hosp.

Path. Rep. (1876-77), 1878, i, 13-14.

Primary cancer of bodies of 2d and 3d vertebrae and heads of corresponding ribs on right side. Secondary masses In ribs, liver and brain. Chronic phtlilsis. Lobar pneumonia. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878. 1, 1416.

A case of hypertrophy and dilatation of the heart; no valvular or arterial disease; no clironlc kidney affection; hydrothorax; pulmonary apoplexy: general venous stasis. Montreal Gen. Hosp. Pat'h. Rep. (1876-77). 1878. i, 16-20.

Aneurism of commencement of thoracic aorta, unsuspected during life: death from general tuberculosis. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 20-21.

Sacculated aneurism of ascending portion of arch of aorta; rupture into the right pleural sac. Montreal Gen. Hosp. Path. Rep. (1876-77), 1S78, 1, 21.

Sacculated aneurism of aorta, at termination of the arch, unsuspected during life. Death from pneumonia. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, 1, 22.

Aneurism of hepatic artery. Right branch almost obliterated. Multiple abscesses In the liver. Montreal Gen. Hosp. Path. Rep. ( 1876-77). 1878, I, 22-.30.

Aneurlsmal dilatation of branches of pulmonary artery on the walls of phtlilsical cavities. Death from ha>mopty8l8. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, I, 30.

Aneurism at second bifurcation of the right midille cerebral artery; rupture; extravasation of blood Into the Sylvian fissure, and laceration of substance of the teniporosphenoldal lobe; death In 36 hours. Montreal Gen. Hosp. Path. Rep. (l.>i76-77). 1878. I, 30-32.


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1


Ossification of greater portion of mucous membrane of trachea. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 32.

Pneumonia of the upper lobe of the right lung; extensive meningeal inflammation. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 33-34.

Almost entire hepatization of left lung; with small pneumonic area in right. Extensive diphtheritic colitis. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 34.

Diabetes, phthisical cavity in right lung surrounded by hepatized tissue. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 34-35.

Chronic phthisis, almost entire destruction of both lungs. Healthy portion involved in a pneumonia. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 35.

Simple pneumonia of left lung, right-sided pleurisy. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 35.

Pneumonia of right lung, uniform involvement of pleura covering it. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 35-37.

Fibroid contraction and induration of entire right lung; cavity at apex; displacement of heart; hypertrophy with dilatation of right chambers. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 38-39.

Chronic phthisis: perforation of lungs; pneumothorax; dermoid cyst of right ovary. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 39-40.

Epithelioma of right side of tongue, extending from base to near the apex. Removal of organ with galvanic gcraseur. Suppuration beneath cervical fascia. Pyjemia. Montreal Gen. Hosp. Path. Rep. (1876-77), 1S7S, i, 41-42.

Chronic phthisis. Miliary tubercles in lungs and pharynx. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 42-43.

Cancer of the cardiac orifice, involving the oesophagus. Secondary masses in other parts of the organ. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, 1, 43-44.

Medullary cancer, involving the pyloric zone of the stomach; perforation, peritonitis. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 44.

Passage of two feet of the ileum through a loop attached to the sigmoid flexure. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 45.

Round ulcer of duodenum. Montreal Gen. Hosp. Path. Rep. (187677), 1878, i, 45-46.

Perforation of typhoid ulcer during convalescence, owing to an indiscretion in diet. Montreal Gen. Hosp. Path. Rep. (187677), 1878, i, 46.

Perforation of a deep ulcer at end of second week. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 46-47.

Typhoid fever. Perforation. Peritonitis. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 47.

Four round ulcers in the ileum. Peyer's patches not generally involved. Sliglit hypostatic pneumonia. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 48.

Slight swelling of Peyer's glands, only one small spot of ulceration.

Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 48. Round ulcer of c<ecum, perforation, general peritonitis. Montreal

Gen. Hosp. Path. Rep. (1876-77), 1878, i, 49.

Abscesses in the mesentery. Suppuration of portal vein. Empyema. Perforation of appendix, general peritonitis. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 51.

Acute tubercular inflammation of the peritoneum. Small caseous mass in left lung. Right-sided pleurisy. General hyperplasia of the bone marrow. Montreal Gen. Hosp. Path. Rep. (187677), 1878, i, 52-56.

Cirrhosis of liver, with enlargement; jaundice; no ascites; delirium tremens ( ?) ; erysipelas of the head. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 56-60. Also: Canada M. & S. J., Montreal, 1877-78, vi, 249-253. Syphilitic ulceration of left frontal bone; large node on left tibia; gummata in liver. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, 1, 60-61. Also- Canada M. & S. J., Montreal, 1877-78, vi, 253.


Primary cancer of the liver; ascites; jaundice; secondary mass in tail of pancreas; small secondary nodules in kidneys. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 61-64. Also: Canada M. & S. J., Montreal, 1877-78, vi, 254-256.

Cancer of neck of the gall-bladder and lymphatic glands in the portal fissure; compression of the hepatic ducts; secondary masses in liver; enormous distension of gall-bladder and haemorrhage into it; gallstones. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 64-65.

Extensive abscesses in the mesentery, following typhoid fever. Suppuration of the portal vein and its branches in the liver. Empyema. Perforation of the appendix vermiformis; peritonitis; miliary tubercles in lungs. Amyloid degeneration of spleen, liver, and mucous membrane of small intestine. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 65-71.

Tuberculous disease of right kidney, pelvis, ureter and bladder.

Tubercles in left kidney and lungs. Perforation of tuberculous

ulcer in bladder. Peritonitis. Montreal Gen. Hosp. Path. Rep.

(1876-77), 1878, i, 72-73. Old scrofulous disease of right kidney, which is converted into

cysts. Recent affection of the left. Montreal Gen. Hosp. Path.

Rep. (1876-77), 1878, i, 73-74.

Old disease of the right kidney, which is converted into five or six cysts, filled with a putty-like material. Extensive tuberculous disease of the organ. Miliary tubercles in lungs. Albuminoid spleen. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 74-75.

Suppuration about right kidney. Pysemic abscesses in elbows, ankles and anterior mediastinum. Peritonitis. Pleurisy. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 75-76.

Stone in the bladder. Prostatic tumors around the urethral orifice. Ulceration on mucous membrane. Pyelitis; ulceration of apices of renal pyramids. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 76-77.

Epithelioma of cervix; obstruction of the canal; dilatation of the uterine cavity. Pyometra. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 77-78.

Dermoid or piliferous cyst of right ovary. Chronic phthisis. Pneumothorax. Montreal Gen. Hosp. Path. Rep. (1876-77),

1878, i, 78-79.

Small cavity and caseous masses in lung. General tuberculosis. Meninges of brain unaffected; central softening. Spinal meninges extensively involved. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 79-81.

Meningeal affection slight. Ventricles distended, walls soft. Very few miliary tubercles in the organs. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 81-82.

Meningeal affection very extensive on the cortex, slight at the base. Ventricles large, walls not soft. Large caseous mass in left lung. Miliary tubercles in lungs and on peritoneum. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 82-83.

Slight meningeal inflammation. One caseous mass and a few tubercles in lungs. Old morbus coxae. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 84.

Profound anaemia without discoverable lesion. Fatty degeneration of organs. Hyperplasia of bone-marrow. Montreal Gen. Hosp. Path. Rep. (1876-77), 1878, i, 84-97.

Ueber die Entwickelung von Blutkorperchen im Knochenmark bei pernicioser Anamie. [Berlin, 1878, L. Schumacher.] Centralbl. f. d. med. Wissensch., Berl., 1878, xvi, 465-467. In his: Published Mem. & Communicat., Montreal, 1882, 8°. [Collect, repr., 1872-82, i, no. 21.]

Osier, W., and Ross, G. : Aneurism of hepatic artery; multiple abscesses of the liver. Canada M. & S. J., Montreal, 1877-78, vi, 1-12. In his: Collect, repr., 1872-82, i, no. 13.

1879 Case of obliteration of vena cava inferior, with great stenosis of orifices of hepatic veins. J. Anat. & Physiol., Lond., 1878-79, xiii, 291-304. In his: Collect, repr., 1872-82, i, no. 24.

Two cases of rare kidney tumors. Canada M. Rec, Montreal, 1879, vii, 164.


July,, 1919]


221


Miner's phthisis (Rep. by R. Dawson). Canada M. & S. J., Montreal. 1878-79. vii. 452-454. Also; Montreal Gen. Hosp. Rep., 1880, 1, 297-299.

Acute Bright's disease in a child; remarkable persistence of bloodcorpuscles and casts in the urine after disappearance of albumin. (Rep. by A. Henderson.) Canada M. & S. J., MonUeal, 1878-79, vii. 455.

Aphasia, with right-sided hemiplegia, coming on fifteen days after delivery. [Rep. bv D. Mignault.] Canada M. & S. J., Montreal, 1878-79, vii, 492-493.

Acute rheumatism treated with salicylate of soda. Delirium apparently caused by the remedy. [Rep. by B. E. Maclcenzie. ] Canada M. & S. J., Montreal, 1878-79, vii, 493-494.

Cobnheim's theory of tumors. Transl. and condensed from vol. I of his Vorlesungen iiber allgemeine Pathologie (Lectures upon general pathologj-). By Dr. Osier. Canada M. & S. J., Montreal, 1878-79, vii. 337-347; 398-408.

1880

Concussion of brain; temporary hemiplegia; general convulsions: rapid recovery. [Rep. by Imrie.] Canada M. & S. J., Montreal, 1879-80, vili, 8.

Aggravated stuttering, following fall on the head. Canada M. & S. J., Montreal. 1S79-S0, viii, 9.

Extreme irregularity of the heart [Rep. by E. J. Rogers.] Canada M. & S. J., Montreal, 1S79-S0, viii, 9.

Chronic pleurisv: flattening of sides of chest Canada M. & S. J., Montreal, 1879-80, viii, 109-111.

Croup or diphtheria; which? Canada M. & S. J., Montreal. 1879-80, vii!, 207-211. In his: Collect repr., 1872-82, i, no. 23.

Three cases of brain disease. Canada M. & S. J., Montreal, 1879-80. viii, 295; 346.

Anomalous case of pyn^mia; suppuration about tissues in left Inferior carotid triangle; pya>mic abscess beneath tensor vaginx femoris; pviemic infarcts in the lungs: septic pleurisy. Canada M. & S. J.. Montreal, 1879-80. viii, 544-548.

Catalogue of a series of specimens illustrative of the morbid anatomy of the brain and spinal cord. Exhibited at Ottawa Meeting of Canada Medical Association, Sept. 1 and 2, 1880.

Case of congenital and progressive hypertrophy of the right upper extremity. J. Anat & Physiol., Lond., 1879-80, xiv, 10-12. In his: Collect repr., 1872-S2, i, no. 25.

Two cases of striated mvo-sarcoma of the kidnev. J. Anat. & Physiol.. Lond.. 1879-80. xiv, 229-233. In his: Collect repr., 1872-82, 1, no. 26.

Cases of cardiac abnormalities. Montreal Gen. Hosp. Rep., ISSO, i. 177-192. In his: Collect, repr, 1872-82, i, no. 27.

On the condition of fusion of two segments of the semilunar valves. Montreal Gen. Hosp. Rep., 1880, i, 233-242. In his: Collect, repr., 1872-82, i, no. 28.

Wound of the central part of the 1st and 2d frontal convolutions on left side. Montreal Gen. Hosp. Rep., 1880, i. 257-258.

Bullet wound of right frontal lobe; entire absence of cerebral symptoms. Montreal Gen. Hosp. Rep., 1880, i, 258-260.

Cases of aneurism of the aorta. Montreal Gen. Hosp. Rep., 1S80, I, 260-265.

Aneurism of Innominate-rupture of saccular dilatation of aorta into pericardium. Montreal Gen. Hosp. Rep., 1880, 1, 265-266.

Aneurism of splenic artery; perforation Into transverse colon. Montreal Gen. Hosp. Rep.. 1880. I. 2r,6-268.

Small aneurism of renal artery. Montreal Gen. Hosp. Rep.. 1S80, 1, 268.

Four cases of intracranial aneurism. Montreal Gen. Hosp. Rep., 1880, i. 268-27.5.

Aneurisms of braflches of pulmonary artery on wall of cavities: hiemoptysis in chronic phthisis. Montreal Gen. Hosp. Rep., 1880, i, 275-276.

Two cases of hypertrophy of the heart. Montreal Gen. Hosp. Rep.,

1880, I, 276-282.


Perforation of pulmonary artery by ulcer of left bronchus; sudden death from hsemoptysis; chronic bronchitis, emphysema, phthisis. Montreal Gen. Hosp. Rep., 18S0, i, 282-283.

Instance of four pulmonary valves. Montreal Gen. Hosp. Rep., 1880, 1, 284.

Bayonet wound of left subclavian artery at its origin. Montreal Gen. Hosp. Rep., 1880, i, 284.

Fatty degeneration of heart In diphtheria; sudden death on the thirteenth day. Montreal Gen. Hosp. Rep., 1880, i, 285.

Two cases of thrombosis of pulmonary artery. Montreal Gen. Hosp. Rep., 1880, i, 285-287.

Thrombosis of branches of right pulmonary artery. Montreal Gen. Hosp. Rep., ISSO, 1, 287-290.

CEdema of right lung: hydrothorax of left pleura; contracted kidneys. Montreal Gen. Hosp. Rep., ISSO, i. 290-291.

CEdema of left lung; morphia poisoning. Montreal Gen. Hosp. Rep., ISSO. i, 291-292.

Pneumonia; ulcerative endocarditis; meningitis. Montreal Gen. Hosp. Rep., 1880, i, 292-295.

Pneumonic phthisis. Montreal Gen. Hosp. Rep., 1880, i, 295-297.

Note on the occurrence of membrane in the trachea and bronchi in

diphtheria. Montreal Gen. Hosp. Rep., 1880, i, 299-300. Foreign body in oesophagus; ulceration; perforation; retro-pharyn geal and oesophageal abscess. Montreal Gen. Hosp. Rep., 1880,

1, 300-301.

Three cases of cancer of the stomach. Montreal Gen. Hosp. Rep., 1880, I, 301-302.

Three cases of ulcer of the stomach. Montreal Gen. Hosp. Rep., 1880, i, 304-306.

Three cases of simple ulcer of duodenum. Montreal Gen. Hosp. Rep., 1S80, i, 306-311.

Typhoid fever: rapidly fatal, with nervous symptoms. Montreal Gen. Hosp. Rep., 1880, i, 311-312.

Perforation of appendix vermiformis; circumscribed abscess: perforation of ileum; haemorrhage from bowels. Montreal Gen. Hosp. Rep., 1880, I, 313-314.

Liver; hydatid cyst Montreal Gen. Hosp. Rep., 1880, i, 314-316.

Primary cancer of liver. Montreal Gen. Hosp. Rep., 1880, 1, 316-317.

Cirrhosis of liver; collateral circulation by means of an enlarged umbilical vein; death from pneumonia. Montreal Gen. Hosp. Rep., 1880, i, 317-318.

Pj-lephlebitis. Montreal Gen. Hosp. Rep., 1880, 1, 318-321.

Extensive scald of thorax; pneumonia; numerous spots of fatty degeneration in kidneys. Montreal Gen. Hosp. Rep., 1880, i, 321-322.

Small contracted kidneys; left organ affected to an unusual degree; right onlv Involved in the lower part; hypertrophy of heart Montreal Gen. Hosp. Rep., 1880, 1, 322-324.

Large cirrhotic kidneys (congestedl ; hypertrophy of heart; apoplexy. Montreal Gen. Hosp. Rep., 1880, 1, 324-325.

Sarcoma of left kidney. Montreal Gen. Hosp. Rep., 1880, I, 325-328.

Dermoid of ovary; ulcerative colitis. Montreal Gen. Hosp. Rep., 1880, i, 328-329.

Cancer of neck of uterus; constriction of right ureter; pyoneph.-osls. Montreal Gen. Hosp. Rep., 1880, 1, 329-331.

Ruptured follicle in right ovary; peritonitis. Montreal Gen. Hosp. Rep., 1880, i, 331-333.

Extra-uterine (abdominal) pregnancy. Montreal Gen. Hosp. Rep.,

1880, I. 333-335. Cryptorchldlsmus. Montreal Gen. Hosp. Rep., 1880, 1, 335-33G.

Medullary sarcoma of axillary glands; secondary masses in heart, lungs, stomach. Intestines, liver, spleen, kidneys, suprarenal capsules, and pancreas. Montreal Gen. Hosp. Rep., 1880, 1, 336-339.

Sarcoma of retro-peritoneal glands: Lobsteln cancer. Montreal Gen. Hosp. Rep., 1880, 1, 339-340.

Lympho-sarcoma of deep cervical glands, Involving the thyroid and simulating goitre. Montreal Gen. Hosp. Rep., 1880, I, 340-342.


222


[No. 341


On Giacomini's method of preserving the brain. Med. Rec, N. Y.,

1880, xvii, 315-316.

On the systolic hrain murmur of children. Boston M. & S. J., 1880, ciii, 29-30. In Jiis: Collect, repr., 1872-82, i, no. 30.

On heredity in progressive muscular atrophy as illustrated in the Farr family of Vermont. Arch. Med., N. Y., ISSO. iv, 316-320. In his: Collect, repr., 1872-82, i, no. 33.

On a remarkable heart-murmur, heard at a distance from chestwall. Med. Times & Gaz.. Lond., ISSO, ii, 432. In his: Collect, repr., 1S72-82, i, no. 34.

Lympho-sarcoma of deep cervical glands, involving the thyroid and simulating goitre. Montreal Gen. Hosp. Rep., ISSO, i, 340-342.

Montreal General Hospital. Pathological reports. 1. (1876-77); 2. (1877-79), Montreal. 1878-80. (2. report repr. from: Montreal Gen. Hosp. Rep., Clin. & Path., ISSO. i.) 1 and 2 also in his: Published Mem. & Communicat., Montreal,

1882. [Collect, repr., 1872-82, 1, nos. 22 & 29.]

Osier, W., ed. Montreal General Hospital. Reports, clinical and pathological, by the medical staff, v. i, Montreal. ISSO. Dawson Brothers, 390 p., S".

18S1

On some points in the etiology and pathology of ulcerative endocarditis. Lond., 1881, J. W. Kolckmann. 8 p., 8°. Tr. Internat. M. Cong., 7. sess., Lond.. 1881, i, 341-346. In his: Collect, repr., 1882-92, ii, no. 44.

Renal cirrhosis; with special reference to its latency and to sudden, fatal manifestations occurring in its course. Toronto,

1881. Dudley & Barnes, 13 p., 8°. Canada Lancet, Toronto, 1880, xiii, 353-359. In his: Collect, repr., 1872-82, i, no. 42.

On some of the effects of the chronic impaction of gallstones in the bile-passages, and on the " fievre intermittente hgpatique " of Charcot. London, ISSl, Pardon & Sons, 15 p., 12°.

Med. Times & Gaz., Lond., 1881, ii, 111-114.

In his: Collect, repr., 1872-82, i, no. 41.

Cases of insular sclerosis. Canada M. & S. J., Montreal, 1880-81, ix, 1-11. In his: Collect, repr., 1872-82, i, no. 31.

Case of medullary neuroma of the brain. J. Anat. & Physiol., Lond., 1880-81, xv, 217-225. In his: Collect, repr., 1872-82, i, no. 35.

Retro-peritoneal cancer. Canada M. & S. J., Montreal, 1S80-81, ix, 161.

Brief description of the new physiological laboratory, McGill College. Canada M. & S. J., Montreal, 1880-81, ix, 198-201.

Cases of Hodgkin's disease. Canada M. & S. J., Montreal. 1S80-S1, ix, 385-397. In his: Collect, repr., 1872-82, i, no. 37.

Clinical lecture on a case of fibroid phthisis. Delivered at the Montreal General Hospital in the summer session course, May 10, 1881. Canada M. & S. J., Montreal, 1880-81, ix. 641650. In his: Collect, repr., 1872-82, i, no. 40.

Notes of the second demonstration in the morbid anatomy course in McGill College. Canad. J. M. Sc, Toronto, 1881, vi, 350-353.

On delayed resolution in pneumonia. Canada Lancet, Toronto, 1880-81. xiii, 99-103. In his: Collect, repr., 1872-82, i, no. 32.

Clinical lecture on idiopathic or pernicious auEemia. Canad. J. M. Sc, Toronto, 1881, vj, 135-141. In his: Collect, repr., 1872-82, i, no. 39.

Infectious (so-called ulcerative) endocarditis. Arch. Med., N. Y., 1881, V, 44-68. In his: Collect, repr., 1872-82, no. 36.

Ulcerative endocarditis. Bull. N. York. Path. Soc, 1881, 2. s., i, 29-33.

Notes on intestinal diverticula. Ann. Anat. & Surg., Brooklyn, N. Y., 1881, iv, 202-207. In his: Collect, repr., 1872-82, i, no. 43.


Published memoirs and communications. (To Jan. 1, 1882), Montreal, 1882, 8°.

Collected reprints. First series, 1872-1882. Montreal, 1882, 8°. [" Published memoirs and communications " the same as " Collected reprints. First series."]

Clinical remarks on cases of inherited syphilis. Canada M. & S. J., Montreal, 1881-82, x, 588-592.

Clinical remarks on leucocythemia. Canada M. & S. J., Montreal, 18S1-S2, X, 719-727.

On the brains of criminals. With a description of the brains of two murderers. Canada M. & S. J., Montreal, 1881-82, x, 38.5-398. In his: Collect, repr., 1S82-92, ii, no. 45.

Case of obliteration of the portal vein (pylephlebitis adhesiva). J. Anat. & Physiol., Loud., 1881-82. xvi, 208-216. In his: Collect, repr., 1882-92, ii, no. 46.

XJeber den dritten Formbestandteil des Blutes. Centralbl. f. d. med. Wissensch., Berl., 1882, xx, 529-531. In his: Collect, repr., 1882-92, ii, no. 47.

Summer session clinics. No. 1. Cases of inherited syphilis. No. 2. Acute Bright's disease. Nos. 3-4. Pneumonia. No. 5. Leucocytha?mia. Montreal, 1882. 44 p., 8°. In his: Collect, repr., 1882-92, ii, no. 48. A clinical lecture on empyema and its antiseptic treatment. Med. News, Phila., 1882, xli, 113-115. In his: Collect, repr., 1882-92, ii, no. 50.

Urcemic delirium and coma at a very early stage of interstitial nephritis. Arch. Med., N. Y., 1882, vii, 213-215. In his: Collect, repr., 1S82-92, ii, no. 51. On certain parasites in the blood of the frog. Canad. Naturalist, Montreal, 1882, x. 406-410. In. his: Collect, repr., 1882-92, ii, no. 52. On Canadian fresh-water polyzoa. Canad. Naturalist. Montreal, 1882, X, 399-405. In his: Collect, repr., 1882-92, ii, no. 53.

On echinococcus disease in America. Am. J. M. Sc, Phila., 1882. n. s., Ixxxiv, 475-480. In his: Collect, repr., 1882-92, ii, no. 62.

Atheromatous plate and ulcers on arch of aorta. Med. News, Phila., 1SS2, xl, 249.

Atheromatous abscess and aneurism of the right iliac artery; general atheroma. Med. News, Phila., 1882, xl, 250.

Fatty diarrhoea. Med. News, Phila., 1882, xli, 580.

Tapping the gall-bladder. Med. News, Phila., 1882, xli, 580.

Hsematemesis in chronic enlargement of the spleen. Med. News, Phila., 1882. xli, 581.

Notes on cells containing red blood-corpuscles. Lancet, Lond., 1882, i, 181.

1883 Cancer of ascending colon: extensive secondary growths in liver. Canada M. & S. J., Montreal, 1882-83, xi, 28.

Obstinate quotidian ague. Canada M. & S. J., Montreal, 1882-83, xi, 29.

Clinical note on hasmatemesis in chronic splenic tumour. Canada M. & S. J., Montreal, 1882-83. xi, 267-270. Also: Canada M. Rec, Montreal, 1SS2-83, xi, 30.

Erosion of internal carotid in cavernous sinus six weeks after a blow on the head ; fatal haemorrhage from the nose. Canada M. & S. J., Montreal, 1882-83, xi, 357.

Aneurism of anterior communicating artery. Canada M. Rec, Montreal, 1882-83, xi, 133.

Empyema discharging through lung; recovery. Canada M. Rec, Montreal, 1882-83, xi, 223.

Aneurism of the anterior cerebral artery. Canada M. Rec, Montreal, 1882-83, xi, 241.

Clinical remarks on a case of Hodgkin's disease. Canada M. & S. J., Montreal. 1882-83, xi, 712-717. In his: Collect, repr., 1882-92, ii, no. 55.

Preataxic tabes dorsalis. A clinical lecture delivered during the summer session of the McGill Medical Faculty. Med. News, Phila.. 1S83. xliii, 197-199. Ill his: Collect, repr., 1882-92, ii, no. 56.




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223


The third corpuscle of the blood. Med. News, Phila.. 1883. xliii, 701-702. In his: Collect, repr., 1SS2-92. li, no. 57.

On some natural modes of cure in empyema. A clinical lecture delivered during the summer session of the McGill Medical Faculty. .June 2it, ISS:!. Med. Rec. N. Y., 1S83, xxiv, 429-481. In his: Collect, repr.. 1882-92, ii. no. 58. Report on the brains of Richards and ORourlce. Canada M. & S. J., Montreal. 1882-83. xi. 461-466. In his: Collect, repr., 1882-92, ii, no. 59. Secondary myeloid disease of pleura and lung, lllust. M. & S.,

N. Y., 1883, ii, 117. Clinical remarks on tlie nephritis of pregnancy. Canad. Pract.,

Toronto, 1883, viii. 133-137. Thrombosis and embolism of the superior mesenteric artery. Med.

News. Phila., 1883, xlii, 693. Scirrhus of pancreas: secondary colloid of lungs. Med. News,

Phila., 1883, xlii, 694. Osier, W.. and Clement. A. W. Cestode tuberculosis. A successful experiment in producing it in the calf. Am. Vet. Rev., N. Y., 1882-83, vi. 6-10. In his: Collect, repr, 1882-92, ii, no. 49. Osier, W., and Clement, .\. W. An investigation into the parasites in the porlt supply of Montreal. Montreal, 1883, Gazette Printing Co.. 14 p., 8 = .' Also: Canada M. & S. J., Montreal, 1882-83, xi, 325-336. In his: Collect, repr.. 1882-92, 11, no. 54.

1884 Ovarian cysts in an infant. Canada M. Rec, Montreal, 1883-84,

xii, 52. Fibro-glioma of upper end of ascending frontal gyrus; Jacksonian epilepsy of fourteen years' standing; the leg-centre. Canada M. Rec., Montreal. 1883-84, xii, 82. Aneurism of aorta; rupture into left bronchus. Canada M. Rec,

Montreal, 1883-84, xii, 98. Cases of dysentery. Canada M. & S. J., 1883-84 xii, 330-333. Syphilitic caries of inner table of skull; great thickening of calvaria: compression and deformity of the brain. Med. News, Phila.. 1884. xliv. 25. Also: Canada .M. & S. J.. Montreal, 1883-84, xii, 351. Also: Canada M. Rec, Montreal, 1883-84, xii, 78.


Remarks on clinical cases. Canada M. & S. J., Montreal, 1884-85, xiil 328-333 In his: Collect repr., 1882-92, ii, no. 60.

A contribution to Jacksonian epilepsy and the situation of the leg centre. Am. J. M. Sc, Phila., 1885, n. s., Ixxxix, 31-37.

In his: Collect, repr, 1882-92, ii, no. 61. The Gulstonian lectures on malignant endocarditis. Delivered at the Royal College of Physicians of London, March, 1885. London, 1885, 31 p., 8'.

Also: Brit. M. J., Lond.. 1885, 1, 467-470; 522; 577.

Also: Lancet, I^nd., 1885, 1, 415; 459; 505.

Also: Med. News. Phila.. 1885, xlvi. 309-313; 337; 365.

In his: Collect, repr. 1882-92, II, no. 63.

Notes on the morbid anatomy of pneumonia. Canada M. & S. J., Montreal, 1884-85, xlii, 596-60.5. In his: Collect, repr, 1882-92, II, no. 64.

Notes on fho mrvrWH onot^r.,.. «f »..-».. IJ » ^- • — ' J^


iiini.ifKiRAriiY (oMPii.Ki) nv MINNIE WRIGHT BLOGG

LiniLVBIAN. JOHNS HOPKINS IIOSPITAI.


Specimen of aneurism of the aorta with rupture into the trachea in two places, and perforation of the oesophagus. Boston M. & S. J., 1885, cxii, 480.

Du dfveloppement de la profession mSdicale en Canada. I'uion ni^d. du Canada, Montreal, 1885, xiv, 481-489; 529-539.

1886

The structure of certain gliomata. Phila. M. Times, 1885-86, xvl, 394. Also: Med. News, Phila., 1886, xlviil, 220.

Aneurism of the cerebral arteries. Canada M. & S. J., Montreal, 1885-86, xiv, 660-666. In his: Collect, repr., 1882-92, ii, no. 75.

A case of retro-peritoneal spindle-celled sarcoma with extensive thrombotic and hemorrliagic changes. Med. News, Phila., 1886. xlviii. 263. In his: Collect, repr, 1882-92, ii, no. 69.

Spindle-celled sarcoma of the retro-peritoneum with extensive thrombotic degeneration. N. York M. J.. 1886, xliii, 136.

Also.- Marvland -M. J.. Halt., 1885-86, xiv, 269-271.

Also: Semi-Month. J. Proc. Path. Soc, Phila., Wilmington, 1886, i, 3. Cartwright ' lectures. Delivered before the Association of Physicians and Surgeons, New York, March 23, 27, 30. 1886. On certain problems of the blood corpuscles. 1. The blood plaque or third corpuscle. 2. Degeneration and regeneration of the corpuscles. 3. The relation of the corpuscles to coagulation. Phila., 1886, 55 p., 8°.

Also: Med. News. Phila., 1886, xlviii, 365; 393; 421.

Also: Med. Rec. N. Y., 1886. xxix, 377; 405; 433.

Also: N. York M. J., 1886. xliii, 341; 369; 397.

In his: Collect, repr, 1882-92, ii, no. 71.

Abstracts of the Cartwright lectures on certain problems in the phvsiology of the blood-corpuscles. Brit. M. J., Lond., 1886, i, 807; 861.

The bicuspid condition of the aortic valves. Tr. Ass. Am. Physicians. Phila., 1886, i, 185-192. In his: Collect, repr, 1882-92, ii, no. 72.

On the use of arsenic in certain forms of anjemia. Detroit, 1886, G. S. Davis, 14 p., 8°. Also: Therap. Gaz., Detroit. 1886, 3. s., ii, 741-746. Also: Coll. & Clin. Rec, Phila., 1886, vii, 231-233. In his: Collect, repr, 1882-92, ii, no. 73. Embolism of right middle cerebral artery; chronic nephritis. Med.

News, Phila., 1886, xlix, 554. On the treatment of pleurisy with effusion by Hay's method.

[Abstr] Med. News, Phila., 1886, xlix, 645. Pyopneumothorax subphrenlcus. Semi-.Month. J. Proc. Path. Soc,

Phila., Wilmington, 1886, I, 5. The relation of the corpuscles to coagulation and thrombosis. Brit. M. J., Lond., 1886, 1, 917-919.

Osier, W., and Henry. F. P. Atrophy of the stomach, with the clinical features of progressive pernicious ana-mia. Am. J. M. Sc, Phila., 1886. n. s., xci, 498-511. In his: Collect, repr.. 1882-92, li, no. 70.

Osier, W., and Hughes, W'. Hiemorrhagic pancreatitis with swelling of semilunar ganglia and Pacinian corpuscles. SemiMonth. J. Proc. Path. Soc, Phila., Wilmington, 1886. i, 7.

1887 Extracts from Pathological Society of PliUadelphla, 1885-1887, xllxlil, Philadelphia 11887), 69 p., 8°.

Duodenal ulcer; clinical and anatomical considerations based on nine cases. Canada M. & S. .1.. .Montreal. 1886-87, xv, 449-461. In his: Collect, repr. 1882-92, II. no. 74.

An address on the haematozoa of malaria. Brit. .M. .1.. lAtwi., 1887, I, 556-562. In his: Collect repr., 1882-92, II, no. 76.

Antlfebrin. Therap. Gaz., Detroit, 1887.. 3. s.. 111. 16.3-167. In his: Collect, repr. 1882-92, II, no. 77.

The cardiac relations of chorea. Am. J. .M. Sc, Phila., 1887, n. s., xclv, 371-386. In his: Collect, repr, 1882-92, II, no. 78.


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[Xo. 341


Notes on hsemorrhagic infarction. Boston M. & S. J.. 1SS7, cxvii, 325-328. Also: Tr. Ass. Am. Physicians, Phila., 1887, ii, 133-141. In his: Collect, repr., 1882-92, ii, no. 79. On the general etiology and symptoms of chorea, based on the records of 410 cases at the Infirmary for Nervous Diseases, Philadelphia. Med. News, Phila., 1887, Ii, 437; 465. In his: Collect, repr., 1882-92, ii, no. SO. Case of cholesteatoma of floor of third ventricle and of the iufundibulum. J. Nerv. & Ment. Dis., N. Y., 1887, xiv, 657-673. In his: Collect, repr., 1882-92, ii, no. 81.


Hereditary angio-neurotic oedema. Am. J. M. Sc, Phila., 1888, n. s., xcv, 362-367. In his: Collect, repr., 1882-92, Ii, no. 82. Note on nitro-glycerine in epilepsy. J. Nerv. & Ment. Dis., N. Y., 1888, n. s., xlii, 38-39. In his: Collect, repr., 1882-92, ii, no. 83. The diagnosis of small-pox. Med. Standard, Chicago, 1888, ill, 97.

In his: Collect, repr., 1882-92, ii, no. 84. Glioma of the medulla oblongata. J. Nerv. & Ment. Dis., N. Y., 1888, n. s., xiii, 172-176. In his: Collect, repr., 1882-92, ii, no. 85. The cerebral palsies of children. Med. News, Phila., 1888, liii, 29; 57; 85; 113; 141. In his: Collect, repr., 1882-92, ii, no. 86. Cases of diseases of the appendix and caecum. Med. & Surg. Reporter, Phila., 1888, lix, 419-422. In his: Collect, repr., 1882-92, ii, no. 87. Puerperal anaemia, and its treatment with arsenic. Boston JI. & S. J., 1888, cxix, 454. Also: North Car. M. J., Wilmington, 1888, xxii, 359-363. In his: Collect, repr., 1882-92, ii, no. 88. On the diagnosis of duodenal ulcer. Med. Rec, N. Y., 1888, xxxiv, 609-610. In his: Collect, repr., 1882-92, ii, no. 89. Note on pachymeningitis hemorrhagica. J. Nerv. & Ment. Dis., N. Y., 1888, n. s., xiii, 608-612. Also: Med. News, Phila., 1888, liii, 563-565. In his: Collect, repr., 1882-92, ii, no. 90. On lesions of the conus medullaris and cauda equina, and on the situation of the aho-vesical centre in man. Med. News, Phila., 1888, liii, 669-671. In his: Collect, repr., 1882-92, ii, no. 91. On a form of purpura associated with articular, gastro-intestinal, and renal symptoms. N. York M. J., 1888, xlviii, 675-677. In his: Collect, repr., 1882-92, ii, no. 92. An accouchement in a railway closet. Canada M. & S. J., Montreal, 1888, xvi, 377. Also: Med. Rec, N. Y., 1888, xxxiii, 97. Pulsating pleurisy. Tr. Ass. Am. Physicians, Phila., 1888, iii, 330 Also: Am. J. M. Sc, Phila., 1889, n. s., xcvii, 43-50. In his: Collect, repr., 1882-92, ii, no. 95. Enlargement and congestion of the right arm following exercise of its muscles. Med. News, Phila., 1888, Iii, 330. Also: J. Nerv. & Ment. Dis., N. Y., 1888, n. s., xiii, 246-248. A case of local syncope and asphyxia of the fingers. J. Nerv. & Ment. Dis., N. Y., 1888, n. s., xiii, 207-208.

1889 The cerebral palsies of children; a clinical study from the Infirmary for Nervous Diseases, Philadelphia. Phila., 1SS9, P. Blakiston, Son & Co., Ill p. 8°.

Aequanimitas. Valedictory remarks to the graduates in medicine of the University of Pennsylvania, May 1, 1889. Phila., 1889, W. F. Fell & Co., 10 p., 8°. In his: Collect, repr., 1882-92, ii, no. 97.

The mortality of pneumonia. Phila., 1889, 7 p., 8°.

Also: Univ. M. Mag., Phila., 1888-89, 1, 77-82.

In his: Collect, repr., 1882-92, ii, no. 93. Two cases of ulcerative endocarditis. Univ. M. Mag., Phila., 188889, 1, 31-32.


The mortality in pneumonia. Univ. M. Mag., Phila., 1888-89, i. 225. Cancer of the stomach, extreme mobility of tumor. Univ. M. Mag.,

Phila., 1888-89, i, 368-370. On the conditions of the brain suitable for operative interference. [Abstr.] Univ. M. Mag., Phila., 1888-89, i, 465-468. Also: Canad. Pract, Toronto, 1889, xiv, 165-167. On certain symptoms of floating kidney. Montreal M. J., 1888-9,

xvii, 416-418. The anatomical tubercle. Montreal M. J., 1888-9, xvii, 418.

Aortic aneurism; hemorrhage from the lungs. Phila. M. Times,

1888-9, xix, 223. Typhlitis and appendicitis. Canada Lancet, Toronto, 1888-9, xxi,

193-196. On phagocytes. An address before the Alumni Association of Bellevue Hospital, New York, delivered April- 3, 1889. Med. News, Phila., 1889, liv, 393; 421. Also: Med. Rec, N. Y., 1889, xxxv, 393-399. Also: N. York M. J., 1889, xlix, 393-400. In his: Collect, repr., 1882-92, ii, no. 94. Annual address. The license to practice. J. Am. M. Ass., Chicago, 1889, xii, 649-654. Also: Maryland M. J., Bait., 1889, xxi, 61-67. Also: Tr. M. & Chir. Pac. Maryland, Bait., 1889, 70-82. In his: Collect, repr., 1882-92, ii, no. 96.

Note on intrathoracic growths developing from the thyroid gland. Med. News, Phila., 1889, Iv, 257. In his: Collect, repr., 1882-92, ii, no. 98. On a case of simple idiopathic muscular atrophy, involving the face and the scapulo-humeral muscles. Am. J. M. Sc, Phila., 1889, n. s., xcviii, 261-265. In his: Collect, repr., 1882-92, ii, no. 99.

Case of syphiloma of the cord of the Cauda equina; death from diffuse central myelitis. J. Nerv. & Ment. Dis., N. Y., 1889, n. s., xiv, 499-507. In his: Collect, repr., 1882-92, ii, no. 100.

Idiocy and feeble-mindedness in relation to infantile hemiplegia; a report of twenty-two cases at the Pennsylvania Institution for Feeble-Minded Children. Alienist & Neurol., St. Louis,

1889, X, 16-23.

1890

On the value of Laveran's organisms in the diagnosis of malaria.

Johns Hopkins Hosp. Bull., Bait, 1889-90, i, II. In his: Collect, repr., 1882-92, ii, no. 101. On fever of hepatic origin, particularly the intermittent pyrexia

associated with gallstones. Johns Hopkins Hosp. Rep., Bait.,

1890, ii, 3-31.

In his: Collect, repr., 1882-92, li, no. 102. Cases of post-febrile insanity. Johns Hopkins Hosp. Rep., Bait., 1890. ii, 46-50. In his: Collect, repr., 1882-92, ii, no. 103. Rare forms of cardiac thrombi. Johns Hopkins Hosp. Rep., Bait., 1890, ii, 56-61. In his: Collect, repr., 1882-92, ii, no. 104. Note on endocarditis in phthisis. Johns Hopkins Hosp. Rep., Bait, 1890, ii, 62-64. In his: Collect repr., 1882-92, ii, no. 105. Tubercular peritonitis; general considerations; tubercular abdominal tumors; curability. Johns Hopkins Hosp. Rep., Bait, 1890, ii, 67-113. In his: Collect, repr., 1882-92, ii, no. 106. Acute nephritis in typhoid fever. Johns Hopkins Hosp. Rep., Bait., 1890, ii, 119-128. /)( his: Collect repr., 1882-92, ii, no. 107. On the amceba in dvsenterv and in dysenteric liver abscess. Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 53-54. In his: Collect, repr., 1882-92, ii, no. 108. On the form of convulsive tic associated with coprolalia, etc Med. News, Phila., 1890, Ivii, 645-647. In his: Collect repr., 1882-92, ii, no. 109. On the symptoms of chronic obstruction of the common bile-duct

by gallstones. Ann. Surg., St. Louis, 1890, xi, 161-185. Ueber die in Dvsenterie und dysenterischem Leberabscess vorhandene Amceba. Centralbl. f. Bacteriol. u. Parasitenkr., Jena., 1890, vii, 736-737.


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225


Multiple thrombi-multiple gangrene. (Proc. Johns Hopkins Hosp. Med. Soc, Oct. 22, 18S9.) Johns Hopkins Hosp. Bull., Bait., 1S89-90. i. 12.

Fatal hemorrhage into a large bronchocele. (Proc. Johns Hopkins Hosp. Med. Soc, Nov. 18, 1889.) Johns Hopkins Hosp. Bull.. Bait, 1889-90, i, 23.

Congenital heart disease. (Proc. Johns Hopkins Hosp. Med. Soc, Dec. 2, 1889.) Johns Hopkins Hosp. Bull., Bait., 1889-90, i. 34.

Filaria sanguinis hominis. (Proc. Johns Hopkins Hosp. Med.

Soc, Jan. 6. 1890.) Johns Hopkins Hosp. Bull., Bait., 1889-90,

1. 48. Weir Mitchell. Remarks on the occasion of the presentation to

the College of Physicians, Phila., of the portrait of Dr. S. Weir

Mitchell, April 22. 1890. Johns Hopkins Hosp. Bull., Bait.,

1889-90, i, 64. Aortic InsufBciency. (Proc. Johns Hopkins Hosp. Med. Soc, Oct.

20, 1890.) Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 109.

Hereditary chorea. (Proc. Johns Hopkins Hosp. Med. Soc, Oct. 20. 1890.) Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 110. In his: Collect, repr., 1882-92, ii, no. 114.

General bronchiectasis of left lung, foetid bronchitis: incision of cavitv; death. (Proc. Johns Hopkins Hosp. Med. Soc, Oct. 20, 'l890.) Johns Hopkins Hosp. Bull., Bait., 1889-90, 1, 109. In his: Collect, repr.. 1882-92, ii. no. 115.

1891

A case of sensory aphasia; word-blindness with hemianopsia. Am. J. M. Sc, Phila., 1891, n. s., cl, 219-224. In his: Collect, repr., 1882-92, ii, no. 110. Rudolf Vlrchow: the man and the student. Boston M. & S. J., 1891, cxxv, 425-427. Also: Johns Hopkins Univ. Circ, Bait., 1891, xi, 17-19. In his: Collect repr., 1882-92, ii, no. 111.

Diagnosis of tuberculous broncho-pneumonia in children. Arch. Pediat, Phila.. 1891, viii, 825-829. Also: Tr. Am. Pediat Soc (N. Y.). 1892, iii, 25-29. In his: Collect repr. 1882-92, no. 112.

Doctor and nurse: remarks to the first class of graduates from the TrainiuK School for Nurses at The Johns Hopkins Hospital. Bait. 1891, J. Murphy & Co.. 11 p. 4°. In his: Collect repr.. 1882-92, ii, no. 113.

Obstruction of the superior vena cava. (Proc. Johns Hopkins Hosp. Med. Soc, Jan. 5, 1891.) Johns Hopkins Hosp. Bull., Bait, 1891, ii, 40. In his: Collect repr., 1882-92, ii, no. 116. Case of multiple cysticerci. (Proc. Johns Hopkins Hosp. .Med. Soc. Feb. 2. 1891.) Johns Hopkins Hosp. Bull.. Bait, 1891, ii, 61. In his: Collect, repr., 1882-92, il, no. 117.

Disease of the coronary arteries: fibroid heart. Tr. Path. Soc.

Phila. (1887-9). 1891, xiv, 106-108. Acute phthisis: erosion of a large branch of the pulmonary

artery; sudden fatal haemoptysis. Tr. Path. Soc. Phila.

(1887-9), 1891. xiv. 169. The diagnosis of broncho-pneumonia (acute and chronic) from

tuberculosis. N. York M. J.. 1891. liv, 666.

Report on the Koch treatment in tuberculosis. Johns Hopkins Hosp. Bull.. Bait, 1891, 11, 714.

Remarks on hysteria with paroxysmal Inspiratory spasm. (Proc Johns Hopkins Hosp. .Med. Soc, Nov. 17, 1890.) Johns Hopkins Hosp. Bull., Bait, 1891, ii, 18.

Two cases of pernicious malaria. (Proc. Johns Hopkins Hosp.

Med. Soc. Oct. 5, 1891.) Johns Hopkins Hosp. Bull.. Bait.

1891, ii, 161-162.

1892 The principles and practice of medicine. Designed for the use

of practitioners and students of medicine. New York, 1892,

D. Appleton & Co., 1079 p. 8'. Teacher and student. An address delivered on the occasion of

the opening of the new building of the College of .Medicine

and Surgery of the University of Minnesota. Minneapolis.

Oct 4, 1892, Bait. 1892, J. Murphy & Co., 22 p. 8°. In his: Collect repr., 1882-92. Ii, no. 123.


Collected reprints. Second series. (January 1, 1882-January 1. 1892.) (Bait. 1892.] 8°.

Remarks on specialism. Boston M. & S. J., 1892, cxxvi, 457-459. Also: .Med. News, Phila.. 1892, Ix, 542-544. Also: Arch. Pediat. Phila., 1892, Ix, 481-488. In his: Collect, repr., 1882-92, ii, no. 118.

The healing of tuberculosis. Climatologist, Phila., 1892, ii, 149153. In his: Collect, repr., 1892-7, iii, no. 119. On the association of congenital wry-neck, with marked facial asymmetry. Arch. Pediat, N. Y., 1892, ix, 81-85. In his: Collect repr., 1882-92, ii, no. 120. Interstitial processes in the central nervous system. Tr. Cong. Am. Phys. & Surg., 1891. N. Haven. 1S92, i'i, 144-146. In his: Collect repr., 1892-7, iii. no. 121.

The cold-bath treatment of typhoid fever. Med. News, Phila., 1892. Ixi. 628-631. In his: Collect, repr., 1892-7, iii, no. 122.

Notes on the diagnosis and treatment of cholera. Med. News, Phila., 1892, Ixi, 290.

License to practice. Northwest Lancet, St Paul, 1892, xii, 838.

An acute my.\oedematous condition occurring in goitre. (Proc. Johns Hopkins Hosp. Med. Soc, Dec. 7, 1891.) Johns Hopkins Hosp. Bull., Bait. 1892, iii, 42.

Chronic cerebro-spinal meningitis. (Proc. Johns Hopkins Hosp. Med. Soc. Oct. 17, 1892.) Johns Hopkins Hosp. Bull., Bait, 1892, iii, 119.

Localized pyo-pneumothorax. (Proc. Johns Hopkins Hosp. Med. Soc, Oct 17, 1892.) Johns Hopkins Hosp. Bull., Bait, 1892, iii, 19.


Note on arsenical neuritis following the use of Fowler's solution. (s4.ilTn.18.) Montreal M. J., 1892-3, xxi, 721-724. In his: Collect repr., 1892-7, iii, no. 130.

Note on a remarkable house epidemic of typhoid fever. Univ. M. Mag., Phila., 1892-3, v, 522-524. In his: Collect repr., 1892-7, iii, no. 131.

Tuberculous pericarditis. Am. J. M. Sc. Phila., 1893, n. s., cv, 20-27. In his: Collect repr., 1892-7, lil. no. 124.

On dilatation of the colon in young children. Arch. Pediat, N. Y., 1893, X, 111-119. Also: (Proc. Johns Hopkins Hosp. Med. Soc, Jan. 16, 1893.)

Johns Hopkins Hosp. Bull., Bait, 1893, iv, 41-43. In his: Collect, repr., 1892-7, iii, no. 125.

Physic and physicians as depicted in Plato. Boston M. & S. J., 1893. cxxviii. 129; 153. In his: Collect repr.. 1892-7. iii, no. 126.

Case of arterlo-venous aneurism of the axillary artery and vein of fourteen years' duration. Ann. Surg., Phila., 1893, xvii, 37-40. In his: Collect repr., 1892-7, ill, no. 127.

The chronic intermittent fever of endocarditis. Practitioner, Lond., 1893, 1, 181-190. In his: Collect, repr.. 1892-7, ill, no. 128.

Remarks on the varieties of chronic chorea, and a report upon two families of the hereditary form, with one autopsy. J. Nerv. & Ment Dls.. N. Y.. 1893. xx. 97-111. In hts: Collect repr., 1892-7. iii. no. 129.

Cases of sub-phrenic abscess. Tr. Ass. Am. Physicians, Phila., 1893. viii. 257-267. Also: Canad. Pract, Toronto. 1893, xvlii, 565-574. In his: Collect repr., 1892-7, ill. no. 132.

Shattuck lecture. Mass. Med. Soc, 1893. Tuberculous pleurisy.

Boston .M. & S. J.. 1893, cxxix. 53; 81; 109; 134. Also: Med. Communicat. .Mass. .M. Soc, Boston, 1893, xvl,

49112. In his: Collect repr., 1892-7, ill, no. 133.

Profound toxemia with slight tuberculous lesions. Med. News, Phila., 1893, Ixiil, 632.

Jean Martin Charcot, memorial notice. Johns Hopkins Hosp. Bull., Bait, 1893, iv. 87-88.


236


[No. 341


On sporadic cretinism in America. Tr. Am. J. Am. Physicians, Pliila., 1893, viii, 380-398. Also: Am. J. M. Sc, Plilla., 1893, n. s., cvi, 503-518. In his: Collect, repr., 1892-7, iii, no. 136. Notes on tuberculosis in children. Arch. Pediat., N. Y., 1893, X 979-986. In his: Collect, repr., 1892-7, iii. no. 137. Hirt, Ludwig. The diseases of the nervous system. A text-book for physicians and students. Transl. with permission of the author by August Hoch, assisted by Frank R. Smith, with an introduction by William Osier, N. Y., 1893. D. Appleton & Co., 698 p. 8°.

1894 Lectures on the diagnosis of abdominal tumors, delivered to the post-graduate class, Johns Hopkins University, 1893. New York, 1894, D. Appleton & Co., 192 p. 8°. Also: N. York M. J., 1894, lix, 129; 161; 193; 260; 385; 417; 481; 545; 577: Ix, 65; 97. In his: Collect, repr., 1892-7, iii, no. 146.

On chorea and choreiform affections. Phila., P. Blakiston, Son & Co., 1894, 125 p. 8°. In his: Collect, repr., 1892-7, iii, no. 149.

Tuberculosis.

In: Am. Text-Bk. Dis. Child. (Starr), Phila., 1894, 94-126. In his: Collect, repr., 1892-7, iii, no. 134.

Diseases of the blood. In: Text-book Theory & Pract. Med. (Pepper), Phila., 1894, li,

182-233. In his: Collect, repr., 1892-7, iii, no. 135.

Diseases of the suprarenal capsules and ductless glands.

In: Text-book Theory & Pract. Med. (Pepper), Phila., 1894, il, 234-246. Toxaemia in tuberculosis. Practitioner, Lond., 1894, Iii, 26-30.

In his: Collect, repr., 1892-7, iii, no. 138. Parotitis in pneumonia. Case of pericarditis treated by incision and drainage. Univ. M. Mag., Phila., 1893-4, vi, 245-249. In his: Collect, repr., 1892-7, iii, no. 139. The army surgeon. An address delivered at the closing exercises of the Army Medical School, Washington, D. C, Feb. 28, 1894. Med. News, Phila., 1894, Ixiv, 3i8-322. In his: Collect, repr., 1892-7, iii, no. 147.

The leaven of science. An address delivered at the opening of the Wistar Institute of Anatomy and Biology of the University of Pennsylvania, May 21, 1894. Univ. M. Mag., Phila., 1893-4, vi, 573-586. In his: Collect, repr., 1892-7, iii, no. 148.

Oliver Wendell Holmes. Johns Hopkins Hosp. Bull., Bait., 1894, V, 85-88. In his: Collect, repr., 1892-7, iii, no. 150.

The heart in chorea minor. Med. Chron., Manchester, 1894, n. s., i, 321-332.

Clinical remarks on a case of typhoid fever, complicated with bronchitis and laryngitis. Maryland M. J., Bait., 1894, xxxi, 1-3.

The registration of pulmonary tuberculosis. Phila. Polyclin., 1S94, iii, 65.

Case of hereditary chorea. (Proc. Johns Hopkins Hosp. Med. Soc, Oct. 1, 1894.) Johns Hopkins Hosp. Bull., Bait., 1894, V, 119-120.

1895

The principles and practice of medicine. Designed for the use of practitioners and students of medicine. 2. ed. New York, 1895, D. Appleton & Co., 1143 p. S".

Report on typhoid fever. I. General analysis and summary of the cases. II. Treatment of typhoid fever. III. A study of the fatal cases. IV. Notes on special features, symptoms and complications. Johns Hopkins Hosp. Rep., Bait., 1894-5, iv, 1-72. In his: Collect, repr., 1892-7, iii, nos. 140-143.

On the neurosis following enteric fever, known as " the typhoid spine." Johns Hopkins Hosp. Rep., 1894-5. iv, 73-82. Also: Am. J. M. Sc, Phila., 1894. n. s., cvii, 23-30. In his: Collect, repr., 1892-7, iii, no. 144.


Typhoid fever in Baltimore. Johns Hopkins Hosp. Rep., Bait., 1894-5, iv, 159-167. In his: Collect, repr., 1892-7, iii, no. 145.

Introductory remarks to course of clinical demonstrations on typhoid fever. Maryland M. J., Bait., 1894-5, xxxii, 79-82. In his: Collect, repr., 1892-7, iii, no. 151.

Cancer of the stomach with very rapid course. Univ. M. Mag., Phila., 1894-5, vii, 248-252. In his: Collect, repr., 1892-7, iii, no. 152.

Teaching and thinking; the two functions of a medical school. Montreal M. J., 1894-5, xxiii, 561-572. In his: Collect, repr., 1892-7, iii, no. 153. Case of sporadic cretinism (infantile myxcedema) treated successfully with thyroid extract. Arch. Pediat, N. Y., 1895, xii, 105-108. In his: Collect, repr., 1892-7, iii, no. 154.

Diseases, the direct or indirect result of infection. Text-book Nerv. Dis. Am. Authors (Dercum), Phila., 1895, 203-226. In his: Collect, repr., 1892-7, iii, no. 157. Studies in typhoid fever; Five years' experience with the coldbath treatment. Johns Hopkins Hosp. Rep., Bait., 1895, v, 321-326. Also: Canada M. Rec, Montreal, 1895-6, xxiv, 56-60. Also: Med. News, Phila., 1895, Ixvii, 393-395. Also: Canada Lancet, Toronto, 1895-6, xxviii, 261-263. /n his: Collect, repr., 1892-7, iii, no. 158.

Studies in typhoid fever: Analysis and summary of the cases: special features, symptoms, and complications; a study of the fatal cases. Johns Hopkins Hosp. Rep., Bait., 1895, v, 281; 283; 459. In his: Collect, repr., 1892-7, iii, no. 159. Neuritis during and after typhoid fever. Johns Hopkins Hosp. Rep., Bait., 1895, v, 397-416. In his: Collect, repr., 1S92-7, iii, no. 160. Chills in typhoid fever. Johns Hopkins Hosp. Rep., Bait., 1895, V, 445-457. In his: Collect, repr., 1892-7, iii, no. 161. The practical value of Laveran's discoveries. Med. News, Phila., 1895, Ixvli, 561-564. In his: Collect, repr., 1S92-7, iii, no. 162.

On the visceral complications of erythema exudativum multiforme. Am. J. M. Sc, Phila., 1895, n. s., ex, 629-646. Also: Select, essays and monog., Lond., 1897, 321-347. 8°. In his: Collect, repr., 1892-7, iii, no. 163. Case of cerebral hfemorrhage in a foetus. Teratologia, Lond. &

Edinb., 1895, ii, 13. Hyperpyrexia in typhoid fever. (Proc. Johns Hopkins Hosp. Med. Soc, Oct. 7, 1895.) Johns Hopkins Hosp. Bull., Bait.,

1895, vi, 143.

Abscess of the liver, perforating the lung. (Proc. Johns Hopkins Hosp. Med. Soc, Oct. 7, 1895.) Johns Hopkins Hosp. Bull., Bait., 1895, vi, 144.

1896 An Alabama student. Baltimore, Friedenwald Co., 1896, 19 p. 12°. Also: Johns Hopkins Hosp. Bull., Bait., 1896, vii, 6-11. In his: Collect, repr., 1892-7, iii, no. 166. Typhoid fever in country districts. Maryland M. J., Bait., 1895-6, xxxiii, 55-62. In his: Collect, repr., 1892-7, iii, no. 155. Visible contractile tumor of the pylorus following ulcer of the stomach. Montreal M. J., 1895-6, xxiv, 81-86. In his: Collect, repr., 1892-7, iii, no. 156. John Keats, the apothecary poet. Baltimore, Friedenwald Co.,

1896. 18 p. 12°.

Also: Johns Hopkins Hosp. Bull., Bait., 1896, vii, 11-16.

I7i his: Collect, repr., 1892-7, iii, no. 164. Thomas Dover, M. D. (of Dover's powder), physician and buccaneer. Baltimore, Friedenwald Co., 1896. 18 p. 12°.

Also: Johns Hopkins Hosp. Bull.. Bait, 1896, vii, 1-6.

In his: Collect, repr., 1892-7, iii, no. 165. Addison's disease. Med. Bull., Phila., 1896, xviii, 81-84.

In his: Collect, repr., 1892-7, iii, no. 168.


.TlI.V, 1!U!I


On the association of enormous heart hypertrophy, chronic proliferative peritonitis and recurring ascites, with adherent pericardium. Arch. Pediat.. N. Y.. 1896, xiii, 1-10. In his: Collect, repr, 1S92-7, iii. no. 169. Hemiplegia in typhoid fever. J. Nerv. & Ment. Dis., N. Y.. 1S96, n. s., xxi. 295-304. In his: Collect, repr.. 1S92-7. iii, no. 170. Diseases of the blood and the ductless glands. In: Am. Text-book Applied Therap., Phlla., 1896. 902-927. In his: Collect, repr., 1S92-7, iii, no. 171. The cerebral complications of Raynaud's disease. Am. J. M. Sc, Phila., 1896. n. s., cxii, 522-529. In his: Collect, repr., 1S92-7, iii. no. 172. Lectures on angina pectoris and allied states. N. York M. J.. 1896. Ixiv. 177: 249; 2S1: 346. In his: Collect, repr.. 1892-7. iii, no. 173. The study of the fevers of the South. J. Am. M. Sc, Chicago,

1896, xxi, 999-1004.

Treatment of fevers. Maritime M. News, Halifax, 1896, viii,

183-186. Association of American Medical Colleges. Bull. Am. Acad. M..

Easton, Pa., 1895-6, ii, 508-510. Chills in typhoid fever. Vniv. M. Mag., Phila., 1895-6, viii. 77-85. Pleuro-peritoneal tuberculosis. (Proc. Johns Hopkins Hosp. Med.

Soc. Nov. 4. 1896.) Johns Hopkins Hosp. Bull.. Bait.. 1896,

vli, 79.

Case of Addison's disease; death during treatment with the suparenal extract. (Proc. Johns Hopkins Hosp. Med. Soc, Oct 19, 1896.) Johns Hopkins riosp. Bull.. Bait.. 1896. vii. 208-209.

Ephemerides. 1895: I. Introduction. 11. Heberden's nodes.

III. Geographical tongue.

IV. Buccal leucoplacia.

V. Acute gout in the United States. VI. Calcification of the auricle. VII. .Arthritis deformans in childhood. VIII. I'nusual types of night-terrors; day-terrors. IX. Tobacco angina. X. Unusually persistent oxyuris. XI. Is the coin sound' distinctive of pneumothorax? XII. Head-swaying in children. Montreal M. J.. 1895-6. xxlv, 518: 631: 694; 777; 877; 969.

1897

Lectures on angina pectoris and allied states. New York. 1897, D. Appleton & Co.. 160 p. 8°.

Collected reprints. Third series. (January 1. 1892-January 1,

1897. [Bait., 1897.1

On six cases of AdJison's disease, with the report of a case greatly benefited by the use of the suprarenal extract. Internat. M. .Mag.. Phila.. 1896-7, v, 3-11. In his: Collect, repr. 1892-7. ill. no. 167.

On the classification of the tics or habit movements. Arch. Pediat.. N. Y.. 1897, xiv. 1-5. In his: Collect, repr.. 18971302. Iv, no. 174.

On certain features in the prognosis of pneumonia. Am. J. M. Sc, Phlla., 1897, n. s., cxill. 1-10. Also: North Car. M. J.. Wilmington. 1897. xxxix. 295-307. In his: Collect, repr.. 1897-1902, iv. no. 175.

Mitral stenosis: sudden death; ball thrombus in the left auricle. Montreal M. J.. 1896-7. xxv. 729-731. In his: Collect repr.. 1897-1902. iv, no. 176.

The diagnosis of malarial fever. Med. News. N. Y., 1897. Ixx, 289-292. In his: Collect repr.. 1897-1902. iv. no. 177.

On certain unusual forms of paraesthetic meralgla. J. Nerv. & Ment. Dis.. N. Y.. 1897. xxlv. 131-137. In his: Collect repr. 1897-1902, iv. no. 178.


The functions of a state faculty. President's address delivered before the Medical and Chirurgical Faculty of Maryland, at the 99th annual session, Baltimore. Md. April 27, 1897. Marvland M. J.. Bait, 1897. xxxvii, 73-77. Tr M. & Chlr Fac Maryland. Bait. 1897. 21-29. In his: Collect repr. 1897-1902. iv, no. 179.

A case of leprosy, with exhibition of patient. Maryland M. J.,

Bait. 1897. xxxvii, 417-419. Hemorrhage from the bowels in typhoid fever. Maryland M. J.,

Bait. 1896-7, xxxvi, 73-75.

Ephemerides. 1897:

XIII. Rheumatic neuritis associated with subcutaneous fibroid nodules.

XIV. Bright's disease or myxoedema.

XV. Remarkable noisy expiration in chronic emphysema. XVI. Chills and fevers in post-partum ansemia. XVII. Linese albicantes. XVIIl. Two cases of general bromidrosis. XIX. Vertigo and ocular defects. Montreal M. J.. 1896-7, xxv. 642; 794: 890; 952. A clinical lecture on the ball-valve gall-stone in the common duct. Lancet Lond.. 1897. i. 1319-1323. 7k his: Collect, repr. 1897-1902, iv, no. 180. Nurse and patient An address. Baltimore. 1897. J. Murphy & Co., 17 p. 8°. In his: Collect repr. 1897-1902. iv. no. 181.

Influence of Louis on American medicine. Johns Hopkins Hosp. Bull.. Bait, 1897. viii, 161-167. In his: Collect repr, 1897-1902, iv. no. 182.

British medicine in Greater Britain. The address in medicine at the British Medical Association. Montreal, meeting. Boston M. & S. J.. 1S97, cxxxvii, 221-227. .llso; Med. News, N. Y., 1897, Ixxi, 293-301. Also: Med. Rec, N. Y., 1897, Hi, 333-340. Also: Montreal M. J.. 1897. xxvi. 186-203. In his: Collect, repr. 1897-1902. iv. no. 183. Hepatic complications of typhoid fever. Tr. Ass. Am. Physicians, Phila.. 1897. xii. 378-398. Also: Edinb. M. J.. 1897. n. s. ii. 423-439. In his: Collect repr. 1897-1902. iv, no. 184. Internal medicine as a vocation. Med. News. N. Y.. 1897. Ixxi. 660-663. In his: Collect, repr., 1897-1902. iv, no. 185. Pneumonia; a review of the cases studied by the third and fourth classes, Johns Hopkins Hospital, session of 1896-97. Nat. M. Rev., Wash.. 1897-8, vii, 177-180. In his: Collect, repr, 1897-1902, iv, no. 186.

Occasional notes on American medical classics; introductory lecture to a course of clinical observations in the Pennsylvania Hospital, delivered there on the 3d of December, 1776. bv Dr Thomas Bond. Univ. M. Mag.. Phila., 1897-8, x. 136140. In his: Collect repr. 1897-1902. iv. no. 187.

Sporadic cretinism in America. Am. J. M. Sc, Phlla., 1897, cxlv. 377-401. .4 Mo; Tr. Cong. Am. Phys. & Surg., N. Haven, 1897, Iv, 169-206. In his: Collect repr.. 1897-1902. iv. no. 188.

Address In medicine. Brit M. J., Lond.. 1897. 11, 576-581. .4/80 [Abstrl: Lancet. Lond.. 1897. ii. 584-589. Also: Brit M. Ass. Dally J., Montreal. 1897. Part 3, 42-50.

Address In medicine, at the sixty-fifth annual meeting of the British Medical Association. Montreal, Aug, 31 to Sept 4, 1897. J. Am. M. Ass., Chicago. 1897. xxlx, 507-512.

U-i medicine anglalse dans la Nouvelle Angleterre. [Trans.] Union mM. du Canada. Montreal. 1897, xxvi, 595-599.

Relapses in typhoid fever. J. Am. M. Ass.. Chicago, 1897, xxlx, 97.

The disguises of typhoid fever Galllard's M. J., N. Y., 1897. Ixiv, 350-352.

Tuberculosis. Syst Pract M. (Loomis), N. Y. & Phila., 1897, 1, 731-848.


228


[Xo. 341


1898 The principles and practice of medicine. Designed for tbe use of practitioners and students of medicine. 3. ed. New York, 1898, D. Appleton & Co., IISI p. 8°.

Spontaneous pneumothorax. Maryland M. J., Bait., 1897-8, xxxviii, 461-463.

Pneumonia. J. Pract. Med., N. Y.. 1897-8. viii, 308-311.

On chronic symmetrical enlargement of the salivary and lachrymal glands. Am. J. M. Sc, Phila., 1898, cxv, 27-30.

In his: Collect, repr., 1897-1902, iv, 189.

On some of the intestinal features of typhoid fever. Phila. M. J., 1898, i. 30-32. In his: Collect, repr., 1897-1902, iv, no. 190.

Ein Fall von Fistula cesophago-pleuro-thoracica. Arch. f. Verdauungskr., Berl., 1898, iii, 383-386. In his: Collect, repr., 1897-1902, iv, no. 191.

The relation of typhoid mortality and sewerage. Maryland M. J., Bait., 1897-8, xxxviii, 217-218. In his: Collect, repr., 1897-1902, iv, no. 192.

Leprosy in the United States, with the report of a case. Johns Hopkins Hosp. Bull., Bait., 1898. ix, 47-49. In his: Collect, repr., 1S97-1902, iv, no. 193.

On diffuse scleroderma; with special reference to diagnosis, and to the use of the thyroid-gland extract. J. Cutan. & Genitourin. Dis., N. Y., 1898, xvi, 49; 127. In his: Collect, repr., 1897-1902, iv, no. 194. Cerebral features of pneumonia. Maryland M. J., Bait., 1897-8, xxxviii, 381-383. In his: Collect, repr., 1897-1902, iv, no. 195.

Cerebro-spinal fever. Maryland M. J., Bait., 1898, xxxix, 717-723. In his: Collect, repr., 1897-1902, iv, no. 196.

The arthritis of cerebro-spinal fever. Boston M. & S. J.. 1898, cxxxix, 641-643. In his: Collect, repr., 1897-1902, iv, no. 197.

Ephemerides, 1897:

XX. The blood coagulation time in jaundice. XXI. Facial paralysis with herpes zoster. XXII. Paralysis of the ocular muscles in albuminuria.

Montreal M. J., 1898, xxvii, 36-38.

Tuberculosis. Am. Text-Bk. Dis. Child. (Starr), 2. ed. Phila., 1898, 270-302.


On the study of pneumonia. St. Paul M. J., St. Paul, Minn., 1899. i, 5-9. In Ms: Collect, repr., 1897-1902, iv, no. 198.

The problem of typhoid fever in the United States. Baltimore, 1899, J. Murphv Co., 13 p. 8°. Also: Albany M. Ann.. 1899, xx, 121-130. Also: Med. News, N. Y., 1899, Ixxiv, 225-229. In his: Collect, repr., 1897-1902, iv, no. 199.

An acute myxoedematous condition with tachycardia, glycosuria, metena, mania, and death. J. Nerv. & Ment. Dis., N. Y., 1899, xxvi, 65-71. In his: Collect, repr., 1897-1902, iv, no. 200.

The clinical features of sporadic trichinosis. Am. J. M. Sc, Phila., 1899, n. s., cxvii, 251-265. In his: Collect, repr., 1897-1902, iv, no. 201.

In memoriam, William Pepper. Phila. M. J., 1899, iii, 607-611. In his: Collect, repr., 1897-1902, iv, no. 202.

Chronic splenic enlargement with recurring gastrointestinal haemorrhages. Edinb. M. J., 1899, n. s., v, 441-453. In his: Collect, repr., 1897-1902, iv, no. 204.

Cavendish lecture. On the etiology and diagnosis of cerebrospinal fever. [London, 1899.] 46 p. 8°. Also: West. Lond. M. J., Lond., 1899, iv, 145-188. Also: Brit. M. J., Lond., 1899. i. 1517-1529. Also: Boston M. & S. J., 1899, cxli, 1; 32.

Also: Canad. Pract. & Rev., Toronto, 1899, xxv [xxiv], 447-455. Also: Lancet, Lond., 1899, i. 1699-1709. .4;so; Phila. M. J., 1899, iv, 26-41. In his: Collect, repr., 1897-1902, iv, no. 205.


After twenty-five years. An address at the opening of the session of the medical faculty, McGill University, Sept. 21, 1899. Montreal M. J., 1899, xxviii, 823-833. In his: Collect, repr., 1897-1902, iv, no. 206.

The diagnosis of typhoid fever. A discussion at the New York State Medical Association, October 25, 1899. N. York M. J., 1899, Ixx, 673-676. In his: Collect, repr., 1897-1902, iv, no. 207.

Clinical remarks on hypertrophic cirrhosis of the liver with bronzing of the skin: hfemochromatosls. Brit. M. J., Lond.,

1899, ii, 1595-1596.

In his: Collect, repr., 1897-1902, iv, no. 208.

On the medical tests for admission to the public services (Discussion). Brit. M. J., Lond., 1899, ii, 574.

The preventive and remedial treatment of tuberculosis (Discussion). Brit. M. J., Lond., 1899, ii, 1155. Blood parasites of frogs. N. York M. J., 1S99, Ixix, 63.

Clinical microscopy at Johns Hopkins Medical School, Baltimore, United States of America. Brit. M. J., Lond., 1899, i, 69-70.

1900

On splenic anapmia. Am. J. M. Sc, Phila.. 1900, n. s., cxix, 54-73. In his: Collect, repr., 1897-1902, iv, no. 209.

The home treatment of consumption. Maryland M. J., Bait., 1900, xliii, 8-12. Also: Med. Mirror, St. Louis. 1900, xi, 165-169. In his: Collect, repr., 1897-1902. iv, no. 210.

A case of multiple gangrene in malarial fever. Johns Hopkins Hosp. Bull., Bait, 1900, xi, 41-42. In his: Collect, repr., 1897-1902, iv, no. 211. The visceral lesions of the erythema group. Brit. J. Dermat, Lond., 1900, xii, 227-245. In his: Collect, repr., 1897-1902, iv, no. 213. An address on the importance of post-graduate studv. Lancet, Lond., 1900, ii, 73-75. In his: Collect, repr., 1897-1902, iv, no. 214.

Elisha Barlett, a Rhode Island philosopher. An address delivered before the Rhode Island Medical Society, Dec. 7, 1899. With an appendix containing Dr. Bartlett's sketch of Hippocrates. Providence, 1900, Snow & Furnham, 43 p. 8°. Also: Boston M. & S. J., 1900, cxlii, 49; 77. In his: Collect, repr., 1897-1902, iv, no. 215. An address on John Locke as a physician. Delivered before the Students' Societies of the Medical Department of the Universitv of Pennsylvania on Jan. 16, 1900. Lancet. Lond., 1900, ii, 1115-1123. In his: Collect, repr., 1897-1902, iv, no. 216. Hemiplegia in typhoid fever. Johns Hopkins Hosp. Rep., Bait.,

1900, viii, 363-371.

In his: Collect, repr., 1897-1902, iv, no. 217. Hepatic complications of typhoid fever. Johns Hopkins Hosp. Rep., Bait., 1900, viii, 373-383. In his: Collect, repr., 1897-1902, iv, no. 218.

Analysis and general summary of the cases [of typhoid feverl from 1889-1899. Johns Hopkins Hosp. Rep., Bait., 1900, viii, 421-422. In his: Collect, repr., 1897-1902, iv, no. 219.

Special features, symptoms and complications [of typhoid fever]. Johns Hopkins Hosp, Rep.. Bait., 1900, viii, 423-486. In his: Collect, repr., 1897-1902, iv, no. 220.

On the study of tuberculosis. Phila. M. J., 1900. vi, 1029-1030. In his: Collect, repr., 1897-1902, iv, no. 221.

General summary of the cases of typhoid fever in The Johns Hopkins Hospital for ten years. Phila. M. J., 1900, vi, 696-697.

Fatal angina pectoris without lesions of the coronary arteries in a young man. Med. News, N. Y., 1900, Ixxvii, 974-976.

The centenary of the Royal College of Surgeons (Correspondence). Maryland M. J., Bait., 1900, xliii, 520-522.

Osier, W., & McCrae, T. Cancer of the stomach. A clinical study. Phila., 1900, P. Blakiston's Son & Co., 157 p. 8°.

Osier, W., & McCrae, T. Cancer of the stomach in the young. N. York M. J., 1900, Ixxi, 581-585.


ll LV. l!ll!l|


Osier, W., & McCrae, T. A study of the blood in cancer of the stomach. N. York M. J., 1900, Ixxi, 757-761.

Osier, W., & McCrae, T. Latent cancer of the stomach. Phila. M. J., 1900, V, 245-247. In his: Collect, repr., 1897-1902, iv, no. 212.

1901 The principles and practice of medicine. Designed for the use of practitioners and students of medicine. 4. ed. New York, 1901, D. Appleton & Co., 1182 p. S^

Sporadic cretinism (infantile and juvenile myxoedema).

In: Cvcl. Dis. Child., M. & S. (Keating), Phila., 1901, v, 359-371. In his: Collect, repr., 1897-1902, iv, 203.

Cerebro-spinal fever.

In: Cvcl. Dis. Child., M. & S. (Keating). Phila., 1901, v, 13331351. Surgical intervention In perforation in typhoid fever. Phila. M. J.. 1901. vii, 138.

On perforation and perforative peritonitis in typhoid fever. Phila. M. J., 1901, vii, 116-119. Also: St. Louis M. & S. J., 1901, Ixxx, 254-264. In his: Collect, repr., 1S97-1902, iv, no. 222. .

Books and men. Remarks made at the opening of the new build• ing of the Boston Medical Library, January 12, 1901. Boston

M. & S. J.. 1901, cxliv. 60-61. In his: Collect repr., 1897-1902, iv, no. 223.

The past century, its progress in great subjects. Medicine. In: Sun, \. Y.. 1901. Jan. 27. In his: Collect, repr., 1897-1902, iv, no. 224.

The progress of medicine in the nineteenth century. [New York, 1901. 8M In: Progr. Cent. New York & Lond., 1901, 173-214, 8°.

[" The progress of medicine" the same as "The past century".] A plea for the more careful study of the symptoms of perforation

in typhoid fever with a view to early operation. Lancet.

Lond., 1901. i, 386-387. In his: Collect, repr., 1897-1902, iv, no. 225.

The medical aspects of carcinoma of the breast, with a note on the

spontaneous disappearance of secondary growths. Am. Med..

Phila., 1901, i, 17; 63. In his: Collect, repr.. 1897-1902, iv, no. 226. Hemorrhage In chronic Jaundice (Correspondence). Am. Med.,

Phila.. 1901, i, 152. On the advantages of a trace of albumin and a few tube casts in

the urine of certain men above fifty vears of age. N. York

M. J., 1901. Ixxiv, 949-950. Also: Indian M. Rec. Calcutta, 1902, xxii. 92-93. In his: Collect, repr., 1897-1902, iv. no. 227. Congenital absence of the abdominal muscles, with distended and

hypertrophied urinary bladder. Johns Hopkins Hosp. Bull.,

Bait., 1901, xli. 331-333. In his: Collect, repr.. 1897-1902, iv. no. 228. On a family form of recurring epistaxis, associated with multiple

telangiectases of the skin and mucous membranes. Johns

Hopkins Hosp. Bull.. Bait., 1901. xil. 33,3-337. In his: Collect, repr.. 1897-1902. iv, no. 229. The natural method of teaching the subject of medicine. J. Am.

M. Ass., Chicago, 1901, xxxvl, 1673-1679. The study of internal medicine. .Med. News, N. Y., 1901, Ixxvlli,

645-647. The spinal form of arthritis deformans. Remarks introductory to

a discussion on the subject. Tr. Ass. Am. Phvsicians, Phila.,

1901, xvl. 687-689.

1902 The principles and practice of medicine. Designer! for the use of practitioners and students of medicine. 5. ed. New York,

1902, D. Appleton ft Co., Iii79 p. 8°.

Collected reprints. Fourth series. (January 1, 1897-January 1, 1902. (Bait, 1902.)

On the diagnosis of bilateral cystic kidney. Am. Med., Phila., 1902, ill, 463-464. In his: Collect, repr., 1902-1907, v, no. 230. On amebic abscess of the liver. Med. News, N. Y., 1902, Ixxx. 673-677. In his: Collect, repr., 1902-1907, v, no. 231.


Amebic dysentery. Therap. Gaz., Detroit, 1902, 3, s., xviii, 217-218. Also: Proc. Phila. Co. M. Soc, Phila., 1902, n. s., iv, 44-46. In his: Collect, repr., 1902-1907, v, no. 232.

Note on the occurrence of ascites in solid abdominal tumors. Phila. M. J.. 1902, ix, 928-929.

In his: Collect, repr., 1902-1907, v. no. 233. Alfred Stills. I'niv. Penn. Med. Bull., Phila., 1902, xv, 126-132.

In his: Collect, repr., 1902-1907, v, no. 234.

Notes on aneurism. J. Am. M. Ass., Chicago, 1902, xxxviii, 14831486. In his: Collect, repr., 1902-1907, v, no. 235.

On heredity in bilateral cystic kidney. Am. Med., Phila., 1902, iii, 951. In his: Collect, repr., 1902-1907, v, no. 236. Some aspects of .American medical bibliography. .Address at the meeting of the Association of .Medical Librarians, Sarato.ga, June 10, 1902. Bull. Ass. .M. Librar., Bait., 1902, i, 19-32. Also: Am. .Med., Phila., 1902, iv, 424-427. In his: Collect, repr., 1902-1907, v, no. 237. Chauvinism in medicine. An address before the Canadian Medical Association, .Montreal, Sept. 17, 1902. Phila. M. J., 1902, X. 432-439. In his: Collect, repr., 1902-1»07, v, no. 238.

On splenic amemia. [Second paper.] Am. J. M. Sc, Phila., 1902, cxxiv, 751-770. Also: Tr, Ass. Am. Physicians, Phila., 1902, xvii, 429-456. In his: Collect, repr., 1902-1907, v, no. 239.

William Beaumont. A pioneer American physiologist. An address before the St. Louis Medical Society, Oct. 4, 1902. St. Louis, 1902, 29 p. 8'. .4/so.- J. Am. M. Ass., Chicago. 1902. xxxix. 12231231. In his: Collect, repr., 1902-1907, v, no. 240.

A note on the treating of the history of medicine. Grit. M. J., Lond., 1902, ii, 93.

Intermittent claudication. Montreal M. J., 1902, xxxi, 81-86.

A visit to the Hunterian Library at Glasgow. Bull. Ass. M. Librar., Bait., 1902, i, 20-23.


Case of leukaemia. Virginia M. Semi-Month.. Richmond, 1902-3, vii, 540.

On the need of a radical reform in our methods of teaching senior students. Med. News. N. Y., 1903, Ixxxii, 49-53. In his: Collect, repr., 1902-1907, v, no. 241.

Aneurism of the descending thoracic aorta. Phila., 1903, J. B Lippincott Co., 40 p. 8°. Also: Internal. Clin., Phila., 1903, 13. s., i, 1-40, In his: Collect, repr., 1902-1907. v, no. 242.

On the educational value of the medical society. Boston M. & S. J., 1903, cxivili, 275-279. In his: Collect, repr., 1902-1907, v, no. 243.

A case of chronic purpuric erythema (eight years' duration) with pigmentation of skin and enlargement of liver and spleen. J. Cutan. Dis. incl. Syph., N. Y., 1903, xxi, 297-302. In his: Collect, repr., 1902-1907, v, no. 244.

On obliteration of the superior vena cava. Johns Hopkins Hosp. Bull.. Bait., 1903, xiv. 169175. In his: Collect, repr., 1902-1907, v, no. 245.

On the so-called Stokes-Adams disease (slow pulse with syncopal attacks, etc.). Uincet. Lond., 1903, li, 516-524. In his: Collect, repr.. 1902-1907, v, no. 246.

Chronic cyanosis with polvcvlha>mia and enlarged spleen: a new clinical entity. Am. J. .M. Sc, Phila., 1903, n. s.. cxxvl, 187-201. .4/so; Tr. Ass. Am. Physicians, Phila., 1903, xvill, 299-325. In his: Collect, repr.. 19021907, v, no. 247,

The master-word in medicine. An address to medical students on the occasion of the opening of the new buildings of the Medical Faculty of the Tniversity of Toronto, Oct. 1, 1903, Baltimore, 1903, J. Murphv Co.. 33 p. 8'.

Also: Brit. M. J.. Lond., 1903. II. 1196-1200.

Also: Canad. J. M. & S.. Toronto, 1903, xlv, 333-347.

Also: Montreal .M. J.. 1903, xxxll. 771-785.

Also: Johns Hopkins Hosp. Bull., Bait., 1904, xv. 1-7.

In his: Collect, repr., 19021907, v, no. 248.


230


[Xo. 341


Typhoid fever and tuberculosis. Am. Med., Phila., 1903, vi, 10151016. In his: Collect, repr., 1902-1907, v, no. 249. The home in its relation to the tuberculosis problem. Med. News, N. Y., 1903, Ixxxiii, 1105-1110. In his: Collect, repr., 1902-1907, v. no. 250. On the visceral manifestations of the erythema group of skin diseases. Tr. Ass. Am. Physicians, Phila., 1903, xviii, 599-624. Also: Am. J. M. Sc, Phila., 1904, cxxvii, 1-23. In his: Collect, repr., 1902-1907, v, no. 251. Diabetes in infancy. Phila. M. J., 1903, xi, 538. The significance of cutaneous angiomata, Med. News. N. Y., 1903.

Ixxxii, 91. The varieties of linese albicantes. Med. News, N. Y., 1903, Ixxxiii,

904. Aneurism of upper part of thoracic aorta. (Proc. Johns Hopkins Hosp. Med. Soc. Oct. 20, 1902.) Johns Hopkins Hosp. Bull., Bait., 1903, xiv, 85.

Certain forms of cyanosis with polycythsemia. (Proc. Johns Hopkins Hosp. Med. Soc, Nov. 17, 1902.) Johns Hopkins Hosp. Bull.. 1903, xiv. 91. Also: Maryland M. J., Bait, 1903, xlvi, 81-82.

Two cases of cirrhosis of the liver in children. (Proc. Johns Hopkins Hosp. Med. Soc, March 16, 1903.) Johns Hopkins Hosp. Bull., Bait., 1903, xiv, 322.

1904

Aequanimitas, with other addresses to medical students, nurses and practitioners of medicine. Phila., 1904, P. Blakiston's Son & Co. 389 p. 12°.

The same. Lond., 1904, H. K. Lewis, 389 p. 12°.

The Ingersoll lecture, 1904. Science and immortality. Boston, 1904, Houghton, Mifflin & Co. 60 p. 12°.

The " phthisiologia " of Richard Morton, M. D. Med. Libr. & Hist. J., Brooklyn, 1904. ii, 1-7. In his: Collect, repr., 1902-1907, v, no. 252.

Ochronosis: the pigmentation of cartilages, sclerotics. and skin in alkaptonuria. Lancet. Lond., 1904, i, 10-11. In his: Collect, repr., 1902-1907, v. no. 253.

On the surgical importance of the visceral crises in the erythema group of skin diseases. Am. J. M. Sc, Phila. & N. Y., 1904, n. s., cxxvii, 751-754.

Also: Johns Hopkins Hosp. Bull., Bait., 1904, xv. 259-261.

In his: Collect, repr., 1902-1907, v, no. 254.

Angina pectoris and arterio-sclerosis. J. Am. M. Ass., Chicago,

1904, xliii, 775.

Chronic cyanotic polycythemia with enlarged spleen. Brit. M. J., Lond., 1904, i, 121.

Korsakoff's disease. N. York M. J. [etc.], 1904, ixxix, 570.

Vasomotor mottling. (Proc Johns Hopkins Hosp. Med. Soc,

Nov. 16, 1903.) Johns Hopkins Hosp. Bull., Bait., 1904, xv, 66. Aneurism of arch of aorta and innominate. (Proc. Johns Hopkins

Hosp, Med. Soc, Nov. 16, 1903.) Johns Hopkins Hosp. Bull.,

Bait., 1904, xv, 66.

Remarks at the unveiling of the memorial tablet to Dr. Jesse AV. Lazear. Johns Hopkins Hosp. Bull., Bait., 1904, xv, 3S7-388.

The home in its relation to the tuberculosis problem. Sanitarian, N. Y., 1904, lii, 322-336. Also: Canada Lancet, Toronto, 1904-5, xxxviii, 600-612.

1905 The principles and practice of medicine, designed for the use of practitioners and students of medicine. 6. ed. N. Y. & Lond.,

1905, D. Appleton & Co. 1143 p. 8°.

Counsels and ideals from the writings of ... . [Selected and edited by C. N. B., Camac] Bost. & N. Y.. 1905, Houghton, Mifflin & Co. 277 p. 12°.

Unity, peace, and concord; a farewell address to the medical profession of the United States. Oxford, 1905, H. Hart, 22 p. 8°. Also: J. Am. M. Ass., Chicago, 1905, xiv, 365-369. Also: St. Louis M. Rev.. 1905, lii, 112-116. Also: Maryland M. J., Bait., 1905, xlviii, 412-422. In his: Collect, repr., 1902-1907, v, no. 255.


The student life. A farewell address to Canadian and American medical students. Oxford [1905.] H. Hart. 32 p. 8°. Also: Canada Lancet, Toronto, 1905-6, xxxix, 121-138. Also: Med. News, N. Y., 1905, Ixxxvii, 625-633. Also: St. Louis M. Rev., 1905, lii, 273-283. In his: Collect, repr., 1902-1907, v, no. 256. • Aneurism of the abdominal aorta. Lancet, Lond., 1905, ii, 10891096. In his: Collect, repr., 1902-1907, v, no. 257. Acute tuberculous pneumonia. Brooklyn M. J., 1905, xix, 57-61. The home in its relation to the tuberculosis problem. Rev. internat. de la tuberc. Par., 1905, vii, 403-413. Also: Rep. Henry Phipps Inst, study .... tuberculosis, Phila.,

1905, i, 141-154. Also: Am. J. Tuberc, Detroit, 1905, i, 9-15. An address on Sir Thomas Browne. Brit. M. J., Lond., 1905, ii,

993-998. The Royal Dental Hospital of London: address. Lancet, Lond., 1905, ii, 1210.

Valedictory address at Johns Hopkins University. J. Am. M. Ass.,

Chicago, 1905, xliv, 705-710. Biliary cirrhosis of family type. (Proc. Johns Hopkins Hosp.

Med. Soc, Nov. 7, 1904). Johns Hopkins Hosp. Bull., Bait.,

1905, xvi, 112-113.

Report of a case of ulcerative endocarditis, with embolism of the aorta. (Proc. Johns Hopkins Hosp. Med. Soc, Dec. 19, 1904). Johns Hopkins Hosp. Bull., Bait.. 1905, xvi, 118.

Report of a case of arterio-venous aneurism of the thigh. (Proc. Johns Hopkins Hosp. Med. Soc, Dec. 19, 1904). Johns Hopkins Hosp. Bull., Bait., 1905, xvi, 119.

A case of arterio-venous aneurism. (Proc. Johns Hopkins Hosp. Med. Soc, Jan. 16, 1905). Johns Hopkins Hosp. Bull., Bait., 1905, xvi, 146.

Resume of history of blood platelets. (Proc. Johns Hopkins Hosp. Med. Soc, March 6, 1905). Johns Hopkins Hosp. Bull., Bait., 1905, xvi, 200.

A letter to graduates of The Johns Hopkins Medical School. Johns Hopkins Hosp. Bull., Bait, 1905, xvi, 410.

1906

Aequanimitas, with other addresses to medical students, nurses, and practitioners of medicine, 2. ed. with three additional addresses. Phila., 1906, P. Blakiston's Son & Co., 475 p. 8°.

The same, Lond., 1906, H. K. Lewis, 485 p. 8°.

Convulsions in typhoid fever. Practitioner, Lond., 1906, Ixxvi, 1-8. In his: Collect repr., 1902-1907, v, no. 258.

On the medical aspects of carcinoma of the breast. Brit. M. J., Lond., 1906, i, 1-4.

In his: Collect repr., 1902-1907, v, no. 259.

Angina pectoris as an early symptom in aneurism of the aorta. Med. Chron., Manchester, 1906, xliv, 69-79. In his: Collect, repr., 1902-1907, v, no. 260.

Religio medici. An address delivered at Guy's Hospital, October, 1905, Lond., 1906, Chiswick Press, 31 p. 8°. Also: Library, Lond., 1906, vii, 1-31. In his: Collect repr., 1902-1907, v, no. 261.

The growth of truth as illustrated in the discovery of the circulation of the blood. Being the Harveian oration delivered at the Royal College of Physicians, London, October 18, 1906. Lond., 1906, H. Frowde. 44 p. 8°.

Also: Brit. M. J., Lond., 1906, ii, 1077-1084.

Also: Lancet, Lond., 1906, ii, 1113-1120.

Also: Boston M. & S. J., 1906, civ, 491-502.

In his: Collect repr., 1902-1907, v, no. 262.

Pracastorius. Proc. Charaka Club, N. Y., 1906, Ii, 5-20. In his: Collect repr., 1902-1907, v, no. 263.

Address of the Vice-President. Nat. Ass. Study & Prevent. Tuberculosis, Trans., N. Y., 1906, i, 20-27.

John Radcliffe [the first possessor of the " gold-headed cane."] Johns Hopkins Hosp. Bull. Bait., 1906, xvii, 163-165.


Jilt, 1919]


231


1907

Collected reprints. Fifth series. (January 1, 1902-January 1, 1907.) (Bait, 1907.1

The Royal Medical Society of Edinburgh: particularly its relations with the profession of the United States and Canada. Scot. M. & S. J., Edinb.. 1907, xx, 239-246.

Cerebrospinal fever. Edinb. M. J., 1907, n. s.. xxi, 199-204.

The earlv diagnosis of cancer of the stomach. Brit. M. J., Lond., 190", i, 746.

On the library of a medical school. Johns Hopkins Hosp. Bull., Bait.. 1907. xviii, 109-111.

On telangiectasis circumscripta universalis. Johns Hopkins Hosp. Bull., Bait., 1907. xviii, 401-403.

A clinical lecture on abdominal tumors associated with disease of the testicle. Lancet, Lond.. 1907. i, 1409-1412.

Note on the use of a medical journal. West. Canada M. J.. Winnipeg. 1907. i. 1-3.

The reserves of life. St. Mary's Hosp. Gaz., Lond., 1907, xiii. 95-98. The evolution of internal medicine.

In: Mod. .Med. (Osier). Phila. & N. Y.. 1907. i. p. xv-xxxiv.

Osier. W., & Churchman. J. W. Svphilis.

In: Mod. .Med. (Osier), Phila. & N. Y.. 1907, iii, 436-521.

Osier, W., & McCrae. T.. eds. Modern medicine, its theory and practice. In original contributions by American and foreign authors, v. 1-3. Phila. & N. Y.. 1907, Lea Brothers & Co., 8°.

Osier. W. \ct nl.]. Discussion on the diagnosis of acute pancreatitis. (Abstr.l Brit. M. J.. Lond.. 1907. ii. 1132-1135.

Krehl, Ludolf. Principles of clinical pathology. A text-book for students and physicians. Authorized transl. from the 4. German ed. by Walter Hewlett, with an introduction by William Osier. 2. ed. Phila. & Lond. 1907. J. B. Lippincott Co. 520 p. S'.

Quarterly (The) Journal of Medicine. Edited by William Osier let al.]. Oxford. 1907. V. 1. roy. 8'.


Thomas Linacre. Cambridge. 1908, University Press, 64 p. 11 pi. 12°.

An Alabama student, and other biographical essays. N. Y., 1908, Oxford Univ. Press, Am. Branch. 334 p. 8 .

La pratique de la m^decine. Traduction frauQaise sur la 6' Edition par M. Solomon et Louis Lazard. Preface du Dr. Pierre Marie. Par.. 1908. G. Steinheil. 12.30 p. 8°.

On multiple hereditary telangiectasis with recurring haemorrhages. Quart. J. Med., Oxford, 1907-8, 1. 53-58.

Splenic polycythaemia with cvanosis. Proc. Rov. Soc. .Med.. I..ond.. 1907-8. 1. Clin. Sect.. 41-43.

A clinical lecture on erythema (polycythemia with cyanosis, maladie de Vaquez). Lancet, Lond.. 1908. i. 143-146.

Note on French and German for medical students. Lancet, Lond., 1908, It, 957.

Splenic enlargements other than leukemic. Brit. M. J.. Lond., 1908. ii. 1151-1154.

Remarks on the functions of an out-patient department Brit. M. J.. Lond.. 1908. i. 1470-1473. Also: St. I^uls M. Rev.. 1908. Iviil. 344-346.

Chronic Infectious endocarditis. Quart. J. Med . Oxford. 1908-9. II. 219-230. Also: Tribune med., N. Y.. 1909, I, v. 29.

Endocardites infectieuses chronlques. Bull, el m6m. Soc. m^'-d. d. h6p. de Par, 1908. 3. s.. xxv. 794-796. Also: Tribune m«d.. Par. 1908. n. s., xl. 773.

The pneumococcus Infections. Clin. J.. Lend.. 1907-8. xxxi, 295-301. Also: Tr .M. Soc, Lond.. 1909. xxxi, 93-116.

Historical note on hereditary chorea. Neurographs. Brooklyn, 1908. 1. 113-116.

Vienna after thirty-four years. J. Am. M. Ass.. Chicago, 1908, 1, 1523-1525.


Acute endocarditis. In: Mod. Med. (Osier), Phila. & N. Y., 1908, iv, 133-150.

Diseases of the arteries.

In: Mod. Med. (Osier), Phila. & N. Y.. 1908, Iv, 426-447.

Aneuo'sm.

In: Mod. Med. (Osier). Phila. & N, Y.. 1908, iv. 448-502.

Osier. W.. & Gibson. A. G. Diseases of the valves of the heart. In: Mod. Med. (Osier), Phila. & N. Y.. 1908. iv. 205-269.

Osier. W., & McCrae. T., eds. Modern medicine, its theory and practice. In original contributions by American and foreign authors, v. 4-5, Phila. & N. Y., 1908. Lea & Feblger 8°.

1909 The principles and practice of medicine, designed for the use of

practitioners and students of medicine. 7. ed., N. Y. & Lond.,

1909. D. Appleton & Co.. 1143 p., 8°. Lehrbuch der internen Medizin. Aus dem Engllschen iibersetzt

und fiir deutsche Verhaltnisse erganzt und bearbeitet von

Priv.-Doz. Dr. Edmund Hoke, mit einem Vorwort von ober sanitatsrat und Hofrat Prof. Dr. R. v. Jaksch. Berlin & Wlen,

1909. Urban & Schwarzenberg, 879 p., 8°. De la paralvsie du nerf recurrent gauche dans les affections

mitrales.' Arch. d. mal. du cceur [etcl. Par, 1909, Ii, 73-76. Paralvsis of the left recurrent laryngeal nerve In mitral-valve

disease. Montreal M. J., 1909. xxxviii. 79-83. Remarks on the medical library in post-graduate work. Brit.

M. J.. Lond.. 1909, Ii, 925-928. Schorstein lecture on syphilis and aneurysm. Brit M. J., Lond..

1909. ii. 1509-1514. The treatment of disease. Lond.. 1909. H. Frowde, 26 p.. 8°. Also: Brit M. J., Lond.. 1909. ii. 185-189. Also: Canad. Lancet. Toronto, 1908-9, xlii, 896-912. Note on the relation of the capillary blood-vessels in purpura.

Lancet, Lond.. 1909. i. 1385. An address on the nation and the tropics. Delivered at the London

School of Tropical Medicine on Oct 26. 1909. Lancet, Lond.,

1909. ii. 1401-1406. Impressions of Paris. J. Am. M. Ass.. Chicago, 1909, Hi, 701; 771. Old and new. Annual oration on the occasion of the opening of

the new building of the .Medical and Chirurgical Faculty of

Maryland, .May 13, 1909. J. .Am. M. Ass., Chicago, 1909, llii.

4-8.

In: 'Sys't. Med. (Allbutt & Rolleslon). Lond., 1909, vl, 620-681.

Raynaud's disease.

In: Mod. Med. (Osier), Phila. & N. Y.. 1909, vi, 625-647.

Angioneurotic oedema; Quincke's disease.

In: Mod. Med. (Osier), Phila. & N. Y., 1909. vi. 648-664. Diffuse scleroderma; ervthromelalgia.

In: Mod. Med. (Osier), Phila. & N. Y., 1909. vl. 665-682. Osier, W.. & Keith. A. Stokes-Adams disease.

In: Syst Med. (Allbutt & Rolleston). Lond.. 1909. vi, 130-156. Osier. W.. & McCrae. T.. eds. Modern medicine. Its theory and practice. In original contributions by American and foreign authors, v. 6. Phila. & X. Y., 1909, Lea & Feblger, 799 p.. 8°.

1910 The principles and practice of medicine, transl. by Philip B.

Cousland. 7. ed. (Chinese text] Shanghai. 1910. Presby. Mis.

Press. 8°. In memorlam. Dr John Hewetson. 1867-1910. Johns Hopkins

Hosp. Bull.. Bait. 1910. xxi. .357. Michael Servetus. Johns Hopkins Hosp. Bull., Bait, 1910. xxi.

Also transl.: Deutsche Rev., Stuttg. u. Leipz., 1909, Iv, 328-347. Certain vasomotor, sensory, and muscular phenomena associated

with cervical rib. Am. J. M. Sc. Phila. & N. Y.. 1910. cxxxix,

469-472. The Lumlelan lectures on angina pectoris. Lancet. Lond., 1910,

I. 697; 839; 97.'!. Female hipmophillacs and de novo cases of hsemophllla. Lancet,

Lond., 1910. I. 1226.


332


[Xo. 341


The faith that heals. Brit. M. J., Lond.. 1910. ii. 1470-1472.

The pupil symptoms in thoracic aneurysm: a clinical lecture: Radcliffe Infirmary. Practitioner, Lond., 1910, Ixxxiv, 417-422.

Ueber angina pectoris. AUg. Wien. med. Ztg.. 1910, Iv, 435.

Osier, W., & McCrae, T., eds. Modern medicine, its theory and practice. In original contributions by American and foreign authors, v. 7, Phila. & N. Y., 1910, Lea & Febiger, 969 p., 8°.

1911 Man's redemption of man. Am. Mag., N. Y., 1910-11, Ixxi, 246-252.

Transient attacks of aphasia and paralyses in states of high blood pressure and arteriosclerosis. Canad. M. Ass. J., Toronto, 1911, i, 919-926.

An address on the hospital unit in university work. Lancet, Lond., 1911, i, 211-213. Also: Northumberland & Durham M. J., Newcastle-upon-Tyne,

1910, xviii, 178-189.

Remarks on organization in the profession. Brit. M. J., Lond.,

1911, i, 237-239.

Treatment; introductory address. Nat. Ass. Prev. Consumpt. Tr.,

Lond., 1911, 119-123. The pathological institute of a general hospital. Glasgow M. J.,

1911, Ixxvi, 321-333.

Sir Astley Cooper's case of ligature of the abdominal aorta. Guy's

Hosp. Gaz., Lond., 1911, xxv, 277. Sulle telangiectasie emorragiche ereditarie. Riforma med., Napoli,

1911, xxvii, 57-58. Vallery-Radot, Rene, The life of Pasteur. Transl. from the French

by Mrs. R. D. Devonshire; with a foreword bv Sir William

Osier, 2 v. Lond., 1911, Constable & Co. 242 p., port; 271 p., S°.

1912 The principles and practice of medicine. S. ed., rev. with the assistance of Thomas McCrae. N. Y. & Lond., 1912. D. Appleton & Co., 1250 p., 8°.

A Drake monument. Lancet-Clinic, Cincin., 1912, cvii, 421.

Dr. Robert Fletcher. Bristol M.-Chir. J., 1912, xxx. 289-294, port.

High blood pressure. Its associations, advantages and disadvantages. Brit. M. J., Lond., 1912, ii, 1173-1177.

Chronic infectious endocarditis, with an early history like splenic anemia. Interstate M. J., St. Louis, 1912, xix, 103-107.

Men and books:

I. Nicolaus Steno. Canad. M. Ass. J., Toronto. 1912, ii, 67-68.

II. Les collections artistiques de la Faculte de Medecine de Paris. Ibid.. 68-69.

III. Samuel Wilkes. Ibid., 70-71.

IV. Jean Astruc and the higher criticism. Ibid., 151-152.

V. Two Frenchmen on laughter. Ibid., 152-155.

VI. An incident in the life of Harvey. Ibid., 246-247.

Vn. Letters of Laennec. Ibid., 247-248.

VIII. Dr. Payne's library. Ibid.. 248-249.

IX. The funeral of Lord Lister. Ibid., 343-344.

X. Gui Patin. Ibid.. 429-430.

XI. George Bodington. Ibid., 526-527.

XII. Histoire de la Charite. Ibid., 527-528.

XIII. The school of Physic. Dublin. Ibid.. 833-835.

XIV. Kelly's American Medical Biography. Ibid., 938-939.

XV. The works of John Caius. Ibid., 1034-1036.

XVI. "William Beaumont. Ibid., 1136-1138.

Meyer, Jesse S.. Life and letters of Dr. William Beaumont, including hitherto unpublished data concerning the case of Alexis St. Martin. With an introduction bv Sir William Osier. St. Lous, 1912. C. V. Mosby Co., 342 p. port, roy., 8".


Man's redemption of man. A lay sermon, McEwan Hall, Edinburgh. Sunday, July 2, 1910. N. York, 1913. P. B. Hoeber, 63 p., 24°.

A way of life. 2. impression. Lond., 1913, Constable & Co., 62 p., 16°.

Address on examinations, examiners and examinees. Brit. M. J., Lond., 1913, ii, 946-948. Also: Lancet, Lond., 1913, ii, 1047-1050. Also: Dublin J. M. Sc, 1913, cxxxvi, 313-327. An arterio-venous aneurysm of the axillary vessels of 30 years' duration. Lancet, Lond., 1913, ii, 1248.

Specialism in the general hospital. Johns Hopkins Hosp. Bull., Bait., 1913, xxiv, 167-171. Also: Johns Hopkins Alumni Mag., Bait., 1913, i, 275-286.

Case illustrating circulatory disturbance with cervical rib. Proc. Roy. Soc. Med., Lond., 1912-13, vi, Clin. Sect. 9-12.

[Introductory remarks on history of medicine.] Med. Mag., Lond., 1913, xxii, 35.

A down survey manuscript of William Petty. Med. Mag., Lond., 1913. xxii. 36-39. Also: Proc. Roy. Soc. Med., Lond., 1912-13, vi. Sect. Hist. Med., 2-5.

Presidential address, British Hospitals Association. Med. Mag., Lond., 1913, xxii, 368-372.

Men and books:

XVII. The young Laennec. Canad. M. Ass. J., Toronto, 1913, iii, 137-140.

XVIII. Mediaeval Medicine. Ibid., 140-141.

XIX. Robert Fletcher. Ibid., 227-228.

XX. Jaques Benigne Winslow. Ibid., 319-321.

XXI. Aristotle, Greek Thinkers by Gempera, vol. iv. Ibid., 416-417.

XXII. Dr. Slop. Ibid.. 612-613.

XXIII. John Shaw Billings. Ibid., 613-616.

Osier, Sir W., & McCrae, T., eds. Modern medicine; its theory and practice. In original contributions by American and foreign authors. 2. ed. v. 1. Phila. & N. Y., 1913, Lea & Febiger, 1122 p., 8°.

Osier, Sir W., AVelch. W. H., [et al.^ Memorial meeting in honor of John Shaw Billings. Bull. N. Y., Public Library, 1913, xvii, 511-535. Also: [Abstr.] Library J., N. Y., 1913, xxxviii, 334-338.

1914

Bacilli and bullets. N. Y., 1914, Oxford Univ., 8 p., 12°.

A way of life. An address to Yale students Sunday evening. April 20, 1913. N. York, 1914. P. B. Hoeber, 62 p., 24°.

Syphilis of the liver with the picture of Banti's disease. Proc. Roy. Soc. Med., Lond., 1913-14, vii, Med. Sect., 1-7.

Splenomegaly; two attacks of hsmatemesis; irregular liver. Proc. Roy. Soc. Med., Lond., 1913-14, vii, Clin. Sect., 108.

Suggested scheme for the restoration of the tomb of Avicenna. Proc. Roy. Soc. Med., Lond., 1913-14, vii. Sect. Hist. Med., 280.

Medical notes on England at war. J. Am. M. Ass., Chicago, 1914,

Ixiii, 2303-2305. The proposed general catalogue of incunabula. Bull. Med. Library

Ass., Bait, 1914, iii, 45-48.

Men and books:

XXIV. Israel and medicine. Canad. M. Ass. J., Toronto, 1914, iv, 729-733.

XXV. " Looking back." 1889. Ibid.. 1012-1014.

XXVI. Nathan Smith. Ibid., 1109-1111.

An address on the medical clinic: a retrospect and a forecast. Brit. M. J., Lond., 1914. i, 10-16.


.Il I.Y. 1!11!»]


233


Early printed medical books. Brit. M. J., Lond., 1914, i, 205. Also: Lancet, Lond.. 1914, 1, 255.

The visceral lesions of purpura and allied conditions. Brit M. J.,

Lond.. 1914, i. 517-525. Some MSS. and books in the Bodleian Library illustrating the

evolution of British surgery. Brit. M. J., Lond., 1914, i, 825 826. An address at the new pathological laboratory at the Royal Mineral

Water Hospital, Bath. Brit. M. J., Lond., 1914, i, 13141315. Also: Lancet, Lond., 1914. i, 16S9-1690. Bacilli and bullets: an address to the otticers and men in the camps

at Churn. Brit. .M. J.. Lond., 1914, ii, 569-570. Also: Med. Mag.. Lond., 1914, xxiii. 580-583.

Sir James Y. Simpson and anesthesia (Correspondence). Lancet, Lond., 1914, ii, 1067.

Long and anipsthesia (Correspondence). Lancet, Lond., 1914. ii, 1219-1220.


Syphilis of the liver with the picture of Banti's disease Lond., 1914, xliii, 462-464.


Clin. J., Brit. M. J., Lond., 1914. i,


Appreciation of Silas Weir Mitchell. 120-121.

The war and typhoid fever. Brit. M. J., Lond., 1914, ii. 909-913.

Also: Tr. Soc. Trop. M. & Hyg., Lond., 1914-15, viii, 45-74. Osier. Sir W., & Churchman, J. W., S.vphilis.

In: .Mod. .Med., 2. ed. (Osier & McCrae), Phlla. & N. Y., 1914. ii, 144-215. Osier, Sir W.. & McCrae, T., eds.. Modern medicine, its theory and practice. In original contributions by American and foreign authors. 2. ed., v. 2-3, Phila. & N. Y., 1914, Lea & Febiger, 8'.

1915 Science and war. Oxford, 1915, Clarendon Press, 40 p., 8°.

Special discussion on the epidemiologv- of cerebrospinal meningitis.

Proc. Rov. Soc. Med., Lond., 1914-15, viii, Epidemiol. & State

Med., 41 45. The Jonathan Hutchinson iconography. A preliminary note.

Johns Hopkins Hosp. Bull., Bait., 1915, xxvi, 82.

A tribute to Dr. Edward L. Trudeau; a medical pioneer. Am. Med., Burlington, Vt. & S. Y., 1915, n. s., x, 20.

Remarks on the diagnosis of polycystic kidney. Internat. Clin., Phila.. 1915, 25. s.. i, 1-5.

The coming of age of internal medicine in America. Internat. Clin., Phila.. 1915. 25. s., iv, 1-5.

Remarks on arterio-venous aneurysm. Lancet, Lond., 1915, i, 949-955.

Note on acute infectious jaundice. Lancet, Lond., 1915, ii, 605.

An address on science and war. Delivered at the University of Leeds Medical School on October 1, 1915. Lancet, Lond., 1915, 11, 795-801.

Cold-bite + muscle-Inertia = trench-foot. Lancet, Lond., 1915, 11, 1368.

Medical notes on England at war. J. Am. M. Ass., Chicago, 1915, Ixlv. 679-680; 1512-1513; 2001-2002. Also: West Canada M. J.. Winnipeg. 1915, ix, 59-65. Also: Dominion M. Month,. 1915. xliv. 41; 125.

Remarks on cerebrospinal fever in camps and barracks. Brit. M. J., Lond., 1915. i. 189.

Discussion on the treatment of cerebrospinal meningitis. Brit. M. J.. Lond.. 1915, ii, 604.

Acute endocarditis. In: Mod. Med. 2. ed. 148-165.

Diseases of the arteries. In: .Mod. .Med. 2. ed. (Osier & McCrae), Phlla. & S. Y., 1915, iv. 449-471.


(Osier & McCrae). Phila. & N. Y., 1915, iv,


Aneurism. In: Mod. Med. 2. 472-525.


ed. (Osier & McCrae), Phila. & .\. Y., 1915. iv.


Raynaud's disease.

In: Mod. Med., 2. ed. (Osier & McCrae), Phila. & N. Y., 1915, iv. 975-997.

.\ngioneurotic ttdema. Quincke's disease.

In: .Mod. .Med. 2. ed. (Osier & McCrae), Phila. & X. Y., 1915. iv, 99S-1013.

Diffuse scleroderma. Erythromelalgia. In: Mod. Med. 2. ed. (Osier & McCrae). Phila. & N. Y., 1915, iv, 1014-1031.

Osier, Sir W., & Gibson. A. C, Diseases of the valves of the heart. In: Mod. Med. 2. ed. (Osier & McCrae), Phila. & N. Y., 1915, iv, 212-274.

Osier. Sir W., & McCrae, T.. cds. Modern medicine, its theory and practice. In original contributions by .American and foreign authors. 2. ed., v. 4-5, Phila. & X. Y., 1915, Lea & Febiger, 8°.

Macmichael, William, The gold-headed cane; with an introduction by Sir William Osier; and a preface by F. K. Packard. N. Y., 1915. P. B. Hteber, 261 p., 8\

1916 Science and war; an address delivered at the University of Leeds

Medical School. N. Y., 1916, Oxford Univ. Press, 39 p., 8°. Discussion on paratyphoid fever. Proc. Roy. Soc. Med., Lond.,

1915-16. ix. .Med. Sect., 38.

An address on the tuberculous soldier. Lancet, Lond., 1916, ii, 220-221.

Local tetanus (Correspondence). Lancet, Lond., 1916, ii, 877.

Osier, Sir W.. Brown. W. L., {et al.] Discussion on trench nephritis. Proc. Roy. Soc. Med., Lond., 1915-16, ix, Med. & Therap. & Pharmacol. Sect., 1-xl.

Osier. Sir W.. Robb, G., [et al.] Discussion on the treatment of cerebrospinal meningitis. Proc. Ro.v. Soc. Med., Lond., 1915-16, ix. Therap. & Pharmacol. Sect., 1-26.

Osier, Sir W.. Rolleston. H. D., |p/ al.] Treatment of cerebrospinal meningitis. Practitioner. Lond., 1916, xcvi, 1-18.

1917 The campaign against syphilis. Delivered before the Medical Society of London. May 14, 1917. Lancet, Lond., 1917, 1, 787-792. Also: Brit. M. J., Lond., 1917. i. 694-696. The problem of the crippled. Recalled to Life, Lond., 1917, i, 265.

War wastage: a note of warning to examiners of recruits. J.Am. M. Ass., Chicago, 1917, Ixix, 290.

Recurrence or redeposit of cancer? Brit. M. J., Lond., 1917. i. 455.

1918

Essai de bibliographie hippique. Edinburgh & Lond., 1918, W. Green & Son, 4 p., 8°.

The science of librarianship. Bull. Med. Library, Ass. Bait., 191718, vii. 70-74.

Typhoid spine. Bull. Canadian Army M. Corps, 1918. I, 78-79.

Graduated exercise in prognosis. Lancet, Lond., 1918, 1, 231.

The primary examination for the P. R. C. S. Eng.: an appeal to

the President of the Koyal College of Surgeons. Lancet, Lond.,

1918. I, 715.

Medicine In America (Speech to University Extension Students, summer meeting at Cambridge). The Hospital, Lond., 1918, Ixlv, 433.

Trench fever: a critical analysis of the report of the American Commission. Lancet, Lond.. 1918. ii, 496-499.

1919

Observations on the severe anaemias of pregnancy and the postpartum sUte. Brit. M. J., Lond.. 1919, i, 1-3.

Influenzal pneumonia: bilateral rigidity, spinal meningitis with hiembrrbage Into the tbeca vertebralis and nerve roots. Lancet. Lond., 1919. i. 501.


234


[No. 341


THE JOHNS HOPKINS HOSPITAL REPORTS


VOLUME I. 423 pages, 99 plates.

VOLUME II. 570 pages, with 28 plates and figures. VOLUME III. 766 pages, with 69 plates and figures. VOLUME IV. 504 pages, 33 charts and illustrations. VOLUME V. 480 pages, with 32 charts and illustrations. The Malarial Fevers of Baltimore. By W. S. Thayeh. M. D.. and J. Hewetson. M. I). „ T, ». r>

A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever. By William Oslee, M. D.. with additional papers hy G. Bldmee. M. D., Simon Flexner. M. D., Walter Reed, M. D., and H. C. Parsons, M. D.

VOLUME VI. 414 pages, with 79 plates and figures.

VOLUME VII, 637 pages with illustrations.

VOLUME VIII. 562 pages with illustrations.

VOLUME IX. 1060 pages, 66 plates and 210 other illustrations.

Contributions to the Science of Medicine, Dedicated by his Pupils to William Heney Welch, on the twenty-fifth

anniversary of his Doctorate. This volume contains 38 separate

papers. VOLUME X. 516 pages, 12 plates and 25 charts, VOLUME XI. 555 pages, with 38 charts and illustrations. VOLUME XII. 648 pages, 12 plates and other illustrations. VOLUME XIII, 605 pages, with 6 plates, 201 figures, and 1 colored chart. VOLUME XIV. 632 pages, with 97 figures.

Studies in Genito-Urinary Surgery. The Treatment of Prostatic Hypertrophy by Conservative Perineal Pro^ • - ' .ilts based on a detailed


14


An nualvsis of cases and cases. "By Hugh H.


G, M. D.


The Johns


Eecto-Urethral Fist'ulie.' Description 'of New Procedures for their Prevention and Cure. By Hugh H. Young. M. D. , ^^ „ , , . .

The Early Diagnosis and Radical Cure of Carcinoma of the Prostate, being a study of 40 cases and presentation of a radical operation which w.is carried out in four cases. By Hugh II. Young, M. D.

VOLUME XV. 542 pages, with 87 illustrations.

Twelve papers on pneumonia. By Des. Chatard, Fabyan, Emerson, Marshall, McCrae, Steiner, Howard and Hanes. ., ,, r. a

A Study of Diarrhea in Children. J. H. Mason Knox, Jr., M. D., and Edwin H. Schorer. M. D. _

Skin Transplantation. By John Staige Davis, M

Epidemic Cerobrospinal Meningitis Hopkins Hospital. By Frank .

VOLUME XVI. 670 pages with 151 figures.

Studies in the Eiperimental Production of Tuberculosis in the GenitoITrinnry Organs. By George Walker, M. D.

The Effect on Breeding of the Removal of the Prostate Gland or of the Vesicula; Seminales. or of Both; together with Observations on the Condition of the Testes after such Operations on ^Vhite Rats. By George Walker, M. D. „ ,, ^^

Scalping Accidents. By John Staige Davis. M. D. , „. v., «„„„„

Obstruction of the Inferior Vena Cava with a Report of Eighteen Cases. By J. Hall Pleasants, M. D. „ ^. m . rt

Physiological and Pharmacological Studies on Cardiac Tonicity in Mammals. By Percival Douglas Cameron. M. D.

VOLUME XVII. 586 pages with 21 plates and 136 figures.

Free Thrombi and Ball Thrombi in the Heart. By Joseph H. Hewitt,

Benzol as a Leucotoxin. By Lawrence Selling. MD.

Primary Carcinoma of the Liver. By Milton C. >Mxternitz. >I- P;^

The St.atistical Experience Data of The Johns Hoi.kins Hospital, Baltimore,

Md.. 1S92-1911. By Frederick L. Hoffman, LL. D., F. b.S. The Origin and Development of the Lymphatic System. By Florence R.

The Nud'ei Tiibe'ris Laterales and the So-called Ganglion Opticum Basale.

hv Edward F. Malone. M. D. „ t, t c, .„„„

Venous Thrombosis During Myocardial Insufficiency. By Frank J. Sladen,

M. D,. and Milton C. Winternitz, M. D » , r. tt „„„ n

Leuk,i>mia of the Fowl: Spontaneous and Experimental. By Harry L.

Schmeisser, M. D. VOLUME XVIII. 445 pages with 124 figures. Fasciculus I.

By


W. GOODrASTDRE,

By E. W. Good


A Study of a Toxic Substance of the Pancreas. M. D., and George Clark, M. D.

Old Age In Relation to Cell-overgrowth and Cancer.

PASTURE, M. D., and G. B. Wislocki, M. D. .

The Effect of Removal of the Spleen Upon Metabolism in Dogs; Preliminary Report. By J. H. King. M. D. t>„ t h

The Effect of Removal of the Spleen Upon Blood Transfusion By J. H. King. M. D.. B. M. Bernheim. M. D.. and A. T. Jone.s, JLD.

<?tiidieson Parathvroid Tetany. Bv D. Wright Wilson, M. D., Thornton Stearns, M. D., J. H. Janney,' Jr., M. D., and Madge DeG. Thurlow,

Some Observations on the Effect of Feeding Glands of Internal Secretion to Chicks. By M. C. Winternitz, M. D.


By


Bj


Spontaneous and Experimental Leukaemia in the Fowl.

Schmeisser. M. D. Studies on the Relation of Fowl Typhoid to Leuktemia of the Fowl.

M. C. Winternitz. M. D., and II. C. Schmeisser. M. D. Hyaline Degeneration of the Islands of Langerhans in Pancreatic Diabetes.

By M. C. Winternitz. M. D. Generalized Miliary Tuberculosis Resulting from Extension of a Tubercular

Pericarditis Into the Right Auricle. By M. C. Winternitz, M. D. Acute Suppurative Hypophvsitis as a Complication of Purulent Sphenoidal

Sinusitis. By T. R. Boggs, M. D., and M. C. Winternitz. M. D. A Case of Pulmonary Moniliasis in the United States. By T. R. Boggs.

M. D., and M. C. Pincoffs, M. D. Gaucher's Disease (A Report of Two Cases in Infancy). By J. H. M.

Knox, M. D., H. R. Wahl, M. D., and H. C. Schmeisser. M. D. A Fatal Case of Multiple Primary Carcinomata. By E. D. Plass, M. D. Congenital Obliteration of the Bile-ducts. By James B. Holmes, M. D. Multiple Abscesses of the Brain in Infancy. By James B. Holmes, M. D. Gastric Carcinoma in a Woman of Twenty-six Years. By R. G. Hussey,

M. D. Subdiaphragmatic Abscess with Rupture Into the Peritoneal Cavity Following Induced Pneumothorax for Pulmonary Haemorrhage. By R. G.

Hussey. M. D. Heart Block Caused by Gumma of the Septum. By E. W. Bridgeman,

M. D., and H. C. Schmeisser, M. D. Analysis of Autopsy Records.

A. The Johns Hopkins Hospital. (Table Showing Percentage of

Autopsies.)

B. The City Hospitals, Bay View. (Table Showing Percentage of

Autopsies.) " The Monday Conferences."

the Staff of the Department of Pathology.

Fasciculus II. The R61e of the Autopsy in the Medicine of To-day. By M. C. Winternitz,

M. D. Experimental Nephropathy in the Dog. Lesions Produced by Injection

of B. brnnchisepticus into the Renal Artery. By M. C. Winternitz,

M. D.. and William C. Quinby. M. D. Mesarteritis of the Pulmonary Artery. By M. C. Winternitz, M. D., and

H. C. Schmeisser, M. D. ,.,„,,..

A Clinical and Pathological Study of Two Cases of Miliary Tuberculosis of

the Choroid. By Robert L. Randolph, M. D., and H. C. Schmeisser,

The Blood-vessels of the Heart Valves. By Stanhope Bayne-Jones, M. D. Equilibria in Precipitin Reactions. By Stanhope Bayne-Jones, M. D. Carcinoma of the Pleura with Hypertrophic Osteoarthropathy. Report of

a Case with a Description of the Histology of the Bone Lesion. By

Stanhope Bayne-Jones, M. D, ^ ,,_,.,. „

The Interrelation of the Surviving Heart and Pancreas of the Dog in Sugar

Metabolism. By Admont H. Clark. M. D. Congenital Atresia of the Esophagus with Tracheo-Esophageal Fistula

Associated with Fused Kidney. A Case Report and A Summary of the

Literature on Congenital Anomalies of the Esophagus. By E. D.

Plass M D Ectopia Cordis, with a Report of a Case in a Fifteen-Month-Old Infant.

Bv James B. Holmes, M. D. „ , „ ^

Studies in the Mechanism of Absorption from the Colon. By bAMOEL

Goldschmidt. M. D., and A. B. Dayton. M. D. „ ^ ... .

Report of Two Fatal Cases Following Percy's Low Heat Treatment of

Carcinoma of the Uterus. By V. N. Leonard, M. D., and A. B. Dayton.

The Relationship in Typhoid Between Splenic Infarcts and Peritonitis Unassociatcd with Intestinal Perforation. By A. B. Dayton, M. D.

Left Duodenal Hernia. By A. B. Dayton. M. D.

Histological as Related to Physiological and Chemical Differences in Certain Muscles of the Cat. By H. Hays Bullard, M. D.

A Method of Clearing Frozen Sections. By H. Hays Bullard. m. u.

On the Occurrence and Significance of Fat in the Muscle Fibers of the Atrio-Ventricular System. By H. Hays Bullard^ M. D.

Studies on the Metabolism of Cells in Acids for Embyonic Chicken Cells.

The Significance of the Lunula ' of 'the Nail. By Montrose T. Burrows,

The Oxygen Pressure Necessary for Tissue Activity.

The Functional' Relation of Intercellular Substances in the Body to Certain Structures in the Egg Cell and Unicellular Organisms. By

Studies'^on'"the Grow'th 'o? c'el'ls in vitro. The Cultivation of Bladder and Prostate Tumors Outside the Body. By Montrose T. Burrows, M. D., J. Edward Burns. M. D.. and YosHio Sczukl, M. D

The Study of a Small Outbreak of Poliomyelitis in an Apartment House, Occu'rring in the Course of an Epidemic in a Large City. By Montrose T Burrows, M. D.. and Edwards A. Park. M. D.

Papilloma of the Larynx. Report of a Case Resultant Chronic Diffuse Thyroiditis.

Analysis of Autopsy Records.

Autopsy Statistics.

(a) Bay View.

(b) Johns Hopkins Hospital. Report of the Photographic Department. General Improvements.


_. The Toxicity of a-Amino By Montrose T. Burrows, M. D.,


By Montrose


Contents

Kortnation of Sinfile-Ovum Twins. (Illustrated.)

By Oeobi:k L. Streeteb 235

Changes in Skin Sensitiveness to TiilxTrulin Durin<; Epidemic Intluenza. By Abthvb L. Bloomfield and .Iohn G. Mateeb . 238

Hemorrhage into a I'oetscarlatinal Orvioal Ahseess. Ligation of tlie Common Carotid. Recovery.

By T. M. Rivers 240

Analysit) of C^rdirospinal Fluids of Cats with Menin<;<-al Infections. Bv Lloyd D. Felto.x 242


Horace (Jreen and His Prohanf;. (Illustrated.) lir Wii.MAM Snow XIii.i.kr


PAOB

. 246


The Correlation of X-Uay Findinjrs and Physical Signs in the Chest in I'ncomplicated Epidemic Intluen/a. (Illustrated.) By Abthi'r L. Uloomkielu and Chahi.ks A. Waters . 252


Dr. tieorge Peirce

By .1. H. -Ma.so.n K.nox, .Ir.


Books Received


254 258


FORMATION OF SINGLE-OVUM TWINS

By (iKOKGE L. Streetkr, PrjHirliiietil of Embryology, Carnegie Inslilutioii of Washington


It ha.< recently been the writer'!; privilege to study the Mateer ovum, a very young, weil-preserveil specimen containing twin embryos. The larger eml)ryo is in the primitivegroove stage, having an embryonic plate 0.92 mm. long and 0.78 mm. wide. In it.« form and attachment to the chorionic tnembrane it is entirely normal and, judging from the best criteria we have at i)re.'*nt, it ha.-; a development of about 17 days.' The smaller embryo consist* of an amniotic vesicle 0.1 mm. in its largest internal diameter, and a yolk-vesicle (0.03 mm. internal diameter) slightly detached from it, the two being suspended in the l<H)st> me.>;enc)iyme in the region of the bmly-stalk of the co-twin. The position of these vesicles and their relation to the larger embryo are shown in Fig. 1. The chorionic membrane with its villi and troplu.blast can be rect»giiized above, while below is shown the yolk-sac of the larger embryo, cut transversely through the region of the bo<Iy-stfllk, Among the loose strands of parietal mesoblast intervening Ix-tween these can be seen the two defaclierl vesicles wliich together constitute the very much smaller twin.

The detailed structure of the amniotic vesicle of the smaller embryo is shown in Fig. 2, where its wall can be seen to be made


' For a complete desrription of this embryo aee " A human embryo (Mateer) of the presomite period." Contributions to Embryology. Vol. 9, 1919. Carnegie Inst. Wash.. Pub. No. 272.


up of an ectodermal layer clearly subdivided into amniotic ectoderm and a thicker plate Ik'Iow of embryonic ectoderm, which is to form the embryonic shield. The ectodermal layer is everywhere surrounded by an irregular membranous layer of mestMlerm. The wall of the yolk-sac consists of a single layer of endo<lermal cells (see Fig. 3) and, like the amnion, is inclosed in a layer of mesodermal tissue. In general form the anmiotic vesicle appears to be normal and corres|)onds in many respects to those seen in the ova describeil by I'eters, Fetzer. Jung and Strahi-Heneke. It ditTers from those, however, in being itimpleti'ly detachetl from the y<dk-sac, and in this respect is jirobably abnormal.

Among the first 2.">00 s|)ecimens in the Carnegie Knibryological (\)llection liicre are 4.1 instances of twinnitig, which is about what would be expected in that number of births if we assume the fretiueiicy to vary between 1 and 2 per cent. In nine of these specimens the embryos are not over 20 mm. long — that is, less than eight weeks old — but in only two arc they under 5 mm. One of the.se is the Mati-er specimen which I am describing; the other is a patliological s|)ecinien ( N'o. S2.5) which was obtained by Dr. Cecil Vest at ojieration for tubal pregnancy. In this case the tube contained two chorions undergoing hydatiform degeneration. Sections of these show respective internal iliameters of M x 12 mm. and 14x10 mm.


236


[Fo. 342


Neitlier chorion contains an amnion, and in only one is there any remnant of an embryo (a nodule 2.5 mm. long). In size and character the chorions correspond to those seen in normal ova about four weeks old. The specimen represents, therefore, about the same stage of development as the Watt (1915) twins, .in which there were 17-19 paired somites. The Ohidester specimen (mentioned by Newman, 1917, p. 68) was at first thought to be twins, one embryo having a development of one month, while the other was supposedly in the primitive


eS^'^^ rT^^^-^s^^w,.







•-Mk^


Fid. 1. — Section of the Mateer ovum showing yolk-sac and body-stalk of the primary embryo, between which and the chorionic membrane are two small ectodermic vesicles constituting the amniotic and yolk vesicles of a twin embryo. X 34.

streak stage. Subsequent study, however, has shown that the smaller structure was not really a twin. If, then, we disregard this specimen, that of Watt constitutes the youngest re])orted case of human twinning.

The Mateer ovum is considerably younger than the Watt specimen. Whereas the latter is in the stage of 17 somites, the primary Mateer embryo is in the presomite stage and has only jtist acquired a primitive groove, while the accompanying twin lias attained an even lesser degree of development. Tlie fact.


therefore, that it affords the earliest picture of twin formation that has thus far been seen, lends to this specimen a particular interest. Furthermore, it possesses additional importance in that it shows this early stage of the twinning process in a single ovum. Both the Watt specimen and No. 835, mentioned above, are double-ovum twins.




i


»^^ X .


Fig. 2. — Amniotic vesicle of the twin embryo showing the thicker embryonic plate below already differentiated from the thinner amniotic ectoderm. The vesicle is surrounded by an irregular membranous layer of mesoderm, X 400.

The exact character of the mechanism by which human twins are derived from a single ovum is still unknown. There are, however, certain mammals in which polyembryony is the normal occurrence, and where it has been possible to obtain all the stages of tlie process. This is the case in the nine-banded armadillo which has been carefully studied by Newman ( 1917 ) and Patterson (1913). According to these authors, at a time



Fig. 3. — Yolk-sac of twin embryo enclosed by an irregular layer of mesoderm. X 400.

when the single amniotic vesicle has reached a considerable amount of differentiation there occurs a physiological isolation of four secondary areas in its wall which undergo iude])endent growth and development, giving rise to four individual embryos with a common anmion. This departs from the conditions existing in human twins, since in the latter there are two separate amnions. This is also the case in sheep.


Adqust, 1919]


237


Very young sheep twins, iio» more tlian seven days old, have been described by Asshcton. His specimen consists of a blastocyst 0.9 X O.T mm., coutainini; two germinal areas, each apparently perfect and presumably capable of forming a perfect cmbrvo. They were completely separated and in each of them the embryonic mtiss consisted of a compact cluster of ectodermal cells with a thin endodermal membrane extending a short distance from its margins — the uncompletinl yolk-sac. There was a slight difference in size between the two areas and both were smaller than normal germinal areas in the same stage of development. Assheton regarded liis specimen as having been produced by fission, or a mechanical splitting apart of the original germinal mass, at the time of the formation of the blastodermic vesicle, which he thinks is rendered more likely in such animals as the sheep, in which the cavity of the blastocyst is produced by an irregular cleft formation which tends to subdi%idc the embryonic mass. The direction of the line of fission was a matter of concern to Assheton, who thought that only sagittal fission could produce twins and double monsters. Transverse fission separating primary and secondary centers of growth of the embryo he believes to be incapable of producing embryos that would subsequently grow and develop.

Although aj)[)arently meeting the requirements in the sheep, it is not probable that this simple mechanical explanation presented by Assheton will be sufficient to explain certjvin features of the problem occurring in other forms. There is doubtless, as Xewman argues, a large physiological element which is not to be explainc<l on morphological grounds. In this connection reference may be made to the interesting experiments of Ijewis (1910), who found that small lateral fragments of the medullary plate in the region of the hind-brain, when transplanted, tend to develop individually into a bilaterally symmetrical medulla oblongata, with a characteristic ventricle, roof, and the typical arrangement of white and gray substance. In my own experiments on the otocyst I always found that fractional parts of the otic cup, when transplanted, tend to form comjdetely closed vesicles, although in this organ there is marked predetermination of ti.«sue. We should, therefore, naturally expect that sub<]ivision into two masses of such a primitive and undifferentiated tissue as the embryonic node would result in the formation of two embryos having all the potentialities of the original node.

The earliest stage of development that has been observed in the human embryo is the one described by Miller. In his specimen the embryo, or embryonic node, consists of a solid cell mass undergoing cleft formation preliminary to the opening up of the amniotic ca\-ity. The embryo and the tissue from which the c.xocteloni is formed arc inclosed by a trojihobla«tic shell of ectoderm possessing irregular syncytial loops which tend to enclose the large blood lacun<-F surrounding the ovum, there being as yet no villi. This stage is shown in Fig. 5. A. Instead of a single embryo, as was the case in the Miller specimen, the embryonic node is represented as having subdivided into two masses — that is, as having given off a hypothetical twin. It is conceivable that the chances of the


secondary bud reacliing maturity would depend upon how large a share of the original mass is contributed to it. If the twin is as large as the priuuiry embryo their chances of developing in an orderly manner would be equal, and this is presumably the case in most instiinces of identical twins, ^^^le^e the secondary bud is merely a fragment of the original mass we should expect that, like the fragments of medullary plate in the Lewis experiments, there would be some degree of differentiation; but the process of development would soon be arrested, and at term the stunted bud would be found as a small epithelial cyst on the placenta near the attachment of



Fio. 5. — ^Schematic drawing, showing tlic probable stops in tlie formation of a single-ovum twin. The 3tage.s are drawn at the same scale of enlargement so that they may be directly compared.

A. Stage corresponding to the Miller specimen, showing a hypothetical twin budding off from the primary embryonic node.

B. Stage corresponding to the Bryce-Teacher specimen. C. The Mateer specimen. The relatively small size of the twin In this specimen, and the detachment of the yolk sac from the amniotic vesicle are Indications of arrest In development.

the timbilical cord. In case the twin-bud is only partially detached from the ])rimary node there would exist the basis for the various types of double monsters an<l teratomata.

A slightly more advanced stage is schematically shown in Fig. 5, B, which may be compared to the conditions existing in the well-known Bryce-Teacher specimen. Here, both embryonic mas-^es have developed into ectodermal (amniotic) vesicles, and at the same time small yolk-sacs are forming near them and j)nibably from cells derived from their wall. The transition from stage B to stage C may be readily followed,


338


[No. 342


the latter showing the conditions existing in the Mateer specimen. Here the size of the cav-ity of the yolk-sac has surpassed that of the amnion, a definite body-stalk has formed, and near it are the two vesicles constituting the twin, which, as compared with the primary embryo, is considerably retarded in



Fui. 4. — Photographs of the twin (above) and the primary embryo (below), talten at the same enlargement (lOO diameters) and through similar portions of the embryonic plate.

development. It is probable that under usual conditions the two embryos would be approximately of the same size, and the small size of the twin is to be accounted for by the incompleteness of the bud given off from the primary embryonic node. A comparison of sections made through the amniotic vesicle of


the twin and through a corresponding region of the primary embryo, as shown in Fig. 4, would indicate that the former was essentially normal in form though much retarded in development. The complete detachment of the yolk-sac justifies us, however, in considering it as abnormal. If the pregnancy had not terminated in this case it is probable that the larger embryo would have gone on to maturity and the smaller one would have remained stationary in the form of two minute epithelial vesicles and been entirely overlooked.

In closing I would call the particular attention of obstetricians to this point, for it is probable that a careful search at the placental attachment of the umbilical cord would frequently reveal the presence of similar minute epithelial vesicles, the remains of stunted twins. We might thus find that the tendency toward twinning in man is even greater than is now supposed.

REFERENCES CITED

Assheton, R., 1898. An account of a blastodermic vesicle of the sheep of the seventh day, with twin germinal areas. Jour. Anat and Physiol., XXXII, 362.

Bryce, T. H. and J. H. Teacher, 1908. Contributions to the study of the early development and imbedding of the human ovum. Glasgow.

Lewis, W. H., 1910. Localization and regeneration in the neural plate of amphibian embryos. Anat. Rec, IV, 19.3.

Miller, J. W., 1913. Corpus luteum und Schwangerschaft. Das jiingste operativ erhaltene menschliche Ei. Berlin klin. Wochenschr., L. S65.

Newman, H. H., 1917. The biology of twins (mammals). University of Chicago Press.

Patterson, J. T., 1913. Polyembryonic development of Tatusla novemcincta. Jour. Morph., XXIV, 559.

Streeter, G. L., 1914. Experimental evidence concerning the determination of posture of the membranous labyrinth In amphibian embryos. Jour. Exper. Zool.. XVI.

Watt, J. C, 1915. Description of two young twin human embryos with 17-19 paired somites. Contributions to Embryology, Vol. 2, Carnegie Inst. Wash., Pub. No. 222.


CHANGES IN SKIN SENSITIVENESS TO TUBERCULIN DURING

EPIDEMIC INFLUENZA

By Aethue L. Bloomfield and John G. Mateee (From the Medical Clinic, of The Johns Hopkins Hospital and University)


The disappearance of the cutaaieous tuberculin reaction in measles was systematically studied in 1908 by von Pirquet' following an observation of Preisich.^ Fifty-nine children all failed to show skin sensitiveness during the exanthematic stage of the disease. A few observations made at the time of onset showed that the reaction disappeared for from one to four days before the eruption, to reappear gradually after from the fifth to the tenth day. Von Pirquet lays great stress on the specificity of the absence of the reaction in measles, pointing out that it does not disappear in scarlet fever, epidemic meningitis, typhoid fever or German measles. He associates the phenomenon with the tendency of tuberculosis to become more active after measles and explains it by assuming a disappear


ance of " ergins " — hypothetical substances which unit* with tuberculin in the tissues to produce the reaction. Griiner ' performed subcutaneous tests in children with measles and showed that with relatively large doses (1 mg.) a reaction could be elicited even during the eruptive stage. He calculated, however, that the skin sensitiveness was reduced about one thousand-fold. The observation of von Pirquet has been confirmed repeatedly in measles, but we have been unable to find reports of any similar constant abolition of tuberculin skin sensitiveness in other acute infectious diseases except during stages of agonal collapse.

During the recent epidemic of influenza we were struck by the remarkably low leucocyte counts encountered even in mild


AuGiST, 1919]


239


or ambulatory ca^s. This suggested that at least some of the reactive processes of the body were in abeyance. It seemed of interest, therefore, to study skin sensitiveness in this disease. The present report deals w-ith tlie results of cutaneous tuberculin tests in 19 consecutive cases of epidemic influenza studied in The Johns Hopkins Hospital during January luid February, 1919. The diagnosis was based on the symptoms, the presence of hyperemic phenomena of the skin tuid mucous membranes, the character and duration of the febrile reaction, and the leucopenia.* It should be emphasized that most of the cases were mild and that the disappearance of the skin reaction was in no way associated witli general collapse. Three of the patients developed bronchopneumonia, but all made imeventful recoveries. Xono of them showed clinical signs of active tuberculosis.

Old tuberculin furnished by the tuberculosis dispensary of the hospital wjus used. Two drops were placed on the forearm about 5 cm. apart. Linear scarification witli a dull scalpel was done through the drops of tuberculin after a control scratch had been made distal to them. The tuberculin wa.'* allowed to dry on the arm. The tests were all made l)y the same observers and read at one-, two- and three-day intervals, the character and e.xtent of the redness and induration being noted. Tests were done during the febrile stage and after the temperature had become normal.

RESULTS

The results of the tests are summarized in Table I. It is apparent that skin .sensitiveness to tuberculin was absent in every case but one, both mild and severe, during the fel)rile stage. During convalescence reactivity returned in 89.4 per cent of the cases, which corresponds to what one would e.xpcct in a group of normal individuals of the same age. The return to maximum reactivity was gradual in most cases, as sliown by successive tests. In two patients a positive skin test was not obtained during the period of observation, even after the temperature had l)een normal for from six to eight days.

It should be emphasized that, as in measles, more delicate tests, such as the subcutaneous, would probably show reactivity to be simply depressed and not entirely obliterated, and on this basis the cases may be divided into several groups. In ten of them th? first test made during the febrile stage failed to elicit any sign of reaction, w^hereas during convalescence the test was markedly positive. In six cases in which the t(>nijierature became normal on the day on which the test was do/ic, or on the following day, slight grmles of reddening and in<luration appeared about the test scratches. These were regarded as delayed and depressed reactions, inasmuch as all these


patients later responded with prompt, strongly positive reactions. It may be that in some of those cases the response was intensified by increased hyper.sensitiveness following the first test. In one instance of moderately severe typical influenza there was a positive test during the febrile stiige. The same degree of reaction was observed in this patient during convalescence.

TABLE I

Summary of Resilts of Tiberculix Skin-Tests i.n Epide.mic

ixfluexza

No. Per cent.

Total cases studied 19

Cases giving a positive reaction while fever

was present 1 5.2

Cases giving a positive reaction after the

febrile stage 17 89.4


Lengrtb of time (days) after temperature ha<l become normal before the skin test became positive 1 2 3 4 5 6 11


Number of cases

3

4 2 2 3 1 1


DISCUSSION Although the literature on alterations of the skin test during acute infectious diseases is meager, it has been generally believed that measles stands out as the only disease in which a constant depression occurs. It is of interest, therefore, to find somewhat similar results in e])idemic influenza. Beyond j)ointing out this fact, it seems diflScult to associate the phenomenon in the two diseases, despite certain rather striking analogies which exist between them.* It would seem wise, however, to restudy in detail the changes in .skin sensitiveness in other acute febrile di.seascs, injismuch !is similar conditions may perhaps be found to exist.

REFERENCES

1. Von Pirquet: Deutsche med. Wchnschr.. 1908, XXIV, 1297.

2. Preisich: Quoted by von Pirquet. loc. cit.

3. Gruner: Miinch. med. Wchnschr., 1909, LVI, 1G81.

4. Bloomfleld, A. L., and Harrop. O. A.. Jr.: Bull. Johns Hopkins Hosp., 1919, XXX. 1.


Note. — Since this article went to press a paper has become accessible (E. Schltfer: Monatschrift fur Kinderh., 1918, XV, 189) dealing with the same question. The writer di<l skin tests on 64 children with "influenza." In 61 the test was negative, in three It was weakly positive. Of 28 reexamined during convalescence, three developed positive tests.


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240


[No. 342


HAEMORRHAGE INTO A POSTSCARLATINAL CERVICAL ABSCESS. LIGATION OF THE COMMON CAROTID. RECOVERY

By T. M. RivEKS


On December 1, 1916, B. M., of North Carolina, female, five and a half years of age, vomited and had a slight fever. Two days later, a doctor was called, who found her severely prostrated. A small membrane was seen on the right tonsil and 15,000 units of diphtheria antitoxin were given intramuscularly. On December 5, the patient's temperature rose to 101° F., but was normal or subnormal from that time imtil her admission to the hospital. Her father developed a sore throat one week after the onset of her illness and a culture from his throat was reported positive for diphtheria bacilli by the bacteriologist of the North Carolina State Board of Health. A culture was not made from the child's throat before admission to the hospital.

About December 5, the cervical glands began to swell. The patient again began to vomit, became stuporous and did not pass urine for 56 hours. After this interval, a small amount of urine was passed which contained a great deal of albumin. Her condition remained about the same until the third week, when a diffuse, dull, red maculo-papular rash appeared, three days before admission. She was considered by her physician to have nephritis following diphtheria and was brought to Baltimore to be admitted to the hospital for that reason.

On admission to the Harriet Lane Home of The Johns Hopkins Hospital, December 23, her temperature was 99° F., pulse 110, respiration 22. The patient was drowsy and emaciated. The tongue was heavily coated. The breath was exceedingly foul. Part of the tonsil, soft palate and posterior pillar on the right side had sloughed, leaving a ragged hole lined with greenish-white pus. The glands on both sides of the neck were enlarged. There was a mass the size of a lemon, deeply situated below the angle of the jaw on the right side, that was obscurely fluctuating and was obviously an abscess. The liver was two fingerbreadths below the costal margin. Over the body and extremities there was a worm-eaten desquamation. The skin of the palms and the soles was very dry and later desquamated in a way typical of scarlet fever. There was also a diffuse maculo-papular eruption over the body and the extremities which was evidently urticarial in character.

White blood count, 31,000. Blood culture, no growth. Throat culture, negative for diphtheria bacilli, but showed long chains of streptococci. Urine: clear; acid; specific gravity, 1.020; albumin, 3 gm. per liter; sugar, absent; hyaline and granular easts; pus cells, red blood cells and epithelial cells.

Shortly after admission the cervical abscess was opened by means of a small puncture and at least two oimces of pus were obtained from which a hemolytic streptococcus was grown.


' From the Department of Pediatrics, The Johns Hopkins University and the Harriet Lane Home of The Johns Hopkins Hospital.


The patient seemed to be doing well tmtil lip. m., December 26, when she was found in a large pool of blood, exsanguinated, pulseless and gasping for breath. The bleeding had stopped spontaneously and the wound was not disturbed. A subcutaneous injection of 300 c. c. of physiological salt solution was given immediately and within two hours the patient received intravenously 225 c. c. of citrated blood from the mother.

There was another haemorrhage of about two ounces at 7 a. m. and at 11 a. m. on the following day. At 1 p. m. blood began to spurt from the wound. Dr. Dandy, the resident surgeon, enlarged the incision into the abscess and found an erosion of the lingual and the external carotid arteries and the internal jugular vein and that the haemorrhage was from these three sources. A ligature was placed around the common carotid and the bleeding from the internal jugular was controlled by packing. The child was greatly exsanguinated and she received a few moments after Ligation of the common carotid 150 c. c. of citrated blood which had been kept on ice since the transfusion the night before. After the transfusion she rallied immediately. Her pulse became very irregular, however, and remained so for two weeks. There was sugar in the urine for one week after the operation, but the blood sugar was always normal.

On December 28 her hfemoglobin was 40 per cent (Sahli). An area of erysipelas developed above the wound and spread over the right side of face. On the 29th she again received 200 c. c. of citrated blood. On the 30th her haemoglobin was 58 per cent (Sahli). Both ear drums were punctured, releasing pus.

On January 1, 1917, another large haemorrhage took place through the wound. Evidently the ligature on the common carotid had sloughed through. The bleeding, however, was successfully controlled by pressure and the patient again received 150 c. c. of citrated blood. On January 3 her ha?moglobin was 40 per cent (Sahli).

The patient developed generalized oedema, insensibility to pain, waxy flexibility, Chvostek's sign, a double Babinski, exaggerated reflexes, double ankle clonus and a distinct loss of memory for recent events. Gradually she improved. The wound healed slowly under treatment with Dakin's solution. On January 22, an internal strabismus of the right eye appeared, which cleared up in a week. The patient was discharged from the hospital February 2, 1917, well, with normal urinary findings. She has been heard from several times since and continues well.

Adenitis with abscess formation, especially about the neck, is one of the complications of scarlet fever. At times the blood vessels are eroded and severe hemorrhages take place. The bleeding may come from an opened abscess or it may occur from the ear or throusjh the mouth and nose. Veins and arteries are


August, 1919]


241


King.

J. de Bal.


8 .Gordon.

9 'othrey.

10 Blood.

11 Bittertbr. U 'sarret.

IS Mill.


14 Dtptnt.

15 lfondi»re.

I« Sedrwiek.

17 Brown.

18 UctciKe. 1» McDonmld. to Brown.

tl Hale.

8 NicboHi.

a Hymn.

t4 HOber.


tS LoTcgroTc.

it iWfrt. t; Budrr.

28 Hoamer, t» Ptpp«r.

80 Mahomeil. 31 M.y.

•o HinnemOller.


iDternal carotid (f)


Internal jugalar

«• 1-, Internal jugular. Internal jugular.

Internal jugular.


External carotid.


Internal jugular.


Internal jugular.


Internal jugular.

Branch interna] maxillary artery

Internal jugular.

Internal jugular.

Internal carotid? Internal jugular. Artery.

Internal jugular. Internal carotid. Artery?

Vein?


S External carotid. F.iternal jugular. Lateral linul.


Artery.

Branch of carotid.


i Internal carotid. Internal carotid ?


Bled from ear and mouth ; 10 d:iya later common carotid ligated, but bleeding continued at intervala (or 3i weeks. Recovery.

Blood spurted at times from ear for i neeks. reaultiog in death.

All died.


Died after bleeding five d; Abscess opened and ( blood obtained. Later dischareed from anotl Opening. Recovery.

Bled from abscess cavity 10 days after it was opened. Common carotid ligated, which controlled the hxmorrhage. Child died later.

Died.


One died after bleedinfc throueb abscess cavity and through mouth. The other bled to death through the mouth.

Recovered.

Died.

I

Bled to death in three days.

Bled to death eleven days afterl abscess cavity was opened.


Died after bleeding 10 days. jBled to death in 2 minutes.


Tumor mass on side of


S-Y»8. 1-No.

Yes.

Yes.


Bled about a pint from between thi' anterior and posterior pillars on left aide of throat. Recovered.

Bled through mouth. RC'

covcry after ligation of left

common carotid. Hemorrhage controlled bv

ligation of common carotid.

Died.


jBled from left ear. Left common carotid ligated. Recovery.

Bled to death through ear and

I mouth.


Yes. Yes.


involved about equally. Haemorrhage under such circumstances is very serious and few of the cases recover. Most of the authentic cases on record are tabulated liere.

BIBLIOGRAPHY

1. Syme: Edinburgh Med. & Surg. J., 1833, XXXIX, 319.

2. Porter: See Kennedy (3).

3. Kennedy: Some Account of the Epidemic of Scarlatina which Prevailed in Dublin, from 1834 to 1842, inclusive; with Observations. Dublin, Fannin & Co., 1843.

4. King: London & Edinburgh Mon. Jour. Med. Sc, 1843, III, 177.

5. de Bal: Jour. d. connaissances m^dico-chirurgicales, Paris, 1845, XIII. 158.

6. Bloxam: Med. Press, Dublin, 1843, IX. 181.

7. Hughes: Med. Press. Dublin, 1846, XV, 241.

8. Gordon: See Hughes (7). S. Oshrey: See Hughes (7).

10. Blood: See Hughes (7).

11. Battersby: See Hughes (7).

12. Barrett: Lancet, Lond., 1847, I, 287.

13. -Mill: Edinburgh Med. & Surg. Jour., 1841. LV, 125.

14. D^peret: L'Union m^dicale, Paris, 1850, IV, 414.

15. Mondidre: Revue medicale, 1842, I, 1S2. Original article not read, reference obtained from: Von Noirot, Histoire de la Scarlatine, Paris, 1847, 216 and 217.

16. Sedgwick: Med. Gaz. Lend., 1851, XLVIII, 581.

17. Brown: Med. Gaz. Lond.. 1851, XLVIII, 887.

18. Metcalfe: N. Y. Med. Times, 1852, I, 35.

19. McDonald: See Metcalfe, (18).

20. Brown: Association Med. Jour., Lond., 1854, II, 991.

21. Hale: Lond. Jour. Med., 1850, II, 720.

22. Nicholls: St. Georges Hosp. Rep., Lond., 1869, IV, 211.

23. Hymes: Lancet, Lond., 1870, II, 431.

24. Huber: Arch. f. klin. Med., Leipz., 1871, VIII, 422.

25. Lovegrove: Lancet, Lond., 1870, I, 729.

26. West: See Lovegrove (25).

27. Baader: Correspondenz-bl. f. Schweizer Aerzte. Basel, 1875, V. 614.

28. Rosmer: Bost. Med. & Surg. J., 1878, XCIX. 835.

29. Pepper: Trans. Clin. Soc. Lond., 1883, XVI, 21.

30. .Mahomed: Ibid. (Discussion.)

31. May: Ann. Surg., 1885, I, 559.

32. Hannemiiller: Gefassarrosionen im Verlaufe von Scharlach, Kiel, 1901.


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243


[No. 342


ANALYSIS OF CEREBROSPINAL FLUIDS OF CATS WITH MENINGEAL INFECTIONS

By Lloyd D. Felton, Contract Surgeon, U. S. Army

(From The Army H euro-Surgical Laboratory, The Johns Hopkins Medical School, Baltimore, Md.)



BOOKS RECEIVED


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The Medical Association oj the Isthmian Canal Zone. Proceedings, January, 1917, to June, 1917. Vol. X, part I. Published by the Health Department, the Panama Canal. 1918. 8°. 149 pages. Panama Canal Press, Mount Hope, C. Z.

Surgical Treatment. A Practical Treatise on the Therapy of Surgical Disease for the Use of Practitioners and Students of Surgery. By James Peter Warbasse. M. D. In three volumes with 2400 illustrations. Volume I. 947 pages: volume II. 829 pages. 1918. 8°. W. B. Saunders Company, Philadelphia and London.

Paper Work of the Medical Department of the United States Army. A Guide for Administrative Work. By Ralph W. Webster, M. D., Ph. D. Approved for publication by direction of the Surgeon General of the U. S. Army. 1918. 8°. 541 pages. P. Blakiston's Son & Co., Philadelphia.


Hygiene in Mexico. A Study of Sanitary and Educational Problems. By Alberto J. Pani, C. E. Translated by Ernest L. de Gogorza. 1917. 12°. 206 pages. G. P. Putnam's Sons. New York and London.

Saint Thomas's Hospital Reports. New Series. Vol. XLIV. 1915. Edited by Dr. J. J. Perkins and Sir Charles A. Ballance, K. C. M. G., C. B., M. V. O. 1918. S". 141 pages. J. & A. Churchill, London.

The Humane Society of the Cotnmonwcalth of Massachu^sctts. An Historical Review, 1785-1916. By M. A. DeWolfe Howe. With illustrations. 1918. 8°. 398 pages. Printed for the Humane Society at The Riverside Press. Cambridge, Boston.

Library of Conprcss. Report of the Librarian of Congress and

Report of the Superintendent of the Library Building and

Grounds. For the Fiscal Year Ending June 30, 191S. S". 191 pages. Government Printing Office, Washington.


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BULLETIN


OF




Contents

InsuBceptiliility of Man to Inoculation with Hlood from Measles Paticnt.s. By AxDRKw Watson Sem-ards 2.1


The Ri'ile of the X-Ray in the Diagnosis of Long-Staniiinj^ Kenal Tuhert-ulo.sis. (Illustrate<l.) By .1. A. C. COL.ST0N and Charles A. Waters . . . 208

In Mcmoriam — Admont Halscy Clark. (Illustrated.)

Bv William G. MacCalli'm 272


Heminiscences of Two Epochs— Anxsthesia and Asepsis. (Illustrated.) By Stephen- Smith 273

Notes on the Group of Symptoms Designated as KfTort Syndrome.

By E. W. Bridgman 279

Notes on New Books. 284

Books Received 285


INSUSCEPTIBILITY OF MAN TO INOCULATION WITH BLOOD FROM

MEASLES PATIENTS

Jiv AxDKKW \\at.sox .Sei.i.aki>.<. -Major, ^1. ('., U. .S. A. (From Bnsr Hospitals. Camp Devens. Mass.. and Camp Mcadr, Md.)


INTRODUCTION III congivsti'd (•omimiiiitit'.-; tlie sanitarian experiences greater • lillieulty in the c-ontrol of disease.-^ of tlie res])iratory tract than in the ease of those infections in wiiich tlie portal of entry is liy way of the alimentary canal. From the stantlpoiiit of e|iideniiologj-, measles should certainly he classified with the respiratory di.sea.ses; it takes a prominent place ainon<; the most liiphly communicalilc infections, heintr excelled, perhaps, only by pneumonic plague. In the mobilization of recruits even the uncomplicated ca.ses of measles may produce a high iion-ctFective rate; in addition to this disadvantage the .<erious l>ulmonnry com])lications of the disease render desirable the development of a protective immunization against the jiriniary infection. Investigations for this purpose would require the inoculation of human subjects on a basis which is necessarily more or less experimental in character. Indeed, of the serious infections of man, the virus of measlejj like that of scarlet fever and yellow fever* can I)e definitely identifieil only by the inoculation of suseeptilde human individuals. Ihiring the recent military emergency, a need and an opportunity arose for the investigation of measles such as would not occur in civil life. Accordingly, Colonel Frederick F. Hus.>iell recommi'iided to (ieneral William C. (torgas and to General Meritte W. Ireland the study in human volunteers of the ques

  • In a recent communication Xogui hi reports the discovery of

the etiologlc agent of yellow fever.'


tion of prophylactic inoculation against niea.<les. In time of need the individual soldier was found ready and willing to offer his services and to accept such risk a.s was inherent in these inoculations. A precedent for this type of work has been firmly established; the conditions in army life seem especially favorable for the ilcvelojinu'iit of preventive medicine as evidenced by the ])rogress in the control of yellow fever, of typhoid anil of trciiih fever.

LITERATURE

Iluiiian liiaculdliun.s. — .\ccurate records of the cxperimcnlal production of measles in man are meager in the extreme. The easy recognition of the disease by it-s clinical syini)tonis would .seem to render of interest the investigations conducted before the bacteriologic era. P'or example, Alayr' in 18.12 reporteil the occurrence of measles afti'r an incubation period of two weeks in two of three subjects inoculated on the nasal mucous membrane with nasal .secretions of a jiatient. I n another ex])erinient, Mayr reports that mild but typical attacks were produced in each of six subject.s by introducing into the skin the 8era|)ing8 from a morbillous lesion. The incubation period is not stated ; no mention is made of any precautions to avoid spontaneous infection,

Kecently Ilerrman' (1!>1">) inoculated 10 infants under five months of age on the na.<al mucous membrane with nasal secretions from cases of measles. This was done, not with the


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idea of producing the disease but with the expectation of establishing an immunity, taking advantage of the relatively high insusceptibility of infants to measles in the first few months of life. None of these 40 infants developed any definite symptoms. About 1 to 2 years later, 4 of these children came in intimate contact with measles cases and two were reinoculated without developing the disease.

The first experimental inoculations of blood were performed by Hektoen* in 1905; this observer conducted two independent tests and reported an attack of measles in each instance. Blood for inoculation was taken during the eruptive stage and was incubated before injection, for one day at 37° C. in ascitic broth (1 part ascitic fluid to 2 parts meat infusion broth). In one patient the specimen of blood was withdrawn 6 hours and in the other 30 hours after the eruption had appeared. Moderate quantities (3 c. e. and 2.5 c. c.) were inoculated into flasks of ascitic broth (50 and 75 c. c. .amounts). After incubation for 24 hours, this mixture was apparently sterile; there was no evidence of secondary contamination or of any multiplication of the virus of measles as indicated by the gross appearance, by microscopical examination and by the subsequent results of sub-inoculation on a variety of media. Accordingly subcutaneous injections were made (4 and 5 c. e.) into two volunteers and apparently a mild but typical attack of measles developed in each case after an incubation period of about two weeks. This volume of broth culture represents a calculated quantity of blood serum of approximately 0.1 c. c. All viruses known to multiply in culture media produce either macroscopic or microscopic evidence of their growth ; both manifestations appear in the vast majority of cases. It would seem from these results, therefore, that a very small amount of measles blood is infective and that it retains its virulence for at least a day in vitro at incubator temperature. Such a conclusion is of far-reaching importance. In the investigation of a disease of unknown etiology a great advantage is achieved by the isolation of its virus in a relatively concentrated form uneontaminated by other micro-organisms; one is then in possession of suitable material for the investigation of fundamental features sucli as immunization of the natural host, transmission to other species and studies in morphology and cultivation. Practically the entire superstructure of modern experimental work in measles rests on these two experimental cases. One may call attention more especially to the reported transmission of the disease to monkeys by inoculations of blood and the isolation of a micrococcus from the blood stream by TunniclifiE.' Inoculation of Monkeys. — Of the recent investigators, Anderson and Goldberger ° were the first to report the successful inoculation of monkeys with measles. Two of their conclusions are of especial interest in connection with the data reported in this paper, namely: (1) that the blood of early cases is infective and (2) that the virus of the disease as it occurs in the blood is capable of passing a Berkefeld filter.


DESCRIPTION OP EXPERIMENTAL WORK In arranging the preliminary protocol of the following work, the reported transmission of measles by the inoculation of blood was accepted as a basis for the first series of injections, arrangements being made to conduct a control for confirming the findings concerning the infectivity of the blood. In order to provide a secure foundation for the more elaborate and timeconsuming experiments it was expected in the course of these investigations to obtain information concerning the constancv with which the blood of individual cases is infective, the minimal quantity which suffices to produce the disease and also tlie extreme limits during which the virus may be demonstrated in the blood. Inasmuch as a very favorable control for the first series of inoculations failed, the question of the infectivity of the blood in measles was accepted as the primary problem; the ultimate object of these investigations consists in determining whether a method of active immunization can be developed, without producing a serious reaction. Injections of blood from jjatients in various stages of the disease have been made into supposedly susceptible individuals but no symptoms of measles appeared in any instance. Two individuals who had been injected with blood were siibsequently inoculated on the mucous membrane of the upper respiratory tract with nasal secretions of an early case of measles but no symptoms developed. There is some reason to believe that these individuals were protected by the preliminary injection of blood.

Arrangements and Preparations for Inoculations. — Those investigations were conducted at Camp Devens, Mass., and at Camp ileade, Md. Camp Devens covers an area of approximately 16^ square miles with a normal capacity for 35,000 to 45,000 troops. The Base Hospital is situated at the extreme end of the cantonment opposite the principal entrance to the reservation. The wards of the hospital itself together with the essential accessory buildings such as the quarters and barracks for officers, nurses, and enlisted personnel, as well as the drill and recreation field, occupy an area of approximately 2 J square miles; this section is separated from the nearest barracks for troops of the line by a distance of about }, mile. The normal capacity of the hospital is 2000 patients which in a time of emergency has been trebled. At the time of these investigations approximately 1000 troops of the enlisted personnel were assigned to the base hospital. Volunteers were obtained largely from this group of enlisted men since the majority of the medical officers had already been exposed to measles; a considerable proportion of these men had not come in contact with patients, being assigned to duty in the barracks and quarters, in the offices and on fatigue work out of doors. Conditions at Camp Meade were fundamentally identical with those at Camp Devens. The work was transferred to Camp Meade, partly for the purpose of obtaining volunteers from the more isolated rural communities, the majority of the volunteers at Camp Devens having come from the smaller towns.

Precautions Concerning Volunteers. — In the accciitiiiui^ o!' volunteers for inoculation with measles there are two cardinal


Septemukk, 1!)I!»|


259


factors which outweigh all other lousiderations, namely : (1) the •leiieral iiealtli of the iiulividual with special consideration of the respiratory tract and ('i ) the assurance tiiat the adult in question has never had a recojrniznhle attack of measles.

Under ordinary circumstances the virus of measles per se d<K?s not produce serious results in normal individuals; its disastrous effects arise from the secondary infections. The most important of these are the pneumonias es|)ccially those from the pneumococcus, the tuiiercle bacillus and the luemolytic streptococcus as in the winter of 1!)1T-1S. In addition to thoroufjh physical examination, si)ecial attention was ^'iven to the points indicated in the followinof outline in order to secure the fullest |>o}:sibIe protection for llie volunteer> :

I. Bacteriolofrical cultures of throats (several examinations at intervals of three to four days) for.

1. Tla-molytic streptococcus.

•.i. I'neumococcus (any type).

3. Jleningococcus.

1. Diphtheria liacilli.

5. Pfeiffer Ijacillus. II. Precautions ajEraiiist tuberculosis,

1. History.

2. Physical examination.

3. .\-ray findinsis.

III. Anatomii-al examination of, 1. Tonsils. 'i. Sinuses. 3. Middle ear. I\'. Special isolation for acceptable individuals in orcler to protect them from intercurrent infections and from s])ontaneous infection with measles. \'. Special nursinjf by per.sons of Ion;; experience with measles for any individuals contractiiiij the disease. If a prospective volunteer showed any of the preceding; or^'anisms in the cultural examination of the throat and nasopharv'nx he was at once eliminated from consideration reftardless of whether the orpanism in question subsequently disaj)peared. A comparatively larpe proportion of individuals proved to be unsuitable either on account of the presence of the hfemolj-tic streptococcus or the pneumococcus. Only a few were rejected on account of a suspected latent tuberculosis. The anatomical examination of the tonsils seemed distinctly inifwrtant. Imlividuals who bad had an infection of the tonsils at all recently were not considered becau.«e, especially under these circumstances, cultural examination of the surface of the gland gives little information concerning the flora contained within the tonsillar crypt**. In view of the dilliculty of rigidly excluding the presence of the ha-molytic streptncoccus by bacteriologic examinations it seemed much safer to conduct these inoculations at a time when infections with this micro-organism were not prevalent in camp. As a practical test of the significance of cultural examinations, licvy and Alexander' have noted a very low incidence of complications due to the ha?molytic streptococcus in measles cases wha«e throat cultures were negative for this organism.


Proper isolation i)osscs.ses a two-fold importance. In the first place it was very neces.sary (hat volunteers found free of l)athogenic micro-organisms should be jirotected from accidental contamination, especially by carriers ; secondly, it is of course essential to provide against the possibility of spontaneous infectidii with measles. With these objects in view, the acceptal)le volunteers were segregated in a ward removed as far as circumstances would permit from the wauls reserved for cases of measles, a distance of aiiout i mile. Satisfactory isolation over the rather long period of these experiments was rendered comparatively simple by the discipline developed in military life and by the faithful cooperation of the volunteers themselves. The attendants on the ward for the volunteers were restricted from seeing any i)atients, but they were not required to isolate themselves. By observing the precautions just outlined, it was felt that the possible dangers inherent in these inoculations would be reduced to a minimum.

Probably the greatest <lilficulty in these investigations consists in the selection of susceptible adults; in the large cities only a very small proportion of individuals, perhaps 5 per cent, come to adult life without having contracted measles. Age per se confers no innnunity. Moreover, the disease runs a clinical course which is remarkal)ly true to form. Unrecognized attacks such as abortive cases without a rasJi constitute, if they occur at all, virtually a negligible factor. The chief difficulty arises from the fact that little or no dependence can be placed on the .statement of even the educated adult that he has never had measles. Information was obtained according to the following plan : A census of the detachment was taken and tho.so individuals were at once eliminated who reported having had either measles," German measles," or scarlet fever.f These three diseases were included on account of possible errors in diagnosis. A limited number were sure that tliey had had none of these infections; tiie parents of these men were consulted. At Camp Devens this was done, whenever possible, by the individual himself in person ; at Camp ^leade a letter was sent to the family of the soldier. Inquiry was made in the first place concerning the individual him.'^elf, and secondly, whether he had been ex])osed to measles through its occurrence in other members of the family. After this information was obtained, an ojjportunity to volunteer was given to the men in wlio.«e eases the replies from the parents were satisfac-tory, provided that the preliminary bacteriologic examination of the individual was negative. The first cultures were made while the history was being ohtaineil; the final examinations were comI)leted only after the individual hail volunteered and had been isolated.

The general ])lan of the inoculations was designed with the jturpose of eliciting the desired information concerning the virus of measles with the production, however, of only an absolutely minimal number of cases of the di.«ease. By employing large series of volunteers, the experimental data could have been obtained ra])idly on an extensive scale but only at the cost of


(A detailed report of tills census will appear in Thn Afililary Surgeon.


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[K'o. 343


increased risk to the individuals. With the passing of the military emergency, less attention was given to the time consumed in tliese experiments, the primary object being to avoid the possible production of measles in man without obtaining results proportionate to the serious responsibility of human experimentation.

PRELIMINARY INOCULATIONS OF HUMAN SUBJECTS

Selection of Measles Cases. — There are two essential criteria which must be met in the selection of measles cases for subinoculation of normal individuals: (1) the patient must be secured in relatively early stages of the disease and (2) he must be free from all other infections, notably syphilis. At the beginning of this work, the collection of blood specimens was purposely delayed until after the rash had appeared ; although the blood might, very possibly, be more infective in the pre-eruptive stage, it seemed advisable to duplicate conditions which had previously given positive results in human experimentation.

For the exclusion of syphilis, dependence was placed on a thorough history in all its aspects, clinical examination and the Wassermann test.

Preliminary Inoculations. — The first inoculations were designed to give preliminary information on the following points :

(1) Whether the serum alone, free from red cells, contains

the virus of measles.

(2) Whether the organism of measles will pass through a

Berkefeld filter.

(3) Whether a series of injections of patient's and con valescent's serum would immunize a human suliject without producing an attack of the disease.

(4) Whether a previous attack of measles confers complete

immunity or whether a modified attack might result in a partially immune subject with possible attenuation of the virus. For these inoculations, blood was taken from a moderately severe case of measles 12 hours after the first appearance of the rash. At this time the Koplik spots had already disappeared, the eruption was profuse over the face, back and chest, less intense over the abdomen and only a few scattered spots had appeared on the thighs.

Immediately after collection, one portion of the blood was defibrinated and another was centrifuged for the collection of serum. Part of this serum was mixed with an equal volume of fresh serum obtained from a typical case of measles 10 days after the temperature had returned to normal. Another portion of the original serum was diluted with nine parts of physiological saline ; one portion of the diluted serum was kept at room temperature for a control and the remainder was heavily inoculated with B. prodigiosiw and passed through a Berkefeld filter (so-called N).t

This was an old filter, much worn, which on several previous tests had successfully held back B. prodigiosus. When immersed


t The gradations of Berkefeld filters into coarse, medium and fine (V-N-W) was found frequently to bear little relation to their actual porosity.


in water, an additional pressure of 50 mm. of mercury was suflBcient to force a fine stream of air through this filter. The time employed in filtering 25 c. c. of the diluted serum was 30 minutes and the pressure was 40 to 50 mm. of mercury; the room temperature was 22° C. Twelve cubic centimeters of the filtrate were inoculated in varying amounts on agar plates and into flasks of broth; the culture media subsequently showed no evidence of growth.

The following subcutaneous injections were made into susceptible individuals: For convenience the susceptible men will be designated by a Roman numeral and the immunes by a letter. One volunteer (I) received 5 c. c. of diluted serum (1-10) unfiltered and kept at room temperature one hour; another (II) received 10 c. c. of filtered serum (1-10 dilution) one hour after collection of the blood; a third (III) received 0.5 c. c. of a mixture of equal parts of patient's and convalescent's sera (undiluted) after incubation for one hour at 37° C.

An immune (A) wlio had measles 28 years previously received 7 c. c. of defibrinated patient's blood 1% hours after collection.

Xone of these four individuals developed any symptoms of measles. Xeither did any local changes appear at the site of injection except in the individual who received 7 c. c. of defibrinated blood ; in this subject a day alter the injection, moderate tenderness on piressure developed accompanied by slight erythema over the injected area. These symptoms persisted for tliree days.

The chief interest in these negative results centers in the control individual who was expected to contract measles. The delay of one hour before injecting this serum and also the absence of red cells might be regarded as factors contributing toward the negative result. It would appear from previous work that the blood retains its infectivity in vitro for at least a day. As regards the red cells, as far as we know, all diseases caused by parasites of the red corpuscles are transmitted by insects whereas droplet infection constitutes the accepted mode of transmission in measles.

The failure of filtered measles serum to infect an apparently susceptible human subject must be borne in mind in connection with the positive result reported by Goldberger and Anderson ° upon the inoculation of monkeys with filtered serum. These investigators conducted four experiments; in the first two, the results were negative; in the third, one of four monkeys presented slight symptoms only; in the fourth experiment one of two monkeys developed an eruption 21 days after inoculation. These authors conclude that the virus of measles is capable of passing through a Berkefeld candle. Xo details are given concerning the size of the filter employed or the manner in which the filtration was controlled and conducted.

For the mixture of measles serum and convalescent patient's serum, it was originally intended to conduct a long series of injections gradually eliminating the convalescent patient's serum. It was also intended to hyper-immunize by several intravenous injections of measles serum the immune (A) who failed to develop symptoms after receiving a large quantity of blood subcutaneously. After an interval of one month, a second injection was given consisting of 1 c. c. of serum intravenously. This was collected from a patient 15 hours after the appearance of the rash. X'o symptoms of any kind resulted from this intravenous inoculation. This work was then sus


September, 191i)]


JOHNS HOPKINS HOSPIT^VL BULLETIN


261


pended pending confirmation of the existence of the virus of measles in the circulating blood.

INOCULATION OF SUSCEPTIBLE INDIVIDUALS WITH MEASLES BLOOD

Inociiliition of Dt'fibriniiltil Bhtod and of lilvoil I ncttbalcd in Ascitic Broth. — The remaiiuler of the work with susceptible individuals has been restricted to an attcnii)t to transmit measles by the injection of patient's blood. Dclil)rinated blood was injected subcutaneousl}- into two men. Cultures of patient's blood in ascitic broth were inoculated in two other men. This duplication of a method for which successful results have been reported seemed essential in view of the negative result following the inoculation of serum without preliminary incubation. None of these four subjects developed measles ; neither did any symptoms appear that could be definitely attributed to the injections. Tlie details are as follows :

Deflbrinated blood from an early case of measles, 12 hours after the appearance of the rash, was injected subcutaneously in 2 c. c. quantities in the interscapular area, after a delay of 15 minutes, into two susceptible volunteers. The patient's blood (4 c. c.) without defibrination was added to ascitic broth (50 c. c. ) consisting of two parts of meat infusion and 1 part of ascitic tluid. The broth was prepared without the addition of sugar and its reaction to phenolphthalein was equivalent to 1 per cent of normal acid. The ascitic fluid was yellow in color, sp. gr. 1.018 and was free from bile pigments. Repeated aerobic and anaerobic cultures showed no evidence of growth; the ascitic fluid was therefore used without preliminary sterilization. In the culture medium prepared by Hektoen the ascitic fluid was heated at 55° C. for 54 minutes. Differences of an altogether minor nature probably occurred also in the reaction and composition of the broth and ascitic fluid which was employed.

This medium inoculated with the patient's blood showed no evidence of growth after 24 hours' incubation; accordingly, two susceptible men (VI and VII) were inoculated subcutaneously in the interscapular area with 10 c. c. of this mixture of blood in ascitic broth, the mixture being shaken to include corpuscles as well as serum. This quantity represents about 0.2 c. c. of patient's serum.

During the incubation period these men were observed with special reference to:

1. Development of symptoms in the upper respiratory tract.

2. Occurrence of Koplik spots. ."?. Body teniporature.

4. Total and diffcreniial leucocyte count.

A record of the temperature by mouth and of the pulse and respiration was taken as a routine at four-hourly intervals during the day. The entire surface of the body was examined for culanoous rashes, since, after inoculation, the initial lesions might appear first not necessarily on the face or chest, but on any part of the body. All of these individuals remained essentially free from symptoms.

fnorulalion witli Skin Lrsion.i. — After an interval of :Vi days one of the men injected with defibrinated blood (IV) and ani)tl)er (Vll) injected with blwid incul)ated in broth were re-inoculated i»y smearing the mucous membranes of the eyes, nose and throat with freshly cxciscil morbiJlous skin lesions. These inwulations pos.^essed a two-fnld interest in that a positive result would demonstrate that the virus of the di.-^easc is present in the skin lesions and that these individuals who were refractory to an injection of iilood were nevertheless sus


ceptible to the disease. No definite symptoms developed. In view of these negative results, the question arose of testing experimentally the .-iusceptibility of these men by inoculating the upper respiratory tract with secretions from the nmcous membranes of active cases. The injections of blood, however, had been made from only one case of measles, a single specimen of blood having been taken. Therefore, if the use of nasal secretions should produce measles in one of these subjects, it would only establish that, in a single case of measles, one specimen of blood at a given stage of the disease did not prove infective for a susceptible host. It seemed desirable to defer tests of susceptibility until individuals could be inoculated with blood from several stages of the disease and preferably from more than one patient.

Inoculation of Blood from Pre-Erupiive and Eruplire Stages. — Accordingly for the next step, two susceptibles were inoculated on two successive days with blood taken before and after the appearance of the eruption. Control inoculations were made simultaneously into two immunes. Blood for these injections was secured from two patients; specimens were obtained from one case 30 hours and again six hours before the ap])earance of the rash and from the other six hours before and 18 hours after the rash appeared. None of tlicso four subjects developed any symptoms of measles.

Of the two susceptibles selected for these injections, one (IX) gave unusually good evidence that he had never contracted measles. This individual had grown up on a farm in West Virginia and had alwavs lived at home. He was 'ifi years of age being the sixth of 8 children of whom the youngest was 20 years and the eldest 38 years of age. Information was received from the mother and the eldest sister to the elTect that measles had never occurred in the household. Then in adult life several older and younger brothers and sisters left home and contracted measles. Of the five older members of the family, the eldest sister contracted measles in 1910; two brothers, tlio second and third members of the family, developed measles in March, 1917 ; the fourth member, a brother, has not had measles; a sister, who was the liftli child, developed measles in 1908. Of the two younger children one, a sister, 20 years of age, has never had measles; the other, a brother, 24 years of age, did not develop measles until he enlisted in the army, having contracted tlie disease at Camp Shelby, ifiss., in December, 1917.

On enlisting this volunteer (I.\) was assigned to tlu! medical detachment, working exclusively in the officers' quarters. lie entered the hospital only on a single occasion, to visit a friend ill with tonsillitis.

In view of the prevalence of measles in the canttniments it might seem that no su.sccptible individual could escape infection for any length of time. However, there has been a slight but constant incidence of measles at the ports of debarkation even among the troops returning from overseas, notwithstanding the fact that measles has been widely distriliutcd throughout the training camps of this country.

The two immunes were injected in order to test the protection alTorded by an attack of measles and also to control


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[Xo. 343


any minor symptoms that might appear in the susceptibles, such as slight changes in the body temperature and in the leucocyte picture. One of these immunes (A) had already been inoculated with blood on two occasions and with secretions from the mucous membranes of patients; the results were negative. The other immune (B) probably had had measles more than 30 years ago and had not previously received any injections in the course of these experiments.

For these inoculations of blood, very favorable cases of measles were obtained during a small epidemic which developed in a country district outside of the camp. Two adult patients were selected. Blood from each of these cases was mixed with 2 per cent sodium citrate in physiological saline; the two specimens of citrated blood were pooled and the mixture was injected into each subject; 24 hours later a second specimen of blood was collected in the same way from each patient and the injections were repeated. Each subject received injections of blood from two patients at two periods of the disease, i. e.. the equivalent of four Injections in all. On the first day 10 c. c. of blood were taken from each patient, and mixed with an equal volume of citrate solution. On examination, the first patient showed numerous Koplik spots at this time and six hours later the rash appeared. The temperature was 102.8°. The second patient showed only a few isolated Koplik spots and the rash appeared 30 hours later. The temperature was 99°. These two specimens of citrated blood were mixed: each of the two susceptibles (VIII and IX) and the two immunes (A and B) were then injected with 6 c. c. of the resulting mixture, the injection being given in part subcutaneously and in part intramuscularly in the gluteal region. The maximum period of time elapsing between the withdrawal and the injection of the blood was 45 minutes tor the first and 15 minutes for the second patient. A duplicate of these injections was made on the next day, 10 c. c. of blood being taken from each case and mixed with 7 c. c. of 2 per cent citrate solution. At this time the Koplik spots had disappeared in the more advanced case; the rash, which had appeared 18 hours previousl.v, was almost confluent over the face, well developed over the chest and very sparse over the abdomen. In the second patient, the Koplik spots were abundant at this time and the rash appeared six hours later. The temperature was 102.2°. After these specimens of citrated blood had been mixed, the same men (VIII, IX, A and B) were injected with 6 c. c. quantities in the same manner in the gluteal region on the opposite side; the time elapsing between the withdrawal and the injection of the blood for the first case, i. e.. the one in which tlie rash had developed, was 40 minutes and for the second case. 10 minutes. These injections were made subcutaneously and intramuscularly in order to duplicate in the first place the manner of inoculation for which successful results had already been reported. It seemed entirely possible that a virus might find better protection for itself in the subcutaneous tissues than when exposed to the fluids and cells of the blood stream. An intravenous injection in addition to those into the tissues was not made in order to determine whether a rash, if one developed, would appear first at the site of inoculation or on the face as in the spontaneous disease. To facilitate these observations the site of inoculation was changed from the interscapular to the gluteal region.

Some slight local reactions followed these injections. .Vt the site of inoculation one of the two susceptibles (VIII) developed well-marked induration appearing eight days after the first injection, persisting very definitely for four days and gradually disappearing during the next 48 hours. In this individual the induration was bi-lateral; in the other (IX) slight induration without any well-defined margin developed at


the site of the second injection. This also appeared 8 days after the first injection but persisted for only 48 hours. In one of these men (VIII) a very transient erythema appeared for a few hours over the area of induration, on one side only, on the 10th and again on the 11th day after injection. Xeither of the two immunes developed any local induration. One of these immunes (A) on being inoculated in a similar manner 5| months previously developed a local induration entirely analogous to these two susceptibles. The local reaction, therefore, to the finst injection of measles blood varied slightly in the two immunes.

SUSCEPTIBILITY TESTS

When it became apparent that no symptoms of measles would develop from these injections of blood, arrangements were made to test the susceptibility of these men by inoculating the mucous membranes of the eyes, nose and throat with the secretions from tlie mucous membranes of an early case of measles.

A favorable patient was found for these inoculations. A child, five years of age, the daughter of a physician was exposed to measles by the occurrence of an attack in an older sister. During the incubation period in this child, examinations were made of the nose and throat for pathogenic microorganisms, especially the pneumococcus and the hjemolytic streptococcus. None were found and as far as secondary invaders were concerned, the secretions were regarded as satisfactory. Twelve days after exposure the patient developed a moderate conjunctivitis and coryza accompanied by a temperature of 100°. During the next two days, the temperature was practically normal but on the following morning, 15 days after exposure, it rose to 102.5° -with a marked increase in the conjunctival and respiratory symptoms. A few Koplik spots were present. On the following morning these symptoms persisted and profuse eruption appeared over the face spreading gradually downward over the body in the course of the next 48 hours.

Inoculations with secretions from the mucous membranes were carried out on the two susceptibles (VIII and IX), on one of the immunes (A) and on another immune (C) who had not previously received any injections. The latter, a man, 23 years of age, had had measles nine years before. Twenty days after the last injection of blood, these four individuals (VIII, IX, A and C) were inoculated on the mucous membranes of the eyes and nose with the lachrymal secretions and also on the nose and throat with the nasal secretions of the patient. This inoculation was performed on the day of the preeruptive rise in temperature in the child, i. e., 12 days after exposure and four days before the eruption. A similar inoculation was made on the day before the eruption, i. e., on the 15th day after exposure. On this occasion, in addition to duplicating the previous inoculations, the buccal secretions were thoroughly rubbed over the mucous membranes of the mouth and throat of the four subjects. On both days all of the.se inoculations were made with a sterile cotton swab slightly moistened with physiological saline. This was rubbed rather firmly over the mucous menihrane of the patient and then immediately over the mucous mcmlirane of the subject, a fresh swab being used for each inoculation. On both occasions the


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four subjects were in the same room with the patient ; on tlie (lav of the first inoeuhitions, the patient not being confinecl to the bed was allowed to play with these men three-quarters of an hour.

Intrarenoits Injeclion of liloutl. — In addition to these inoculations with secretions of the mucous membranes, one more susceptible (X) was inoculated with measles blood. A s]iccinien was taken from this same child within from li tn 10 hours after the appearance of the rash ; 0..5 c. c. was injcited subcutaneouslv and l.-"i c. c. intravenously immediately after withdrawal before the blood had time to clot.

Neither the intravenous injection of blood nor the inoculations of the secretion ]iroduced. in these five subjects, any respiratory symptoms or any rash. Only insifrnificant fluctuations occurred in the temperature and in the total and ditfcrential leucocyte count.

For the susceptibility tests in tliese men it might naturally be e.\jx'cted that control inoculationswould have been conducted with a susceptible individual who had not had any previous inoculations of blood. The production of measles in a control case would furnish some additional evidence but certainly would not in any sense afford proof that these men were susceptible and had been immunized by the injections of measles blood.

In rlrawing conclusions concerning these inoculations of blo<jd and mucous secretions in these susceptible men, there are two unknown factors to be determined, namely :

(1) Whether the individuals in question (VIII and IX) at the conclusion of the inoculations were immune and if so

(*) Whether the immunity was conferred by the injection of blood or acquired possibly through a previous attack of measles.

The results of the .susceptibility tests leave little doubt but that these men were immune; they were exposed to natural infection by an early case of measles and they were al.so thoroughly inoculated artificially. The high degree of communicability characteristic of the disease leaves little room to suppo.se that these men might be infected by exposure now to a second ca.se. The evidence of susceptibility of one of these volunteers ( I .\ ) is icrtainly much more concrete than the general argument.s that can be lirought in favor of a ])revious attack of measles. It woulil seem di>tinctly j)ossible that the injection of idood had jiroduced an artive immunity.

.1 priori one would not ex])ect that sulistantial immunity could be obtainol without the production of marked local or general symptoms. However, in the case of varicella, Iless and I'nger' re])ort active immunizjition by the intravenous injection of the +++++ CONTENTSs of vesicles without the production of subjective symptoms. It is noteworthy, however, that control individuals inoculated on the muious membranes faile<l to develop varicella. Kecent work by IJichartlson and Connor,' though affording no final proof, suggests the possibility of obtaining active imnninity against measles without the production of definite symptoms.


Lastly it should be emphasized that conclusive demonstration of the non-infectivity of measles blood ujion injection into a susceptible individual would still fail to prove the absence of the virus of the disease in the circulating blood. It is very doui)tful, for example, whether a susceptible human being would be infected by the injection of a moderate amount of blood of a typhoid patient taken during the stage of bacteriannia. It is a theoretical possibility that the blood of a measles patient might reproduce the disease when inoculated on the mucous membranes though not upon injection into the body tissues.

For the sake of convenience, the inoculations rcjiortcd in the preceding jiagcs have been collected in the following taldc:

TABLE OF INOCULATIONS


SusceptiblF I. Susceptible II.


1 month later. 21 months after

2d injection.

2 months after 3tl injection.

1 day after 4th injection.

3 oeelis after 4th injection.

31 weeks after 4th injection.


Susceptible V. Susceptible VI.

Susceptible VII.

3 weeks later. Susceptible VIII.

1 day later.

3 weeks later.

3| weeks later.

Susccptibit IX.

Susceptible X. Immune 11.


Blood serum, eruptive sta^e.


Dellbrinated blood, eruptive stage. Blood serum, eruptive stage. Mucous secretions, eruptive stage.

Citrated blood, pre-eruptive stage.

Citrated blood, pre-eruptive and eruptive sta}<e.

Mucous secretions, pre-eruptive

stage. Mucous secretions, pre-eruptive

stage.


Deflbrinated blood, eruptive stage.


Blood, eruptive stage, incubated

in broth. Rubeolous skin lesion.

Citratcil blood of two patients,


^ta^•.•


Citrated blood of two patients, preemptive and eruptive stages.

Mucous secretions, pre-eruptive stage.

Mucous secretions, pre-eruptive stage.

Duplicate of 4 inoculations of Susceptible VIII.

Whole blood, eruptive stage.

DupliealK of the flrst and second injections of VIII and IX.

Duplicate of the tbir<l ami fourth injections of VIII and 1\.


'Calculated amouiK.


0.6 c.c. 0.6 c.c.


Subcutaneous. Subcutaneous.

Subcutaneous.


•8 c.c. •8 c.c.


Subcutaneous.

Intravenous.

On mucous membranes. I Subcutaneous and I intramuscular.


Jn mucous mem*

branes. 3n mucous mem


Subcula

On nnicous m<

brane. Subcutaneous.

Subcutaneous.


Subcutaneous.

On mucous membrane.

Subcutaneous and intramuscular.

Subcutiincuus and intramuscular.

On mucous membrane.

On mucous membrane.


CONTROL INOCULATIONS

Injeclion of Ascitic Urolh and Xormal Blood. — For I be intensive inoculation of susccjitible individuals with measles blood it might .seem only natural t« have included the injection of measles blood incubated in ascitic broth in addition to the other injections. .\ control series of injections, however, had already shown that normal blood in ascitic broth was not altogether free from toxic action.

The same lot of broth an<l ascitic fluid already described for the incubation of measles blood was mixed with normal human blood


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(4 c. c. to 50 c. c. of ascitic brotli) and incubated for 24 hours. Quantities of 5 to 7 c. c. were injected subcutaneously into 10 individuals; six remained practically free from symptoms. Of the other four, one immediately after injection maintained a temperature of 99° to 99.5° for nine days; another, six days after injection, developed a temperature of 100.2° accompanied by a few large papules over the forehead and a moderate degree of inflammation of the pharynx; the two others, nine days after injection, developed temperatures of 100° and 101° with definite pharyngeal symptoms but unaccompanied by any rash.

In a second group of controls with the same technique but with another lot of broth and of ascitic fluid, the reactions were similar but rather less marked. Of 10 individuals, three remained entirely without symptoms. The results in the others were as follows: in two cases, 10 days after injection, the maximum temperature in one was 99.8° and In the other 100.2°; three other cases reacted much earlier, the temperature in one on the fifth day being 100° and in the other two 99.4° on the sixth day. One case presented a slight rise in temperature on several days as follows, 99.2° on the fourth and fifth days, 99.4° on the sixth day. On these days, this man also developed a fairly extensive maculopapular eruption appearing first over the chest and then over the arms. When his temperature returned to normal the rash faded leaving pigmented areas which gradually desquamated. Another subject on the third, fourth and fifth days after injection developed a well-marked erythema which was widely distributed over the chest, back, abdomen and extremities. The temperature continued normal, except on the 13th day when it rose to 99.4°. In this second group of controls the leucocytes were counted whenever a rise in temperature occurred, but no leucopcenias were observed.

The-se reactions, though ver_y mild, indicate the advisability of conducting control inoculations when similar injections are performed to test for the presence of a virus; this is especially true in view of the difficulty of duplicating exactly a rather complex culture medium. Although these symptoms did not .simulate measles in any way, nevertheless the interpretation of atypical temperature curves or rashes might be confusing; the detection of a pre-eruptive rise in temperature might be very difficult when complicated by the possible effects of ascitic broth.

CLINICAL EVIDENCE

Intra-uterine Infection. — Medical literature, especially the text-books, frequently contain the statement that pregnant mothers, having contracted measles, occasionally give birth to a child with a fully developed rash. These reports of intrauterine infection do not bear complete evidence of authenticity. In many instances, satisfactory evidence is lacking for the diagnosis of measles especially in the child ; in other cases, the period elapsing after birth before the rash appears is sufficiently long to permit of extra-uterine infection. Although the cases are comparatively rare, it appears, on the other hand, that a pregnant mother developing measles at term does not ordinarily infect the child in utero. Lastly, the development of measles in a new-bom child would not harmonize with the view that infants during the first three months of life are immune from the disease. This apparent discrepancy might be explained by Herrman's " statement that children of susceptible mothers are not immune from measles, a view, however, which is not supported by the natural immunity of infants to some other acute infections, notably scarlet fever and diphtheria.


Characteristics of tlie Eruption. — The question whether the virus of measles gains access to the circulating blood requires for a completely satisfactory answer the explanation of a striking clinical symptom. A priori the remarkably constant appearance of the rash widely spread over the body would seem obviously to point to the distribution of the virus by the blood-stream. Unlike the rashes of other infections, of serum disease and of the food and drug intoxications, the eruption of measles always appears first on the upper part of the body, commonly on the face, from where it spreads steadily downward over the trunk and arms reaching the lower extremities on the second or third day. This phenomenon is very striking and very constant. It has been recognized as one of the distinguishing features of the eruption of measles. The average l^eriod for this progress over the body is usually stated as two or three days with extreme limits of one to five days. In a fairly definite but less striking manner the eruption fades in the order of its appearance ; thus the rash often almost disappears on the face before it is fully developed on the feet. Virtually no explanation has been suggested for this characteristic progress of the skin eruption. Von Pirquet,*" assuming that the virus is present in the blood stream, advances the view that the rash is a manifestation of allergic and that the order of appearance of the skin lesions is directly proportional to their distance from the heart and great vessels. In support of this view, figures are given in detail of the distance from the skin lesions by way of the arteries to the heart. It is very difficult to conceive of any explanation that is consistent with the mechanical features of the circulatory system. Moreover, other exanthems which certainly are distributed by the bloodstream do not progress in this manner over the body. A notable example is small-pox; the portal of entry is probably similar to that of measles, but one commonly examines the palms for the first nodules. Von Pirquet departs widely from the accepted views in considering that the rash of small-pox resembles measles in its origin and progress over the body. 

Possibly the lymphatic system offers a more satisfactory

basis than the circulating blood for the explanation both of the usual point of origin of the rash and its subsequent distribution. The mucous membrane of the upper respiratory tract and of the eyes may safely be regarded as the portal of entry of the virus of measles and the seat of the primary lesion. Notwithstanding some variation in individual cases as well as some minor differences of opinion, the skiu lesions usually appear first on the face. It is conceivable that the virus travels by way of the lymphatics not unlike tlie primary infection of the nasal mucous membrane in leprosy with the subsequent involvement of the skin of the face. The gradual progress of the measles rash has certain features in common with the spread of erysipelas, an infection which travels by way of the lymphatics. The plexus of lymphatics forming a complete network over the body would furnish anatomical communications consistent with the distribution of the rash. The valves of the lymphatic system which normally direct the flow of lymph in certain definite channels would not necessarily constitute an effective barrier against the spread of an infec


SErTK.MUKR, 1!»l!t|


265


tious agent; a rapidly multiplying virus could conceivably grow airaiust this feeble current of lympli and also grow throujili the delicate valves.

The preeedinj: discussion has been based on the hypothesis that the niorbillous cxanthem is produced, not by an extracellular toxin but l)y the action of the virtis of the disease itself. in a manner analogous to what occurs in small-pox and chickenpox. A toxin could hardly distribute itself cither by the blood stream or by the lymphatics in a manner that would explain the symptoms observed in measles. The virus of the disease, if it is distributed by the lymphatics, would almost inevitably be swept into the blood stream where it might readily persist teni]K)ranly even though it did not multiply. The clinical evidence, however, can only be regarded as suggestive; experimental proof must be obtained before any final decision is permissible. The ultimate explanation of the progress of the rash of measles will be of distinct interest and value.

DISCUSSION OF RESULTS

There is. unfortunately, a striking discrepancy between tiio negative results following these inoculations of measles blood and the successful experiments previously reported uiulcr essentially similar conditions. A careful examination of the data recorded in this paper has failed to suggest any correlation of these diametrically opposite results. Eight apparently susceptible individuals have been inoculated with blood in various ways but none developed measles. In the selection of measles patients for these inoculations, the diagnosis both of the disease it'elf, especially during an epidemic, and also the stage of the disease offers little difficulty. In any negative results in adults the crucial factor is the question of susceptibility. While some of these eight individuals may in reality have been immune, it .seems that, at the least, several of them must have been susceptible. As already suggested, the two who received intensive inoculations of measles blood and responded negatively to susceptibility tests may have been immunized by the injections; if one is not willing to consider the possibility of inununization there still rcn)ain six other cases requiring explanation.

There are certain points of especial interest concerning the two exjierimental cases reported by Ilektoen. The extremely small quantity of serum, approximately 0.1 c. c, employed by this author constituted one of the significant features of his experiment. A few but not many infections can be readily reproduced by the injwtion of minimal quantities of blood. In cattle plag\ie as little as ]/(iO c. c. of blood may prove infective : " Marehoux, .Salimbeni and Simond " produced yellow fever with <>.l c. c. of serum.

It will be recalled that these successful experiments witii measles were conducted prior to our knowledge of scrum sickness: however, only homologous proteins were employed and typical serum-disease can therefore be eliminated. In the control tests reiwrted in this paper the injection of mixtures of normal blood, ascitic fluid and broth produced a slight temperature and rash in occasional instances, but in no case I


could the symptoms have been confused clinically with measles.

Spontaneotis Infections. — Sporadic cases of measles may develop so insidiously that even with careful isolation, the possibility of spontaneous infection during experimental inoculations must be borne in mind. A typical illustration occurred at the base hospital at Camp Dcvens, JIass. A patient had been in the general wards of the hospital for two months ; during this period it was not possible to trace any contact with a case of measles. lie was then transferred to the p.sychopathic ward where, after thorougli isolation for one month he developed a typical attack of measles. The tcmperaturechart showeda characteristieprc-eruptive rise accompanied by conjunctivitis and toryza. The symptoms increased ; Koplik spots appeared, the temperature rose again, a characteristic rash developed followed by the usual pigmentation. It was not possible to locate any third person who might have carried the infection to this patient. Such examples are, however, so rare that it is by no means plausilde that both of Ilektoen's cases could be explained in this manner. This is especially true in view of the fact that the experimental subjects in question underwent a period of isolation much longer than the normal incubation time of the disease before any injections were made and they were subsequently carefully jirotected from spontaneous exposure.

The diagnosis of these experimental cases was ba.sed essentially on the rise in temperature after a typical period of incul)ation and the development of a definite rash. In both patients the rash started on the face. In one case the progress of the rash over the body is described; its distribution was almost complete in about five hours. This period would be extremely short for spontaneous measles, being much more characteristic of rubella. Infomiation concerning the lymphatic glands in these patients would have been of some value in differentiating these two diseases. Although the injections were made over the chest and over the back it is of interest to note that the rasii appeared first on the face just as when the virus enters the body by way of the mucous membrane. In one of these ca.ses a typical bran-like desquamation is descrii)ed.

Respiratory sym])tonis were al)sent in one of these cases, a feature which has led TJstvedt" to .suggest the possibility of doui)t concerning the diagnosis of measles. However, it is not at ail surprising that the nnicous membrane of the respiratory tract should escape involvement when one considers that the portal of entry and very jiossibly the seat of the primary lesion was changed from the mucous membranes to the body tissues. Such absence of respiratory involvement in measles iiiorulala would constitute a hopeful point in securing active inmiunization without running the risk of i)ulmonary coml)lications. Likcwi.<c. from the standjioint of protective inoculation, it is encouraging to note that evidence of malaise was absent altogether in one patient and very mild in the other.

It is noteworthy that the charts in neither case exhibit any pre-cruptive rise in temperature, a characteristic which though very common is not constant in spontaneous infections and it is eertainlv not an essential criterion for the diagnosis of


266


[No. 343


measles inoculata. It is desirable that certain deficieucies concerning these cases should be supplied, more especially the observations concerning the leucocyte count and the occurrence of Koplik spots. This information would be helpful in the differential diagnosis.

In some respects, therefore, these experimental cases differed from the usual course of spontaneous measles notably in the rapidity of the spread of the rash, in the absence of a preeruptive rise in temperature, in the absence of respiratory symptoms in one case and of malaise in the other. Such modifications, however, are of an essentially minor nature and might readily be explained as the result of the subcutaneous injection as contrasted with spontaneous infection. The occurrence of such modifications in the disease, however, would require thorough confirmation.

General Considerations. — Some of the infectious diseases of man can be readily transmitted from infected to susceptible individuals by the injection of blood; such transmission has been fully demonstrated for yeUow fever," malaria" and trench fever." According to the conclusions of Hektoen this same statement would also apply to measles. To appreciate fully its importance, it must be clearly borne in mind that for trench fever, malaria and yellow fever the natural portal of entry is through the skin; in measles the primary lesion occurs in the mucous membrane. By radically altering the portal of entry or the seat of the primary lesion of a given virus remarkable changes may be produced in its effect even on a highly susceptible host ; the vibrio of Asiatic cholera produces infection when ingested by way of the alimentarj- tract but relatively large amounts of living and virulent cultures can be injected subcutaneoush' with impunity.

After noting certain definite exceptions it would seem possible to develop some general rules concerning fundamental principles involved in the artificial immunization against any given infection. Precise data, from the very nature of the subject, are not available on account of the difficulty of obtaining information concerning the infectivity of pathogenic micro-organisms for man. The subject may be conveniently considered imder three headings :

1. For those infections in which the mucous memlrane constitutes the portal of entry and in vjhich the classical lesions of the disease are in general limited to the tissues accessible bi/ direct continuity, the causative organism may in many instances be injected subcutaneously in a- viable condition in moderate dosage with impunity.

In the case of bacillary dysentery and Asiatic cholera, living attenuated cultures of the causative organism have been used freely by subcutaneous injection as a vaccine. For the pneumococcus, Cecil and Blake,§ at the Army Medical School, have recently demonstrated in monkeys {Macacus sy rictus) that as little as one-millionth of a cubic centimeter of a broth culture may produce a fatal pneumonia upon intratracheal injection. The subcutaneous injection of one-thousandth of a cubic centimeter of the same culture may or may not produce a

§ Personal communication.


seisticaemia. In either case, those animals which recover possess a distinct immunity. In the case of B. diphtherice virulent strains growing on a wound usually produce no symptoms in man. From the clinical evidence one would not expect that the hypothetical organisms of whooping cough and of influenza would produce an infection upon subcutaneous injection.

2. As a corollary to the first statement, when, the natural portal of entry of a pathogenic organism occurs through the skin, then artificial injection into the tissues or blood stream causes an infection which reproduces the typical manifestation of the spontaneous disease.

Of the more important diseases in which the portal of entry occurs through the skin we may consider bubonic ])lague, tetanus, glanders, anthrax, malaria, trypanosomiasis, hydrophobia, kala azar, relapsing fever, typhus fever, yellow fever, dengue fever, trench fever and the spotted fever of the Kocky ^Mountains. In the case of plague, malaria, yellow fever, trench fever, typhus and probably dengue, it has been demonstrated experimentally that the subcutaneous or intramuscular injection of the virus, in virulent form, reproduces the typical features of the spontaneous diseases ; a similar result could be confidently expected in the remainder of the diseases just mentioned.

The disease, plague, occupies a position of an intermediate type which is unique. B. pestis exhibits the characteristic of possessing two distinct portals of entry resulting in the production of two clinical types of disease, the pneumonic and the buljonic form of plague. If insect transmission of B. pestis were unknown, bubonic plague would not occur spontaneously; experimentally it could be designated appropriately as plague inoculata inasmuch as it differs markedly from the pneumonic form.

3. For those infections in which the virus enters by way of the mucous membrane and gives rise to metastatic lesions in other tissues of the body, the injection of the virus into the body tissues usually produces an infection; sometimes the essential clinical characteristics of the disease are duplicated, but in other instances a modified infection results quite unlike the spontaneous disease.

The first and third groups must be looked upon merely as extremes between which there can be no sharp dividing line ; for instance, typhoid fever constitutes a somewhat intermediate example. Although B. typhosus can infect in moderately small numbers by way of the mucous membrane, nevertheless, living cultures can be injected subcutaneously with the production of nothing more than a local reaction.

The meningococcus, M. melitensis, Treponema pallidum and the causative organism of poliomyelitis may conveniently be considered together. Injection of monkeys with the virus of poliomyelitis and the accidental injection of man with T. pallidum have produced typical infections; similar results could probably be obtained with the meningococcus and with M. melitensis, two organisms which produce little or no local lesion on their passage through the mucous membrane.

Small-pox and chicken-pox present important conditions for consideration. AVhen the virus of small-pox is inoculated


September, 1919]


267


on the skin instead of on the nnicous membranes, small-pox inoculata develops and the disease, as it occurs spontaneously, cannot be reproduced in this manner. According to Hess and TJnger ' the virus of chicken-pox, when injected intravenously, gives rise to no symptoms but apparently reproduces some immunity.

E.xceptional conditions occur in two of the diseases of lower animals. In cattle plague extensive primary lesions occur on the mucous membrane of the intestinal tract and eventually a septiciBmia develops. Experimentally the virus behaves in an almost unique manner in that small doses of blood injected subcutancously set up a fatal infection. Besson" states that the influence of tlie site of injection of the bacillus of -symptoniatic anthrax is very marked. A dose of the virus which will kill an ox on injection into the cellular tissues of the body will produce merely a benign infection when injected into the connective tissues of the neck, tail or ear and is followed by permanent immunity.

In the preceding discussion the objection may at once be raised that the normal healthy adult can readily withstand the inoculation of a few living and fully virulent pathogenic organisms. A distinct step would be gained if it can be shown that those organisms which normally enter the body through the skin can, as far as injections into the tissues are concerned, set up an infection from the introduction of much smaller numbers than in the case of those micro-organisms which first infect the mucous membranes. In attempting prophylactic immunization against a given disease it is fundamentally nece.ssarj- to consider the natural portal of entry of tlie virus in question.

RESUME

An eifort has I)cen made to determine whetlicr the virus of measles exists in the circulating blood of a patient, permitting the transfer of the disease from man to man by the inoculation of blood. The prominent data bearing directly on this subject are:

(1) The successful transmission in two cases previously

reported by Hektoen,

(2) The failure in eight instances recorded in this paper

to transmit measles by the injection of blood,

(3) The clinical phenomenon of the origin of the rash on

the face or upper part of the body with its gradual progress downward requiring from one to three days to complete this march.

The symptoms of the t^vo experimental eases that have been reported were not entirely characteristic of the classical type of measles. Although the disease varies extremely little in its clinical manifestations, distinct modifications might readily occur under experimental conditions.

As regards the negative results obtained in these eight individuals, the principle difficulty arises in establishing, by the clinical history, the susceptiliilitj- of an adult to a disea.«e so generally prevalent as measles. In some of the men who were inoculated the circumstantial evidence of susceptibility was unusually strong.


Failure to transmit the disease by the injection of blood does not preclude the existence of the virus in the blood stream even in moderate amount. There is some evidence that these men not only failed to become infected but that they were actively immunized by the injection of blood ; .such an assumption would, of course, presuppose the existence of the virus in the blood stream. Indeed the agent which excites the rash might readily gain access at least temporarily to the bloodstream regardless of whether its distribution takes place by the lymphatics or by the circulating blood.

The constant origin of the eruption on the upper part of the body and its gradual and orderly extension downward is quite unlike the development of eruptions in which the virus is known to be distributed by the circulating blood.

Measles originates as an infection of the respiratory and conjunctival mucous membranes and the virus does not set up metastatic infections in the viscera of the body in the spontaneous disease. Failure to reproduce the disease by subcutaneous injection of the virus is in keeping with the behavior of several other pathogenic micro-organisms of the respiratory and gastro-intestinal tract.

The virus of measles per se does not produce serious effects, but one attack of the disease gives rise to a well-marked immunity. With appropriate isolation of the virus it would seem that a substantial active immunity should be obtainalile with a minimum of inconvenience to the individual.

CONCLUSIONS

1 . The question of the transfer of measles from man to man by the injection of a patient's blood is entirely reopened by the eight successive negative inoculations recorded in this paper.

2. The failure to transmit the disea.se in this manner does not necessarily exclude the possibility of the occurrence of the virus of the disease in the circulating blood; some evidence was obtained indicating the possibility of producing active iniinunity by the injection of ])aticnfs blood.

This experimental study of measles by the inoculation of volunteers was authorized by General Gorgas and General Ireland at the request ot Colonel Frederick F. Russell. The ofllcors and men volunteering for this work signed the following statement:

" I hereby volunteer as a subject for inoculation with measles In order to promote the work undertaken In the United States Army for securing a protective inoculation against this disease."

Having seen the serious consequences ot measles In camp life, these men, for no reward to themselves, gladly accepted the risk inherent In these inoculations simply from a desire to be of service. Throughout this work they co-operated cheerfully and conscientiously in carrying out the long isolation essential during these investigations.

The Surgeon General's recognition of their services was made by Colonel Russell in the following letter:

" The Surgeon General has been informed of the fact that you volunteered for the measles Investigation. He desires me to express to you his appreciation of the patriotism and devotion to duty that you have shown and to assure you that your contribution to the cause is appreciated by him just a.s much as was the bravery of the men who went into the fight In France."

It is a pleasure to acknowledge the constant co-operation of Colonel Frederick F. Russell throughout these investigations. I


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[No. 343


am especially indebted to Lieutenant-Colonel Channing Frothingham for his assistance at Camp Devens and to Lieutenant-Colonel Henry J. Nicliols for his kind co-operation at Camp Meade and at M'ashington, D. C.

BIBLIOGRAPHY

1. Noguchi. H.: Etiology of Yellow Fever. Jour. Exper. Med., 1919, XXIX; 547.

2. Mayr. F.: Beobachtungen iiber Maseru. Ztschr. d. k. k. Gesellsch. zu Wien, 1S52, I, 6.

3. Herrman, C: Immunization against Measles. Arch. Pediat., 1915, XXXII, 503.

4. Hektoen, L. : Experimental Measles. Jour. Infect. Dis., 1905, II, 23S.

5. Tunnicliff, R.: Observations on the Bacteriology and Immune Reactions of Rubeola and Rubella. Jour. Infect. Dis., 191S. XXII, 462.

6. Anderson, J. F. and Goldberger, J.: Experimental Measles in the Monkey. Public Health Reports, 1911. XXVI, 847 and 887.

Goldberger, J. and Anderson, J. F.: The Nature of the Virus of Measles. Jour. Am. Med. Assn., 1911, LVII, 971.

7. Levy, R. L. and Alexander, H. L.: The Predisposition of Streptococcus Carriers to the Complications of Measles. Jour. Am. Med. Assn., 1918, LXX, 1827.


8. Hess, A. F. and Unger, L. J.: A Protective Therapy for Varicella. Am. Jour. Dis. Children, 1918, XVI, ii.

9. Richardson, D. L. and Connor, H.: Jour. Am. Med. Assn., 1919, LXXII, 1046.

10. V. Pirquet, C: Das Bild der Maseru auf der Aeusseren Haut. Ztschr. f. Kinderh., Orig., 1913, VI, 1

11. Nicolle, M. and Adil-Bey: Etudes sur la peste bovine. Ann. de rinst. Pasteur, 1901, XV, 715.

12. Marchoux, Salimbeni and Slmond: La fievre jaune. Ann. de I'inst. Pasteur, 1903, XVII, 665.

13. Ustvedt, Y.: Norsk Magazin f. Laegevidensk, 1906, LXVII, 128.

14. Di Mattel, E.: Beltrag zum Studium der experimentellen malarischen Infection am Menschen und an Thieren. Arch. f. Hyg., 1895, XXII, 191.

15. McNee. J. W., Renshaw, A. and Brunt, E. H.: Trench Fever. Brit. Med. Jour., 1916, I, 225.

Strong, R. P., et ah: Trench Fever. Oxford University Press, 1918.

16. Besson, A.: Practical Bacteriology. Trans, by Hutchens, H. J., Fifth Ed., 1913, 553.


THE ROLE OF THE X-RAY IN THE DIAGNOSIS OF LONG-STANDING

RENAL TUBERCULOSIS

By J. A. ('. CoL,sroN and Charles A. Wateds (From the James Buchanan Brady Urological Institu-te, The Johns Hopkins Husijital. BcUimore. Md.


The progress which lias been made in the htst decade in the investigation of diseases of the urinary tract, thanks to the use of the cystoscope and ureteral catheter, has made possible a differentiation of lesions which before that time had been unrecognizable.

There is no disease of the kidney which can be more certainly diagnosed by the use of these modern methods than renal tuberculosis. The demonstration of diminution in the renal function, together with the presence of pus cells and of tubercle bacilli in the catheterized specimen of urine collected from one side, leaves no possibility of doubt as to the condition with which one has to deal.

In the majority of cases a diagnosis is possible by the use of these methods. But in many cases of renal tuberculosis, especially those of long duration, cystoscopy and ureteral catherization are impossible on account of the changes which have taken place in the bladder mucosa. It may be impossible to recognize the ureteral orifices or they may not admit the ureteral catheter; and there are also some cases in whicli extensive ulcerative processes have led to such contracture oL" the bladder as to make the introduction of the cystoscope impossible or too paiuful for the patient to bear. In many of these cases, although tubercle bacilli may be demonstrable in the bladder urine, owing to the fact that the ureters cannot be catheterized, it is impossible to determine in which kidney the lesion is located, because it must be remembered that in most cases of renal tuberculosis there are a few definite symptoms referred to the kidney itself.


When it is possible to introduce the ureteral catheter, the diagnosis is usually easy, but there are types of long-standing chronic tuberculous processes with sluggish ulceration in which only a few pus cells can be demonstrated and tubercle bacilli may not be found even in repeated catheterized specimens.

In some cases in which the disease has progressed to complete destruction of the kidney terminating in caseation and deposition of calcium salts — the so-called auto-nephrectomy — the deposition of calcium salts will east a shadow on the x-ray negative varying in density in proportion to the extent of the process. It is in just these cases where for any of the above reasons a definite diagnosis cannot be made that the s-ray will often be the determining factor in the recognition of the lesion.

When the normal kidney substance has been largely replaced by calcified caseation, a complete outline of the kidney and even the ureter may be seen on the x-ray plate and in sudi cases a definite diagnosis can be made immediately without the demonstration of tubercle bacilli and without recourse to ureteral catheterization except to determine the integrity of the opposite kidney.

It should, therefore, be a routine procedure to precede cystoscopy and ureteral catherization by plain x-ray examination of the urinary sy.stem in all suspected cases of renal tuberculosis.

When the calcification is limited to a single area in the kidney there may be .some difficulty in differentiating this process from calculus, but a critical c.bservation of the


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density, shape and position of the shadow, will leave little room for doubt. Where tlie kidney has been completely destroyed, the charaeteristie lobular appearance of the shadows due to the caloitied caseous cavities is very definite and is never seen in any other type of kidney lesion.

By means of stereoscopic plates the iiulividiial abscess cavities can be dearly distinj;uished from each other, provided, of course, that the process has been of a duration long enough to produce deposition of calcium salts in the areas of caseation. Calcification of the ureter is rare, but when it does appear it is perfectly characteristic, the ureter showing on the negative as a dense shadow, tiie calcification involving the upfwr portion, the lower portion or indeed its entire course.

In addition to what is shown by the sclerosis of the ureter itself, a shadow may be cast by the caseous material which is sometimes seen filling the lumen of the ureter and which represents the +++++ CONTENTSs of the cavities in the kidneys.

The fact that calcification occurs as a late process in renal tuberculosis and that this calcification will show an opacity on the x-ray plate has long been known, but tlie practical value of this simple method has been too little emphasized.

During the past few years several cases of renal tuberculosis have been recognized at the Brady Urological Institute from the x-ray plate alone, and a summary of some of the more interesting of these cases will be given in order to emphasize the value of the routine x-ray examination.

Case 1. — A physician, aged 39. was seen in 1907. The family and past histories were unimportant. The patient had had attaclts of duU pain in the back and left flank at the age of fourteen which were diagnosed at that time as indigestion. He first noticed frequency and burning on urination at tlie age of twenty associated with hematuria. He lost some weight, had chills and fever and was incapacitated for about one year. A careful urinary examination was apparently not done at this time. The blood, however, soon disappeared and the frequency was greatly improved by instillations of silver nitrate. The dull pain in the back and left side, however, persisted, varying in intensity from time to time, and this was the patient's only complaint when he came for consultation.

The physical examination was negative and there was no tenderness In the region of the kidney nor could either kidney be felt. The urine was clear and contained no shreds or pus cells and on this account no examination for tubercle bacilli was made. There was evidence of a chronic prostatitis on rectal examination and the prostatic secretion contained an excess of pus cells.

The patient improved under prostatic massage, irrigation, instillation and dilatations of the prostatic urethra, until the pain completely disappeared. He was then referred to a gastrointestinal consultant and in the course of an x-ray examination of the gastro-lnteatinal tract following the ingestion of bismuth a remarkable shadow was seen in the region of the left kidney. This shadow occupied the position of the kidney and showed a definitely lobulated appearance. Nothing similar had been seen at the Johns Hopkins Hospital at this time and a positive diagnosis was not made. Cystoscopic examination showed a normal bladder with the exception that the left ureter could not be seen. The right ureter was easily catheterizcd and the specimen obtained was normal. A diagnosis of ureteral stricture with destruction of the left kidney was made, but the tuberculous nature of the process was not recognized.


The patient went to a western clinic where a nephrectomy was done and the kidney substance was found to have been entirely replaced by caseation and masses of calcification.

A letter dated April, 1919, states that the patient has been " free from pain and a great deal better siiue the operation."

The correct diagnosis of this case should have been made from the x-ray alone, but at this time no similar shadow had been seen in the x-ray department. The entirely negative urinary examinations and the fact that the patient responded so well to local treatment were also confusing factors which contributed to the failure to recognize the true nature of the process. (Fig. 1, Case 1.)

Ca.se 2. — A male, aged 24, consulted Dr. Geraghty in June. 1914, complaining of frequent urination. His father and two uncles had died of pulmonary tuberculosis. The past history was unimportant.

Frequency with burning had existed for the past two years with little or no improvement, at times associated with terminal hematuria. There was also at times a dull aching pain in the back mostly on the left side. A left epididymitis had appeared two years before, followed ten months later by a right epididymitis.

On examination there were no evidences of pulmonary tuberculosis. Neither kidney could be felt. The left testicle was normal; the epididymis was thickened at the globus minor where it was adherent to a scar in the scrotum. The right testicle and epididymis were much obscured and the globus minor was firmly adherent to a scar in the lower portion of the scrotum. The vasa defeiientia were normal. The urine contained some pus cells but no tubercle bacilli.

Ci/siosropic examination showed a contracted bladder. The mucosa showed some areas of reddening especially in the trigone, but there was no active tuberculosis. The right ureter was seen but it was impossible to catheterize because the cystoscope could not be introduced far enough to permit a ureteral catheter to enter it. The left ureteral orifice could not be seen.

Plain x-ray examination showed a definite dense shadow occupying the region of the left kidney. This shadow suggested a lobular form, but it also presented a somewhat granular appearance. The ureter, which was not enlarged, could also be I)lainly seen in its entire course from the kidney over the pelvic brim to the bladder.

A diagnosis of left renal tuberculosis was made and nephrectomy was done by Dr. Geraghty. Convalescence was uneventful. The kidney was lobular, twice the normal size and had been entirely converted into a cheesy mass. The ureter was very thick and fibrous, its lumen entirely filled with caseous material and practically obliterated. (Fig. 2, Case 2.)

Cask 3. — A man, aged 24, came for a consultation in June, 1914, complaining of frequent urination. The patient's father an<l two uncles had died of pulmonary tuberculosis. The past history was unimportant. The patient had first had frequency, strangury and hematuria two years before and shortly after the onset a left epididymcctomy was done for epididymitis. A year and a half later the left testicle was removed on account of a persistent sinus.

Since this date the frequency liad persisted and there had been pains in the region of the bladder but none in either kidney region.

Physical examination revealed no signs of pulmonary tuberculosis, the left kidney was palpable but not tender. Rectal examination revealed irregular induration of the left lobo of the prostate and seminal vesicle.

Plain x-ray examination showed both kidneys definitely outlined and larger than normal. A definite, rounded mass was seen in the region of the left kidney which closely resembled


270


[Xo. 343


the shadow of a stone. On the right side there was a definite, lobulated irregular shadow not so dense as that on the left side but much larger, the process evidently involving the left kidney more than the right.

Cystoscopy showed a reddened trigone and some areas of cystitis but no active ulceration. The ureters were easily catheterized and the specimens from each side contained a few pus cells and a few large colon-like bacilli. The 'phthalein excretion from each side was 18 per cent. No tubercle bacilli could be found in these specimens, nor had any been demonstrated in the bladder urine after repeated examination. A guinea-pig innoculation was also negative.

A pyelogram showed a normal right pelvis, the calyces being somewhat elongated, the superior caljic extending as far as the shadow seen on this side. The ureter was not dilated. The left pelvis was normal but the calyces were greatly elongated and extended out so that they more or less surrounded the oval shadow previously seen on this side. The results of this examination tended to support the tentative diagnosis of calcified tuberculous areas in each kidney.

It was decided to explore the left kidney to determine definitely the nature of the shadow. At operation. Dr. Geraghty immediately confirmed the tentative diagnosis from the appearance of the kidney delivered in the wound. On account of the involvement of the right side the kidney was replaced and the wound closed. Convalescence was uneventful. (Fig. 3, Case 3.)

Case 4. — Physician, aged 41. This patient was seen by us in a base hospital in France having been referred on account of hematuria. His mother had died of pulmonary tuberculosis. His past history was negative except for a left empyema in 1903.

He had noticed blood in his urine first in 1S98 and this had continued for about two years with few or no bladder symptoms. The diagnosis of prostatitis had been made and local treatment given. In 1902, blood had reappeared in his urine and continued for a short time. In 1906 for the same symptom the patient had gone to a western clinic where cystoscopy was performed but it was found impossible to catheterize the right ureter. From this time on the same slight frequency of urination had persisted. Following the exposure incident to foreign service the hematuria had reappeared in October, 191S. Physical examination was negative except for the scar of the empyema operation. Examination of the urine showed numerous pus cells and red blood cells but no tubercle bacilli.

Cystoscopic examination showed a small ulcerated area on the anterior bladder wall and rather marked injection of the trigone. The left ureter was readily catheterized but no definite right ureteral orifice could be made out in spite of repeated attempts. The urine from the left kidney was normal.

A definite diagnosis could not be made but tuberculosis of the right kidney was suspected and the patient invalided home to the States for further study.

On entrance to the Brady Urological Clinic after repeated examination of the urine a few tubercle bacilli were found, the cystoscopic findings were corroborated and the plain x-ray examination showed a clear outline of both kidneys, the right kidney being smaller and the shadow remarkably opaque. On careful observation a definite dense lobulated appearance was seen and the ureter which was distinctly opaque could be easily made out in its course to the bladder.

In the plain x-ray of the pelvis the lower end of the right ureter showed the same distinct opacity and its shadow could be seen coursing over the brim of the pelvis. The outline of the left kidney showed no opacities and the organ could be definitely seen to have undergone compensatory hypertrophy.

From the characteristic dense lobular shadows seen in the plain x-rays and the demonstration of tubercle bacilli in the


urine a diagnosis of right renal tuberculosis was made and a nephrectomy was performed by Dr. Geraghty, December 13, 1919. Convalescence was uneventful.

The kidney was found to be entirely destroyed, all kidney substance having been replaced by caseated masses separated from one another by thin layers of fibrous tissue. The ureter was entirely obliterated.

This case was evidently one of very long standing, slowly progressing, the initial symptoms dating back twenty years. In spite of this long duration the bladder had become only very slightly involved and tubercle bacilli were found only on one occasion among many examinations.

It is this type of slowly progressing lesion which results most commonly in the so-called auto-nephrectomy and it is in just this class of lesions that calcium salts are deposited in amounts large enough to permit a diagnosis to be made from the plain x-ray plate positive. (Fig. 4, Case 4; Fig. 5, Case 4.)

Case 5. — A man, aged 46, entered the Brady Urological Institute in May, 1919, having been referred with a diagnosis of left renal tuberculosis. His family history was negative. At the age of nineteen an abscess of the left testicle had been opened and eighteen months later two abscesses had been opened in the right lumbar region. Six years before he came to us a severe attack of renal colic on the right side had been followed by the passage of a small calculus and four years later a similar attack occurred on the same side. There had been no frequency, hematuria or pain on urination, but the patient had had a dull aching pain in the region of the left kidney and soreness in the left hip for the past few years. The patient was seen about one year before but the left ureter could not be catheterized.

Physical examination was negative except for slight tenderness elicited on deep pressure over the left kidney. Neither kidney could be felt on account of the thick abdominal wall. The scars of the old abscesses in the right lumbar region were well healed. The urine was clear, contained no pus cells and no tubercle bacilli.

Stereoscopic x-ray plates were taken qf the left kidney and the whole organ was represented by a series of lobulated shadows which without doubt represented the calcification of the individual areas of caseation. Nine such lobules could be easily counted on the stereoscopic plates. The shadow of the right kidney showed that it had undergone compensatory hypertrophy. There were also evidences of an old healed tuberculous process involving the first, second and third lumbar vertebrae. The total function as measured by an intramuscular injection of 'phthalein was normal. The patient was advised to return later for nephrectomy.

Although operation has not as yet been carried out on this patient there can be no doubt as to the diagnosis or as to the integrity of the right kidney. One may also assume that the left ureter has been occluded and that the process commonly called auto-nephrectomy has also occurred in this case. (Fig. 6. Case 5.)

A dogmatic classification of the shadows cast liy various types of tuberculous kidneys cannot be made and all graduations may occur, from the small indefinite shadow cast by a calcified, tuberculous area about a calyx, to the beautiful lobulated shadow which results from a completely destroyerl kidney, consisting entirely of calcified abscess cavities. The x-ray of such a kidney is quite unmistakable, but the smaller, indefinite shadows which may be seen are occasionally difiicult to differentiate from renal calculi and also from various extrarenal shadows such, for example, as the +++++ CONTENTSs of the intes


THE JOHNS HOPKINS HOSPITAL BULLETIN, SEPTEMBER. 1919


PLATE XXXIl



1 (Case I I. -rlKirarii risiic lobiilatrd appearance of a kidnoy conily destroyed.


Fio. 3 (Case 111 ).— Comi'li t. d.sini<tion of the upper pole with beginnins deposition of calpiiini sails in lower pole of a kidn.'V not yet completely destroyed.



Fii;. 2 (Case III.— Typical mottled appi'arance due to the Irregular diposition of calcium salts in a kidney completely destroyed. The outline of the ureter is plainly seen.


Fio. 4 (Ca.se IV».— Completely occluded kidney with d. portion of calcium salts througliout Its entire extent.


I lit


THE JOHNS HOPKINS HOSPITAL BULLETIN, SEPTEMBER. 1919


PLATE XXXIIl



Fu.. ".- Drawing of tlie stereoscopic plates of Case V, showing the clear differentiation of the individual calcified lobules.


Kiti. 5 (Case IV I. — Cak-ilication of the lower end of ihe ureter in Case IV. Same side.



Kii.. 6 (Case Vi. — Kidiuy i ..lui.i. ;• r. ..;-; i ..;•• .i. -....wing typical lobulated form with deposition of calciiini salts in the caseated areas. Old healed tuberculous process of the twelfth thoracic and first and second lumbar vertebrae.


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tine, calcified glands, gallstones, etc. It must also be remembered tliat the extent of tlie shadow on the x-ray plate does not represent the extent of involvement of the kidney and many kidneys have been seen, on removal, totally destroyed, which, on x-ray examination, showed only small indefinite shadows, or none at all.

The presence of a true renal caKulus, in association with renal tuberculosis is rare, but several sucli cases have been seen in which a calcium oxalate stone occupied Ihe pelvis of a tuberculous kidney. In all probability such a stone arises from the deposition of calcium salts in a tuberculous ulceration of a calyx. We have seen several cases of early tuberculosis in which the only focus found in the kidney after the operation was an ulceration of a single calyx. In a few of these cases there was a definite deposition of calcium salts and it is easily conceivable that a small portion of such a calcified area could break off, fall into the pelvis and form the nucleus of a large stone.

Such a stone gives a picture quite different from that occasionally encountered when a tuberculous area in a kidney, wrongly diagnosed as a stone, is exposed at operation. If an attempt is made to remove the supposed stone it will be found to consist of a grumous, putty-like material which cannot be taken out as a whole. If such a condition is encountered and its true nature recognized at operation, it is far better to do a nephrectomy provided previous studies have demonstrated that tlie remaining kidney is normal. However, if the x-ray shows the presence of similar areas in the remaining kidney or if the evidence of its involvement has been demonstrated, no operative procedure should be attempted, as the trauma incident to operation may very readily convert a slowly progressing, partially walled-o(T process into an acute exacerbation or may even lead to a general miliary tuberculosis.

It is not tlie purpose of this paper to discuss the very great assistance of the data which may be obtained from the pyelogram and cystogram. In an occasional case when sufficient information cannot be obtained by other means, a diagnosis can be made by these studies. It has been the practice at tiie Brady Clinic, however, to refrain from a ])yelographic study if a definite diagnosis of renal tuberculosis can be made by the usual methods. There have been no bad results following this method but we have not felt that in cases where the diagnosis was already certain the additional instrumentation was justified.


CONCLUSION

(1) X-ray studies of the entire urinary tract should be carried out in all cases of suspected renal tuberculosis.

(2) In some cases, when other methods of examination have failed, a definite diagnosis of renal tuberculosis can be made from the plain x-ray alone but, whenever possible, catheterization of the other ureter sliould be done to establish the integrity of the opposite kidney.

(3) The shadows depend entirely upon tlie amount of calcification which has taken place in the diseased kidney.

(4) Various types of shadows may be seen in tiie plain x-ray of a tuberculous kidney varying from the indefinite shadows cast by small areas of calcification to the characteristic lobulated shadow wliiih is typical of a completely destroyed kidney.

(5) Pyelography and cystography may clear up the situation in some cases but these procedures should not be carried out if a diagnosis can be made by other and simpler methods.

Note. — Since this article was written a paper by Braasch and Olson (Roentgenographic Diagnosis in Renal Tuberculosis, Surgery, Gynecology and Obstetrics, XXVI II, 6, p. 5551) has appeared in which virtually Hie same conclusion has been reached.

BIBLIOGRAPHY

1. Striiter: Zeltschr. f. Rbntgenk.. 1908, p. 41.

2. Mankiewicz: Deutsche Med. Woch., 1908, p. 1290.

3. Grassner-Hurter: Zeltschr. f. Rontgenk., 1910, p. 376.

4. Fenwick: The value of expert radiography and cystoscopy In the detection of obsolesced tubercle kidney. Brit. Med. Journal. July 3, 1919, Vol. 2, p. 16.

5. Dietlen: Zeitschr. t. Rontgenk., 1911, p. 85.

6. Casper: Zeitschr. t. Urol., 1913, VII, p. 532.

7. Marlon: Une nouvelle cause d'erreur dans la radlographle des calculs du rein. Jour. d'Urol., 1912, 1, p. 655.

8. Papin: Localisation de la tuberculose rfinale par la radiographic. Archives urologiques de la cllnlque de Nechar, fasc. 2, juin, 1913. p. 177.

9. Heitz-Boycr: Exclusion parllelle dans un rein tuberculeuif avec urines clalres. Jour. d'Urol. 1914, V, p. 297.

10. Plllet: Tuberculose r^nale a forme anormale. Jour. d'Urol. 1914, V. p. 595.

11. Legueu. Papln and Malngot: Exploration radlographique de I'apparell urinairo. Paris, 1913.

12. O'Nell: Renal tuberculosis. Cabot's Modern Urology, Vol. II.

13. Ratine: Tuberculose rOnale. Encyclopfdle Francalse d'urologle. Paris. 1914, t. 2.


REPRINT OF THE OSLER NUMBER OF THE BULLETIN


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The Johxs Hopkins Press, Baltimore, Md.


[No. 343


IN MEMORIAM

ADMONT HALSEY CLARK

Bv William G. MacCallum


A memorial meeting was held on June 9, 1919, in the lecture room of the Pathological Laboratory of The Johns Hopkins University to uncover a tablet placed there by colleagues and friends to the memory of Dr. Admout H. Clark, associate professor of patholog)', who died on October 13, 1918. The admiration and affection of all who had known him were expressed in brief addresses by Dr. Welch, Dr. Howell, Dr. Sabin and Dr. MacCalhun. The following short biographical sketch was read :

Admont Halsey Clark, the eldest child of Cyrus Alonzo and Harriet Gulick Clark, was born near Kyoto, Japan, on August 25, 1888. His father, who came from Genesee County, New York, had graduated as a minister at Oberlin College. His mother, whose family, the Gulicks, had for generations been missionaries, was born in the Caroline Islands.

Their married life has been almost entirely spent in missionary work in Japan and there Admont lived and went to school until he was 13 years old. After that he was sent to America to be educated and came to live with his mother's sister and her husband, who is Professor Jewett, of Oberlin College. With them he remained through his school and college life, becoming deeply attached to this aunt and uncle who in some degree took the place of his distant parents.

All through his student career, both at Oberlin and later in the medical school, he earned money by every kind of outside work to support himself. Nevertheless, he found time enough for his studies to stand well in his classes, and playtime enough to excel at athletic sports. He was a particularly good player at football and was on the University and the Maryland State teams. JIusic, too, he loved and during this whole time he studied the violin and learned to play it very well, so that later he derived great pleasure from taking part in trios and quartets.

After his graduation at Olierlin College in 1910 he formed one of a party of biologists on an expedition to Point Pelee on Lake Erie to observe the migratory flight of birds and to learn whether they flew boldly across great bodies of water or tried to take advantage of the islands scattered across the lake. Here he contracted typhoid fever which was so severe that he lost a whole year before entering The Johns Hopkins Medical School in 1911. During part of this time, however, he acted as assistant in chemistry at Oberlin College.

When fully recovered, he began work with a new zest. At college he had taken up scientific subjects, showing especial interest in chemistry toward which he had probably been led by Professor Jewett. Again he stood high in his class and, in addition, he proved to be one of the men who can and must work on special problems which carry them beyond the routine work of the class.


Each year he seems to have been hard at work on one or more problems, as his published papers show. In the first year he worked under Dr. Sabin's direction on the development of tlie lymphatics, in the second under Dr. Whipple on the chemical tests of the function of the liver. In his fourth year he substituted as interne in the hospital for two months and there devised and worked out a method for studying venous pressure in disease. He graduated with the degree of Doctor of Medicine in 1915 and entered immediately the department of pathology where each year he advanced, beginning as an assistant and becoming successively instructor, associate and associate professor of pathology.

In these positions he showed liis ability to carry out serious investigations independently and proceeded to a long and most laborious study of the internal secretion of the pancreas in its relation to sugar metabolism. This was brilliantly successful in demonstrating the presence of a secretion essential to the consumption of sugar by the beating heart.

Nest he turned to the study of the filtrable toxin which he and Pelton had produced by growing the hemolytic streptococcus in blood. They completed and published a short paper on this subject, but much more work was planned to control and confirm their results. At the same time and before this he was working in a more leisurely way on the effect of diet upon the healing of wounds and had obtained some interesting results which were left in the form of notes from which IMrs. Clark has WTitten and published his paper.

He was married at Portland, Maine, on July 9, 1917, to Jliss Janet Howell, and his daughter, Anne Janet, was born on May 15, 1918. This was a j'ear of extraordinary happiness for him. Since December, 1917, he had held a commission as first lieutenant in the medical reserve corps of tlie army and was very anxious to be assigned to active service, but the surgeon-general's office, recognizing the importance of his work on the streptococcus, supported it generously and kept him in Baltimore. In the autumn there came the epidemic of influenza and he was one of the many stricken. He appeared to recover from its first effects and returned to the laboratory for a day or two, but then developed a streptococcal pneumonia from which he died on October 13, 1918. His loss was among the greatest caused by that terrific epidemic.

Clark was a young man, prematurely slightly gray with an honest face and bearing which captivated everyone at once. He was so intelligent, so completely trustworthy and so efficient that there was never any hesitation in entrusting to him, when occasion demanded, the whole charge of the department, nor was there the slightest doubt of the propriety of his extraordinarily rapid advancement to the place of associate professor only three years after his graduation from the I medical school.


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PLATE XXXIV


^^7-2-'



Admont Hai.sky Clahk.







^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^EP~ - -1 y "^^^^^^^^^^^^^^H


i


Lj-i


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273


Aside from his undoubted ability iu the routine work of such a department and his deserved jwpuhirity amonj: the students and assistants who recojrnized at once his value as a teacher, he had a jrrcat talent for tlie investigation of the problems which interested him. Genius is a much misused word and can hardly bo applied to Clark, because he was essentially well balanced and sane and went about his work upon a carefully devised plan which partook of genius only in that he had great enthusiasm, an almost unlimited capacity for concentrated work and a remarkalde quality of efficiency. He worked early and late, even moving a bed into one of the rooms of the laboratory in the summer, when his wife and child were away, so that he could stay there continually and watch his experiments at night. When he constructed apparatus with much difficult glass-blowing and grinding of stopcocks, it worked. When he carried out a series of experiments to prove a point, they worked and there were few if any false steps. Foresight and rational judgment as to the relative importance of necessary evidence helped him greatly to advance. His problems were large and complicated and their solution involved long and difficult experiment'; — especially in the case of the pancreatic secretion, where he had to perfuse a surviving pancreas and a surviving and beating heart, analyzing the fluid from time to time as it passed ; and it was only with very perfect apparatus, all of which he constructed himself, that it could be done. It was thoroughly good work and full of the most brilliant promise. He was only 30 when he died.

His interests were by no means limited to the laboratory. He loved the outdoor life, and all games and sports, but more


especially, perhaps, the life of the woods with shooting and fishing. His vacations during his course at the medical school were spent working at summer camps for his uncle. Dr. Luther Gulick. and his honeymoon was a camping and lishing trip on Lake Temagami. He seems to have had the same skill in everytliing he did in the woods that he showed in the laboratory.

His loss is a very great one not only to us who knew and admired him, but also to science. He seemed destined to do great things.

His published papers were as follows :

On the Fate of the Jugular L}inph Sacs and the Development of the Lymph Channels in the Xeck of the Pig. .;Vmer. Jour, of Anatomy, l!il>, XIY, 4:.

Tests for Hepatic Function and Disease Under Experimental Conditions. (Wliipple, Peightal & Clark.) Johns Hopkins Hosp. Bull., 1913, XXTV, 243.

A Study of the Diagnostic and Prognostic Significance of Venous Pressure Observations in Cardiac Disease. Arch. Int. Med., 1915, XVI, 587.

The Interrelation of the Surviving Heart and Pancreas of the Dog in Sugar Metabolism. Jour. Exp. Med., 1916, XXIV, 621.

The Same. Second Paper. Ibid, 1917, XXVI, 721.

A Filtrable Toxin Produce of the Hivmolytie Streptococcus. (Clark and Felton.) Jour. Amer. Med. Assoc, 1918, LXXI, 1048.

The Effect of Diet on the Healing of Wounds. Johns Hopkins Hosp. Bull., 1919, XXX, 117.


REMINISCENCES OF TWO EPOCHS-AN/ESTHESIA AND ASEPSIS

By Stephen- Smith, A. M., M. D.. LL. D., Xew York


The development of an art is characterized by a succession of events each of which signifies progress. These events may, singly, appear unimportant, but, as Sir James Paget truthfully remarks, " Closely studied they are links in an endless chain of events leading to a higher development as we witness in the embrjo." In this chain of events there occasionally occurs one which far transcends others in the radical and fundamental changes which it effects in the practice of the art under review. It stands a beacon light which illumines with ever-increasing brilliancy the pathway of the humblest practisor. Such an event creates an epoch — " .\ point of time from which succeeding years are numbered " (Cent. Diet.) .

Baas, the eminent historian of medicine, regards epochs as the es.<ential features of the development of an art and from an educational viewpoint urges that they be studied by every practiser. Impressively he remarks:

An acquaintance with the views and knowlctlKe of epochs submerged in the shoreless ocean of time, free.s the mind from the fetters and currents of the day with Its often oppressive reatraints. widens the horizon for a glance into the past, and an insight into the present of human activity, deepens the view for a comprehension of the ideas which guided the earlier and more recent


physicians, and gives on the other band to our daily professional labor a high consecration.

Though two of the most remarkable epochs in the history of surgery — ana-sthesia and asepsis — occurred within my personal experience, it is unfortunately true that with the profession at large the views and knowledge of these great events have long been submerged in the shoreless ocean of time.

This general ignorance of the great events in the recent history of surgery is due to tlie failure of the schools to include in their courses of instruction a wcll-devisod system of teaching the " views and knowledge of epochs." No department of science has a more interesting and instructive history than medicine, inasmuch as every advance tends to the betterment of the race. My experience as a teacher for many years emphasized the fact that students are not only greatly interested in historical incidents connected with the subject, but that thoiic incidents proved suggestive to the memory wlien the subject was recalled in actual jiractice in later life.

Deeply impressed with the truth and moral significance of the historian's sentiments and their quite general application, it has occurred to me that it would he peculiarly appropriate to the present occasion if I recalled some of my experiences


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and observations on the introduction of these two greatest epochs in the history of surger)'.

ANAESTHESIA October 16, 1846

When I entered tlie office of Prof. Frank H. Hamilton, of Buffalo, N'ew York, in May, 1847, as a student of medicine, ansesthesia was on trial. Though it bore the impriraature of the surgeons of the Massachusetts General Hospital, headed by the honored name of Dr. John C. Warren, several deaths had been reported during its use, which served to make conservative surgeons cautious. Prof. Hamilton was of that class and he resorted to ansssthesia only occasionally and in cases believed to be especially adapted to its use. This fact gave me ample opportunity to compare the old-time method with that promised by the new discovery.

The first operation without anesthesia that I witnessed was so disquieting on account of the sufferings of the patient that I was nearly driven from the profession. Its cruelty was so shocking to my untrained nervous system that I begged to be excused from attending another operation, but the professor, made merry of my sensitiveness, assuring me that the most successful surgeons had fainted at the first operation but that in the " long run " extreme sympathy for tiie patient made a cautious and conservative operator. The case referred to illustrates the ordinary operative proceedings in hospital practice at that time :

The patient was a workman from a shop and was suffering from a strangulated hernia. No other preparation was made than to remove his exterior clothing and sponge the surface over the hernia. The surgeon came in haste, put on a hospital apron and urged haste in bringing the patient to the table. Several strong-armed attendants were selected to hold the patient if he made resistance. AVith a conspicuous display of the knife the surgeon made his first incision with lightning rapidity which was followed by the violent screams and struggles of the patient and a volley of oaths. It required several minutes to place him again in position and meantime the surgeon, with knife poised in the air, awaited nervously an interval when he could cut twice in the same place. A second incision intensified the shrieks and efforts of the patient to escape from the table. All was now indescribable confusion, but the attendants succeeded in overcoming the patient now exhausted by his struggles and shock and at length the exciting tragedy came to an end, witb all parties completely exhausted.

That this is not an overdrawn description of every day operations in the great hospitals of the country I will quote a reliable author's experience, the patient being a woman :

She Is cheered hy kind words, and the information that it will

soon be over She is enjoined to be calm and to keep quiet

and still But of what avail are all her attempts at fortitude! At the first clear crisp cut of the scalpel, agonizing screams burst from her and with convulsive struggles she endeavors to leap from the table. But the force is nigh. Strong men throw themselves upon her and pinion her limbs. Shrieks upon shrieks make their horrible way into the stillness of the room until the heart of the boldest sinks in his bosom like a lump of lead. At


length it is finished, and prostrated with pain, weak from her exertions and bruised by the violence used, she is borne from the amphitheatre to her bed in the ward to recover from exhaustion.

The screams and struggles of patients submitted to operation, which we then heard and witnessed, were but the echo down the ages of those heard when the primitive surgeon first applied the " chipped-knife "' to human flesh to remove the broken fragment of a war missile. There were screams and struggles in the home of Moses when Zipporah, his highbrow Midianite wife " Took a flint and cut off' the fore-skin of her son " (Ex. iv. 24). There were abundant screams and struggles in the Jewish families when " Joshua made himself knives of flint and circumcised the children of Israel " (Joshua v. 3).

Pain and suffering was regarded as the chief obstacle to success in operative surgery from the time of that first operation with the knife or flint. Even Hippocrates, in lofty phrase, expressed the prevailing sentiment : Divinum est opus sedare dolorem.

Two methods of mitigating suffering seem to have been suggested to primitive surgeons, viz.:

1. Celerity of operation to diminish the time of suffering, and,

2. The discovery of an agent which would safely cause insensibility.

CELERITY OF OPERATION

Of these two methods the first was the most practical, as it involved no danger, and was, therefore, adopted at once. Successful celerity of operation required two conditions: (1) Such a variety of instruments as may be necessary to meet promptly every possible emergency; (2) Dexterity in the use of instruments. Fortunately the early Huns and Egyptians, by nature and training, were especially adapted to devise the instruments and use them dexterously — conditions necessary to success in celerity of operation.

In the field of invention the oriental excelled. Centuries before the Christian Era we have descriptions of instruments in familiar use by Plindus and Egyptians which in perfection of finish and adaptation to special uses are equal to the " kit " of the modern surgeon. For example, the forceps devised to extract the fragments of the rude missiles employed in the tribal wars were thus described by a contemporary writer:

They ought to be about nine inches long; their mouths be respectively like those of a lion, tiger, wolf, hyena, bear, elephant, cat, hare, antelope, crow, heron, dog, jay, vulture, falcon, owl, kite, cock, crouch, the bee, rat, mouse or bullock. Each half must be united to the other by a nail of the form of a lentil seed being bent inwards at the handles like the elephant-driver's hook.

There was also tlie same great variety of probes and tubular instrvmients each being designed to meet a special emergency during the operation. The following directions in preparation for an operation illustrate the care exercised by the primitive surgeon to render a rapid operation safe:

A surgeon contemplating to operate .... should first have ready the following: blunt instruments (forceps, etc.), sharp instruments, potential cauteries, horns, catheters, leeches, a dry


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gourd, a cauterizing needle, stuffing materials, fat, milk, oil, string, board, bandage, honey, soothing decoctions, injections, lotions, fan, cold and warm water, a frying pan, able, steady and attached servants. During the operation let the patient be seated, who has taken very little food, offered sacrifices and made ablutions, with his face towards the East. The surgeon should stand with his face toward him and plunge his instrument after the proper incision until matter comes out, and withdraw it, avoiding vital parts, vessels, muscles, articulations, bones and arteries .... Boldness, rapidity of action, sharp instruments, operation without trembling, fear or doubt, are always praiseworthy of the surgeon.

As a ' show-fad "' dexterity in the u.<e of instruments was at its climax when I entered the profession. At hospital clinics attended by students operators performed fantastic tricks with instruments often brandishing them in the air when about to make an incision. An amputation was a favorite occasion for these displays of dexterity. The Catlin, glittering for a moment above the head of the operator, was plunged through the limb and with one artistic sweep made the flaps or coml>leted a circular operation. After several aerial gyrations the saw severed the bone as if driven by electricity. The fall of the amputated part was greeted with tumultuous applause by the excited students. The operator acknowledged the compliment with a formal bow. The clinics of these operators were as popular as tiieatrical performances and about as instructive.

Celerity of o|icration as I witnessed it, while accomjilishing little in the mitigation of the sufferings of the victims of operation, often had \ery serious features. Wounds of blood vessels and nerves, puncture of viscera and similar accidents not unfrequently occurred in the clinics of operators famous for the display of dexterity and celerity. The movement of a struggling patient at the moment the operator plunged his knife resulted in wounding the femoral artery. Puncture of the urinary bladder and intestines, division of im])ortant nerves and similar accidents were reported from clinics. These acc-idents usually were the interesting feature of the operation, as they tested the ability of the operator to meet the emergency. The accident itself did not reflect upon the operator's skill but was attributed to the unfortunate movement of the ]iatient at that critic-al moment when the surgeon was to exhibit his ilexterity. Thus the tragedy that resulted in a coroner's ini|iiest contributed to the reputation of the operator as a most .-kilful surgeon.

AN AN.ESTHETIC

-Mlusions to the u.se of " pain-killing " agents are frequent in medical histon,- from prehistoric periods. In general their discovery has l>een accidental as in the ca.<c of ga.ses from the earth. More frequently the narcotizing agent was foiind in vegetables, the poppy, the mandragora, l)elladonna, hyoscyamus. cannabis Indica, etc. Cutting operations without pain under the narcotizing effect of these vegetables are mentioned by many writers at different periwls. Homer describes two operations in that picturesque style which suggests that he must have been present and witne.«.sed them. He says :

Machon was summoned to remove an arrow which was driven through the belt of Menelaus, King of Sparta: he extracted the


arrow from the well-fitted belt, but while it was being extracted the sharp barbs were broken: then he loosed the variegated belt and the girdle beneath and the plated belt beneath, which the brass-workers had forged, when he perceived the wound where the bitter shaft had fallen: having sucked out the blood, he skilfully sprinkled on it soothing remedies.

Eurypylus wounded with an arrow in the thigh called upon Patroclus to remove it. Patroclus, laying him at length, cut out with a knife the bitter, sharp arrow from the thigh, and washed the black blood from it with warm water. Tlien he applied a bitter pain-assuaging root, rubbing it between his hands, which checked all his pains: the wound indeed dried up, the bleeding having ceased.

The following prescription for making the famous anaesthetic of Theoderic (1-378) illustrates the efforts to discover an anaesthetic :

Take of opium and the juice of unripe mulberry, of hyoscyamus, of the juice of the hemlock, of the juice of the leaves of the mandragora, of the juice of the wood ivy. of the juice of the forest mulberry, of the seeds of lettuce, of the seed of the burdock, which has large and round apples, and of the water-hemlock, each one ounce: mix the whole of these in a brazen vessel, and then in it place a new sponge, and let the whole boil, and as long as the sun on the dog-days, till it [the sponge] consumes it all, and let it be boiled away in it. As often as there is need of it, place this same sponge in warm water for one hour, and let it be applied to the nostrils till he who is to be operated on has fallen asleep and in this state let the operation be performed. When this is finished, in order to rouse him place another dipped In vinegar, frequently to his nose. Or let juice of the roots of fenigreek be squirted into his nostrils. Presently he awakens.

The story of the researches and efforts to discover a reliable and safe ana'sthetic does not differ from that attending the introduction of all great epochs. Repeatedly the di.-covery was announced and the prize seemed won, only to be followed by a disa])pointment the more depressing because so often repeated. Indeed, these disappointments had so crystallized professional opinion against the possibility of di.«covering a safe and reliable ana-sthetic that on the very eve of its announcement the most eminent surgical authority of tlie period, Velpeau, thus voiced the ])revailing .sentiment of the profession (1839) :

To escape pain in surgical operations is a chimera which we are not permitted to look for in our day. A cutting instrument and pain in operative medicine arc two words which never present themselve's. the one without the other. In the mind of patients, and it is necessary for us surgeons to admit their association.

It is creditable to the profession that the cliief otistncle to an earlier discovery of a safe and reliable ana'sthetic was the fear of fatal results in making the necessary tests on human subjects. l?icc. author of the " Trials of a I'ublic Henefactor." remarks :

It Is probable the deadly results which must have often ensued from their use, the long-continued depre.islon which they exert upon the nervous sy.sleni, the confirmed stupor and the congestiona and other accidents which are so liable to follow, all conspired to prevent their use, or even examination.

The only interesting feature in the centuries of search for an anesthetic relates to the incidents by which the inhalation


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of nitrous oxide gas (laughing-gas) led to the discovery of scientific ansesthesia. In 1799, Sir Humphrey Davy, then au assistant in the " Pneumatic Institution " of Dr. Beddoes, Penzance, England, experimented with nitrous oxide gas and described in a familiar way its exhilarating and intoxicating effects. He even used it for the relief of pain in the head and teeth and finally suggested its possible use in surgical operations :

As nitrous oxide in its extensive operations seems capable of destroying pliysical pain, it may probably be used with advantage in surgical operations in which no great effusion of blood takes place.

The suggestion of Davy was so natural that it is surprising that nearly half a century elapsed before the subject again attracted attention, though nitrous oxide (laughing-gas) was in popular use for amusement in social circles.

The circumstances attending the actual employment of nitrous oxide to allay the pain of a surgical operation not only fulfilled Davy's prediction, but gave to our country the great honor of discovering a safe and reliable ana?sthetic and also of placing anaesthesia on a scientific basis.

Dr. Crawford Williamson Long (1815-1878) of Danielsville, Ga., a graduate of the medical department of the University of Pennsylvania, was impressed, while attending an exhibition of "laughing-gas," with its power of causing a harmless delirium, and ventured to test its effects personally. In his performances under its influence he received a painful injury of his leg of which he was not conscious until he had recovered from the effects of the gas. Like Davy he became imbued with the idea that surgical operations might be performed without pain while a person was in this state of delirium. Long seems to have been a very unpretentious practiser of his profession in a small rural town quite remote from even the current medical topics. He engaged in general practice and performed all the surgical operations that came under his observation. In 1842 he first operated on a patient under the control of nitrous oxide and removed a tumor from the neck of a lady without pain. Subsequently he used this gas in his operations but did not think the method of sufficient importance to publish an account of it until the question of priority of discovery of an antesthetie became the subject of Congressional inquiry on the petition of Dr. W. T. G. Morton, of Boston, 1847.

In 1844 nitrous oxide attracted the attention of Horace Wells, a dentist of Hartford, Conn., in the same manner it had Davy and Long, while being used as a " laughing-gas." AVells tested it by having a tooth extracted while under its influence and on returning to consciousness, exclaimed : " A new era in dentistry." He adopted it in practice and related his experience to Dr. W. T. G. Morton, a dentist of Boston and former partner in business. Morton was an enterprising young man who recognized the importance of the new treatment, if it really proved to be capable of accomplishing the objects claimed. He, therefore, thoroughly tested it and became convinced of its value in the practice of dentistry, the logical result of this conclusion being that it would prove


equally valuable in the field of operative surgery. To test this question by high authority Morton applied to Dr. John Collins Warren then at the head of the surgical staff of the Massachusetts General Hospital. The day fixed for a trial operation was October 16, 1846. The operation was advertised widely and a notable gathering of the most distinguished members of the profession in Boston and vicinity was in attendance.

Prior to the date of the operation Jlorton had been advised by a chemist. Dr. Jackson, that sulphuric ether had the same effect as nitrous oxide and was more manageable. Accordingly Morton prepared to give this gas which occasioned a few minutes delay in his arrival at the hospital. This delay was construed by the skeptics in the audience as a complete failure of Morton to meet the test, and when he appeared a few minutes later he was greeted with derisive laughter. Even Dr. Warren had apologetically informed the audience that he had little faith in the alleged anEesthetic.

The operation, the removal of a vascular tumor of the neck, was a complete success. A profound silence fell upon the witnesses of a great epoch in surgery as Dr. Warren declared in homely phrase, " Gentlemen ! This is no humbug." This announcement, heard around the world, ushered into human history the great epoch — Anjssthesia — freedom from pain in the practice of operative medicine.

ASEPSIS 1867 The discovery of a safe and reliable antesthetic seemed to cut the cords which restrained the progress of operative surgery and this branch of practice went forward in leaps and bounds. Medical periodicals were filled with descriptions of new, unheard of, and even unthinkable operations, and the clinics became interesting for the novelty of the operations and the perfection of details, now so much more carefully completed.

THE ANTISEPTIC PRINCIPLE 1867

But important as was the reform in the manual of the operation, it was painfully apparent that in the final summary of results the mortality of operated wounds had not diminished. The chief element of disaster, suppuration, still remained in full force and determined by its relative intensity the final result. Of this fact I had an opportunity for ample experience. On entering the Bellevue Hospital Resident Staff (1850) my duty as the junior member was to carry the " pus-pail," the receptacle into which the senior surgeons placed the pus-saturated dressings. Two and often three times daily he had to renew these dressings, each change attended by great suffering and exhaustion. I vividly recall our painful disappointment on witnessing the gradual failure of the vital powers of patients with such an outflow of pus. Daily the visiting surgeon examined the pus to see if it was not becoming " laudable " and pressed iron tonics, but the final result was general infection.


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From the time of Hippocrates there were two scliools of surgeons based on the question of the treatment of wounds with and without pus. Althougii pus was almost universally present in healing wounds, still there were occasional instances where the wound healed witiiout any discharge, but remained dry throughout the process. This incident gave rise to two methods of treatment, the " dry " and the " wet," the former being our healing by " first intention,'" and the latter by suppuration or granulation (second intention). Though the intuitive genius of Hippocrates led him to teach healing by the " first intention," as the correct practice, he was violently opposed in the schools of Greece, and the '"wet" treatment prevailed, its advocates regarding it important even to apply irritating dressings when pus was not freely secreted. These two schools continued to our time, the " wet " method being generally taught in the colleges and practised in the hospitals. Pus was not regarded as injurious to the wound except when of unhealthy quality and it was the quality, not the quantity, that interested the surgeon. Good pus was thick like cream and was called " laudable pus " ; it was thought to indicate healthy healing. Practically we had a continuation of the old controversy of the healing of wounds by " first intention," the " dry method," or by suppuration, the " wet method."

Lister's series of experiments by which he demonstrated the element in pus which renders it prejudicial to the healing of wounds, and the discovery of an etTective remedy by which that element can be rendered inert from the moment of operation, are the most brilliant in the annals of science. Impressed with the fact that he had a mortality of 45 per cent in his cases of amputation, though great care was exercised to protect the wound, his mind recalled Pasteur's theory that microorganisms arc the cause of putrefaction and that in his observations putrefaction was present only when there was suppuration. He at once began experiments to test the truth of the theory of Pasteur by employing such agencies as he could command to destroy any germs present and still not harm the wound. He was finally led to the use of carlwlic acid which proved satisfactorv'.

Lister began his experiments in ISC).! and priiilcd his first ])aper entitled. " On the Antisejitic Principle in the Practice of Surger}-." in 1S(!7. No one but a contemporary of that period can realize the storm of criticism and ridicule wiiich greeted the author of that paper. He was accused of not iwing original in his work : of not obtaining k'tter results than the old method of practice; of rendering operations tedious; of employing childish and ridiculous apparatus and dressings.

Lister answered his critics by the performance of new and more incredible operations without pus or fever and in the meantime ini[)roved the details. His reported excision of a knee-joint. ISTS. and wiring a fractured patella. 188:?. without suppuration, brought to a climax the amazement of older surgeons at his jiretensions. liut what aitpcaled to the elders as recklessness inspired the juniors with a commendable desire to test the truth of his statement-s in actual practice. I introduced the practice into the wards of Bellevue Hospital greatly


to the disgust of many of my colleagues who refused even to visit the wards where the patients were under treatment. I had the satisfaction, however, of a visit of Mr. Lister himself, while on a tour in this country, who generously commended my work and in his autobiography gives me the credit of introducing asepsis.

On visiting Lord Lister at his London residence in 1894, I found him quite pessimistic as to the then state of asepsis. He remarked that he believed true asepsis was rarely practised. " Why," he said, " I was in Berlin a few days ago and at the urgent request of friends attended the clinic of a noted a.*eptic surgeon. All his methods were excellent but on becoming confused in the operation he stopped, scratched his head, and completed the operation without sterilizing his fingers. That was an infected wound and its suppuration will be attributed to the failure of asepsis."

On relating this incident to a former house surgeon to Lister's ward while he was experimenting with diU'erent agents, he said : '" Lister was very much subject to pers])iration especially when intently engaged in an operation, and I have often seen the sweat of his face fall into the wound without attracting his attention." Lister's great success, even under such unfavorable conditions, depended, probably, upon the thoroughness with which he finally applied disinfectants, for he dwelt especially upon that feature of aseptic treatment.

AX.KSTHESIA AXU ASEPSIS 18G7

With the introduction of asci>sis into practice the art, operative medicine, became a true science. The entire process was governed by rules which ensured success. Compare Lister's statement that his best results in amputations showed a mortality of 4-5 per cent in 18C4-18GG by the best methods then in use, with a recent report of a hospital in New York that in fifty consecutive cases of laparotomy, involving many varieties of intra-abdominal affection, 100 per cent of the patients made a good recovery.

It was very gratifying to me to learn of the following incident which occurred at the Bellevue Hospital recently where pus reigned supreme prior to 1867. A professor in one of the medical schools wished to exhibit a specimen of fresh pus to his class and naturally directed the messenger to apply at Bellevue Hospital. On making his errand known he was informed that pus in operation wounds had long since disappeared from the wards. Prior to the year 18G7 healing by first intention in that ho.spital Mas neither expected nor .sought by the surgeojis. One of the most distinguished operators merely brought the surfaces of tiie wound together with adhesive strips and placed the wound in such a position that the pus would flow into a vessel, thus avoiding tlie necessity of frequent renewal of the dressings.

Now all is changed. Healing by first intention is always sought and the presence of pus in operation wounds is a severe reflection upon the care and skill of the staff in charge. But perhajts the greatest and most l)eneficent result of the im


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proved methods of treatment in operative surgery in this ansesthetic-aseptic era is the rapid convalescence of patients. The operation which formerly was the beginning of the end, owing to the exhaustion due to the suppuration which ensued, is now the beginning of a rapid convalescence. The feeble, nervous sufferer whose heart nearly ceased its action on the thought of an operation now approaches the operating room with a firm stej), a normal pulse, and mounts the table with a smile. As operations under the old-time system were illustrated by the description of concrete cases, the vast improvement effected by the combined methods of ana?sthesia and asepsis will be most thoroughly appreciated by a similar report of cases treated according to the principles established by these great epochs.

A young woman, aged 18, had suffered from a suppurative disease of the knee-joint five years, and was reduced in vitality to a helpless state. Her fear of an operation rendered her nervous system so sensitive that she had attacks of fainting when an operation was mentioned in her presence. And yet delay of an operation seemed more dangerous than its possible fatal results. A medical friend suggested the preparation for the operation be made in an adjoining room and he would visit her as chaplain and induce her to inhale chloroform to unconsciousness when she could be quietly removed to the operating table.

The ruse worked admirably. The patient was delighted with the perfumery, as the physician called it, and required but three or four inhalations to become insensible. Excision was performed, requiring an hour to complete it and its aseptic dressings, but her pulse continued good under the influence of hypodermic injections of heart stimulants. For several days she was in ignorance of the operation and was surprised that she had no longer pain in the knee but occasionally in her toes. One morning she saw a spot of blood on the sheet over the knee and was greatly alarmed as she had been told there was danger of fatal hemorrhage. On being assured that there was no danger and that the operation had been performed and she was recovering, she became frantic with joy. A vigorous appetite now developed and with freedom from pain and refreshing sleep, her rapid recovery was daily noticeable. The first dressing mad-e was on the twenty-ninth day and there was only slight yellow staining but no pus. She had gained eight pounds in weight.

The following incident led me to adopt a method of anaesthetizing very feeble patients which has proved very serviceable. I was aiding a colleague in an operation for cancer of the breast on an old lady who was very fat, with a feeble intermittent pulse and nervous excitement. She had been prepared in the usual way with purgatives and simple diet. She had taken but little ether when her face became purple, her pulse disappeared and after a struggle to restore her she was pronounced dead.

It happened that I bad a duplicate of this case on which I was to operate on the following day. I was so shocked by this experience that I delayed the operation and studied the


situation. The result was the conclusion that probably these patients' feeble and intermittent heart-action was due to overlaying and interstitial fat and required supporting rather than the depressing treatment then employed. Though this indication could be met by hypodermic heart stimulants 1 recalled two facts that determined my course, viz.: (1) Larre)', in his memoirs of the Napoleonic wars advised operations on soldiers while they are drunk, for they neither fear nor feel pain, and (2) hot milk is a quick nutrient and sustains a weak heart. Here were the remedial agents which my patient required to prevent fatal collapse.

After preparatory treatment I directed that at 8 o'clock on the day of the operation which was at 3 o'clock, the patient should receive one ounce of hot whiskey in a glass of hot milk, and the same must be repeated at 10 and 13 o'clock unless she was much disturbed. On visiting my patient at three o'clock on the day of the operation I found her in a most satisfactory condition. She had not required the stimulant the third time, having become quite excited about the details of the operation which had taken fantastic forms in her enlivened but disordered imagination.

On entering the ward she greeted me with some affectionate tenns, expressed her delight that the operation was about to be performed and wished she could see the medical students present. Her face was flushed, eyes suffused, skin warm and her pulse full and regular at ninety-six. She came under the influence of the anaesthetic without a struggle and required an amount estimated at one-tenth that ordinarily given, the whiskey having already secured partial anaesthesia as Larrey suggested when he ordered wounded soldiers to be operated on while drunk. The pulse remained at ninety-six during the time occupied by the operation and the application of the aseptic dressings. She made an unusually rapid recovery, the pulse continued at ninety-six for several days; her appetite became vigorous ; her happiness that the operation was over was extreme. But one dressing was employed and when it was removed there was no sign of pus and only the yellow staining of serum.

During the many years that I have used tliis anaesthetic, hot milk and whiskey, I have not seen a patient fear an operation, nor suffer from shock or collapse.

I trust these desultory reminiscences of the introduction of the two greatest epochs in human history may lead us to a proper appreciation of the labors, trials and skill of the surgeons of the pre-an£esthetic period, who amid the heartbreaking screams and uncontrollable struggles of patients devised and successfully performed the great operations wliich adorn the annals of surgery.

There is a profound truth in the remark of the historian, that " such knowledge widens the horizon, for a glauce into the past, and an insight into the present of human activity, deepens the view for a comprehension of the ideas which guided the earlier and more recent physicians, and gives on the other hand to our daily professional labor a high consecration."


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NOTES ON THE GROUP OF SYMPTOMS DESIGNATED AS EFFORT

SYNDROME

Bv E. W. Bridgmax,

Instnirliir in Mnlirine. The Jolt us Ihipkit'.-' Medical ^School (Itecerilly ( 'iijitinii, Meilical Corps. ('. .S. Ariiii/ )


A little less than three years ago, when the stage was being set for the comedy entitled " The Second Mexican War," the writer was called into military service and assigned to the duty of physically examining the Maryliuid militia before its federalization. It was his first experience in the examination of large numbers of men and several interesting lessons were forthcoming which were later to prove most valuable. In the first place, an opportunity was afforded to appreciate the wide range of what may fairly be called the norm of the cardiovascular system. The prevalence of apical and conus systolic nmrnmrs. the presence of short, scratchy, systolic murmurs near the sternum, the intensity of the second sounds at the base of the heart and their relation to age, third sounds, presystolic snunils, sharp clicks heard only in systole near tlie apex of tlu' heart, tlie relation of posture to the jwsition of the apex — all, witii many other variations, are subjects well worth individual discussion, which may be dismissed here with the remark that for a proper valuation of such findings a competent knowledge of the normal is indispensable. Secondly, the variation in the pulse-rates of healthy individuals was noteworthy, and the dependence of this rate upon the condition of the mind and body was emphasized. Thus, tachycardia might be foimd in certain healthy young men who, having been told by a physician that they had heart trouble, did not believe they could pass the examination ; or, again, men suffering from venereal infection and fearing its discovery might show an increased pulserate. Confirmed neurasthenics, a few men who had been forced into sen-ice by the jilws of their friends, those who were doubtful of their right to expose dependents to the charity of the world, any of these soldiers might appear for examination with a rapid heart. The association of certain organic physical diseases generally of an infectious character with tachycardia waa constantly exemplified in the men with early or outspoken tuberculosis, bronchitis, or even with furunculosis.

A mentiil note was made of the high percentage of infected gums and carious teeth among the otherwise healthy and welldeveloited farmers, while the underdevelopment of the clerk group of the city men was conspicuous. One company having been re<-ently organizetl in the vicinity of the m<)l)ilization camp was still below the numerical standard, and on the day before the examination, its officers, dependent for their positions upon the acceptance of the company by the anny. collectetl a lot of young l)oys to supply the deficit. These lads claimed 18 years, but many of them were evidently younger.

During the three weeks of my duty at this camp, quite a number of men appeared at the hospital for re-examination because they were unable to perform their daily tasks. Many were young boys, a bit shaky, a little short of breath, with


acro-cyanosis of the extremities, sweating freely, and often complaining of sharp pains which they localized in the precordial region. A second physical examination, less hurried, disclosed nothing further of importance and it seemed that one was witnessing the attcm])t of a youth to do a man's work and the subsequent natural exhaustion. At the same time, others, many of whom had i)cen noted as underdevelojjed on the first examination, returned with similar complaints — they also had given out.

The rest of the summer was spent at the Artillery School at Tobyhanna where the Yale batteries and a few national guard organizations were training. During this period a few men were brought up for examination because they had not been able to stand the hard work — they had become irritable, did not get along with their fellows, and had lost weight. During the examination, they were apt to be a little shaky, the perspiration would roll down from their arm-pits, although the weather was comfortably cool; some degree of tachycardia was generally noted, and in response to slight exercise the rate would become excessive. Some of the soldiers had, in the course of the summer, slight attacks of tonsillitis or average colds of a few days' duration. It was interesting to follow these men. Whereas some of them went back to duty after a few days in the hospital and soon forgot their illness, others would remain below par for several weeks and have difficulty in doing the work that had caused them no discomfort before they had become sick. A few men showed a sensitive vago.sympathetic balance, and were apt to faint in the ranks during a protracted muster. The different vaccinations were administered at this camp, and it was not infrequent to have in line husky, strong soldiers who were obviously afraid — the skin cold and clammy, with rapid heart and panting res])iration. Others, i)latantly brave, would faint from the prick of tlie needle.

The result of the .summer's work was an aijjircciation of the infinite variations that arc to be found among individuals — the variation in the sensitiveness of their reflex arcs, the variations in their bodily and mental reaction to physical and p.sychical trauma and so fortli. Indeed each individual is so different in his bodily make-up and in his reaction to out.-iide stimuli that the normal is very difficult to delineate and standardization becomes |)ractically imjiossible.

Some of you have taken part in athletics at college, and will recall |)crsonal ext)erienccs similar to those that the writer himself remembers. Often, immediately before a footl)all game or his race in a track meet, he suffered what now sometimes comes l)ack in the form of a nigl^tmare. Although, in excellent physical condition, he would go out on the field all Btremble, with his heart racing and trying to l)eat its way throu^rh the chest, breath short and insufficient l)ecause of


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[Xo. 343


a suffocative band that seemed to constrict the lower thorax and to prevent the ingress of air. Occasionally, after some particularly inspiring speech from a well-wishing alumnus, he would go out sweating profusely, with involuntary micturition, and even crying. The actual start of the game was always suflBeient to bring back the normal functioning of the body. Again, you may remember your own condition or have seen others at the end of a short period of extreme bodily exertion, as at the end of a hard race for a quarter of a mile. Some men become pale with slight bluing of the mucous membranes, the cheeks sunken, trembling, occasionally fainting; others quite purple with puffed cheeks, watery eyes, nauseated even to vomiting, and often with blood-tinged sputum — both groups representing the signs of acute fatigue, the result of extreme exertion.

How often in the course of a wearing season does the coach tell one of his men that he is overtrained ! The man is irritable, has lost weight, is not sleeping, his pulse-rate is sensitive to slight exertion, he is constantly sweating in cool weather, his general physical strength is decreasing, and he cannot approach his average record; while his team-mates are doing well and are improving under exactly the same work. Eest and a change of scene may soon return the overtrained man to his former condition, but the trainer has been to blame for the loss of time ; he was treating all his athletes according to one standard, and this cannot be done with success. It is generally known that the captain of an athletic team is rarely so good during his tenure of office as he was the season before when he did not have to worry about the condition of the whole team in addition to performing his own individual work. It mav even become necessary to send such a man away to continue his training by himself.

Experience in the training of track men develops the opinion that there are two outspoken tj-pes of athletes with nmnberless gradations between, the one capable of supreme concentration of energy for a short period of time, the dash man, the other slow-going and very resistant to fatigue ; the former nervous, high strung, the hyperthyroid type, the latter steady and plodding, a successful long-distance runner. The training of the two groups should be quite different. The training of the sensitive dash man is always difficult. His work reflects his mental attitude^ and the worry of a failure in recitations will be recorded by the reduction in his speed, whereas the phlegmatic distance runner plods along comparatively uninfluenced by his surroundings. Reverse these men, and the long-distance man is a failure in the sprints and the dash man will not only be unsuccessful in his new work but may also develop typical signs of efort syndrome.

One more observation from the field of athletics. Perhaps some of you have gone back some time after you left college, and have been asked by some enthusiastic coach to change your clothes and line up on the scrubs or to take out the hurdlers and show them some of the fine points of that race. All of us hate to admit that we are getting old, and perchance you have tried to do what you could. Just one such attempt may teach you the symptoms of effort syndrome and, in that event, you become


very sympathetic towards individuals suffering with this condition. The writer attempted such work within a few years of active athletic participation, at a time when he was in fair condition from tennis playing. Pride kept him from acknowledging failure before the crowd, and he kept up his unusual exercise for an hour or so ; but for days afterwards he felt the effects — not only stiffness, but shortness of breath, untoward pulse acceleration, trembling, and precordial pain on slight exertion.

The same general reaction may be experienced during convalescence from even a slight infection. Those of you who have had influenza appreciate the long period that may elapse before you can comfortably perform your daily tasks. A physical examination may reveal no abnormality, but short walks are very tiring, and any continued mental labor is exhausting. Protracted asthenia after tonsillitis or slight colds is not infrequent in the medical dispensary.

It is an interesting fact, in this condition, that, bar an untoward accident such as an embolus or a ruptured valve, athletes or patients convalescent from acute disease never die during the period of activity. The will-power of individuals varies, and some men endure discomfort and withstand bodily punishment to a greater degree than others, but the limit in every case is always short of complete exhaustion of any organ of the body. This fact is intimately associated with some sort of protective mechanism of which the nervous system plays an important part and in wliich the resulting physical signs are manifested to different degrees as well as in different ways.

These observations serve as examples of conditions in which the symptom-complex called efort syndrome may obtain. Suggestions are made which point to a similarity of these signs to those manifested by the body in fear and in acute exhaustion.

In June of 1917, the writer was sent with The Johns Hopkins Unit to France where he was stationed for eight months in a base hospital. Here several facts were generally appreciated. The preliminary physical examination of the early recruits had been unsatisfactory, and for a while many of the patients were men who should never have been admitted to the service. There were not a few examples of dementia precox, constitutional inferiority, grave neurasthenia, besides organic physical diseases. Many of these men showed, in addition to the signs peculiar to the individual organic disease, sym])toms comparable to those already described. Then there were soldiers who had had no previous training, and who broke down under the strenuous physical demands which were especially exacting in the face of the poor housing facilities and unsatisfactory hygienic surroimdings. There were cases of tuberculosis, infectious arthritis, horrible teeth, old infected tonsils, and similar chronic infections, and many of these men showed the same excessive reaction to exercise. iMany soldiers who had come to base hospitals with acute diseases such as pneumonia, aciite bronchitis, or acute tonsillitis and who had been discharged apparently well, had returned to the hospital with symptoms of fatigue on slight exertion. These symptoms were very apt to be referred by the battalion medical officers to the cardiovascular system because of the rapid heart or tlie sliortness of breath. Moreover, the lack of knowledge on the part of


Septkmiiek, 1919 1


281


many medical officers of the range of the findings in the normal heart, cjuised, in face of symptoms so commonly associated with cardiac disease, a patliological interpretation of conus murmurs or third sounds, and the [)atient would be told that he had heart disease. After the wcasional man sulTering from organic disease had been weeded out and disposed of, and the better diagnosis of effort syndrome made, it was found that there was no satisfactory arrangement for the treatment or disposition of sui-h patients. As the demand for acute beds increased, some of them would be sent back to duty, while others would be transferred to other base liospitals where they would lie around for a few weeks and tlien again be put on the active list. Or tliey might sigain be regarded as sulFcrcrs from organic heart disease, be put to beil and given digitalis. After this treatment, they would generally get out again with their symptoms made worse, which more tlian ever convinced the patients that they were suffering from heart trouble which could not be cured. Such a belief always militated against the patient being willing to take active exercise.

When the medical consulting staff was established under tieneral \V. S. Thayer, an effort was made to rectify this unfortuinite condition and thereby avoid the resulting vicious circle in transportation, as a consequence of wiiich tliese .soldiers were spending most of their time in transit to and from the front line. Convalescent camps were to be established where treatment could be carried on intelligently, and where more protracted study of these patients might be made. At this time the writer was .«ent to England where he was attiiched to the British Military Heart Hospital which was doing excellent work under the direction of Dr. Thomas Lewis. Here were to be found the most extreme tyjies of effort syndrome listed under the British medical nomenclature — disordered action of the heart. Dr. Ijewis's work was fundamental. He showed that graduated exercises furnished a method for the functional testing of individuals and their subsequent classification for different degrees of physical work. This treatment, furthermore, proved to have an important curative value, so that he sent many of his patients back to front-line duty. The British medical corps was unfortunate in not having a psychiatric division, and, indeed, there was no special hospital in England for the treatment of psychoneuroscs. A patient was either demented, whereupon he was sent to an insane asylum, or he wiLs mentally correct. Such treatment a.s could be accorded the functional mental disorders was, as a rule, oidy that found in any base hospitjil conducted by a busy staff which must first meet the demands of the acutely ill. The treatment for the p.syclioneurotics was just the same as for the cases of effort syndrome, but this lack of differentiation furnishes one of the ex[)lanations of the high jjcrcentages of D. A. H. cases among the British. Dr. Lewis was preaching the gospel throughout England that these patients were made worse by l)eing put to bed and being given digitalis; but it was slow work, and the general lack of knowledge as to what physical signs of the cardio-va.«cular .system coulil he classified under the normal was a great handicap to overcome. Moreover, England was short of man power; uuderdevelopcd men had to be


used for front-line duty, convalescence from acute infections was apt to be too short, and underaged as well as overaged men were constantly exjw.sed to the demands of campaigning. Again, his hospital was well away from the firing line, and, as a result, his patients had passed through a series of base hos])it^ds before he saw them, and by tiiat time they had l)e(ome thoroughly convinced, from their diagnosis cards and from information ol)tained from difi'erent medical officers, tliat they iiad delinite lieart trouble, whicli, to tiieir minds, was incurable, ("ertaiidy the sul)jective !iym|)toms strengthened that conception, and, moreover, four years of warfare had deprived some of them of any excess enthusiasm for staying in tiie army if there were any fair way of getting out.

Dr. Lewis and his staff had made many careful studies of their patients.' Controlled pharmaeo-dynamic tesfj^ were employed with the following results: Atropin showed no difference between patient and control. Apocodeine generally gave a greater pulse-rate rise and there was a more marked cutaneous reaction in the patient group. Amyl nitrite had the same result. Pilocarpin ])roduced more marked reaction among the jjatients. Digitalis had no more i)ower to control the pulse-rate of the patients than of the controls, and the subjective symjjtoms were uninfiuenced. Adrenalin, on the other hand, showed that the patients had a definite susccpti-* bility to this drug so far as subjective symptoms go, but the rise in pulse-rate and blood pressure was about the same in the two groups. Another interesting study showed that the ]3atients were ajit to require a longer period after measured exercise before tlieir pulse-rate lost its increase — five minutes, often, as compared to two minutes in the average control. X-rays and electrocardiograms showed no essential difference in the two groups. All in all, the work suggested that the disorder had to do with the peripheral nerves rather tlian with the central nervous sj'stem, and there seemed to lie a !iy])ersensitiveness of the sympatlietic with no cliange in the vagal system.

After a stay of two moiitiis in England, the writer was .sent inick to France and assigned to duty at Convalescent Camp Number Two. This camp was the convalescent section for a large ba.se hospital group, and had a capacity of 2000 patients. The work was very active and, at first, was complicated by the considerable amount of organization that was to be expected in the estai)lishment of a new system. (Jraduated exercises were instituted under military discipline, so that each ])aticnt was tested as to his ca|)acity for work ailTl was not discharged to front-line duty unless he was able to jierform comparable work. Each patient was carefully studied during his stay and any indicated laboratory tests were made. Mr)reover, a followup system was instituted wliich enal)icd us to arrive at definite conclusions alxiut the method of treatment, and (•ontrolle- E. Handerson. A. M. M. D. With a Biography of the Author. 1918. 8°. 77 pages. The Cleveland Medical Library Association, Cleveland, Ohio.

Human Infection Carriers. Their Significance, Recognition and Management By Charles E. Simon, B. A.. M. D. 1919. 8'. 250 pages. Lea & Febigcr. Philadelphia and New York.

Michigan Slate Board of Health. Forty-aixth Annual Report of the Secretary of the State Board of Health of ilie State of Michigan for the Fiscal Year Ending June 30, 1918. 8'. 180 pages. Fort Wayne Printing Company, Fort Wayne, Indiana. 1919.


Clinical Microscopy and Chemistry. By F. A. McJunkin, M. A., M. D. Illustrated. 1919. 8°. 470 pages. W. B. Saunders Company, Philadelphia and London.

Essentials of Surgery. A Textbook of Surgery for Students and Graduate Nurses and for Those Interested in the Care of the Sick. By Archibald Leete McDonald, M. D. 46 illustrations. Lippincotfs Nursing Manuals, 1919. 8°. 265 pages. J. B. Lippincott Company, Philadelphia and London.

Tuberculosis of the Lymphatic System. By Walter Bradford Metcalf. M. D. 1919. 8°. 216 pages. The Macmillan Company, New York.

The Early Treatment of War Wounds. By Colonel H. M. W. Gray. 1919. 8°. 299 pages. Henry FYowde; Hodder & Stoughton, London. Oxford University Press, American Branch, New York.

Lice and Their Menace to Man. By Lieut. L. L. Lloyd, R. A. M. C. (T.) With a chapter on Trench Fever. By Major W. Byam, R. A. M. C. 1919. 8'. 130 page;;. Henry Frowde; Hodder & Stoughton, London. Oxford University Press, American Branch, New York.

The Operative Treatment of Chronic Intestinal Stasis. By Sir W. Arbuthnot Lane, Bart, C. B. Fourth edition revised and enlarged. 1918. 8°. 328 pages. Henry Frowde; Hodder & Stoughton, London. Oxford University Press, American Branch, New York.

Surgical Clinics of Chicago. Vol. 3, No. 1. With 75 illustrations. 1919. 8°. 236 pages. W. B. Saunders Company, Philadelphia and London.

The Whole Truth About Alcohol. By George Elliot Flint With an Introduction by Dr. Abraham Jacobi. 1919. 12°. 294 pages. Macmillan Company, New York.

.Military Surgery of the Ear. Xose and Throat. By Hanau W. Loeb, M. D. Medical War Manual No. 8. 1918. 24°. 176 pages. Lea & Febiger, Philadelphia and New York.

Vegetative Keurology. The Anatomy, Physiology, Pharmacodynamics and Pathology of the Sympathetic and Autonomic Nervous Systems. By Dr. Heinrich Hlgier. Authorized translation by Walter .Max Kraus, A. M.. M. D. Nervous and Mental Disease Monograph Series No. 27. 1919. 8°. 144 pages. Nervous and Mental Disease Publishing Co., New York and Washington.

A Study of the Mental Life of the Child. By Dr. H. Von HugHellmuth. Translated from the German by James J. Putnam, M. D. and .Mabel Stevens. B. S. Nervous and Mental Disease Monograph Series No. 29. 1919. 8°. 154 pages. Nervous and Mental Disease Publishing Company, Washington.

The Anatomy of the Peripheral Serves. By A. Melville Paterson, M. D., F. R. C. S. 1919. 8°. 165 pages. Oxford Medical Publications. Henry Frowde; Hodder & Stoughton, London.

Surgiral Aspects of Typhoid and Paratyphoid Fevers. Founded on the Huntcrian Lecture for 1917 — Amplified and Revised. By A. E. Webb-Johnson, D. S. O. With foreword by Lieut.General T. H. Goodwin, C. B., C. M. G., D. S. O. 1919. 8°. 190 pages. Henry Frowde: Hodder & Stoughton, London.

A TcTt-Book of Biology. For Students In General, Medical and Technical Courses. By William Martin Smallwood. Ph. D. (Harvard) Third edition, enlarged and thoroughly revised. Illustrated with 235 engravings and S plates in color and monochrome. 1918. 8°. 30C pages. LeLa & Febiger, Philadelphia and New York.


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[No. 343


THE JOHNS HOPKINS HOSPITAL KEPORTS


VOLTTME I. 423 pages, 99 plates.

VOLUME II. 570 pages, with 28 plates and figures.

VOLUME III. 766 pages, with 69 plates and figures.

VOLUME IV. 504 pages, 33 charts and illustrations.

VOLUME V. 480 pages, with 32 charts and illustrations.

The Miilnrial Fevers of Baltimore. By W. S. Thayek, M. D.. and

J. Hewetson. M. D. A Study of some Fatal Cases of Malaria. By Lewellys P. Barker. 11. B.

Studies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Blumer. M. D., Simon Flexner, M. D.. Walter Heed, M. D., and II. C. Parso.ns. M. D.

VOLUME VI. 414 pages, with 79 plates and figures.

VOLUME VII. 537 pages with illustrations.

VOLUME VIII. 552 pages with illustrations.

VOLUME IX. 1060 pages, 66 plates and 210 other illustrations. Contributions to the Science of Medicine.

Dedicated by Ms Pupils to William Henky Welch, on the twenty-fifth anniversary of his Doctorate. This volume contains 38 separate papers.

VOLUME X. 516 pages, 12 plates and 25 charts.

VOLUME XI. 555 pages, with 38 charts and illustrations.

VOLUME XII. 648 pages, 12 plates and other illustrations.

VOLUME XIII. 605 pages, with 6 plates, 201 figures, and 1 colored chart.

VOLUME XIV. 632 pages, with 97 figures.

Studies in Genito-Urinary Surgery.

The Treatment of Prostatic Hypertrophy by Conservative Perineal Prostatectomy. An analysis of cnses and results based on a detailed report of 145 cases. By Hugh H. Young, M. D.

Recto-Urethral Fistulee. Description of New Procedures for their Prevention and Cure. By Hugh H. Young. M. D.

The Early Diagnosis and Radical Cure of Carcinoma of the Prostate, being a study of 40 cases and presentation of a radical operation which was carried out in tour cases. By Hugh H. Young, M. D.

VOLUME XV. 542 pages, with 87 Illustrations.

Twelve papers on pneumonia- By Dns. Ciiatard, Fabyan, Emerson,

Marshall, McCrae. Steiner, Howard and Hanes. A Study of Diarrhoea in Children. J. H. Mason Knox, Jr., M. D., and

Edwin H, Schorer, M. D. Skin Transplantation. By John Staige Davis, M. D. Epidemic Cerebrospinal Meningitis and Serum Therapy at The Johns

Hopkins Hospital. By Frank J. Sladen, M. D.

VOLUME XVI. 670 pages with 151 figures.

Studies in the Experimental Production of Tuberculosis in the Genitourinary Organs. Bv George Walker. M. D.

The Effect on Breeding of the Removal of the Prostate Gland or of the Vesiculae Seminales. or of Both : together with Observations on the Condition of the Testes after such Operations on White Rats. By George Walker, M. D.

Scalping Accidents. By .John Staige Davis, M. D.

Obstruction of the Interior Vena Cava with a Report of Eighteen Cases. By J. Hall Pleasants. M. D.

Physiological and Pharmacological Studies on Cardiac Tonicity In Mammals. By Percival Douglas Cameron, M. D.

VOLUME XVII. 686 pages with 21 plates and 136 figures.

Free Thrombi and Ball Thrombi in the Heart. By Joseph H. Hewitt,

M. D. Benzol as a Leucotoxin. By Lawrence Selling. M. D. Primary Carcinoma of the Liver. By Milton C. Winternitz, M. D. The Statistical Experience Data of The Johns Hopkins Hospital. Baltimore,

Md.. 1892-1911. By Frederick L. Hoffman. LL. D., F. S. S. The Origin and Development of the Lymphatic System. By Florence R.

Sarin. M. D. The Nuclei Tuberis Laterales and the So-called Ganglion Opticum Basale.

By Edward F. Malone, M. D. Venous Thrombosis During Myocardial InsufBciency. By Frank J. Sladen.

M. D., and Milton C. Winternitz. M. D. Leuk-Temia of the Fowl : Spontaneous and Experimental, By Harry C.

SCHMEISSER. M. D.

VOLUME XVIII. 445 pages with 124 figures. Fasciculus I.

A Study of a Toxic Substance of the I'ancroas. By E. W. Goodpasture. M. "D.. and (Ieorge Clakk. M. D.

Old Age in Relation to Cell-overgrowth and Cancer. By E. W. Goodpasture, M. D., and G. B. WiSLOCKi. M. D.

The Effect of Removal of the Spleen Upon Metabolism in Dogs ; Preliminary Report. By J. H. King. M. D.

The Effect of Removal of the Spleen Upon Blood Transfusion. By J. H. King, M. D.. B. M. Bernheim. M. D.. and A. T. Jones, M. D.

Studies on Parathvroid Tetany. By D. Wright Wilson, M. D., Thornton Stearns, M. D., J. H. Janney, Jr., M. D., and Madge DeG. Thcblow, M. D.

Some Observations on the Effect of Feeding Glands of Internal Secretion to Chicks. By M. C. Winternitz, M. D.


Spontaneous and Experimental Leukaemia in the Fowl. By H. C.

SCHMEISSEII. M. D.

Studies on the Relation of Fowl Typhoid to LeukEemia of the Fowl. Bj

M. C. Winternitz. M. D., and U. C. Schmeisser, M. D. Hyaline Degeneration of the Islands of Langerhans in Pancreatic Diabetes.

By M. C. Winternitz. M. D. Generalized Miliary Tuberculosis Resulting from Extension of a Tubercular

Pericarditis Into the Right Auricle. By M. C. Winternitz. M. D. Acute Suppurative Hypophysitis as a Complication of Purulent Sphenoidal

Sinusitis. By T. R. BoGGS. M. D.. and M. C. Winternitz, M. D. A Case of Pulmonary Moniliasis in the United States. By T. R. BoGGS,

M. D., and M, C. Pincokfs, M. D. Gaucher's Disease (A Report of Two Cases in Infancy). By J. H. M.

Knox, M. D., H. R. Wahl. M. D., and H. C. Schmeisser, M. D. A Fatal Case of Multiple Primary Carcinomata. By E. D. Plass, M. D. Congenital Obliteration of the Bile-ducts. By James B. Holmes. M. D. Multiple Abscesses of the Brain in Infancy. By James B. Holmes. M. D. Gastric Carcinoma in a Woman of Twenty-six Years. By R. G. Hussey,

M. D. Subdiaphragmatic Abscess with Rupture Into the Peritoneal Cavity Following Induced I'ncumothorax for Pulmonary Iliemorrhage. By R. G

Hussey, M. D. Heart Block Caused by Gumma of the Septum. By E. W. Bridgeman,

M. D., and H. C. Schmeisser, M. D. Analysis of Autopsy Records.

A. The Johns Hopkins Hospital. (Table Showing I'ercentage of

Autopsies.)

B. The City Hospitals, Bay View. (Table Showing Percentage of

Autopsies.) '* The Monday Conferences."

Clinical Representatives on the Staff of the Department of Pathology. Donation.

Fasciculus II. The ROle of the Autopsy in the Medicine of To-day. By M. C. Winternitz,

M, D. Experimental Nephropathy in the Dog. Lesions Produced by Injection

of B. hronchisepticus into the Renal Artery. By M. C. Winternitz.

M. D.. and William C. Quinby. M. D. Mesarteritis of the Pulmonary Artery. By M. C. Winternitz, M. D., and

H. C. Schmeisser. M. D. A Clinical and Pathological Study of Two Cases of Miliary Tuberculosis of

the Choroid. By Robert L. Randolph, M. D., and H. C. Schmeisser,

M. D. The Blood-vessels of the Heart Valves. By Stanhope Bayne-Jones, M. D. Equilibria in Precipitin Reactions. By Stanhope Bayne-Jones, M. D. Carcinoma of the Pleura with Hypertrophic Osteoarthropathy. Report of

a Case with a Description of the Histology of the Bone Lesion. By

Stanhoi'E Bayne-Jones. M. D. The Interrelation of the Surviving Heart and Pancreas of the Dog in Sugar

Metabolism. By Admont H. Clark, M. D. Congenital Atresia of the Esophagus with Tracheo-Esophageal Fistula

Associated with Fused Kidney. A Case Report and A Summary of the

Literature on Congenital Anomalies of the Esophagus. By E. D.

Plass M. D. Ectopia Cordis, with a Report of a Case in a Fifteen-Month-Old Infant.

By James B. Holmes, M.D. Studies in the Mechanism of Absorption from the Colon. By Samuel

Gni.DSCHMiDT. M. D., and A. B. Dayton. M. D. Report of Two Fatal Cases Following Percy's Low Heat Treatment of

Carcinoma of the Uterus. By V. N. Leonard, M. D., and A. B. Dayton,

M. D. The Relationship in Typhoid Between Splenic Infarcts and Peritonitis

I'nassnciatorl with Intestinal Perforation. By A. B. Dayton, M. D. Left Duodenal Hernia. By A. B. Dayton, M. D.

Histological as Related to Physiological and Chemical Differences in Certain Muscles of the Cat. By H. Hays Bullard, M. D. A Method of Clearing Frozen Sections. By H. Hays Bullard. M. D. On the Occurrence and Significance of Fat in the Muscle Fibers of the

Atrio-Ventricular System. By H. Hays Bullard. M. D. Studies on the Metabolism of Colls in vitro. 1. The Toxicity of a-Amino Acids for Embyonic Chicken Cells. By Montrose T. Burrows, M. D.,

and Clarence A. Neymaxn. M. n. The Significance of the Lunula of the Nail. By Montrose T. Burrows,

M. D. The Oxygen Pressure Necessary for Tissue Activity. By Montrose T.

Burrows, M. H. The Functional Relation of Intercellular Substances in the Body to Certain Structures in the Egg Cell and Unicellular Organisms. By

Montrose T. Burrows. M. D. Studies on the Growth of Cells in vitro. The Cultivation of Bladder and

Prostate Tumors Outside the Body. By Montrose T. Burrows, M. D.,

J. Edward Burns, M. D., and Yosmo Suzukl. M. D. The Study of a Small Outbreak of I'oliomyelitis in an Apartment House,

Occurring in the Course of an Epidemic in a Large City. By Montrose

T. Burrows. M. D.. and Edwards A. Park. M. D. Papilloma of the Larvnx. Report of a Case Treated with Radium with

Resultant Chronic Diffuse Thyroiditis. By William C. Duffy, M. D. Analysis of Autopsy Records. Autopsy Statistics.

(n) Bav View.

(b) Johns Hopkins Hospital. Report of the Photographic Department. General Improvements. Donations.

The set of eighteen volumes will be sold, bound in cloth, for $100.00 net. Volume II will not be sold separately. Volumes I. Ill, IV. V. VI. VII. VIII. X, XI, XII, XIII, XIV, XV, XVI, XVII and XVIII will be sold for $6.00, net. bound in paper, and $5,50, net, bound in cloth. Volume IX will be sold for $10.00 net. Orders should be addressed to The Johns Hopkins Press, Baltimore. Md.


The Johns Hopkins Hospital Bulletins are issued monthly. They are printed ly the LORD BALTIMORE PRESS, Baltimore. Subscriptions, $3.00 i iicar (foreign postage, 50 cents), may be addressed to the publishers, THE JOHNS HOPKTNS PRESS, BALTIMORE ; single copies n-iU be sent by nail tor fifty cents each. Single copies may also be procured from the BALTIMORE NEWS CO.. Baltimore.


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THE JOHNS HOPKINS HOSPITAL

Entered aa Second-Clan Matter at the Baltimore, Uarj-land, PostofBcc Aecertaace (or mailing at ipecial rate ol postage provided tor in Section 1103, Act of October S, 1917. Aothorized on Jul7 S, 1818.


Vol. XXX— No. 344]


BALTIMORE. OCTOBER, 1919


IPrlce, 50 Cents


CONT

PAGE

Dr. Howard A. Kelly. Professor of Gynecology in Tlie .Tohns Hopkin-i University and Uynecologistin-Cliief to The .Tolins Hopkin.s Ho>|)ital. (Illustrated.)

By TiloM.\s S. CiLLEN 287

Bibliography of Howard A. Kelly, M. D., LL. D., Hon. F. R. C. S.

By MiNMK U'BiGiiT Hlogo 293

Chronic Pemphigus Vegetans of Several Years' Ouration. (Illustrated.) Bv Lewellts F. Babkeb and David W. Cabteb, Jb. . 302


ENTS

.Studies oil Blood Sugar. IV. Klfects upon the Blood Sugar of the Repeated Ingestion of Glucose.

By Lori.s Hammax and I. I. HinsciiMAN .... Benzine Poisoning, with Report of a Chronic Case.

By RrssELL L. Haden, M. D

The Reaction of Monkeys to the Inoculation of Measles Blood.

By -Andrew Watso.n Seli.aru.s

Xotes on Xew Books, .314

Books Received . 315


30G


301


.1


DR. HOWARD A. KELLY

PROFESSOR OF (rYNECOLOGY IN THE JOHNS HOPKINS UNIVERSITY AND GYNECOLOGIST-IN-CHIEF TO THE JOHNS HOPKINS HOSPITAL

Bv Thomas S. Cullen


Howard Atwood Kelly was born in Camden, New Jersey, on Febniary 20, 1858. He received his bachelor's dejrrce at the University of Pennsylvania in 1877 and graduated in medicine from the same university in 1882. He settled in Philadel|)hia and early attracted attention by his marked success in iiandliii^ cases therctofure .<up|)o^ed to l)e inoperable.

During the year 1882-83 Dr. Kelly, while a roi^ident physician in the Episcopal Hospital, built up a remarkably good gynecological dispensary clinic, demonstrating what might be accomplished by paying especial attention to this group of hitherto much neglected cases. After his interneship was completed he began practice in an office on West Front Street in Philadelphia, and established a modest hospital on D Street consisting of two rooms on the second Hoor of a two-story house; Mrs. Wood, the wife of a working-man, taking care of the patients.

In 1^84 the young surgeon removed his hospital to a threestory hou.-io on Cumberland Street, and a year and a half later to Xorris .Square to a four-story hou.'se on Diamond Street. Here the new hospital grew rapidly and became the Kensington Hospital. Established in 1883, it was incor[)orated in 1887, and has been supported by voluntary contributions. At this period Dr. Kelly took up his residence on Hancock Street across the square from the hospital.

Dr. Kelly has always been an indefatigable worker and his e.nrly labors in Philndelfihia, especially in the Kensington


Ifospifal. are vividly remembered to this day. Thus, when an important post became vacant in the University of Pennsylvania and several men were being considered for the position. Dr. Osier, when asked whom he favored, replied, " I am backing the Kensington colt." ' With his characteristic excellent judgment of men, he had picked out Dr. Kelly as a man of exceptional promise and it was little wonder that a short time later Kelly was called from the University of Pennsylvania to The .Johns Hopkins Hospital to become its first professor of gynecology and obstetrics.


'Since the above was written the following note has been received by Ijr. Hurd from Dr. Csler;

"The circumstances were these: Goodell had re.slgnod. and there was no end of discussion as to who should take his place. On several occasions I had gone to Kensington to see Kelly operate, and 1 happened to mention to Pepper that I had never seen anylMdy do abdominal work with the same skill. He knew of Kelly, but had not, I believe, seen him operate, which he Immediately arranged to do. Then one evening at tlie Biological Club, Horatio Wood and Mitchell were discussing Goodell's successor, and I said that Pepper and I were backing a dark horse — a Kensington colt. With that. Leidy chipped In with a remark that if it was young Howard Kelly, his former prosector, he would iMick him heartily. This is how I remember the story.

•' How extraordinarily successful he has been! Only those of us who know the work as It was, realize how much the profession (and the public) owes to such men as Kelly. \


288


[No. 34-t


Kelly went abroad for the first time in 1886, visiting England, Scotland and Germany. Among the well-known men whom he met were : Brennecke, in Magdeburg ; Sanger, in Leipzig ; Sehroeder and Martin, in Berlin : Fehling, in Basle ; Hegar, in Freiburg: Koeberle, in Strasburg; and Berry Hart, in Edinburgh.

While in England Dr. Kelly attended the meeting of the British Medical Association at Brighton. Lawson Tait gave the address on surgery; his topic was gall-bladder surgery. Kelly was invited to take part in the proceedings of the gjnecological section and reported a case in which he had diagnosed and removed an unruptured extra-uterine pregnancy. Tait, who at this period was studying extra-uterine cases, in discussion claimed that the diagnosis was a matter of " expert instinct " and therefore hardly attainable by the average man. Kelly in reply pointed out that in his case the signs were: a definite cessation of the menses, a small tumor to the right of the uterus, gradually increasing in size month by month and very tender, followed by a cessation of growth and a gradual shrinkage; at operation an unruptured right tubal pregnancy was found. Tait remarked that he did not concur in the " cock-sure diagnosis " of the young man and made light of his communication. Thus, early in his career, the future leader of American gj-necology had an encounter with the then dominant figure in abdominal surgery in England.

In 1888 he again visited Europe, this time in company with Hunter Robb and Constantine Goodell. In Berlin he met Virchow, secured permission to work on cadavers in the Charite and spent much time in determining from an anatomical standpoint just how the ureters could best be catheterized. From Berlin the party went to Prague and saw Pawlik catheterize the ureters through the water-filled bladder.

In 1889 he returned to Germany on a still more important mission. On June 27, he was married to Letitia Bredow in the Danzig Cathedral.

In 1888 Dr. Kelly was appointed associate professor of obstetrics in the University of Pennsylvania and held this position until his departure for Baltimore, in 1889.

In 1889, at the age of 31, he entered upon his duties as professor of gynecology and obstetrics in The Johns Hopkins University and as gynecologist and obstetrician-in-chief to The Johns Hopkins Hospital. At that time The Johns Hopkins Medical School was still a thing of the future, but the hospital and pathological laboratory were already giving courses to a large number of medical men and surgeons who came to do postgraduate work.

In these early days Dr. Kelly's hospital \"ork was limited exclusively to gynecology, for as yet no accommodations had been .supplied for obstetrical cases. Witli the opening of tlie medical school in 1893 it became imperative to provide facilities for caring for obstetrical patients. This branch was gradually developed by the efforts of Dr. J. Whitridge Williams, and in 1899 the two important branches, gynecologj' and obstetrics, were separated and became independent departments. From then on Dr. Kelly concentrated all his endeavors to the develop


ment of gynecology. Garrison terms Professor Kelly " a recognized leader of his science in America." He adds :

He was a pioneer in the use of cocaine anesthesia (1884), in the treatment of retroflexion of the uterus by suspension (1887), in the introduction of the operations of nephro-ureterectomy, nephroureterocystectomy, vertical bisection of the cervix for tumors and inflammation, and ideal appendectomy; the procedures of aeroscopic examination of the bladder and catheterization of the ureters, exploration of the rectum and sigmoid flexure, diagnosis of ureteral and renal calculi by wax-tipped bougies, diagnosis of hydronephrosis by injection and measurement of the capacity of the renal pelvis, operation on the kidney by the superior lumbar triangle, treatment of malignant tumors by radium, and various improvements in the treatment of vesico-vaginal fistulae. He is the inventor of the Kelly pad, new rectal and vesical specula, and his Operative Gynecology (1898) and Medical Gynecology (1908). both illustrated with Max Brodel's drawings, are full of improvements in the science which have made these books among the best American Treatises of the time.

He is also known by his valuable historical contributions on hypnotism, American gynecology, appendicitis, vesico-vaginal fistula, medical botanists, medical illustration, and American medical biography (1912). His "Stereo-Clinic" (1910-13) is a permanent photographic record of recent surgical procedures.

The tendency of recent gynecology to become merged into general abdominal surgery has been wittily signalized by Dr. Kelly as follows:

" The vital question which now affects gynecology is this: Is she destined to live a spinster all her days? For we see her on one hand courted by her obstetrical ancestor, who seeks to draw her once more into an unholy, unfruitful alliance, destined to rob her of virility, to be rocked into innocuous desuetude for the rest of her days' in the obstetric cradle, sucking the withered ancestral finger in the vain hope of nourishment (with apology for mixed metaphor). On the other hand, we see her wooed by a vigorous, manly suitor. General Surgery, seeking to allure her from her autonomy into his own house, under his own name, obliterating her identity. "

No one connected with Tlie Johns Hopkins Hospital has written more or has added more to the knowledge of his department than has Dr. Kelly. A glance at his bibliography will give the reader a fair idea of the magnitude of his work. Here it is only possible to mention his more important papers.

The first article from his pen was entitled " Some Eare and New Anomalies in Man ; with Three Cases of Double Femoral Artery" (1882).

Among his subsequent papers we find " An Ovarian Cyst Weighing One Hundred and Sixteen Pounds Successfully Removed "(1885) ; " Hysterorrhaphy "(1886) ; " Extra-Uterine Pregnancy" (1886); "Asepsis Not Antisepsis" (1886); Csesarean Section " (1888) ; and " Palpation of the Ureters in the Female" (1888).

In The Johns Hopkins Hospital Bulletin of January. 1890, appears his article on " Hysterorrhaphy." This operation was a marked improvement on the method hitherto employed to hold up the retroverted or retrofiexed uterus, and remained in vogue for nearly 20 years, after which Dr. Kelly himself abandoned it for the improved method of shortening the round ligaments — a method which holds the uterus up equally well


^Garrison, History of Medicine, 2. ed.. Phila., W. B. Saunders, 1917, 639-640.


THE JOHNS HOPKINS HOSPITAL BULLETIN. OCTOBER, 1919


PLATE XXXVI



I Hi IIOWAWD A. KKM.V


Professor of Gviucology in Tli.- Johns Hopkins University and Cynerologistin-Chlet to The Johns Hopkins Hospital for thirty years— from the opening of the Hospital In 18S9 to 1919.


OCTOBEK, 1919]


289


and which is rarely, if ever, followed by difficulties at childbirth.

From his article " The Gynecological Operating Room in The Johns Hopkins Hospital, and the Antiseptic ajul Aseptic Bules in Force," published in 1890, we get a pleasant glimpse of Uie plan of proi-edure followed in the pioneer days of the hospital. One can hardly realize that at that time after nearly every abdominal operation a glass drainage-tube was used for several days and that each day this glass tube was not only pumped out with a syringe to which a rubber tube was attached, but once a day the tube was turned around in order that the omentum might not insinuate itself tli rough the small holes in it and become fixed.

Dr. Kelly's interest in the \ireteral work continued and in 1892 we find a paper entitled " My Recent Ureteral Work." In 1892 he devoted much time to the study of the bladder and ureter and in these investigations he was assisted by Albert L. Stavelv, William W. Russell, Thomas S. CuUen and John G. Clark.'

The Bulletin' for 1893 contains the results of his labors under the title " The Examination of the Female Bladder and the Catheterization of tlie Ureters under Direct Inspection." For years he had been catheterizing the ureters with varjnng success by paijiation, or as he called it by the fishing method." Dissatisfied, however, \vith this relatively blind method, he decided to put the patient in the knee-chest posture and introduce a tube into the bladder hoping that this viscus would balloon out as the vagina does when the speculum is introduced. This procedure succeeded admirably and he was able to see clearly not only the ureteral orifices, but also nearly all parts of the bladder. At once he grasped the possibilities of this method of studying the bladder and ureters in women and immediately developed and perfected the necessary instruments. This armamentarium was so complete that hardly another instrument, vesical or ureteral, has been added since. To Dr. Kelly alone belongs the credit of not only discovering, but also of working out in detail this fundamental and important method of gaining an insight into the secrets of the bladder, ureters and kidneys. The procedure has been adopted throughout the world.'

Profiting by his experience in distending the bladder with air when the patient was in the knee-chest posture, he applied the same principle to the inspection of the rectum, and finding the exposure equally good he had a series of proctoscopes made. These varied in length and caliber and enabled the surgeon to inspect the rectum and sigmoid for a distance of from eight to ten inches and to bring clearly into view pathological conditions that otherwise would have been overlooked. Proctologists agree that the Kelly method has aided tliem greatly in the study and treatment of diseases of the rectum.'

In no department of abdominal surgery has there been greater advance tlian in the handling of uterine myomata.

• A more detailed report of this method appeared In the American Journal of Obstetrics for 1894.

  • "A New Method of Examination and Treatment of Dtaeasea

of the Rectum and Sigmoid Flexure." Annalt of Surgery. 1895.


In the early days of the hospital it was customary to place a rubber ligature around the growth and then cut the tumor away. Sometimes the stump would slip through the rubber ligature and alarming hemorrhage would follow. Many surgeons must be credited with a share in simplifying the technique of removing the myomatous uterus, but Kelly's " left and right method " must be regarded as one of the most important advaJices in the simplification of such hysterectomy cases.'

In The Johns IIopki.vs Hospital Bulletin of 1898 there appeared an article by Dr. Kelly entitled " The Catheterization of the Ureters in the Male through an Open Cystoscope with the Bladder Distended with Air by Posture." The cystoscope wiis similar to his female cystoscope, but a good deal longer. With this instrument the late Dr. James Brown, a pioneer urologist, demonstrated catheterization of the ureters in the male before The Johns Hopkins Hospital Medical Society.

Probably one of the most practical operations independently devised by Dr. Kelly was the apron method ' of treating complete perineal tears. I say independently, because in the Atneri^^an Journal of Obstetrics, 1899, XL, 515, Dr. Kelly says : " I find, through the kindness of Dr. Chadwick, that Dr. Wanoii has some time since described the apron method of treating complete tears and I desire to accord him full credit."

In 1899 Dr. Kelly digressed to write a paper on "The Recognition of the Poisonous Serpents of North America." He had long been interested in snakes and for several years many of his visitors had entered his library on Eutaw Place very cautiously, not knowing just what surprise might be in store for them. No one who was at that memorable meeting of The Johns Hopkins Hospital Jlcdical Society the night he spoke on snakes will ever forget the tenseness of the audience ; some of the brave ones sat up near the front apparently unconcerned, while the more timid migrated to the back seats, some actually sitting on the backs of the seats. When Dr. Kelly grasped a large diamond-headed rattler by the nape of the neck with his left liand, held tiie tail in his right hand and with the inde.\ finger of his right hand pointed out the more important marks on the snake's head, a shudder ran through the audience. A sigh of relief was clearly audible when the snake had been put back into the bag. At this moment, however, through the bag it bit Dr. Kelly's finger and the audience awaited breatblessly and in alarm for the after effects. Dr. Kelly sucked his finger, looked very pale, but went right along with his talk. In a few minutes the meeting closed and he returned home none the worse for his experience. A few hours before the meeting the snake had been teased and had discharged nearly all, if not all, of its venom.


'For a detailed description of this method soe: "Hysterectomy and HyFtero-Salplngo-Oophorectomy by Continuou-s Incision from Left to Itlght or from Right to Lett." J. H. H. Buli.ctin, 1896.

"This method was described In the Journal of the American Medical Association, 1898, XXXT. 1469.


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[No. 344


In 1899 Dr. Kelly published a timely paper entitled " The Exploration of the Abdomen as an Adjunct to Every CeUotomy." We now know that when the abdomen is opened it should be most carefully explored to see that no pathological lesion has been overlooked. In 1899 few realized liow essential was a systematic examination of the abdominal cavity.

In 1900 he published another epoch-making paper entitled " Ureteral Calculus ; its Diagnosis by Means of the WaxTipped Bougie, Escape of the Calculus per vias naturalcs After Forcible Dilatation of the Ureteral Orifice." Here was a method that gave positive evidence in the majority of cases when a stone was present in the iireter and usually when one existed in the pelvis or in the kidney. At the present day the X-ray will generally reveal stones in the kidney, in the pelvis and in the ureter, but every now and then the wax-tip will show a tell-tale scratch-mark when the X-ray has failed to give any e-\adence of the existing calculus. The Kelly scratch-mark method is a most valuable detector of stone ; it is here to stay.

In the past nearly all pelvic surgeons have encountered dense pelvic inflammatory masses so glued to one another and to the pelvic wall that their removal has been fraught with the greatest difficulty. In 1900, under the title " The Removal of Pelvic Inflammatory Masses by the Abdomen after Bisection of the Uterus," Dr. Kelly gave us a method that enables us to handle otherwise inoperable cases.'

In 1910 Dr. Kelly contributed to Surgery, Gynecology and Oh-^tetrics a paper entitled " Lipectomy, an Operation for Removal of Redundant Fat from the Abdominal Wall." In this operation a large wedge of the redundant fat is removed and the edges of the wo\md in the fat and skin are then approximated. Wliile this simple operation has given many a patient physical relief, it has a more important sphere of usefulness. Take, for example, a patient with a superabundance of fat in the lower abdomen who may have at the same time a carcinoma of the body of the uterus. In order to expose the uterus satisfactorily a very long abdominal incision must be made and the distance from the surface to the pelvis is very great. By a preliminary lipectomy the thick abdomen is converted into a very thin one at the site of the operation and the litems can then be removed with comparative ease.

For years Dr. Kelly has been interested in the surgical treatment of cancer and was often troubled by the large number of inoperable cases presenting themselves in the clinic. He became impressed by the work of Wickham, who was a personal friend, and within a short time began the use of radium. He presented a paper on radium at a meeting of the Baltimore Medical Society, April 11, 1913, which was published in the Maryland Medical Joui-nal in June, 1913, imder the title "A Talk on Radium." In Internation-al Clinics in 1914 we find another interesting article by Dr. Kelly entitled " What Radium can Do," and in the Journal of the American Medical Association of the same year, " Radium in the Treatment of


' After publication of tlie approved metliod. Dr. Kelly found that his procedure had been anticipated by Dr. J. L. Faure, of Paris. His method, however, was devised without any knowledge of Dr. Faure's work.


Uterine Hemorrhage and Fibroid Tumors," by Dr. Kelly and Dr. Curtis F. Burnam. In the Journal of the American Medical Association in 1915 Kelly and Burnam gave their results with " Radium in the Treatment of Carcinomas of the Cervix Uteri and Vagina." In 1918, Professor Kelly contributed to Surgery, Gynecology and Obstetrics a paper entitled " Two Hundred and Ten Fibroid Tumors Treated by Radium."

From boyhood, Dr. Kelly has been greatly interested in natural history and in outdoor life and has been particularly fond of mineralogy. He spent several summers in Mexico looking carefully into the subject of mining and the extraction of precious metals. The knowledge thus obtained proved most valuable when it was definitely determined that there were deposits of radium in Colorado. Secretary Lane, of the Department of the Interior, was quick to see what an ample supply of radium would mean to the people of this country in the treatment of cancer. Dr. Kelly and Dr. James P. Douglas, of New York, imdertook to extract radium from the Colorado deposits and Secretary Lane, with wise foresight, placed at their disposal the best brains of the mining experts in his department. Professor Joseph A. Holmes, head of the Bureau of Mines, rendered invaluable service in all phases of the project.

Dr. Douglas gave his share of the radium thus obtained to the General Memorial Hospital of New York, and Dr. Kelly's share came to Baltimore. Kelly and his associate, Burnam, have five grams, the largest single supply of radium in the world. The Johns Hopkins Hospital is imder many obligations to them for their liberality in giving free radium treatment to many poor but worthy people who have needed such jjrocedures at the hospital in recent years.

Let us now turn to the books published by Dr. Kelly. In 1898 there appeared from the Appleton press " Operative Gynecology," in two large volumes, which covered the subject in such a manner that it instantly commanded the attention of the surgical world both here and abroad. It was no stereotyped production; every page breathed the individuality of the author and portrayed his methods and his ideas. It also embodied the many new and improved operations that he had devised.

Shortly after Kelly decided to publish " Operative Gynecology " he asked the late Professor Franklin P. Mall where lie could procure a good artist and received the name of Max Brodel, who had made excellent illustrations for Professor Karl Ludwig, the famous physiologist of Leipsic. In 1894 ho secured his services. Brodel took hold with enthusiasm and with tmusual fidelity pictured Kelly's operative procedures and also the gross and microscopic specimens. Not only that, he brought into the pictures such a marked degree of artistic finish that the illustrations elicited unstinted praise. By this book the professor of gynecology, already well-known, became the recognized leader in his specialty, and Brodel's illustrations set a new standard for medical illustrations in the United States. " Operative Gynecology " had numerous printings and a new edition appeared in 1906.


THE JOHNS HOPKINS HOSPITAL BULLETIN, OCTOBER, 1919


PLATE XXXVII



DR. HOWARD


Dr Kelly at 31. wheii ho entered upun liij. (Uni.^ as ITofessor of GynecoloKV and Obstetrirs in The .lolins Hopkins Inivpislty and as CJynecologist and Obstetridanin-Chlef lo The Johns Hopkins Hospital.


October, 1919]


In 1905 there appeared a large volume entitled " The Vermiform Apjicndix." The authors were Dr. Kelly and Dr. Elizabeth Ilurdon. This work is a mine of information and the subject has been considered from every sUnidpoint. It goes thoroughly into the pathology and describes the operative technique in a lucid manner. Chai)ters on embryology and anatomy are furnished in large part by Max Brcidel, and there is an excellent bibliograpiiy. Altogether it is the best work that has ever appeared on the subject; in fact it is nearly the last word on the appendix.

In 1906 Dr. Kelly's volume on " Walter Reed and Yellow Fever " was published. Those who were at The Johns Hopkins Hospital in the early days really felt that Reed belonged to the Hopkins group. It was there that lie worked with William H. Weldi ; it was there that we learned to love Reed, for his unassuming manner, his sterling worth and his delightful companionship. It seems but yesterday that we saw him at Union Station in Baltimore when he had come down from his summer home at Blue Ridge on his way to New York, there to catch the l)oat for Havana to study yellow fever. lu one interested in the study of yellow fever, in the vicissitudes in the building of the Panama Canal, and in the life of the charming and brilliant scientist, this book will touch a sympathetic chord. To those of us who knew Reed it has been an inspiration.

" GjTieeology and .\bdoniinal Surgery ", by Howard A. Kelly and Charles P. Xoble, was published by Saunders. The first volume appeared in 1907, the second in 1908. The editors wrote extensively on the subjects in which they were particularly interested and for the remaining chapters were fortunate in securing surgeons peculiarly well adapted to treat of their special subjects. The chapters on gynecological fVitholopy are esfieeially valuable, being written by Dr. Elizabeth Hurdon of the gynecological department of The Johns Hopkins Hospital. " Kelly-Noble " has had an extensive and well-merited recognition by tlie profession.

Dr. Kelly's " Medical Gynecolog)' " appeared in 1908. It was a work of nearly seven liundred pages and was in reality the counterpart of " Operative Gynecology "; but it appealed more especially to the general practitioner. It contained much that was of necessity omitted in " Operative Gynecologj' "; it has had a wide distribution, numerous printings being required and a second edition in 1912.

In 1909 Kelly and Cullen publislied " Myomata of the Uterus," a volume of over seven hundred jiages devoted to an analysis of nearly seventeen hundred cases of ut«^rine myomata occurring in The Johns Hopkins Hospital and in other hospitals with which the authors were connected. The development of myomatJi, their various degenerations, the condition of the uterine mucosa and of the adnexa were thoroughly considered, and the various operative procedures necessary were given in detail. The excellent drawings rejjroduced in this volume were made by Hermann Becker and August Horn.

Kelly has always been interested in liis fellow-men and particularly in those who have had a large share in bringing American medicine to tlie forefront. In jiis operating room he


has had the rare privilege of coming in contact with physicians and surgeons from all parts of the country. In tlie social hours following the day's labor the conversation frequently drifted to a consideration of tiie lives of the outstanding men both past and present who had lived in the neighborhood of his guests. As a result he decided to gather in book-form short biographies of the eminent medical men and enlisted the hearty co-operation of prominent persons in all parts of the coimtry who helped him to obtain the names of deceased physicians and surgeons and often funiislied sketches of tlieir lives.

The " Cyclopedia of American Medical Biograpliy," comprising the lives of about eleven hmidred eminent deceased phj'sicians and surgeons from lClO-1910, publislied in 1912, contains a wealth of material which will become more and more appreciated as the years pass. In a biography whore many judges pass upon the names of those wlio shoulil lie included, some omissions are inevitable. Kelly has for several years been laboring industriously over a new edition. He has been most appreciative of the constructive criticism that has been accorded the first edition, as it has already enabled him to add a number of biographies omitted in the work when first published. The American profesison is under many obligations to Dr. Kelly for gatliering together in book-form the life liistories of the medical men of the past, men of whom tliis country is so justly proud.

Kelly's " History of Gynecology," found in his " Cyclopedia of American Medical Biography," is a not^iblo piece of work. Dr. Garrison says of it: " The best account of American gynecology is the essay by Howard A. Kelly in the introduction to his ' Cyclopedia of American Jledical Biogra])hy.' "'

One hardly expects to find a surgeon writing on botany or botanists, but those who have been privileged to spend one or more sunmiers witli Dr. Kelly in the backwoods of Canada and have watched ids eiitliusiasm in the study of ])lant and animal life were not surjirised to see his attractive little book " Some American Medical Botanists in Our Botanical Nomenclature," publislied in 1914.

Long i)efore Kelly came to Baltimdrc and wliilc hi' was still laboring in Kensington he was deeply interested in the study of the bladder, ureter and kidney and from the jireceding pages we have learned what a large share he has had in the development of bladder, ureteral and kidney surgery. As the years went on his interest in this field grew more inten.se and the results of his experience are to be found in " Diseases of the Kidneys, Ureters and Bladder, with Special Reference to the Diseases in Women," brought out by Dr. Kelly and Dr. Curtis V. Burnam in 1914.

In the early days of the hospital Dr. Kdly Ijccame acquaintefl with Anthony S. ilurray. an enthusiastic amateur photographer, who came to the hospital each operating day to photogra])h the various steps of the o])eration and frequently the pathnlogical specimens. Mr. JIurray was beloved by every one who came in contact with him and at once became an im


• Garrison, History of .Medicine, 2. ed.. Plilla., W. B. Saunders. I!tl7. p. 801.


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[No. 344


portant member of the happy gynecological family. Many of his photographs were nsed in Dr. Kelly's early papers and in articles published by other members of the staff. Mr. Murray also made many excellent lantern slides which were used in our teaching courses and at the various medical meetings.

Dr. Kelly, largely as a result of Murray's enthusiasm and excellent work, became much impressed with the value of photography as an adjunct in teaching surgery and had stereopictures made, so that students could follow clearly the steps of the various operations. Finally, he decided that it would be an admirable idea to have the operations of individual operators photographed in this manner, and thus started the " Stereo-Clinics." The work of operators in various parts of the country has been brought out in stereo-form so that to date tliere have been 43 sections issued. These have been published by the Southworth Company under Dr. Kelly's direction and have enabled many a surgeon in the quiet of his study to obtain a clear view of each step in a given operation. The idea proved most practical and the results have been beyond Dr. Kell3s sanguine expectations. In his enthusiastic prosecution of this work he visited many parts of this country and also England and Scotland in search of interesting and instructive subjects.

One can never forget the delightful evenings of The Johns Hopkins Hospital Historical Society. In the early days meetings were held in the library of the hospital and later when the attendance increased, in a large room vinder Ward H. It was a rare privilege to listen to Osier, Welch, Kelly, and others who brought with them treasured volumes. After these had been described and passed around, the speaker usually gave a short account of the author, of the school with which he had been associated and frequently of his confreres. Dr. Kelly thus presented many books and read numerous papers before the Historical Society.

Among the biographical sketches whicli he lias published are: "Horatio Keese Holmes," 1897; '".lules Loniaire, the First to Recognize the True Nature of AVcmnd Infection and Inflannuation, and the First to Use Carbolic Acid in Medicine and Surgery," 1901; "James Carroll," 1908; " Frore Jacques," 1908; "Theodore Caldwell Janeway." 1918; "Joseph Price," 1918; and "A Tribute to Dr. W. W. Keen," 1918. Kelly's paper on John R. Yoimg attracted unusual attention, as few had any appreciation of the fundamental work that this Marylander had accomplished. Recently Dr. Kelly gave an interesting paper on Florence Nightingale and presented to The Johns Hopkins Training School for Nurses a richly bound volume containing seven of her unpublished letters.

Dr. Kelly has been accorded distinguished recognition both in this countrv' and abroad. He is an honorary fellow of the Chicago Gynecological Association; he was President of the Southern Surgical and Gynecological Association, one of the most active surgical societies in the United States, in 1907; President of the American Gynecological Society in 1912 ; Fellow of the British Gynecological Society ; Honorary Fellow of the Obstetrical Society of London, of the (Glasgow Obstetrical and Gynecological Society, of the Royal College of Surgeons,


Edinburgh, and of the Royal Academy of Medicine in Ireland. He is a member of the Association Frangaise d'Urologie, Paris; of the Societe d'Obstetrique, de GjTiecologie et de Pediatric de Paris, and of the Gesellschaft der Aerzte in Wien. He is honorary member of the Societa Italiana di Ostetricia e Ginecologia, Roma; of the Gesellschaft fiir Geburtshiilfe zu Leipzig, and other societies. He was honored with an LL. D. by the University of Aberdeen in 1906, by the Washington and Lee University in 1906 and by his alma mater, the University of Pennsylvania, in 1907.

Dr. Kelly's generosity has been strikingly shown in his gifts to The Johns Hopkins Hospital. In 1905 he learned that the extensive collection of portraits collected by the late Dr. G. F. Fisher, of Sing Sing, was offered for sale. Fisher, a medical historian, an eminent practitioner and collector of books, had also accumulated valuable engravings and portraits of the leaders in medicine both in this country and in the old world. His medical library was secured for Vassar Hospital and Dr. Kelly obtained the large collection of portraits and engravings and presented them to The Johns Hopkins Hospital.

In 1897 Dr. Kelly gave to The Johns Hopkins Hospital the sum of $5000 for a much needed addition to the gynecological operating roem.

In 1901, in order to furnish additional accommodations for patients recovering from gynecological operations and to secure facilities for an examining room and laboratory in connection with the gynecological ward. Dr. Kelly, gave to the hospital the sum of $10,000. For two years Dr. Kelly also paid the salary of a visiting nurse for the care of patient.«  discharged from the hospital.

Probably the most valuable gift made by Dr. Kelly to The Johns Hopkins Hospital was that of a choice collection of books from his library. An extended reference to this gift appeared in Thk Johns Hopkixs Hospital Bulletin, 1915. page 415, and is as follows: " During the past year, through the unparalleled liborality of Professor Kelly upward of fo\ir thousand volumes of books, periodicals, monographs and theses from his private library have been presented to The Johns Hopkins Hospital and placed on the shelves of the library, ilanv of them, and, in fact, the majority, are books connected with his own special work in gynecology and obstetrics, and represent his zeal as a collector while pursuing his special studies. They include the best treatises upon these important branches of study in German, French and English, and are invaluable for the student of medicine and the physician. They comprise many very rare works also in anatomy, medicine and general surgery, and bear remarkable testimony to the breadth of the donor's interest in the whole science of medicine." "

A word of a jiersonal nature is appropriate in such a tribute as this. Kelly, in his relations with the members of his hospital staff, has always been most kind and considerate. He


"There are many editions of Avicenna, Boerhaave, Celsus, Falloppio, Galen, Hippocrates, Vesalius; and works of Argelata, Aristoteles, Fracastorius, Haller, Harvey. Malpighi, Rhazes, Spigelius, Sylvius, and others.


OCTOBEB, 1919]


293


has placed responsibilities upon them and has treated them as friends and younger brothers ratlier than as assistants. He has given them material aid in prosecuting studies in this country or abroad and has often assisted them iu bearing the expense of the publication of books and their illustrations. Many of his assistants have spent one or two years as internes, a year each as second assistant, and first assistant, and iinally a year or more as resident. Under these circumstances it is not strange that many excellent men have been developed by him, who are now occupying prominent places in Baltimore and in other parts of the country. Among tliese may be mentioned: Hunter Kobb, late of Cleveland; A. L. Stavely, in Washington ; W. \V. Russell, in Baltimore ; John G. Clark, in Philadelphia; Thomas S. Cullen, in Baltimore; Otto G. Ramsay, at Yale (until his untimely deatli) ; Ernest J. Stokes, in North Carolina; G. Brown Miller, in Washington; G. L. Hunner, in Baltimore; B. J. Schenck. in Detroit; John A. Sampson, in Albany; Curtis F. Burnam, iu Baltimore; Henry T. Hatchins and Stephen Eushmore, in Boston; E. H. Rich


ardson, in Baltimore; E. K. Cullen, in Detroit; Elizabeth Ilurdon, in Baltimore, and many others.

The activities of Dr. Kelly have not been confined to his profession. He has been much interested in many problems of a religious and philanthropic character which have occupied no small share of his time ixnd thoughts. He has also been a liberal contributor to many worthy philanthropic and religious enterprises.

He has taken, as a rule, a vacation of at least two months everj- year and for many years has occupied a delightful and simple camp in Canada. Here he has wandered through the woods, studied wild flowers and mushrooms, has taken long canoe trips and has maintained his record as a long-distance swimmer. In this way he has recruited and conserved his wonderful physical energy.

In his retirement from the active management of the Gynecological Department of The Johns Hopkins Hospital, he carries with him the cordial good wishes of his colleagues, associates, pupils and friends.


BIBLIOGRAPHY OF HOWARD A. KELLY, M. IX, LL. D., HON. F. R. C. S.


PREP.\BED BY

MINNIE WRIGHT BLOGG

I.lllB.Mtl.VN, THK JOHNS HOPKINS llOSl'ITAI.


Dr. Kelly's bibliography covers the i)eriod from 1882 to 1910 inclusive. The lis.") titles include books, pamphlets and journal articles. Most of these are in the Library of The Johns Hopkins Hospital and are of sjiecial value as gifts from I>r. Kelly.

1882 Was the thoracic duct injured in tlie case of President Garfield? (Correspondence). Med. News, PMla., 18S2. xl, SO.

Some rare and new auomalios in man; with tliree cases of double femoral artery. Am. J. M. Sc, Phila., 1882, n. s., Ixxxili, 138-142.

1883

Uterus septus bicollis. .Med. News, Phila.. ISS.T, xlil. 4U.

On a method of postmortem examination of the tlioracic and abdominal viscera. Through vagina, perineum, and rectum, and without incision of the abdominal parletes. .Med. News. Phila., 188.-!, xlii, 733-734.


.Med. News, Phila.,


An Improved attachment for the head-mirror. 1883, xlUl, 390.

On the mapping out of visceral diseases, in an aniline color, on the surface of the body. (Correspondence). Med. News. Phila.. 1.S8.!. xliil, 417-418.

The use of oleale of aconltla as a local anodvne. Med. News. Phila.. 1883, xliil, 702-703.


The occurrence of the Ascarls Mystax (Rudolplii) in the human body: with a case. Am. J. M. Sc. Phila.. 1884, n. a.. Ixxxvill, 483-486.

The external use of the oleate of aconltla. (Correspondence). Med. News, Phila., 1884, xllv, 201-202.

Death from a pes.sary. .Med. News, Phila., 1884. xlv, 4.'?0.

On the anesthetic use of the hydrochlorate of cocaine upon parta

of the body other than the eye. Med. .News. Pliila., 1884,

xlv, 713-714.

1885

An ovarian cyst weighing one hundred and sixteen pounds successfully removed. Am. J. Obst.. N. Y. 1885, xvlli, 795-798.


Cocaine in diphtheria. Med. News, Phila.. 1S85, xlvi, 455.

1S8C

A case of removal of two sessile cervical fibroid tumors by abdominal section. Am. J. Obst., N. Y., 1886, xix, 44-49.

Hydro-salpinx with congenital deficiency of tubes and broad ligaments. Am. J. Obst. N. Y., 188G, xix, 618. Also: .Med. & Surg. Reporter, Phila., 1886, liv, 712.

Cellulitic contraction of right broad ligament with disappearance of the meso-salpinx, and coherence of ovary and tube. J. Am. M. Ass., Chicago, 1886, vi, 677.

Hysterorrhaphy, or the suspension by suture of a viciously posed uterus. .1. Am. M. .\ss,, Chicago, ISSti, vii, 660. Also: Med. .News. Phila., 1SS6, xlix, 636.

Ha^matoma of the ovary, with adherent Fallopian tube. N. York M. J., 1886, xliil, 222. Also: Am. J. Obst., N. Y., 1886, xix, 503-504.

Extra-uterine pregnancy; complete removal of the sac and +++++ CONTENTSs: recovery. N. Yorl< M. J., 1886, xliil, 617-619. Also: J. Am. M. Ass. Chicago, 1886, vl, 668-670. .l/»o; Med. & surg. Reporter, Phila.. 1886, liv, 803-806.

Ovarian tumor that weighed at normal 100 pounds. Maryland .M. J., Bait., 1886, xv, 49.

Ovaries and tubes from a case of chronic ovaritis; salpingitis and pelvic peritonitis: also tlie right ovary and tube from a case of cellulitic contraction of riglit broad ligament witli disappearance of tlie mesosalpinx and rolierence of ovary and tube. Maryland M. J., Bait., 1886, xv, 49-51. Also: Am. J. Obst., N. Y.. 1886, xix, 838-841.

A unique ca.se of extra-uterine pregnancy: complete removal of the sac and +++++ CONTENTSs: recovery. With a critical examination of the cases of faradic feticide and remarks upon its dangers by R. P. Harris. .Marvland .M. J.. Bait., 1886, xv, 51-54. Also: Am. .1. Obst.. N. V., 1886. xix, 841-843.

Asepsis not antisepsis; a plea for principles, not paraphernalia, in laparotomy. .Maryland .M. J., Bait., 1X.S6, xv, 110-112. Also: N. York M. J., 18S6. xliil, 672-674. Also: Am. J. Obst., N. Y., 1886, xix, 1076-1079.

The Munich meeting of the German Gynecological Congress. (Correspondence). Med. News, Phila., 1886, xUx, 81-82,


294


[No. 344


Gonorrhosal tubo-ovarlan abscess; right side; laparotomy; removal of Fallopian tube and ovary; recovery. Med. News, Phila., 1S86, xlix, 205-207. Also: Am. J. Obst., N. Y., 1886, xix, 1169.

The obstetrical section of the British Medical Association. (Correspondence). Med. News, Phila., 18S6, xlix, 276-278.

GynEecological operations in Germany. Med. News, Phila., 1886, xlix, 301-304.

Hematoma of the ovary, with adherent Fallopian tube. N. York M. J., 1886, xliii, 222.

1887

Hysterorrhaphy. Am. J. Obst., N. Y., 1887, xx, 33-46.

Perineal and ovariotomy cushions. Am. J. Obst., N. Y., 1887, xx, 1029-1031.

Results of some general work in abdominal surgery, performed during seven and one-half months of 1886. Proc. Phila. Co. M. Soc, 1887, Phila., 1888, vlii, 43-50. Also: Polyelin., Phila., 18S7, iv.

Pelvic measurements. Obst. Gaz., Cincin., 1887, x, 123.

Measuring the conjugata vera. Med. News, Phila., 1887, 1, 277-278.

A contribution to hepato-phlebotomy. Med. News, Phila., 1887, 1, 617-619.

Removal of the uterus through the vagina. Med. News, Phila., 1887, li, 276-277.

De rhysterorrhaphie (nouvelle operation pour le redressement de I'uterus retroflechi). [Abstr. transl. by E. Thomas, from: Am. J. Obst., N. Y.] Gaz. de gynec. Par., 1887, ii, 65-70.

Results of some general work in abdominal surgery, with cases and specimens. Med. & Surg. Reporter, Phila., 1887, Ivi, 425-429.

A new leg-holder, securing a perfect lithotomy posture without assistants. Med. & Surg. Reporter, Phila., 1887, Ivi, 747.

Letter from Leipzig. Med. & Surg. Reporter, Phila., 1887, Ivii, 210-211. Also: Pittsburgh M. Rev., 1887, ii.

Letter from Bremen. [" Gynecologist " tour through Germany in 1887.] Pittsburgh M. Rev., 1887, ii.


Injuries and lacerations of the perineum and pelvic floor. In: Syst. Pract. Gynec. (Mann), Phila., 1888, ii, 719-778.

Remarks on Alexander's operation. Ann. Gynaec, Bost., 1887-8, 1, 142.


Hysterorrhaphy. Am. J. M. Sc, Phila.,


n. s., xcv, 468-481.


Removal of the uterine appendages for disease in which pain is a prominent symptom. Med. News, Phila., 1888, lii, 36-39. Also: Proc. Phila. Co. M. Soc. 1887, Phila., 1888, viii, 278-289. Also: Maryland M. J., Bait., 1887-88, xviii, 226-231.

A case of Caesarean section. Med. News, Phila., 1888, liil, 320-322. Also: Am. J. Obst., N. Y., 1888, xxi, 1193. Also: Polyclinic, Phila., 1888-89, vi, 117.

An aseptic two-way uterine catheter. Med. News, Phila., 1S88, lii. 326-327. Also: Am. J. Obst., N. Y.. 1888, xxi, 721.

The Whitechapel murders. (Correspondence). Med. News, Phila 1888, liii, 430-431.

Resuscitation of the asphyxiated new-born child. Am. J Obst N. Y., 1888, xxi, 419-420; 421.

A cotton packer. Ibid., 721.

Knife-blade tenaculum. Ibid., 942-944.

A self-retaining speculum. Ibid.. 945.

Operation upon a laceration of the cervix and perineum: peritonitis; abdominal section; death. Med. & Surg. Reporter, Phila., 1888, Iviii, 489-491.

Rubber cushions for surgical purposes. N. York M. J., 1S8S, xlvii 104-105. Also: Med. & Surg. Reporter, Phila., 1888, Iviil, 145.

Notes explanatory of sixty-six consecutive abdominal sections recorded herewith. Pittsburgh, M. Rev., 1888, ii, 25; 35.


Palpation of the ureters in the female. Tr. Am. Gynec. Soc., Phila., 1888, xiii, 50-65. Also: Am. J. Obst., N. Y., 1888, xxi, 1032-1034.

Discussion on the new Csesarean section. Tr. Am. Gynec. Soc, 1888, xiii, 130-141.

[Remarks on Blaikie's directions for exercise.] N. York M. J., 1888, xlvii, 136.

Description of a new pad for general surgical purposes. N. York M. J., 1888, xlvii, 473.

1889

Report of twenty-five abdominal sections performed for the most part in the Kensington Hospital for Women, since the summer of 1888. Univ. M. Mag., Phila., 1888-9, i, 400-407.

Cholocystorrhaphy, followed by cholocystotomy: evacuation of one hundred and eighty-eight gall-stones; recoverv. Ann. Gynec, Bost., 1888-89, ii, 517-519. Also: Am. J. Obst., 1889, xxil, 1191-1193.

A new method of performing hysteromyomectomy. Am. J. Obst., N. Y., 1889, xxii, 375-385.

Hysteromyomectomy. Boston M. & S. J., 1889, cxx, 40-41.

Carcinoma of the corpus uteri. Obst. Gaz., Cincin., 1889, xii, 57.

Glass catheters. Am. J. Obst., N. Y., 1889, xxii, 184-185.

Kelly, H. A. & Robb, H. Craniotomy for hydrocephalus, with the use of the obstetric pad. Univ. M. Mag., Phila., 1888-89, i, 514-519.

1890

Diseases of the ovaries and tubes. In: Cycl. Dis. Child., M. & S. (Keating), Phila., 1890, iii, 731-740.

On hysterorrhaphy. Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 17-19.

Ligation of varicose ovarian veins. Ibid., 23.

The more remote results of removing the ovaries and tubes. Ibid.,

57-58.

Hysteromyomectomy. Ibid., 96.

Tubercular peritonitis [operation.] Ibid., 96-97.

A consideration of three successful Csesarean sections in Philadelphia. Am. J. Obst., N. Y., 1890, xxiii, 225-246.

Supra-vaginal hysterectomy. Hysteromyomectomy with suspension of the stump in the lower angle of the abdominal incision. Med. News, Phila., 1890, Ivi, 695-698.

Treatment of recto-vaginal fistulae. (Editorial). Med. News, Phila., 1890, Ivii, 516-517.

CephalhEematoma. A case of sub-pericranial blood-tumor in the new-born child. Med. News, Phila., 1S90, Ivii. 229-231.

A successful Csesarean section for a large bony tumor choking the pelvis. Med. & Surg. Reporter, Phila., 1890, Ixii, 100-106.

The gynecological operating room in The Jolms Hopkins Hospital, and the antiseptic and aseptic rules in force. Jolins Hopkins Hosp. Rep., Bait., 1890, ii, 131-139.

Tlie report of the' autopsies in two cases dying in tlie Gynecological wards without operation. Johns Hopkins Hosp. Rep., Bait, 1890, ii, 167-176.

Composite temperature and pulse cliarts of forty cases of abdominal section. Johns Hopkins Hosp. Rep., Bait., 1890, ii, 177-183.

The gonococcus in pyosalpinx. Johns Hopkins Hosp. Rep., oalt., 1890, ii, 195-200.

Tuberculosis of the Fallopian tubes and peritoneum; ovarian tumor: removal of the ovaries and Fallopian tubes with drainage, followed by recovery; demonstration of the tubercle bacillus in sections of the tube. Johns Hopkins Hosp. Rep., Bait., 1890, ii, 201-204.

General gynecological operations from October 15, 1889, to March 4, 1890. Jolms Hopkins Hosp. Rep., Bait., 1890. ii, 205-215.

Ligature of the trunks of the uterine and ovarian arteries as a means of cliecking hemorrliage from tlie uterus and broad ligaments in abdominal operations. Johns Hopkins Hosp. Rep., Bait., 1890, ii, 220-223.


OrroBER, 1919]


295


Elephantiasis of. the clitoris. Johns Hopkins Hosp. Rep., Bait., 1890. ii, 227-230.

Kolpo-ureterotoniy; incision of the ureter through the vagina, for the treatment of ureteral stricture. Johns Hopkins Hosp. Rep., Dalt., 1890. ii. 234-242.

Record of deaths following gynecological operations. Abstracted from the recoriis of the pathological department. Johns Hopkins Hosp. Rep.. Bait., 1890, ii. 243-252.

Extra-uterine pregnancy. Review and discussion. Paper read before the Obstetrical and Gynecological Society of Baltimore City. January 14 and February 11, 1890. Tr. Obst. & Gynec. Soc., Bait.. 1S90. 33-48.

Vaginal puncture and drainage for pelvic abscess. An address before the Gynecological and Obstetrical Society of Washington, December 5. 1890. (Not published).

Cephalaematoma verum externum; sub-pericranial blood-tumor of the new-born. Tr. Am. Gynec. Soc. Phila., 1890, xv. lS9-2(i9.

Kelly, H. A. & Ghriskey, A. A. Report of the urinary examination of ninety-one g\-necological cases. Johns Hopkins Hosp. Rep., Bait., 1890, ii, 216-219.

Kelly, H. .\. & Robb. H. The laparotomies performed in the gynecological department from October 16. 1889, to March 3, 1890. Johns Hopkins Hosp. Rep., Bait, 1890, ii, 141-166.


A death caused by a uterine dilator, with some remarks as to the proper method of using the dilator. Am. J. Obst., N. Y., 1891. xxiv, 42-46.

The palpation of normal ovaries. Am. J. Obst., X. Y., 1891, xxiv, 129-142.

The steps of the Csesarean section; the do's and the don't's. Am. J. Obst., N. Y., 1891. xxiv, 532-544.

Hand disinfection. Am. J. Obst., N. Y., 1891, xxiv, 1414-1419.

The ideal dressing for the abdominal wound. Am. J. Obst, N. Y., 1891, xxiv, 1439-1441.

Abstracts from " The picture of Philadelphia." etc. Read before the Historical Societv of the Johns Hopkins Hospital. Med. News, Phila.. 1891. Iviii. 19T-198.

Cancer of the cervix uteri in the negress; physometra in the negress. due to cancer: mania following operation; recovery. Tr. South. Surg. & Gynec. Ass., 1890. Phila., 1891, iii, 386-390.

Antisepsis and asepsis before and after major gynecological operations. Am. J. M. Sc, Phila., 1891, n. s., ci, 44-55.

Letter to Dr. G. H. Kirwan. |The modern treatment of wounds. by G. H. Kirwan. 1 Lehigh Valley M. .'Mag.. 1890-1891, ii, 213-214.

Report from Gynecological Clinic. (A case of tubercular peritonitis treated with Koch's lymph). Johns Hopkins Hosp. Bull., Bait, 1891, il, 15.

Twin pregnancy. Breech and transverse presentation. The placentae and the membranes. (Proc. Johns Hopkins Hosp. .Med. Soc., Dec. 15, 1890). Ibid.. 44.

The treatment of large myomatous tumors of the uterus. Myomotomy and hysteromyomectomy. Ibid., 45-49.

A case of ronser^'atlve Ca^sarean section. (Proc. Johns Hopkins Hosp. .Med. Soc., Feb. 2, 1891). Ibid.. 62.

Israel Sparhlus'.s Gynecology. (Proc. Johns Hopkins Hosp. HIat Club, Oct. 12. 18911. Ibid.. 164.

My fourth Csesarean section. N. York M. J., 1891, 1111. 500-503.

1892 Diseases of the broad ligaments, tubes, and ovaries.

In: Syst. Pract Therap. (Hare). Phila.. 1892. Ill, 80.,-834. The ministry of nursing. An address delivered to the second class of nurses graduating at The Johns Hopkins Hospital, June 3, 1892. Bait.. 1S92. Griffln, Curley & Co., 14 p. 8°.


A letter to my a-sststant on the method of securing asepsis In the preparation of Instruments, ligatures, and dressings in my private office. Am. J. Obst, N. Y., 1892, xxv. 184-189.

The ureteral catheter. Am. J. Obst., N. Y., 1892, xxv, 768-771.


Clinical report of cystectomy for polycystic ovarian tumor. Med. & Surg. Reporter, Phila., 1892, Ixvii, 241-246.

Confinement on the obstetric pad. Med. Rec, N. Y., 1892, xlii, 663.

Gynwcological technique; a brief summary of the principles involved, as well as the technique of the gyniecological operations performed in The Jolins Hopkins Hospital; the significance of the operation and its technical surroundings to gyna-cological practice. N. York J. Gynaec. & Obst, 1892, ii, 667-674.

Address to nurses. Delivered at the third annual commencement of the Training School for Nurses of Wilkes Barre City Hospital, July 1, 1892. In: Rep. 3d ann. comm. Training School for Nurses, Wilkes Barre City Hosp., 1892.

Presentation of Foesius' Hippocrates. (Proc. Johns Hopkins Hosp.

Hist Club, March 14, 1892). Johns Hopkins Hosp. Bull.,

Bait, 1892, iii, 43. On methods of illustrating lectures with a lantern-slide exhibition

of injuries at the vaginal outlet. Times & Reg.. Phila., 1892,

xxiv, 649-650. i

1S93

Drainage in abdominal surgery. Practice, Richmond, 1893. viii,

69-70. My recent ureteral work. Ann. Gyna?c. & Pediat, Phila., 1892-93,

vi, 449-460. Catheterization of the ureters. Ann. Gyna?c. & Paediat., Phila.,

1892-93, vi, 641-644. The ethical side of the operation of oophorectomy. Am. J. Obst.,

N. Y., 1893, xxvii, 206-208. Glass trocars for tapping large ovarian cysts. Am. J. Obst.,

N. Y., 1893, xxvii, 581. The best needle holder. Am. J. Obst., N. Y., 1893, xxvii, 870-872. The examination of the female bladder and the catheterization

of the ureters under direct inspection. Johns Hopkins Hosp.

Bull., Bait., 1893, iv, 101102. Extra-uterine pregnancy treated by vaginal incision. Johns

Hopkins Hosp. Bull., Bait., 1893, iv, 109. A case of uterus duplex solidus. with atresia of the vagina and

cervix. Johns Hopkins Hosp. Bull., Bait., 1893, iv. 109-110. Exhibition of a convalescent case of peritonitis due to ruptured

tubal abscess. Johns Hopkins Hosp. Bull., Bait, 1893, iv,

111-112. Suspensio uteri. J. Am. M. Ass., Chicago, 1893, xxi, 332-333. Prolapsus uteri. N. Am. Pract, Chicago, 1893, v, 337-347. The early treatment of carcinoma uteri. N. York M. J., 1893,

Iviii, 433-434. The examination under anjesthesia: its uses and its limitations.

N. York M. J., 1893, Iviii, 617-618. A preliminarv report on the morphology of ovarian and myomatous

tumors. N. York J. Gyniec. & Obst, 1893, ill, 465-484. Also: Tr. South. Surg. & Gynec. Ass., 1892. Phila., 1893, v, 211-217. Al.w: Am. J. Obst.. N. Y., 1893, xxvii. 31U-312. Epitome of an address on sepsis, antisepsis and asepsis, in relation

to operative gjnecology. Tr. M. Soc, N. Y., Phila., 1893,

375-377. Abstract of a paper on urinalysis in gyntecology. Am. Med. Surg.

Bull., N. Y.. 1893, vl. 934-93.5. .i;so.- Am. J. Obst.. N. Y.. 1S93, xxviil, 429-431.

1894 The technique of gynecological operations.

In: Am. TextBk. Gynec. (Baldy), Phila., 1S94, 54-80.

I.rf»ceratlons of the soft parts.

In: Am. Text-Bk. Gynec (Baldy). Phila., 1894, 245-266.

Genital fistul-T. In: Am. Text-Bk. Gynec. (Baldy), Phila.. 1894, 267-277.

Diseases of the urethra, bladder, and ureters.

In: Am. Text-Bk. Gynec (Baldy), Phila., 1894, 615-659.

The gynecological operating room. Johns Hopkins Hosp. Rep.,

Bait, 1S92-4. ill, 301-302. An external direct method of measuring the conjugata vera,

Johns Hopkins Hosp. Kep., Bait., 1892-94, 111, 303-309.


296


[Xo. 3-1


Prolapsus uteri without vesical diverticulum, and with anterior

enterocele. Ibid., 311-320. Lipoma of the labium majus. IMd., 321-326. Deviations of the rectum and sigmoid flexure associated with

constipation a source of error in gynecological diagnosis.

Ibid.. 327-342. Operations for the suspension of the retroflexed uterus. Ibid..

343-35S. Gynecological operations not involving coeliotomy. Tabulated by

A. L. Stavely. Ibid.. 377-410. The employment of an artificial retro-position of the uterus in

covering extensive denuded areas about the pelvic floor. • Ibid., 411-417. Some sources of hemorrhage in abdominal pelvic operations.

Ibid., 419-422. Traumatic atresia of the vagina with haematokolpos and hsema tometra. Ibid., 429-431. Resuscitation in chloroform asphyxia. Ibid.. 507-508. Abdominal operations performed in the gynecological department

from March 5, 1890, to December 17, 1892. Ibid.. 547-673.

A study of intra-abdominal pressure with practical deductions.

Cleveland M. Gaz., 1893-94, ix. 239-247. .The diagnosis of pelvic inflammatory diseases. Ann. Gynsec. &

Pediat., Phila., 1893-94, vii, 185-190. Uretero-ureteral anastomosis; uretero-ureterostomy. [Remarks by

Dr. Bloodgood.] Johns Hopkins Hosp. Bull., Bait., 1893,

iv, 89-90. Also: Ann. Surg., Phila., 1894, xix, 70-77.

The direct examination of the female bladder with elevated pelvis; the catheterization of the ureters under direct inspection, with and without elevation of the pelvis. Am. J. Obst., N. Y., 1894, xxix, 1-19. Also: Johns Hopkins Hosp. Bull., Bait., 1894, v, 16.

The cystoscope. Am. J. Obst, N. Y., 1894, xxx, 85-90.

Resuscitation, from impending death due to concealed hemorrhage, bv an infusion of a litre of normal salt solution centrally into the radial artery. Am. J. Obst.. N. Y., 1894. xxx, 184-189.

Electric illumination of the field in abdominal surgery. Am. J. Obst., N. Y., 1894, xxx, 348-353.

The advantage of atmospheric distention of tlie rectum, with dislodgment of the small intestines, in the bimanual examination of uterus, ovaries, and tubes. Am. J. Obst., N. Y., 1894, xxix, 607-610.

An improved lock for paired instruments. Ann. Surg., Phila.. 1894, xix, 231-235.

Dysmenorrhoea. N. York J. GynaE'C. & Obst., 1894, iv, 408-411. Also: Tr. M. Soc. N. Y., Albany, 1894, 177-181.

Introduction of bougies into the ureters preceding hysterectomy and the removal of densely-adherent structures adjacent to the ureter. (Proc. Johns Hopkins Hosp. Med. Soc. Dec. IS, 1893.) Johns Hopkins Hosp. Bull., Bait., 1894, v. 17.

Lantern slides as an aid to clinical teaching. (Proc. Johns Hopkins Hosp. Med. Soc, Jan. 15, 1894). Ibid.. 35.

The methods employed in securing statistical tables for Emmet's Gynecology. Exhibition of original tables presented by Dr. Emmet. (Proc. Johns Hopkins Hosp. M. Soc, Feb. 19, 1894). Ibid., 51-52.

Ligation of both internal iliac arteries for hemorrhage in hysterectomy for carcinoma uteri. (Proc. Johns Hopkins Hosp. M. Soc, March 5, 1894). Ibid.. 53-54.

Myoma complicating pregnancy and preventing delivery. PorroCiesarean operation modified by dropping the pedicle. (Proc. Johns Hopkins Hosp. Med. Soc, April 2, 1894). Ibid., 80-81.

Infusion of normal saline solution in connection with gynecological operations and the accidental hemorrhages of parturition. (Proc. Johns Hopkins Hosp. Med. Soc, April 2, 1894). Ibid., 81-82.

Recent results in hysteromyomectomy. (Proc. Johns Hopkins Hosp. Med. Soc, May 7, 1894). Ibid.. 99-100.

Ureterotomy. Ibid., 137.

A new method of exploring the rectum and sigmoid flexure Ibid . 137-138.


Recent results in hysteromyomectomy. The direct examination of the female bladder and catheterization of the ureters under

direct inspection, [n. p., 1894, vel subseg.^ 8°. Kelly, H. A., & Cullen, T. S. Record of deaths occurring in the gynecological department from June 6. 1890, to May 4. 1892. Abstracted from the autopsy notes of the pathological department. Johns Hopkins Hosp. Rep., Bait., 1892-94, iii, 675-762.

Kelly, H. A. & Sherwood, Mary. One hundred cases of ovariotomy performed on women over seventy years of age. Ibid., 509-545.

1895 Extra-uterine pregnancy.

In: Am. Text-Bk. Obst. (Norris & Dickinson). Phila., 1895, 273-294.

Diseases of the female bladder and urethra.

In: Twentieth Cent. Pract., N. Y.. 1895, i, 663-726.

Diagnosis of ureteral and renal diseases in women. J. Am. M. Ass., Chicago, 1895, xxv, 272-274.

Suspensio uteri — the proper method of performing it, and its results. (Abstr.) J. Am. Med. Ass., Chicago, 1895, xxv, 318.

Suspension of the uterus; the operative treatment of retroflexion based on a consideration of 200 cases. J. Am. M. Ass., Chicago, 1895, xxv, 1079-1081.

Diagnosis of renal calculus in women. Med. News, Phila., 1895, Ixvii, 593-596.

Gonorrhoeal pyelitis and pyo-ureter cured by irrigation. Johns Hopkins Hosp. Bull., Bait., 1895 vi, 19-21.

Uretero-cystostomy performed seven weeks after vaginal hysterectomy. Ibid., 27-28.

Sigmoido-proctostomy; an anastomosis of the lumen of the sigmoid fiexure through the lateral wall of the rectum at the pelvic floor, without suture. Ibid., 30-31. Also: Mathews' M. Quart, Louisville, 1895, ii, 212-216.

A new method of examination and treatment of diseases of the rectum and sigmoid flexure. Ann. Surg., Phila., 1895, xxi. 468-478. Also: [Abstr.] Centralb. f. Chir.. Leipz.. 1895. xx, 961-962.

"Female" or woman. (Correspondence). Am. J. Obst., N. Y.. 1895, xxxi. 394. Also: Pittsburgh M. Rev.. 1895, ix, 160.

Tlie renal catheter and its use in the diagnosis and treatment of renal diseases. Tr. Am. Gynec. Soc, Phila., 1895, xx, 20-29. Also: Boston M. & S. J., 1895, cxxxiii, 469. Also: Am. J. Obst., N. Y., 1895, xxxii, 120-123.

1896

State regulation of the social evil. Washington, 1896, Puritv Publ. Co., 15 p. 8°.


Personal purity. Health Mag., Wash., 1895-96, iii, 590-596.

A criticism on Prof. Howard A. Kelly and his discoveries in the domain of urinary diseases, by W. Rubeska. M. D. My work on the diseases of the urinary tract in women. Being a reply to the above. (Correspondence). Am. J. Obst., N. Y., 189G, xxxiii, 394-405.

Meine Arbeit iiber die Krankheiten der weiblichen Harnwege. Antwort auf Mittheilungen des Herrn Prof. W. Rubeska. Centralbl. f. Gynak., Leipz., 1896, xx, 489-498.

Five cases of ovariotomy in women over seventy vears of ago. Am. J. Obst, N. Y., 1896, xxxiv, 222-227.

A reply to Prof. Pawlik's claim to the discovery of my method of examining the bladder and catheterizing the ureters in women. Am. J. Obst, N. Y., 1896, xxxiv, 259-261.

Delivery by traction on the scalp of the child. Am. J. Obst, N. Y., 1896, xxxiv, 356-357.

Conservatism in ovariotomy. J. Am. M. Ass.. Chicago, 1896, xxvi, 249-251.

Unchastity and credibility. (Letter to the editor of the Journal of the American Medical Assoi-iation ) . J. Am. M. Ass., Chicago, 1896, xxvi, 992-993.

The treatment of large vesico-vaginal fistula-. Johns Hopkins Hosp. Bull., Bait, 1896, vii, 29-30. Also: Am. J. Obst, N. Y., 1896, xxxiii, 930-931.


OCTOBKB, 19191


297


Nephro-ureterectomy; extirpation of the kidney and ureter simultaneously. Jolins Hopkins Hosp. Bull., Bait., 1896, vii, 31-37.

The treatment of pyo-ureteritis and pyonephrosis by ureteral and renal catheters. Ibid.. 48-50.

Women in medicine. Ibid., 50-52.

The treatment of ectopic pregnancy by vaginal puncture. (Proc. Johns Hopkins Hosp. Med. Soc., Oct. 19, 189ti). Ibid.. 209-211.

Hysteromyomectomy and hystero-salpingo-oophorcctomy by continuous incision from left to right or from right to left. Tr. South. Surg. & Gynec. Ass., 1895. Phila., 1896, viii, 133-138. Also: Johns Hopkins Hosp. Bull., Bait.. 1896. vii, 27-29.

The treatment of extra-uterine pregnancy, ruptured in early months, bv vaginal puncture and drainage. Am. Gvnec. & Obst. J., N. Y.. 1896. ix, 129-151.

Also: Tr. Am. Gynec. Soc. Phila., 1896, xxi. 180-208.

Also: Am. J. Obst.. N. Y.. 1896, xxxiv, 103-105.

The treatment of backward displacements of the uterus. Am. J. M. Sc. Phila., 1896, n. s., cxii, 629-649.

[Letter to the editor of the Medical Sews in regard to Dr. Pryor's article, entitled "A new and rapid method of dealing with intra-ligamentary fibromyomata.") Med. News, N. Y., 1896, Ixviii, 501.

Some recent important advances in the diagnosis and treatment of urinary diseases in women. Pittsburgh M. Rev., 1896, x, 1-8.

Abdominal hysterectomy for fibroma uteri. South. Pract., Nashville. 1896, xvili, 7-21.

Entgegnung an Prof. Dr. Pawlik. Centralbl. f. Gynak.. Leipz.,

1896. XX. 1266-1273.

Use of the renal catheter in the diagnosis of stone in the kidnf^y. Maryland M. J., Bait., 1896, xxxv, 100.

The Johns Hopkins Medical Students. (Correspondence). Pittsburgh M. Rev., 1896, x, 315.

Ovarian cysts weighing over one hundred pounds. Read at the Johns Hopkins Hospital Medical Society. May 18. 1S96. (Not published).

1897

The sources and diagnosis of pyuria. Med. News. N. Y., 1897, Ixxi. 756-761. Also: Tr. South. Surg. & Gynec. Ass., 1897, Phila., 1898, x, 99-124. Also: Am. J. Surg. & Gyna?c.. St. Louis, 1S98-99. xi, 5.5-56.

Excision of a parovarian cyst without removal of its ovary or tube. Johns Hopkins Hosp. Bull., Bait., 1897. viii, 50-51.

Horatio Reese Holmes, 1856 96. Tr. Am. Gvnec. Soc, Pliila.,

1897, xxll, 310-312.

The conservative treatment of myomatous uteri. J. Am. M. Ass.. Cbicaeo, 1897, xxix. 668-669.

Operative treatment of pelvic inflammatory disease. Compt. rend. Cong, period, internal, de gyn^c. et d'obst. 2. sess., 1896. Geneve. 1897. 133-150.

Address before the Central College of Physicians and Surgeons of Indianapolis on method of ureteral catheterization. Indiana M. J.. 1897. xvl. 211-214.

Kelly. H. A. & Ramsay, O. De Tusage du catheter rfinal dans le diagnostic et le traitement des maladies des reins et des uret^res. Rev. de gyn€c. et de chlr. abd.. Par., 1897, 823-842.

Kelly, H. A.. Noble. C. P. [«•/ a/.). Abdominal hysterectomy for fibroma uteri. South. Pract.. Naslivllle. 1897. xix. 7-21.


Operative gynecology. 557 p. 24 pi. 8 .


1898 v. N. Y., 1898. D. Appleton & Co. .".si p.


Conservation of the ovary In hysterectomy and hvrilero-mvomectomy. Brit. M. J.. Lond.. 1898, I, 288-291.


Ureteral anastomosis. 725-741.


Am. Gyntec. & Obst. J,


N. Y.. 1898, xll. Am. J.


The hand basins in use In surgical operating rooms Obst., N. Y., 1898. xxxvl. 188-193.

The preservation of the hymen. Am. J. Obst.. N. Y., 1898, xxxvii, 7-14.


The catheterization of the ureters In the male through an open cystoscope with the bladder distended with air by posture. Johns Hopkins Hosp. Bull., Bait., 1898, ix, 62.

A preliminary report upon the examination of the bladder and the catheterization of ureters in men. Ann. Surg., Phila..

1898, xxvii, 71-73.

Cystoscopy and catheterization of the ureters in the male. Ann. Surg., Phila., 1898, xxvii, 475-486.

Catgut sutures and ligatures. Med. News, N. Y., 1898, Ixxiil,

293-294. Bact^riologie de I'appareil gfnital de la femme. Tr. S. Bonnet,'

Semaine gyn6c.. Par., 1898, ill, 268.

Principes g^n^raux concernant les operations plastiques. [Transl.l Semaine gyn^c. Par.. 1898, ill, 353-356.

The treatment of complete rupture of the perineum by dissecting out the sphincter muscle and its direct union by buried sutures. J. Am. M. Ass., Chicago, 1898, xxxi, 1469.

Also: Maryland M. J.. Bait.. 1899, xli, 29.

Also: Memphis Lancet, 1899, ii, 29-32.

.ilso: Am. J. Obst., N. Y., 1899, xxxix, 216-217.

Discussion on the papers of Drs. Smith and Pryor. Tr. Am. Gynec Soc, Phila., 1898, xxiii, .59-61.

Abtlominal myomectomy. /&i(/., 221-239.

Discussion: Should non-absorbable ligatures be discarded in gynecological surgery. Ibid., 262-2G5.

Discussion on the papers of Drs. Dudley and Bovee. Ibid.. 284-286.

Kelly. H. A., & MacCalluni. W. G. Pneumaturia. J. Am. M. Ass., Chicago. 1898, xxxi, 375-381.

1899

The operation for complete tear of the perineum. Am. J. Obst., N. Y., 1899, xl, 202-213. Also: Tr. Am. Gynec. Soc, 1S99, xxiv. l.Sfi-202.

Some new instruments to facilitate the operation of myomectomv. Am. J. Obst., N. Y., 1899, xl, 218-221.

A new handle and grip for scissors for plastic and other delicate work. Ibid., 229-233.

The use of the renal catheter in determining the seat of obscure pain in the side. Ibid.. 328-334.

The reflux of air into the ureters through the air-distended bladder in the knee-breast posture. Ibid.. 468-470.

The apron method of treating complete tear of the perineum. (Correspondence). Ibid.. 515.

A curette for cervical cancer. Ibid.. 829-830.

The dissection and liberation of the sphincter and muscle followed by its direct suture in cases of complete tear of the perineum, with a splinting suture passing between the outer and inner margins of the muscle. Johns Hopkins Hosp. Bull., Bait.,

1899, X, 1-7.

A new operation for vesico-vaginal fistula. (Proc Johns Hopkins

Hosp. Med. Soc, Feb. 6, 1899.) Ibid.. 115. New use for renal catheters. (Proc. Johns Hopkins Hosp. Med.

Soc, Feb. 20. 1 899.) 76id.. 116. Report of gynecological cases: I. Extensive destruction of the

sphincter; II. Carcinoma uteri; III. Excessive growth of fat.

(Proc Johns Hopkins Hosp. Med. Soc.) Ibid.. 196-197.

The recognition of the poisonous serpents of North America. Ibid., 217-221.

Further uses of the ureteral catheter. Maryland M. J., Bait., 1899, xll, 141.

A new operation for vesicovaginal fistula. Ibid.. 106.

A new method of treating complete tear of the rectovaginal septum by turning down an apron into the rectum and by burled suture tlirougli the sphincter muscle. Med. News. N. Y., 1899, Ixxv, 334-335.

The exploration of the abdomen as an adjunct to every celiotomy. Mod. News, N. Y.. 1899. Ixxv, 784-788. Also: Ann. Gynec & Pcdlat., Bost., 1900, xili, 322-324.


1900


An Improved vesical speculum. 818-823.


Am. J. Obst., N. Y . 1900, xll,


298


[Xo. 344


The evolution of my technique in the treatment of fibroid uterine tumors. Am. J. Obst., N. Y., 1900, xlii, 289-307. Also: Tr. Am. Gynec. Soc, Phila., 1900, xxv, 207-221.

The removal of pelvic inflammatory masses by the abdomen after bisection of the uterus. Am. J. Obst., N. Y., 1900, xlii, 818-839. Also: Nashville J. M. & S., 1900, Ixxxviii, 208-211. Also: Am. J. Surg. & Gynec, St. Louis, 1901, xiv, 91-92. Also: Ann. Gynec. & Pediat., Boston, 1901, xiv, 174-177. Also: Johns Hopkins Hosp. Bull., Bait., 1901, xii, 1-4.

A new method of making applications to the vaginal vault, and a new instrument to facilitate cleansing the vagina in leucorrlicea. Am. Gynec. & Obst. J., N. Y., 1900, xvi, 193-195.

Notes on an improved method of removing the cancerous uterus by the vagina. Johns Hopkins Hosp. Bull., Bait., 1900, xi, 55-56.

A preliminary report on the surgical treatment of complicated fibroid tumors of the womb, with a description of two methods of operating. Ibid., 56-58.

Poisonous snakes. (Proc. Johns Hopkins Hosp. Med. Soc, Feb. 5, 1900.) Johns Hopkins Hosp. Bull., Bait, 1900, xi, 73.

Uncontaminated urine. Ibid., 91-92.

A note on a series of new vesical specula. Ibid.. 93.

Ureteral calculus; its diagnosis by means of the wax-tipped bougie. Escape of the calculus per rias naturales after forcible dilatation of the ureteral orifice. J. Am. M. Ass., Chicago, 1900 xxxiv, 515-517.

The present status of operations for cancerous uteri Ibid 12151220.

Resection and anastomosis of the divided ureter J Am M Ass Chicago, 1900, xxxv, 860-863.

A rapid and simple operation for gall-stones found by exploring the abdomen in the course of a lower abdominal operation Med. News, N. Y., 1900, Ixxvii, 959-963.

What precautions shall we take to avoid leaving foreign bodies in the abdomen after operations? N. York M. J., 1900, Ixxi,

Normal prophylactic appendectomv. Med. Rev St Louis 1900 xli, 207.

Medical Sermonets, No. 21. A plea for the humanities in nursini? Phila. M. J., 1900, vi, 179-180.

Methods of teaching gynecology. Phila. M. J., 1900 vi 391-393 Also: Indian M. Rec, Calcutta. 1901, xx. 105-107. '

Gynecology, its present, past and future. Phila. M. J. 1900 vi 550-551. » , .

Kelly H. A.. & Brown, T. R. A note on the use of nitrous oxid and ether as an anaesthetic Phila. M. J., 1900, vi. 869-871.

1901 Diseases of the ovaries and Fallopian tubes

In: Cyel. Dis. Child., M. & S. (Keating). Phila., 1901, v, 906-930.

Necessity of employing the newer methods of diagnosis in rectal

??^ol'r°^-^' diseases. Tr. Am. Surg. Ass., Phila., 1901, xix,

Kircher et Lemaire 1658-1900. Rev. de gvnec. et de chir abd Par., 1901, V, 829-850.

Erythrism from external stem pessary. Am. J Obst N Y 1901 xliii, 72. . •.

A new and better method of opening and of draining the bladder in women. Am. J. Obst., N. Y., 1901, xliv, 23-25.

Scratch-marks on the wax-tipped catheter as a means of determining the presence of stone in the kidney and in the ureter Am. J. Obst., N. Y., 1901, xliv, 441-454.

How to deal with the vermiform appendix. Some forms of complicated appendicitis. Am. Med., Phila., 1901," i, 109-110.

A historical note upon diptera as carriers of diseases Pare Declat. Johns Hopkins Hosp. Bull.. Bait., 1901, xii, 240-242.'

Drainage of the bladder and cystoscopic examinations. Johns Hopkins Hosp. Bull., Bait, 1901, xii, 298.


Jules Lemaire. The first to recognize the true nature of wound infection and inflammation, and the first to use carbolic acid in medicine and surgery. J. Am. M. 'Ass., Chicago, 1901, xxxvi, 1083-1088.

Discussion of Dr. A. H. Cordier's paper " Post-operative hemorrhage." J. Am. M. Ass., Chicago, 1901, xxxvii, 18.

Some further notes on the extension of the principle of bisection in abdominal surgery. St. Paul M. J., 1901, iii, 380-386.

Kelly, H. A. & Faure, J. L. L'extirpation des masses inflamma' toires pelviennes par I'abdomen, apres hemisection de I'uterus. [Trad.] Gynecologie, Par., 1901, v, 260-279.

1902 Extra-uterine pregnancy. In: Am. Text-Bk. Obst., 2. ed. (Norris & Dickinson), Phila., 1902, 324-346.

Nephrectomy; panhystero-myomectomy, with double salpingooophorectomy and appendicectomy; fixation of right kidney; suspension of uterus, with resection of a corpus-luteum haematoma; salpingo-oophorectomy, followed by resection of the sigmoid for carcinoma. Internat. Clin., Phila., 1902. 12. s., ii, 232-246.

Some notes upon the management of a modern private hospital. Internat Clin., Phila., 1902, 12. s., ii, 261-273.

The mimicry of pregnancy bv fibroid and ovarian tumors. Am. Gynec, N. Y., 1902, i, 449-462.

Further notes on the uses of the wax-tipped catheter in the diagnosis of stone in the kidney or ureter. Am. J. Obst., N. Y., 1902, xlvi, 66-70.

On methods of incising, searching, and suturing the kidney. Brit. M. J., Lond., 1902, i, 256-261.

Exhibition of a case of pelvic tuberculosis. Johns Hopkins Hosp. Bull., Bait., 1902, xiii, 141-142.

The treatment of vesico-vaginal and recto-vaginal fistulas high up in the vagina. Johns Hopkins Hosp. Bull., Bait., 1902, xiii, 73-74. Also: Indian M. Rec, Calcutta, 1902, xxii, 632-634.

The true spirit of the nursing profession. An address at the

annual meeting of the visiting nurse association of Baltimore.

Johns Hopkins Nurses Alumnae Mag.. Bait. 1901-2, i. 117-119. The advantages of the knee-chest posture in some operations upon

the vesical end of the ureters. J. Am. M. Ass., Chicago, 1902,

xxxix, 291-293.

Stricture of the ureter. J. Am. M. Ass.. Chicago, 1902, xxxix, 363-368.

Under what circumstances is it advisable to remove the vermiform appendix when the abdomen is opened for other reasons? J. Am. M. Ass., Chicago. 1902, xxxix, 1019-1021.


Labia urethrse and Skene's glands. Am. Med. Phila., 1903. vi, 429-431; 465-468. .ilso: Ann. Gynec. & Pediat., Bost, 1903, xvi, 104-108.

Removal of vesical papilloma through an incision in the septum with the patient in the knee-chest posture. Am. J. Obst., N. Y., 1903, xlvii, 28-31.

Instruments for use through cylindrical rectal specula with the patient in the knee-chest posture. Ann. Surg., Phila., 1903, xxxvii, 924-927.

Les debuts de I'histoire de I'appendicite en France. Bull, et mem. Soc. de chir. de Par., 1903, n. s., xxix, 632-649. Also: Presse med.. Par., 1903, i, 437-441.

The early history of appendicitis in Great Britain. Glasgow M. J., 1903, Ix, 81-97.

The selection of methods in abdominal hysterectomy. Glasgow M. J.. 1903, Ix, 241-254. Also: J. Ubst & Gynec. Brit. Emp., Lond., 1903. iv. 343-354.

A method of sequestrating the urinary bladder in extensive operations involving its peritoneal surfaces. Johns Hopkins Hosp. Bull., Bait, 1903, xiv, 96-98.

The danger of methods often used at present in dusting waitingrooms, cars, and other public places. J. Am. M. Ass., Chicago, 1903, xli, 861-862.


October, 1919]


299


Indications for particular methods In extirpating the diseased pelvic viscera. Lancet, Ix)nd., 1903, ii, 30-32.

The expansion of a specialty. Med. Rec., N. Y.. 1903, Ixiii. 693-698. 1904

My experience with the renal catheter as a means of detecting renal and ureteral calculi. Am, J. Urol., N. Y., 1904, i, 14-21.

Ideal method of removing the vermiform appendix. Am. Med., Phila., 1904, viii. 1123-1125.

Myomectomy in its relation to pregnancy. (Proc, Johns Hopkins Hosp. .Med. Soc. March 7, 1904.) Johns Hopkins Hosp. Bull., Bait.. 1904. XV. 259.

The piezometer, an instrument for measuring resistances. Ibid., 293.

Injuries to the rectum caused by gynecologic examinations. J. Am. M. Ass., Chicago, 1904, xliii, 1604-1606.

The treatment of simple rectal fistula by excision and suture without cutting tlie external sphincter muscle. Med News, N. Y., 1904, Ixxxv. 640.

Rubber cushions for general surgical gynecological and obstetrical use. Med. News, N. Y., 1904, Ixxxiv, 699-700.

Verletzungen des Rectums bei gynakologischen Untersuchungen. Berl. klin-therap. Wchnschr., 1904, i. 775-778. AUo: Wien klin-therap.. Wchnschr, 1904, xl. 775-778.

1905

Kelly, H. A. & Hurdon. E. The vermiform appendix and its diseases. Phila., 1905. W. B. Saunders & Co. 848 p. 3 pi. roy. 8°.


The great opportunity of the physician and the nurse. An address delivered at a service for physicians and nurses, Nov. 19, 1905, N. Y. 1905, Loizeaux Bros., 15 p., 32°.

The uterine curette. Am. J. Obst.. N. Y., 1905, li, 662.

The treatment of the nonmalignant strictures of the rectum. Am. Med., Phila., 1905, x, 479-480.

Some surgical notes on tuberculosis of the kidnev. Brit. GvnEPC. J.. Lond., 1905, xxi, 130-153. AUo: Brit. M. J., Lond., 1905, i, 1319-1323. .4Jso; Lancet, Lond., 1905. i. 1630-1632. Also: Med. Press & Circ, Lond., 1905, n. s., Ixxix, 663-668.

The surgical treatment of renal tuberculosis. Dominion M. Month., Toronto, 1905, xxiv, 125-132.

What is the right attitude of the medical profession toward the social evil? J. Am. M. Ass., Chicago, 1905, xliv, 679-681.

The best way to treat the social evil. Med. News, N. Y., 1905, Ixxxvi, 1157-1163.

The treatment of pyelitis. Med. Rec, N. Y., 1905, Ixvii. 521-524. Professor Smith on the Jersey mosquito. (Proc. .lolins Hopkins

Hosp. Med. Soc, Nov. 21. 1904.) Johns Hopkins Hosp. Bull,,

Bait.. 1905, xvi, 115116.

1906 Operative gj-necology. 2. ed. revised and enlarged. 2. v. N. Y. &

Lend., 1906. D. Appleton & Co. 680 p. 5 pi. 656 p. 17 pi. 8'.

Walter Reed and yellow fever. N. Y., 1906. McClure, Philips & Co. 293 p. 12 pi. 12'.


The treatment of cystitis. Canada I.,ancct, Toronto, 1905 6, xxxix, 385-398. Also: Maritime M. News. Halifax, 1905, xvil, 445: 1906, xvlll, 17. Also: Canad. J. M. & S., Toronto, 1906, xix, 67-82. Also: Canad. Prar. & Rev., Toronto. 1906, xxxi. f;i-7.".. Also: Old Dominion M. Month., Toronto, 1906, xxvi, 1-16.

The aseptic removal of an Infected fibroid uterus. Am. J. Obst., N. Y., 1906, liil, 493.

The use of a steel comb for dissection in the axilla. Ann. Surg., Phila., 1906, xliv, 104-105.

Two cases of stricture of the ureter: two caaes of hydronephrotlc renal pelvis successfully treated by plication. Johns Hopkins Hosp. Bull . Bait., 1906, xvil, 173175.

The regulation of prostitution. J. Am. M. Ass., Chicago, 1906, xlvi, 397-401.


Resections of the bladder in rebellious cystitis. N. York State J. M., N. Y., 1906, vi, 145-148.

Starvation and locking the bowels for from ten days to two weeks in complete tear cases. Tr. South. Surg. & Gynec. Ass., 1905, Phila.. 1906, xviii, 95-107. .4Jso.- Surg. Gynec. & Obst., Chicago, 1906, ii, 179-181.

The suprapubic route in operating for vesical fistulae. Tr Am Gynec Soc, Phila., 1906, xxxi, 225-253.

! In mcmoriam. Arthur Weir Johnstone, M. D. (1853-1895). Tr. Am. Gynec. Soc, 1906, xxxi, 427-430.

Some lessons from the life of Major Walter Reed. Med. Libr & Hist. J.. Brooklyn, 1906, iv, 332-338.

A satisfactory vesical evaeuator. Surg. Gynec. £ Obst., Chicago 1906, iii, 330.


ed. N. Y.. 1907. McClure,


Walter Reed and yellow fever. Philips & Co., 310 p., 12°.

Kelly, H. A., & Noble, C. P., eds. Gynecology and abdominal surgery. Vol. 1. Phila. & Lond., 1907, W. B. Saunders Co 859 p., 8°.


Byron Robinson and his work. Am. M. Compend., Toledo, 1907, xxiii. 3-4.

Success in life. Jeffersonian, Phila., 1906-7, viii, 86-98.

A g>'necological clinic — A case of stricture of the ureter due to stone, causing severe attacks of colicky pain and finally demanding operative interference: the removal of the kidney. Am. J. Clin. M., Chicago, 1907, xiv, 737-740.

The protection of tlie innocent. Am. J. Obst., N. Y., 1907, Iv, 477-481.

Remarks on dermographic tracings in clinical demonstrations. Internat. J. Surg., N. Y„ 1907, xx, 188.

On a method of preserving outlines of visceral lesions on nainsook or Suisse material. Jolins Hopkins Hosp. Bull., Bait., 1907, xviii, 120-122.

Bimanual vibratory palpation. J. Am. M. Ass., Chicago, 1907, xlviii, 1841.

Mensuration in urinary diseases. Tr. Am. Gvnec. Soc, Phila., 1907, xxxii, 302-346.

Surgical treatment of tuberculosis of the kidney. Surg. Gynec & Obst., Chicago, 1907, iv, 257-262.

The lesson of little things: the conquest of yellow fever. Youth's Companion, Bost., 1907, Ixxxi, 15.

1908 Medical gynecology. N. Y., 1908. D. Appleton & Co. 676 p. 8°. Kelly, H. A., and Noble, C. P., eds. Gynecology and abdominal

surgery. Vol. 11. Phila. & Lond., 1908, W. B. Saunders Co.,

862 p., 8°.


Anuria and nephrostomy by the ureter. Johns Hopkins Hosp. Bull., Bait, 1908, xix, 48.

The barred road to anatomy. Ibid.. 196-201.

Art applied to medicine and surgery. [Illustrated.) Tr. South. Surg. & Gynec Ass., 1907. N. Orleans, 190S, xx, 1-18.

My faith. Appleton's Mag., N. Y.. 1908, xl, 722-724,

Out of uncertainty and doubt, into faith. (Leaflet). [An abridgement of " My faith."]

A personal testimony. (Loaflot). [.\n abridgement of "My faitli.")

On Bible study. A letter to a friend. Our Hope, N. Y,, 1908 (October).

James Carroll, 1854-1907. Proc. Wash. Acad. Sc, 1908, x, 204-207.

Kelly, H, A. \rt nl.]. James Carroll. M. D., U. S. A., 1854-1907. Johns Hopkins Hosp. Bull., Bait, 1908, xix, 1-12.


Appondiritis and other diseases of the vermiform appi^ndix Pliila & Lond., 1909, J. B. LIppincott Co. 502 p. 8°.


300


[No. 344


Kelly, H. A., & Cullen, T. S. Myomata of the uterus. Phila., 1909. W. B. Saunders Co. 723 p. 8°.


Frere Jacques. Aesculapian, N. Y., 190S-9, i, 145-1.51. Amputation of the uterus in the corpus to preserve the menstrual function. Am. J. Obst., N. Y.. 1909, lix, 570-581. Also: Tr. Am. Gynec. Soc, Phila., 1909, xxxiv, 536-549.

The fat appendix. Ann. Surg., Phila., 1909, 1, 474-476. Post-operative psychoses. Surg. Gynec. & Obst., Chicago, 1909, ix, 515-521.

Also: Tr. Am. Gynec. Soc, Phila., 1909, xxxiv, 426-455.

Also: Am. J. Obst.. N. Y., 1909, lix, 1035-1037.

McDowell's successors in America. Tr. Am. Gynec. Soc, Phila.,

1909, xxxiv, 592-599.

1910 Treatment of an anteuterine pelvic abscess by sequestration and

drainage. Am. J. Obst., N. Y., 1910, Ixi, 921-925. An operation for umbilical hernia. Ann. Surg., Phila., 1910, li.

694-696. A chart to aid In the treatment of cystitis by distentions of the

bladder. Ann. Surg., Phila., 1910, 111, 664-667. Transurethral operations in women. J. Am. M. Ass.. Chicago, 1910,

liv, 1606-1607. Oral prophylaxis. Dominion Dent. J., Toronto, 1910, xxii, 563-570. Suspensio uteri. Klin.-therap. Wchnschr., Berl., 1910, xvll, 916-918. The ebb and flow of hypnotism since 1660. Maryland M. J.,

Bait., 1910, lii. 81-97. Social diseases and their prevention. Social Dis., N. Y., 1910, 1,

No. 3, 12-25. The gj'necological examination and topical treatment. In: Stereo-Clinic, Troy, N. Y., 1910, Sect, i, 2-38, 24 stereos.

Removal of a dermoid cyst of the ovary. Ibid.. Sect, iii, 2-11,

7 stereos. Vaginal incision and drainage for pelvic abscess. Ibid.. Sect, iii,

2-17, 12 stereos. Abdominal hysterectomy for a fibroid uterus. Ibid., Sect, iv,

2-42, 25 stereos. Bisection for the removal of a large dermoid cyst. Ibid., Sect, v,

2-48, 4 stereos. The relaxed vaginal outlet. Ibid.. Sect, vi, 2-64, 49 stereos. Examining and recording a pelvic or other abdominal tumor.

Ibid., Sect, vil, 2-14, 9 stereos. Dilatation and curettage. Ibid.. Sect, vii, 2-28, 15 stereos. Removal of the vermiform appendix. Ibid., Sect, ix, 2-26, 18 stereos. Closing incisions in the renal pelvis. Surg. Gynec. & Obst,

Chicago, 1910, xi, 201-202. Excision of the fat of the abdominal wall; lipectomy. Surg.

Gynec. & Obst., Chicago, 1910, x, 229-231. Movable kidney and neurasthenia. Tr. Am. Surg. Ass., Phila.,

1910, xxviii, 513-524.

Incisions in the abdominal wall to expose the kidney: incisions in the kidnev to explore its pelvis. Tr. South. Surg. & Gynec. Ass., 1909, [Phila.], 1910, xxii, 294-306.

Operations for hydronephrosis. Tr. Am. Urol. Ass., 1909, Brookline, 1910, iii, 377-395.

A physician's view of Christ's miracles. Sunday School Times, Phila., 1910, lii, 133.

Bible readers and Bible perusers. Bible Student and Teacher, N. Y., 1910, xiii, 11-13.

Two great questions addressed to every man and the Bible answers. Bible Student and Teacher, N. Y., 1910, xiii, 266-268.

Some opening verses in Luke. Bible Record, N. Y., 1910, vii, 229230.

1911 Pyuria. Am. J. Surg., N. Y., 1911, xxv, 1-5.

The abdominal incision — the removal of the wedge of skin and fat to facilitate intra-abdominal operations. Ann. Surg., Phila.,

1911, Uii, 364-366.


Graduated dilatation of the uretero-vesical orifice and the ureter above It. Canad. M. Ass. J., 1911, n. s., 1, 849-858.

Abdominal pain. Interstate M. J., St. Louis, 1911, xviii, 194-196.

A new and simple method of removing a renal calculus. .1. Am. M. Ass., Chicago, 1911, Ivii, 19-20.

Some American medical botanists. J. Am. M. Ass., Chicago, 1911, Iviii, 437-441. Also: Bull. Soc N. Hist, Chicago, 1911-12, i, 1-14.

Carcinoma of the clitoris. In: Stereo-Clinic, Troy, N. Y., 1911, Sect, xx, 2-10, 8 stereos.

Hsematoma of the vulva. Ibid.. Sect, xx, 2-7, 5 stereos.

Removal of cyst of Bartholin's gland. Ibid., Sect, xx, 2-8, 4 stereos.

The best method of exposing the interior of the bladder in suprapubic operations. Surg. Gynec. & Obst., Chicago, 1911, xii, 30-33. Also: Tr. South. Surg. & Gynec. Ass., Nashville, 1911, xxiii. 64-71.

Getting up early after grave surgical operations. Surg. Gynec. & Obst., Chicago, 1911. xiii, 78-79.

Boys, are you trying for the prize? Youth's Instructor. 1911. lix, 16 and IS.

Kelly. H. A. & Burnam. C. F. Reply to " A criticism of the technique of ureteral catheterization of Dr. Howard A. Kelly" Am. J. Surg., N. Y., 1911, xxv, 220-222.

1912 Medical gynecology. 2. ed. N. Y., 1912. D. Appleton & Co.

713 p. 8°. Walter Reed and yellow fever. Rev. ed. Bait., 1912. Med. Stand.

Book Co. 329 p. 12°.

A cyclopedia of American medical biography, comprising the lives of eminent deceased physicians and surgeons from 1610-1910. Illustrated with portraits. 2 v. Phila. & Lond., 1912. W. B. Saunders Co. roy. 8".


The treatment of incontinence of urine in women. Therap. Gaz. [etc], Detroit, 1912, 3. s., xxviii, 685-687.

The history of the vesicovaginal fistula; an address. Tr. Am. Gynec. Soc, Phila., 1912, xxxvil, 3-29.

To convert sentiment into action in fighting vice. [Baltimore], 1912. 41 p. 8°.

The Influence of segregation upon prostitution and upon the public. [Phila.T, 1912. 15 p. 8°. Also: Med. Press. & Circ, Lond., 1912, n. s., xciv, 158-162.

Some scattered thoughts on the prostitution question and about the attitude of our judges and our police. Social Dis., N. Y., 1912, No. 3, 13-34.

The social evil: what is the Church doing? The Living Church.

1912. 449-451 (July 27).

1913

Success in life. Jeft'ersonian, Phila., 1912-13, xiv, 1-9.

Talk on radium, delivered at the Medico-Chirurgical Faculty, April 11, 1913. Maryland M. J., Bait., 1913, Ivi, 151-154.

The allotment of renal and ureteral stones in shadow diagram of the body. Old Dominion J. M. & S., Richmond, 1913, xvi, 229-231.

Status praesens of the prostitution question. Tr. xv, Internat Cong. Hyg. & Demog. . . . , Wash. (1912), 1913, iv, 663-673.

Incontinence of urine in women. Urol. & Cutan. Rev.. St. Louis,

1913, xvii, 291-293.

The treatment of cancer with radium. An interview with Dr. Howard A. Kelly, of Baltimore. Reported by Burton J. Hendrick. Am. Rev. of Rev., N. Y., 1913, xlviii, 722-726.

-Address delivered at dedication of new building Oct. 16. 1913 [Univ. of Nebraska I. Proc, 4. Ann. Alumni Week, U. of N., Coll. of Med., Omaha, 1913.

Dr. Howard Kelly's appeal for Church civic service. Address at the New York Probation and Protective Association. Tlie Survey, N. Y., 1913, xxx, 118-119.


W October, 1919 J


301


Illustrated immorality. [Appeal for pictures.] (Communicationa.) The Survey. N. Y.. 1913. xxx, 151.

Letter on Miss Eberle's white slave statuette. (Communications.) The Survey. N. Y.. 1913. xxx. 312.

Commercialized vice must go. N. American. Phila., 19 1:; (Feb. 15).

Kelly. H. A. & Lewis, R. M. Skiagraphic demonstration of vesical

tumors. Surg. Gynec. & Obst.. Chicago. 1913, xvi. 308-312. Kelly. H. A. & Lewis, R. M. Silver iodine emulsion: a new medium

for skiagraphy of the urinary tract. Ibid., 707-708.

Kelly. H. A. & Neel, J. C. Carcinoma of the cervix of the uterus. Johns Hopkins Hosp. Bull.. Bait.. 1913, xxiv. 231-242.

Kelly, H. A. & Neel, J. C. Cauterization of "inoperable" carcinoma of the cervix of the uterus. Johns Hopkins Hosp. Bull.. Bait.. 1913, xxiv. 372-375.

1914

Some American medical botanists commemorated in our botanical nomenclature. Troy, N. Y., 1914. The Southworth Co. 215 p. S".

Kelly, H. A. & Burnara. C. F. Diseases of the kidneys, ureters and bladder, with special reference to the diseases in women. 2 V. N. Y. & Lond., 1914. D. Appleton & Co. 582 p. 652 p. S°.


What radium can do. Internal. Clin., Phila., 1914, 24. s.. iv, 41-43.

Radium in surgery. South. Calif. Pract., Los Angeles, 1914. xxix. 31-34.

The treatment of vesical fistuls at the vaginal vault following surgical operations. Tr. South. Surg. & Gynec. Ass., 1913, Atlanta. 1914, xxvi. 93-99.

A wonderful surgeon. [Theodor Kocher.] Am. Mag.. N. Y., 1914. Ixxvii. 59.

Smo and Drin — an Allegory. Union Signal. Evanston, 111., Ifll4, xl, 5 and 7.

Kelly, H. A. & Burnara, C. F. Radium in the treatment of uterine hsemorrhago and fibroid tumors. J. Am. M. Ass., Chicago. 1914. Ixiii. 622-628.

Kelly, H. A. & Dumm. W. M. Urinary incontinence in women, without manifest injury to the bladder: a report of cases. Surg. Gynec. & Obst., Chicago, 1914, xviii. 444-450.

Kelly, H. A. & Lewis. R. M. Diagnosis of the particular forms of hydronephrosis due to movable kidney. Surg. Gynec. & Obst., Chicago, 1914, xix, 601-603.


Suspension of the kidney. Trov. N. Y.. 1915. The Southworth Co., 21 p. 4'. In: Stereo-Clinic, Sect. xxix.

History of retrodisplacements of the uterus. Surg. Gynec. & Obst., Chicago, 1915, xx. 598-599.

The treatment of cancer by radium. Maryland .M. J.. Halt.. 1915, Iviil. 161-163.

The radium treatment of fibroid tumors. Tr. South. Surg. & Gynec. Ass., 1914, Ashvllle, 1915, xxvil, 230-235. Also: Surg. Gynec. & Obst.. Chicago, 1915, xx. 271-273.

Auto touring for civic righteousness. Christian Advocate. N. Y., 1915. xc, 712-713.

The virgin birth. Our Hope. N. Y., 1915 (October).

Kelly, H. A. & Burnam. C. F. Radium in the treatment of carcinomas of the cervix uteri and vagina. J. Am. M. Ass.. Chicago, 1915, Ixv. 1874-1878. Also: Radium. Pittsburgh. 1916, vl, 73-82.

1916

Some radium achievements. Am. J. Surg., N. Y.. 1916. xxx. 73-77.

Radium therapy in cancer of the uterus. Tr. Am. Gynec. Soc., Phila., 1916, xli, 532-541.

Treatment of fibroid tumors with radium. Women's M. J., Cincinnati, 1916. xxvi. 1-3.

Radiotherapy. Tr. M. Ass.. Alabama. 1916.


The double shame of Baltimore, her unpublished vice report her

indifTerence. Delaware State M. J.. Wilmington, 1916, vll', 2-5.

.4/ao.- Reprinted for wider circulation by Howard A. Kelly, M. D.

A surgeon's view of Billy Sunday, Surgeon. Sunday School Times Phila., 1916, Ivlii. 249.

Baker. E. C. Victims . . . . : with an introd. bv Howard A Kellv Bait, 1916. 20 p. ,S .

Kelly, H. A. & Burnam. C. F. A rfsum^ of results in the radium treatment of three hundred and forty-seven cases of cancer of the uterus and vagina. Am. J. Obst.. N. Y., 1916. Ixxiv, 326.

Kelly. H. A. & Neill. W. Caiiterization and fulguration of bladder tumors. J. Am. M. Ass.. Chicago, 1916, Ixvi. 721-723.


Methods and results of radium treatment of uterine hemorrhage due to other causes than malignancy. Tr. Am. Gynec Soc Phila.. 1917. xlii, 408-423. Also: Am. J. Obst., N. Y., 1917. Ixxvi. 513.


Fibroid tumors of the uterus treated witli radium Charlotte IX. CI M. J.. 1918. Ixxvii 135-137.

John R. Young, pioneer American physiologist. Johns Hopkins Hosp. Bull., Bait., 1918. xxix, 186-191.

Fibroid tumors and radium. Virginia M. Month.. Richmond. 1918 xlv. 1-3.

Two liundred and ten fibroid tumors treated by radium. Surg. Gynec. & Obst.. Chicago. 1918. xxvii, 402-409. Also: Tr. Am. Gynec. Soc, Phila.. 1918, xliii. 317-335.

Theodore Caldwell Janeway, 1872-1917. Boston M. & S. J., 1918, clxxix, 597-599.

Joseph Price, 1853-1911. Boston M. & S. J.. 1918. clxxix, 681-684.

John Herr Musser, 1856-1912. Boston M. & S. J.. 1918, clxxix, 772.

Dr. Keen on medical research. Science, N. Y.. & Lancaster, Pa , 1918, n. s., xlvii, 419.

Whiskey and the "flu." Manufacturers Record. 1918. Ixxiv. 72n.

A message to my three boys who have enlisted. The Evangelical,

1918. 8-9 (January 2). When a nation prays then victory will come. The Evangelical.

1918 (February 6).

How radium's rays point to Christ. When nature speaks in a sparkling parable. The Sunday School Times. 1918. 109 (F'ebruary 23).

1919

American medical biography. Bait., 1919, Norman. Remington Co. [In Press.]


The treatment of papillary tumors of the bladder in women. Am. J. Obst.. N. Y.. 1919, Ixxx, 328-335.

Reginald Heber Fitz, 1S43-1913. Boston M. & S. J., 1919, clxxx, 75-77.

The treatment of uterine hemorrhages from the mmlern viewpoint. Therap.. Gaz., Detroit. 1919, xUll, 229-233.

Dilatation and curettement. Therap. Gaz„ Detroit, 1019, xliii. 305-314.

The early recognition and treatment of cancer — the duty and the opportunity of the general practitioner. Therap. Gaz., Detroit. 1919, xllll, 381-389.

Muahrooms and toadstools. Therap. Gaz.. Detroit, 1919. xliii. 465-478.

Cancer of the uterus. Therap. Gaz., Detroit, 1919, xliii. 611-621.

A tribute to Sir William Osier. South. M. J.. Birmingham. Ala.. 1919, xli, 346-347.

Osier as I knew him In Philadelphia and in the Hopkins. Johns Hopkins Hosp. Bull., Halt.. 1919, xxx, 215-216.

Address delivered before the World's Conference of Anti-Saloon I.*ague Workers, Washington. I). C, June 4. 1919. Bait., 1919. Anti-Saloon League of Maryland. 12 p. 10°.

DATE OF PUBLICATION NOT ASCERTAINED

On Bible study. New York. n. d.. Loizeaux Bros.. 14 p. 32°.


302


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Then and now. New York, n. d., Loizeaux Bros., 8 p. 12°.

The Sabbath and the body. Educational campaign for Sunday

Schools and young people's societies. Lesson 2. Philadelphia

Sabbath Association. On Bible study. Daily Bible leaflet No. 3. World's Morning

Watch, Clitton-Springs, N. Y.


What a great doctor says. American Sunday School Union, Phila. In favor of votes for women. Testimonio personal.


Many articles by Dr. Kelly signed " H. A. K." appear regularly in the Christian Citizen.


CHRONIC PEMPHIGUS VEGETANS OF SEVERAL YEARS' DURATION

By Lewellys F. Barker, Professor of Clinical Medicine, Johns Hopkins University, Baltimore,

AND

David W. Caeter, Jr. {Formerly Resident Physician in Charge of the Private Ward Service, Johns Hopkins Hospital), Dallas, Texas


Though pemphigus vegetans is described as terminating fatally usually within one year from onset, a few eases of long duration are known, notably one recorded by Neumann of ten years' duration and another of similar duration described by Kobner in 1894. We have recently had under observation, in the private ward of this hospital, a patient who has already suffered from the disease for more than five years and who is still living, the condition exhibiting remarkable remissions and exacerbations. The malady is so rare and its nature is so obscure that even single cases that deviate in any way from the ordinary type should be recorded in the hope that data may gradually be accumulated that will clear up the mysterjthat still enshrouds the disease.

Pemphigus vegetans was clearly differentiated and first described as a clinical entity by Neumann' in 1886. The first English ease to be reported was the well-known one of Crocker' (1889). In 1891 Hyde' described the first case recognized in America. A fatal case from our clinic was reported with careful clinical history, autopsy findings, together with histological and bacteriological examinations, in 1903, by Hamburger and Eubel.* They reviewed the literature thoroughly and showed the gradual differentiation of the diseases once grouped together as " pemphigus." No review of the development of our knowledge of the disease is included, therefore, in the present paper.

Personal Observations

The case to be reported here is that of a young, tmmarried \\'oman, age 20, born in the United States, who was admitted to the medical service of the private wards, Johns Hopkins Hospital, on July 2, 1917. She complained of a " skin eruption " and of " colitis."

The family history was negative. One paternal aunt had died of cancer. There was no history of any skin disease in the family.


Syph., Wien,


'Neumann: Vierteljahrschrift tiir Dermatol. 1886, p. 159.

'Crocker: Brit. M. J., 1889, I.

'Hyde, J. N.: J. Cutan. Dis., 1891. IX. 412-456.

•Hamburger, L. P., and Rubel, M.: Bull. Johns Hopkins Hosp., 1903, XIV, 63-70.


As to her own past history, the patient had never been robust. She had the usual diseases of childhood without complications. At the age of three years, she suffered from " intestinal indigestion " and a diagnosis of " follicular colitis " was made ; and at the age of six, she is said to have had a similar attack, during which she had abdominal pain, " indigestion," diarrhea, and blood in the stools. Whenever she has been " run-down," from childhood on, she has had somewhat similar intestinal attacks. For some time past, she has had a chronic conjunctivitis and blepharitis. Her habits and mode of life have been normal. She has made a practice of sleeping out-of-doors.

About six years prior to admission the patient lived for a time in Constantinople. While there she had digestive disturbances, and on the way home to the United States a most distressing " urticaria " developed. Somewhat later she was " covered with an eruption much like that present at the time of admission."

There has been some intestinal trouble ever since her trip abroad. Thus, in 1913, the patient was seriously ill for some time with " colitis." In 1914, an appendectomy was performed, followed by general improvement. In August, 1915, lesions appeared in the mouth; in November, 1915, the eyes became inflamed and in December of the same year lesions reappeared in the mouth and also made their appearance on the external genitals (vulva) for the first time. A diagnosis of " herpes " was made at this time ; but, later on, the opinion was that the lesions were luetic in origin and the patient received numerous intravenous injections of salvarsan. In August, 1916, another physician made the diagnosis of " neurotic herpes," but he also soon changed his opinion and made the diagnosis of syphilis, treating the patient accordingly. There was some improvement following this arsenical treatment. In October, 1916, the lesions, which were described as " superficial ulcerations developing after small blisters had burst," reappeared in the mouth and about the vulva. Another series of intravenous injections was administered and five weeks later the lesions had disappeared. In December, 1916. ulcerative lesions again appeared in the mouth. In April of the following year, 1917, lesions in the throat were troublesome and tliose on the vulva were also noticeable, but were


THE JOHNS HOPKINS HOSPITAL BULLETIN, OCTOBER, 1919


PLATE XXXVIII


/H^


$M




W


.",0




' ' ' !'• " I'liigus vegetans. The appearanre of the axillary lesions on January 6, 1918, is here shown.


OCTOBEB, 1919]


303


not pronount-ed until May when the severe attack that led till' patient to apply for treatment at tlii;; h(is]iital beu^jin.

Physical Examination. — At the time of admission, the physilal examination showed a marked degree of emaciation, the patient being 3() pounds below her calculated ideal weight. There was sliglit pallor of the skin and mucous membranes. The eyes showed a >light conjunctivitis and a moderate degree of blepharitis. On the lips, palate and pharyn.v tliere was extensive superticial ulceration, which, over the lips, had involved the adjoining skin and had gone on to crust formation. The examination of the genitalia showed extensive excoriations of the labia majora, labia minora and vaginal mucosa. Tlie labial lesions varied in size, all the way from -small isolated vesicles to areas 1.5 to 2 cm. in diameter. The edges of the larger lesions were definitely elevated and consisted of clo.'^ely-.-^et vesicles containing turliid fluid. The lesions were covered with a foul, mucoid discharge. The inflammatory areola about the lesions was slight. There was no general glandular enlargement and the spleen was not palpable. The remainder of the physical examination showed no significant abnormality. The temperature was !»!t.6° F. and the pulse-rate 00. The patient complained mudi of pain in the region of the vulva and in the throat. She could not eat and was rapidly losing weight.

Laboratory Examinations. — At the time of admission (July, 1917) the blood examination showed: Hemoglobin 60 per cent (Sahli). and 1.").800 leucocytes. An examination made a month later showed R. B. C, 4,600,000 ; W. B. C, 8 100 ; lib. (.'^ahli), 81 i)er cent. In February, the examination showed K. B. C. I,o00,000; W. B. C, 8200; Hb. (Sahli), 88 per cent; and in the differential count PM. X., 68 per cent: I'M. B., 0.0 per cent ; PM. E., 1.5 per cent; S. M., 18 per cent; L. M., 12 per cent : Trans., l.o per cent.

The examination of the stools chemically and microscopically was negative.

The urine on a number of examinations was normal, except for the presence, occa.«ionally, of a trace of alliumin.

The Wassermann test of the blood-serum was negative on two occasions, as it had previously always been.

A culture for bacteria, made from the mouth lesions, showed no unusual organisms, though colonies, chiefly of Slaphijloroccus aureus, grew out. Smears made fr')m the lii>s, mucous membrane of the checks and pharyngeal pillars were all quite similar, showing only a few cocci and bacilli. There was nothing suggestive of the organisms that are found in Vincent's angina; there were no bacilli that resembled B. diphtheria'. nor were any pathogenic moulds found.

Roentgenogrnms of the ga-strointestinal tract showed a large, ptosed, cowhorn-shaped stomach, which was drawn well over to the right and downward. There was sluggish peristalsis and delayed emptying time. There were, however, no filling defects. There was some cecal sta-sis, enteroptosis and evidence of (post-operative?) adhesions in the lower right quadrant.

No.<te and Throat Report. — An examination made by Dr. S. J. Crowe on July 6 showed moderate enlargement of the posterior cervical lymph glands and superficial ulieration of


the soft palate, of both tonsils, pharynx and cheeks. The larynx and naso-pharynx were not involved in the ulcerative process. The paranasal sinuses showed no evidence of infection.

Xeuroloijical and F.fi/chic Examination. — There were no ol)jective disturbances of sensation, and subjectively only pain and some itching were complained of. Motility and reflexes were normal. Psychically, the jiatient reacted normally in l>eriods of remission, though during periods of exacerbation she was depressed, irritable and capricious.

I'rotein-Sensitization Tests. — In order to rule out, if possil)le, all the ordinary proteins (foods, pollens, etc.) that act as causes of allergic states, cutaneous test-s were made with egg, cocoa, casein, peas, barley, wheat (bread), potato, golden-rod pollen, rag-weed pollen, tiniotliy pollen, Iiorse-dander, and staphylococci. The results were all negative.

Course in the Hospital. — About three weeks after admission tlie patient developed an outspoken diarrhea. At this time a considerable amount of mucus and several large blood-clots were found in the stools. Microscopically, there were numerous leucocytes, fatty acid crj-stals, neutral fat and some muscle fibers in the feces. Cultures of the stool and of the washed mucus showed only the colon bacillus. Because many of the stools were large, light-colored and pultaceous, a quantitative diastase determination was niaile. The quantity present was above the normal minimum.

Throughout tiie patient's stay in the hospital, the diarrhea and intestinal symptoms, the colicky pains, the vague abdominal distress and the " indigestion "' were the most distressing symptoms, causing more trouble at most times than the skin lesions." There were seldom less than three, and often as many as ten, stools a day. Occasionally, there were attacks of vomiting, the vomitus being at times blood-tinged.

By the first of August the lesions in the mouth had disappeared and those about the vulva were much improved. On this date groups of several small vesicles were seen on the hard palate. The fluid was clear and small in amount. Each vesicle was surrounded i)y a slight erythematous areola. The vesicles did not persist for more than 21 hours and, after rupturing, coalesced to form very superficial ulcers varying in size from .25 to 1.5 cm. in diameter. The ulcers were grayish-white in color and seemed to be covered with a pellicle, the surrounding areola was slight. At this stage, the resemblance to the mucous patches of syphilis was striking.

Ten days after the reappearance of those in the mouth two symmetrical lesions developed on the breasts. These attained the size of a quarter and resembled closely the lesions of the vulva, except that there was more inflammatory reaction about them and less discharge from the surface. They persisted for three weeks, disappeared spontaneously and left no scars.

About the time of the development of tlie brea-st lesions the patient's temperature became elevated, reaching 102.6° F. It subsided within 48 hours. This was the only febrile episode of moment A blood culture made at this time showed no growth. Xo adequate explanation of the fever was arrived at.


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About the last of August, 1917, there developed pain on defecation and the amount of blood and mucus in the stools increased. A proctoscopic examination at this time showed a superficial ulcerated area, rather dark blue in color ; it covered the entire circumference of the rectum and extended upward about four inches, where it merged with mucosa of normal appearance. Ten days later the appearance of the rectal mucosa was again normal.

During September, October and the first half of November, tlie patient was somewhat better. The lesions recurred from time to time in the mouth, but were transient. There were brief attacks of diarrhea, but the abdominal pain was less disturbing than it had been.

About the third week in November, extensive ulceration again occurred in the mouth; the lesions about the vulva, which had almost cleared up, became more extensive and painful ; several small lesions appeared in the left axilla ; the diarrhea became more intractable. The body-weight which had increased from 107^ pounds to 129^ pounds began, at this time, to decrease, and the patient lost steadily up to the time of her discharge from the hospital.

The axillary lesions appeared first as groups of small vesicles. They ruptured, coalesced and formed very superficial ulcers. At no time were any true bullae seen.

The lesions on the vulva and in the axilla progressed steadily and the condition of the axilla on January 6 is shown in Pig. 1 (colored drawing). Fig. 3 (a photograph) shows the appearance of the vulval lesions on January 21, 1918.

During February, 1918, the axillary lesions spread, covering the entire axilla and extending down the thoracic wall for several centimeters. The perigenital lesions spread, extending over the mons veneris and down the thighs for a short distance. As the lesions progressed, the granulomatous and vegetative character became more evident. The edges were definitely elevated and had a " rolled " appearance. The secretion from the large lesions was abundant, fOul, yellowish in color and mucoid. A number of small lesions now appeared over the face, abdomen and buttocks, but they were of short duration.

Two weeks before discharge from the hospital, which was on March 12, 1918, a distinct improvement in the condition of the lesions had set in. They no longer increased in size, were less elevated and there was less discharge from them. The diarrhea continued, however, to be troublesome. The body-weight was 112-| pounds, only five pounds more than on admission.

Subsequent Course. — Upon discharge from the hospital, the patient returned to the care of Dr. J. A. Fordyce, under whom she had previously been for a time. He has kindly supplied us with the following information :

For three or four weeks she seemed very much better, but about May 1, 1918, she became decidedly worse again. There was an extensive outbreak of lesions about the vulva, thighs and lower part of the abdomen. About the middle of May, lesions appeared over the scalp, neck, back and chest and intractable diarrhea again developed.


When seen by one of us on June 1, 1918, the patient's condition appeared to be worse than at any time previous. There was marked pallor and emaciation; the lesions were more extensive than ever and the process appeared to be very active.

Later she improved somewhat, and left New York City for her home. On September 25, 1918, the patient's mother wrote :

She has not suffered so acutely as she did from the attack she had in New York, but the trouble never clears up and now the outbreak is more extensive than ever before. Twice her head has been entirely free from the eruption, and then it has broken out again; now it is clearing for the third time. She has had a great deal of digestive trouble

The patient has not been seen by us since, but in response to a note of inquiry, we learned at the end of January, 1919, that she was again having a remission, attributed this time to Christian Science. She says in her letter :

You will be glad to hear that, though I am not entirely well, I have every hope of being so, having been so far healed through Christian Science as to be able to be about and lead a normal life. When I was desperately ill last fall and no one held out any hope

of my recovery. Dr. , an old friend of my father's, advised

my turning to Christian Science. I was prejudiced against Science and was too weak at the time to be troubled, but I am firmly convinced that I was literally pulled from the brink of the grave by the power of prayer. Certainly, all medical means had been exhausted. Later, when I was still very ill, I turned to Christian Science and have since steadily improved.

Histological Study. — On January 21, 1918, a bit of the cutaneous lesion, indicated by the arrow in Fig. 2, together with some of the surrounding normal tissue was excised for histological study. The sections were stained for acid-fast organisms, for ordinary bacteria, by Gram's method, and by the Levaditi method for spirochetes. An examination of these sections failed to show any bacteria or parasites.

The following is a report on the histology by Dr. I. K. Pels, of the Department of Dermatology :

The sections are stained with hematoxylin and eosin. With the low power one sees a marked thickening and irregularity of the rete layer. The striking features of the section are the dilatation of the lymph spaces and blood-vessels, with marked infiltrations, especially about the latter, and extending in particular to the vessels deep down in the corium. In one place there is marked edema of the papillary layer, with a suggestion of beginning vesicle formation. The adnexa of the skin appear normal.

Under the high power one sees that the rete is thickened irregularly with some hyperkeratosis, acanthosis, and elongation of the rete pegs. The granular layer is increased in thickness in certain places. There is some edema of the prickle-cell layer and occasional infiltration with small mononuclear cells. The pars papillaris shows in some places a marked edema. There is dilatation of lymph-vessels and blood-vessels, and there are also many large lymph spaces. In one area the papillae have been entirely obliterated, apparently through pressure. There is marked infiltration with mononuclear cells; these are collected particularly around blood-vessels; the infiltration, in some instances, extends to a level directly beneath the rete layer. There is some edema in the corium. There are many small blood-vessels, probably newly formed. No marked changes are to be made out in the elastic or connective-tissue fibers. The blood-vessels are enlarged, but there is no definite endarteritis to be seen. The walls of the arteries.


ii THE JOHNS HOPKINS HOSPITAL BULLETIN. OCTOBER, 1919


PLATE XXXIX



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OCTOBEE, 1919]


305


however, are thickened, and there is a suggestion of occlusion of some small vessels. Many of the vessels are filled with red bloodcells and there is a marked cellular infiltration of the vessel walls and of the tissues just outside them. Even the deepest bloodvessels of the cerium show a perivascular exudate of round cells. The infiltration cells consist for the most part of small mononuclear elements, but there are a few polymorphonuclear cells, some of which have a reddish-staining protoplasm, suggesting an eosinophilic granular +++++ CONTENTS. There are. also, a few plasma-cells. Mast-cells were not seen (special stain required). My impression is that we are dealing with an inflammatory reaction, sub-acute in type, with formation of new vessels, giving rise to a granuloma. There is, on the part of the blood-vessels, apparently a reaction to some agent causing extravasation of cells with edema and subsequent enlargement and thickening of the rete layer. It is not a picture of syphilis or of tuberculosis; it corresponds more to the histologic picture of pemphigus vegetans.

2'realment. — During the patient's long stay of oiglit and a half months in the hospital many and various local and general measures were tried. None had any directly curative effect upon the lesions of the skin and mucous membranes.

Upon admission, the most urgent indication stx-mcd to be to overcome the emaciation, anemia and diarrhea. With this in view, the patient was kept in bed, in charge of a special nurse, and placed upon a bland diet to which liberal amounts of milk and cream were added. Dilute hydrochloric acid, Blaud's pills and various anti-diarrhcal mi.xtures were also u.*ed. There wa.s a steady gain in weight and improvement in the anemia until the last severe attack began i^hortly before slie left the hospital. For the intestinal condition, yeast was tried for a wiiile. half a cake twice a day. without any apparent effect. Later, hj-podermic injections of emetine hydrochloride were given, but no improvement followed.

Locally, many different ointments, lotions and dusting j>owders were used ; aside from alleviating the pain temporarily, they were of no value.

Several courses of sodium cacodylatc, in larger and in smaller doses, were given. No definite effect upon the lesions was observed.

In November, autohemothcrapy was tried, the patient re<eiving two injections of whole blood. This treatment had to Ik; given up l)ecause of the patient's condition.

In January, radium (180 mgm.) was ap]>licd to the axillary lesions by Dr. Curtis Burnam for ;3.j minutes. There was no ob.eervabic effect.

In Feliruarj-, two intravenous injections of arsphcnaniine (0.4 and 0.5 gm.) were given. Early in March the axillary lesions were twice treated with x-rays. Following the arsenical and Roentgen-ray treatments both the axillary and vulval lesions improvcfl markedly. There was also great improvement in the patient's general condition, but six weeks later the eruption was more widespread than ever before.

Throughout the cour.sc, most benefit was derived from general upbuilding measures and, perhaps, from injections of salvarsan (or arsphenamine). though remissions and exacerbations seemed to recur quite independently of any therapy.

Discussion. — We have had, then, under our ob.«ervation, over a long period, a young woman who has suffered from a


remarkable form of vesiculo-ulcerative, granulomatous process, which has involved the skin and mucous membranes, which has exhibited a marked tendency to spontaneous remissions and exacerbations, and has proved refractory to all kinds of therapy thus far employed.

That the diagnosis of chronic pemphigus vegetans is a correct one seems certain from: (1) The character of the lesions and especially their resemblance to those of syphilis (for which, as in so many cases of pemphigus vegetans, the disease was for a time mistaken) ; (2) the clinical course of the case; (3) the histological examination of the excised tissue; and (4) the exclusion of tuberculosis, syphilis and other common causes of granulomat<^)Us processes. In this diagnosis. Dr. J. A. Fordyce, of New York, and Dr. J. W. Lord and Dr. I. R. Pels, of Baltimore, all experienced dermatologists, concur.

Certain features, it is true, made one hesitate, at first, to make a diagnosis of pemphigus vegetans. Thus, as Dr. Fordyce pointed out, it is uncommon in pemphigus vegetans to have the lesion remain localized for so long a time to the oral mucosa and the genital organs ; and, besides, the lesions seemed to be deeper than in most cases of pemphigus. For these reasons, the diagnosis of " Periadenitis mucosa necrotica recurrens " (see Sutton's Text-book) was seriously considered ; but. as Dr. Fordyce emphasizes, the character and the localization of the lesions, the chronic course and the resistance to all therapeutic measures employed, confirm the diagnosis of pemphigus vegetans. Jloreover, the histological study revealed a perivascular granulomatous infiltration rather than a periadenitis.

What can be the etiology of this remarkable malady? Wc have been unable to answer this question satisfactorily, though there are several features that have interested us especially; the.<e may give clues to etiology ;in(l spur us on to further studies in similar cases.

Thus, in the first place, though the disease docs not apjicar to be contagious (in the sense in which this word is ordinarily used), still there is much to make us believe that it is due to a chronic infection. Its resemblance, clinically, to syphilis, the episodic ])yrexias and transitory Icucocytoses that accompany it, the chronicity and resistance to therapy, the tendency of the lesions to eccentric extension, and the histolr)gical picture of a granulomatous process (similar to, but not identical with, granulomatous processes due to known infectious agents like the Treponema pallidum of syphilis, the Trepunema pertenue of yaws, the Bacillus tuberculosis, the liacilhis mallei, the Ji. rhinoscleromatis, the Bnfillus leprw, the Slreplothric.es, the Sporotrichum schenckii, the Cryptococcus (/ilchrislii (of so-called blastomycetic dermatitis) and the Posadasia esseriforme (of coccidioidal granuloma or the San Joaquin Valh-y di.sease), are all features that make us su.'spect strongly that ue must h> dealing u-ith soinr chronic hnctcritil infection or jmrasitic invasion.

In the second place, one must he struck with the elective affinities of the disease-process for certain parts of the skin and mucous membranes. Thus, though any part of the skin


306


[No. 344


may be involved, the disease shows an especial tendency to attack the perigenital region, the inguinal regions, and the axillEe. Again, the mucous membrane most often attacked first is that of the mouth and throat, though it is not uncommon to have the vagina and the rectum also involved. In our patient, besides the rectal involvement, there had been a history of " colitis " and of severe gastrointestinal attacks from earliest life on, a point that may be of some importance. Our patient suffered also from chronic conjunctivitis and blepharitis; in a case described hy Ludmg (1897) the preputial sac and urethra were first affected ; and in Hamburger and Kubel's case, hoarseness due to the involvement of the laryngeal mucosa was the first symptom. These sit^s of predilection of the lesions can, of course, be no accident, and we shall doubtless, sometime, find an explanation of them.

In the third place, we lay a good deal of stress upon the fact


that, in the lesions, the infiltration of the tissues with small mononuclear cells is predominantly perivascular. The chemotactic influence, exerted upon the small mononuclear elements (and to a slight extent upon the polymorphonuclear elements), is chiefly localized (in the corium of the affected areas of skin) in the immediate neighborhood of the blood-vessels. Though this does not prove that the causative microorganisms are similarly situated, the fact is suggestive.

In the fourth place, the occurrence of marl-ed exacerbations and remissiotis in the course of the disease pi-esents a striking analogy with what we knoiv of recrudescences a7id ameliorations in some of the treponemal diseases, especially syphilis and yaws. Though analogies of this sort are not to be taken too seriously, we must, in a grave disease like pemphigus vegetans, pay close attention even to straws, in the hope that tliey may show us which way the wind blows.


STUDIES ON BLOOD SUGAR

IV. EFFECTS UPON THE BLOOD SUGAR OF THE REPEATED INGESTION

OF GLUCOSE

Louis Hamman and I. I. Hirschman


In a previous communication the authors ' have demonstrated the blood sugar response to the ingestion of a single large dose of glucose in normal persons and in others suffering from various diseases. For this study 100 grams of glucose were administered in the early morning after the night fast and the blood sugar and urine sugar estimated at short intervals thereafter. It was demonstrated that there are two important types of reaction, the normal type and the diabetic type, and still a third type, not nearly so clearly distinguished as these two, the reaction of increased carbohydrate tolerance. Although the reaction in normal persons varies in different individuals and in the same individual under different circumstances, its general characters are as follows: the blood sugar rises rapidly, but seldom exceeds 0.15 per cent; it falls somewhat more slowly to the original level, the whole reaction being over in less than two hours. In diabetics the rise is liigher and longer sustained. If the blood sugar surpasses 0.18 per cent, sugar usually appears in the urine, but sometimes it appears at a somewhat lower level and at other times it fails to appear even though 0.2 per cent of blood sugar is exceeded. From two to five hours pass before the blood sugar reaches the original fasting level. When tlie carbohydrate tolerance is increased, there is only an insignificant rise in the lilood sugar, wliich has usually a low fasting level.

Epstein " and Woodyat ' have raised the objection that these variations in blood sugar following the ingestion of glucose represent not real variations in the sugar +++++ CONTENTS of the blood, but apparent variations due to changing blood volume. This possibihty had suggested itself to us, but the investigations of Mosenthal and Hiller ' show conclusively that there is no constant relation between variations in blood sugar percentage and the water +++++ CONTENTS of the blood. Indeed, these two factors


show such bizarre relations that the one surely cannot depend entirely upon the other.

There is every possible gradation in the response to glucose ingestion, from the low insignificant curve of high glucose tolerance to the extreme and prolonged curve obtained in severe diabetes. However, the so-called diabetic curve is not peculiar to diabetes, for similar curves, though usually not so extreme, are obtained in nephritis, in hyperthyroidism and in many other conditions of lowered carbohydrate tolerance. These innumerable gradations force upon us the conviction that disturbances of carbohydrate tolerance are quantitative, not qualitative, variations. In other words, that diabetes represents functionally a disturbed, not an altered, mechanism of carbohydrate control.

For many years investigators have sought to distinguish between the glucosuria of diabetes and the glycosurias due to a great variety of other conditions. Of the many distinguishing marks that have been proposed only two are still urged as pertinent, namely, the paradoxical law of Allen and the diuretic effect of sugar in diabetes. Under normal conditions, when sugar is injected intravenously in large quantity, it acts as a diuretic ; administered otherwise, it diminishes the output of urine. In diabetes sugar acts as a diuretic by whatever route it be administered. But although this distinction is true for normal and totally diabetic animals, it is only relatively true for human beings. The ease with which sugar acts as a diuretic depends upon the degree of diabetes; in mild cases conditions are much nearer tlie normal than in the completely diabetic. In other words, the ease with which sugar produces diuresis depends directly upon the degree of carbohydrate tolerance and it varies with this tolerance. Here again tlie distinction is purely quantitative and the varying diuretic


October. 1919]


307


t'ffett of sugar surely eaunot be pointed out as a mark of di?^tim-tion between dialietes and other glycosurias. How convincingly the ol)scrvations of Woodyat and his co-workers ' eonfirm this statement! By carefully measured and timed intravenous injections of glucose the tolerance of an individual ean be accurately detenwined and sugar begins to act as a diuretic when tliis limit is overstepped.

It follows, then, that the only remaining feature that can be drawn upon to point a qualitative distinction between diabetes and other glycosurias is Allen's paradoxical law. Allen ' enunciates this Unv in these words: " Whereas in normal individuals the more sugar is given the more is utilized, the reverse is true in diabetes." .\pparently this law was enunciated to lit conditions in totally diabetic animals to which it applies aptly enough, but if we understand properly what is meant by the law. it is not applicable to diabetes in human beings. A\"hen carbohydrate tolerance is reduced only mildly the level of tolerance is by no means ai)solute. For instance, if the ingestion of SO grams of glucose be followed by the excretion of 1 gram of glucose in tlie urine, the ingestion of 100 grams will not caus«> an excretion of 51 grams. Far from it! Sudi experiments liave been frequently made and only a small jiroportion of the excess iuis been recovered from the urine. Only when excessive amount,-; of glucose are administered intravenously and at a uniform rate is the proportion of excretion constant. Here again the difference seems distinctly to be quantitative and not qualitative.

It occurred to us that further important evidence bearing upon this point could be obtained by testing the reaction of patients to the repeated ingestion of glucose. If there be a qualitative difference in the utilization of glucose by normal l>ersons and by diabetics, such tests should certainly give evidence of the difference. The only observations upon this point that we were able to find in the literature are a few experiments upon rabbits reported i)y Bang. In normal rabl)its Bang' finds that the .second administration of a certain do.^c of gluco.se given during the decline of the reaction from the first administration is followed by a much less marked reaction than was the first.

EXPERIMENTAL RESULTS In normal persons the administration of a second dose of glucose immediately after the reaction to the first dose produces a much less marked reaction upon the blood sugar than did the first dose. The protocols of experiments I and II illustrate this.

Experiment I E. L. C, male, single. Age: 28. Healthy physician.



Blood luKir Iririr t'r


nc »


Time


pfr cent c. c. per hour gran


» !« 


8.30


0.086


9


Glucose :


100 grams In 300 c. c. water.



9.00


0.118 88



9.30


0.110 74



10.30


0.087 162



Glucose:


100 grams In 300 c. c. water.



11.00


0.087 150



11.30


0.078 150



12.30


0.096 111




niood lugar Urine Urine auKar

Time per cent c. c. per hour grams per hour

Glucose: 100 grams in 300 c. c. water.

1.00 0.080 31

1.30 0.087 26

2.30 0.094 ' 26


Experiment II B. H.. male, single. Age: 29. Healthy physician. The patient, when previously tested, had shown a low renal threshold; that is, sugar had appeared in the urine when the blood sugar reached 0.14 per cent.

Blood sufrar I'riue Tritie siiRar

Time percent e. *•. per hour firunis iier hour

9.15 0.110 28

9.16 Glucose: 100 grams in 300 c. c. water. 9.45 0.162 28 Trace

10.15 0.127 30 Trace

10.45 0.130 26

10.50 Glucose: 100 grams in 300 c. c. water. 11.20 O.no 28

11.50 0.122 21

12.20 0.115 26

These experiments indicate that the mechanism of carbohydrate utilization, once stimulated, works more efTiciently than when called upon abruptly to manage large amounts of glucose. Probably to this fact is largely due the better utilization of sugar slowly absorbed, and the almost unlimited power of the body to utilize starch.

In diabetics the same difference is observed as in normal persons, although the difference is not so marked. The following protocols illustrate this point:

ExrERI.MF.NT III

A. B.. male, white, married. Age: 46. Dispensary No. 467.")0. A moderately severe diabetic who had become sugar-free on a carbohydrate free diet.


Time

8.25

8.30

9.00

9.32

10.30

11.30

11.35

12.05

12.30

1.30

2.30


Blood suRar per cent

0.161


tTr


Trine sugar


. c. per hour K:rams per hon 42

Glucose: 20 grams in 300 c. c. water.

0.205 51 0.3

0.244 5ti 1.57

0.196 45 0.9

0.180 68 0.66

Glucose: 20 grams in 300 c. c. water.

0.161 63 0.23

0.188 55 0.26

0.205 117 0.44

0.164 113 0.34

EXI'ERIMKNT IV

A. T., male, white, married. Age: 4ii. Hospital No. .^7026. Diagnosis: Hypertension, myocardial insufflclency. emphysema, artprlo-sclerosls, diabetes mcllltus, obesity. The patient had only a small amount of sugar in the urine, easily controlled by a moderate regulation of the diet.


Time 8.35 8.38 9.10 9.42 10.45 11.15


Blood auitar per ci'iit


Irin


- hour


Irin


0.150 4

Glucose: 100 grams In :U)0 c. c. water.

0.206 .1

0.272 33 0.68

0.222 76 2.66

0.190 49 1.63


308


[No. 344


Ur


Urine sugar grams per hour


Time per cent c. c. per hou

11.18 Glucose: 100 grams In 300 c. c. water.

11.45 0.212 41 1.36

12.27 0.209 54 1.69

12.57 0.173 37 0.56

Per.sons with lowered carbohydrate tolerance but without outspoken diabetes react in a similar way. Even if the second dose of glucose be much larger than the first the reaction following is not so marked.

Experiment V W. G., male, white, single. Age: 47. Hospital No. 36926. The patient had a mild infection of unknown cause and mental symptoms. No definite medical diagnosis had been made. Sugar had never been found in the urine on ordinary ward diet.


Time


Blood sugar per cent c


Urine c. per Iiour


Urine su grams pe


8.40


0.120


8.5



8.49


Glucose: 50 grams


in 300 c. c.


water.


9.20


0.176


314



9.53


0.200


463


1.7


10.55


0.166


242


O.S


10.57


Glucose: 50 grams


in 300 c. c.


water.


11.30


0.178


246


0.5


12.00


0.136


132


0.6


12.45


0.130


79




Experiment


VI



J. H., male, black, married. Age: 39. Surgical No. 42151. Diagnosis: Exophthalmic goitre, adenoma of thyroid. No sugar had been found in the urine on the usual ward diet.

Blood sugar Urine Urine sugar

Time per cent c. c. per liour grams per hour

8.30 0.097 36 Glucose: 100 grams in 300 c. c. water.

9.00 0.130 64

9.30 0.196 31

10.05 0.177 73

10.45 0.161 49

11.00 Glucose: 100 grams in 300 c. c. water.

11.30 0.173 57

12.00 0.164 142

12.30 0.148

1.00 0.116 25

Experiment VII Aurelius N.. male, white, married. Age: 37. Medical No. 36828. Diagnosis: Bilateral facial palsy, psychoneurosis. No sugar appeared in the urine on the ordinary ward diet.

Blood sugar Urine Urine sugar

Time per cent c. c. per hour grams per liour

8.25 0.093

8.30 Glucose: 100 grams in 300 c. c. water. 9.00 0.161 32

9.30 0.096 97

10.05 0.100 129

10.07 Glucose: 150 grams in 300 c. c. water.

10.35 0.148 84 11.05 0.097 60

11.36 0.094 114

In the following patient the utilization of glucose is normal, although a small amount of sugar appears in the urine. The patient has a low renal tlireshold, that is, a mild gi-ade of renal diabetes.


Urinn Urine sugar

. c. per hour grains per hour 43


Experiment VIII W. A. C, male, white, married. Age: 36. Diagnosis: Hyperthyroidism, psychoneurosis, renal diabetes. Small amount of sugar occasionally found in urine. A good deal of sugar in the urine after the ingestion of 75 grams of glucose.

Blood sugar Time per cent

8.30 0.088

8.40 Glucose: 100 grams in 300 c. c. water. 9.10 0.125 92 Trace

9.35 Glucose: 100 grams in 300 c. c. water. 9.43 0.105 251 0.2

10.10 0.085 658

10.50 0.084 216

11.40 0.084 68

It was found in testing several patients that they reacted to levulose in the same way that they did to glucose, only that the blood sugar rise was less marked. For instance, the diabetic whose response to glucose is detailed in experiment III gave the following response to levulose :

Experiment IX A. B., (same patient as In Experiment III). Male, white, married. Age: 46. Dispensary No. 46750. A moderately severe diabetic who liad become sugar-free on a carbohydrate diet.

Blood sugar Urine Urine sugar

Time per cent c. c. per hour grams per hour

8.30 0.167 66

8.34 Levulose: 20 grams in 300 c. c. water. 9.01 0.177 36

9.33 0.194 68 0.5

10.32 0.177 150

11.00 0.177 329

11.02 Levulose: 20 grams in 300 c. c. water. 11.35 0.167 178

12.10 0.184 103

1.00 0.184 144

CONCLUSIONS

1. The ingestion of glucose in some way stimulates the mechanism of carbohydrate disposal so that the repeated ingestion of the same amount causes a less marked hyperglycemia.

2. The same stimulating effect is noted in diabetes; the second dose is followed by a less marked hyperglycemia and glycosuria. However, the difference between the effects of the two doses is less marked than in -normals and varies in different stages of the disease. Possibly, when the diabetes is very severe, the difference may completely vanish.

3. In renal glucosuria the normal stimulating effect of the ingestion of glucose is retained.

4. Levulose produces a much less marked hyperglycemia and glycosuria than does an equal amount of glucose.

5. The difference in the reaction of the normal and the diabetic is a quantitative not a qualitative difference.

REFERENCES

1. Hamman and Hirschman: Archiv. Intern. Med., 1917, XX, 761.

2. Epstein: Discussion: Soc. for Clinical Inves., May, 1916.

3. Woodyat: Discussion: Assoc. American Phys., May, 1917.

4. Mosenthal and Hiller: Jour. Eiolog. Chem., 1916. XXVIII, 197.

5. Joslin: Treatment of diabetes mellitus, 2d Edition, 1917.

6 Woodyat, Sansum and Wilder: Jour. Am. Med. Assn., 1915, LXV, 2067.

7. Allen: Glycosuria and diabetes, 1913, Harvard Univ. Press.

8. Bang: Der Blutzucker, Wiesbaden, 1913.


OCTOBEB, 1919]


309


BENZINE POISONING, WITH REPORT OF A CHRONIC CASE

By RissKi.i. L. ir.viiKX, M. D.. Detroit. Midi. (From the Medical Clinic of The Johns Hopkins Hospital)


Benzine rarely causes poisoning, although it is largely used in the industrial world, especially for vulcanizing rubber, driving motors, cleaning, and as a drier in paints. Poisoning may be caused by eitlier drinking or inhaling large amounts of the substance. The absorption of small quantities seldom produces ill effects.

Benzine is a product of petroleum. It is not to be confused with benzene or benzol which is obtained by the fractional distillation of coal tar. It is not a chemically pure body, but consi.<ts of that part of petroleum which distills over between 70° and 90° C. The mixture is made up of hydrocarbons of the general formula CnH^,„. but consists principally of hesane, C«H,j, and heptane, C;H,„.

Numerous e.vperiments have been made to determine the physiologic and toxic effects of benzine. Lehman ' found that the inhalation of fumes by animals caused an irritation of the respiratory mucosa, muscular twitchings, and a slowly increasing narcosis. Felix ' experimented on prisoners in Bucharest, administering benzine as one would chloroform for anesthesia. Small doses produced nausea, smarting of tlie conjunctivje, and, in some cases, buniing in the chest and drowsiness. Larger doses caxised sleep and anesthesia, succeeded by nausea, vomiting, headache, dizziness, depression, and drowsiness, llontalti,' after the internal administration of certain quantities, noted vomiting, uncomfortable feelings in the stomach, difficult breailiing, miosis, muscle tremors, and symptoms of paralysis of the central nervous system. He concluded that gastrointestinal and cerebral toxic syni])toins are characteristic for benzine into.xication. The action he thought to be due to the aflinity of benzine for the fat, cholesterin, and lecithin group, which causes a change in the ganglion cells.

Hamilton ' interviewed nine interior house-painters who had experienced the effects of using a quick-drj-iug paint containing large quantities of benzine in small and practically unventilated nxmis. Dizziness, headache, spots before the eyes, dryness with choking in the throat, and burning of the eyelids were complained of by all, while some also had nausea, vomiting, pains in various parts of the aljdomen, and dysuria. In .several instances the worst discomfort developed on leaving work, the dizziness and staggering coming on in the open air.

A number of cases of acute poisoning are recordeil in the literature; some in children who had drunk the benzine, while others had resulted from inhaling large amounts of the funics, usually in cleaning tanks or vats in which there was very little ventilation. The symptoms noted as resulting from jtoisoning from drinking lienzine have been cyanosis, miosis, weak pulse, uncon.<ciousne.ss, and convulsions. Friediger* has collectetl 14 ca.«es of poisoning by it, eight of which resulted in death. The fatal cases were all in children. Autopsy in all cases showed hemorrhages into the lungs.


The most prominent symptom in all cases of acute poisoning from the inhalation of fumes, according to Wichern,* is the muscle tremor which may take the form of tonic or clonic cramps, the victims remaining almost without interruption in a condition of shaking fit. Wichern describes two cases: A workman was overcome by the fumes and fell into a tank of benzine. He was unconscious and showed wide, inactive pupils, spasticity, acrocyanosis, chills, and vomiting. In a second case, developing in a cleaning establishment, the symptoms were similar. Wichem states that in animal experiments muscle tremor is prominent also. Other observers have reported cases similar to those of Wichern. Peters ' describes tlie occurrence of retrobulbar neuritis in a girl of 14, the daughter of a glove-cleaner, who was addicted to the habit of inhaling benzine. The child was apathetic, stubborn, and learned slowly.

Chronic benzine poisoning seems to be of rare occurrence. According to Hamilton, ordinary' workmen in American oil fields and refineries show no ill effects. Russian writers state that much ill health is caused by the constant inlialation of benzine fumes in establishments where the working conditions are bad. Only four cases of chronic poisoning are to be found in the literature, all occurring in a rubber factorj', and two of which are reported in detail by Dorendorf.' The first man after eight months in the factory began to have tearing pains in the muscles and joints of the extremities. Later he suffered from fibrillary twitching of the tongue and a fine tremor of the hands. After a rest he went back to work. Sixteen months later he returned to the hospital complaining of pressure in the head, weak memory, difficulty in speaking, anorexia, a feeling of heaviness in the limbs, and a feeling of cold in the right hand and leg. Examination .showed psychic depression, hesitant speech, weakness of the right hand, hyperactive knee reflexes, and active tremor of the tongue, eyelids, and hand. The blood was normal except for the presence of free pigment. The second man wa,s a worker in the vulcanizing room. A few weeks after beginning work he lost his appetite, he l)egan to suffer from constipation, later from diarrhea, and linally from vomiting. He complained of iieadache and insomnia and had to stop work on account of colicky pains. He also had drawing i)aiiis in both arms and a sense of a leaden weight in the right arm with a feeling of coldness and formication. Examination showed tlie knee reflexes to be much increased and there was an after-tremor of the knee tendon. Striking the patella tendon evoked a contraction of the epigastric muscles and diapliragm. There was also tremor of the hands and tongue. Free pigment was found in the blood plasma, as in the first case. Dorendorf states that two other men were found in the same factory presenting similar symptoms. He allowed guinea-pigs to breathe the fumes of benzine


310


[No. 344


daily and found that they developed paresis and died in convulsions in 15 days.

The following case has been observed by us at The Johns Hopkins Hospital :

J. H. N., a white man, age 42, by occupation a cleaner in a llthographing factory, was admitted to the hospital October 4, 1915, complaining of weakness and dizziness.

Family History. — His father and four brothers died of pulmonary tuberculosis, but the patient has not been associated with his family for 25 years.

Previous Personal History. — The general health has been good up to two years ago. He had pneumonia at 28 and malaria twice yearly for 10 years. He has not had an attack of malaria for the past eight years. During the past four years he has had at times severe night sweats with cough lasting for three to four weeks. The last attack occurred two weeks before admission. He has never been jaundiced until his present illness. He had dysentery with blood and mucus in the stools In Cuba in 1S97. Three years ago his appendix was removed and his right kidney suspended. For 11 years previous to this operation he had had attacks of abdominal pain with a sensation of a sliding mass in the abdomen.

Present Illness. — The patient states that he has not been strong since the operation, but in July, 1914, he felt fairly well except for some weakness. Two months after beginning his present work he began to have generalized pains over his abdomen with nausea and vomiting after meals. He also had a feeling in his head which he describes as a " compression on the inside " or a "presslng-ln like." On October 1, 1914, he went to a hospital. At this time he also had a feeling of heaviness in the arms and legs, which made them feel like leaden weights. These symptoms cleared up. but on going back to work the nausea, vomiting, and dizziness returned and have become progressively worse. The nausea and dizziness have often been so severe that he has had to leave work. He has been gradually losing strength, the weakness before admission being so extreme that It often took an hour to walk to his home when it had ordinarily required only 12 minutes. At times he has fallen in the stree;. For the past three months he has been getting drowsy, his memory has been falling, and he has had difficulty in thinking. He has had a feeling of coldness in his legs for the past two months, which he describes as a feeling " as if menthol were rubbed on them." He has had shooting pains In the arms with cramp in the muscles ending in hyperextension of the fingers. Recently he has had spontaneous cramps of other muscles. His legs felt as if " a thousand needles were stuck In them." The sense of heaviness of the limbs continued until they felt like " bags of cement." He has noticed, also, tremor of the fingers and eyelids and failing memory: his head has not felt clear, and the left ear feels as if bubbles were flowing out of It. During all this time the nausea, vomiting, dizziness, and weakness have been progressive. He has had some dimness of vision. Five weeks before entering the hospital he noticed that his urine was becoming dark. Two days ago someone told him that he was jaundiced. He has had marked anorexia and constipation.

Physical Examination. — The patient is undernourished and looks sick. He is very dull mentally, and answers questions slowly. He does not seem able to think clearly. The lips are cyanosed. There is well-marked jaundice of the skin and mucous membranes. There is a sweetish odor to the breath. The pupils are equal and active. There is no glandular enlargement. There are signs of fibroid changes at both apices. The heart is negative. Blood pressure 100/65. The liver edge extends two fingerbreadths below the costal margin and is firm and tender. The


spleen is palpable. The tendon reflexes are very active everywhere, but equal on the two sides. When the patella tendon on one side Is struck there is a contraction of the thigh muscles on the opposite side. The superficial reflexes are present. Babinskl and Oppenhelm negative. There is no clonus; sensory examination is negative.

Laboratory Examination. — Wassermann (blood) negative. Sputum negative for tubercle bacilli. The urine had a specific gravity of 1022 and was negative throughout except for an occasional trace of albumin and a positive bile test on admission. Blood (October 6): R. B. C, 4,332,000; "W. B. C, 4550; Hb., 77 per cent; differential: P. M. N., 54.6 per cent; P. M. E., 2.6 per cent; S. M., 33.3 per cent; L. M., 5.0 per cent; trans., 3.0 per cent; unclassified, 1.3 per cent. Gastric analysis: Free HCL, 44 per cent, and total acidity, 72 per cent. The stool was dark brown and gave a positive bile test. There were no parasites or ova. On October 8 the white blood cells were 5400. A Calmette tuberculin test was negative with 1 per cent and 5 per cent. Four other blood counts showed the white blood cells to be below 5000. A second test meal was given with the same findings as in the first. On November 23 the white cells had risen to 7280.

Course in Hospital.— The symptoms rapidly disappeared. The reflexes continued active for a long while. At times striking the patella tendon would cause a contraction of nearly all the larger muscle groups. The jaundice and cyanosis cleared up. He gained weight rapidly and no longer had difficulty in thinking. He was discharged from the hospital November 23, 1915. At this time the reflexes were moderately exaggerated. Examination otherwise was negative. When seen several months later there had been no return of the symptoms.

The factory at which the patient worked was visited. It was found that the lithographing rolls were dropped into a trough, six feet long and one foot wide, filled with benzine, and scrubbed clean. About two gallons of benzine evaporated from the trough daily. The room in which the work was done was large, btit from the nature of the lithographing inks it had to be tightly closed to prevent the ink from drying. The patient had worked for over a year five hours daily at this trough where he was continually inhaling the fumes. No other workmen showed signs of benzine intoxication, but there were no otliers engaged in the same kind of work.

Formerly each printer had been required to clean the rolls from hi.< machine, and this took only a few minutes each day. The patient had been cleaning all the rolls for the entire factory.

SUMMARY

Chronic benzine poisoning is uncommon, but may occur. The symptoms complained of are referable almost entirely to the gastrointestinal tract and the central nervous system.

REFERENCES.

1. Quoted by Hamilton.

2. Quoted by Zornlaib: Wien. Med. Wchnschr., 1906, LVI, 366.

3. Hamilton: Kober and Hanson, Diseases of Occupation and Vocational Hygiene, Phil., 1916.

4. Friediger: Miinch. Med. Wchnschr., 1912, LIX, 252.

5. Wichern: Miinch. Med. Wchnschr., 1909, LVI, 2.

6. Peters: Deut. Med. Wchnschr., 1900, XXVI. 249.

7. Dorendorf: Miinch. Med. AYchnschr., 1901, XLVIII. 236.


October, 1919]


311


THE REACTION OF MONKEYS TO THE INOCULATION OF

MEASLES BLOOD

By Andrew A\'atsox SellvViids,

-1/(i>or, M. C. U. S. A.

(From the Base Hospital. Camp Meade, Md.)


In attempting the transmission of an iul'eutious disoiu^e from man to lower animals it is not to be expected, in the case of a refractory species, tiiat the typical clinical sj-mptoms will be reproduced exactly. A distinct advance has been aceomplisiied if one can obtain regularly even a single characteristic feature of the diseiu^e; a definite reaction occurring with reasonable constancy as the rt>sult of inoculation of the virus would enable one to determine many of the essential characteristics of the disease in question. Such reactions have i)ecn described as the result of the inoculation of monkeys with tlie l)lood of measles patient.s; one may mention more especially reports of the occurrence of rashes, of leucopa-nia and of Koplik spots. Wentworth and myself attempted to confirm tin's work.' The rcsult.< of tiie intensive inoculation of a small group of monkeys were very discouraging ^nd led to the conclusion that tlie reactions were too indefinite ami inconstant to permit the practical use of monkeys in testing the lilood of jiatients for the virus of measles. The present note will record .some further observations on the question whether the occasional slight and indefinite symptoms observed in monkeys represent a reaction to the virus of measles. It is of theoretical interest to determine whether the virus of the disease can at times multiply and produce minor symptoms in an occasional individual animal.

Summary of Literature. — Josias ' in 189S reported the successful transmission of mea.sles to tliree monkeys (" Sajous capucin " and "Sajous robustus"). These animals were inoculated on tlie mucou.s membrane with the mucous secretions from cases in full eruption and one monkey received in aildition an injection of blood. The incubation periods were 27 days. 1.'! days and II days, respectively, in these three animals; the rash was not remarkable, and the rise in temperature was not striking. .Anderson and Goldbcrger' were the first investigators to report the infection of monkeys with measles by the Injection of blood alone. Successful rf-aults were obtained in all species tested, namely. Macacus rhesus, eynomoltius and ninii us. The work was carried out on an extensive scale. The symptoms observed most commonly consisted of coryza and rhinitis, slight rash, malaise and occasionally some febrile disturbances. The rash was sometimes pink, sometimes copper-colored; it appeared, as a rule. 10 days after injection though the extreme limits varied widely, being from seven days to 21 and possibly 26 days. The febrile disturbance, in those experiments in which the temperature reaction was described in detail. wa,s extremely slight, being Insufllcieut of Itself to permit a diagnosU. .Moreover. It is noteworthy that sometimes the febrile period and the eruptive period did not coincide. In working with secretions from the mucous membranes these authors produced symptoms by subcutaneous injection of the secretions, but not by inoculation on the mucous membranes of monkeys.

Hektoen and Eggers • Inoculated three monkeys with blood from measles patients. Each of these animals developed more or less leucopwnia though, as emphasized by these authors, the leucocyte count in normal monkeys fluctuates rather widely and without any apparent cause. Two of the three animals remained free from any rash; the other developed a faint eruption about the eyes and the groin 15 days after injection. No Koplik spots wore found.


Subinoculations were made from monkey to monkey in three instances under conditions which were not especially favorable; the results were not striking.

Lucas and Prizer' injected two monkeys with blood from a preemptive case of measles. They noted a subsequent leucopoenia, and the development of Koplik spots ten days after injection. On subinoculatiou of two other monkeys, one also developed Koplik spots ten days after injection. No definite rashes developed, but these animals showed a tran.sient erythema limited to the face. In one animal an erythema and a conjunctivitis were noted as occurring three days after the appearance of Koplik spots and one day after the administration of ether. No febrile reactions developed in any of these animals.

Tunnicliff reported the development of a leucopoenia in a monkey injected with measles blood, whereas a control monkey maintained a normal white count after the injection of normal blood. No mention is made of the occurrence of any rash or other symptoms of measles.

Nicolle and Conseil ' injected one monkey (M. sinicus) with measles blood withdrawn 24 hours before the appearance of the eruption. A rise in temperature occurred, but no mention is made of any rash.

Jurgelunas " inoculated monkeys with blood of measles patients, with secretions from the mucous membranes and exposed some animals in a measles ward. The results were essentially negative. Especial attention was given to the nasal secretions; of the animals inoculated with blood, one died 11 days after injection from an undetermined cause; another received only a subcutaneous Injection; for a third, the blood tor injection was not taken until the second day of the patient's rash.

From this summary it is seen tiiut there are definite reports of the successful tran.smission of measles to monkeys. Attempts to infect other animals have been uniformly disappointing. According to the literature, all of the important features of measles have been reproduced in monkeys, namely, the rash, Ko])lik spots, leucopoenia, respiratory sj-mptoms, fever and malaise. It is rather striking, however, that no single investigator has ever obtained all of these features in any single individual or even in a series of animals. Moreover, there is no single symptom which appears at all constantly. The periods of incui)ation vary widely. Even under favorable conditions a large proportion of animals remain entirely normal.

EXPERIMENTAL WORK

In the course of some investigations involving the inoculation of Inimaii volunteers, advantage was taken of the opportunity to conduct simultaneous injections of monkeys, thereby permitting a compari.son of the results obtained in a refractory and in a highly su.«ceptible species.

Injection of Blood. — .Specimens of blood were collected in an ap])roximately equal volume of citrate solution from two cases of measles in the pre-emptive stage. The two specimens of citrated blood were mixed and injected as follows: 4 c. e. were injected into each of two adult monkeys {Macacun rhesus), half being given subctitnneously and the rest intrapi-ritfiiieally ; c. c. of the mixed specimens were injected into


313


[No. 344


each of two susceptible liuman volunteers, part of the material being given subcutaneously and the remainder intramuscularly. On the next day, blood was again taken from each of the measles patients; one had developed a rash 18 hours previously and the other was free from any eruption, the rash appearing six hours later. The specimens of blood were mixed and injected as on the preceding days into the two animals and also into the volunteers.* The relative dosage and the mode of injection for the monkeys, therefore, differed from that employed in the volunteers; it seemed desirable for the inoculations of the monkeys to adhere to conditions which would give the maximal opportunity for producing an infection.

These monkeys were examined for any evidences of respiratory symptoms, of malaise, of an exanthem and also Koplik spots. The temperatures (rectal) were taken twice daily, at about 9 o'clock in the morning and at 4 o'clock in the afternoon, before the feeding periods. The white counts were made, as a routine, in the morning only. Xeither animal developed any significant rise in temperature. Ehesus I showed a low leucocyte count which persisted for only two days and did not appear until the 11th day after injection. Ehesus II developed a leucopcenia which began on the sixth day after injection and persisted for three or four days. The counts in this animal subsequently became complicated by the development of a severe pneumonia. The records are as follows :

INOCULATIONS OF MONKEYS WITH MEASLES BLOOD


Days


Rhesus I


Rhesus II



after first


Temp.


White count


Temp.


White count


Additional observations on


lation


A.M.


P.M.


A.M.


P.M.



1


101.2


18,900



101.8


13,900



2


99.0


102.0


11,100


100.4


102.2


10,700



3


99.4


101.8


10,100


101.8


101.0


18,500




101.0


102.4


11,800


102.0


102.0


10,000



5


101.2


102.0


12,600


100.6


102.0


11,800



6 8


100.8

101. a

100.8


102.2 101.8 101.2


14,900

13,1001-2 8,300 9,7001 9,500


102.2 102.4 101.2


102.8 102.0 101.8


6,500 6,6001 5,200 5,6001 6,400


At noon, temperature 102.4. Count, 6,300.

Bleil for inoculation of volunteer.


9 10


100.8 101.6


102.4


4,700

7,4001-3

7,400


101.6 101.2


102.0


7,900 6,0001 9,900


At noon, temperature 102.0. Count 7,700.


11 12


101.4 101.2


101. S 102.6


4,400 4,000 5,700 4,6001 7,800


102.8 101.0


103.6 101.4


11,110 10,8001 12,600


Room temperature, forenoon

65% in afternoon SO'. Slight rash.


13


101.6


102.0


101.0


102.0


8,200


Slight rash.


14


100.9


102.2


9,200


100.0


101.0


6,400



15


101.4


102.0


8,900


100.0


100.0


6,000


Early signs of pneumonia.


16


100.6


101.0


8,300


99.4


99.8


6,600


Definite pneumonia.


17


100.6


102.2


17,300


98. 8


100.6


18,400


Critically in.


18


102.0


102.2


13,900


101.0



9,400


Critically ill.


20


101.2



14,500


100.8



44,000


Marked improvement by crisis.


1 White counts in atte

= At noon, temperature 101.0, <

=1 At noon, temperatur


  • The precautions observed in the protection and selection of the

volunteers (VIII and IX). as well as the details concerning their inoculation, are given in the September number of this Bulletin.


Ehesus I developed no respiratory or constitutional symptoms and no evidence of an exanthem or of Koplik spots. Ehesus II was bled on the second day of his leucopcenia and at the beginning of the seventh day after the first of his two inoculations. Three c. c. of blood were mixed with 2 c. c. of 2.5 per cent sodium citrate in physiological saline and injected intramuscularly and subcutaneously in the gluteal region into a susceptible himian volimteer. No local or general symptoms developed; the temperature and white count remained normal.

Ehesus II at the beginning of the 12th day after the first injection developed a faint but distinct rash over the face and uppermost part of the thorax. In some areas, especially over the chest, a diffuse erythematous blush was present. Around the eyes and nose there occurred discrete macules from 1 to 2 mm. in diameter; these were especially marked around the hair follicles. Moderate but definite malaise was present on this day only. On the second day the rash faded almost completely, leaving beliind only very slightly pigmented areas ; by the third day this pigmentation had disappeared. On the next day an outspoken and very severe pneumonia developed, probably as the result of the deep and prolonged etherization employed during the collection of blood in the previous week. A blood culture, taken after the pneumonia was fully developed, showed no growth.

The rash developing in this animal after an incubation period corresponding to that in human eases was in no way characteristic of the exanthem as it occurs in man. However, it is not to be expected that the skin eruptions developing in a lower animal would necessarily conform to the human exanthem. This consideration greatly increases the difficulty of determining whether an atypical rash is due to the virus of measles. The principal points bearing on the inter[jretation of this exanthem are :

1. The period of incubation.

2. The results of the inoculation of blood from the monkey into a susceptible individual.

3. The behavior of susceptible human volunteers inoculated with the same specimen of blood which was injected into the monkeys.

4. The exclusion of other factors.

The period of incubation in this animal, 12 daj's, would conform very well with the diagnosis of measles.

The. negative result of the inoculation of blood from tlio monkey into man might be explained on two grounds; either the supposedly susceptible volunteer may in reality have been immune or the single specimen of monkey's blood may not have been taken at the most favorable period for transmitting the disease.

The absence of any symptoms in the two volunteers inoculated from the same specimen of blood that was used for the monkeys does not constitute final proof, but it speaks very strongly against ascribing this rash to the virus of measles. It does not seem plausible that a highly refractory animal would be overwhelmed by a large inoculation intrapehtoneally, if an extremely susceptible host escapes infection after a moderately large subcutaneous and intramuscular injection.


OCTOBEK, 191 9 J


313


Of other factors which might give rise to a rash under the conditions of the experiment the question of serum sickness requires consideration. This possibility is importiint, even thougli anaphyhixis has not been described in monkeys; and serum rashes, which are presimiably a manifestation of anaphylaxis, have not been produced in lower animals. The two conditions, measles and serum sickness, have certain features in common. In either condition, the constitutional symptoms may be very mild. The incubation periods are almost identical, the 12th day being known as the critical day in serum disease. The rash of serum disease is altogether protean in character; the e.xantliem under discussion resembled serum rashes more closely than the eruption of measles.

The eruption in monkeys does not occur constantly after the injection of measles blood. Indeed, the indefinite character of the rash and its comparatively low incidence considerably increases the difficulty of determining its cause. There are certain points which would favor the view that the rashes observed by Anderson and Goldberger were not due to serum disease. These authors report that several monkeys developed no rasli when injected with moderately large amounts of liuman blood from advanced cases of measles which presumably did not contain the virus of the disease. Moreover, in performing subinoculations, a rash sometimes developed when monkeys were injected with the blood of other monkeys ; from their description it would seem that these rashes were less striking than tho.^e obtained with measles blood from human cases. Anderson and Goldberger also observed rashes after the inoculation of nasal secretions, thereby affording conditions in which anaphylactic manifestations would not occur. These rashes developed only in animals injected subcutaneously with secretions; two monkeys inoculated on the mucous membranes developed no symptoms. The possibility of producing bacterial septicicmia by these injections must be borne in mind ; in one instance it was noted that, at the time a rash appeared, blood cultures showed the presence of a micrococcus.

It seemed desirable to test the possibility of producing a serum rash in monkeys. Human serum was employed for one group of animals and, in order to obtain more favorable conditions for the production of anaphylaxis, another set was injected with normal horse serum. Ten animals in all were inoculated. Eight of these (Macacus syriclus) had received no previous treatment with serum; the two (.V. rliesm) which were injected with measles blood were reinjected with normal serimi. All of the animals were injected intravenously and the majority also received intraperitoneal or subcutaneous injections either at the time of the intravenous injection or after an interval of one or two days. A.«suming that .serum sickness represents a reaction between antigen and antib<jdy it was considered that the injection of large amounts of serum by different routes would afford a maximal opportunity for the coexistence of antigen and antibody within the organism.

Observations were continued over a period of three weeks. Of these ten animals six remained entirely negative and four


developed a very faint erytliematous blush eight to ten days after injection. This appearetl on the face and uppermost part of the chest, persisting for two or three days. It disappeared on pressure and was not followed by pigmentation or desquamation. Some of these animals showed slight loss of appetite at this time, but there was no definite evidence of malaise. The erj-thcma in Rhesus II appeared 10 days after the second injection and persisted for three days. The s}'mptoms were less definite than after his first injection with measles blood. These two rhesus monkeys were of the same size and apparently the same age; one reacted slightly both to the injections of measles blood and normal blood, while the other reacted to neither. The second injection of human serum in these animals produced no clinical symptoms of anaphylactic shock. The following table gives the details of these injections :



INJECTIONS OK MONKliVS WITl


SERIM



Species

of monkey


Material injected


Amount injected



Serial number


c =


Result


1

10 weeks later

2 10 weeks later 3 days later

3 2 days later

2 (lays later

&

6 1 day later

7 1 day later

8 I Hay later

9

10

I day later


.V. rhesus !U. rhesus

.V. syriclus

.V. si/rictus

M. syriclus M. syrictus

M. syriclus

M. syrirlus

M. syriclus M. syriclus


Measles

blood Human

serum Mrasles

blood Human

serum Human

Human

scrum

Human

Human

Human

serum Horse

serum Horse

serum Horse

serum Horse

serum Horse

serum Horse.

scrum Horse

serum Horse

scrum Horse

serum Horse


Ic.c. None Ic.c. None None 3c.c. None 2c.c. None None Ic.c. None None None None None Sec. None None


c.c.

None

Ic.c.

None 10 c.c.

None 1 c.c.

Sec. n c.c.

None

None 10 c.c.

None 10 c.c.

8 c.c. 10 c.c.

None

None IC c.c.


None

6 c.c. None Sec. None

7 c.c. None Sec. None Sec. S c.c. None See None See None 7 c.c. See None


No effect. No effect . Deflnite rash.

Slight erythema 10 days later.

, Slight erythema 8 days later. 

No effect.

No effect.

1 Slight erythema r 8 days later.

Slight erythimn days later.

J- No effect. No effect.

> No effect.


The slight erythema produced in some of these animals was by no means sufficient to permit of its interpretation as a siTuin rash : the symptoms, however, did appear to correspond fairly well with some of the indefinite rashes to which some authors attach significance in the diagnosis of measles. A very slight reaction is sufficient to complicate the interpretation of the delicate and inconstant effect resulting from the injection of measles blood.

SUMMARY

I. Blood from two early cases of measles in the pre-eruptive and later in the early eruptive stage was injected subcutaneously and intraperitoneal ly into two monkeys. One


314


[No. 344


animal remained free from symptoms; the other developed a moderate leucopoenia and later a slight rash.

2. A portion of the same specimen of measles blood was injected subcutaneously and intramuscularly into two susceptible human volunteers. Xo symptoms resulted.

3. A specimen of blood from the monkey which subsequently developed a rash was injected into a susceptible volimteer, but produced no symptoms.

4. Normal serum injected into monkeys was followed by a very slight erj'thema appearing about eight to ten days after injection in four of ten animals.

5. The weight of evidence in these experiments is against the interpretation of the symptoms in this monkey as representing a reaction to the virus of measles.


LITERATURE

1. Sellarda, A. W., and Wentwortli, J. A.: Bull. Johns Hopkins Hosp., 1919, XXX, 57.

2. Josias, A.: Tribune med., 1898, XXIX, 211.

3. Anderson, J. F., and Goldberger, J.: Pub. Health Rep., 1911, XXVI, 847, 887; Jour. Amer. Med. Assn., 1911, LVII, 113, 476, 971, 1612.

4. Hektoen, L., and Eggers, H. E. : Jour. Amer. Med. Assn., 1911. LVII, 1833.

5. Lucas, W. P., and Prizer, E. L. : Jour. Med. Research, 1912, XXVI, 181.

6. TunniclifE, R.: Jour. Infect. Dis., 1912, XI, 474.

7. Nicolle, C, and Conseil, E.: Compt. rend. acad. sclen., 1911, CLIII, 1522.

8. Jurgelunas, A.: Centralbl. £. Bakteriol., Orig., 1914, LXXII, 483.


NOTES ON NEW BOOKS


The Nervous Heart. By R. M. Wilson and J. H. Carboll. (London: Henry Froude; Hodder and Stoughton, 1019.)

The book represents an attempt to explain " Disordered Action of the Heart " (D. A. H.) , as well as post-febrile ' functional heart disorders " by disturbances of the nervous control of the heart. The basic theories need more proof before the deductions can be accepted. Nothing new is added to the prognosis or treatment of the functional heart disorders described.

V. R. M.

Burns and Their Treatment. By J. M. H. Macleoii. Cloth. $2.00. (London: Henry Froude; Hodder and Stoughton, 191S.)

The subject of burns and especially their treatment is always of vital significance; and although the author has added nothing really new or radical to our general knowledge of the subject, he has given us a brief and excellent epitome of the modern conception of burns. Better still, the fact that he has recorded his personal experiences based on contact with a vast amount of material adds additional interest.

In the eleven chapters the different aspects of the subject are taken up as follows: Burns from Heat (five chapters) , Electricity, Lightning, X-Rays and Radium, Solar Burns, Corrosives, High Explosives.

The fact that the author is a dermatologist of note makes his descriptive and pathological comments especially valuable. It Is regrettable that compactness has allowed a place for so few Illustrations. Despite its small size, however, the book, which is intended apparently to fit the coat-pocket, contains a great store of information.

The subject matter is attractively presented. The book has been carefully edited and is well printed. It should certainly serve the purpose of assisting the reader in keeping abreast of modern advances in this interesting subject.

I. R. P.

A Study of the Mental Life of the Child. By Dr. H. Vox HuGHellmuth. Paper, $2.00. (Washington: Nervous and Mental Disease Publishing Company, 1919.)

The author divides her study into two periods, the period of infancy and the period of play. Thirty-nine pages are devoted to the former, the rest of the book to the latter. It is not possible to summarize the detailed observations which are found throughout the book, or to refer to the author's interpretations of many


of the phenomena of childhood, but the chief value of the book lies in these detailed observations, and in the endeavor to interpret them in terms of the actual driving forces of human life.

In discussing the child as he actually is, there is no topic censored, and thus in a way we have the most honest book on child psychology available. The author, however, goes even further than showing lack of embarrassment in dealing with the sexual life of the child, with its interest in matters of the toilet and so on; she exhibits the Freudian tendency to identify pleasure with sexual pleasure, and thus a sexual interpretation of very doubtful validity is given to many phenomena. She comes to her topic steeped in the Freudian dogmas, sharing the tendency of the Freudian School to generalize, to push hypothesis to an extreme, and to equate hypothesis with actual observation of fact.

Notwithstanding this extreme attitude, which to some extent distorts its proportions, the book is one that deserves the serious study of any one interested in the psychology of childhood.

C. McF. C.

Physiology and Biochemistry in Modern Medicine. By J. J. R. MACLEOD. (St. Louis: C. V. Mosby Company, 191S.)

This book is intended by the author to be " an advanced text in physiology for those about to enter upon their clinical instruction and, at the same time, a review for those of a maturer clinical experience who may desire to seek the physiological interpretation of diseased conditions." It is published in an attractive form and contains many good illustrations. The treatment of the subject matter is, in general, clear, and would appear to be well done for the reader for whom it is intended. Of particular present day interest from the point of view of the clinician are those sections dealing with the respiration, the circulation, and the excretion of urine. The book is a most praiseworthy production, and deserves a wide reading among those who have at heart the closer union of physiology and the allied sciences with clinical medicine.

H.


THE JOHNS HOPKINS HOSPITAL BTILIETIN.

It is Issued monthly. Volume XXX is in progress. The subscription pi-ice Is $3.00 per year. (Foreign postage, 50 cents.) Price of clothbound volumes, $3.50 each.

A complete index to Vols. I-XVI of the Bulletin has been Issued. Price. 50 cents, bound in clotli. Orders should be addressed to Thb Johns Hopkins Press. Baltimore, Md.


OCTOBEB, 1919]


315


BOOKS RECEIVED


TXe Works of John Caius. M. D. Second Founder of Gonville and and Caius College and Master of the College 1559-1573. With a Memoir of His Life. By John Venn. Sc. D. Edited, at the request of the Governing Body of the College and of the President and Fellows of the Royal College of Physicians, by E. S. Roberts. Master, in Commemoration of the Four-hundredth Anniversary of the Birth of John Caius in 1910. 1912. 8°. 108 pages. University Press, Cambridge.

Royal College of Physician^ of London. Catalogue of tlie Library. 1912. 8°. 1354 pages. Spottiswoode £ Co.. Ltd.. London.

Colloids in Biology and Medicine. By Prof. H. Bechhold. Authorized Translation from the Second German Edition, With Notes and Emendations. By Jesse G. M. Bullowa, .\. B., M. D. 54 Illustrations. 1919. 8°. 464 pages. D. Van Nostrand Company, New York.

Diseases of the Siiii. By James H. Sequeira. Third edition, with 52 plates in color and 257 text-figures. 1919. S°. 644 pages. P. Blakiston's Son & Co., Philadelphia.

Medical Society of London. Transactions of the Medical Society of London. Volume the forty-first. Edited by Hugh Lett, F. R. C. S. and Edmund Cautley, M. D. 1918. 8°. 302 pages. Printed for the Society, by Harrison & Sons. London.

Vnivcrsity of Iowa Studies in Medicine. First Series No. 24. Collected Studies and Reports. Volume 1. Number 5, January. 1919. 8'. Published by University, Iowa City.

Monographs of the Rockefeller Institute for Medical Research. No. 10, April 16, 1919. The Pathology of the Pneumonia in the United states Army Camps During the Winter of lUn-tS. By William G. MacCallum. M. D. 1919. 8°. 147 pages. The Rockefeller Institute for Medical Research, New York.

Transactions of the Section on Qenito-Vrinary Diseases of the American Medirnl Association. At the Sixty-ninth Annual Session. Held at Chicago, June 10 to 14, 1918. 8°. 302 pages. American Medical Association Press, Chicago.

American Surgical Association. Transactions of the .American Surgical Association. Volume the thirty-sixth. Edited by John F. BInnie, M. D. 1918. 8°. 602 pages. Printed tor the Association, Philadelphia.

Ocorge Williams Hooper Foundation for Medical Research. The Department of Re.'search Medicine of the University of California Medical School, San Francisco. Collected Reprints. Volume III. 1917-1918. San Francisco. California.

Colloid Chemistry. An Introduction, With Some Practical Applications. By Jerome Alexander, M. Sc. Illustrated. 1919. 16°. 90 pages. D. Van Nostrand Company. New York.

The Blind. Their Condition and the Work Being Done for Them In the United SUtes. By Harry Best. Ph. D. 1919. S'. 763 pages. Macmlllan Company, New York.

Clinical Case-Taking. An Introduction to Elementary Clinical Medicine. By Robert D Keith. M. A., M. D. (Aberd.). 1919. 12°. 104 pages. Paul B. Hoeber. New York.

The Soldier's Heart and the Effort Syndrome. By Thomas Lewis. M. D., F. H. C. P., F. R. S.. D. Sc. 1918. 8°. 144 pages. Shaw ft Sons. London: Paul B. Hoeber, New York.

The Internal Secretions and the h'ervous System. By Dr. M. Laignel-Lavastlne. Authorized Translation by Dr. F. T. Robeson. Nervous and Mental Disease Monograph Series No. 30. 1919. 8°. 59 pages. Nervous and Mental Disease Publishing Company. New York and Washington.


Aspects of Death and Correlated Aspects of Life in Art. Epigram, and Poetry. Contributions Towards an Anthology and an Iconography of the Subject. Illustrated Especially by Medals, Engraved Gems. Jewels. Ivories. Antique Pottery, etc. By Frederick Parkes Weber, M. A.. M. D.. F. R. C. P.. F. S. A. Third edition, revised and much enlarged. With 145 illustrations. 1918. 8°. 786 pages. Paul B. Hoeber, New York.

Association of American Physicians. Transactions of the Association of American Physicians. Thirty-third Session Held at Atlantic City, N. J., May 7 and S, 1918. Volume XXXIII.

1918. 8°. 427 pages. Printed for the Association. Philadelphia.

Xational Tuberculosis Association. Transactions of the Fourteenth Annual Meeting, Boston, Mass., June 6-8, 1918. 8°. 608 pages. National Tuberculosis Association, New York.

The Smithsoniati Institution. Annual Report of the Board of Regents of the Smithsonian Institution. Sliowing the Operations. Expenditures, and Condition of the Institution for the Year Ending June 30, 1910. 1917. 8°. 607 pages. Government Printing Office, Washington.

Oeriatries. A Treatise on Senile Conditions. Diseases of Advanced Life, and Care of the Aged. By Malford W. Thewlis, M. D. With introduction by A. Jacobi, M. D., LL. D., and I. L. Nasrher. M. D. 1919. 8°. 250 pages. C. V. Mosby Company, St. Louis.

American College of Surgeons. Sixth Year Book 1918-1919. 8°. 543 pages. Chicago.

Mortality Statistics of Insured Wage-Earners and Their Families. Experience of the Metropolitan Life Insurance Company Industrial Department, 1911 to 191G, in the United States and Canada. By Louis I. Dublin. Ph. I>. With the collaboration of Edwin W. Kopf and George H. Van Buren. 1919. 8°. 397 pages. Metropolitan Life Insurance Company, New York.

The Peritoneum. Volume I. Structure and Function in Relation to the Principles of Abdominal Surgery. Volume II. Diseases and Their Treatment. By Arthur E. Hertzler. M. D., F. A. C. S.

1919. S". 870 pages. C. V. Mosby Company, St. Louis.

A Manual of Exercises for the Correction of Speech Disorders. By May Kirk Scripture, B. A., and Eugene Jackson, B. A. Illustrated. 1919. 12°. 236 pages. F. A. Davis Company, Philadelphia.

The Realities of Modern Science. An Introduction for the General Reader. By John Mills. 1919. 12°. 327 pages. The Macmlllan Company, New York.

The Erotic Motive in Literature. By Albert Mordell. 1919. 12°. 250 pages. Bonl and Liverlght, New York.

Symptoms of Visceral Disease. A Study of the Vegetative Nervous System in its Relationship to Clinical Medicine. By Francis Marion Pottenger. A. M., LL. D., F. A. C. P. With 86 text illustrations and nine color plates. 1919. 8°. 328 pages. C. V. Mosby Company, St. Louis.

Oynoplastic Technology. With a chapter on "Sacral Anesthesia." By Arnold Sturmdorf, M. D. Illustrated with 152 half-tone and photoengravings in the text, some in colors, and 23 fullpage plates, with 35 figures, all in colors. 1919. 8°. 334 pages. F. A. Davis Company, Philadelphia; Stanley PhillipB, London.


The Don Quixote of Psychiatry. By Victor Robinson. 339 pages. Historico-Medlcal Press, New York.


1919. 8°


316


[No. 344


THE JOHNS HOPKINS HOSPITAL REPORTS


VOLUME I. 423 pages, 99 plates.

VOLUME II. 670 pages, with 08 plates and figures.

VOLUME III. 766 pages, with 69 plates and figures.

VOLUME IV. 504 pages, 33 charts and illustrations.

VOLUME V. 480 pages, with 32 charts and Illustrations.

The Mal.nrl.il Fevers of Baltimore. By W. S. Thayek, M. D., and

J. Hewetson. M. D. A Study of some Fatal C.ises of Malaria. By Lewellts F. Barker. M. B.

Studies in Typhoid Fever. By William Osleb. M. D., with additional papers by G. Blomer. M. D.. Simon Flexnek. M. D., Walter Reed, M. D., and H. C. Parsons, M. D.

VOLUME VI. 414 pages, with 79 plates and figures.

VOLUME VII. 637 pages with illustrations.

VOLUME VIII. 662 pages with illustrations.

VOLUME IX. 1060 pages, 66 plates and 210 other illustrations. Contributions to the Science of Medicine.

Dedic.Tted hv his Pupils to William Henky Welch, on the twenty-flfth anniversary of his Doctorate. This volume contains 3S separate papers.

VOLUME X. 616 pages, 12 plates and 25 charts.

VOLUME XI. 655 pages, with 38 charts and illustrations.

VOLUME XII. 648 pages, 12 plates and other illustrations.

VOLUME XIII. 605 pages, with 6 plates. 201 figures, and 1 colored chart.

VOLUME XIV. 632 pages, with 97 figures.

Studies in Genito-Urinary Surgery.

The Treatment of Prostatic Hypertrophy by Conservative Perineal Prostatectomy. An analysis of cases and results based on a detailed report of 145 cases. By Hugh H. YotiNG, M. D.

Recto-Urethral Fistulse. Description of New Procedures for their Prevention and Cure. By Hugh H. YonNG. M. D.

The Early Diagnosis and Radical Cure of Carcinoma of the Prostate, being a study of 40 cases and presentation of a radical operation which was carried out in four cases. By Hugh H. Young, II. D.

VOLUME XV. 542 pages, with 87 illustrations.

Twelve papers on pneumonia. By Drs. Chatard. Fabyan, Emerson, Marshall, McCrae, Steiner. Howard and Hanes.

A Study of Diarrhoea in Children. J. H. Mason Knox, Jr., M. D., and Edwin H. Schoker, M. D.

Skin Transplantation. By John Staigb Davis, M. D.

Epidemic Cerebrospinal MeniuKitis and Serum Therapy at The Johns Hopkins Hospital. By Frank J. Sladen, M. D.

VOLUME XVI. 670 pages with 151 figures.

Studies in the Experimental Production of Tuberculosis in the Genitourinary Organs. By George Walker. M. D.

The Effect on Breeding of the Removal of the Prostate Gland or of the Vesiculse Seminales. or of Both ; together with Observations on the Condition of the Testes after such Operations on White Rats. By George Walker, M. D.

Scalping Accidents. By John Staige Davis. M. D.

Obstruction of the Inferior Vena Cava with a Report of Eighteen Cases. Bv J. Hall I'leasants, M. D.

Physiological and Pharmacological Studies on Cardiac Tonicity in Mammals. By Percival Douglas Cameron. M. D.

VOLUME XVII. 586 pages with 21 plates and 136 figures.

Free Thrombi and Ball Thrombi in the Heart. By Joseph H. Hewitt, M. D.

Benzol as a Leuootoxin. By Lawrence Selling. M. D.

Primary Carcinoma of the Liver. By Milton C. Wintebnitz, M. D.

The Statistical Experience Data of The Johns Hopkins Hospital. Baltimore, Md., 1802-1911. By Frederick L. Hoffman, LL. D., F. S. S.

The Origin and Development of the Lymphatic System. By Florence R. Sabin, M. D.

The Nuclei Tuberis Laterales and the So-called Ganglion Opticum Basale. Bv Edward F. Malone. M. D.

Venous Thrombosis During Myocardial Insufficiency. By Frank J. Sladen. M. D., and Milton C. Winternitz. M. D.

Leuliiemla of the Fowl : Spontaneous and Experimental. By Harry C. Schmeisser, M. D.

VOLUME XVIII. 445 pages with 124 figures. Fasciculus I.

A Study of a Toxic Substance of the Pancreas. By E. W. GoODrASTCRE, M.'D.. and George Clark. M. D.

Old Age in Relation to Cell-overgrowth and Cancer. By E. W. Goodpasture. M. I)., and G. B. Wislocki. M. D.

The Effect of Removal of the Spleen Upon Metabolism in Dogs ; Preliminary Report. By J. H. King. M. D.

The Effect of Removal of the Spleen Upon Blood Transfusion. By J. H. King, M. D., B. M. Bernheim, M. D., and A. T. Jones, M. D.

Studies on I'arathvroid Tetany. By D. Wright Wilson, M. D.. Thornton Stearns, M. D.. J. H. Janney, Jr., M. D.. and Madge DeG. Thdrlow, M. D.

Some Observations on the Effect of Feeding Glands of Internal Secretion to Chicks. Bv M. C. Wintebnitz, M. D.


Bj


Spontaneous and Experimental Leukaemia in the Fowl. By H.

Schmeisser, M, D. Studies on the Relation of Fowl Typhoid to Leukaemia of the Fowl.

M. C. Winternitz, M. D., and U. C. Schmeisser, M. D. Hyaline Degeneration of the Islands of Langerhans in Pancreatic Diabetes.

By M. C. Winternitz. M. D. Generalized Miliary Tuberculosis Resulting from Extension of a Tubercular

Pericarditis Into the Right Auricle. By M. C. Winternitz, M. D. Acute Suppurative Hypophysitis as a Complication of Purulent Sphenoidal

Sinusitis. By T. R. Boggs. M. D.. and M. C. Winternitz, M. D. A Case of Pulmonary Moniliasis in the United States. By T. R. BoGOS,

M.D., and M. C. Pincokfs, M. D. Gaucher's Disease (A Report of Two Cases In Infancy). By J. H. M.

Knox. M. D., H. R. Wahl. -M. D., and H. C. Schmeisser, M. D. A Fatal Case of Multiple Primary Carcinomata. Bv E. D. Plass, M. D. Congenital Obliteration of the Bile-ducts. By James B. Holmes, M. D. Multiple Abscesses of the Brain in Infancy. By James B. Holmes. M. D. Gastric Carcinoma in a Woman of Twenty-six Years. By R. G. HcssEY,

M. D. Subdiaphragmatic Abscess with Rupture Into the Peritoneal Cavity Following Induced I'neumothorax for Pulmonary Haemorrhage. By E. G.

HussEY, M. D. Heart Block Caused by Gumma of the Septum. By E. W. Bridgeman,

M. D., and H. C. Schmeisser. .M. D. Analysis of Autopsy Records.

A. The Johns Hopkins Hospital. (Table Showing Percentage of

Autopsies.!

B. The City Hospitals, Bay View. (Table Showing Percentage of

Autopsies.) '* The Monday Conferences."

Clinical Representatives on the Staff of the Department of Pathology. Donation.

Fasciculus II. The R61e of the Autopsy in the Medicine of To-day. Bv M. C. Winternitz,

M. D. Experimental Nephropathy in the Dog. Lesions Produced by Injection

of B. bronchisepticus into the Renal Artery. By M. C. Winternitz,

M. D.. and William C. Qoinby. M. D. Mesarteritis of the Pulmonary Artery. By M. C. Winternitz, M. D., and

H. C. Schmeisser, M. D. A Clinical and Pathological Study of Two Cases of Miliary Tuberculosis of

the Choroid. By Robert L. Randolph, M. D., and H. C. Schmeisser,

M. D. The Blood-vessels of the Heart Valves. By Stanhope Bayne-Jones. M. D. Equilibria in Precipitin Reactions. By Stanhope Bayne-Jones, M. D. Carcinoma of the Pleura with Hypertrophic Osteoarthropathy. Report of

a Case with a Description of the Histology of the Bone Lesion. By

Stanhope Bayne-Jones. M. D, The Interrelation of the Surviving Heart and Pancreas of the Dog in Sugar

Metabolism. By Admont H. Clark. M. D. Congenital Atresia of the Esophagus with Tracheo-Esophageal Fistula

Associated with Fused Kidney. A Case Report and A Summary of the

Literature on Congenital Anomalies of the Esophagus. By E. D.

Plass. M. D. Ectopia Cordis, with a Report of a Case in a Fifteen-Month-Old Infant.

Bv James B. Holmes, M. D. Studies in the Mechanism of Absorption from the Colon. By Samuel

Goldsciimidt, M. D., and A. B. Dayto.v. M. D. Report of Two Fatal Cases Following Percy's Low Heat Treatment of

Carcinoma of the Uterus. Bv V. N. Leonard, M. D., and A. B. Dayton,

M. D. The Relationship in Typhoid Between Splenic Infarcts and Peritonitis

Unassociated with Intestinal I>erforation. By A. B. Dayton, M. D. Left Duodenal Hernia. By A. B. Dayton. M. D.

Histological as Related to Physiological and Chemical Differences in Certain Muscles of the Cat. By H. Hays Buli.ard, M. D. .\ Method of Clearing Frozen Sections. By H. Hays Bullard. M. D. On the Occurrence and Significance of Fat in the Muscle Fibers of the

Atrio-Ventricular System. By H. Hays Bullard. M. D. Studies on the Metabolism of Cells in vitro. 1. The Toxicity of o-Amino Acids for Embyonic Chicken Cells. By Montrose T. Burrows, M. D.,

and Clarence A. Neymann, M. D. The Significance of the Lunula of the Nail. By Montrose T. Burrows,

M. D. The Oxygen Pressure Necessary for Tissue Activity. By Montrose T.

Burrows. M. D. The Functional Relation of Intercellular Substances in the Body to Certain Structures in the Egg Cell and Unicellular Organisms. By

Montrose T. Burrows. M. D. Studies on the Growth of Cells in vitfo. The Cultivation of Bladder and

Prostate Tumors Outside the Body. By Montrose T. Burrows, M. D.,

J. Edward Burns. M. D., and Y'oshio Suzukl. SI. D. The Study of a Small Outbreak of Poliomyelitis in an Apartment House.

Occurring in the Course of an Epidemic in a Large City. By Montrose

T Burrows, M. D.. and Edwards A. Park. M. D. Papilloma of the I.arynx. Report of a Case Treated with Radium with

Resultant Chronic Diffuse Thyroiditis. By William C. Duffy. M. D. Analysis of Autopsy Records. Autopsy Statistics.

(a) Bay View.

(b) Johns Hopkins Hospital. Report of the Photographic Department. General Improvements.

Donations.



BALTIMORE, NOVEMBER, 1919

Contents

The Fate of Baotcriii Introduced into the Upper Air Passages.

By ARTnuR L. Hi.ooiiFiEi.D 317

The Influenza Bacillus in Paranasal Sinus Infections.

By S. .1. Crowe and \V. S. Thackkr-Nevili.e . . . 322

Meniiigoi'oci-us Pnt-uniunia. I. The Occurrence of Post-Influenzal Pneumonia in Wliich the Diplococcus Intracellularis Meningitidis Was Isolated. From Ohservations at Camp Coetqiiidon. A. E. F., France. By M. L. Holm and Wilbubt C. Davison .... 324


Meningococcus Pneumonia. II. Tlie Epidemiology of Postinfluenzal Pneumonia in Wliicli the Diplococcus Intracellularis Meningitidis Was Isolated. From Observations at Camp Coetquidon, A. K. F., France. (lUustratt d.) By Wn.BURT C. Daviso.v. M. L. Holm and Robert V. B.

Emmons 329

The Occurrence of the Pfeifl'er Bacillus in Measles.

By Andrew Watson Sei.i.ards and Krnest Sturm . . 331 The Reaction of the Leucocytes in Ejjidcmic Influenza.

By Beverly Douglas ,338

Books Received . 340


THE FATE OF BACTERLV INTRODUCED INTO THE UPPER AIR

PASSAGES

By -Artiiir Ti. Bi.oomfield (From the Medical CHnic. The Johns Hopkins University and Hospital.)


In considcrinfT the pathogenesis of infectious diseases in which the portal of entry is in the upper respiratory tract, three factors must be reckoned with : first, the means wliereby the virus is conveyed to the individual; secondly, the fate of the organism from the time it reaches the mouth or nose until it is eliminated or until invasion takes place; and third, the actual invasion of the virus into the body. Although many details of the mode of conveyance of bacteria from one host to another have been adequately determined, we possos.s little exact information about the localization, prowth and disposal of such orpani.<ms, and the factors which determine a longer or shorter period of survival in the upper air passages before or after invasion has taken place. Studies of contact infection and of carrier incidence and persistence under various conditions afford indirect information, which is, however, inadequate to solve the detailed problems of particular infections. By actually introducinf: bacteria into the ujjper air pas.«,i:.'es in such a way that the do.sc, exact time and site of inoculation, and other conditions can be controlled, and by studyinfr the fate of such organisms, it seems probable that knowledge of the details of the spread of bacteria and of the development of the carrier state can be extended.


It seemed advisable to make a preliminary study of the fate of non-pathogenic organisms before employing possible disea.se producers. To be satisfactory for this purpose, an organism was sought which was non-pathogenic, not normally jircsent in the upper air passages of man, which could be readily grown on simjile media, which could be easily recognized both in culture and in smear, and which would not be overgrown in culture by the normal mouth flora. After examining a number of strains, a sarcina lutea was selected as fulfilling those criteria. The organism employed * had tlip following characteristics:

Morphology. — Rather small sarclnfp, varying In size, occurring for the niost part In regular packets, singly or in pairs, but sometimes In Irregular groups. They measure 0.66 to 1.13 microns in 20-hour cultures on plain agar.

Motility. — Non-motile.

Btaining Properties. — Gram positive.

Cultural Characteristics.^Agar slant. Growth lemon yellow, at first translucent and rather dull, later, opaque and bright In color, rather thick, raised.

Agar Colonies, — Round with smooth edges, lemon yellow, opaque: f^urface smooth and glistening. Under low power — margin smooth, sharply defined, surface finely granular, color yellowish grey.

• The culture was kindly supplied by Dr. W. W. Ford.


318


[No. 345


Broth. — Liquid clouded at first with small amount of viscid sediment; later, liquid clear, with large amount of sediment, very viscid and stringy, yellow, no pellicle.

Peptone Solution. — Less growth than in broth.

Litmus milk. — Unchanged.

Pigment formation often not marked until after the lapse of 48 hours; on very acid or alkaline media, or when grown with certain other organisms, pigment formation may be very slight, but there is always a definite yellowish tint.

The organism grows well in mixed culture with the bacteria usually present in the mouth, and it does not tend to be overgrown except in occasional Instances in which a " spreader " rapidly covers the entire plate. The colonies of sarcina lutea grow well side by side with, and at times partly superimposed on, those of the mouth bacteria.

This organism was not found in the air passages of any of the controls; and it is entirely non-pathogenic for human beings.

METHODS

Individuals were selected who.?e mouths and upper air passages presented no acute disease or abnormality other than those usually encountered, such as pyorrhea, dental caries, adherent tonsils, and minor grades of septal or turbinate deformity. From the point of view of this experiment, they could be regarded as normal. The patients were kept under direct observation during the first hour of the experiment and for the most part took nothing by mouth during this time. The inoculations were always made several hours after eating, when the mouth was free from gross food particles.

Solid masses of a 24-hour growth of sarcina lutea on plain agar were swabbed on the selected site, and cultures taken at regular intervals thereafter. They were made for the most part by scraping the mucous membrane with a heavy platinum loop, 0.5 cm. in diameter, and rubbing up the mucus obtained in this way in a drop of sterile salt solution. This was spread over several agar plates in varjing dilutions. It was foimd that many more organisms were recovered by this method than by the usual swab technique. There was usually a uniform discrete spread of colonies. This point is emphasized because we feel that overgrowth in the plates was eliminated and that we obtained a true representation of the percentage of viable organisms present in the swab. The plates were kept for at least a week and the organisms identified by the appearance of colonies and by smears.

Experiment I. — Sarcina lutea was swabbed on the tongue and cultures were made immediately, and at 10-minute, 1-hour, 24-hour and 4S-hour intervals. The results are summarized in Table I.

Summary. — Sarcina lutea swabbed on the tongue disappeared very rapidly. Only a few colonies could be recovered from the site of Inoculation after ten minutes, and practically none at the end of one hour. Simultaneous cultures from the pharynx, except in one ir stance, yielded only a few colonies during the first ten minutes.

Experiment II. — Sarcina lutea was swabbed on the nasal mucosa and cultures made immediately and at 10-minute, 1-hour. 24-hour and 48-hour intervals. The results are summarized in Table II.

Summary/. — Sarcina lutea swabbed on the nasal mucosa persisted longer than on the tongue, but in only one of five cases could a few colonies (7) be recovered after 24 hours. In spite of the heavy inoculation, only a few colonies could be obtained in nasopharynx cultures made simultaneously with the nose cultures.


Experiment III. — Sarcina lutea was introduced into tonsil crypts and cultures were made immediately, and after 10-minute, 1-hour, 24-hour and 48-hour Intervals. The results are summarized in Table III.

Summary. — Sarcina lutea introduced in large amounts into tonsillar crypts could no longer be recovered after 24 hours, and even at the end of an hour the organisms had disappeared in two out of four cases. There seemed to be no tendency toward the development of a carrier state.

THE MECHANISM FOR DISPOSAL OF BACTERIA IN THE UPPER AIR PASSAGES

Despite the frequent presence of pathogenic bacteria in the upper air passages, both in health and in disease, it is clear that a highly effective mechanism is present in these localities which, except under extraordinary conditions, protects against invasion by foreign organisms. Were this not so, it is obvious that the spread of such organisms would soon become universal among the human race, with an attendant high incidence of disease. The effectiveness of this protective mechanism varies with various bacteria, and with the same bacteria at various times, as illustrated by the epidemiological facts of Iniman disease. The details, however, of its action in particular instances of infection have not been completely worked out. A survey of the literature discloses studies on a number of factors which probably combine in making up the complex protective mechanism of the upper air passages. These factors may be classified as : (1) Mechanical (including the flushing action of secretions with the associated acts of swallowing and the ejection of nasal and mouth secretions) ; (3) chemical (including the effects of the reaction of the mouth and nose secretions with other possible bacterial inhibitory factors) ; and (3) biological (including such processes as phagocji:osis and the effect of bacteria already present on the invader). These factors can be most conveniently discussed from a topographical standpoint.

The Conjunctivce. — Maxcy ' states that the lachrymal secretion has no bactericidal action. Stort " found that colon bacilli instilled into the conjunctival sac of rabbits could no longer be recovered in culture after one hour. If the lachrymal duct were tied, the bacteria persisted in the conjunctiva for a much longer time. He concludes, therefore, that the organisms are swept rapidly into the duct, and that the mechanism for preserving the normal sterility of the eye — at least in the case of the organism studied — was a mechanical one, and not dependent on bacterial inhibitory action of the secretions. Maxcy ' was able in man to recover B. prodigiosus from the nose within five minutes after it had been introduced into the conjunctival sac.

The Nasal Passages. — Although the nasal secretion is normally scant, still the mucous surfaces are constantly moistened. The cilia of the epithelium and the secretion of the mucous membranes and that discharged into the nose from the lachrymal duct create a steady current toward the posterior nares.^ Furthermore, the configuration of the nasal cavities is such that bacteria and foreign particles are for the most part arrested near the anterior nares. Thus, cultures made in normal individuals vield large numbers of organisms


November, 1919]


319


TABLE I.— FATE OF SARCINA LUTEA SWABBED ON THE TONGUE



Name


OlaKnoais and


  • «re


Procedure


Number of coloniea of sarcina lutra per plate recovered from Consul, and pharynx


Con


trol



Date


lAimediately


After 10


min.


After Ihr.


After 24 bra.


After 48 hra.


inoculation




1


1


1

0.


1


c


1


B


1 1


S

1

a.


3



9 1


<• ja



June 10.


M. Cardiac. compcn-'oO eated. .Mouth in average condition. Scarred tonsils.


i slant S. L. swabbed on anterior half of tongue.


Plate almost pure S. L.


00

Plate about JS.L.


60


1


8


No S. L.


No S. L


No No S.L. S.L


No S.L.


No S.L.


No

S.L.


Took nothing by mouth until' after 1-hour culture.


June 10.


G. Tuberculous poly- l.'i '• serositis. Mouth ' clean. Ragged tonsils.


  • slant S. L. 50

swabbed on anterior half of tongue. 1


2


6


No S. L.


7


Nv S. L.


No S. L.


No S.L.


No S.L.


No S.L.


No S.L.


No S.L.


Took small amount of liciiiid between second and third cultures.


Jane 8.


Mo. Cardiac, cnmpen- 60 sated. Mouth in average condition.

1


i slant S. L. ' x swablied on Almost anterior half pure of tongue. plate.


10


ISO


No S. L.


No S. L.


No S. L.


No

S.L.


No

S.L.


No S.L.


No S.L.


No S.L.


No S.L.


Took small amount of water between second and third cultures.


May 31.


H. Cardiac, compen- 1 30 sated. Mouth in 1 average condition. 1


» slant S. L. =c swabbed on Plate anterior half almost of tongiie. pure.


No S. L.


No S. L.


No S. L.


No S. L.


No S. L.


No S. L.


No No S. L.S. L.


No S.L.


No S.L.


No S.L.



May 31.


L.


Cardiac, compen- 50 sated. Mouth in average condition.


i slant S. L. swabbed on anterior half of tongue.


00

Plate


3


A few

cols. S. L. (confluent).


4


No

S. L.


No S. L.


N'o S.L.


No S. L.


No

S.L.


No S.L.


No S.L.


No

S.L.



May 31.


D.


Nephritis. Mouth 40 in average condi- | | tion. 1 !

1 1


i slant S. L. oc swabbed on Plate anterior half almost of tongue. 1 pure.


No S. L.


1


No S. L.


No

S. L.


No S. L.


No S.L.


No No S. L.S. L.


No S. L.


No S.L.


No S.L.


Took water between second and third cultures.


TABLE II.— FATE OF SAUCIN'A LUTEA SWABBED ON NASAL MUCOSA


June 21


June 19.. B


Abdominal aneur- 3S ism. Nose and mouth normal.


i Cardiac, compen- 60 I sated. Nose and mouth normal.


Cardiac,


compen

sated.


\ose and


mouth


normal.


Scarred


tonsils.


Cardiac,


compen

sated.


Nose and


mouth


normal.


Large


scarred


tonsils.



} agar slant of S.L. swablied on nasal septum.


Number of colonies of sarcina lutea per plate recovered from no8o and nasopharynx


00 I No About S. L. i the plate is S.L.


No

About S. L, i the plate is S.L.


} agar slant of » No _

S.L. swabbed About S. L. About


on nasal sep- i the

turn. I plate |

is S.L.


4 agar slant of I oo S.L. swablied .\bout on nasal septum.


No

S. L.


if the

plate I

isS.L.'


C


No

S. L,


i. of plate is S.L


Psychoneurosis. Nose and mouth normal.


12 i agar slant of « No No S. L. 3

S.L. swabbed About S. L.l on nasal sep- 1 of I tum. I plate

I IS S.L.

i 20 : i agar slant of I « I No oo No

S.L. swabbed About S.L. About S.L.

on nasal sep- i of I i of

I tum. , plate plate |


About i the plate is S.L


About i the plate is S.L

6


No S. L,


No S.L


No S.L.


No S.L.


No S.L.


No No S. L.S. L


No S.L.


No No S. L.S. L


No I No S. L.S. L.


No

S.L.


No

S.L,


No S. L.


plate is S.L.


plate

Is S. L.l


No

S.L.


No No No No 8. L. S.L. S.L. .S.L.


No

S.L,


No

S. L.


Control

culture

before

noculution


No S. L.


No S.L


No

r.S. L


No S. L.


No S. L.


Took nothing by month until aft»r the l-hoiir culture.


Took nothing by mouth until after the 1-hour culture.


Drank water after the 10-minuto culture.


Drank water after thelO-minute culture.


Took nothing by mouth until after the Ihour culture.


320


at the nasal orifices and few or none from the deeper nasal passages.' Maxcy' recovered B. prodigiosus from the nasopharynx 15 minutes after instilling it into the conjuuctiva. and we found sarcina lutea in the pharynx 10 minutes after swabbing it on the anterior part of the septum.

With regard to the bacterial inhibitory effect of the nasal secretions, the literature is contradictory, some writers finding a marked inhibitory action and others failing to do so. Variations in the method of collecting and diluting the secretions, in the organism used, and in the method of plating, may account for these discrepancies. Kligler ' has shown recently that small amounts of nasal secretions added to cidture media at times promoted the growth of organisms such as maningococci. He believes this action to be due to " vitamins.'^ The experiments of Calvino,' however, which approximate most closely natural conditions, indicate that the nasal mucosa is an imfavorable medium at least for some types of organism.

It seems clear, therefore, that the normal tendency is to preserve sterility of the deeper nasal passages and that no true permanent nasal flora exists.

The Mouth and Throat. — The mouth affords an especially favorable opportunity for some types of bacterial growth ; food particles, carious teeth, desquamated epithelium and saliva furnish media whose effectiveness is attested by the enormous numbers of bacteria constantly present even in so-called clean and well-kept mouths. There is, however, a continuous shift in the " normal " flora, so that cultures made from the same individual on successive days may yield different quantitative and qualitative results. Such variations are to be expecterl with changing food and fluid intake and variations in mouth hygiene. Furthermore, the abundant salivary and moutli secretions with the constant flushing effect of ingested fluids, swallowing and expectoration, undoubtedly constitute a cleansinjc mechanism.


[No. 345 J saliva and^|


With regard to the bacterial inhibitory effect of saliva and' mouth secretions in vivo, no satisfactory data are at hand, althougli numerous test-tube experiments are on record. Thus, Sanarelli ' found that streptococci, staphylococci, M. tetragenus and cholera spirilla were rapidly destroyed by fresh filtered saliva in vitro, unless an enormous number of organisms were used. The pneumococcus, on the other hand, throve in saliva better than in broth. Barnes ' using a similar method, found that saliva had no bactericidal action on streptococci or pneumococci. Variations in the results of such experiments are to be expected under various experimental conditions.

The importance of the normal mouth flora in over-growing and suppressing invading pathogenic organisms is indicated only in an indirect way. On artificial media, meningococci, pneumococci and influenza bacilli grow well in certain pro])ortions with the normal mouth organisms. They may, however, be rapidly overgrown by " spreaders," particularly of the aerobic spore-bearing types. It is possible that such organisms may actually exert a similar effect in the mouth, although this is not directly demonstrated.

It is clear, therefore, that a complex mechanism exists in the upper air passages, which under certain conditions suffices to dispose of invading pathogenic microorganisms. The details of its operations are obviously variable, and as is to be expected, it often breaks down. Thus, such factors as dosage of the organism, local pathological processes or aoatomical anomalies, variations in the biological activities of the organisms themselves, may play a part in explaining why certain bacteria may gain a foothold at one time; and at another, or in a different individual, be promptly wiped out. From the standpoint of epidemiology it seems more profitable, therefore, to observe the actual fate of organisms introduced into the upper air passages than to try to anal3'ze their exact method of disposal.


TABLE III.— FATE OF SARCINA LUTEA INTRODUCED INTO TONSILLAR CRYPTS


Date


Name


June 26.


C.


June 26.


F.


June 25.


M.


June 25.


Fi.


Diagnosis and i


Syphilis. Nose and moutli essentially normal. Small, clean tonsils with sealed orypts.

Hodgkin's disease. Large, ragged tonsils.


Cardiac, compensated. Large, ragged tonsils with open crypts.

Tuberculous pericarditis. Large, scarred adherent tonsils.


i agar slant of S. L. introduced int o a tonsil crypt.


i agar slant of S. L. introduced into a tonsi 1 crypt.

i agar slant of S. L. introduced into a tonsil crypt.

i agar slant of S. L. introduced into a tonsil crypt.


Number of colo


s per plate of sarcina lutea recovered

from tonsil crypt


(Almost pure plate.)


(Almost pure plate.)


(Almost pure plate.)


(Almost ' (Almost pi.re I pure

plate.) I plate.)


No S. L.


(Almost pure plate.)


No S. L.


No S. L.


No S. L. No 3. L.


No S. L.


No S. L.


No S. L.


No S. L.


No

S. L.


No S. L.


Took nothing by mouth until after the 1-hour culture.


Took nothing by mouth until after the 1-hour culture.


Took nothing by mouth until after the 1-hour culture.


Took nothing by mouth until after the 1-hour culture.


XOVEMBER, 1919]


321


None the less, an attempt was made to determine, at least approximately, the mechanism which led to the rapid disappearance of sarcina lutea. The reaction of the mouth secretions, the etfect of moiluuiical cleansing, and bacterial inhibitory clTccts of the mouth secretions were studied.

1. Effect of the Reaction of Mouth Secretions. — Saliva and mouth secretions were collected from each of the patients inoculated with sarcina lutea. The mucous membranes were siTa|)ed with a larfje platinum loop, after which the patient expectorated the saliva which had accumulated in the mouth. The entire mixture was diluted with an equal amount of fresh, sterile distilled water, and tlie reaction immediately tested. The colorimetric comparison method, as now generally used in bacteriological work * was employed with phcnolsulphonephthalein and alizarin as indicators. The pll of the various specimens is indii-ntcil in tlie I'ollowini: tabli(Table IV).

T.ABLE IV

pH ok Spkcimk.ns Of- Salha from I.NDiviDrALS Ixocn.ATa) With

Sakcina Lutea

pll or Siiliva pH after staiulirig

Name iinmcihittelv oiip hour

Mo 5.9 5.9

G 5.9 —

H 5.9 —

P. 6.0 6.0

Mu 6.0 —

L. 7.0 6.9

F. 7.0 7.0

D 7.2 7.1

T 7.2 7.0

Ho. 7.3 —

Gr 7.4 7.1

Pi 7.6 7.3

Ma 7.6 —


The range of growth of sarcina lutea was next tested. Tubes of plain agar with reaction adjusted from pll 5.0 — to 8.0-1- were inoculated. Sarcina grew with equal luxuriance on all the tubes within this range. It seems clear, therefore, that the reaction of the mouth secretions cannot alone accoimt for the disposal of sarcina lutea.

2. Mechanical Influences. — .\n attemjit was made to asiertain to what extent the normal wiisliing processes in the nuiuth

TABLE V

BAt'n;RiAL Coi'.NTS fbom Tongue Befork and Affeb Iiuiioatixo

Mouth With Salt Solutio.n


Name


Ko. cols, from I loop

of tongue acrapinics

before irrigation


No. cola, from 1 loop

of tongue scrapings

immediatf'lv after

irrigation


No. cola, from 1 loop

of tongue KCrjpinpgs

lOmin. after mouth

irrigation


B

M


ICOO

00


800

Plate contains about as manycoluiiiesas before.'


so

00


serve to remove organisms present. The mouth was thoroughly rinsed with one liter of sterile salt solution. The patient tcKiperated in making this washing effective by churning the fluid in the mouth and scraping the tongue with the teeth. Such an irrigation would be expected to remove more organisms than the ordinary acts of swallowing and expectoration. The tongue was scraped with a large platinum loop just before and just after the washing and at subsequent intervals. The loop of scrapings was diluted and plated in a standard manner. In no case was it possible to nnluce the bacterial count by more than 50 per cent, even by such exten


TABLE VI.— EFFECT OF SALIVA ON THE GROWTH OK SARCINA LUTEA


One standard loop

from each tube

plated at following

tntcrrali


O.t c.c. saliva


0.2 c. c. auapenalon

S. L. + 0.2 c. c. aalt

solution


0.2 c. c. suspension of

mixol mouth bacteria

+ U.2 c. c. suspension

8. L.


0.2 c. c. saliva +

0.2 c. c. auapenalon

S. L.


0.2 c. c. saliva +

0.1 c. c. suspension

S. L.


. saliva +

. suspension


Imineiliat«lv


About 500 roU. of various kinds '


About 300 cols, of variouH kinds,


1 hour .\bout .'iOO cols, i

of variouK kinds.


S baun.


About 2()U cols, of various kinds.


M hours About .500 cols. \ 

of various kinds.


oD cols. S. L.


00 colft. S. L.


00 cols. S. I.,, witb 00 coIk. S. ].•. witb « cols. S.L. with 2<'>0 rols. S. L.

1 about 50 cols. I a few muutli a few mouth { Mouth biicteria.

mouth bacteria. | bacteria. bacteria.

00 cols. S.L. with 1 About \ as many 10 cols. S. L. No S. L. Mouth

about 50 cols. I colonies S. L. an (appeared iift- bacteiiii.

mouth bacteria. I in previous pla- er -18 Imurs).

te, with a good .Mouth bac I ' miiny mouth tcria. I bacteria.

o3 cols. S. I>. with 2 ciiIh. S. L. (ap- 1 col. S. I,, (ap- Xo S. L. Mouth

about 100 cols. pi-ared after •!« penred nft<'r 4 , bacteria,

mouth bacteria. Iiours), with days). .Mouth

a good many bacteria.

mouth bacteria.

X coIh. S. L. with ' Ko .'^. L. Mouth No S. L. .Moutli No S. I.. MomII,

about 100 cols. bacteria. bacteria. Iiititirin. moutli bacteria.

X cols. S. L. with ! No S. L. .Mouth , No S. L. Mouth No S. L. Mouth

about iOO cols, i bacteria. bacteria. bacteria, mouth bacteria.


100 cols. S. L. Mouth bacteria.


1 col. S. L. (appeareil after 4 days). Mouth bacteria.


7 cols. S. L. (appeareil after 3 days).


No S. L, .Mouth bacteria.


Xo S. L. Mouth bacteria.


322


[]Sro. 345 J seen. Xo^f


sive irrigation. It seems, therefore, that mechanical processes alone cannot adequately account for the rapid disappearance of sarcina lutea. Table V shows an illustrative protocol.

3. The Inhibitory Ejfect Upon Bacteria Exerted by the Mouth Secretions and Saliva. — An attempt was made to reproduce the conditions present in the mouth as nearly as possible by the following method. 0.2 c. c. of fresh saliva was placed in each of a series of tubes. To each was added decreasing amounts of a thick suspension of sarcina lutea. One standard loop of the mixture of saliva and sarcina lutea was removed from each tube immediately and at various intervals, and plated on plain agar plates. The results which coincided in numerous experiments with various specimens of saliva, except as to slight quantitative variations, are illustrated by the following typical protocol (Table VI).

From this protocol, the following facts are apparent:

1. Cultures made from a specimen of saliva at various intervals up to 24 hours yielded about the same number and kind of organisms.

2. Cultures made at various intervals up to 84 hours from a suspension of sarcina lutea in salt solution yielded the same number of colonies.

3. Cultures made at various intervals up to 84 hours from a mixed suspension of mouth flora and of sarcina lutea yielded the various organisms in about the same proportions. Sarcina lutea was not overgrown or inhibited.

4. Cultures made at intervals up to 24 hours from suspensions of varying concentration of sarcina lutea in saliva yielded rapidly decreasing numbers of colonies of sarcina lutea. The number was miich reduced in 15 minutes, only an occasional organism could be recovered after 1 hour, and none after 2 hours. Furthermore, the growth of the few organisms obtained after the first culture was inhibited for intervals of 1 to 4 days before the colonies appeared in the plates.

Smears were made from each tube in the above exjieriment at 15-minute, 1-hour and 2-hour intervals. After 15 minutes, abundant sarcinse were seen in all tubes. They were normal in staining qualities and in groiiping. After 1 hour the smears from the mixtures of saliva and sarcina lutea showed the sarcinse to stain poorly and to be pale and gran


ular. After 2 hours few definite organisms could be seen. Ifi agglutination was apparent. The organisms from the control tubes stained normally.

It may be concluded, therefore, that saliva exerts a rapid bactericidal effect on this organism and that this effect is independent of the bacteria normally present in the saliva.

DISCUSSION

The general result of these experiments indicates that even after a short period of time it is usually impossible to recover sarcina lutea swabbed in large amounts on the tongue, nasal mucosa, or into the crypts of the tonsils. Disappearance from the nose was somewhat slower than from the other sites; in only one instance could any organisms be recovered after 24 hours, and in no case after two days. Cultures made in this way do not, of course, prove the complete absence of the organism in the mouth and nose, but the general trend of the quantitative relations indicates a rapid disappearance. The fact that the estimated dose of 50 to 100 billion organisms was vastly greater than that in any natural infection, indicates the remarkable efficiency of the mechanism present in the upper air passages for disposing of this organism. An analysis of the possible factors active in effecting this disposal indicated that reaction of mouth secretions, mechanical cleansing, and the mouth bacteria play little if any part, but that the saliva and mouth secretions exert a prompt and marked bactericidal effect.

Similar methods are being used in studying the fate of other organisms introduced into the upper air passages.

REFERENCES

1. Maxcy, Kenneth F.: Journal A. M. A., 1919, LXXII, 636.

2. Stort, A. G.: Arch. f. Hyg., 1891, XIII, 395.

3. Piersol, G. A.: Human Anatomy, 1906, p. 1416.

4. Hasslauer: Centralbl. f. Bakteriol., 1906, ]. Abt.. Ref. Bd. XXXVII, p. 1.

5. Kligler, I. J.: Jour. Exp. Med., 1919, XXX. 31.

6. Calvino, V. E. M.: Arch. Itallano di otologia, etc., 1899, VIII, 169.

7. Sanarelli: Centralbl. f. Bakteriol., 1891, 1 Abt., X, 25.

8. Barnes, B. S.: Trans. Chicago Path. See, 1907-09, VIII, 249.

9. Clark, W. M., and Lubs, H. A.: Jour. Bacteriol., 1917, II, 1.


THE INFLUENZA BACILLUS IN PARANASAL SINUS INFECTIONS

By S. J. Ckowe and W. S. Thacker-Neville, Baltimore (From the Departments of Surgery and Pathology of The Johns Hoitkins Medical School.)


There is some difference of opinion as to the nature of the organism primarily responsible for the influenzal epidemic of 1918-1919. Pfeiffer's bacillus was found in a sufficient number of cases to raise the question as to whether it was the primary agent, or, like the streptococcus and pneumococcus, a secondary invader.

We were interested to determine whether or not this bacillus occurred more frequently in a series of infected nasal sinuses observed immediately following the epidemic, than


in a series of such cases observed during a period when there \ was no epidemic. During the height of the epidemic in Baltimore, it was impossible, owing to the press of work, and the I scarcity of skilled help, to make bacteriological examinations j of the infected sinuses. Within six weeks after the epidemic j had subsided, however, one of us (Neville) undertook a careful bacteriological study of every case of "maxillary sinusj infection treated at The Johns Hopkins Hospital. We limited] our studv to the maxillarv sinus, because this cavitv is the


NOVEMBEB, 1919]


323


one most frequently affected, and because the material for culture can be obtained from this situation with less risk of contamination than from the ethmoidal, frontal or sphenoidal cells.

We present for comparison two series of cases. The first series of seventy includes every case of accessory nasal sinus infection treated at The Jolms Hopkins Hospital during the years 1913-1918. in which we have a report on the cultures made from the antrum.* Of these 70 observations, made during a period when there was no epidemic of influenza, we have 15 cases in which the influenza bacillus was found in the antrum. The 30 cases of the second series were all observed during February. March and April of 1919. In eight of these cases we found B. influenzce in the antrum. It is of interest that the percentage of cases in which the influenza bacillus was found in the antrum is about the same in each group.

The material for culture is obtained by a very simple method. A small piece of cotton on the end of a steel applicator is moistened with a 20 per cent solution of cocaine and 1 : 1000 adrenalin. The excess of cocaine is removed by pressing the cotton between two layers of gauze ; this will insure against s}-mptoms of cocaine poisoning. A small piece of cotton moistened with cocaine and adrenalin is also placed between the anterior end of the inferior turbinate and the septum, and both are left in place for ten or fifteen minutes. A curved trochar, a small rubber ear syringe, a nasal speculum and a finger bowl are then boiled for at least five minutes. The patient's nose is cleansed of all visible discharge. The trochar is passed under the anterior end of the inferior turbinate into the antrum, and the stilette removed. The patient bends 90° forward, and often the pus will drop from the cannula. If not, air or a few drops of sterile salt solution are blown into the antrum with the rubber syringe, and the material returning through the cannula is caught in a sterile test-tube. It is important that enough adrenalin be u.«cd to make the procedure absolutely bloodless, for we have found, in agreement with Rivers, that a few drops of blood mixed with the material obtained for culture will inhibit the growth of the influenza bacillus.'

The bacteriological technique employed is as follows : The material is plated immediately on agar containing defibrinated rabbit's blood, and the plates are incubated at 37° C. for twenty-four hours. The various colonies are tiien examined in stained smears and transferred to blood-agar slants. After twenty-four hours the colonies showing the cultural characteristics of the streptococcus and pneumococcus are differentiated by Xcufeld's bile soluble test. The pneumococci are grouped according to the method of Avery, Chickcriiig. Cole and I)ochez.' The serum used was obtained from tlie


• It was formerly our custom to take cultures from Infected Blnoses (chiefly at operation) on cotton swabs. These swabs were sent to the regular bacteriological laboratory of the hospital but had often completely dried up before reaching the laboratory. This accounts for the comparatively small number In which we have a bacteriological report.


Rockefeller Institute. The influenza bacillus grows freely on blood-agar but not at all on plain agar. This differentiates it from the micrococcus catarrhalis. This latter organism may be differentiated from other gram-negative cocci by the use of Hiss's serum sugar media, and the Elser and Huntoon classification.

In the first series of 70 cases observed during the period from 1912 to 1918, the influenza bacillus was found in the antrum in 15 cases (21 per cent). The streptococcus was found in 33 cases (47 per cent) ; in 10 of these the organism was hipmolytic. The pneumococcus occurred 12 times (17 per cent). The staphylococcus was found in 16 cases (22 per cent) , in one of which it was haemolytic ; the proteus was found once : and the diphtheria bacillus twice.

In the second scries of 30 cases observed during the three months immediately following the subsidence of the influenzal epidemic, the influenza bacillus was found in the antrum in eight cases (26 per cent). The streptococcus was again the predominating organism (14 cases, or 46 per cent) ; of these 14 cases, in four it was haeniolytic. The following organisms were occasionally found : the ha?raolytic staphylococcus in four cases, the pneumococcus in three cases, the micrococcus catarrhalis in two cases, and a gram-negative diphtheroid bacillus in three cases. The diphtheria bacillus was found in one case, the bacillus lactis .Tprogenes once, and the proteus vulgaris in two cases.

The influenza bacillus was recovered from the antrum in pure culture in four cases. In four other cases it was found associated with other organisms: streptococcus ha?molyticus, streptococcus mucosus, micrococcus catarrhalis, micrococcus tetragenus, and the staphylococcus albus. The ha^molytio staphylococcus occurred four times, once in pure culture. The staphylococcus albus was found in eight ca.=es, but was probably in each case a contamination from the nasal cavity.f The pneumococcus was recovered in three cases (in two Type III and in one Type IV), twice in pure culture, once mixed with a staphylococcus albus.


t The healthy nasal cavity is apparently a normal habitat for the staphylococcus albus. We toolc cultures from the middle turbinate In seven individuals with clinically normal nasal cavities. A little mucus was obtained from the middle turbinate with a platinum loop and implanted on plates of rabbit bloodagar. We found: staphylococcus albus 01 per cent; diphtheroids, 41 per cent; pneumococcus, Type IV, 16 per cent; micrococcus catarrhalis, 8.9 per cent.

Park and Wright, In 1898, took cultures with a platinum loop from far back In the nose and showed that the nasal secretion has no bacteriocidal action. Of 3C examinations only six were sterile. The predominating organism was the staphylococcus.

Hasslauer' In 1902, made bacteriological examinations from the normal na.sal cavities of 111 Individuals. He found: staphylococcus in 2.T per rent: pneiimoroccus In 20 per cent; streptococcus in 17 per cent; diphtheroid In 1.T per cent.

He also investigated the bacteriological +++++ CONTENTS of the nasal discharge In 78 cases with a coryza and found much the same varieties of organisms in both healthy and pathological nasal cavities. The only difference was that they were far more numerous In infected nasal cavities.


324


[No. 345


CONCLUSIONS

1. The influenza bacillus was found in infected maxillary sinuses in practically the same percentage (21 per cent) in a series of cases observed during a period of six years when there was no epidemic, as in a second series observed immediately following the epidemic in Baltimore during the winter of 1918-1919 (26 per cent).

2. The influenza bacillus is not infrequently found in pure culture in the antrum.

3. Clinically B. influenzw is a pyogenic organism.

4. The predominating organism in all antrum infections is the streptococcus.

5. We infer from these observations that the influenza bacillus, like the streptococcus and pneumocoecus, is a secondary invader, and not the primary cause of the disease known as influenza.

LITERATURE

1. Rivers, T. R.: The effect of different bloods on the growth of

B. influenza;. Johns Hopkins Hosp. Bull. Balto., 1916, XXX, 129 131. [B. influenza: grows better on rabbit blood- and cat blood-agar

than on human blood-agar; and defibrinated human blood and


normal human serum are very bactericidal for the strains of influenza bacillus studied as compared with defibrinated rabbit blood, normal rabbit serum and normal guinea-pig serum.]

2. Avery, Chickering, Cole and Dochez: Acute lobar pneumonia. Monogr. Rockefeller Inst. M. Research, N. Y., 1917, No. VII, p. 25.

3. Hasslauer, W. : Die Bakterienflora der gesunden und kranken Nasenschleimhaut. Centralbl. f. Bakteriol., 1. Abt., Jena., 1902, XXXIII, 47-51.

Gibson, G. H., Bowman, B., and Connor, J. I.: Etiology of influenza, Brit. M. J., Lond., 1919, I, 331-335. [The influenza epidemic was due to a minute flltrable microorganism of coccoid shape grown by Noguchi's cultural methods.]

Lewis, C. T., and Turner, A. L. Suppuration in the accessory sinuses of nose: a bacteriological and clinical research. Edin. M. J., 1905, n. s., XVIII, 395-421; ibidem., 1910, n. s. IV, 293-318. [In 43 antral cultures taken without reference to an influenza epidemic the influenza bacillus was recovered three times. In another series of 57 cases it was recovered once. In both series streptococcus, pneumocoecus and staphylococcus were the chief organisms found.]

MacCallum, W. G.: The pathology of the pneumonia in the United States army camps during the winter of 1917-1918. Monogr. Rockefeller Inst. M. Research, N. Y., 1919, No. X, 140. [Of 48 cases of pneumonia of influenzal origin 16 contained the influenza bacillus in the bronchioles and occasionally in the alveoli. In six other cases the B. influenza: was found in the sputum.]


MENINGOCOCCUS PNEUMONIA. I

THE OCCURRENCE OF POST-INFLUENZAL PNEUMONIA IN WHICH THE DIPLOCOCCUS

INTRACELLULARIS MENINGITIDIS WAS ISOLATED. FROM OBSERVATIONS

AT CAMP COETQUIDON, A. E. F., FRANCE

By M. L. Holm, Lansing, Mich. Major, Medical Reserve Corps, U. S. Armi/ (Discharged), Director of Lahoratory at Camp Hospital Xo. 15, A. E. F.


WiLBURT C. Davison, Baltimore, Md. Captain, Medical Corps, U. S. Army (Discliarycd), Assistant to Director, Base Lahoratory, Base .Section Xo. 1, A. E. F.


Whatever may be the cause of primary influenza, it would seem that the secondary' pneumonia may be caused by difl'erent organisms in different regions. As MacCallum' has pointed out, this variation " may depend on an endemic or epidemic distribution of organi.sms as inhabitants of the nasopharynx." Pneumococci,' streptococci ' and staphylococci ' have been the most frequent secondary invaders and evidence now appears '• * '• "• '• ' that the diplococcus intracellularis meningitidis (Weichselbaum) may produce fatal pneumonia. The cases reported in this paper were studied at Camp Hospital Xo. 15, Camp Coetquidon, Base Section No. 1, A. E. F., France, during the epidemic of influenza from September 1, 1918, to February 15, 1919.* Table I shows the total number of cases of influenza, pneumonia and cerebrospinal meningitis admitted to the hospital during this period.


  • Prior to September 1, 1918, there had been but three deaths in

this hospital due to the epidemic. They occurred in the last week of August, 1918. Cultures from the lung tissue at autopsy showed B. influenza; pneumocoecus Type III and pneumocoecus Type II, respectively. They are not included in this study be


Prior to the outbreak of the epidemic of influenza, there were no cases of meningococcus meningitis in the hospital. It will be noted that coincident with the occurrence of meningococcus pneumonia, there occurred a considerable number of meningococcus meningitis cases.

The presence of influenza at Camp Coetquidon was first noted about September 1, 1918, and many cases of pneumonia

cause other data for comparison are not available. This study was terminated on February 15, 1919, because the evacuation of troops, begun at that time, rendered records for comparison unreliable and difficult to secure. On February 15. 1919, there were still eight cases in the hospital diagnosed as meningococcus pneumonia. These are included among the total cases recorded but their final disposition is not included.

Camp Coetquidon was an artillery training area occupied by troops which arrived from the United States during the latter part of August, September and October. 1918, and remained until February 15, 1919. These together with the permanent camp personnel numbered approximately as follows: September, 16,657; October, 19,177; November, 16,303; December, 12,850; January, 13,9S February, 14,780.


XOVEMBER, 1919]


325


developed. On Sept<?nil)er 3, 1918, bacteriological cultures at autopsy from the lungs of a case of pneumonia showed a pure growth of meningococci (Type A Pasteur). A description of the bacteriological and serological technique employed is appended. On Scpteml)er G, 1918, a similar case showed meningococcus Type 15 in the lung culture. Both cases occurred early in the epidemic, the patients were in the same ward at the same time, but tlie fact that different types of meningococci were isolated would seem to preclude tlie possil)ility of cither of the two cases having been infected from the other or that both were infected from the same source.

On September V\ and 15 meningococci were recovered from the sputa of two ])ncumonia cases.

TABLE I



Sept.


Oct.


Nor.


Dee.


Jan.


Feb. (i)


Total!


Cases of influenza admitted


847


263


170


38


80


112


1510


to hoopital.

Total cases of pneumonia ad

136


107


53


2!


36


30


403


mitted to liospital.

Total deatlis from pneumonia.


27


30


12



3


6


78


Cases of pneumonia showing


20


15


27


2


13


8


85


meningococci in sputum.

Deaths from pneumonia show

6


3


6


U


1


5


23


ing menin^'ococci in lungs

at autopsr.

Cases of meninROCoccus nicn

4


7


/


3


1



22


inpitis.

Deaths from meningococcus


4


2


3


3


1



13


meningitis.


E.XPLANATION OF TABLE I

Total ea»t» of pneumonia include pneuraonius due to all causes. Many cases admitted aa Induenaa developed pneumonia after admission. Such cases are recorded aapoeumonia and not influenza.

Cases 0/ pneumonia ihou-inff meningococci are inc'uded among the total cases of pneumonia. This croup, however, d.jes not include any of the cases in which cerebrospinal menincritis was present.

Total deathi from pneumonia include all deaths from pneumonia. The deaths from pneumonia showing meningococci are included in this group.

Catei of meningoeoecuM meninffitis include all cases of cerebrospinal meningitis Caused by meningococci, with or without pneumonia involvement.

It seemed, tlicii. tliat the possibility of the meningococcus Ijcing an important factor in the epidemic was worthy of careful investigation. Cultures were therefore taken (September 19, 1918) from the throats of all respiratory cases in the hospital. Among lit thus cultured meningococci (Type B Pasteur) were isolated from seven patients, six of whom had pneumonia.

On September 20, 22, 23, 25, 27 and 29 throat and sputum cultures of meningococci were recovered from 12 additional cases of pneumonia.

During the period studied, 78 ca.«es of pneumonia came to autopsy. Cultures on blood agar were made from sections of the various parts of the affected lungs in all ca-ses. The findings arc of interest here for the purposes of comparing the frequency and the association of the various species of bacteria found during the epidemic. >[oningococci were recovered from the lung tissue in a total of 'i'.\ cases (in pure culture in 7 cases and in mi.xed culture in IG). The complete bacteriological results in these 78 pneumonia autopsies are recorded in Table II.


The majorit)' of the meningococci isolated were Pasteur Type B and were also agglutinated by Gordon's meningococcus sera, Types II and IV (corresponding to the Rockefeller Institute normal meningococcus). The cultural and serological findings in tliese cultures were confirmed at Base Jjaboratory Xo. 1 at St. Xazaire and at the Central Medical Laboratorj' at Dijon.*

In our experience, ilespite certain contradictory statements in the literature in regard to the correlation of the American, English and French classification of meningococcus t)7>es. Lieut.-Col. Gordon's Types I and III and the Rockefeller


Bactekia Isolated from the Lungs at Autopsy from 78 Cases or Pneumonia at Camp HosriTAL No. 15, A. E. F., Fbance


B. influenstr Pure cultures 7 cases ♦Mixed " 23 " , assoc Total " 30 ••


TMeningococcus. . .11 times Pneur


. neumococcus IV 7 times •iated with-! f^trept. hemolytic. times

I Strept. vir 1 time

I It. tulierculosis. . . 1 time Pneumococci IV

Pure cultures 11 cases, HI. influenza 7 times

  • Mi\ed " 14 " , associated with-! Strept. hcmol ... . 4 times

Total " 25 " , I Meningococcus . . 3 times


Meningococci Pure cultures 7 cases, Mixed " 16 " , associated with Total " 23 " ,


rn. inlluen/.a 11 times

.Strept. hemol. . . . fi times Pneuniococcus IV 7 times

Strept. vir I time

H. tulH-rculosis. . . 1 time


Streptococcus hemolyticus Pure cultures !( cases.


Mixed Total


{ n. influenza. . . . Pneumococci IV


20


associated w ith-| Meningococci . I B. tul>erculo8i8.


B. tuberculosis Pure cases, Mixed " , associated Total 6 " ,


fstaphylococcus..

.,, Strept. hcmolvt.

with -; . ,. ' .

I Strept. vir

I H. inllucn?;!' . . . .


I tunes times times times

times times time time


Streptococcus viridans 2 ca.«c8 ~1

Staphylococcus aureus 2

Pneumococcus I 1 case

Streptococcus mucosus 1

Itacillus aerogenes capsulatus. . . I " Staphylococcus alhus 1 "


Associated with other organisms as indicated


  • Uixetl cultures refer to two or more species of bacteria

Institute paranormal sera usually agglutinate tlie same cultures as Pasteur Type A. Colonel Gordon's sera II and IV and the Rockefeller Institute normal meningococcus scrum usually agglutinate the same cultures as Pasteur Tyjie B. Pasteur Types C and I) are rare.

Gram-stained smears of the sputa from the pneumonia cases in which mcningoiocci were isolated showed so many intracellular gram-negative diplocwci as to resemble smears of spinal fluids from acute cases of meningococcus meningitis.

CLINICAL COURSE OF MENINGOCOCCUS PNEUMONIA In the severe ca.ses the onset was usually acute, after a period of indisposition la.sting from a few days to a week. Inuring the prodromal period there was generally a history of chills,


• Thanks are due to CapUin E. H. Mason, M. C, U. S. Army, for assistance In conflrming these cultures.


326


[Xo. 345




Days Hosp.


Laboratory findings durir


g illness



Autopsy


fin<dings



Case


Organization


Urine


W. B. c.


Blood cultures.


Sputum cultures


Date of death


Lung gross anatomy


t Lung cultures


topsy number


V. F


133 d F. A.


2


Alb. and casts


6400


^eg.


Mixed


9/3


Lobar pneumonia..



Meningo. A.


25


T. R


44th Engrs. 141st F. A.


a 12


Alb. and casts


4400 7000


Neg.

Neg.


B. inf


9/6 9/21


Bronchopneumonia . Bronchopneumonia .



Meningo. B. Meningo. B.


28


J.B


Meningo. B


36


S.C


114th T.M.B.


6



13!i00^


^o.g.


Pneumo IV. . .


9/22


Bronchopneumonia .



Meningo. B. Pueum. IV.


38


J. O'N. . .


61st Engrs.


7



7600


N«g.


B. inf


9/25


Lobar pneumonia, bronchiolitis.


Sup.*


Meningo. B.


44


C. S


141st F. A.


2






9/29


Lobar pneumonia. .



Meningo. B. Pneum. IV,


49





A. C


141st F. A.


17



4400


Neg.


Meningo. B. diphtheroid.


10/3


Bronchopneumonia, bronchiolitis.


Sup.


B. inf. Meningo. B.


57


M. D....


141st A. T.


7



9600


Neg.


Meningo. B


10/3


Lobar pneumonia. .



Meningo. B. Strept. vir.


58


R.S


329th F. A.


6



9400


Neg.


Meningo. B


10/8


Lobar pneumonia..



Meningo. B.


66


W. C...


329th F. A.


11



f6200\ \ 9000 J


Neg.


B. inf. Pneu. IV.


10/24


Bronchopneumonia, bronchiolitis.


Sup.


B. inf. Jloningo. B.


86


R. C


328th F. A.


2


Alb. and casts


5400


Neg.


B. inf


10/27


Bronchopneumonia .



B. inf. Meningo. B.


89





F. N


329th F. A.


3



4200


Nee



11/2


Bronchopneumonia, lung.


Wet


B. inf. Meningo. A.




B. P


Vet. Hosp.


3


Alb. and casts


2200


Neg.


B. inf


11/3


Bronchopneumonia, lung.


Wet


B. inf. Men

98



ingo.



L. F


330th F. A.


9


Alb. and casts


r 2600 \ 14200/


Neg.


B. inf


11/4


Bronchopneumonia..



B. inf. Meningo. C.


100





O.A


113th A. T.


8


Alb. and casts


18400


Neg.


Meningo


11/9


Bronchopneumonia, bronchiolitis.


Sup.


Meningo. Strept. hemol.


105


E.N


Vet. Hosp.


11


Alb. and casts


8000


Neg.


Meningo


11/13


Bronchopneumonia, bronchiolitis.


Sup.


B. inf. Meningo.


106


A. P


131st F. A.


13


Alb. and casts


J 9200 1 1 20,400 C


Neg.


B. inf. Meningo. .


11/23


Empyema. Bronchopneumonia. Sup. bronchiolitis.


B. inf. Meningo. Strept. hemol.


111


C. G


133d F. A.


9


Alb. and casts


2200


Neg.


Meningo. B


1/29


Bronchopneumonia, bronchiolitis.


Sup.


Meningo. B.


124


G.S


133d F. A.


6


Alb. and casts


/11,200\ \25,000J


Neg.


Pneu. IV'. Meningo.


2/1


Bronchopneumonia, bronchiolitis.


Sup.


Meningo. B. Pneu. IV.


125


A.J


7 th Vet. Hosp.


8


Alb. and casts


r5200"\ 1 9600 J


Neg.


B. inf. Meningococcus


2/1


Broncliopneunionia. bronchiolitis.


Sup.


Meningo. B.


127


J. D


132d F. A.


3


Alb. and casts


7200


Neg.


Meningo. B


2/3


Broncliopneunionia. bronchiolitis.


Sup.


Meningo. B. B. inf.


128


D.K


705th M.T.C.


6


Alb. and casts


ri400\ 1 4400 J"


Neg.


Meningococcus. . .


2/3


Lobar pneumonia. .



Meningo. C. B. int.


129


R. L


P. W. 38.


It)


Alb. and casts


7800


Neg.



2/4


Bronchopneumonia, bronchiolitis.


Sup.


Meningo. A. B. inf.


130





  • Sup. Bronch. = Suppurative Bronchiolitis. + Predomiimting org,i


coriled under lung cultures.


November, 1919]


32^


fever, headache, cough, pain in the chest and general malaise. The skin was pale blue. The patient looked very toxie; the chest examination showed variable areas of dullness and numerous moist rales, quite generally distributed. A few cases showed distinct lobar consolidation. The temperature was 103°-106°, pulse 85-100, respiration 25-30. The urine showed albumin and casts, usually early in the disease. The blood findings were negative blood cultures and a normal or reduced white cell count. The sputum was at first thin and watery, but rapidly changed to a creamy white which, on microscopic examination, showed numerous pus cells and gram-negative diplococci. Severe cases grew rapidly worse; the cyanosis increased; the lung consolidation extended and the patient died within a few days. Among those who survived the first week, there appeared to be a marked tendency toward suppurative bronchiolitis and protracted recover}-. As the areas of consolidation diminished, the bronchioles filled with thick muco-purulent secretions ; marked emphysema frequently developed ; such patients showed marked evidence of dysphonia. At this stage, there was usually a marked rise in the white cell count. Later in the disease, the meningococci in the sputum became considerably reduced and other organisms correspondingly more prominent.*

AUTOPSY KIXDIXGS IN MENINGOCOCCUS PNEUMONIA

The lung findings at autopsy were usually of the bronchopneumonic type with numerous points in the consolidated areas that exuded purulent fluid on pressure. Six cases were distinctly lobar in distribution. On section, the consolidated areas showed a peculiar pale violet color that appeared almost characteristic of meningococcus pneumonia. The pleura was generally quite free from exudate and the pleural surfaces were generally dry. Fibrinous pericarditis was present with very little increase of pericardial fluid. Endocarditis occurred in over half of the ca.ses. Cloudy swelling of the liver, acute splenic tumor and parenchymatous nephritis were constant. The abdominal recti muscles were found ruptured in five cases. The upper bronchi were generally inflamed and covered with creamy pus. Meningococci were always found to be most numerous in the purulent exudate from the bronchioles. Cultures from the pericardium and pleural cavities never showed meningococci. One patient dcveloiwd an empyema from which a pure culture of streptococcus hemolyticus was recovered from the fluid; yet, the lung cultures showed great predominence of meningococci. Jlcningococci were never recovered from any of the accessory sinuses. B. influemce was recovered from the sphenoidal cells in pure cultures in four cases.

Table III shows the laboratory findings in tiie 23 fatal cases of meningococcus pneumonia (without cerebrospinal involvement) .

That virulent meningococci were prevalent among the troops in Camp Coetquidon is shown liy the f a< t tiiat from Siptombcr


1, 1918, to February 15, 1919, 22 cases of cerebrospinal meningitis developed with 13 deaths. The meningococci isolated were of similar type to those found in the lung tissue of the meningococcus pneumonia cases.

BACTERIOLOGICAL FINDINGS IN CASES OP MENINGOCOCCUS MENINGITIS

Of tlie 22 cases of meningococcus meningitis that occurred during this period, blood cultures were taken in 16 with three positive results. The positive results were all obtained from early cases; and no positive blood cultures were obtained after the first day of tlie disease. In one case the spinal fluid was clear at the time the positive blood culture was secured. In this culture, the meningococci numbered 2 per c. c, yet on the following day, when the spinal fluid showed a high-cell count and numerous meningococci, a second blood culture gave negative results.

Spinal fluid cultures all gave positive results at tlie time the first turbid fluid was secured. In nearly all cases, however, cultures failed to grow meningococci after the third or fourth day, even though the white cell count remained high for much longer periods.

Panophthalmitis developed in one case and meningococci were recovered from the eye after enucleation. Among the 13 cases that came to autopsy, meningococci were recovered from the ventricles or base of the brain in six and from the pericardium in two cases. There was distinct evidence of pneumonic involvement in ten cases, from whidi cultures from section of the involved lung showed meningococci* in six cases (four times alone and twice associated with B. infiuenzw) . The other four ca.ses gave lung cultures of streptococcus hemolyticus, pneumococcus Type IV, pneumobacilli and staphyloc-occus aureus, respectively. Eighteen meningococcus cultures, secured from cases of cerebrospinal meningitis that were typed, proved to be Type B Pasteur.

M eninfiococcii.s Carriers. — During the progress of the epidemic, efforts were made to segregate the carriers of meningococci in the various organizations that were showing tlie greatest number of cases. The carrier rate varied greatly at different times and in different barracks at the same time, the general rate being much higher early in tiie epidemic than later. Some of these carrier surveys were made on groups of men too small to furni.sh reliable figures. Rut four sun'cys were made at different times on fairly large numbers of men as follows:


Time


Numbpr of men cultur«<l


Carriers found


Percentile


Sept. 20/18

r)rt. 20/18

Dec. 6/18

Feb. 10/18


llfiO 22Sfi I2.-.J ll!IO


198 2S0 110

f.O


10 12

8 5


•Thanks are due Captain W. M. Rhett. M. C. and the Medical Staff of Camp Hospital No. 15 for much of the clinical data.


These figures are of interest because they show an unusually high meningococcus carrier rate while the epidemiological waves were at their highest. The greatest number of carriers generally appeared to be present in the barracks where


328


[No. 345


respiratory affections were most numerous. Carriers isolated were reeultured twice each week. Very few of them continued to be carriers over prolonged periods and no so-called " permanent carriers " were found during the investigation.

DISCUSSION It will be observed that in this series meningococci rank third among the bacteria found most frequently in the lungs at autopsy in cases of pneumonia, being exceeded only by pneumocoeci and B. influenzae. However, if cerebrospinal meningitis cases be included, the meningococcus becomes the most frequently found organism in the lesions causing death during the epidemic. Out of 50 strains of meningococci typed from carriers selected at random 44 were Type B, four Type C, and two Type A Pasteur. Eighteen cases of cerebrospinal meningitis were caused by Type B meningococcus. Xineteen autopsy cultures from cases of meningococcus pneumonia showed 14 Type B, three Type A, and two Type C Pasteur. It is, therefore, evident that the prevailing type of meningococcus during this period was Type B Pasteur and was responsible for all of the meningitis cases as well as the larger proportion of meningococcus pneumonia cases. The frequent association of meningococci with B. influenzcB is of special interest. On artificial media, the two organisms grow together exceedingly well. The possibility of a symbiotic pathogenicity of these organisms is worthy of further study.

CONCLUSIONS

1. That meningococci were an important factor in the causation of post-influential pneumonia at Camp Coetquidon, from September 1, 1918, to February 15, 1919.

8. That the meningococci present in the lungs in cases of meningococcus pneumonia were essentially the same tj-pe of organisms as those found in the spinal fluids in cases of epidemic cerebrospinal meningitis.

3. That cases of meningococcus pneumonia may arise from contact with cases of meningococcus cerebrospinal meningitis and vice versa.

4. The meningococci may produce either bronchopneumonia or lobar pneumonia.

TECHNIQUE OF BACTERIOLOGICAL EXAMINATIONS

Blood Cultures. — Eoutine blood cultures were made on all cases of pneumonia. The medium used for such routine cultures was prepared as follows: Peptone, 10.0; salt, 5.0; glucose, 5.0; beef infusion, 1000.0. This was titrated to -1-0.4 acidity to phenolphthalein ; tubed in large test-tubes and sterilized in an autoclave at 30 pounds for 15 minutes.

Blood for culture was drawn from one of the arm veins with a sterile 10 c. c. syringe. This amount of blood was then injected into 40 c. c. of medium after which the mixture was incubated for 72 hours, unless growth occurred earlier. This method gave good results with pneumoeocci, streptococci and B. influenzce, but trial cultures with meningococci were unsatisfactory.


Blood cultures for meningococci were made on a medium prepared by adding 2 per cent agar to the above-mentioned bouillon and sterilizing as before. This medium was melted and cooled to 45° C. The amount of blood drawn for each culture was 10 e. c. as before. This was mixed with 30 c. c. of the melted medium and poured into sterile petri dishes, allowed to set and placed inverted in the incubator for 72 hours unless growth occurred earlier.

Cultures of spinal fluids and sputa were made on a petri dish medium prepared by adding 2 per cent of fresh sterile human blood (kept fluid by citration) to the previously mentioned agar medium, after melting and cooling to 50° C. This was poured into sterile petri dishes and allowed to set. Spinal fluids were collected in sterile test-tubes and centrifuged. Preliminary examinations were made by microscopic examination of smears stained by Gram's method. Cultures were made Ijy smearing the centrifuged sediment over the surface of the l)lood agar plates and incubating over night.

Sputa were obtained by having the patient cough and collecting the material directly into a sterile petri dish, from wliich direct smears were stained by Gram's method and examined. Cultures from sputum were made by selecting representative portions, smearing on blood-agar plates and incubating over night.

Agglutinaiion Tests. — The sera used for preliminary' agglutinations were Ijederle's and the Rockefeller polyvalent antimeningococcus serum. The sera used for type determinations were Pasteur Institute Types A, B and C. All routine agglutinations were read macroscopically. The standard dilution was 1 : 50. Colonies resembling meningococci were smeared and stained by Gram's method and if found to be gram-negative diplococci, agglutination tests were made with standard sera. Subcidtures, whenever necessary, were made by subculturing suspicious colonies either on Loeffler serum tubes or on blood-agar plates. The suspected colonies were emulsified with normal saline and this emulsion was mixed in equal proportion with polyvalent antimeningococcus serum diluted 1:25 with normal saline. A control tube containing normal saline instead of the antimeningococcus serum was set up in each case. In the early part of our work, control tubes made with normal horse serum were also set up. Later, these were discarded. The tubes containing the above mixtures were incubated for four hours at 37° C.

Positive cases were typed by substituting Pasteur Institute antimeningococcus sera A, B and C for polyvalent serum, using the same dilutions, controls and temperature of incubation as used for the preliminary agglutinations.

REFERENCES

1. MacCallum, W. G.: Journal A. M. A., March 8, 1919, LXXII, 720-23.

2. Chickering, H. T., and Park, J. H., Jr.: Jour. A. M. A., March 1, 1919, LXXII, 617-626.

3. Jacobitz: Zeitschr. f. Hyg., 1907, LVI, 175-192.

4. Gordon, M. H. (Temp. Hon. Lt.-Col. R. A. M. C): Personal communication.


NOVEMBEB, 1919]


329


5. A few cases of pneumonia In which meningococci have been isolated have been reported in army cantonments in the U. S. A.

6. Fletcher, W.: Lancet, Jan. IS, 1919, I. No. 3, 104. Meningococcus bronchopneumonia in influenza.

7. Kinnicutt, R., and Dinger. C. A. L.: Am. Jour. Me^lical Sciences, Sept., 1919, CLVIII, No. 3. 360-369. Isolation of the meningococcus from cases of so-called influenza.


8. Meader, P. M., Means. J. H.. Hopkins, J. G.: Am. Jour. Medical Sciences, Sept.. 1919. CLVIII. No. 3. 370-397. " Account of an Epidemic of Influenza .VmonK .American Troops in England."

9. Osier, \V. : Principles and Practice of Medicine. Sth ed. p. 113. ' This was found in eight of the Boston cases and in one it was so extensive that it could have been mistaken for the ordinary croupous pneumonia."


MENINGOCOCCUS PNEUMONIA. II

THE EPIDEMIOLOGY OF POSTINFLUENZAL PNEUMONIA IN WHICH THE DIPLOCOCCUS INTRACELLULAHIS MENINGITIDIS WAS ISOLATED. FROM OBSERVATIONS AT CAMP COETQUIDON, A. E. P., FRANCE

By WiLBiitT C. Davison, Baltimore, lid. Captain, Medical Corps, U. S. Army (Discharged)

ir. L. Holm, Lansing, Mich.

Major. Medical Reserve Corps, U. S. Armij {Discharged)

AND

EoBEKT V. B. Emmons, B. A., Ilanible, England Medical Corps, U. S. Army {Dijfcharged)


Because of the occurrence of the cases of meningococcus pneumonia described in the preceding paper,' the Base Surgeon, Base Section No. 1, A. E. F., France, requested us to investigate the epidemiology of this condition.

This study includes all of the bacteriological examinations made at Camp Hospital No. 15, Camp Coetquidon, A. E. F.,


Situation of ni(


Receiving wards ! 102

Other hospital wardb 450

Discharged patients 596

Contarts in barracks of UUt , 261

Field Artillery.

Contartii in barracks of 142d I 86

Field Artillery.

Contacts in barracks of 114tli 'SO

Trench Motor Battery.

Contacts in barraksof I14tii 6

Ammunition Train. 1

ToUl 1573


Number found positive. I. f.

with raeninfrococci in the rbinophftrynx


Perccntanre of positive or carrier rate


8 per cent.

7 per cent. 14 pi-r cent. 14 per cent.

1» per cent. 20 per cent.

per cent.


12 per cent.


  • Tlw grnt majorjtr of tbne cirrieri were of the temportrr claaa. Of 162 menlncococcua carriers cultured on the third daj only 37 were found poiitlre. Of IWcarriera

mt the next examination the aixth day only 15 were poaltlve.

France, of contacts of meningococcus pneumonia and meningococcus meningitis cases during the latter part of Scptenil)er and the early part of October, 1918.

In order to determine whether the incidence of these ca-sea was due to contact or infection in the hospital or in the barracks, cultures from the rhinopharyn.x were taken : ( 1 1 from

' See p. 324 of this issue.


every new patient at the time he was received into the hospital; (2) from all patients and attendants in the hospital; (3) from all patients at the time of their discharge from the hospital, and (4) from all contacts of recent cases of meningococcus meningitis in the barracks.

Until their cultures were reported negative, patients were held in strict quarantine in special wards of the hospital and discharged patients and contacts were held in " working quarantine " in the barrack.s, i. e., they could drill and mingle with other troops out of doors but had to sleep in isolated barracks.

In all, 1573 dilTerent patients, attendants, and contacts were cultured. Cultures were repeated at three-day intervals on all men found harboring meningococci until two successive negative cultures were obtained.

In Table I the results of these cultures are summarized.

The numbers of cases of cerebro-spinal meningitis and pneumonia from which meningococci were recovered and the number of carriers found in each organization as a result of the surveys of patients in hospit.jil and of contacts in barracks are indicated in Tabic II.

SUMMARY From the necropsy and cultural investigations described in the preceding paper (Meningococcus Pneumonia I), there can be no doubt that the post-influenzal pneumonia in Camp Coetquidon was due in at least 23 cases to infection with the meningococcus. This conclusion is further substantiated by the epidemiology. The IJOth, 141st and M2d brigades of field artillery came from Camp Beauregard (Ix)uisiana) in which numerous ca.ses of cerebrospinal meningitis (meningococcal) had occurred rluring the previous winter. Probably many men of these organizations still harbored meningococci in their throat.s. The epidemic of influenza with its coughing greatly increased the nunilx-r of the.se meningococcus carriers.


330


[>fo. 345


The cultural surveys of the hospital patients and barrack contacts (Table I) show an average meningococcus carrier rate of nearly 13 per cent. From the wide distribution, as sho^vTi


Organization


Number of

meningococcus

pneumonia

cases


Number of meningococcus meningi

Number of meningococ found wbile

patients in

hospital


Number of meningococcus carriers found in survey of barrack;


Total number of meningococcus carriers found in each organization


131st Field Artillery. 132dF.A.


5

1




3

3


No survey. No survey


3 33


133d F.A.


2 (1 fatal).



5


No survey.


5


UOtli F. A.


3 (1 fatal).



12


No survey.


12


141st F. A.


5 (4 fatal).


4(1 fatal).


34


38


72


142d F. A.



2 (2 fatal) .


10


8


18


328th F. A.


1



1


No survey.


1


329tli F. A.


1 (fatal).



14


No survey.


14


330th F. A.



1


2


No survey.


2


114th Ammunition Train.

310th A. T.


1 (fatal).


1


29 2


No survey.


29

2


114th Trench Mot. Bat.

61st Engineers.

Casuals . . .


1 (fatal) .

2 (1 fatal). 1 (fatal).


1 (fatal).




3

7


13

No survey. No survey.


13

3

7


Total . . .


23(11 fatal).


9 (4 fatal).


125


59


184


in Table II, it was impossible to state definitely whether the infections occurred after the patients were received into the hospital or whether they had occurred in the barracks, but it it probable from the high carrier rates in both places that the influenza patients might well have acquired their secondary infection in either location.

It would seem evident, therefore, that the meningococcus was both endemically and epidemically distributed in the rhinopharj-nges of the troops in Camp Coetquidon and that this explained the relatively large number of cases of postinfluenzal pneumonia in which meningococci were isolated.

TECHNIQUE USED IN EXAMINATION OF MENINGOCOCCUS PNEUMONIA AND MENINGITIS CONTACTS

Swabs were taken from the posterior rhinopharyngeal wall (curved wire swab "A" and tongue depressors "B" being used) and immediately inoculated on a small area of a hemoIj-sed blood-agar plate. (Veal infusion agar -1-0.2 per cent to phenolphthalein, or Ph. 7.8 was used; 3.0 c. c. of human, sheep, or rabbit's blood, hemolysed with 10 c. c. of sterile distilled water, were added to each 100 c. c. of melted agar at 50° C, immediately before pouring plates). This inoculation was then spread over the whole surface of the plate by means of a sterile wire spreader (C), (either immediately or on return to the hospital laboratory) and the plates incubated for from 18


to 24 hours at 37° C. They were then examined for suspicious colonies with the naked eye or a 10-power hand-lens. Meningococcus colonies are round, transparent, light gray and not umbilicated. Suspicious colonies were fished to hemolysed blood agar or Loefiler coagulated serum slants and iucubated over night. A gram-stained smear was then made from each subculture.

Those containing gram-negative cocci were emulsified in normal saline as follows :

1. Saline was added to the cultures with a pipette according to the amount of growth (t. e., 2 to 3 c. c.) .

2. The growth was carefully washed off by means of a dropping pipette (i. e., one fitted with a nipple) and transferred to a second tube.

3. Saline solution was added to these suspensions so that all were distinctly and equally cloudy.

4. The emulsions were agglutinated with meningococcus serum, the following technique being used : Five drops, or




TABLE HI




To the


1st


5 drops or 0.25


5 drops or 0.25


Previously


Making


tube.



c. c. of the


c. c. Rockefel

diluted to


the final




bacterial sus

ler Institute


1:25.


dilution




pension.


or N. Y. Board of health polyvalent meningococcus serum.



1:50.


To the


2d


« 


5 drops or 0.25


.<


« 


tube.




c. c. Pasteur type A meningococcus serum.




To the


3d


..


5 drops or 0.25


« 



tube.




c. c. Pasteur type B meningococcus serum.




To the


4th


..


5 drops or 0.25



.<


tube.




c. c. Pasteur type C meningococcus serum.




To the


5th


<.


5 drops or 0.25



..


tube.


Gth



e. c. Pasteiir t}'pe D meningococcus serum.

5 drops or 0.25




To the


Control.


tube.




c. c. normal saline.



0.25 c. c. of the bacterial suspension and the same quantity of various meningococcal type sera were placed in each of five agglutination tubes as indicated in Table III.

The five tubes were then incubated at 37° C. preferably for two hours in a water-bath or three hours in a dry incubator.

Lt. Col. M. H. Gordon's meningococcus type sera, I, II, III and IV or the Eockefeller Institute normal, paranormal, and intermediate type sera may be substituted for the Pasteur Institute type sera A, B, C and D.

When many cultures are to be agglutinated it will be found more economical of time and material if onlv tubes 1 and 6


NOVEMBEH, 1919]


331


are used. If after two hours tliere is positive agglutination with a polyvalent serum, the original suspension may then be typed by agglutinating in tubes 2, 3, 4 and 5.

The men whose cultures gave positive agglutination with a polyvalent serum were reported immediately as carriers, placed under hospital or working quarantine (vide supra), and re


'..^


examined at three-day intervals until two successive negative cultures were obtained.

APPARATUS A. Ordinary hay wire was cut into six-inch lengths and the distal half-inch was bent at an angle of 135° with the shaft. Non-absorbent cotton was twisted around this distal curved


end. These were sterilized by dry heat in lots of 25 in metal containers or glass jars, the tops of which were covered with paper. In our opinion, this swab is more convenient than the West tube swab not only on account of its greater simplicity of preparation but from the fact tliat any one with a little practice



can swab the posterior rhinojjliaryngcal wall of an adult without touching the mouth structures.

B. It was found that requiring each man to use his own mess spoon as a tongue depressor was often convenient.

C. To make spreaders six-inch lengths of hay wire were bent as shown in the diagram. These were sterilized by dry heat in lots of 25 in metal or glass containers.


THE OCCURRENCE OF THE PFEIFFER BACILLUS IN MEASLES


By Andrew Watson Sellards, JIajor, M. C, U. S. A.,

AND

Ernest Sturm, Second Lieutenant, S. C, U. S. A. (From the Base Hospital, Camp Devens, Mass.)


Certain similarities between measles and influenza were especial!}' noticeable when these disea.ses were prevalent during the early part of last autumn. With the onset of influenza at Camp Devens, ^lass., the symptoms in the earlier cases were distinctly less fulminating than at the height of the epidemic. The possibility of measles in the prc-eruptive stage required consideration in establishing the diagnosis of the first group of influenza patients admitted to the base hospital. The acute onset of conjunctival and respiratory symptoms was accompanied by a pronounced leucopoenia. There are other noteworthy similarities between the two diseases. Both arc highly contagious and are frequently complicated by pneumonia in its various forms. The occurrence of the Pfeifl^cr bacillus in a high proportion of patients has been reported in measles as well as influenza. As we were engaged at this time in the study of measles, it seemed advisable to investigate the occurrence of PfcifTer and Pfeifi'cr-like organisms in measles patients.

Summanj of Literature. — ^Thc literature contains fairly numerous reports of the occurrence of B. influenza of PfeifTer in cases of measles. Unfortunately a considerable number of the reports fail to furnish the information upon which the identification of the bacillus was based. In some, reliance seems to have been placed upon microscopic examination of smears stained by Gram's method ; in other instances typical cultures were obtained upon blood-agar but no evidence was furnished to show that haemoglobin was essential for successful


cultivation. Such results are open to doubt since other organisms may simulate closely the growth of B. influenza: on bloodagar. In the following review, as a rule, those papers will be omitted in which pneumonia and a Pfeifl"cr bacillus infection are reported as remote sequchv of measles.

The association of measles and the influenza bacillus was flrst mentioned by Paltauf ' in 1899. He reports the occurrence of B. influenza' in two cases of bronchopneumonia foUowiuK measles: the details concerning the means of identification of the bacillus are not stated.

Giarr& and Picchi ' were the first investigators to report the occurrence of Pfeiffer-llke organisms in active Ciises of measles, pure cultures being recovered readily from the conjunctival and bronchial secretions. These authors raise the question of a possible specific efiologic r6lD of these organisms in measles.

Albrecht and Ghon ' in 1901 describe one case of bronchopneumonia developing three weeks after an attack of measles. At autopsy the Influenza bacillus was isolated from the lung.

In the autopsy of 23 cases of measles Jehle ' reports the occurrence of the PfeifTer bacillus In the heart's blood In 15 and In the lungs in 18 cases. This author regards the Influenza bacillus as a common secondary Invader In the acute exanthemata.

SiisHwrin' in lOiil studiod measles patients clinically and at autopsy; he recovered the PfeiiTer bacillus In 10 of 21 cases. The positive cases were considered to be mixed infections of measles and influenza.

Liob.scher* In autopsies of 11 ca.sea of meaalcs, recovered the Pfelffer bacillus In 3 cases from the lungs; his work Is of especial Interest In that two of three cases showed a pneumonia with the Influenza bacillus present In pure culture.


333


[No. 345


Klienberger ' reports cultivation of " hsemopliilic " bacilli from the conjunctiva: in 3 of 9 patients of measles during life, and in one of two cases at autopsy a pure culture of " hsemophilic " bacilli was obtained from the heart's blood.

Davis" examined uncomplicated cases of measles during the stage of eruption. Cultures were taken from the sputum or from throat swabs, a single examination being made in each case Organisms indistinguishable from the Pfeiffer bacillus were isolated in 13 of 22 cases.

Pacchioni and Franchioni » obtained Pfeitfer-like organisms readily from the mucous membrane of measles cases. Careful blood cultures in 25 patients were negative for this organism in all except one case; one positive culture was obtained shortly before death from a case complicated by bronchopneumonia. These authors give serious consideration to the possibility that measles may be caused by a Pfeiffer-like organism.

Reiss and Gins " report the cultivation of the influenza bacillus from the blood 17 days before death from a case of postmeasles bronchopneumonia.

Of especial interest are tho.-;e reports which record the presence of the Pfeiffer bacillus in the uncomplicated cases of measles during life. The bacillus has been found, as a rule, only in the mucous membrane of the conjunctivee and in the respiratory tract. Only rarely has it been recovered by blood culture and then only in cases complicated by pneumonia. It is noteworthy that Liebscher in 1903 reported the occurrence of the Pfeiffer bacillus in pure culture in the lungs in two fatal cases of pneumonia following measles.

EXPERIMENTAL WORK

The following examinations were conducted chiefly at Camp Devens, Mass., and were commenced immediately after the decline in the epidemic of influenza in September and October, 1918. The latter began on September 8, reached its maximum 8 days later and declined very rapidly during the next week. In the remainder of September and October a few cases were admitted practically every day ; by the first of November the admissions for influenza had virtually ceased. Small foci of the infection probably remained in camp throughout the winter. A full account of the epidemic was reported by Woolley." The measles parents were examined with the object of determining the relative frequency of Pfeiffer or Pfeifferlike organisms and the period for which these organisms persisted after the subsidence of the symptoms of measles. Numerous cultures of hffimoglobin requiring organisms were isolated ; these strains were, superficially at least, identical with B. influcnzce of Pfeiffer.

Technique. — The cases of measles were examined during the stage of eruption, the first examination being made as a rule within from 24 to 36 hours after the appearance of the rash; subsequent examinations were made at intervals of one to two weeks. Only a single examination was made during the eruptive stage in the cases which were negative. All of the patients showed the usual respiratory symptoms but only two of the cases were complicated with a definite pneumonia. As a routine the sputum of patients was examined, material being secured, as far as possible, which had been coughed up from the trachea or bronchi. In the hope of eliminating some of the commoner saprophytes, the sputum was injected in quantities of 0.25 to 0.5 c. c. intraperitoneally into white mice according to the technique recommended


by the Rockefeller Hospital for the isolation of the pneumococcus. The mice were sacrificed when they were markedly ill, usually after about 10 to 12 hours, spontaneous deaths being for the most part avoided. Cultures were made on blood-agar plates. Throughout this work human blood-agar has been employed — 10 per cent blood in meat infusion agar with a reaction to phenolphthalein equivalent to 0.1 per cent of normal acid. These plates were inoculated from the peritoneal exudate, from the heart's blood and from any early pneumonic or ha^morrhagic patches in the lung.

The growth from the heart's blood and from the lung often showed an almost pure culture of Pfeiffer-like organisms, i. e., a small nonmotile Gram-negative bacillus (about 0.2 by 0.5 micron) without capsule or spore formation, growing aerobically on human blood-agar as minute discrete colonies without producing hcemolysis. The need for haemoglobin was tested by substituting

TABLE I

Incidence of PFErFFES-LiKE Bacilli in Sputum of Measles

Patients


Nov. 12 " 12 " 12 " 12 " 12 " 12 " 26 " 26 " 26 " 26 " 26 " 26 " 28 " 28 " 28 " 30 " 30 " 30 " 30 " 30 " 30 Dec. 2 2 4 4


Period of observation


Negative Positive Negative Positive Negative Positive

Negative Positive


Negative Positive


Positive 19, or IH


10 to 14 days liter eruption


Negative Positive Negative


Positive Negative


Positive Negative


Positive Negative


20 to 25 Aaj3 after eruption


Negative

Negative Positive

Negative


Positive Negative


Positive 6, or 24^


Positive 6 or 26^


40 days after eruption


Negative


Negative


Negative Negative


ascitic fluid for blood in the culture medium — 10 per cent of unhealed ascitic fluid, free from bile pigments, with a specific gravity of 1.018. Blood serum was not employed on account of extremely minute amounts of hfemoglobin which may sometimes sufiice for the growth of the Pfeiffer bacillus. In testing the hjemoglobin requirements of a given strain, blood and ascitic media were prepared from a common stock of agar. Heated blood-agar (chocolate-agar) was occasionally employed. Agar of the same composition as used for the fresh blood medium was mixed with human blood (10 per cent). The mixture was maintained at a temperature of about 95° C. for approximately ten minutes.

Strains of a Pfeiffer-like organism were recovered from five of the first six cases of measles that were examined. Seven normal men on duty at the base hospital were tested in the same way. Two of these men had had influenza 6 weeks before. No organisms resembling the Pfeiffer bacillus were found; these tests were repeated three and seven days later with nega


NOVEMBEB, 1919]


333


tive resiilts. The following table gives the incidence of the Pfelffer-like organisms found in 25 additional cases of measles.

The cases in Table I are given in chronological order to show that the positive results occurring on the first examination ♦ere distributed rather equally throughout the series.

Distribution of the Pfeiffer-like Organisms. — Examinations were made for determining the extent to which the hivmoglobin requiring organisms are distributed throughout the body in cases of measles. Cultures for this purpose were made during the first day of the rash from the conjunctivae, from morbillous lesions of the skin, from the blood and in two cases from Ijrmphatic glands.

Conjunctiva. — Inoculations from the inflamed conjunctiva; were made with a cotton swab on blood-agar plates. The secretions showed comparatively few bacteria of any kind. Fourteen cases were examined and Pfciffer-like cultures were recovered from six; in two of these ca^es the organisms were present in relatively large numbers in almost pure culture.

Skin Les'ion-s. — Small pieces of skin showing morbillous lesions were excised and smeared on blood-agar. Eight cases were examined but no hajmoglobin-roquiring organisms were recovered.

Blood Cultures. — In view of the almost constantly negative results of blood cultures for the Pfeiffer bacillus in influenza, comparatively few examinations were made in the measles cases. Meat infusion broth containing a little lakcd human blood was inoculated with the patient's blood during the first 12 to 24 hours of the rash, from 1 to 5 c. c. of patient's blood with 75 to 100 c. c. of broth being u.«ed. Large Erlenmeyer flasks were employed as containers for the broth in order to give a large surface area. After incubation for 24 to -18 hours, subinoculations were maile from these flasks on ordinary bloodagar and on heated blood-agar plates. The results in seven cases were negative. Six of these were uncomplicated. One patient developed early pneumonic lesions; the cultures were continued during the 2d, .3d and 4th day of tlie rash, but only a non-ha'molytic streptococcus was recovered from the l)lood.

Lymphatic Glands. — In a rather large number of the infcctiou.s diseases the causative organisms can be recovered from the lymphatic glands more readily than from the blood stream. In measles there is at least a theoretical possibility that the virus is disseminated by way of the lymphatic sy.«tem. In two cases, a superficial gland was excised from the inguinal region as soon as the rash had advanced to thi.s area. Smears from tlie gland were made on blood-agar and on heated blood-agnr plates. The results in one case were negative; in the other. "> or colonies in all were obtained on the heated blood-agar, no growth developing on the unheated media. Sub-cultures were obtained either on heated or unheated blood media but only with difiicult)'; no growth was obtained on ascitic agar. Even on heated blood-agar the colonies were always much smaller than the typical Pfeiffer colonies; sometimes growth (otild be definitely demonstrated only by the microscopical examination of a stained smear. In its morphology and staining reactions, this organism corresponded to the Pfeiffer bacillus except that, even in very young cultures on unheated blood-agar, numerous


forms were present which were from two to four times the length of the typical Pfeiffer organism. After four subinoculations the strain died out.

CO.MPARISON OF PFEIFFER STRAINS FROM CASES OF MEASLES AND OP INFLUENZA

These strains of organisms from the conjunctivic and the sputum were propagated on human blood-agar, transfers being made at intervals of four or five days. They were compared with similar strains of the Pfeiffer organism isolated at autopsy from the lungs of influenza cases occurring during the epidemic. Morphologically the strains from the two diseases were almost identical. The cultures from the measles cases showed little tendency to develop bizarre forms even on heated blood-agar and then never in extreme degree. Davis ' has reported the isolation of a strain of Pfeiffer bacillus possessing feeble haemolytic properties. Xo haemolysis was produced by our strains on human blood-agar or broth media made of 5 per cent of blood in meat infusion broth just acid to phcnolphthalein (0.1 per cent normal acid). Only very scanty growth occurred in the unheated blood broth medium. Fairly abundant growth was secured in liquid media by partially laking the blood with two volumes of water.- Preliminary observations were carried out on the spectroscopic changes occurring in cultures. L'ninoculated control flasks of media showed typical absorption bands of o.xyha^nioglobin. With whole blood slight growth occurred without any apparent change in the absorption bands. With laked blood after 48 hours the cultures showed bands characteristic of methajmoglobin ; after 72 hours, in acidified samples a broad band also appeared in the green. Cultures from measles cases produced changes more readily than those obtained from the influenza patients, but these differences might readily be explained by a difference in the rate of growth.

The principal object of the comparison of the measles and influenza strains consisted in an Httem])t to find some fundamental biological differences between tlie organisms obtained from the.se two sources. Observations were conducted on the reactions of agglutination and complement fixation, on tlic resistance of the organisms to freezing and drying and on the effect of bile and of sodium hydroxide. A comparison was made of the local reaction of the two strains upon intracutaneous inoculation of rabbits; strains from measles cases were also inoculated into monkeys and into some human volunteers.

Immunity licaction.t. — Botli the agglutination test and the complement fixations failed to show any constant differences between tiie two strains of organisms; some of the measles strains reacted with the serum of measles and influenza convalescents and also with normal individuals. In some instances the serum of a measles convalescent fixed complement witii strains of organisms obtained from either measles or influenza patient^?. No evidence was ol)tained whidi possessed any significance regarding the etiology or diagnosis of measles. In some experiments on phagocytosis, Pacchioni and Franchioiii ' re


334


[No. 345


port that the serum of measles patients possesses a high opsonic index for Pfeiffer-like organisms.

For the agglutinations, a moderately heavy suspension of bacteria was prepared in physiological saline from a 4S-hour growth on blood-agar. This suspension was mixed with an equal volume of serum in dilutions varying from 1-10 to 1-100. The mixtures were incubated at 37°C. for from 2 to 24 hours and at 55°C. for 12 hours. The majority of all the results were negative; only a comparatively few preparations showed well defined clumping.

The complement fixations were carried out with a sheep cell rabbit serum hsemolytic system, two units of complement being used. The antigen was prepared by digesting a saline suspension of the bacteria at 37°C. for 5 to 6 days. After centrifugalization, the opalescent supernatant fluid was titrated for its antigenic power; one-half of the maximum quantity permitting complete haemolysis was employed in the tests. The serum to be tested was inactivated at 55°C. and 0.1 c. c. was employed; the total volume of the final preparation was 2 c. c. One series of antigens was prepared by alcoholic extraction of a saline suspension of bacteria that had been allowed to autolyze for one week at 37°C. Since these immunity reactions were essentially negative the results are not recorded in detail.

The results of the agglutination tests conducted by Wollstein " indicate that the Pfeiffer-like bacilU can be subdivided into smaller groups. Such evidence, unless very striking differences are obtained, does not constitute proof of distinct species. Accordingly, we did not carry the work on immunity reactions any farther. Some of the more general biological characteristics of these two strains of Pfeiffer organisms liave been investigated in the search for evidence that might indicate the existence of distinct species in the htemoglobinophilic group.

TABLE II Showing Effect of FtaiEziNo on Pfeiffeb-Like Obqanisms


Growth on blood-agar afte


STRAINS FEOM MEASLES CASES



Slight Heavv


Slight Heavy


Heavy None


Heavy



STRAINS FROM


INFLUENZA CASES



A


Heavy


Slight


Heavy


B




None


C



Heavy


Heavy


D



Slight


None


E




Heavv


P



Heavy


None


G



None



H



Heavy


"


Effect of Freezing.— Many of the Pfeiffer cultures were found to be susceptible to even moderately low temperatures whereas others were resistant. The measles and the influenza strains did not fall into distinct groups. However, six of eight


cultures from measles cases in contrast to three of eight cultures from influenza patients were resistant to freezing.

Technique. — Emulsions of the Pfeiffer bacillus in physiological salt solution were rapidly frozen and thawed 15 times, a freezing mixture of ice and salt at about — 10° to — 12° C. being used. After each 5 freezings, cultures were made on human blood-agar plates. Table II gives a typical result.

Several repetitions of this experiment on these same cultures showed that the behavior of the Individual strains was almost constant. Some of the strains were not only unable to withstand alternate freezing and thawing but were destroyed by continuous freezing at about — 10° C. maintained for from two to three hours.

Effect of Drying. — These cultures of the Pfeiffer bacillus succumbed rather readily to drying for a short period. Under

TABLE III Showing Effect or Drying on Pfeiffeb-Like Organisms


Serial number


Growth on blood-agar


After i minutea


After. 8 minutes


STRAINS FROM MEASLES CASES


2


None


None


4


"


"


7


Alive


Alive


10



"


12



"


26


None


None


27


Alive


Alive


29


"•


"


STRAINS FROM INFLUENZA CASES


None Alive None Alive None


Alive None Alive None


None


the conditions of the experiment, the measles strains survived a little longer than those from influenza patients but the differences were not marked.

Technique. — A coarse coil of platinum wire was dipped in a saline suspension of young cultures of the organism to be tested. The moistened coil of wire, free from any gross droplets of the emulsion, was suspended in a dessicator at room temperature for periods of 4, 8 and 12 minutes. Cultures were then made on bloodagar. A characteristic result is given in Table 111, these results being constant on two repetitions except in the case of one culture (4) which was dead in one and alive in another of the two succeeding tests.

Action of Bile. — In contrast to their resistance to freezing and drying, the measles strains seemed more susceptible to the action of bile than the cultures obtained from influenza cases.

Technique. — Saline suspensions of 4S-hour cultures of the Pfeiffer organisms were mixed with an equal volume of varying dilutions of bile. The mixture was incubated for 1 hour at 37°C. in a water-bath. Occasionally there was some macroscopic evidence of clearing, but in order to obtain definite results, cultures were made upon blood-agar. A similar technique was used in the later


November, 1919]


335


experiments in which bile salt and sodium hydroxide were substituted for bile. The dilutions given in the tables represent the final strength after mixture with the bacterial emulsion. The action of bile is illustrated in Table IV.

The difference in behavior of the two strains towards bile appears at first to be very striking; moreover, the indiviilual

TABLE IV Showing Growth on Blood-Ag.\k Afteb Exi-osire to Bile


Final dilution of bile


Serial number



STBAINS


FROM MEASLES CASES



1


None


None


None


Slight


2



"


Slight


"


4




'*


Heavy


7




•'


•'


10




"


•'


12




None


Slight


26




Slight


Heavy


27




•'


•'


29




"


Slight


STRAINS FROM INFLtTENZA CASES


B


Heavy


Slight


Heavy


Heavy


C


"


Heavy


"



D


Slight


Slight


Slight


Slisht


E


None


None


None


None


F


Heavy


Heavy


Heavy


Heavy


G



Slight


Slight


•'


H


Slight


Heavy


Heavy



cultures in four repetitions of this test behaved constantly in this manner. ITowever, the total number of cultures tested is small and even in moderate dilutions of 1 : 40 the difference disappears altogether.

Action of Sodium Hydroxide. — The effect of sodium hydro.xide upon the cultures was rather variable, but the results

TABLE V

Showing Gbowtu o.n Blood-Agab After ExrosiEE to Sodium

Htdroxide


Serial



Final dilution of sodium hyilroxidc



number


N/8


N/10 N/M


N/60 1


N/100



I


itraiks from measles cases



1 None


None


Slight


Heavy


2




Slipht



None



Heavy


7




"


10


'




12




.«1i«ht


26



None


None


27


"


Slight


Heavy


29



None



Heavv Sllfiht Heavy


Slight Heavy


STBAi:«8 FROM INFLtTENZA CASES


B


None


None


None


Slight


I leavy


C




"


None


SliKht


n





Slight


Heavy


E




"


'


Slight


p




"


None


"


G




Slight


Heavy


Heavy


H




None


Slight


Slight


in general were the reverse of those obtained with bile. The following data in Table V are characteristic.

From Table V it will be seen that there is only a small rauge of dilutions within which it is possible to demonstrate differences with sodium hydroxide ; moreover, with some strains of organisms it is very difficult to obtain constant results under apparently identical conditions.

Action of Bile Salts. — Whole bile contains not only the biliary salts but an appreciable amount of alkali ; since bile and the hydroxide act in a somewhat different manner on these Pfeitl'er strains, it seemed desirable to ti-y the action of bile salts alone. As in the case of other manifestations of the action of bile, the effect of the purified salt was less striking than the action of the whole product. Sodium taurocholate in 2.J per cent concentration killed all cultures tested ; at 1 per cent the majority of the cultures were killed, whereas with one-half per cent about half of the measles and also lialf of the influenza strains were killed ; at one-tenth per cent, all but 3 of IG strains lived. Certain strains of the Pfeiffer bacillus are therefore approximately as susceptible as the pneuniococcus to the purified bile salt.

Effects of Inoculation. — These cultures exhibited very little virulence upon inoculation into the smaller laboratory animals. Four cultures of measles strains and three of the influenza strains were tested upon rabbits, guinea-pigs, and mice by intraperitoneal inoculation. The rabbits and guinea-pigs showed no symptoms ; occasionally the mice were killed in from two to three days by the injection of the growth from one to two blood-agar slants. A series of rabbits was inoculated intracutaneously with the two strains of organisms. Seven cultures from measles patients were tested ; in all cases well marked oedema and inflammation developed during the first 24 hours, these symptoms persisting for from two to four days. Of seven cultures from influenza cases, tested in a similar manner, five showed virtually no reaction and two behaved precisely like the cultures from measles cases. The influenza cultures had been isolated approximately two months earlier than those obtained from measles patients; the two influenza strains producing inflammation were obtained earlier in the epidemic than the five causing little or no reaction.

Two adult monkeys (Macacus rhe.fiis) were inoculated with a mixture of eight strains obtained from the sputum and conjunctivsB of measles cases. These cultures had been isolateij for periods varying from one to three weeks. The growth from 48-hour cultures on blood-agar plates was suspended in salt solution. This emulsion was thoroughly rubbed over the mucous membranes of the eyes, nose, mouth and throat. In one monkey the mucous membrane of the mouth was scarified slightly on the right side ; on the left side 0.5 c. c. of the bacterial suspension was injected under the mucous membrane. The scarified mucous memlirane healed promptly and no local lesion developed at the site of the inoculation under the mucous membrane. Each of the.se animals also received intraperi toneally 2 c. c. of a moderately heavy saline suspension of these cultures.


336


[No. 345


Daily temperatures and white counts were made upon both monkeys. One remained entirely normal ; the other, after an incubation period of six days developed definite malaise as evidenced by the loss of strength and loss of appetite. This animal had been under close observation for four months prior to tliese injections and had remained entirely free from any symptoms. During the period of malaise a suggestive drop occurred in the leucocyte count, unaccompanied, however, by any febrile reaction. The symptoms disappeared before the normal white count was fully re-established. At frequent intervals after inoculation, cultures were made from the mucous membranes on blood-agar. PfeifEer-like organisms were not recovered from either monkey. The temperature and counts in the monkey which became ill were as follows:

INOCULATION OF MONKEY WITH PFEIFFER-LIKE STRAINS OF ORGANISMS


Days after inoculatioa


Temperature


White count


Room temperature




101.8


13,750


66°



1


100.8


25,250


63.5°



2


101.6


13,600


67°



3


100.2


23,800


77°



4


101.4


15.300


78.8°



5


100.4'


H,600


66°



6


101.2'


10,000


68°



7


101.0 =


10,800


68°



8


101.6 =


10.600


68°



9


101.2'


15,500


68.9°



10


102.6*


9,700


66°



11


102.0


11,100


68.9°



12


101.8


15,400


68°



13


101.6


16,000


68°



14


103.2


13,300


68.9°



15


102.5


15,300


68.9°



16


101.6


16,200


68.9°



17


102.0


17,300


68°



18


101.2


15,700


67°



19


100.6


16,400


68.9°



20


100.4


17,400


66°


^ Cyanosis, conjun 2 Deep cyanosis, ci 3 Marked improve

  • Apparently norn


and loss of appetite, ill. 'es clearing, appetite good.


A few inoculations of human volunteers were undertaken with the Pfeiffer strains obtained from measles eases. A mixture of five strains was employed, three of which were obtained from the sputum and two from the conjunctivae. These cultures had been under artificial cultivation approximately six to eight weeks. All were easily killed by bile and all were resistant to freezing.

For the protection of the individual, the precautionary measures were taken, which have already been outlined for the inoculation of volunteers with the virus of measles ; * these precautions include observations for the exclusion of the Pfeiffer bacillus. As an additional safe-guard for the first inoculation, an individual was chosen who was immune to measles and who had had influenza in the recent epidemic. The mucous membrane of the eyes, nose and throat was inoculated with a saline emulsion of the five strains. During the next two weeks cultures were made at three-day intervals on blood-agar and mice were inoculated with sputum for the re


' Bull. Johns Hopkins Hosp., 1919, XXX, 257.


covery of the Pfeiffer organism. The cultures were negative and the individual himself developed no symptoms.

Accordingly, a volunteer was inoculated who had had influenza recently but not measles. No symptoms appeared and the cultures failed to colonize. Two additional volunteers were inoculated, who as far as could be determined, had had neither measles nor influenza. Both of these subjects remained entirely free from symptoms; the white blood count and the temperature did not vary beyond the normal limits, and the cultural examinations failed to show any evidence of colonization of the inoculated organisms. Under natural conditions, the Pfeiffer bacillus can readily establish itself in the mucous membranes. Hence the failure to produce symptoms would have possessed much more significance if successful colonization of the inoculated cultures had been obtained. These negative results are of some interest in view of the discussion regarding the occurrence of B. influenza in normal throats ; in some instances, at least, it does not persist when heavily inoculated into healthy individuals.

Davis * found the Pfeiffer organism in a high percentage of cases of pertussis. Under the more favorable circumstances of an interepidemic period, this investigator reports the production of respiratory sjTuptoms with prolonged colonization of the bacillus in man.

DISCUSSION

A comparison of dift'erent strains of the Pfeiffer bacillus showed considerable variation, more especially as regards their resistance to freezing and to the destructive action of bile. The attempt to separate the cultures into two distinct groups becomes very difficult during an epidemic on account of the opportunity for mixed and for cross infection. It is to be expected, for example, that a group of cultures obtained from measles cases would contain some strains behaving like the majority of those obtained from influenza. Such variations wore numerous, but the individual strains were not consistent in the series of tests that were employed. Thus, two of the measles strains were susceptible to freezing. In this respect they behaved like the influenza cultures ; yet these same strains were resistant to drying and susceptible to the action of bile, conforming in these tests to the majority of the other cultures from measles. The complete record of these strains that were tested is shown in the following outline.

VARIATIONS IN PFEIFFER-LIKE ORGANISMS







Intracu

Tests employed


Freezing


Drying


Bile 1-10


NaOH N/20


taneous







tions


Serial number of



2





measles strains


4


4


None




resembling i n

7


26



26


17


fluenza cultures





29


29


Serial letter of in

A






fluenza strains


c


B




B


resembling


E


D


B


G


I


measles cultures







Our information concerning the Pfeiffer bacillus is as yet extremely meagre; satisfactory methods have not yet been


XOVEMBEB, 1919]


JOHNS IIOPKIXS HOSPITAL BULLETIN


337


devised for performing tests for pathogenicity or for fermentation and immunity reautious. At present this bacillus is identified by its size, the lauk of motility, its decolor ization by Gram's stain and its multiplication only iu the presence of haemoglobin.* The situation may be illustrated by comparison with the very broad typhoid-colou group of organisms. As regards B. coli and B. typliosiis these orgauisms are virtually identical in their size, motility and staining characteristics. Without either fermentation tests or immunity reactions it would become a difficult problem to separate them into perfectly distinct species or even to determine the etiology of typhoid fever.

In the absence of definite information it seems unwise to attempt any final statements concerning B. in/lucitzw and its possible etiologic role in the respiratory diseases in which it is most commonly found. Certainly the general opinion at present is decidely against the acceptance of the bacillus as the specific etiologic agent of influenza. This opinion is held largely because of the frequent failure to find the organism in typical cases and because of its common occurrence iu other respirator)' diseases. As in pneumonia it is conceivable that various organisms might give rise to more or less definite symptoms of influenza; the Pfeiffer-like bacilli, moreover, are not more widely distributed in healthy individuals than is the pneuniococcus. Some consider that B. influenza; is purely a secondary invader in a variety of diseases initiated by other agents; when the bacillus is found in pure culture in lesions of the lungs, the natural explanation of a primary etiologic action is set aside and a hypothetical virus is postulated. However, there is good reason to believe that serious symptoms may result when an infection with the Pfeiller bacillus has become established ; its acceptance as a specific etiologic agent, however, seems to us to be contingent upon some division of these organisms such as the recognition of distinct species or of virulent and avirulent varieties.

StJMWARY 1. The examination of a group of measles cases occurring a few weeks after an epidemic of influenza showed tlie presence of an organism indistinguishable from the Pfeifl"cr bacillus in 2.5 of 31 cases.


• Neisser " reports that the PfeifTer bacillus can he cultivated Indefinitely on plain agar in " symbiosis " with ordinary micrococci.


2. This organism was obtained readily from the sputum and with little difficulty from the conjunctiva;. A highly parasitic, haunoglobin-requiring organism was obtained iu one of two cases from an excised inguinal gland. The Pfeiller organism was not obtained from the blood stream nor from the excised skin lesions.

3. With the subsidence of tlie active symptoms of measles these micro-organisms disappeared rather rapidly in about three-fourths of the cases.

4. Cultures of the Pfeiller organism from cases of measles failed to colonize when inoculated on the mucous membrane of four healthy volunteers; two of these individuals supposedly had not had either measles or influenza.

5. A comparison was made of the strains of the Pfeifler bacillus isolated from measles and from influenza. The results showed considerable variation iu the behavior of the individual strains. It is theoretically possible that the haemoglobin requiring bacilli represent a group of micro-organisms containing distinct species.

6. The occurrence of the Pfeifl'er bacillus both in measles and in influenza constitutes suggestive evidence against its etiologic relationship in either disease. This evidence would be materially strengthened provided the identity of the strains from these two sources were accurately established.

7. The evidence which is available at present is not sufliciently complete to exclude the specific etiologic role of the Pfeiller bacillus in some of the acute respiratory diseases.

LITERATURE

1. Paltauf, R.: Wien. klin. Wchnschr., 1899, XII, 576.

2. Giarre, C, and Picchi, L.: Clin, mod., 1900, VI, 178. Sperimentale. Arch, di biolog., 1903, LVII, 475.

3. Albrecht, H., and Ghon, A.: Ztschr. f. Heillc, Abt. f. palholog. Anat, 1901, XXII, 29.

4. Jehle, L.: Ztschr. f. Heilk., Abt. f. Int. Med., 1901, XXII, 190. . 5. Susswein, J.: Wien. klin Wchnschr., 1901, XIV, 1149.

6. Liebscher, C: Prag. med. Wchnschr., 1903, XXVIII, 85.

7. Klicnberger, C. : Deutsche med. Wchnschr., 1905, XXXI, 575.

8. Davis, D. J.: Jour. Infect. Dis., 1906, III, 1.

9. Paccbioni, D., and Franchioni, C: Jahrb. f. Kinderh. u. physische Erzieh., 1908, LXVIII, 39.

10. Reiss, E., and Gins, H. A.: .Miinch. med. Wchnschr., 1911, LVIII,' 2211.

11. Woolley, P. G.: Jour. Labty. and Clin. Med., 1919, IV, 330.

12. Wollstein, M.: Jour. Exper. Med., 1905, VII, 335.

13. Neiaser, M.: Deuteche med. Wchnschr., 1903, XXIX.462.


JOHNS HOrKINS HOSPITAL BULLETIN.


The Hospital Bulletin contains details of hospital and dispensary practice, abstracts of papers read and other proceedings of the llcdical Society of the Hospital, reports of lectures, and other matters of general interest in connection with the work of the Hospital. It is issued monthly. Volume XXX is in progre.«s. The subscription price is $3.00 per year.

(Foreign postage, 50 cents.) Price of cloth-bound volumes, $3.50 each.

A complete index to Vols. I-XVI of the Bulletin has been issued. Price 50 cents, bound in cloth.


338


[No. 345


THE REACTION OF THE LEUCOCYTES IN EPIDEMIC INFLUENZA

By Beverly Douglas


Duriug the epidemic of influenza occurring in the fall of 1918, the presence of a leucopenia in praeticall}' all the cases was commented on by numerous observers. An opportunity was afforded during the course of the epidemic in The Johns Hopkins Hospital to make rather extensive and careful studies of the blood, which it seems worth while to put on record. The data can best be presented in the form of tables, with notes appended thereto. .

1. General Course of the Leucocyte Curve in Uncomplicated Epidemic Influenza. — It seemed that information of most value about the general course of the leucocyte curve could be obtained by compiling the averages of counts made in a number of cases on various days. The results of such compilations are recorded in Table I and graphically represented in Chart 1. The following points may be commented on :

f T.. /


SffiHaiftffia


l-jJMiMM


Leucopenia is present, even on the day of onset of symptoms, the count falling somewhat on the following day and then gradually rising. One might almost imagine that there is some initial shock which depresses the leucocytes and from which they gradually escape during the subsequent days of the disease. It is also noteworthy that the return to normal count comes gradually, the average count still being subnormal on the twenty-first day.

Table I also shows the reaction of the leucocytes in the cases of influenza complicated by bronchopneumonia. These


counts bear out the impression obtained at the time of the epidemic that a complicating bronchopneumonia, as a rule, does not lead to leucocytosis. An attempt was made to see if

TABLE I.— AVERAGE LEUCOCYTE COUNTS COMPILED

FROM HISTORIES OF 250 EPIDEMIC INFLUENZA

AND SUSPECTED INFLUENZA PATIENTS

Epidemic of Oct.-Nov., 1918. J. H. H.


3 or more days before onset.

2 days before on set.

Day before onset.

Day of onset

2d

3d

4th

5tli

6th

7th

Sth

9th

10th

llth

12th

13th

14th

15th

16th

17th

ISth

19th

20th

21st

22 days or more. . Grand average . . .


25 »

6833

48

5323

41

5644

33

5838

18

5681

31

5412

13

6036

28

6203

14

6985

21

7050

17

7100

25

7340

25

7790

25

8350

23

7900

12

7560

15

8850

7

8370

2

5600

6

9030

5

8752

2

5230

436

6673


u.


4

13120

7

8130

5

7054


1

8800

1

8000

1

4850

7

8450



3



3127



1



2625



2



4705


1


6 =


5800


4250


°


4



5440


2


4


6700


6260


1


2


5760


3280


>


3



8550


i



5200



1



9450



3



6910




25



5040


7

3430

5

4580

5

4010

16^

4204

15

5408

15

5564

10

5850

11

8644


126 6745


1 Index number = miniber of counts averaged for that day.

- Onset of pneumonia.

» All except uncomplicated flu.


4

3656

4

4818

3

3880

10 =

4175

11

5396

11

5305

8

6492

8

8677

7

7530

4

8860

4

13960

5

9740

5

8432

4

7810

4

10860

2

9340

1

9800

4

7630

1

8120


174' 7066


the severity of the case from the clinical standpoint could be correlated with the extent of the leucopenia. For this purpose the cases were divided into mild, moderate and severe.


XOTEIIBER, 1919]


339


Counts made on or before the fourth day after onset showed in the mild cases an average of 5500, in the moderate, an average of 5800, and in the severe, an average of 5400. The lowest single count observed — one of 1900 cells, was in an extremely mild case. It seems, therefore, that in a general way, the extent of the leucopenia does not vary with the scveritj- of the disease.

TABLE II.— SUPPLEMENTARY TABLE SHOWING HIGHEST AND LOWEST COUNTS ON EACH DAY. (See No. 1)

I.NFLl'ENZA EPIOE.MIC OCT.-NOV., 1918. J. H. H.


3 or more days before

onset

2 days before onset. .

Day before onset ....

Day of onset

2d

3d

4th

5th

6th

7th

8th

9th

10th

11th

12th

13th

14th

loth

16th

17th

18th

19th

20th

21st

22d


10700

3440 10440

2500 11720

2640 12000

2240 12500

2520 10600

3000 10300

2400 10100

2120 11500

3260 12000

2640 12640

4720 14600

3100 10600

5200 16000

2500 13440

4000 10600

3320 30800

44S0 14600

6250

7000

4040 14600

6080 12500

7100


22480 6000 9200 7000

10000 4800


8800 8800 8000 8000 4850 4850 11980 5440


Kluc

broiicho pneuin.

fatal


Too Few.


4960 2000 2625 2625 4760 4650 6400 3400

10200 2460

14600 2600 3320 3240

18200 2200


noii-futal


4960 2640 6000 3800 5050 3140 6400 2675

13000 2440

13100 2075

18400 2320

31360 2360

11900 4650

14480 5760

24720 8160

11920 6120

10200 6300 9800 3640

13120 8640

10280 8400 9800 9800 8750 5080 8120 8120


2. In Table II, which should be studied in connection with Table T, are presented the highest and lowest individual counts encountered in the various cases on each day of the disease. From this table, it is apparent that despite the general tendency to a leucopenia, there may in some cases be a mndrrjii.' Icucocvtosis.


TABLE III.— AVERAGES OF PER CENT PMN. AND TOTAL

LEUCOCYTE COUNTS CO.MPILED FROM 250

INFLUENZA HISTORIES IN J. H. H.

Epidemic of Oct.-Nov., 1918


Day of iliscas


Av. WUC


PMN- l)...vo(.lis<.,.se


Av. WUC


Av. PMS


Onset

2(1

3d

4th

5th

Gth


4'

5220

13

5575

6

7900

9

5675

2

7350

1

6600

3

6330

5

6456

4

9950


72% 66% 59% 53% 61%

62% 607o 56% 66%


11th

12th

13th

14th

15th

16th

17th

18th

19th

20th


3

6387

6

7843

3

8870

6

7930

11

7450

3

6560

4

8330

1

7400

11

8080

2

9870


45% 60% 57% 61% 62% 69% 62% 79% 73% 47%


7th

8th

9th

10th


' Small index number = number of counts averaged.


TABLE IV.— INFLUENZA. VARIATION OF PERCENTAGE OF

PMN. CELLS C. W. B. COUNTS (COUNTS AND

DIFFERENTIALS ON SAME DAYS)

Epidemic op Oct.-Nov., 1918. J. H. H.


WBC %PMX


WBC %P.MN 4000-4500


WBC %PMN


WBC %PMN


WBC %PMN


300O-S500


5000-6500


8000-8500


7000-7600


8000 40


4300 64


6040 «8


6080 65


7000 75


8100 51


4410 75


5120 6',l


6US0 66


7310 78


8160 S7


45110 78


6200 71)


6100 67


7400 78


8140 47


—


5440 A3


etoo isr


7400 79



Av. 4413 6B


6410 67


6100 80



Av. 8175 48.8



6480 61


6350 65


At. 7285 76



4600-5000


—


6320 81



SSOO-4000 SSOO 8< 3«I0 GU


4520 40 4620 60 4700 66


Av. 6296 63 6500-6000


6440 62 6480 68 6500 67


7500-8000 708U 66 7800 62


Av. 3600 51


6000 53


5760 75 6800 63


Av. 6283 84.7


7840 64 7910 k7t



Av. 46S6 40.5


68.<!0 66

SS80 icr


6500-7000


7l>60 62




6'.i00 63


6000 63


Av. 7810 56





6800 47 f





Av. 6844 64.6


eiOa 68 61>.'0 64

Av. 67S0 00.6



8000.4000


4000-6000


6000-6000


6000-7000


7000-8000


°v'." !*"• *'••


At. 4750 67.8


At. 6546 <8.7


At. 6404 61


AT. 75'.'4 06


8000-BSOO



0000-9500



10000 and above


SOnO SB



OlIOO 69



10000 88


80110 «l



0040 67



10500 71


MHO n



MOO 67



10600 67


8080 78



U200 68



10620 60


81«n 60



0480 70



10S80 60


8810 «8





ir5no 60


MOO 76



Av. 0184 68



11080 50


8440 66






^-^



060O-I0O00



At. 10970 62.8


At. 6180 M.t



None.







No dilTercntfala


8500-9000





on WBC above


8«tn 66





thia iwlnt.


8«sn 57






8090 «3






At. 8740 68.8






SOOODOOO



Booo-ionon



10OOO-I2O0O


0'*° [8882 84.6



•184 88.2



10096 82


340


[No. 345


3. Table III attempts to correlate the polymorphonuclear leucocytes with the total count. In this relatively small number of eases, no significant relationship is made out.

4. Table IV shows the relationship of the polj-morphonuclears to the total count from another point of view — namely, the total count rather than the day of the disease.

Condusions. — From these tabulations, the following general conclusions may be drawn :

Leucopenia is the rule in epidemic influenza, although a few eases may show normal counts or a slight leucocytosis.

The leucopenia frequently is present on the first day of the disease, after which it may become more marked for a few days, with a subsequent gradual tendency to rise imtil the


normal mark is reached. In some cases the normal mark is overshot during convalescence, and leucocytosis may be present.

There is no constant relation between the leucocyte count and the severity of the disease.

The persistence of the leucopenia is the rule, even where bronchopneumonia, fatal or non-fatal, supervenes.

Difl'erential counts show an absolute relative decrease in polymorphonuclear cells, as well as during the stage of leucopenia, varying to some extent with the total count.

Acute non-influenzal respiratory infections, as a rule, are accompanied by a leucocytosis.

A leucopenia is. therefore, a reliable diagnostic sign in epidemic influenza.


BOOKS RECEIVED


American Pediatric Society. Transactions of the American Pediatric Society. Thirtieth Session. Held at the Curtis Hotel, Lenox, Mass., May 27, 28, and 29, 1918. Edited by Oscar M. Schloss, M. D. 1918. 8°. 331 pages.

The Control of Hookworm Disease iy the Intensive Method. By H. H. Howard, M. D. Publication No. 8. 1919. 8°. 189 pages. The Rockefeller Foundation International Health Board, New York City.

Manual of yeiiro-Surgeiy. Authorized by the Secretary of War under Supervision of the Surgeon-General. Prepared under the direction of the Neuro-Surgical Section of the Division of Surgery, in collaboration with the Sections of Head Surgery, General Surgery, Orthopedic Surgery, and Neuro-Psychiatry, the Army Neuro-Surgical Laboratories, and the Instruction Laboratory of the Army Medical Museum. 1919. 8°. 492 pages. Government Printing Office, Washington.

A Te.Tt-Book of Urology i7i Me7i. Women and Children. Including Urinary and Sexual Infections. Urethroscopy and Cystoscopy. By Victor Cox Pedersen, A. M., M. D., F. A. C. S. Illustrated with 362 engravings, of which 152 are original, and 13 colored plates. 1919. 8°. 991 pages. Lea & Feblger, Philadelphia and New York.


Pulmonary Tuberculosis. By Maurice Fishberg, M. D. Second edition, revised and enlarged. Illustrated with 100 engravings and 25 plates. 1919. 8°. 744 pages. Lea & Febiger, Philadelphia and New York.

Roentgen Interpretation. A Manual for Students and Practitioners. By George W. Holmes. M. D., and Howard E. Ruggles, M. D. Illustrated with 181 engravings. 1919. S°. 211 pages. Lea & Febiger, Philadelphia and New York.

The Principles of Nursing. By Charlotte A. Brown, R. N. Illus- j trated. 1919. 12°. 262 pages. Lea & Febiger, Philadelphia and New York.

Pneumotorair Artificial, y Otras Intervenciones en la Tuberculosis Pulmonar. Estudlo Critico y Cllnico. Por el Doctor Juan B. Morelli. 2 volumes. 1918-1919. 8°. 1246 pages. Imprenta Nacional, Montevideo.

iledical Report of the Durand Hospital of the John McCormick Institute for Infectious Diseases. For the First Five Years, March 12, 1913 to March 12, 1918. George H. Weaver, M. D., Physiciau-in-Charge. 1919. 4°. 32 pages. Chicago.


The following eight monographs :


PUBLICATIOx\S

The Origin and Development of the LvTiiphatic S3'stem. By


Free Thrombi and Ball-Thrombi in the Heart. By J. H. Hewitt, M. D. 82 pages. Price, $1.00.

Benzol as a Leucotoxin. By Laurence Sellixg, M. D. 60 pages. Price, $1.00.

Primary Carcinoma of the Liver. By JI. C. Wixteexitz, M. D. 42 pages. Price 15 cents.

The Statistical Experience Data of The Johns Hopkins Hospital, Baltimore, Md., 1892-1911. By Frederick L. Hoffman, LL.D., F.S.S. 161 pages. Price, $2.00.


Florence E. Sabin. 94 pages. Price, $3.00. Venous Thrombosis During Myocardial Insufficiency.


Bv


Fr-ank J. Sladen, M. D., and Milton C. Winternitz.

M. D. Price, 75 cents.

Leukaemia of the Fowl: Spontaneous and Experimental. By Harry C. ScmiEissER, M. D. Price. $2.00.

The Structure of the Normal Fibers of Purkinje in the Adult Human Heart and Their Pathological Alteration in Syphilitic Myocarditis. By 0. Van Der STRicm aud T. Wingate Todd. Price, $2.00.



BALTIMORE, DECEMBER, 1919


Contents

Kenry Mills Hurd. The First Superintendent of The Jolins Hopkins Hospital. (Illustrated.)

«y Thomas S. Cillen 341

Bibliography of Henry Mills Hurd, M. 1)., 1.1.. D.

Prepared by Mix.me Wbioht Blogg, Librarian, The Jolins Hopkins Hospital 370

Index to Volume XXX of The Johns Hopkins Hospital Bulletin 373


HENRY MILLS HURD

THE FIRST SUPERINTENDENT OF THE JOHNS HOPKINS HOSPITAL

lU- Tho-m.vs S. Cullkn *


The sultjcft of this sketch, probablj' the best kiinwii hospital superintendent in the United States, an expert on li()si)iUil orfranization and management, professor of psyeliiatry, author and editor, was a product of Michigan, a state that has furni.shed many well-known figures in American medicine.

Sliortly after Dr. Hurd came to Baltimore a charming sketch of his early life and of his manifold activities in Kalamazoo and Pontiac appeareil from the ])en of Dr. C. B. Burr, his successor at the Eastern Michigan A.sylum at Pontiac. This tribute appeared in the American .Jounwl of InxanUy,


• I have written this article at the request of Judge Henry D. Harlan, president of the Roard of Trustees of the hospital, and of Mr. George K. McGaw, one of the trustees of the hospital — one of Dr. Hurd's warmest friends and the donor of a large sum of money towards the erection of the Henry M. Hurd Library Building which Is to be on the hospital grounds.

It was my good fortune to come to the hospital in 1891, just two years after It opened. In my early years I viewed Dr. Hurd's work from the immature standpoint of the junior intern, later as a senior house offlcer, and for at least 15 years Dr. Hurd has been one of my very best friends.

It has been a delight to browse through his early writings, to digest the chief events of the hospital a« they were sketched by him in the yearly reports, and to epitomize the results of his labors since he retired from the active management of the hospital In 1911. I had always looked upon Dr. Hurd as an Indefatigable worker, but until now I have never had the slightest conception of the tremendous amount he has accomplished and of how largely he has been responsible for the phenomenal success of The Johns Hopkins Hospital.


1809, Vol. 46, p. 303. As it cMiiiiof he impnixi'd u|h,ii I sli:i!I give it in detail:

Henry M. Hurd, A. M., M. D., the recently appointed director of The Johns Hopkins Hospital, Baltimore, and the subject of our photogravure, was born May 3, 1843, at Union City, Branch Co., Michigan. His parents, Theodore C. and Ellen E. (Hammond) Hurd, were of New England (Connecticut) stock. His father, a pioneer physician, eamo to Micliigan in 1834; and. worn out by laborious practice amid the hardships and privations of pioneer life In a malarious country, died at the early age of 39, leaving a wife and three little boys.

His mother remarried In 1848, and in 1854 the family removed to Galesburg. 111. In 1858 he entered Knox College, where he spent two years. Subsequently he devoted a year to teaching and general study, and in 1861 entered the junior class of the T?nlversity of Michigan. He graduated from the university in 1863. and In the same year began the study of medicine with his stepfather, who was also a physician. He attended lectures at the Rush Medical College. Chicago, and at the Cnlverslty of Michigan, and graduated from the department of medicine and surgery of the university in 1866. The year following graduation he spent in New York In study and hospital work. Subse(|uently he removed to Chicago, where he engaged In dispensary and general practice for two years. It was during the time of his residence In Chicago, In 1870. that ho received the appointment of assistant physician to the Michigan Asylum for the Insane at Kalamazoo, and entered that field of medical practice In which he has achieved so much distinction. He served the asylum in the capacity of assistant physician for eight years, at the end of which time he became assistant superintendent. On the opening of the Eastern Michigan Asylum at Pontiac In the fall of the same year he was appointed Ita first superintendent, and occupied this position continuously for 11 years. Possessing rare skill as an organizer, broad culture, literary attainments of a high order, a thorough medical


343


[No. 346


training and a long asylum and hospital experience, he brought to the work of organizing the Eastern Michigan Asylum those qualities which enabled him to place it at once among the progressive asylums of the country. He early identified himself with the Association of Medical Superintendents, and was an earnest, faithful and zealous member of this body.

During the period of his administration of affairs of the Eastern Michigan Asylum he has seen the treatment of the insane revolutionized. For the abolition of restraint, the employment of the insane, the extension of the system of night-nursing, the development of the " cottage plan," and the introduction of home comforts into the dull, unattractive institutional life of previous years, he has been an ardent and enthusiastic advocate. To him, perhaps, as much as to any other man among the present generation of alienists in this country Is due the rapid growth of progressive methods in the care of the insane, and the advanced position which American psycliiatry is taking. His mental culture, which enabled him to grasp intricate problems in all their details, his philanthropic instincts, his ready sympathies and his keen insight into the needs of the insane, conjoined with the quick perception of the skilled physician, made him an ideal asylum superintendent. His personal presence was inspiring; he infused his own spirit of tireless energy among his subordinates, he unified his staff and his corps of employes, and could always rely upon their thorough cooperation. In 1S81 he visited Europe for travel and investigation in the special lines of work in which he was engaged. The results of this trip were the subject of a special communication to the joint Boards of Trustees of the Michigan asylums, and were published in connection with the biennial report of the Eastern Michigan Asylum for 1882. His writings upon the subject of mental medicine have been voluminous and of a high order. Aside from the numerous papers published in the American Journal of Insanity, as reference to its files for the past 11 years will show, many of great merit have appeared elsewhere.

Among his recent and most scholarly productions is his presidential address in 1889 before the alumni association of the medical department of the University of Michigan, on " The Mental Hygiene of Physicians." His reports of the Eastern Michigan Asylum are written in a masterly and finished style, and have been warmly received and favorably noticed by the profession of this and foreign countries. He was a vice-president of the Ninth International Medical Congress, Is a member of the Michigan State Medical Society and of the Detroit Academy of Medicine, and is corresponding member of the Detroit Medical and Library Association.

In June of the present year there came to him, without previous intimation, the tender of the position of director of The Johns Hopkins Hospital. The offer came as a gratifying surprise, but he hesitated to accept it. He was reluctant to relinquish the work to which he had devoted his best years, to separate himself from his. patients — may of whom had long been objects of his care and solicitude — and from friends endeared to him by the strongest ties. He hesitated to abandon the work in which he had been so long and successfully engaged, and in which the prospects for future usefulness opened wide and ever wider before him; but considerations, paramount among which were the increased opportunities for the education of his children, constrained him to accept the position.

By mental endowments and education he is peculiarly well fitted for the responsible and delicate duties of a hospital director. He is thoroughly deserving of his recent very great honor, and will adorn the position to which he has been called; but as we write these lines, the feeling returns with ever-increasing force, that in the gain of The Johns Hopkins Hospital, the profession of


psychiatry sustains an irreparable loss, and the asylum system ot Michigan is deprived of its most illustrious exponent.

When Dr. Hiird came to Baltimore to see Tlie Johns Hopkins Hospital and to meet the trustees of the hospital one of the trustees from the Eastern Michigan Asylum at Pontiac came with him with the intention of urging his superintendent to decline the call. After he had met the trustees and had visited the hospital he turned to Dr. Hurd and said : " My object in coming with you was to see that you returned to Slichigan, but I have changed my mind. If they offer you this jiosition and j'ou do not accept it, you will make the mistake of your life."

PAPERS ON PSYCHIATRY PUBLISHED BY

DR. HURD PRIOR TO HIS COMING

TO BALTIMORE

Amid his many a.sylum duties Dr. Hurd found time to do much writing and, as intimated by Dr. Burr, contributed a great deal to our knowledge of insanity. In 1880 he published a paper on " Recent Judicial Decisions in Michigan Relative to Insanity." This was followed in 1881 by " A Plea for Systematic Therapeutical, Clinical and Statistical Study." In this paper Dr. Hurd carefully analyzed the methods employed in the various asylums and clearly pointed out where improvements might with much profit be inaugurated. On page 11 he says :

Mucli of the present statistical information contained in the published reports of the institutions for the insane is unsatisfactory. There are tables enough, but they lack uniformity, precision in statement and practical utility.

Their lack of uniformity is well illustrated by the varying number of tables given in different reports, taken at random from a package before me.

In concluding this article Dr. Hurd says:

In this earnest plea for more systematic therapeutical, clinical and statistical inquiries. I would not be understood as criticizing the thorough work now done in connection with asylums. I have merely attempted to point out the necessity for further progress, and have suggested methods which would tend to increase the efficiency ot asylum work.

In 1883 Dr. Hurd published papers on " Practical Suggestions Relative to the Treatment of Insanity " and " The Treatment of Periodic Insanity."

At a sanitary convention held in Pontiac in January, 1883, Dr. Hurd gave a most interesting address on " The Hereditary Influence of Alcoholic Indulgence Upon the Production of Insanity." His views as expressed 36 years ago t«lly so well with our present conception of this most important subject that I quote his conclusions :

In the foregoing paper I have endeavored to show that inebriety in parents is a frequent cause of insanity in their children, because drunkenness produces a transient Insanity, even in a healthy brain; chronic drunkenness produces organic brain diseases, bringing in their train impairment of the memory, inactivity of the reason, a weakening of the will, and a loss of the natural affections; also moral perversions and vicious propensities, and finally, unmistakable diseases of the mind and nervous system — all of which are capable of transmission to children.


THE JOHNS HOPKINS HOSPITAL BULLETIN. DECEMBER. 1919


PLATE XLI



Tli.-uil..r.-. iiKfil a

Charles. " 4

Henry. " 6

(Jalesliurs. 111.



10


1 ...,,a..ir Henry. Charles. " 8 Taken about 1853. Galesburg. 111.


Il>iir> .\L 1 1 11 III in lSti;i. agi'il 20. .\nn Arbor. Mirli.



Henry M. Hurt!

in 1868. aged 2o.

Galesburg, III.



i'lrd. t an : • \) Hurd

iiK'jil .7. .\prll. 1870. UaleHburg, 111.



Hcnrv .M. Ihinl.

ag'-tl .n, in 1S74.

Chicago. 111.


THK KVOMTIO.N OF HEN'KY M. Ill KU. These pictures were carefully treasured by Ur. Hurds mother. They were obtained surreptitiously and no one will be more

surprised to see them here than Ur. Hurd himself.


Decembeh, 1919]


JOHXS HOPKINS HOSPITAL BULLETIN


343


That the children of inebriate parents inherit diseases, such as epilepsy, liysteria, chorea and idiocy, or if not actual diseases, nervous systems which are abnormally responsive to every form of disturbing influence and are easily disordered.

That between the ages of 20 and 45 insanity is liable to be developed in the children of inebriates, and that insanity of this type is recovered from imperfect^' or not at all.

And finally, that however much people may differ as to the expediency of " prohibition," so-called, in the present state of public sentiment, there should be no difference of opinion among thinking men as to the right and duty of the state to take strenuous measures to prevent the transmission of an inebriate heredity to children.

During 1S83 Dr. Hurd also puljli^ihoil a paper entitled " Future Provisions for the Insane in Michi<ran." In this article he sketched in a most interesting way tlie hai)hazard manner in whic-ii insane patients were looked after in Michigan until the opening of the asylum for the insane at Kalamazoo. He spoke in no imcertain terras of tiie duty of the state to care for the insane within her borders. The concluding paragraph in this article reveals very clearly the wise statesmanship of Dr. Hurd :

I would reiterate the conviction that it is the duty of the state to continue to care for her insane in the state asylums: that no consideration of false economy should prevent her from doing everything which can be done for the comfort and restoration of every insane person. If he requires the restraint and seclusion of an asylum for the dangerous insane, he should have it. If he requires curative treatment in a hospital, or suffers from a form of disease which calls for constant nursing, he should have that. If his welfare will be promoted by giving him labor, the liberty of home, and a manner of life nearly resembling that of a private family, he should receive them. No money should be wasted upon buildings, surroundings, or care. Sufficient, however, should be expended to render each unfortunate as comfortable as his condition will permit. Anything less than this is unworthy a great state like Michigan.

Dr. Hurd in 1883 also published " The ilinor Treatment of Insane Patients." In 1886 he published an interesting article on " Paranoia." During the year 1886 we find two articles from his pen " The Relation of General Paresis and Syphilitic Insanity" and "The Data of Recovery from Insanity." In 1887 "Gastric, Secretory and Other Crises in General Paresis " and " The Colony System of Michigan " appeared. In 1888 Dr. Hurd published an important article on " The Religious Delusions of the Insane," also an article on " Imbecility with Insanity." In 1880 he aUo contributed a paper entitled " A Case of Inebriety with Insanity ; with Remarks."

DR. HURD, thp: FIR.ST SUPERIXTKXDHXT of THK JOHNS HOPKIXS HOSPITAL Dr. Hurd vras appointed superintendent of The Johns Hopkins Hospital in June, 1889, and assumed the duties of the position on .\ugust 1, at which time President Oilman, who had acted as director of the hospital since the preceding February, and Dr. John S. Billings, who had been medical advisor to the Board of Trustees for 12 years, terminated their connection with the hospital. Dr. Hurd, as has already been mentioned, was the first superintendent of the P^istern Michi


gan Asylum at Pontiac. Here he had taken charge of a brand new institution, had worked out the details of its management and had piloted its destiny most successfully for 11 years. Here at tlie Hopkins he had a similar opportunity, differing only in that the patient.s were suffering from bodily instead of mentiil ills. In this institution he was destined to establish later the most harmonious relationship between the hospital and The Johns Hopkins Medical School which opened its doors in 1893. His wise council, liis broad vista and his tact have in large measure been responsible for the continuous cordial and intimate relations that have always existed between the medical school and the hospital.

Dr. Burr in his tribute to Dr. Hurd said, " His reports of the Eastern Michigan Asylum are written in a masterly and finished style, and have been warmly received and favorably noticed by the profession of tliis and foreign countries." The same standard of excellence shown in the Michigan reports has been maintained in the annual reports of The Johns Hopkins Hospital. In fact, when the history of this institution is written it will only be necessary to amplify what has already been succinctly reported in the yearly record of the hospital.

The annual report has given the list of the trustees together with their various committees, the consulting physicians, the medical hoard, the house staff and the names of the physicians connected with the out-patient department. Dr. Hurd then briefly chronicled the important events occurring during the year, referred in detail to the changes in the personnel of the staff and pointed out where certain departments needed to expand or where new departments should be created. It is interesting to watch how a suggestion of his would bring forth fruit. In one report he would advise the innovation, in the next it would be briefly stated that tentative plans were under way. The next report would probably say that the building was under construction, and in the report of the following year would be a detailed description of the building together with splendid illustrations, and in addition there would be a succinct rejrort of the addres.ses given at the dedication of the building. A more detailed report of the proceedings would usually be contained in the hospital Bulletin or form the theme for an address.

The report of the Training School for Xurses has always been given a prominent part in the superintendent's report and since 1895 there has been a very full report of the colored orphan a.sylum. Dr. Hurd has always made it a rule to make acknowledgment of gifts tx) the hospital no matter how small they have been, and since tlie ijcginning he has never failed each year to thank the clergy who have held services in the hospital on the Sabbath. The statistical tables relating to the patients treated in the hospital and in the dispensary have been most exact and very full.

The annual reports of The Johns Hopkins Hospital from 1889 to 1911 breathe the very atmosphere of Henry M. Hurd and in no other way can the reader gain a better insight into his make-up and into the tremendous amount of work this splendid medical stati'sman has accomplished than by reading these records.


344


[N"o. 346


A Synopsis of The Johns Hopkins Hospital Reports From 1889 to 1911

No description of Dr. Hurd's work woiild be complete without a reference to that splendid Board of Trustees and that rare medical staff with whom he was associated in the early days of the hospital. I have accordingly had the first and second pages of the first report reproduced. All who were fortunate enough to have been connected with the hospital in the early days will never forget that splendid, candid, wholesouled face of Miss Isabel Hampton. One never thought of Mr. Emory without instantly associating him with Mr. Joseph Hopkins, and everybody in the hospital, both young and old, looked upon Miss Rachel Bonner as an elder sister.

For convenience I have divided the reports into the regular calendar year, although, as a matter of fact, the hospital year began February 1 and ended January 31.

1889 (May, 1889— January 31, 1890)

Dr. Hurd's first report begins as follows : To the Trustees of The Johns Hopkins Hospital:

Gentlemen. — I present herewith a summary of the operations of the hospital during the past seven and one-half months, or since its opening in May last. It has seemed best, all things considered, to make this first report for the fractional year, so that in future the hospital year may correspond with the fiscal year, which runs from February 1 to January 31.

ORGANIZATION

The organization of The Johns Hopkins Hospital differs in some essential features from that of other general hospitals in the United States. The service is divided into three distinct departments — medical, surgical and gynecological each under a responsible chief with continuous service. The heads of these departments are non-resident, but arrangements are made for them to give as much time to the work of the hospital as the necessities of patients demand.

Each department has a responsible resident physician who has had a long and varied experience in a general hospital, and is abundantly able to fill the place of the chief of the department whenever he is absent from the hospital. Each resident physician has a staff of assistants who give aid in case-taking, surgical operations, clinical notes, examinations of urine, sputum, blood, etc. — also in dispensary work generally. The resident and assistant resident physicians, surgeons and gynecologists, are resident in the hospital.

The dispensary has a chief who directs and arranges the work of the different departments, and each department in turn is under the special direction and control of a responsible head, who takes care of the work and has a continuous service. Each head of a dispensary department has as many assistants as the proper work of his department requires, whose medical work he directs and controls.

The nursing work of the hospital is under the charge of the superintendent of nurses, who also acts as the principal of the training school. She has the responsibility of the management of the nurses' home and the instruction of nurses. She selects and accepts probationers, prescribes courses of study and arranges duties. She supervises all nursing-work.

The purchase and delivery of provisions and the cooking, distribution and serving of food, are placed in the hands of a purveyor, who is made responsible for this branch of hospital work.


The care of rooms and buildings and the oversight of the work of the laundry come upon the matron, who is charged with the duty of purchasing bedding, dry goods, clothing, household and laundry supplies. In addition to these offices there is a comptroller of accounts, who supervises the receipt of money and the payment of bills; an apothecary, who purchases medicines and prepares and delivers prescriptions; a supervisor of grounds, who looks after all outside labor; and an engineer, who has the care and oversight of the engines, boilers, filters, pumping apparatus, machinery, warming and ventilating apparatus, water-tanks, sewers, water-closets, lavatories, steam-cooking apparatus, water, gas, electrical and steam distribution.

HISTORICAL

Upon the opening of the hospital in May, 1889, Dr. W. H. Welch had been appointed pathologist. Dr. William Osier, physician-inchief, and Dr. William S. Halsted, acting surgeon and chief of the dispensary; Dr. Henry A. Lafleur, resident physician, and Dr. F. J. Brockway, resident surgeon; with Dr. H. A. Toulmin, assistant physician, and Dr. George E. Clarke, assistant surgeon.

Subsequently in June Dr. Howard A. Kelly was appointed gynecologist and obstetrician, and Dr. Hunter Robb, resident gynecologist. The value of the services of Dr. Billings in planning and building the hospital cannot be too highly estimated. His foresight as to the future of the hospital, his high ideals of hospital requirements, his familiarity with hospital work and his versatility in adapting means to ends, have done much to bring The Johns Hopkins Hospital to its present state qf excellence.

President Gilman's services as an organizer were of great value. By an unusual occurrence of events it was possible for him to bring the university idea into hospital management, and to give to the inauguration of the hospital enterprise a breadth and liberality which it might have lacked had it been exclusively organized by a purely hospital officer.

COURSES OF MEDICAL INSTRUCTION

Beginning with January 6 of the present year [1890] courses of postgraduate instruction in medicine, surgery and gynecology have been inaugurated at the hospital. Daily lectures have been given in the clinical amphitheatre, and clinics in medicine, surgery and gynecology have been given three times a week, at which time the wealth of clinical cases afforded by the hospital and dispensary have been utilized. Rare opportunities to study diseases have been afforded in the dispensary and the hospital wards; and to witness surgical operations in the private operating rooms.

LABOR.i.TORIES

The work of the pathological laboratory, formerly carried on by the university, was assumed by the hospital September 1, 1889. No change, however, has been made in any of its arrangements or courses of study, and the work of instruction and original research has gone on as in former years. The pathological material afforded by the hospital has proven unusually rich. It has been most carefully and thoroughly studied by Professor Welch and Drs. Councilman and Abbott.

The clinical laboratory has been in successful operation under the direction of Professor Osier. Analyses of the blood have been made carefully and systematically as a matter of routine, both to determine its constitution and to ascertain the presence of malarial or other organisms and parasites.

The hygienic laboratory has also been equipped and made ready for practical work under the direction of Dr. Billings and Dr. Abbott. Its work thus far has been confined to meteorological observations, the study of ventilation, the analysis of groundair, and the bacteriological examination of water.


December, 1919]


345


THE TRUSTEES AND MEDICAL STAFF OF THE JOHNS HOPKINS HOSPITAL IN 1889.

These are facsimile pages .from the first annual report of the Hospital giving the Trustees, Consulting Physicians, Medical Board and Hospital Staff at that time.


TRUSTEES.

1889-90.


President : FRANCIS T. KING. Tretuwer: JOSEPH MERKEFIELD. Secretary : LEWIS N. HOPKINS Member) oj Ihe Board : Geoboe William Urown, Charles J. M. Gwinjj,

James Carev, Lewis N. Hopkins,

George W. Corner, Francis T. Kino,

William T. Dixon, .\lan P. Smith, M. D.,

Geoboe W. Dobbin, C. Morton Stewart,

Joseph P. Elliott, Francis White.


COMMITTEES. Ezeculive CommiUee. Geoboe W. Corner, Francis T. Kiko, ex offao,

George W. Dobbin, Alan P. Smith,

Francis White.

Finance CommiUee: George W. Corker, Francis T. King, ez officio,

William T. Dixon, Francis White.

Building OommiUet: George W. Corner, Fba-scis T. Kino, ez officio,

Georme W. Dobbin, Alan P. Smith,

Francis White.


CONSULTING PHYSICIANS.

Alan P. Smith, M. D., representing Hospital Trustees, James Carey Thomas, M. D., reprenenlinj; Univereitj Trustees, I. E. .\TKiNfiON, -M. D., T. S. Latimer, M. D.,

8. C. Chew, .M. D., F. T. Miles, M. D.,

F. Donaldson, M. D., O. W. Miltenberoer, M. D.,

W. T. Howard, .\I. D., L. McLane Tiffany, M. D.,

C. Johnston, M. D., W. C. Van Bibber, M. D.,

H. p. C. Wilson, M. D.


MEDICAL BOARD.

Alan P. Smith, M. D., representini; Hospital Trnstees, James Carey Thomas, M. D., representing University Trustees, W. S. Hai-'»ted, M. D., Howard A. Kelly, M. D.,

Henrt M. Hubd, M. D., William Osler, M. D.,

WiLUAJi H. Weix;h, M. D.


HOSPITAL STAFF.

Superintendent : Henrt M. Hcrd, M. D. Phyticiart : Resident Physician :

William Osler, M. D. Henry A. Laflecr, M. D.

Attislanl Resident Physieianf: Harry Toulmin, M. D., D. Meredith Reese, M. D.

Surgeon: Resident Surgeon :

WiuJAM S. Halsted, M. D. F. J. Brockway, M. D.

Assistant Resident Surgeon : Georoe E. Clarke, M. D. Gynecologist and Obstetrician: Resident Oynecologisl :

Howard A. Kelly, M. D. Hunter Robb, M. D.

Assistant Resident Gynecologists: W. W. Farr, M. D. a. L. Ghriskey, M. D.


Pathologist : Associate in Pathology :

William H. Welch, M. D. W. T. Councilman, M. D.

Assistant in Bacteriology and Hygiene: Alexander C. Abbott, M. D.


OUT-PATIENT DEPARTMENT.

CAi>/ of the Dispensary : William S. Halsted, M. D. Department of General Medicine:

William Osler, M. D. Department of Diseases of Children :

William Osler, M. D., and W. D. Booker, M. D. Department of Nervous Diseases :

William Osler, M. D., and H. M. Thomas, M. D. Department of General Surgery:

W. S. Halsted, M. D., assisted bv J. M. T. Finney, M. D. Department of Genito- Urinary Diseases:

W. S. Halsted, M. D., and James Brown, M. D. Department of Gynecology:

H. a. Kelly, M. D., assisted by Hunter Robb, M. D. Department of Ophthalmology and Otology:

S. Theobald, M. D., and R. L. Randolph, M. D. Department of Ixiryngology :

John N. Mackenzie, M. D. Department of Dermatology:

R. B. MoRisoN, M. D.


Mibs Isabel A. Hampton, Superintendent of Nurses and Principal of the Training School.


L Winder Emory, Purveyor. Miss Rachel A. Bonner, Matron.


Stanley Hutchins, OcmplroUer of Accounts.


346


[No. 346


THE nurses' training SCHOOL

The Nurses' Training School was fonnally opened in October, 1889. A full report of this momentous occasion is given by Dr. Hurd in the first number of The Johns Hopkins Hospital Bulletin published on December 1 of that year. After a short address by the president of the Board of Trustees, Mr. Francis T. King, Miss Hampton spoke at length on " The Aims of The Johns Hopkins Hospital Training School for Nurses," and was followed by Dr. Hurd who took as his theme " The Eelation of the Training School for Nurses to The Johns Hopkins Hospital." I quote briefly from his address on that occasion :

The beneficent work of The Johns Hopkins Hospital antedates by many years its formal opening in May last. From its inception in the mind of its founder, and the subsequent elaboration of the idea by the trustees so wisely chosen by him — during the preparation of its plans and in the whole course of its erection — from the first foundation stone to the last tile upon the roof, it has constantly been fulfilling its mission. It has all along stimulated hospital construction to an unprecedented degree. From a personal knowledge of hospitals east and west, I do not hesitate to say that there is not a single hospital in this broad land which has not felt the influence of its construction, either directly or indirectly, or has not been energized by its example to make more perfect provision for the care and treatment of sick people. It has taught hospitals the practical application of the laws of hygiene to heating, ventilation, house drainage, sewerage and hospital construction in general. It has commanded attention to the importance of sunlight and air space, and to the absolute necessity of an abundant supply of pure air to each individual — a supply properly tempered to meet the varying conditions of summer heat and winter cold. The cardinal principle of the hospital has been to give the sick the most perfect hygienic surroundings attainable in a city. It has so prepared the way for better provision for the comfort of the sick, whether rich or poor, that the public now demand it. So great, in fact, has been the force of its example for good, I do not hesitate to say that had the hospital never received or treated a single patient, the work it has already accomplished in showing the way to better hospital construction would have fully justified the expenditure of every dollar it cost.

To-day we are assembled to witness the inauguration of one of the departments of this hospital which we hope will influence in a similar manner, even if not in an equal degree, training schools for nurses throughout the country. Tliis school has been established in compliance with the instructions of the founder of the hospital, in tlie following language: " I desire you to establish in connection with the hospital a training school for female nurses. This provision will secure the services of women competent to care for the sick in the hospital wards, and will enable you to benefit the whole community by supplying it with a class of trained and experienced nurses." The Board of Trustees has carried into effect this injunction in no grudging manner. No school in this country has been more worthily housed or more fully equipped for class-room and practical work and none has ever started out with broader views or more comprehensive plans for the proper training of nurses.

"What has the hospital a right to expect from the pupils of this school?

1. They should have an adequate conception of the responsibilities assumed by the nurse when she enters the school. The hands of a nurse are a physician's hands lengthened out to minister to the sick. Her presence at the bedside is a trained vigilance supplementing and perfecting his watchful care; her knowledge of the patient's condition an essential element in the


diagnosis of disease; her management of the patient, the practical side of medical science. If she fails to appreciate her duties the physician fails in the same degree to bring aid to his patient.

2. The nurse should have an enthusiasm in the work of nursing. No one should assume the work without feeling it to be of all occupations the one best suited to the tastes and capacity of the individual. Nursing to be well done should be entered upon with an " enthusiasm of humanity " which will lighten every hardship, and render the nurse happy and +++++ CONTENTSed in her chosen calling.

3. She should consider nursing a profession and view it as a life work. It is not a trade, nor an occupation solely, nor a means of support simply, but a vocation which brings into activity the best sentiments of the human heart and enlists the finer sympathies of our better natures.

4. She should seek to fit herself to be a teacher of others. It should be her ambition to learn the duties of her calling that she may become competent to impart instruction. From this school as from a center of knowledge should go forth graduates to found similar schools throughout the land.

5. For her highest usefulness a nurse should have a capacity for sustained mental effort. Having chosen her life work and proven her fitness for it by a satisfactory period of probation, she should pursue her vocation " without haste, without rest," steadily, persistently and courageously, with a mental equipoise which keeps constantly in view a high ideal of excellence. The sweetest rewards of earth come to earnest effort and faithful accomplishment in lines of philanthropic work. They are not gained by fitful toil or half-hearted endeavor.

Lest there may be a misconception I ought to add that enthusiasm in work, devotion to duty, unresting fidelity to high ideals of efficiency, keen humanitarian impulses and love of scientific truth, cannot and must not be considered obligations peculiar to nurses. The trustees and ofiicers of the hospital accept similar obligations for themselves, and expect equal enthusiasm and devotion from all connected with the hospital in any responsible capacity.

What, on the other hand, has the pupil in the training school a right to expect from all who are connected with the hospital?

1. The pupil nurse has reason to expect, and should receive, the respect, confidence and cooperation of every right-minded person.

2. She should enjoy every facility for securing instruction, and an opportunity to obtain a higher training in every branch of knowledge which promises to increase her efficiency and usefulness.

3. She should have proper hours for work, proper hours for study and recreation, pleasant apartments, healthful surroundings, refining associations and every incentive to effort, and every aid to accomplishment of her work.

Many hopes cluster about this training school. The work of many years of patient labor spent in construction is over. The scaffold has been swept away, and the completed edifice stands before us. The work of the hospital cannot be complete until this school is open and in successful operation. The poor of Baltimore in their homes, suffering for lack of proper nursing and adequate attention, look to this school for a solution of the problem of district nursing among the poor. The homes of the wealthy need no less the skilled nursing which this school aims to supply. The trustees and officers of the hospital welcome the school and bid it God-speed.

PUBLICATIONS

In the first annual report Dr. Hurd says :

There has been established, as an organ of the hospital, a monthly publication known as The Joii.xs Hopki.ns Hospit.\l Bulletin, which is to contain announcements, programs, reports


THE JOHNS HOPKINS HOSPITAL BULLETIN, DECEMBER, 1919


PLATE XLII



DK. HIC.NKV M. HCIM) WIIKN UK CAMK TO THK .KiHNS HOI'KIN> IKlSl'ITAI. IN 1S89.


December, 1919]


347


of societies and minor medical contributions. The Bulletin has met with much success and seems to have found a place in medical literature. In addition to the Bi-llkti.\ a volume of Hospital Reports is published in fasciculi which will constitute a volume of about 500 pages during the year 1890. The first fasciculus contained 64 pages, and had the following list of articles: "On Fever if Hepatic Origin. Particularly the Intermittent Pyrexia Associated with Gall-Stones," by Dr. Osier

Throujrli tlic medium of The Johns Hoi'kin.s Hospital Bulletin tlic munorous activities of the hospital have been duly chronirlcil and mtuiy important events have been recorded. The numerous discoveries in the various departments have been brougrht to the notice of the medical world through this journal. It has been a faithful mirror of The Johns Hopkins Hospital and its establishment was one of the most iniportjint moves ever made by the hospital. It has enabled the institution to tell the civilized world promptly just what it has accomplished. The Johns Hopkins Hosintal lie ports contain the lengthy articles — those that are too extensive for a monthly journal. They now comprise 18 volumes.

Dr. Hurd started both the Bi"LLETin and the Beports and was editor of both from the initial issue until he relinquished his position in 1911. He was the editor in every sense of the word. Many of the articles which were rather crude in their English con.'itruction were entirely recast by him. Any member of the staff wlm wandered into the superintendent's oflicc late at night when all was quiet or on a Sunday afternoon woidd find Dr. Hurd busily engaged in correcting galley proofs for the IUlletin or for the Heporls.

Both of these publications possess a dignity and style rarely noted in medical periodicals. The printing has been good, the illustrations excellent and the text remarkably free from typographical errors.

The Hopkins Rvlletin and the Reports are to be found in medical libraries the world over. Dr. Hurd deserves the lion's share of credit for the marked success of these publications.

societies In the first report Dr. Third refers to the medical societies of the hospital.

A flourishing hospital medical society has been established under the direction of Dr. Welch, which meets bi-monthly and is regularly attended by members of the hospital and dispensary staff. At these meetings papers are read, patients are exhibited, morbid pathological specimens are presented anil the results of original investigations in the clinical, pathological and hygienic laboratories are reported. These meetings have been of great value, and the amount of work which has been done compares most favorably with that accomplished by any other similar society.

A Journal Club, composed of members of the hospital and dispensary staff, also meets bi-monthly. At these meetings the current literature in the various departments of medicine, surgery and gynecology is presented in abstract by persons previously appointed to report from these departments. This enables all members of the staff to keep fully informed as to what Is being accomplished by workers In every branch of medical science with the least expenditure of time.

In November. 1890, a Historical Club was organized to hold monthly meetings for the study of medicine in Its historical


aspects. These meetings have been well attended and have proven interesting and profitable.

The Historical Club still continues. Scattered throughout the various volumes of The Johns Hopkins Hospit.\l Bulletin are many articles which were read at the Historical Society. They are of much interest and value.

1890

(February 1, 1890— January 31, 1891)

In tlie report for the year ending January 31, 1891, Dr. Hurd refers to the work of the hospital among the poor of Baltimore and emphasizes the fact that care must be taken to see that people who are financially able should not be given free treatment :

The added experience of a year has demonstrated the necessity of the medical, surgical and gynecological work which this hospital is doing among the poor of Baltimore. The free work has constantly grown in importance and usefulness since the opening of the hospital and hundreds of poor people have received relief who could not have obtained it otherwise. This work has been done cheerfully and ungrudgingly both among hospital and dispensary patients. It is evident, however, that some persons who apply for gratuitous advice and pi'escriptions in the dispensary, and free beds in the liospital are not objects of charity, and should not receive the benefits of the institution.

In some of the New York hospitals the names of all persons applying for relief, when any doubt exists as to the propriety of granting it. are reported to the Charity Organization Society, and a systematic investigation is made by an agent of this society. After a careful review of the whole subject I am strongly of the opinion that the time has come when an arrangement should be made with the Charity Organization Society of Baltimore, whereby all suspected cases may receive a prompt investigation. It demoralizes any man to receive as a gift what he is able to pay for wholly or in part. Indiscriminate and haphazard charity begets habits of improvidence and of wastefulness, if not of actual vice among its recipients.

In addition to the evil effect upon the community of indiscriminate charity there is also danger of doing injustice to the profession of medicine, which numbers among its members so many persons actively engaged in charitable work. Neither the hospital nor dispensary should interfere with the sources of support of these men by affording free medical or surgical treatment to those who are able to pay for it.

In this connection mention may be made of the excellent provision which exists at this hospital for the accommodation of private or pay patients— a provision which is not excelled in any general hospital In tliis country.

Dr. Hurd in the report also refers to the Training ."School for Nurses:

Each month demonstrates the value and necessity of the work of the Training School for Nurses. The school Is developing a new field of usefulness for the young women of Baltimore and Maryland and Is growing in popular favor. The dignity and Importance of the profession of nursing were never so well appreciated in this community as now.

From the early days of tlie hospital to the present it has been a matter of frequent conmient that for intellectual refinement and for mental cajjacity few if any hospitals in America have been as fortunate as The .Johns Hopkins Hospital in tlie personnel of its Training School for Nurses.


348


[No. 346


1891

(February 1, 1891— January 31, 1892) The report for the year ending January 31, 1892, contains the names of the first class of nurses who graduated from the training school. Among them are Mary E. Gross (Mrs. John M. T. Finney), Georgie M. Nevins the superintendent of Garfield Hospital, Washington, D. C., M. Adelaide Nutting who later became superintendent of nurses in The Johns Hopkins Hospital Training School and who is doing such excellent work as professor in the Treachers' Training School at Columbia University, New York. This list also contains the name of Susan C. Eead (the late Mrs. William Sydney Thayer).

1892

(February 1, 1892— January 31, 1893) MEDICAL INSTRUCTION

In the report for the year ending January 31, 1893, Dr. Hurd makes a most important announcement relative to the opening of The Johns Hopkins Medical School.

By the endowment of the medical school through the generosity of Miss Garrett and others, the university is now in a condition to assume the responsibility of medical instruction, and commencing with October 1, 1893, both graduate and other work will cease on the part of the hospital. It is gratifying, in the review of the past three years, to notice that women have not in any respect proven a disturbing element. They have pursued their work under the same conditions as men, and have done faithful, honest and successful work. Although the hospital ceases to do any more medical teaching, the fact that the governing Idea in its erection was the promotion of medical teaching cannot be lost sight of. The construction of the wards, the location of the laboratories, the arrangement of the dispensary and amphitheater, the divers systems of heating and ventilating, and the facilities for their demonstration, all point to a preconceived plan that the hospital should do its share in the work of practical instruction. It is confidently believed that no other hospital in the United States is better equipped to do medical teaching, or in its brief career has done more thorough and suggestive work. The same faithful work will be continued by the same men, under the direction of the university in future, as a part of the curriculum of the medical school.

LYING-IN AND CHILDREN'S WARDS

The approaching opening of the medical school renders it important that no time be lost in arranging for the erection of a lying-in ward, to provide for the proper instruction of medical students and nurses. In many respects it seems most desirable that this ward be situated adjacent to the hospital, so that nurses may be readily provided, and yet far enough removed to render it free from the stir and publicity of a large general hospital, and a numerously attended out-patient department. This building ought eventually to be built upon a well-approved plan, and should furnish ample accommodations for women who are awaiting confinement, for parturient women, and for those who suffer from any form of puerperal infection.

A children's ward, separate and distinct from other wards, must be erected. Such a ward alone will give children the proper opportunity for comfort and recovery.

The children are now well provided for in the Harriet Lane Home. After long years of waiting it is a pleasure to know


that in the near future the obstetrical department is to have adequate and most satisfactory accommodations.

1893

(February 1, 1893— January 31, 1894) In the report for the year ending January 31, 1894,

Dr. Hurd describes the colored ward:

The colored ward, of which mention was made In the last report,

has also been erected during the year and is now ready for the

reception of patients. It consists of two stories surmounted by

a halt story.

This addition to the hospital has been of great value as it brings all the colored patients under one roof instead of having them scattered in various portions of the institution.

Dr. Hurd then refers to important changes in the library.

The opening of the medical school, and the increased demand for medical books on the part of medical students, have rendered it desirable to pay special attention to the library of the hospital. Miss Thies, who has received a careful training in the Enoch Pratt Free Library, has accordingly been employed at the joint expense of the university and hospital to catalogue and arrange the collections which have grown rapidly during the year. It is evident that by the close of another year the shelving will be filled, and no more room will be available for future additions. It consequently becomes important to know how increased accommodations can be secured.

In this connection it seems eminently proper to refer to the great advantages which the medical officers of the hospital and the students in our medical courses have derived from the proximity of the library of the Surgeon General's Office. The enlightened policy of this library, whereby valuable books of reference otherwise unattainable are loaned to the hospital under satisfactory guarantees against loss, cannot be too highly praised. The medical officers of the hospital, and the instructors and students of the medical school, are under many obligations for the uniform promptness and courtesy of those who have charge of this unrivaled collection of books in meeting the frequent demands made upon them.

THE WHITE ROSE FUND

By the generous act of Mrs. W. E. Woodyear, of Baltimore, the " White Rose Fund " has been established and the sum of $5000 has been placed at the disposal of the trustees, the interest of which is to be used for the comfort and happiness of sick children. It was not proposed to endow a bed or to establish a charity, but to use the income of the fund in such a way as to promote the comfort and happiness of poor, sick children who occupy beds in the public wards of the hospital.

It was the intention of the liberal donor to provide means by which flowers, books, pictures, excursions, music and other means of amusement could be afforded for the children in a more liberal manner than would be practicable if these extra expenses were paid out of the income of the hospital.

It is doubtful if any gift to the hospibil, no matter how large, has yielded more downright satisfaction to the donor than this gift has. Year after year Dr. Hurd has referred to how much it has meant to the children and what added pleasures this fund has made possible. He has alw^ays been most entluisiastic when speaking of it in report after report. It reminds one of a thread of gold carried through from year to year. Mrs. Woodyear gave this money in memory of her little daughter, Eose Blanche Woodyear.


December, 1919]


JOHXS HOPKINS HOSPITAL BULLETIN


349


1894

(February 1. 1894— January 31, 1895) In the year 1894 si'veral important advances were made. Experience having shown that the work of the pathological department was of great value and Importance to every other department, it was decided by the trustees, after a thorough consideration of the subject by the medical board, to organize this department, and to give it an equal standing in the medical staff by appointing a resident pathologist and an assistant resident pathologist. In consequence of this action. Dr. Simon Flexner, associate in pathology in the medical school, was appointed resident pathologist, and Dr. L. F. Barker, the associate In anatomy, was appointed assistant resident pathologist.

As far as is known at present, this is the first instance where similar officers have been appointed with staff standing in connection with any hospital in the United States.

OUT-PATIENT OBSTETRICAL SERVICE

This service has been placed under the immediate charge of Dr. J. Whitridge Williams, the associate in obstetrics in The Johns Hopkins Medical School, who has received the appointment of assistant obstetrician to The Johns Hopkins Hospital. Dr. G. W. Dobbin has been appointed an additional assistant in the gynecological department to look after this work in a special manner, both in the dispensary and in attending patients in their homes. It is contemplated that poor patients expecting to be confined, and unable to pay the expenses of a physician, shall visit the dispensary to arrange for the services of the resident obstetrician. In arranging for this service it is hoped to be able to bring relief to patients who require the services of a physician, and to furnish the attention of a skilled nurse during the first 24 hours following confinement. It Is expected that this service will eventually grow into a branch of district nursing.

In this report Dr. Hurd refers to the resignation of Miss Hampton.

Shortly after commencement exercises in June last, 1894. Miss Hampton, who had been the superintendent of the training school ever since its opening, tendered her resignation. Her services to the school had been of great value, and her resignation and relinquishment of all training school work must be regarded a serious loss to trained nursing throughout the country.

Upon her resignation, Miss M. A. Nutting, who had been her assistant for the previous two years, received the appointment of acting superintendent. Subsequently, In December last, she was appointed superintendent, and given leave of absence for eight months from February first to visit other hospitals and training schools in this country and Europe, to see their methods and to perfect herself in nursing work.

THE COLORED ORPHAN ASYLUM

In Dr. Hurd's report for the year ending January 31. 189."), we find the first report of the colored orphan asylum.

By the will of the founder of the hospital, the erection and maintenance of a colored orphan asylum was enjoined, and provision was made for Its support out of the income of the hospital fund.

A tract of land on Remington Avenue and King Street has been purchased as a permanent site for The Johns Hopkins Colored Orphan Asylum, and the children have been removed to their new home.

A detailed report of the committee on the colori-d orphan asvlum follows that of Dr. Hurd.


1895

(February 1, 1895— January 31, 1896) In Dr. Hurd's report for the year ending January 31, 1896, we find an account of an addition to the dispensary :

In accordance with the recommendation of the medical board, the trustees erected, during the summer of 1895, In connection with the dispensary four class-rooms for the accommodation of classes from the medical school.

Dr. Hurd in this report also records the death of one of tlie most picturesque members of the hospital family :

Upon the 16th day of October, 1895, Mr. L. Winder Emory, who had discharged the duties of purveyor with conspicuous ability and fidelity, died suddenly of angina pectoris. The vacancy thus created was filled January 1. 1896. by the appointment of E. H. Read, of Baltimore, who immediately entered upon the discharge of his duties.

1896 (February 1, 1896— January 31, 1897)

THE CLINICAL LABOR.\.TORY

In the report for the year ending January 31, 1897, Dr. Hurd refers to tlie new clinical laboratory :

By an unexpected gift of $10,000 from a generous donor, whose name we are prohibited to mention, It has been practicable to erect a large and convenient clinical laboratory for the use of the hospital and medical school between the amphitheatre and dispensary. This portion of the building, wliich was formerly one story in height, has now been raised to three stories, and the additional room furnishes ample accommodation for medical classes.

iliss Nutting's report to the superintendent for the year 1896 announces the inauguration of the three-year course in the Training School for Nurses.

The demand for information concerning the school remains about as usual:

The number of written applications for

circulars 1143

Applicants formally considered 160

Accepted applicants 61

Among the acknowledgments for the year ending January 31, 1897, Dr. Hurd mentions ilr. Spence's gift of a reproduction of Tliorwaldseii's statue of Christ:

One of the most noteworthy and appropriate gifts which the hospital has ever received Is a reproduction of Thorwaldsen's celebrated statue of Christ, by Stein of Copenhagen, which has been placed in the rotunda through the liberality of William Wallace Spence • of Baltimore. A full account of the interesting exercises at the unveiling of this statue, together with the addresses delivered on that occasion, was published in the Buixxrix for January, 1897,

The superintendent's report for the year ending January 31, 1897, gives for the first time the " By-Laws, Rules and Regulations of The Jolins Hopkins Hospital." A perusal of this 18-page article gives a most illuminating idea of the inner working of this hospital.


  • The reader will be interested to know that Mr. Spence

rounded out his century — be died a short time after his 100th birthday.


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[No. 346


1897

(February 1, 1897— January 31, 1898)

In 1897 the first class of The Johns Hopkins Medical School received their degrees from The Johns Hopkins University, and the 12 students who stood highest in their class were eligible for positions in the hospital. Dr. Hurd in his report for the year ending January 31, 1898, says:

Beginning with the first of September, 1897, 12 members of the graduating class of The Johns Hopkins Medical School are in future to be appointed resident medical officers. These physicians are divided Into three groups, and serve four months in each department of hospital service, the service being determined by lot. In this manner each resident medical officer secures four months service in medicine, surgery and gynecology.

In addition to these resident medical officers, the resident physician, surgeon and gynecologist each is supplied with a iirst and second assistant, who are appointed from those who have had previous hospital experience. The working of this plan has thus far been satisfactory.

In accordance with this arrangement the following-named persons were appointed resident medical officers *: Drs. G. L. Hunner, J. F. Mitchell, 0. B. Pancoast, L. P. Hamburger, Thomas R. Brown, E. L. Opie, R. P. Strong, W. G. MacCallum, W. S. Davis, I. P. Lyon, C. A. Penrose and Mary S. Packard.

The rotation system was abandoned after a few years.


  • Taken as a whole this was the most remarkable group that

has ever graduated from The Johns Hopkins Medical School. Several of them have international reputations.

Dr. Walter S. Davis died in September, 1898, and in the Annual Report of the Hospital for that year Dr. Hurd paid a fitting tribute to his worth.

Recently Dr. Clement Andariese Penrose, another member of this group, died. He received his A. B. degree from The Johns Hopkins University in 1893 and immediately entered the Medical School. After his year as intern he located in Baltimore and in a few years was recognized as one of the most promising of the younger physicians.

In 1903 he served as Vice-Director and Surgeon of the Bahama Expedition. His report of the medical conditions noted on the trip is very interesting. The most valuable paper was that on Leprosy. This paper graphically depicted the deplorable condition existing in the Bahamas due to leprosy and to degeneracy resulting from close intermarriage.

In the spring of 1917 he was appointed Chairman of the Baltimore Food Economy Commission and did much to further food conservation.

In August 1917 he was commissioned major in the United States Army and was sent by the surgeon general to make an exhaustive study on army sanitation in the English and French armies. General Gorgas in speaking of Dr. Penrose's report said: "This report has been of great value to the Medical Department of the United States Army."

After completing his work on sanitation he took charge of a three-hundred bed hospital at Gondricourt, France. Here he contracted a septic bronchitis which nearly caused his death at the time. He partially recovered but was left with an impaired heart.

He returned to America late in December and for a time was able to resume his practice. In March 1919 the infection again became pronounced. He gradually lost ground and died early on the morning of July 4, 1919.

Penrose was an excellent medical consultant, a man of rare judgment, beloved by his patients and a loyal friend. His death was a great loss to the citizens of Baltimore.


Dr. Kurd's report for this year also contains an account of the addition to the gynecological operating room rendered possible by the generosity of Dr. Howard A. Kelly, who gave $5000 to assist in defraying the expenses.

In Dr. Hurd's report for this year scholarships and honorable mention in the Training School for Nurses are recorded for the first time. |

Dr. Hurd says : '

The experience of another year has demonstrated the feasibility and desirability of extending the course of training of nurses from two to three years. The changes in the course of study have enabled nurses to spend more time in learning the fundamental branches of their work, and the shortening of hours of duty has enabled them to bring greater freshness and vigor of mind to their studies and regular duties. The result has been to improve the standard of nursing, and to give a greater state of efficiency to the school than it has ever previously had.

1898

(February 1, 1898— January 31, 1899) In his report for the year ending January 31, 1899, reference is made to an incident that cast a pall over the hospital family. It is vividly remembered to this day :

It is my sad duty to report the death of Dr. L. E. Livingood who had filled the position of assistant resident pathologist for two years, and who had secured a leave of absence to go to Europe for further study. He left his duties July 1 and was drowned a few days after in the destruction of the ill-fated steamer La Bourpoyne. He possessed unusual ability, great industry and a finely trained mind, a combination of qualities which gave every promise of success as a teacher and research worker. In his death the hospital and the medical school have experienced a severe loss.

The hospital lost another of its young medical men during this year, Dr. Walter S. Davis died of Addison's disease on September 27, 1898. In referring to him Dr. Hurd says:

Dr. Davis was full of energy and enthusiasm, and during his medical course and his year of hospital residence showed himself thorough in his work, conscientious in the discharge of duties and efficient and faithful in all he attempted to do. His teachers and associates anticipated high success for him in his chosen profession, and all lament his untimely death.

A glance through the list for this year of those who secured » scholarships in nursing is particularly interesting. Among I the names in the senior class is Elsie Lawler, our present ' superintendent of nurses. In the junior class the name of Agnes Hartridge, one of the present assistant superintendents of the hospital. The steady advancement of these two members of the training school for nurses is ample proof that Miss Nutting made no mistake in her selection of her pupils meriting scholarships.

1899

(February 1, 1899— January 31, 1900) GEADUATES FILLING POSITIONS AS SUPERINTENDENTS OF TRAINING SCHOOLS FOR NURSES

One of the most interesting items in the report for the year ending January 31, 1900, is a list of the graduates of the


December, 1919]


351


training school who are filling positions as superintendents of training schools for nurses. This list contains the names of 24 graduates of The Johns Hopkins Training School who are now themselves the heads of training schools. Nothing could show more grapiiicaily how much the graduates of this school are appreciated throughout the United States and Canada.

1900 (February 1. 1900— January 31, 1901) In the report for the year ending January 31, 1901, Dr. Hurd refers especially to Volumes VIII and IX of The Johns Hopkins Ilospilal Reports:

The past year has been one of considerable activity in the publications of the hospital. Volume VIII of the Reports, containing exhaustive studies by Dr. Osier and his staff in typhoid fever, has recently been published, and Volume IX, which contains 38 elaborate articles prepared originally by his students to celebrate the 25th anniversary of the doctorate of Professor W. H. Welch, the pathologist of the hospital, was published in April last and constitutes a volume of nearly 1100 pages. In point of e.\cellence of matter and thorough presentation of scientific work the volume is fully equal, if not superior, to any of similar character ever published in this country.

In addition, the Billetix has been regularly published with increasingly valuable contributions each month. Volume XI which was completed with the December issue, contains 340 pages and numerous illustrations.

1901

(February 1, 1901— January 31, 1902) In the report for the year ending January 31, 19Qi2, Dr. Hurd again refers to the great value of The Johns HopKixs IIosi'iT.4L BuLLETix and of the Reports. He says:

Volume X of The .Johns Hopkins Hospital Reports is in progress and will be completed during the present summer. The Bulletin of the hospital has been issued monthly during the year and has now reached an annual volume of nearly 400 pages. It Is gratifying to observe how extensively it is circulated and quoted both in this country and in Europe. It is evident that this publication has made a permanent place for itself in medical literature and our publishers inform me that the series of volumes Is already In active demand to supply libraries. The papers presented in it during the past 12 years form, in fact, a good commentary upon the advance of scientific medicine in America.

During the past year, it may be added, the volume of the BulLETi.N has furnished upward of 900 octavo pages of reading matter.

Dr. Hurd also mentions the suhstantial addition to the public gynecological ward :

During the year. In order to furnish additional accommodations for patients recovering from gynecological operations, and to secure facilities for an examining room and laboratory in connection with this ward, Dr. Kelly, with great liberality, gave to the hospital the sum of $10,000. This sum has been expended in building upon the north side of the public gynecological ward, a large two-story annex which affords accommodations for 12 patients.

The superintendent also gave a complete list of the larger donations made to the hospital from the time of its completion ap to the end of 1901.


1902

(February 1, 1902— January 31. 1903) From Miss Nutting's report to Dr. Hurd for the year ending January 31, 1903, we learn of the esteem in which graduates of the training school are held. This is shown by the large number of requests for nurses to fill important positions in other schools :

Letters requesting us to sena our graduates to fill positions as follows:

Superintendents 26

Assistants 6

Head nurses 15

1903

(February 1, 1903— January 31, 1904) Nearly every hospital board of trustees has its period of anxiety and perplexity wondering just how it will meet its financial obligations. The trustees of The Johns Hopkins Hospital have been men of affairs — men possessing a broad vision — and they have in every instance found their way out of the dilemma. Early in 1904,* however, without a day's warning, their annual income was for the time being markedly impaired. Dr. Hurd in his annual report published early in 1904 refers to this critical period in the liospital's career in detail : To the Board of Trustees of The Johns Hopkins Hospital:

Ge.ntlemen. — The close of the past year of the hospital has been marked by the most serious calamity which has befallen the hospital during its existence. On the morning of February 7, almost before it had been possible to sum up the results of the operations of the previous fiscal year, which closed February 1, a general conflagration swept over the city of Baltimore and proved most disastrous to the real and lease-hold property of the hospital. During the fire 64 stores, warehouses and office buildings, widely scattered in the business portion of the city, representing an assessed valuation of more than a million and a quarter dollars, were destroyed, entailing a loss of income for at least two years of about $120,000. A portion of this loss was made up by Insurance. In accordance, however, with the policy of the hospital, an insurance liad not been secured against a total loss, but merely for a sum which had been deemed sufficient to provide for rebuilding in case of partial destruction by fire. The results, however, proved that such insurance was wholly inadequate to repair the effects of a wide-spread calamity, and a loss of capital funds of between $300,000 and $400,000 resulted.

For several weeks thereafter great anxiety was felt lest It should become necessary to curtail seriously the work of the hospital by closing wards and cutting down the staff of nurses and employes. Through the liberality, however, of Mr. John D. Rockefeller, of New York, who liad familiarized himself thoroughly with the work of the hospital. Its financial standing, and its loss of income and capital, a half million dollars have been placed at the disposal of the trustees to repair these losses and to enable the work to go on without diminution. Never was assistance more timely to the Institution. The magnitude of the work of


  • As it often requires six months to assemble the data of the

preceding year the annual report appears about the middle of the following year: hence the Baltimore fire of February, 1904, was mentioned In the report for 1903.


353


[No. 346


the hospital and the need of increasing clinical facilities to meet the growing demands of the medical school had hitherto consumed all its income and had left no available fund to meet the unforeseen emergency of rebuilding its warehouses. Hence the peculiarly timely character of the aid afforded by Mr. Rockefeller, and the critical condition of the institution without such assistance. The thanks of the medical staff of the hospital and of the officers of the medical school are due to him for his prompt and generous recognition of the educational work of the hospital.

At a special meeting of the Board of Trustees of The Johns Hopkins Hospital on Thursday, April 7, 1904, the following action was unanimously taken in reference to the gift of Mr. Rockefeller:

" In view of the donation of $500,000 made to The Johns Hopkins Hospital by John D. Rockefeller:

" Resolved, That the Trustees of The Johns Hopkins Hospital desire to express their grateful appreciation of the gift of Mr. John D. Rockefeller to The Johns Hopkins Hospital, announced to the trustees by his son, Mr. John D. Rockefeller, Jr., in a letter to Dr. William Osier. This munificient donation will enable the hospital to continue its works of charity, medical education, medical research and the training of nurses; and the trustees hope and believe that by a wise use of this donation they will be able to expand and improve the great institution committed to their custody."

The report for the year ending January 31, 1904, contains the following sentence : " In the out-patient obstetrical department there were 385 cases treated, with no deaths." This speaks volumes for the splendid work being done by tlie obstetrical department.

This year brought another liberal donation to the hospital.

Through the liberality of Mr. Henry Phipps, of Pittsburgh, the sum of $20,000 has been given to the trustees of the hospital to increase the facilities of the out-patient department for the study and treatment of tubercular patients. It was the wish of the donor that one-half of this sum should be used to construct a separate dispensary for tubercular patients so as to render it possible to segregate these from other patients. It was his further wish that the remaining $10,000 should be so invested that the income may serve to promote special work and investigation.

In this report Dr. Hurd quotes extensively from a splendid paper by a member of the hospital staff. This article is entitled " The Eolation of The Johns Hopkins Hospital to Medical Education and the Promotion of Medical Knowledge." It gives a clear and concise view of the close connection between the work of the hospital and the medical school. It takes up in succession :

1. Construction of the hospital.

2. Medical organization of the hospital.

3. Relation of the hospital to medical education.

4. Relation of the hospital to the advancement of medical knowledge.

5. The treatment of patients.

6. The Training School for Nurses.

7. Relation of the medical school to the university and to the hospital.

This paper should be read by all interested in medical teaching and in hospital management.

In the report for the year ending January 31, 1904, we find the first annual report of the x-ray department. Dr. F. H. Baetjer has been in charge of this department from its incep


tion up to the present time. He has made an tmusual success of this important branch of the work.

In the annual report for 1903 Dr. Hurd has made a splendid innovation. He gives a complete list of the trustees of the hospital from 1867 to the present. There is also a complete list of the officers of The Johns Hopkins Hospital from 1889 to 1903. This list includes not only all the senior members of the staff, but also every resident physician, resident surgeon, resident gynecologist, resident obstetrician, resident pathologist, assistant resident physician, assistant resident surgeon, assistant resident gynecologist, assistant resident obstetrician, assistant resident pathologist, and every house medical officer. It is in reality an up-to-date directory of every medical man who is or has been connected with the hospital since its opening. It will be of the greatest value in succeeding years.

1904

{February 1. 1904— January 31, 1905)

Dr. Hurd in his report for this year refers to the new clinical building.

The amphitheatre and surgical building, to which reference was made in the last report, were completed and made ready for occupancy in October. 1904. A full description was given in the last report, and need not be repeated here.

The building has proven extremely useful, and has added very much to the convenience of the surgeons in their operative work, and has afforded needed facilities for those who are engaged in teaching.

The basement of the building has been fitted up for a genitourinary clinic, under the charge of Dr. H. H. Young.

The new surgical building and clinical amphitheatre were formally opened on October 5, 1904. Appropriate addresses were made by Henry D. Harlan, president of the Board of Trustees; Dr. Lewis A. Stimson, of New York; Dr. T. Clifford Allbutt, of Cambridge, England; Dr. A. Jacobi, of New York; and Dr. D. C. Gilman, ex-president of The Johns Hopkins University. At the unveiling of the tablet in memory of Dr. Jesse W. Lazear, addresses were made by Dr. James Carroll, of the United States Army, and by Dr. William S. Thayer.

Dr. Hurd in this report also refers to the opening of the Phipps Tuberculosis Dispensary.

The Phipps dispensary was opened with appropriate ceremonies on the 21st of February of the present year. Short addresses were made by Mr. Henry Phipps; Dr. William Osier; Dr. H. M. Biggs, of New York City; and Dr. Henry Barton Jacobs, president of the Laennec Society, a society for the study of tuberculosis.

Mr. Phipps subsequently gave $5000 to be used for the purchase of books and apparatus and for the endowment of the dispensary. Under the arrangements which were made, the sum of $10,000 from Mr. Phipps's former donation was used in the construction of the Phipps dispensary, and the remaining $10,000 was set aside as a permanent endowment.

1905

(February 1, 1905— January 31, 1906) The effects of the fire were felt for a long period of time, and in Dr. Hurd's report to the trustees for the year ending


December, 1919]


353


January 31, 1906, we find the following reference to the financial stress that was still felt by the hosi)ital :

The work of the hospital during the past year has been attended with unusual cares and anxieties, due largely to the disturbed finances of tlie Institution, consequent upon a diminution of Income. When the last report was presented, it was hoped that, by speedy rebuilding, increased rentals from the buildings which were erected might become available at an early day so that the necessity of pinching economy might be removed. Unfortunately, however, the expense and delays of rebuilding, due to the rush to erect a large number of buildings at the same time in the burnt area, rendered it Impossible to regain the full income of the hospital during any portion of the year, and we are forced to conclude it with a large deficit. It is hoped that the coming year will be more properous.

RESIGXATION OF DB. OSLER

The departure of Professor Osier wrenched the heart-strings of each aiul all of the Hopkins family. Dr. llurd in his report said:

In May last Dr. William Osier, who had filled the position of physicianin-chief to the hospital since its opening in 1889, resigned to accept the position of professor of medicine at the University of Oxford. This closed a most faithful, efficient and active service on the part of Professor Osier, covering a period of 16 years. During this time he had given himself untiringly to the work of the hospital and had won reputation as one of the most accomplished clinical teachers in America. Through his energ>' and foresight the organization of the medical service of the hospital was early perfected, and his long period of service enabled him to fully develop the plans formed upon his coming to the hospital. He was much beloved by his patients and by the members of the medical staff. The trustees in liis departure have lost an inspiring and a stimulating personality. It is gratifying to know that he is to return at stated intervals to Baltimore, in order to keep himself in touch with the work of the hospital and of the medical school.

APPOINTMENTS OF DR. BARKER AND DR. THAYER To fill the vacancy occasioned by the resignation of Dr. Osier, Dr. Lewellys P. Barker, of the University of Chicago, once an Intern and later a resident pathologist in the hospital, and for several years a teacher in the medical school, was appointed physlclan-In-chlef, and Dr. William S. Thayer, for many years resident physician at the hospital, and former associate in medicine, was appointed associate physician. Under the experienred guidance of these able men. It Is confidently felt that the medical work of the hospital will continue with undiminished efficiency.

The ncconiniodation for children in the past had been totally inadequate and through the cooperation of the trustees of the Harriet l.rf»nc Home and those of the hospital it looked as if ample facilities would be afforded.

Miss Helen Skipworth Wilmer, a graduate of The Johns Hopkins Training School for Nurses, gave $30,000 in memory of her father, and the trustees contemplated using this money in erecting an additional building for the accommodation of the ever-increasing number of pupil nurses.

Dr. Hurd in his report on these projects said :

By the will of the late Mrs. Harriet Lane Johnston, of Washington, a home for invalid children from the state of Maryland has recently been established with an ample endowment, to be known


as the Harriet Lane Home for Invalid Children of Baltimore City. After considerable thought upon the matter, the trustees of the home deemed it wise to establish a working relation between the proposed institution and some well-organized hospital. Accordingly, upon mature consideration on the part of the trustees of The Johns Hopkins Hospital and of the Home for Invalid children an arrangement has been made whereby the home will be placed as a cliildren's hospital for medical and surgical cases upon the grounds of The Johns Hopkins Hospital. The hospital will provide a site for the building free of charge, furnish heat and light, and assume the maintenance and nursing of the children at a specified price. The home will remain under the charge of the Board of Trustees as established by its founder, and an agreement has been made which will insure a wholly harmonious relation between tlie two institutions.

In December last Miss Helen Skipworth Wilmer of Baltimore, offered to the hospital the sum of $30,000 to be used to erect a memorial to her father, the late Skipworth Wilmer, Esquire, a prominent citizen of Baltimore, and for a number of years a member of the Board of Trustees of The Johns Hopkins Hospital, Mr. Wilmer, during his entire connection with the hospital, felt a special interest in the education of nurses, and it seems peculiarly fitting that his daughter should thus desire to perpetuate his memory. The trustees have accepted the gift, and propose to erect in connection with the nurses' home an additional building to be used as dormitories for the nurses.

Strangers going to and from the hospital often linger to examine the sun dial and in sunny weather to see how closely their watches tally with the dial.

Mr. George K. McGaw, one of the trustees of the hospital, has placed in the circle upon the terrace immediately in front of the hospital entrance an ornamental bronze sun dial upon a pedestal, after a novel design by Albert C. Crehore, of Yonkers, N. Y., and so arranged as to tell the time during the entire day as well as the time of sun-rise and sun-set throughout the year. This dial from its original design and beautiful workmanship Is highly ornamental to the grounds of the hospital.

Award at the Loiisiana Purchase Exposition

In 1904 the Maryland Commission of the Louisiana Purchase Exposition made an appropriation of $700 to defray the expenses of transporting and setting up an exhibit of The Johns Hopkins Training School for Nurses at St. Louis.

The exhibit was duly Installed under the direction of Miss Ross, and excited much Interest among those who visited the exposition. The grand prize, consisting of a diploma and a bronze medal, was awarded by the Board of Awards. Unfortunately, owing to the high price of labor and tlie difficulties Incident to the transportation of the exhibit and fitting It up in St. Louis, an Indebtedness of about $350 was incurred, wlilch was assumed personally by Mr. William A. Marburg, one of the members of the Maryland commission and a trustee also of the hospital.

1906 (February 1, 1906— January 31, 1907)

The report for 1906 was made by Dr. Rupert Norton, who had been appointed acting superintendent during the superintendent's absence. In his report to the trustees Dr. Nortf)n says :

In the absence of Dr. Henry M. Hurd, superintendent, to whom you have granted a year's leave of absence to date from November 1. 1906. I have the honor to submit the following report on the work of the hospital during the year ending January 31, 1907.


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Since the last report was presented the hospital has had a most successful financial year, and it looks as though the coming years would be free of many of those cares and anxieties which have troubled the hospital in the past; the present year ends with a small surplus to its credit.

Dr. Norton's report also chronicles the splendid Marburg bequest.

Mr. William A. Marburg, Mr. Albert Marburg, Mr. Theodore Marburg and the Misses Marburg gave to the hospital the sum of flOO.OOO in memory of their brother the late Charles Marburg. The money was expended in the erection of a four story private ward called "The Marburg." This building has enabled the hospital to handle many more private patients than was heretofore possible.

DR. HURD's vacation

Early in November, 1906 Dr. Hurd commenced his wellmerited year's leave of absence. He left for New York and there boarded a steamer for Havana. After a short stay in Cuba he journeyed to Mexico and remained there, visiting various points of interest, until January.

In January he returned to Baltimore, and in a short time left Boston for Europe accompanied by Mrs. Hurd, Miss Hurd and Miss Anna Hurd. Their first stop was at the Azores. They thoroughly enjoyed a visit to Gibraltar and to Algiers. They visited in succession the chief cities of Italy and also went to Sicily. After a stay at Lake Como they went to Switzerland. Here Dr. Hurd left his family and journeyed to England where he renewed many old acqtiaintanceships and visited the asylums and hospitals. He greatly enjoyed an extended tour through Scotland. Here also he was royally treated.

Leaving Scotland Dr. Hurd rejoined his family in Holland and attended the International Congress of Alienists in Amsterdam.

He returned to America thoroughly rested and greatly pleased with what he had seen during his happy year of leisure. He resumed his hospital duties on November 1, 1907.

1907

(February 1, 1907— January 31, 1908) In the report for the year ending January 31, 1908, Dr. Hurd refers at length to the Training School for Nurses and dwells especially on the los.s the hospital had sustained through the resignation of Miss Nutting.

The training School for Nurses during the past year has been called upon to part with its superintendent and principal, Miss M. Adelaide Nutting, who had ably supervised its work since 1894, when she succeeded Miss Hampton, now Mrs. Robb, upon the resignation of the latter

Miss Nutting, her immediate successor, graduated from the first class of nurses trained by Mrs. Robb, and subsequently held important teaching positions in the school. Her connection with tlie school in fact as pupil and teacher covered a period of about IS years, and during this period she inaugurated many Improvements in the methods of teaching which contributed much to the evolution of the school as we have it at present.

Hence, when Miss Nutting decided to accept the call to the Chair of Institutional Management in Columbia University, it was generally recognized that the training school had lost a most valuable officer, whose place would be filled with great difficulty.


The best wishes of the trustees, officers and pupils of the hospital and school for her success accompany her in her new field of labor.

It is gratifying to be able to add that Miss Georgina C. Ross has taken up the work which Miss Nutting laid down, and has prosecuted it with intelligence and vigor. She, like Miss Nutting, had been connected with the school tor many years. She was trained here as a nurse, and after her graduation had filled many positions in connection with the school. As acting superintendent she has had charge of the school for several months, and has discharged a difficult range of duties with discretion, faithfulness and efficiency.

THE DEPARTMENT OF SOCIAL SERVICE

Dr. Hurd in this report referred at length to the social service department which had just been inaugurated.

It has long been evident that the work of the hospital, both in its wards and in the various out-patient services, has been incomplete by reason of the limitation of the sphere of physicians and nurses, who, from the nature of their connection with patients, necessarily confine themselves to the treatment and care of their physical ailments only. When the care of the hospital is withdrawn and the patients return to their homes, they frequently lose the benefit which they receive, because of bad social conditions, lack of proper food and improper hygienic surroundings. With the hope of relieving many of these conditions and helping to render permanent the good received while under treatment, the trustees of the hospital, largely through the initiative of Mr. John M. Glenn, one of their number, for many years closely identified with the public and private charities of Baltimore, have established a department of social service under the special charge of Miss Helen B. Pendleton, for many years a trusted and efficient agent of the Charity Organization Society of Baltimore. It is her duty to look after those persons who need something more than medical advice and prescriptions, and to bring them into relation with such charitable agencies or philanthropic persons as will enable them to improve their former unfavorable conditions of life. She has in her work the advice and council of Dr. Charles P. Emerson, who has for several years organized and directed a very extensive friendly visiting work among the poor of East Baltimore, and the assistance and active cooperation of a large number of friendly visitors from among the medical students of The Johns Hopkins University and other charitable workers.

The work under Miss Pendleton is still in its infancy, having been fully inaugurated only in September last, but its success already has been gratifying and encouraging. A kindred but less comprehensive work on the part of the officers of the hospital and the medical students of the university, as before intimated, had been carried on under Dr. Emerson's efficient and wise direction during the past five years.

1908 (February 1, 1908— January 31, 1909)


THE PHIPPS PSYCHIATRIC CLINIC

Dr. Hurd's report for the year ending January 31,


1909,


speaks of the Phipps Psychiatric Clinic.

The Phipps Psychiatric Clinic, which was given by Mr. Henry Phipps last June, will soon be begun, and arrangements for the conduct of this department upon the completion of the building have been satisfactorily settled. The architect, Mr. Grosvenor Attebury, of New York, has the working plans well under way.


December, 1919]


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This is the most important gift that the hospital has receive! since its original foundation, and one which will undoubtedly add much to its usefulness. It is a matter of great satisfaction that we have been able to secure Dr. Adolf Meyer, of New York, as director, a man who in knowledge and experience ranks with the first men in the United States and Europe in his special calling.

The superintendent's report for the year ending January

{1, 1909, contains three reports of exceptional merit — Report

of the Piiipps Dispen.-iary Nur.«e; Report of tlie Phipps Dispensary, and the First Annual Report of the Social Service Department. Tlieso clearly show how nuuli the hospital is doing for the welfare of the citizens of Baltimore in their own homes.

1909

(February 1. 1909— January 31, 1910) In the report for the year ending January 31, 1910, is a splendid record of the work done hy the new social service de|)artnu'nt.

To Dr. Hinry M. Hiird. Superintendent of The Johns Hopkins

Hospital:

Sir. — The second year of the social service department ending

February, 1910, shows a decided growth in the work. There are

now 980 cases recorded as compared with 414 in the preceding

year

That the hospital physicians recognize the usefulness of this department is shown by the Increase in the number of cases referred to us from the wards. During the first year there were 4S

cases, this year there have been 123

Mabcakkt p. BitniiBKX, In charge of

social service department.

1910 (February 1, 1910— January 31, 1911) l>r. Iliird's report for the year ending January .^1, l!tll. refers to the resignation of Miss Ross, the superintendent of nur.«es and the ai)i)ointment of her .successor:

At the beginning of the fiscal year Miss Ross, in consequence of ill health, resigned her position and Miss E. M. Lawler was appointed superintendent of nurses and principal of the training school in her place. Miss Ross had been connected with the hospital since her graduation in 1894, and had served faithfully in many capacities in nursing service. She devoted herself assiduously to her work, and her failure in health was much deplored by all connected with the hospital. Her successor, Miss Lawler, is also a graduate of the training school, and for a time was assistant superintendent. Later she held responsible positions in connection with hospitals at Toronto. Ontario, N'iagara Falls, N. Y.. and Pittsburgh. Her training has been varied, her opportunities for acquiring familiarity with the duties of superintendent have been unusual, and she consequently comes to us an expert teacher. She has now given nearly a year's faithful service to the hospital, and her success gives every prospect of continued and Increasing usefulness.

rur. PROFESSOR OF r.SYClIl.VTHY

In this report Dr. Hurd also referred to the development of the p.<ychiatrie department and to its director who had recently joined The Johns Ilupkins Hospital staff:

The professor of psychiatry. Dr. Adolf Meyer, has been appointed psychiatrist to the hospital, and although the psychiatric clinic is not ready for occupation. Dr. Meyer has been able to do


very effective work in connection with the hospital wards and the out-patient department. It seems fortunate that prior to the opening of tlie Phipps Psychiatric Clinic it has been possible to utilize his services in connection with various charitable agencies in Baltimore. Tliere is reason to anticipate wlien the clinic is opened that these relations may be productive of great good by promoting cooperation with the clinic on the part of many charitable organizations.

In the report for 1910 Dr. llurd gave a complete list of the large gifts made from the ojicning of the hospital in 1889 up to the end of 1910.

1911

(February 1. 1911— January 31, 1912)

THE RESUiNATIOX OF DR. HUKD

In the '2'M report of The Johns Hopkins Hospital for the year ending January 31, 1912, on tlie ])age headed " Trustees " we find : President, Henry D. Harlan ; vice-president, William A. Marburg: treasurer, John C. Thomas; secretiiry, Henry M. Hurd, M. D, On scanning the report still riirtlicr we rciul [page 27] :

In May, 1911, Dr. Henry M. Hurd resigned from the superintendency of the hospital to become secretary of the board of Trustees, and Dr. Winiord H. Smitli, general medical superintendent of Belle\Tie and Allied Hospitals, in New York, was appointed his successor.

Dr. Hurd was the first superintendent of the hospital, and held the office for 22 years. Dr. Hurd"s wise administration, his higli ideals, liis example and his readiness at all times to give of Ills knowledge to others, have contributed largely to the general development of hospitals throughout the country.

The man of small calibre is ])rone to pick out as his successor one who has even less ability than he possesses — one who by contrast will compare unfavorably with him. The man of vision, on the other hand, is anxious to have the work that he has carried on so successfully continue to broaden out and will suggest for the post he is relinquishing the best available man. Dr, Ilurd with Jiis u^ual good judgment of men recommended the best man he could find. The wisdom of his choice has been continually evident and it has ever been a delight to sec how hapjiy and how proud Dr. Hurd has been of the well-merited success of his successor, Dr. Winford II, Smith, Dr. Hurd's pride has been akin to that of a father who views with the greatest satisfaction the splendid achievemcnt.s of his son; the more he accomj)lishes and the greater recognition his work receives the happier he is.

DR. liriM) I\ Ills {{KL.VTIOX TO Till'] IIOSi'IT.\L

.S'i'.\l-'i When The Johns iio|ikins Hospital opened there was no me<lieal .school from wliich to draw hospital interns and they consequently were continindly recruited from all parts of the United States and Canada, This system had its advantages. Nearly every man came from a dilTerent school. The men compared notes, tohl one another of the methods in vogue in the school or hospital from which they had ( ome, and thus each man scmn betame fairly familiar with what was being done in a medical way all over the country.


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Some of these iuteriis had had several years' training or by instinct immediately dropped into line. There were others of us who were young and immature and who needed careful and persistent training. Dr. Hurd was a past master in stimulating the house men to do their best. He did not mollycoddle them in the least. This good old state of Maryland is celebrated for its Maryland or beaten biscuits and it is a well-known fact that the more they are hammered in the making the better they are. Dr. Hurd with his keen perception soon learned this fact and he applied the principle to good purpose in his training of these men.* By a gentle but firm hint here and a rather emphatic suggestion there he soon transformed the raw recruit into a splendid house officer. Some of the men in the beginning hardly knew just how to take this discipline, but in a short time all thoroughly appre


  • I had often heard of an interesting interview the superintendent had with an incoming group of interns and also vague

accounts of a very apt story related by the director on that occasion. I asked Dr. Hurd if he would mind repeating it. Here it is:

"THAT STORY"

" When the men who had been selected for the positions of interns at The Johns Hopkins Hospital out of the first graduating class of The Johns Hopkins Medical School came on duty, they found an organization for their work which had already been in successful operation for about eight years. They were bright enterprising students who were peculiarly receptive to all new ideas and much inclined to adopt them with little regard to their bearing upon the former routine of hospital service. As all were men of marked ability, some of the innovations which they wished to inaugurate were improvements without doubt and made for better service, but the general effect of their combined action caused confusion and a lack of co-ordination in the different departments. In fact, since the changes of hours of duty and general methods of work caused so much trouble, it was felt that some steps were needed to check a similar individualism on the part of equally active and zealous young men who were to enter hospital service in succeeding years. After the interns for the coming year had been appointed I called them into my office for a friendly talk about their duties and without referring to the embarrassments of the past year I rehearsed the tale of the small boy who while on his way to school trudging through the deep snow was overtaken by a gentleman, in a fine turnout with a dashing span of horses, who kindly asked him to ride with him. The invitation was joyfully accepted and the boy was soon making fine progress when the idea occurred to him that the driver of the horses was not driving them properly. He knew that he could drive them much better and suggested a transfer of the reins to him in order that he might display his superior skill. To his great surprise and discomfort his host stopped his sleigh and gravely but decidedly Informed him that an invitation to ride did not carry with it the privilege of driving and that he might get out if he thought otherwise. I added that it gave the management of the hospital much pleasure to know that they were willing to ride with us during the coming year and I felt sure that such a journey together would be of great service to them and to the hospital, but I deemed it my duty to say frankly that the management of the hospital must do the driving and would continue to do so in future as it had in the past.

" The parable was promptly and correctly interpreted and there was never any difficulty in this respect with the Interns at the hospital. They have always been loyal and co-operative in measures calculated to add to the efficiency of the hospital."


ciated the value of the standards set by the superintendent, and they would, later on, view with amusement and pleasure the probationary period of those w^ho came after them. One and all soon came to realize that Dr. Hurd was their best friend. Many a time when one of the interns was in deep water — when illness occurred at home and he was called suddenly away, some one would quietly slip up beside him, place his hand on his shoulder and casually say " Can't I do something for you ? " " Don't you need some money ? " — many a man has had his load greatly lessened by this quiet, unostentatious friend.

A former student recently told me that toward the close of his second year he had reached the end of his resources and was preparing to leave the medical school and go to work.

Just after he had packed up and was arranging to leave that night Dr. Hurd met him in the hall and said, " By-theway, I have been wanting to ask you how your father's estate has turned out," and the young chap told him the facts. Dr. Hurd took him into his private office, told him he must under no circumstances give up his studies and insisted on furnishing him with sufficient funds to see him through to the end of the college year, and next year saw that it was possible for him to continue his studies. This young man is now one of the most promising investigators in this country. He told me that he knew of at least five or six other students who had also been helped out by the same genial superintendent.

Dr. Hurd did not hold himself aloof from the house staff, but after the evening meal often dropped into the reading room to have a chat with the men congregated there. Every now and then an informal invitation came to dine with Dr. Hurd, Mrs. Hurd and his daughters. These were red letter occasions — events never to be forgotten.

Every one of the men who was connected with the hospital during Dr. Hurd's time has a vivid recollection of that tall, slender figure passing silently down the corridors with his head bent slightly forward and apparently walking on air, his tread was so light. He rarely was +++++ CONTENTS to mount the stairs one step at a time, he invariably went up two at a time with his arms outstretched as if he contemplated an aerial flight.

Celebrated men who are closely associated with large numbers of young men are often given a special name as a mark of the esteem and affection in which they are held. When the men of the hospital staff of 20 years ago gather together and discuss old times they always refer to " Uncle Hank " with the warmest regard.

The visitor to the hospital — the one who comes to stay a few weeks or months — while impressed by the good work done in the various departments and by the original articles published by the hospital is more impressed by the spirit of cooperation and good fellowship that exists in the hospital and medical school. Dr. Hurd and the " Big Four " — Drs. Osier, Halsted, Kelly and Welch — have in large measure been responsible for this delightful atmosphere.

Many of the senior members of the hospital staff have been geniuses and it is a well-known fact that geniuses frequently become so engrossed in their individual subject that they are temporarily totally oblivious to the fact that other people have


Decembeh, 1919]


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to be considered and tliat these people have precisely the same rights and privileges as they. A tactful, gentle but firm tug emanating from the superintendent's office would awaken such an individual from his revery. It was tiiis absolute fairness on the part of Dr. Hurd that won for him the confidence and affection of the senior staff. They knew that they would always get a square deal.

Dr. Kurd's relations to the trustees have always been most pleasant. The trustees in their selection of the first superintendent looked the field over for the most able hospital executive they could find, and, when they had selected Dr. Hurd and he had accepted, they wisely abided by his mature judgment on all medical matters, and when he felt that it was wise for him to relinquish the exacting duties as superintendent of the hospital they insisted that he retain a connection with the institution and made him secretary of the Board of Trustees.

As we look back, it does seem a pity that Dr. Hurd did not have an assistant to relieve him of the many time-cousuming and incidental details connected with his office. It was not until the last few years of his life in the hospitiil that he was relieved of these by the appointment of the late Dr. Rupert Norton as assistant superintendent.

Dr. Hurd was an ideal superintendent. In addition to the satisfactory administration of the hospital he was deeply interested in the fundamental education of the medical student and of the nurse. He was continually stimulating the house officers to do their best and was ever mindful of the welfare of the patient. He was no bureaucrat, but a man who had the interest of all connected with him at heart.

ARTICLES PUBLISHED BY DR. HURD WHILE

SUPERINTENDENT OF THE JOHNS

HOPKINS HOSPITAL

Most men after caring for the many details of such a large institution as The Johns Hopkins Hospital and editing the Bulletin and Reports would find little or no time for other labors; not so with Dr. Hurd. With the indomitable energy which has always been so characteristic of him he kept right on with his literary work, each year writing one or more articles. His papers have in large measure been limited to four main subjects — psychiatry, hospital management, medical education and the education of the nurse.

In 1890 we find in the Maryland Medical Journal a paper on " Periodicity in Melancholia." Dr. Hurd in the same year was chairman of the Committee on Hospitals for the United States and made his report at the National Conference of Charities and Corrections held in Baltimore, May, 1890. Immediately after reading this report he addressed the assemblage on " The Relation of the General Hospital to the Medical Profession." In this address he clearly outlined what the general hospital should stand for. His ideas for that period were so advanced that I quote them.

The mission of the general hospital may be summarized to be: (1) To furnish metltcal treatment and proper nursing to the sick poor, and especially to the homeless and friendless; (2) to furnish similar treatment to those who are able and willing to


pay for It, and especially to those who are without families and homes; (3) to provide aseptic operating rooms where antiseptic surgery may be done with full confidence In Its results — this confidence being based upon the knowledge that all scientific requirements have been met by proper construction and thorough manasement; (4) to provide Instruction in and full demonstrations of the most approved methods of treatment of the sick to medical students and medical men; (5) to train capable, highminded, self-sacrificing women as nurses; and finally (6) to advance medical study and increase medical knowledge.

It is evident that the old-time idea that the hospital is designed for the destitute and homeless alone must be materially modified to meet the present exigencies of modern life. Many persons in moderate circumstances live comfortably as long as they can labor and produce, but, when ill, can procure skilled medical attendance and proper nursing only at the cost of future debt and a weary struggle to pay the obligations incurred. The expenses of living are constantly Increasing [1890] and the competition of modern life is intense, so that the majority of laboring men, of necessity, spend their earnings as they receive them, with little prospect of laying up a reserve for the traditional " rainy day." Hence, whether it be considered a good policy or not, provision must be made to care for many of tliese wageearners in public hospitals in the event of long continued or serious illness. The same is true of the more wealthy classes. Many of them cannot procure at home the constant medical care and the thorough nursing required, and certain portions of the public hospital must be set apart for them.

In the Transactions of the Medical and Chirurgical Faculty of Maryland for 1891 appears a memoir to the late Richard Gundry, a well-known asylum superintendent and later a member of the Faculty of the College of Physicians and Surgeons of Baltimore. Dr. Gundry was an old and valued friend of Dr. Hurd.

In the American Jo^umal of Insanity for 1892 Dr. Hurd published an article on " Journal Clubs." In this paper he spoke most enthusiastically of the value of such clubs and pointed out how they should be conducted :

For the success of a journal club it is essential:

1. That the work be made obligatory. It will not do to rely upon a zeal for study which may be cooled by other duties or by social obligations. The work should be made a part al the regular routine of the Institution, and should not be pushed aside by any trivial matter. The same rule which governs excuses from any regular professional duty should govern all absences from the journal club. No new man should be added to the staff who does not Intend to devote himself as loyally to this as to any other hospital or asylum duty. If outaiders are admitted — and I should say the more the better— they should come Into the work under the same conditions.

2. A definite hour which will be reasonably sure to be tree from Interruption should be selected, and rigidly adhered to. Such an hour ought not to be at the close of an exhausting day's work.

3. The proceedings should be Informal, and free discussion should be expected. The journal study should have the widest possible range. French, German and Italian journals should all bo laid under contribution.

4. The work should be thoroughly supervised by the superintendent or some person whom he may select. Whoever takes charge of the club ought specially to prepare himself to sum up each subject and to present Us practical bearings upon the better study or the better treatment of Insanity. This will often Involve


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study and extra exertion; but such mental effort is recreative, and a grateful change from routine work.

The advantages of a journal club are manifold. A few of them may be mentioned:

1. It develops a spirit of professional study among the members of the hospital or asylum staff. The spirit of investigation and inquiry is easily lost unless special efforts are made to develop it. This is especially true where routine duties constantly press themselves upon the attention. Unless a spirit of study and inquiry is sedulously cultivated among the younger members of a medical staff, the zeal for professional advancement speedily disappears.

2. It provides for the systematic acquisition of knowledge by a division of labor; and the least possible waste of time on the part of each person concerned. This is an age of cooperation in literary work. Library and subject catalogues are undertaken by associated laborers; and enterprises which would be impossible to an individual become practicable to the many. Witness the success of H. H. Bancroft's gigantic historical enterprises. The work which he has finished by the aid of collaborators would have consumed 400 years of individual effort, had such a length of years been granted to the head of the undertaking. It is in keeping with the spirit of modern study to economize time and effort by multiplying workers. Psychiatry and neurology are so vast that each student cannot read the good, the bad and the indifferent. The grain should be winnowed before it is gathered into storehouses.

3. It supplies a common field of study where the members of the staff may meet for contact of mind with mind. By means of it, individual tastes and aptitudes for study may be utilized for the common good. It gives a broader professional aspect to asylum work by bringing each member of the staff into relation with the whole field of psychiatry. It also effects the readier training and more speedy assimilation of new members of the staff. Young men come to asylum work fresh from medical schools and hospitals with a keen zest for scientific work. This should be utilized, and habits of regular study in lines of psychical research should be acquired as speedily as practicable. The journal club will also contribute materially to the unification of a staff which may have been brought together from different schools of medicine. This is too often neglected in large asylums.

In 1893 Dr. Hurd published an article on " Post-Febrile Insanity." After discussing the subject in detail he recorded three cases of this character that had occurred in The Johns Hopkins Hospital, one after laparotomy for removal of diseased ovaries, one following pneumonia and a third during convalescence from typhoid fever.

In 1893 we find an article entitled " The Relation of Hospitals to Medical Education." This appeared in the Boston Medical and Surgical Journal, csxis, p. 1-41.

In the medical writings of a physician one rarely has the opportunity of catching a glimpse of the personal charm or of the depth of sympathy of the writer. On October 14, 1894, a meeting was held in memory of the late George Huntington Williams, professor of geology in The Johns Hopkins University. Dr. Hurd had known him since he was a boy and was closely related to him by family ties. Dr. Kurd's tribute to his deceased friend brought out ^dvidly that personal charm and sympathy which has always so endeared him to those with whom he has been closely associated.

In 1894 Dr. Hurd published a lengthy article on " Some Mental Disorders of Childhood and Youth," and in the Bul


letin of the Ameri-can Academy of Medicine, 1895-6, an article on " Laboratories and Hospital Work."

In the Maryland Medical Journal for 1896 we find a second article on " Paranoia."

In the American Journal of Insanity for 1895-6, p. 477, Dr. Hurd says :

It has been the custom of the Journal of Insanity during more than half a century to publish full details of new Institutions erected for the better care and treatment of the insane; hence the recent opening of the new McLean Hospital at Waverly, near Boston, calls for more than a passing notice.

Dr. Hurd then describes in a most interesting manner this large institution for the care of the insane. He also gives illustrations and plans of the various buildings. The paper is a most complete one, occupying 26 pages.

On February 17, 1897, Dr. Hurd gave an address on " Hospital Organization and Management " before the Training School for Nurses at the hospital of the University of Pennsylvania. This was published in the University Medical Magazine, ix, p. 488. It contains much of interest and I quote some of the remarks made by Dr. Hurd on that occasion.

I cannot resist the temptation to say a word respecting the improvements which have been made in hospital construction during the past 30 years. These improvements I believe to be largely due to the experience of the Crimean War in Europe and of the Civil War in America. The first gave us training schools for nurses and trained nurses, and the latter improved hospital construction. These waves of progress from the East and West crossed the ocean in turn and brought to the whole world better facilities for the care of the sick and better methods of treatment.

The most noteworthy improvement in hospital construction has been in the direction of better sites for buildings, which are no longer crowded into narrow, dingy streets with unpleasant surroundings, and amidst insalubrious and unsanitary conditions, but are placed in open squares. In commanding situations, where sunlight and fresh air can freely come upon their joyous and health-giving missions.

The buildings themselves are more scattered, and sickness and suffering are diluted by differentiation and segregation rather than concentrated by piling one ward upon another. Hospital wards also have been more conveniently arranged to do their appointed work, and have had comforts and conveniences In the way of service-rooms, tea-kitchens, rooms for the dangerously ill and dying, and the like, which have contributed immeasurably to the comfort of the sick. Special efforts have been made in the construction of wards to provide for heating, ventilation, the isolation of infectious, harmful, or offensive patients, and for all sanitary needs. Laboratories for the investigation of disease have also been built and fitted with instruments of precision for the more accurate and scientific study of disease processes. Operating rooms have been planned and erected at lavish expense to carry out as strictly as in a laboratory all the requirements of antiseptic surgery. Disinfecting plants have been joined to every hospital to destroy the germs of disease and to prevent the transmission of infection from one patient to another.

It is related that a surgeon-general of the United States Army, now deceased, once stated that it was no part of the work of the army medical corps to study disease or to engage in any work of research, but rather to cure sick soldiers, forgetting that the cure of sick soldiers is more promoted by the spirit which leads to the study of disease than by the narrow view that the indi


December, 1919]


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vidual soldier at morning sick-call alone should engross the attention of the army surgeon.

The best method of keeping the torch of knowledge lighted is to pass it along from hand to hand. Hence I have little sympathy with those who deplore the use of hospital wards as means of Instruction. They should be used for the training of nurses and for the instruction of medical students, and by their very use for these purposes their efficiency for the cure of disease will be augmented.

In a well-ordered hospital, as in a well-ordered state, there should be an ultimate and final authority, a proper subdivision of duty, and a tliorougli adjustment of all portions of a complex and often cumbrous mechanism to its special uses. It is the part of a Board of Trustees to establish the policy of the hospital, to give an impetus fo the machinery, to oil and readjust It from time to time, to watch its operations, and to scrutinize its results.

A friend of mine used to say that responsibility without power is weakness. Responsibility and authority must go hand in hand.

If I were asked to indicate the best machinery for hospital government. I should say a Board of Trustees to be sovereign and responsible for the whole institution, a medical board to advise the trustees in all medical matters, a chief executive officer to be known as director, secretary, or superintendent, whose duty It should be to coordinate and supervise all qther departments, a purveyor to look after food-supplies, a matron to supervise the household and a superintendent of nurses to have charge of the training school and the- nurses. Under these heads of departments there should be subordinate cliiefs of departments, like the engineer, chief cook, laundry man. diet-school teacher, storekeeper and the like.

A word as to discipline. From the character of the work of a hospital and the necessity of the development of kindly instincts and humane methods of thought and action among all employes. It is unwise to establish and enforce a semi-military discipline or even one which would be practicable or advisable In a railway, a large factory, a corporation, or other business enterprise. There should be a rigid discipline and a strict accountability for the performance or neglect of duty, hut this discipline should be sustaining in its nature and calculated to develop tlie individual. Through Its kindly control the tlioughtless or untrained nurse or employs should be lead to a higher level of conduct and feeling until her better nature becomes the governing power. To many hospital employes the life becomes truly educational, and the officer who does not strive to make it so fails of an important duty. A wisely directed enthusiasm, a kindlinp of the moral nature, a glimpse of a higher, broader, and more satisfying life can thus be given to all wlio have to do with the sick in the hospitals. Hospital work, when done with loving, eager enthusiasm, blesses the patient and the nurse alike. It should be the aim of all to do charitable work in a charitable, kindly way. 1 have little patience with those who look upon the medical treatment of the sick In hospitals as a business matter only, and the nursing of the sick as an avocation, a trade, a preparation for getting a living, a matter of hours on duty to be endured as patiently as possible for the relief which is afforded by getting through with them. Vnless the care of the sick can bo glorified by sympathy, kindly feeling, enthusiasm and personal Interest It becomes drudgery and heartless routine. Hence the necessity of developing the best Instincts of all wlio have to do with the sick by a sustaining, fostering and kind discipline which regards the individual and not the mass.

Much of the alleged lack of sympathy sometimes complained of on the part of the hospital physicians, nurses and employes, I believe to be due to overwork.

In 1897 Dr. Hurd and Dr. John B. Chapin, physician-inchicf and superintendent of the department for the insane of


the Pennsxlvimia Hospital of Phihidelphia, Pa., were asked by the " Joint Select Committee to Investigate the Charities and lleformatory Institutions in the District of Columi)ia " to maJie a report on the hospitals of the District of Columbia. This they did and their findings were embodied in a paper presented to the committee on November 24, 1897. This report embraced a full description of the Asylum and Almshouse Hospital: the Children's llospitjil; tiie Columbia Hospital for Women and Lying-in Asylum ; the Central Dispensary and Kmergency Hospital; the Freedman's Hospital; the Garfield ilcmorial Hospital; the National Ilomieopathic Hospital and the Home for Incurables. The report is an exhaustive one. It points out the excellent features in each institution, draws attention to the weak spots, and makes numerous admirable recdnimcndations looking to the more systematic and the better handling of patients in the District of Columbia.

In the Albany Mfdiriil Annuls for February, 1898, we find an article entitled " The Medical Service of Hospitals," and in the Maryland Medical diiurnal for 1898-9 Dr. Hurd considers " The Non-Medical Treatment of Epilepsy."

At a meeting of the Gynecological and Obstetrical Society of Baltimore, December 13, 1898, Dr. Hurd gave a paper on " Post-Operative Insanities and Undetected Tendencies to Mentiil Disease." This article appeared in the Amrricun Journal of Olisfelrics, Vol. xxxix, 1899. It is interesting to read Dr. Hurd's views on the subject. They are of much importance to the laity as well as to the surgeon.

Post-operative insanity may be considered a complex affair, comprising symptoms which may differ In cause, manifestation, course and termination. There would seem. In fact, to be little ground for the use of the term, were It not for the existence of infectious processes accompanied by delirium or prolonged depression. In other words, if an operation is free from septic infection in a case destitute of any tendency to insanity, tliere can be no ground to think that tlie operation ;>('»• sr produces mental disease or that the insanity is post-operative In the sense that the operation bears a causative relation to the insanity. There are disturbing factors, it is true, in connection with surgical operations, which may be competent to produce an Insanity, and I will briefly refer to some of them; but the insanity wlilch they produce can only he considered post-operative in point of sequence rather than of causation. It is unquestionable that the prolonged use of ana-stlietlcs like ether, chloroform, or nitrous oxide has produced excitement, delirium, mental confusion, and often prolonged mental alienation without the accompaniment of any operation whatever. Instances are also not at all unr-ommon wliore. following an operation, excitement has followed the local application of Iodoform, the instillation of atropia or the administration of the salicylate of soda, and where, notwithstanding the surgical operation, the symptoms of Insanity subsided wholly upon the withdrawal of the intoxicating agent.

Similarly, we may have mental symptoms following an operation clearly ascrlbablo to shock, loss of blood, excessive exhaustion from the fatigue of a constrained and unnatural position, long-continued vomiting from an anapsthetlc. or abstinence from food owing to anorexia. There may also be a poisoning of the blood and consequent interference with proper cerebration from defective action of the kidneys, due wholly to the withdrawal of water by the mouth lest it may excite vomiting after an abdominal operation; or the ang-sthetlc may have caused a transitory neph


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ritis with accompanying loss of kidney function. These and similar causes which are not surgical in character, but are necessarily an accompaniment of a surgical operation may produce insanity which cannot in any manner be differentiated from actual post-operative insanity due to infection.

In 1899 Dr. Hurd was president of the Medical Psychological Association. On that occasion he took as the theme for his address " The Teaching of Psychiatry." That his interest in the care of the insane never flagged is clearly shown by the fact that from the first meeting of this association in 1879 up to the time of his presidency in 1899 he had missed but two annual meetings.

In this address he paid a touching tribute to an old friend : While engaged in writing this address the crushing news comes of the sudden death of Dr. Godding. It is difficult to realize that our noble-hearted and cultivated associate has gone from earth. He had a poet's soul, the charity of a saint and the heart of a child. He loved poetry, literature, art and music; above all, he loved his fellow-men.

In 1900 Dr. Hurd published a splendid article entitled " Hospitals, Dispensaries and Nursing." At the end of tliis paper he gave a list of the principal hospitals of the United States that had been established during the last century.

In the Bulletin of the Iowa State Institution for 1901 appears a paper by Dr. Hurd entitled " Reception Hospitals for Cases of Acute Insanity."

On November 21, 1901, Dr. Hurd delivered an address on " Psychiatry in the Twentieth Century," at the opening of an additional building at the New Jersey State Hospital at Morris Plains. After paying a tribute to the late Miss Dorothea L. Dix, whose work had been such a benefit to New Jersey as well as to the entire country, he sketched the gradual changes that had taken place in the treatment of the insane in the United States. He then pointed out where improvements might with profit be made in the handling of mental cases. The pith of his remarks is contained in his concluding paragraph :

The future of psychiatry in America is bright with hope. The era of foundation and construction is nearly over; institutions have been evolved, developed and perfected; pathological institutes have been established and liberally equipped and supported; trained men with broad learning and technical knowledge have been raised up for special study, and an earnest spirit of investigation has been developed. We are on the threshold of new discoveries and important improvements in the treatment of the insane.

In 1908 Dr. Hurd addressed the graduating class of the training school of the Garfield Hospital at Washington, D. C. He took as his theme " The Educated Nurse and Her Future Work." This paper was later published by the Friedenwald Press in Baltimore. It should be carefully read by every undergraduate and graduate nurse. It will also give to the lay reader a very clear idea of what real nursing means — it portrays in no uncertain terms how much the medical profession owes to the trained nurse.

Dr. Hurd gave a charming address on "The Duty and Responsibility of the University in Medical Education," at the gr-aduating exercises in the Yale Medical School on June


23, 1903. After briefly considering the subject of his discourse he said :

To discuss an educational question before university men suggests the appropriateness of the quotation from Confucius with which an eminent scientist once prefaced an address made under similar circumstances: "Avoid the appearance of evil: do not stoop to tie your shoe in your neighbor's melon patch." A member of the teaching staff of one of the newest schools of medicine ought to display a degree of modesty in the presence of medical teachers whose thoughts and activities have been molded by the traditions of one of the oldest medical schools in the United States, the sixth in point of time of establishment, and should hesitate above all to urge the duty and responsibility of a university in medical education.

Perhaps I may also plead in mitigation of my indiscretion a degree of hereditary relationship to Yale in the fact that my father graduated here in medicine in 18.30; my grandfather was a student about 1795, but did not graduate; my great-grandfather graduated in 1778; and my great-great-grandfather in 1739, and may speak as one whose speech can be tolerated because of kin, albeit remote.

In his remarks directed especially to the graduating class he said :

In your chosen profession be students and productive workers always. Do not look for speedy results and do not be discouraged if the secrets of nature are not wrested from her jealous grasp without a severe struggle. The foundations of our art are broad and deep, and the superstructure should be erected slowly and with care, by accurate observation of disease and painstaking deductions. In your life as physicians be prepared for trials, disappointments and adversities. Take for your motto the words written by Sir Thomas Browne, that eminent physician, more than two centuries ago: " In this virtuous voyage of thy life hull not about like the Ark without the use of Rudder, Mast or Sail and bound for no Port. Let not disappointment cause Despondency nor difficulty Despair. Tliink not that you are sailing from Lima to Manillia, when you may fasten up the Rudder and sleep before the Wind; but expect rough Seas, Flaws, and contrary Blasts; and 'tis well if by many cross Tacks and Veerings you arrive at the Port; for we sleep in Lyons Skins in our Progress unto Virtue and we slide not but climb unto it."

Have a purpose and carry it out with fortitude. There can be no more absorbing or inspiring career than is afforded by the study of medicine at the present time. The scaffolding reared by countless workers during thousands of years around the fair temple of medicine, necessary for the building doubtless, but concealing its proportions and too often defacing its beauties, has been swept away, and for the first time it is permitted to us to know something of the dimensions and architectural possibilities of the completed edifice. Can there be a nobler aspiration for any man than to assist in the completion of the work of transforming the ancient art of healing into the science of medicine?

In 1902 Dr. Hurd was the chairman of the Section on Neurology and Psychiatry of the Medical and Chirurgical Faculty of Maryland. At a meeting of the section held November 14, 1903, he took for his subject "The Future Policy of Maryland in the Care of Her Insane." When in Michigan he did not hesitate to tell the state Just what her duty was in the care of the insane. In Baltimore he spoke out in the same fearless manner. He had carefully studied the situation in Baltimore and in the various counties. Maryland was far behind the times and at the meeting of the Medical


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and Chirurgical Faculty in 1897 a symposium on the state care of the insane had been arranged. The papers read on that occasion brought forth much resentment on tlie part of the state authorities.

Dr. Hurd in his address in 1902 pointed out what had been accomplished in the interim, but also stated in no uncertain terms that in many places throughout tlie state the conditions were still deplorable. He did not generalize as is so frequently done, but was specific, mentioning the institutions at fault. He then indicated how these appalling conditions should be rectified.

A man who has the nerve and patriotism to come out boldly and draw attention to the glaring faults in his own state and at the same time to indicate the means by which these conditions can be ameliorated is without a doubt a most valuable man in his community — he is a real citizen.

Dr. Hurd's concluding paragraph addressed to the medical profession was peculiarly apt to the occasion :

Those who have read the recently published life of Pasteur (every physician ought to read it) must have been impressed by the fact that in the mind and life of this wonderful man scientific knowledge was Invariably regarded as the hand-maiden of humanity. In the height of Pasteur's interest in the study of ferments, which opened the way to our present antiseptic surgical methods, he turned aside from his chosen work for five years to study the diseases of silk-worms, because of the sufferings of the people In certain portions of France consequent upon the destruction of the silk industry. His subsequent studies In puerperal fever, charbon. chicken cholera, plague and hydrophobia were Inspired by a similar notion ; to use his own words, " To give the heart its share In the progress of science." We may not be able to imitate Pasteur in scientific achievement and In broad and vivifying generalization from isolated scientific facts, but we can Imitate his broad humanity and his desire to ameliorate the lot of the unfortunate. We can at present do no greater service to humanity and the commonwealth than to use our professional Influence and personal effort to promote the hospital treatment of acute cases of insanity and appropriate state care for the insane poor of the chronic class.

All interested in the care of the insane should read this article in full. It appeared in the Maryland Medknl Journal, February, 1903.

Thanks to Dr. Hurd and his colleagues the disgraceful condition that then existed has long since been corrected. The State Lunacy Commission, then more of an advisory board, now has ample authority and at the present time Dr. Hurd is the most valuable member of the commission.

In 1904 Dr. Hurd gave the address to the graduating class of the Training School for Nurses at the Albany Hospital. He took as his theme "Is Nursing a Profession?" This paper was published in the Albany Medi<-al Anncds, September, 1904.

In his address at the graduating exercises of the Lakeside Hospital School for Nurses in Cleveland, in 1906, his paper was entitled " Shall Training .Schools for Nurses be Endowed ? " This is a theme that is engrossing the attention of more than one institution.

In 1906 Dr. Hurd read a paper entitled " The Medical Organization of General Hospitals." before the eighth annual


meeting of the Association of Hospital Superintendents. This article was published in the National Hospital Pecord in October of that year. At the annual meeting of the Canadian Hospital Association, held in 1908, Dr. Hurd spoke on " The Proper Length of the Period of Training for Nurses." This paper was published in the American. Journal of Nursing in June, 1908.

In May, 1908, Dr. Hurd gave a paper on '• Psychiatry as a Part of Preventive Medicine." This was published in the American Journal of Inmnity, 1908-9.

The object of preventive medicine being to lessen the burdens of mankind by obviating preventable diseases. It is deemed appropriate at this time to inquire in what manner the experience of those who are familiar with the problems of psychiatry may be utilized to assist in this good work. It needs no elaborate demonstration to show the evils of insanity and the heavy public and private burdens which it entails upon every community. Next to alcoholism it is probably the most potent cause of pauperism and dependence.

The article is a most instructive and important one. The conclusions are particularly interesting:

The methods of rendering the teachings of psychiatry more effective to prevent disease should be:

1. To instruct children in the schools the art of healthy and useful living. Teaching should be more thorough and not restricted to fit one to get on in the world, but rather to inculcate Ideals which will give him a conception of the prime importance of self-control and moral rectitude. It should also include a knowledge of the dangers of immorality and Intemperance.

2. To use the newspapers and the special reports of ofllcers of institutions for the Insane and defective classes, to scatter broad cast a knowledge of the laws of bodily and mental healtli, and the best means of preventing the development of mental disorders.

3. To give a better recognition of psychiatry in the curriculum of every medical school, so that physicians may become familiar with the diagnosis and treatment of insanity. To this end psychopathic hospitals should be established to give clinical instruction, so that the family physician may recognize insanity, may be able to scrutinize carefully the mental condition of neurotic children and may give wise advice upon all educational problems.

In tlie Nursing Mirror for 1908-9, Dr. Hurd published an important paper on " State Registration and the Education of Nurses in the United States."

On November 30, 1910, a Health Conference was held in Pittsburgh. On that occasion Dr. Hurd gave a short but most practical paper on " Cooperation Among Hospitals." In this address he emphasized the great value of cooperation. He said :

Hospitals are often established by too zealous friends for these medical men, or established hospitals fall under the dominion of two rivals In the profession. Under the circumstances, cottperatlon between the two hospitals becomes difficult and often impossible. I know many cities where such bitter feelings have In the past destroyed all hope of cooperation and where the friends of able physicians or surgeons formed two armed camps. Even the ladies become enlisted and fight under one or the other banner. I am glad to say, however, that the days of bitter rivalry between hospitals are passing away. The whole world is becoming more tolerant and the odium mrdi'um Is following the course of the odium Iheologicum. May Its departure be as speedy.


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In referring to the purchase of hospital supplies he mentioned a method that has given splendid results :

A very obvious form of cooperation is for all the hospitals of the city to adopt a common standard of ordinary every-day supplies and to arrange for their purchase through a common purchasing agent.

In the city of New York recently also an attempt has been made with very gratifying success to establish a hospital bureau, which is a central supply bureau under a purchasing agent, whose duty it is to make contracts for gauzes, cottons, surgical instruments, rubber goods, furniture, fixtures, bedding, blankets, linen and the like. These supplies are purchased in large quantities according to a definite standard of excellence and at the lowest market prices. The saving of expense in the cost of supplies is considerable, but the saving to the hospitals in the payment of salaries to the officers to purchase is probably equally great. The same is true of breadstuffs, fuel, machinery, etc. Every department of the New York hospitals has profited by the central bureau.

Hospital officers often do good in secret and the community at large does not appreciate how much is done by the unpaid and unselfish men and women who are managing our great hospitals. The good work they do should be better known and this can only be known by a wide publication of their work. They should not put their candle under a bushel, but on a candlestick, that all may see and cooperate in helping on their good work. There are hundreds of men and women who long to do good, but who need to be set at work. Tell the public what you are doing and do not hesitate to ask for substantial support.

At the graduating exercises of the Nurses' Training School of The Johns Hopkins Hospital on May 19, 1910, Dr. Hurd gave a delightful address on " Florence Nightingale — a Force in Medicine." He said :

I desire rather to speak of her career as a constructive philanthropist, as a sanitarian and as an organizer of nursing service in city and country, of her statesmanlike grasp of the problems of army nursing and of the influence of her life work upon the medicine and surgery of the past half century.

In the course of his address he refers to the visits the late Francis T. King, the late Mrs. Eobb, and Miss Nutting had with Miss Nightingale. Dr. Hurd's address was most interesting from beginning to end. I shall quote a few paragraphs.

It is my task this afternoon to tell you in what manner she has influenced the wonderful progress of medicine during the past 50 years.

1. First, and probably to a larger degree, she has wrought for medical progress through her reform in nursing. She found it an occupation and has made it a calling. From the very beginning of her career she insisted that any woman who engaged in nursing should qualify herself as thoroughly for it as a man qualifies himself for any calling in which he expects to succeed. She believed that the object of training was to teach not only what was to be done, but how to do it. The physician or surgeon should order whatever needs to be done for the patient's care, but the training of the nurse should teach her how to do it to his order. Training, also, should teach the symptoms of disease, so that the nurse may know what certain symptoms indicate about any disease and whether the patient is worse or better when the symjptoms change. Telling the nurse what to do is not enough and cannot be enough to make her work perfect.

2. In all her writings Miss Nightingale has constantly dwelt upon the value of sanitation and obedience to the laws of health. She speaks with endless iteration of the need of pure air, pure


water, efficient drainage, perfect cleanliness and sun-light in the sick room

Her books in fact have been an immense influence in promoting the sanitation of the home and of the public and private hospital. They furnished principles for the guidance of those who would work out their own plans, when principles had once been enunciated and detailed and specific plans for those to follow, who cannot plan for themselves. Her suggestions and directions for the care of patients in their own homes are invaluable and have never been equaled by any other writer. She cries aloud and spares not for good sanitation and for the care of the patient. She may not always be in accord with present theories of the bacterial origin of many diseases and may err in ascribing measles and other infectious diseases to a lack of sanitation, but her main thesis that bad air and all dirt are dangerous is unassailable

It may be called to mind that at this hospital its founder, Johns Hopkins, made provision equally for the care of the sick, the instruction of medical students and the training of nurses, each duty being equally obligatory

3. One of Florence Nightingale's most important contributions to medical progress is to be found in her " Notes on Matters Affecting the Health Efficiency and Hospital Administration of the British Army, Founded Chiefly on Experiences of the Late War." This work in my opinion constitutes one of the most valuable contributions ever made to hospital organization and administration in time of war. Had the conclusions which she reached been heeded in the Civil War in America or in the Boer War in South Africa or in the Spanish-American War, hundreds of thousands of lives might have been saved and millions of people might not have mourned over a useless and needless sacriflce of the flower of their young men. Her ability to analyze dry statistics and army returns and her rare power to draw correct conclusions from them seems remarkable.

Probably one of the most interesting articles that Dr. Hurd ever penned was entitled " The Site of the Johns Hopkins Hospital." This paper was read at The Johns Hopkins Hospital Historical Club in December, 1910, and published in the Johns Hopkins Nurses Alumna Magazine, April, 1911.

A plat of the site of The Johns Hopkins Hospital which was prepared to facilitate the sale of the property to the late Johns Hopkins has recently come to light among the records of the hospital and an examination of the survey has suggested to me that it will be interesting to all persons connected with the hospital to see it and to learn something of its previous history.

The site of the hospital has been used for hospital purposes for somewhat over 100 years. A general hospital was established on this site in 1797 or in the early part of 1798. In an old report it is spoken of as a beautiful site upon a hill, about a mile from the city of Baltimore. When 1 came here 21 years ago, the town extended but a little to the east of the hospital and most of the neighboring streets have been opened since the present site was selected.

Dr. Hurd then sketches the early history of Baltimore in a most fascinating way and refers to the epidemic of yellow fever that invaded Baltimore. In 1808 the old hospital was leased to a firm of physicians, Drs. Sm}i;h and Mackenzie. In 1834 it was used as a lunatic asylum, later called The Maryland Hospital for the Insane.

From Dr. Hurd's paper we learn that at one time the town of Joppa on the Gunpowder Eiver was larger than Baltimore and that from this town there was a brisk trade in tobacco, many ships sailing from Joppa to England. The old Joppa


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Road ran from Joppa through Baltimore to Auuapolis. It crossed the present hospital ground a few feet north of the present administration t)uilding. A house that faced on the Joppa Road existed until a few weeks ago (June, 1919) and its front foundation can still be seen on the south side of Monument Street between Bond and Caroline streets. It was located direc'tly behind the moving picture parlor frequented b)' colored people. This building was clearly visible from Monument Street when the picture parlor was beijig constructed. Judging from the front of the house the Joppa Road crossed the present Monument Street, going northward and westward between Bond and Caroline streets. In 1836 land was bought bv the hospital on the north of tlie Joppa Road and this once busy main thoroughfare was closed.

Johns Hopkins died the day before Christmas, 1S73. and early In the following February the trustees organized for the first time as a board and arranged to take over what property was

ready for them They made an effort to get competitive

plans, but finally gave it up and Dr. J. S. Billings, who is now at the head of the New York Public Library, went abroad with a set of plans which he submitted to all persons who were skilled In hospital construction. In 1874 the original buildings had been torn down, but it was not until 1S76 that Dr. Billings returned with his plans

The buildings were begun in 1877, but were erected no faster than the trustees had the money to pay for them. They built them wholly out of income and when money was not available to continue the work they ceased building operations until more money came Into the treasury. The result was a delay of full 12 years before the buildings were completed. The trustees were bitterly attacked by the newspapers, especially in the columns where the letters of the people appear, but they went on in their own way and when the buildings were completed and opened in 1889, they had been constructed wholly out of income and the capital fund of the hospital had been increased more than $100.000 during the process of building. Many hospitals are built after a different plan and must contend with poverty and debt for many years. The trustees of The Johns Hopkins Hospital were more sensible. They knew that the hosi)ital was to last for a long time and that there was no reason why they should cripple It for all time In order that It might be opened a few years sooner.

Dr. Ilurd then gave a short account of Johns Hopkins's life. Accompanying the article is a picture of the old Maryland Hospital ; the real estate plat of the present hospital area showing the position of the original Maryland Hosjiital on this ground and the location of the Joppa Road. The last picture shows the site of the present liospital — a broad fence around it, a tent on the site, and many men and horses, ready to begin the excavation for the foundation of Tlie Joims Hopkins Hospital. Every one interested in the institution will be delighted witli Dr. llurd's article.

DR. IirRD. SKCRHTARY OF TTIK BO.\RI) OF

TRF.STFKS OF TIIF JOHNS

IIOPKIXS HOSPITAL

Shortly after Dr. Hurd relinquished his duties as su|)erin tendent of the hosjiital lie moved "across town" to 1023

St Paul Street where he has since resided. His secretarial

duties have occupied much of his time, but he has nevertheless


always somehow made time for his literary work. The first article from his pen after he became secretary was " Early Days of The Jolms Hojikins Hospital and Medical School." \ perusal of this splendid historical sketch gives one a graphic jncture of the hospital in its formative days. To one who was on the scene in those delightful days it brings back priceless memories. In order that the reader may recall some of the milestones I will quote sections of this sketch :

The late Johns Hopkins procured an act of incorporation of his future hospital from the Maryland Legislature in 1867 and named 12 able men, nearly all of them intimate and trusted friends or relatives, to act as incorporators and trustees. Hoyond deeding to this Board of Trustees a site for the institution, which consisted of the buildings and grounds of the old Maryland Hospital for the Insane, founded in 1797, he had taken no further steps towards Its erection at the time of his death in

December, 1873 The actual work of construction did not

begin until 1877, and the hospital was not opened until 1889.

The medical school, for wliich Mr. Hopkins made provision in his will, when he made his hoquost to the university, was not opened until 1893, 20 years subsequent to his death. These delays and disappointments were due to financial difficulties, for which the trustees of the university were in no way responsible

In August, 1889, when I came to Baltimore to assume charge of the hospital as superintendent, I found four wards In commission, ri;.. a pay ward for men and women, two public wards tor men and a public ward for women. An outpatient department liad also been opened under the charge of Dr. Halsted. The pathological laboratory, under the charge of Dr. Welch with a corps of assistants, had been operated as a branch of tlio university since 1886. although recently under the joint control of the hospital and the university, owing to the financial difficulties wliich hampered the university at that time.

Dr. W. H. Welch was in the full tide of his brilliant career as a teacher, and had attracted to Baltimore such men as the late Christian A. Herter and W. S. Halsted. of New York, W. T. Councilman, now of Harvard, A. C. Abbott now of the University of Pennsylvania, F. P. Mall, later at Clark University and the University of Chicago, and many others of equal prominence, who were all deeply engaged in medical research. Possessing encyclopedic knowledge, unusual geniality and largemindedness in his relations with other men, and the gift of exposition, so essential to the true teacher, he has been an active factor In the university and hospital for many years. He is above all an investigator with a judicial cast of mind and with the ability to stimulate his associates and students to productive work, and the greater ability to exercise a wise control over them.

Dr. W. S. Halsted was at the head of the surgical work of the infant hospital which he had organized in accordance with the newer teachings of Lord Lister, along the line of a better technique based upon the teachings of bacteriology. He possesses the faculty of constructive work not alone in the principles of surgery, but also in the details and minutla? of surgical technique. He Is eminently thorough in all that he undertakes to do and whatever principles of surgery lie has established have been firmly founded upon experience as a surgeon, diligence as an Investigator and experimental studies upon the lower animals. He was then beginning to develop wliat was to become during the next 20 years a school of surgery, not only In what was accomplished, but also in the influence which he exerted upon new men and the training which they received.

Dr. William Osier h.ul lately come from Philadelphia aa physician-ln-chief of the hospital and had already attracted mucli


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attention by reason of his unique personality, his versatility In medicine and his literary facility. He was a master of English, deeply versed in the history of medicine, an expert pathologist, a well-trained diagnostician, filled with knowledge of practical medicine, and a remarkable clinical teacher. He had unwearied industry and a wonderful ability to utilize his gifts to accomplish beneficial results for medical science and for the world. His call to Oxford in 1905 was a serious blow to the hospital.

It is remarkable that three such men as Welch, Halsted and Osier should have been found to launch the hospital on its successful career, each possessing different powers and yet all working harmoniously to supplement the activities of each other.

In October Dr. H. A. Kelly, came from Philadelphia to assume his duties as gynecologist-in-chief of the hospital, and established a public and private ward for surgical diseases of women. He was and is a brilliant operator whose mechanical deftness and manual skill have been the admiration, envy and despair of all who have followed his work in the operating room. His ability to devise new operations and to meet emergencies in surgery is phenomenal. In addition to an extensive surgical work he early became interested in the preparation of surgical books which were clearly written and beautifully illustrated by the best medical artists procurable in this country or Europe. His interest in art as applied to medicine and surgery has been an Important contribution to the profession and has influenced widely medical literature in America. Equally with Osier, Welch and Halsted, he has trained students to do excellent work as operators and teachers throughout the country.

All of these leaders were young men. the eldest not being more than 40 years of age and many of them much younger. Gray hairs thus far have not adorned the heads of most of those who were interested in the development of the hospital, although it must be acknowledged that some might have grown gray if they had retained their original covering. All were wisely Interested in the public welfare and used their influence in the city, state and country at large to improve sanitation, to give better care to the poor, earlier help to the tuberculous and to institute healthier conditions of living eenerally

In the Journal of the American Medical Association, 1912, Vol. lix, p. 1677, Dr. Hurd published a paper on "The Proper Division of the Services of the Hospital."

In 1912 he was president of the fourteenth annual meeting of the American Hospital Association. He took for his theme on this occasion " Hospital Problems." This address appeared in the International Hospital Record for that year.

In the Bulletin of the Medical and Chirurgical Faculty of Maryland for 1912-3 he published an interesting paper entitled " Extracts from the Laws of Maryland and Virginia Regarding the Early Care of the Insane."

Dr. Hurd's paper " Three-Quarters of a Century of Institutional Care of the Insane in the United States " appeared in the American Journal of Insanity, 1912-3, Vol. Ixix, p. 469. He divided the care of the insane during this period into four stages :

1. The period of neglect.

2. The era of awakening.

3. The period of state care of the insane.

4. The period of scientific care.

After considering each of these stages in detail he took up : Laws for commitment of the insane in every state ; the criminal insane ; detention hospitals ; hospitals for the chronic insane ; after-care of the insane; architectural changes and improve


ments ; scientific work ; biographies, et<:'. The article is a very instructive one even for those who know little about psychiatry.

In the Modern Hospital for 1913 we find two articles from Dr. Hurd's pen, " The Hospital as a Factor in Modern Society " and " Hospitals and the Eeform of Medical Teaching."

During the year 1914 Dr. Hurd contributed eight papers to the literature, " Some of the Writings of the Late Eugene Fauntleroy Cordell " ; " Relation of the General Hospital to the Training School for Nurses"; "Hospital Medical Statistics " ; " The Small Hospital a Factor in Medical Education"; "Mental Cases in General Hospitals"; "The Human Side of Florence Nightingale " ; " Rupert Norton " ; " State Registration of Nurses."

Dr. Cordell was the medical historian of the University of Maryland and had published a most valuable history of medicine in Maryland. His book is a very interesting one and will long remain the source of information relative to medical events in this state.

Dr. Rupert Norton had been associated wUh Dr. Hurd for several years. He remained assistant superintendent when Dr. Winford H. Smith succeeded Dr. Hurd. In 1914 Dr. Norton developed typhoid fever and died.

Dr. Hurd in his article paid a well-deserved tribute to his luimer associate.

A reference to Dr. Hurd's bibliography shows that he published no less tlian eight papers in 1915. Among them were " The Early Years of The Johns Hopkins Hospital " ; " FortyFive Years Ago and Now "; " The Treatment of Mental Cases in General Hospitals " ; " The General Government of State Hospitals."

In 1916 Dr. Hurd in addition to a tremendous amount of editorial work he had tmder way published sis papers. They were " Some Sources of Friction in the Management of Hospitals"; "Another Source of Friction in Hospital Administration"; "Who Shall Manage the Training School for Nurses?"; "The Advantages of the Budget System"; " Nathan Smith, Nathan R. Smith, and Alan P. Smith — a Medical Family "; " Need of Segregation of Imbecile Women."

On March 12, 1917, Dr. Hurd read a paper on " Johns Hopkins and Some of His Contemporaries " before the Historical Club. This was published in the July number of the Bulletin for the same year. In his introductory remarks Dr. Hurd says :

The primary object of our Historical Club, when it was founded, was the study of medical history. To-night I have thought it wise to speak of the life of one who was not directly connected with the history of medicine, but who, because of the influence which the university and hospital he established have had upon medical education in this country, seems closely allied to medicine. I have also an additional reason for speaking briefly of his personal history before this club, because as the years pass I find that the career of Johns Hopkins becomes less familiar to the present generation, and there is danger that he may become a mythical personality. This is my reason for speaking of his origin and personal characteristics and giving some account of his career in Baltimore. I also wish to speak of his personal interest


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in the hospital and of the men he selected to carry out the enterprises.

Dr. llurd then briefly sketched the life of the founder of The Johns Hopkins Hospital and also gave a short account of the original trustees of the hospital.

With a record of so much work done after resigning the superintendency the reader will naturally ask why Dr. Hurd did not remain at the helm. Physically, mentally and in every way he was still in his heyday, but he felt that he had borne the heat of the day long enough and that the running of the hospital should now be placed in younger hands. One of the trustees of the hospital who spent several weeks traveling with Dr. Hurd some years after he had retired from the superintendency was so much surprised at his agility that he turned to me and said, " I have never seen a man who can jump out of bed, ."ay his prayers, shave and dress as quickly as Dr. Hurd does, and he does not in any way curtail the length of his prayers."

BOOKS WRITTEN BY DR. HURD

HospiT.\Ls, Dispensaries and Nursing

Edited hy John S. Billings, M. D., and Henry M. Hurd, M. D.

The International Congress of Charities, Correction and Philanthropy was held in Chicago, June 12 to 17, 1893. Section 3 was devoted to the hospital care of the sick, training of nurses, dispensary work and first aid to the injured. Dr. John S. Billings was chairman and Dr. Henry M. Hurd secretary of this section ; Miss Isabel A. Hampton was chairman of the subsection on Nursing.

Many valuable papers were read in the section and it was clearly evident that the addresses should be published, but the necessary funds were lacking. Dr. Billings and Dr. Hurd came to the rescue and at their own expense published and also edited the large volume of over 700 pages. This splendid publication is of much interest to Baltimorcans not only on account of the many valuable papers, but also because Baltimoreans contributed in no small measure to the success of the Congress.

Dr. Billings' chairmanship address was entitled " The Relations of Hospitals to Public Health." Miss Hampton took for her theme " Educational Standards for Nurses," and Miss L. L. Dock spoke on "The Relation of Training Schools to Hospitals."

Dr. Hurd's address was on " The Relation of Hospitals to Medical P^ducation." Mr. Henry C. Burdett, of London, England, the Honorary Chairman of the Section, in discussing Dr. Hurd's paper said :

I should like to say that I thlnlt it Is very Important that wc should have a paper of this kind read this session. It is important because it clearly lava down and hrings out clearly to the non-tochnical mind the reason why the cost of administering hospitals tends steadily to increase, and what those who give to hospitals really get back in return for their money. A man is often amazed by the demands which are constantly made for more and more money, especially for bulldlnKs, and I do


think that Dr. Hurd's paper will fulfill a very useful purpose, and I hope it will be printed and widely circulated among hospitals

Miss M. A. Boland, the dietitian of The Johns Hopkins Hospital, gave an interesting address on " Hospital Dietaries."

Dr. Hurd gave a second paper " Description of The John.s Hopkins Hospital." After briefly detailing the gift of Johns Hopkins and speaking of the plans and building of the hospital, he described the institution in detail, giving numerous illustrations and plans. The picture that will appeal most to the older members of the faculty is the one of the isolation ward, with the old boardwalk extending from the northern exit of this building over to the steps of the pathological building. One can even now vividly see those going from the hospital to the laboratory in rainy weather, turning up their coat collars and sprinting rapidly over to the i)athological department.

The Congi-ess was honored by a paper " Sick Nursing and Hcaltli Nursing " by Florence Nightingale, and by an address by our own Cardinal Gibbons on " Work Done by Religious Communities Devoted to the Relief of the Sick."

Too much credit cannot be given to Dr. Billings and to Dr. Hurd not only for editing, but also for bearing the cost of this volume which contiiins valuable articles from sjiecialists in all parts of the world.

SVGGESTIONS TO HOSPITAL VISITORS

In 1895 Dr. John S. Billings and Dr. Hurd brought out a small book entitled " Suggestions to Hospital and Asylum Visitors."' The need for such a book was very evident and S. Weir Mitchell prevailed upon these well-known hospital authorities to "WTite it. Dr. Mitchell's introduction is so much to the point that I quote it in full :

For several years I have been urging upon Professor Billings the need for a small manual suited to the wants of hospital visitors. I have many times been asked by laymen who have to manage eleemosynary institutions where they could learn liow critically to inspect them with a reasonable chance of seeing what is wrong and learning how to value what is praiseworthy. It is useless to point the ln(iulrer to the greater works on hygiene. These presuppose such knowledge as few possess who are not educated physicians. There is needed a condensed statement of ichat to see In a hospital and how to see it.

Every new domain of observation requires a peculiar ami individualized training. The acute microscoplst might be a dull observer of the facts of disease which we call symptoms: the clever artist may be a sad failure when called upon to see with critical eyes the phenomena of the laboratory. How, then, can we expect that quite untrained people should of a sudden become useful observers in a field as new to them as Is a hospital?

Boards of managers are chosen out of the every-day life of commerce and professions other than that of medicine. The members are presumed to study results into which enter questions of cooking, dietetics, ventilation, medical and surgical clpanllncsa, which Involves disinfection, and many other matters exacting careful attention, and only to be thoroughly understood after years of training. This little manual is meant to assist untrained observers, yet even the most expert manager of a hospital or the ablest medical observer ought to find In it valuable bints. This guide to the hospital visitor 1 have asked leave to


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introduce. It lias cost an amount of care and thought out of proportion to its size. While in manuscript it was critically read by Professors J. M. DaCosta, J. William White, and myself, and certain changes or additions were suggested. Finally, Dr. Hurd, the accomplished director of The Johns Hopkins Hospital, was kind enough to associate himself with Professor Billings and to take the utmost interest in the work. Out of their joint labor and the criticism of able physicians and nurses has come at last the helpful little book which originated in my suggestion, and which I confidently commend to all who, being managers, trustees, or in any way connected with hospital work, are not +++++ CONTENTSed to assume an official name and remain ignorant of how honestly to fulfill the duties which should go with it.

S. Weie Mitchell, M. D.

It is doubtful if any small book of 43 pages was ever so crammed full of iuformation and good advice. It should be reprinted and be read by every hospital trustee and by all in any way interested in hospitals. A perusal of its pages will give the reader a very clear idea of the manifold details of hospital management, will enable him to render valuable advice without unjust criticism and will make the path of the superintendent or director of the Jiospital a much smoother one. In short, it will promote the maximum efficiency with friction reduced to the minimum.

The copy of the book that fell into my hands contains a few notes in Dr. Kurd's hand writing. These I venture to reproduce here without his knowledge or permission :

SUGGESTIONS FOR THE ORGANIZATION OF AUXILIARY BOARDS OF VISITORS

1. Composed of men and women who are interested in humanitarian and philanthropic work.

2. They should be absolutely free from any partisan or political bias.

3. They should feel at liberty to make suggestions as to the policy of the hospital, as to purchasing, administrative details, etc. They should be +++++ CONTENTSed to present their \iews to the governing body with whom must rest the responsibility of the final decision.

4. They should seek to assist in all social service matters. The officers of a hospital, as a rule, are not widely acquainted with the possibilities of social help in the community or the sources of aid. The Board of Visitors can do incalculable good by bringing the hospital into relation with all helping agencies.

5. Boards of Visitors should never lose sight of the fact that they are privileged to assist in a most important public service. The increasing wealth of the country and the growth of a leisure class can only do harm if these become a source of personal pleasure to those who have leisure and abundant means. If. however, they use their good fortune for the public good, new aspirations are aroused and new and most satisfying channels of activity are found which dignify and ennoble the individual and bless the community. Personal service to hospitals and similar charities thus become not only a duty but a pleasure, and life is enlarged and made purposeful by the performance of good work.

The Institutional Caee of the Insane in the United States and Canada At the 66th annual meeting of the American MedicoPsychological Association held in Washington, D. C, in May, 1910, Dr. Hurd gave an address entitled " A History of Institutional Care of the Insane in the United States and Canada."


This paper was published in the American Journal of Insanity, 1910-11, Vol. Ixvii, p. 587. In the course of his address Dr. Hurd said :

The movement to write a history of the association and its work had its origin at the Baltimore meeting in 1895, when Dr. Powell, of Georgia, presented a very interesting outline of the " rise and progress of a vast system of charities in the 15 commonwealths of the South," with detailed accounts of institutions in Virginia, North Carolina and Georgia. It was evident from the interest which was then excited that much had been done by similar foundations in all the states of the Union, and from this conviction grew the original resolutions subsequently presented by Dr. J. W. Babcock, of Columbia, S. C. These resolutions were considered and favorably acted upon, and a committee was appointed, but nothing seems to have come of it, although progress has been reported from time to time, and an effort, has been made to stir up a general sentiment in favor of completing the work. For this and other reasons, although not aware of any special personal fitness for the work, I did not feel at liberty to decline the appointment made at the Cincinnati meeting, and of which, by the way, I learned for the first time in June last at Atlantic City. Since that time I have made an intermittent effort to organize the work and to collect such material as I could find.

The full committee consisted of Dr. Henry M. Hurd, chairman; Dr. William F. Drewry, for the South; Dr. Richard Dewey, for the West; Dr. Charles W. Pilgrim, for the middle states ; Dr. G. Alder Blumer, for New England ; Dr. T. J. W. Burgess, for British America.

The object of the present paper is to give some account of the progress of the work and to say what needs to be done. I hope, also, to stir up in the minds of the members of the association a feeling of responsibility for it, so that there may be cooperation in gathering the material and preparing it for publication at the proper time. The difficulties in the task are very great. Those who have been interested in the construction of the institutions for the insane in the United States have been largely isolated workers, and their records are. consequently, widely scattered throughout the different states of the Union

In his concluding paragraph Dr. Hurd says :

I have taken the liberty to embody the substance of this paper in a resolution which I now offer to ascertain the will of the association in the matter of the publication of the book. 1 shall be very glad to have it modified, revised, or in any way changed so as to bring out more completely the wishes of the association in this matter. I am not wedded to any theory of publication, or any form of work. I am anxious that the work go on with as much rapidity as possible. It is equally important, however, that the work be done thoroughly, so that in future all may know who in the past contributed to the success of an important philanthropic achievement.

Volumes I, II and III of this stupendous work appeared from The Johns Hopkins Press in 1916 and Volume IV in 1917. These four volumes contain in all 2926 pages.

A glance at the preface to Volume I gives the reader a clear idea of the tremendous amoimt of labor entailed in the preparation of these volumes. After taking up nearly three pages of the preface in thanking various men for their cordial cooperation in furnishing data the editor says :

The obligations of the committee to the individual superintendents of nearly 200 institutions in the United States and Canada are very great; in fact, without their cooperation it would


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hare been Impracticable to prepare any adequate history of the movements in the various states and provinces.

It is evident from a careful study of all the material which has come into the hands of the committee that a gradual evolution has occurred in the care of the insane in America during the past halt-century, which bids fair to change materially the discouraging views as to the hopelessness of their cure which have prevailed for many years in the United States and Canada.

The movement towards the prompt treatment of curable cases without the formality of legal commitment and under the same conditions as in admission to a hospital for general bodily disease, gives every hope that at an early day cases of recent attack may be received everywhere promptly, and that greatly increased numbers can be cured. Cases of a chronic nature are also now much more satisfactorily dealt with in institutions on the cottage plan, with outlying colonies for the employment of patients, and have a correspondingly better opportunity to attain selfsupport. These movements promise to make material changes in future methods of caring for the insane.

Volume I i.-i historical in character. It gives a clear account of the Association of Medical Superintendents of American Institutions for the Insane from 1844 to 1803 and of the American Medico-Psychological Association from 1803 to 1913. It then describes what the American Journal of Insanity has accomplished. Volume I was written by Dr. Hurd and the reader can best obtain an idea of the wide range of subjects considered in tiiis volume by glanriiis throuLh its list.-; of contents

I. Introduction 5

II. The Association of Medical Superintendents of American Institutions for the Insane, 18441893 11

III. The .\mcrican Medico-Psychological Association,

1893-191.3 53

IV. The American Journal of Insanity 75

Chapter II

I. Early and Colonial Care of the Insane 81

II. The Era of Awakening 93

Chapter III I. Dorothea Lynde Dix and Her Work 101

Chapter IV

1. Evolution of Institutional Care in the United States.. 139

II. County Care of the Insane 144

III. Chronic and Incurable Insane 147

IV. The Colony System 156

V. State Care 163

VI. The Wisconsin System of County ("are 168

ClfAPTF;R V

I. Evolution of the Administration of Hospitals 179

II. Present Government of Institutions for the Insane .... 183

III. Methods of Investigation of Public Institutions 196

IV. Development of Hospital Architecture 204

Chapter VI

I. The Propositions 217

II. Reforms in Caring for the Insane 223

III. Medical Treatment of the Insane 230

IV. Non-Medical Treatment of the Insane 234

V. Employment for the Insane 242

VI. Asylum Periodicals 250


VII. Individual Treatment 254

VIII. Experimental Removals 256

IX. Origin of the Psychopathic Hospital in the United

States 258

X State Psychopathic Hospital at the ITnlversity of

Michigan 266

XI. Boston Psychopathic Hospital 276

XII. Research Work in Hospitals 281

Chapter VII

I. Training Schools for Nurses and the First School in

McLean Hospital 289

II. First Training Scliool for Attendants at the Buffalo

State Hospital (Asylum), 1883-1886 301

Chapter VIII I. Private Care of the Insane 313

Chapter IX

I. Growth of the Law of Insanity 321

II. Commitment of the Insane 331

III. Conditions of Discharge 338

IV. Admission of Voluntary Patients 344

V. Care of the Criminal Insane 348

Chapter X

I. Immigration and the Care of the Insane 355

II. The Alien-Born in Relation to the Cost of State Care. . 362

Chapter XI

I. Insanity among the Negroes 371

II. Insanity among the North American Indians 381

III. Insanity among Indians in South Dakota 386

IV. The Chinese and Japanese Insane in the United

States 393

Chapter XII

I. Institutional Population 399

II. Census of the Insane 411

III. Feeble-Mindod in Institutions 421

Chapter XIII

I. Laws for the Commitment of tlie Insane in Canada. . . 427 II. Care of the Insane in Canada Previous to the Establishment of Provincial Institutions 446

III. Establishment of Provincial Institutions 454

IV. System of Care In the Provinces of Canada, and Gov vernment and Inspection of Provincial Institutions. 458

V. The Contract System In the Province of Quebec 467

VI. Immigration and the Care of tlie Insane in Canada. . . . 472

VII. Census of the Insane In Canada 478

VIII. The Chinese and Japanese in Institutions in British

Columbia between the Years 1871 and 1913 480

IX. Dorothea L. Dix and Canadian Institutions 481

Volumes II and III and part of Volume IV are devoted to a detailed description of tlie institutions for the care of the insane in the United States and Canada. Volume HI also includes the institutions in Hawaii and in the Philipi)incs. Pictures of many of tlie institutions are given and often plan.s of the buildings accompany them. In each article is a detniled list of the medical personnel of the institution from its beginning to the time the volume appeared, so that the previous activities of any man who has devoted his life to psychiatry can be readily followed.


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The latter half of Volume IV is devoted to biographies of prominent psychiatrists in the United States and Canada.

The picture in Volume I that will interest Baltimoreans most is that of the Maryland Hospital for the Insane as it appeared in 1833. It faces on the old Joppa Road and in the background is the present Church Home and Infirmary, then the Washington Medical School. The site of the Old Maryland Hospital for the Insane is, as has been mentioned elsewhere, now occupied by The Johns Hopkins Hospital.

In Volume II is a splendid plate of the Sheppard and Enoch Pratt Hospital. The frontispiece of Volume IV is a reproduction of a portrait of Miss Dorothea L. Dix, to whose pioneer labors American psychiatry owes so much.

These volumes have brought forth much praise. Scien-ce for July 28, 1916, in reviewing Volume I, which was written in its entirety by Dr. Hurd, says :

This is one of the few worlcs in the English language in which the history of a separate branch of medicine has been exhaustively treated Tlie present volume, although it professes

to deal only with the general history of institutional care of the insane on this continent, is, in reality, an exhaustive history of American psychiatry in all its phases, and is therefore likely to remain the authoritative work on the subject for an indefinite period

Dr. Hurd modestly regards this work as a source-book for the historians of the future but it is undoubtedly a permanent history which may be extended, but will hardly be duplicated. The chapters are complete in themselves, the book is well illustrated, and the style is charming in its simplicity, sobriety and its traces of delicate humor.

The American Journal of Insanity for October, 1916, in the course of the review of Volumes I and II, says :

Too much praise cannot be given to the manner in which the task imposed upon this Editorial Committee has been carried out, and as one of the members of the committee. Dr. Burgess, said at the meeting in New Orleans in April last, while all the committee liave tried to help, the burden of the work has been on Dr. Kurd's shoulders.

The Nation on February 8, 1917, says:

No survey of the treatment of American insane during the last two centuries has before appeared; it is pleasant to find the difficult task so well executed as in this volume.

The British Medical Journal for December 8, 1917, in referring to the four volumes said :

Dr. Hurd is to be congratulated upon the success with which he has carried out the collection and colligation of the numerous interesting records contained in these volumes. Naturally they will appeal most strongly to readers across the Atlantic; but in their record and analysis of success and failure in attacking a problem of great importance in all civilized communities — namely, the care of the insane — they should find many readers throughout the world.

In another foreign review we find the following tribute : This monumental work, is, in the main, the product of the veteran Dr. Hurd, emeritus professor of psychiatry in The Johns Hopkins University, and formerly medical superintendent of the Pontlac State Hospital, who is well known on this side of the Atlantic as the most distinguished of American alienists. Dr. Hurd has retired from active practice, but his abundant energy would not suffer him to be idle, and he has employed his leisure wisely and well In producing this great work, which will be a classic from the day of publication.


It must be remembered that during the immense amount of labor entailed in the preparation of these volumes Dr. Hurd had been greatly troubled with his eyes and it was only his indomitable will that continually spurred him on to the completion of these labors that were a fitting climax to his many successful years of hospital directorship.

SUMMARY *

Dr. Hurd in addition to his other editorial duties has been one of the editors of the American Journal of Insanity since 1897 and of the Modern Hospital since 1913.

He is a member of the Association of American Physicians ; of the American Academy of Medicine, and was its president in 1896 ; of the American Medico-Psychological Association, of this he was secretary from 1892 to 1897 and president in 1898-9, he also edited three volumes of its proceedings; of the American Anthropological Association ; of the American Hospital Association and its president in 1912. He is also a member of the American Public Health Association.

In 1895 Dr. Hurd was given the degree of LL. D. by his alma mater, the University of Michigan.

On September 16, 1874, Dr. Hurd married Miss Mary Doolittle, of Utica, N. Y. They had three children, a son and two daughters. The son died in childhood.

Mrs. Hurd was always greatly interested in her husband's labors and ever manifested the same cordial relation to the hospital interns and to the senior staff that Dr. Hurd did. A year or two after they left the hospital Mrs. Hurd's health began to fail and her death on March 14, 1913, was keenly felt by the host of friends of the family.

Miss Eleanor and Miss Anna Hurd are the constant companions of their father and it is a delight to see the manner in which they watch over his welfare and literally force him to conserve his unbotmded energy.

Dr. Hurd is a Presbyterian. He has shown the same fidelity . to his church that he has ever manifested in his professional duties.

From the preceding pages of this article the reader will see from what an intellectually sturdy stock he came and few men have had such a long medical ancestry. Step by step he rose until he was not only the first superintendent of a large asylum in Michigan, but also a dominant figure in that commonwealth. His fame as an administrator was not confined to his own locality, but was widely known. It was for this reason that he was later called to Baltimore.

All through his career he has been a thoroughly consistent and industrious psychiatrist. He has published many valuable papers dealing with the study and treatment of the insane, has for years been one of the editors of the American Journal of Insanity and less than three years ago edited a monumental work of four volumes on " The Institutional Care of the Insane


  • This article together with " Random Recollections " by Dr.

Hurd will be issued in book form from The Johns Hopkins Press In a few weeks.


%


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in the United States and Canada." As mentioned before he wTote Volume I and edited Volumes II, III and IV.

For years he has been a most valuable membur of the ilaryland State Lunacy Commission. A foreign journal speaks of Dr. Hurd as " The most distinguished of American alienists." It is clearly evident that in psychiatry he has reached the top rung of the ladder.

The trustees of The Johns Hopkins Hospital manifested rare discernment when they selected Dr. Hurd to become the first superintendent of the hospital. It fairly blossomed under his wise generalship until its fame spread far beyond the confines of this continent — until it was known in every civilized land.

The Johxs Hopkins Hospital Bulletin and the Hospital Reports under his able editorship added greatly to the prestige of the institution. As an expert in hospital organization and in hospital management he is recognized as tlie leader in America. His advice in hospital and nursing problems is continually sought. His is invariably the final word on these subjects.

His writings on hospital organization, hospital management, medical education and nursing are numerous and most valuable and he has ever aimed to publish historical records in order that they may not be lost — in order that they may be preserved for future generations. Whatever he has undertaken he has finished.

A prominent publisher who has come in contact with him nearly every week for at least 25 years said to me recently " Dr. Hurd is the most practical and business-like physician that I have ever met " — and he meets an unusually large number. It is undoubtedly this practical bent, coupled with rare discernment, a broad knowledge of men and a wide knowledge of psychiatry and medicine that has enabled him to accomplish .'io much apparently with so little effort.

From time to time brilliant statesmen advanced in years have been spoken of as " grand old men." Dr. Hurd is the grand old hospital statesman of America. Early in his career he wanted to become a surgeon in the navy, but was disqualified on account of his frail phjsical make-up. He would have undoubtedly made his mark in government service, but what a loss the asylums and hospitals of this country would have sustained, and how much psychiatry and the profession of medicine in general would have missed had he successfully passed the physical requirements for the navy !

His has been a life well spent — a life full of labor for his fellow man. In a memorial tribute to the late Dr. William Whitney Godding, Dr. Hurd unconsciously gave a most vivid description of himself. " You felt instinctively that you had to do with one who knew no guile or self-seeking, but who api)reciatcd it to be his duty to place his powers of mind and heart unreservedly at the disposal of his associates or his fellow men." But Dr. Hurd is not gone, he is still with us, actively engaged in writing the historj- of The Johns Hopkins Hospital. That he may long be spared to browse in the Henry M. Hurd Library, which my friend George K. McGaw is building as a mark of ajipreciation and esteem to our mutual


friend, the first superintendent of The Johns Hopkins Hospital, is our earnest prayer.

THE LATE GEORGE KEEN McGAW

For several months ilr. McGaw had been failing in health, and in June he went to his summer home at Buena Vista. The erection of the Henry JI. Hurd library was uppermost in his mind, and the last thing he did on the morning he left for the mountains was to turn over to Judge Harlan additional funds for the building. He was particularly anxious that Dr. Hurd should not only see, but also have the opportunity of often enjoying the library bearing his name. My account of Dr. Kurd's manifold activities was accordingly promptly undertaken and as soon as it was completed, early in July, Judge Harlan and I spent a delightful day with Mr. McGaw and his family in the mountains. For fully two hours Mr. McGaw listened with great interest to the recital of tlie many tilings his friend had accomplished and again expressed himself as so happy that the library plans were well under way. That was the last time I saw tlmt whole-souled and true friend. He had a fairly comfortable summer. He died suddenly on the morning of September 9, 1919.

Dr. Ilurd and Mr. McGaw had known one another for many years, as they both were prominent members of the First Presbyterian Church and Mr. McGaw was also one of the Trustees of The Johns Hopkins Hospital.

In March, 1911, Mr. McGaw suggested a trip Soutli and a few days later Dr. Hurd, Air. AIcGaw and myself left for an extended trip, visiting Pinehurst, Columbia, Savannah, Jacksonville, Knights Key, Havana, Key West and Miami. It was on this trip that the lasting and intimate companionship and friendship was cemented between these two splendid men, and since that time they liave been together week in and week out. It was this close companionsliip that revealed to Mr. ilcGaw Dr. Hurd's wonderful breadth of character, and that prompted him to plan this tribute to his friend — a tribute that will not only be a constant reminder of the first superintendent of The Johns Hopkins Hospital, but that will also be of inestimable value to the succeeding generations of students in The Johns Hopkins Medical School.

Dr. Hurd's estimate of his departed friend rings so true and is so beautifully expressed in a recent letter to me that I cannot help reproducing it here.

Seal Hakbou, Me., Sept. 13, 1919. Dear Cullen : Many tlianks for your telegrams and your thoughtfulness in sending them. I iiave been greatly shocked by the unexpected death of the i)est of friends and I know of no one who may occupy the vacant place in just the same way. He was so noble in his ])lans and modest in carrying them out, so that his own work might be minimized. I always felt him to be a rare man. We all of us ought to be better men for having known him. I have written to Mrs. McGaw, but I feel that I could not in any way tell her properly how much I loved

him

Sincerely,

Henry M. Hurd


370


[No. 346


BIBLIOGRAPHY OF HENRY MILLS HURD, M. D., LL. I).


PREPARED BY

MINNIE WRIGHT BLOGG

LIBBAEIAN, THE JOHNS HOPKINS HOSPITAL


Recent judicial decisions in Michigan relative to insanity. Am. J. Insan., Utica, N. Y., 18S0-81, xxxvli, 23-35.

1882

A plea for systematic therapeutical, clinical and statistical study. Read before the Association of Medical Superintendents of American Institutions for the Insane, at the annual meeting in Toronto, June, 1881. Am. J. Insan., Utica, N. Y., 1881-82, xxxviii, 16-31.

Practical suggestions relative to the treatment of insanity. Physician & Surg., Ann Arbor, Mich., 1882, iv, 385-399.

1883

Future provision for the insane in Michigan, n. p., 1883. 9 p. 8°

The treatment of periodic insanity. Am. J. Insan., Utica, N. Y. 1882-83, xxxix, 174-180.

Ducking in asylums. A refutation (letter). Am. J. Insan., Utica N. Y., 1882-83, xxxix, 506-507.

The hereditary influence of alcoholic indulgence upon the production of insanity. A paper read at a sanitary convention held at Pontiac, Michigan, January 31 and February 1, 1883. Re printed from a Supplement to the Annual Report of the Secretary of the State Board of Health of Michigan, for the year 1883. Physician & Surg., Ann Arbor, Mich., 1883, v, 49-57.

1884

The minor treatment of insane patients; summarv. Am. J. Insan., Utica, N. Y., 1883-84, xl, 205-209.


Paranoia. Am. J. Insan.


1886 Utica, N. Y., 1885-86, xlii, 473-483.

1887


The relation of general paresis and syphilitic insanity. Insan., Utica, N. Y., 1886-87, xliii, 1-18.


The data of recovery from insanity. 1886-87, xliii, 243-255.


Am. J. Insan., Utica, N. Y.,


The colony system of Michigan. 1887, xiv, 215-220.


Proc. Nat. Confer. Char., Bost.,


Gastric, secretory and other crises in general paresis. Am. J. Insan., Utica, N. Y., 1887-88, xliv, 60-65.

The religious delusions of the insane. Am. J. Insan., Utica, N. Y., 1887-88, xliv, 471-487. Also: Tr. ix. Internat. M. Cong., Wash., 1887, v. 253-263.

Hurd, H. M. & Christian, E. A. The ultimate results in a case of exsection of the head and upper third of the humerus. Ann. Surg., St. Louis, 1888, vii, 431-434.


Imbecility with insanity. 261-269.


1889 Am. J. Insan.,


1890


Utica, N. Y., 1888-89, xlv,


First report of the superintendent of The Johns Hopkins Hospital from May 15, 1889, to January 31, 1890. Bait., 1890, The Johns Hopkins Press. 47 p. 8°. Also: Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 77-89.

A case of inebriety with insanity; with remarks. Am. J. Insan., Utica, N. Y., 1889-90, xlvi, 61-70.

The relation of the Training School for Nurses to The Johns Hopkins Hospital. Johns Hopkins Hosp. Bull., Bait., 1889-90, i, 7-8.


Periodicitv in melancholia. 269-270.


Maryland M. J., Bait., 1890, xxiii,


Proc. Nat. Confer. Char., Bost.,


Report of committee on hospitals. 1890, xvii, 155-156.

The relation of the general hospital to the medical profession. Proc. Nat. Confer. Char., Bost., 1890, xvii, 156-162.

1891

Second report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1891. Bait, 1891, The Johns Hopkins Press. 76 p. 8°. Also: Johns Hopkins Hosp. Bull., Bait., 1891, ii, 124-132.

Memoir of Richard Gundry, M. D. Tr. M. & Chir. Fac. Maryland, Bait., 1891, 178-183.

1892

Third report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1892. Bait., The Johns Hopkins Press. 63 p. S°. Also: Johns Hopkins Hosp. Bull., Bait., 1892, Hi, 97-102.

Journal clubs. Am. J. Insan., Utica, N. Y., 1891-92, xlviii, 372-375.

Post-febrile insanity. Maryland M. J., Bait., 1892, xxvii, 661-666. Also: Am. J. Insan., Utica, N. Y., 1892-93, xlix, 26-34.


Fourth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1893. Bait., 1893. The Johns Hopkins Press. 69 p. 8°.

The relation of hospitals to medical education. Boston M. & S. J., 1893, cxxix, 141-143.

1894

Fifth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1894. Bait., 1894. The Johns Hopkins Press. 69 p. 8°.

Hurd, H. M. & Billings, J. S. eds. Hospitals, dispensaries and nursing. Papers and discussions in the International Congress of Charities. Correction and Philanthropy, section iii, Chicago, June 12-17, 1893. Bait., 1894, Johns Hopkins Press. 733 p. S".


Internat. Cong.


The relation of hospitals to medical education. In : Hospitals, Dispensaries and Nursing. . . . Char, [etc.], 1893, Bait. & Lond., 1894, 98-105.

Description of the Johns Hopkins Hospital, Baltimore, Md. I7i: Hospitals, Dispensaries and Nursing. . . . Internat. Cong. Char, [etc.], 1893, Bait. & Lond.. 1894, 429-443.

George Huntington Williams. The minutes of a commemorative meeting held in the Johns Hopkins University, October 14, 1894. Baltimore, 13 p. 8°.

Some mental disorders of childhood and youth. Boston M. & S. J.,

1894, cxxxi, 281-285.

Also: Baltimore, 1895, Friedenwald Co., 16 p. 8°.

1895 Sixth report of the superintendent! of The Johns Hopkins Hospital

for the year ending January 31, 1895. Bait., 1895. The Johns

Hopkins Press. 74 p. 8°. Hurd. H. M. & Billings. J. S. Suggestions to hospital and asylum

visitors. With an introduction by S. Weir Mitchell. Phila.,

1895. J. B. Lippincott Co., 48 p., 8°.


The alienists of the past half century. Proc. Am. Med. Psychol. Ass., 1894, Utica, N. Y., 1895, i, 167-171.

1S96 Seventh report of the superinter^dent of The Johns Hopkins Hospital for the year ending January 31, 1896. Bait., 1896. The Johns Hopkins Press. 66 p. 8°.


Decembeb, 1919]


371


The new .McLean Hospital. .-Vm. J. Insan., Chicago, lS9o-6. lii, 477502.

Laboratories and hospital work. Bull. Am. Acad. M., Easton, Pa., 1895-6, ii, 483-495.

Paranoia. .Maryland M. J.. Bait., 1896, xxxv, 1-4. Also: [Abst.] Virginia M. Semi-Month., Richmond. 1896-7, i, 263.


Eighth report of the superintendent of The Johns Hopkins Hospital for the .vear ending January 31, 1897. Bait., 1897. The Johns Hopkins Press. 88 p. 8°.

Hospital organization and management Address before the Training School for Nurses of the University of Pennsylvania, February 17. 1897. Univ. M. Mag., Phila.. 1896-7. ix. 4SS-500.

Kurd, H. M., Burr, C. B. & Wise, P. M. Report of the committee on statistical tables, to the American Medico-Psychological Association. .\m. J. Insan., Chicago, 1896-7, liii, 105-116.

Hurd, H. M. & Chapin. J. B. Report on the hospitals of the District of Columbia. To the Joint Select Committee to investigate the charities and reformatory institutions in the District of Columbia. Washington, 1897.

1898

Ninth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1898. Bait., 1898. The Johns Hopkins Press. 91 p. S".

The medical service of hospitals. Albany M. Ann., 1898. xix. 137142.

The non-medical treatment of epilepsy. (Proc. Johns Hopkins Hosp. Med. Soc, November 7, 1898). Johns Hopkins Hosp. Bull., Bait., 1898. ix, 296-297. Also: .Maryland M. J., Bait., 1898-9, xl, 53.

1899

Tenth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1899. Bait., 1899. The Johns Hopkins Press. 92 p. 8°.

Post-operative insanities and undetected tendencies to mental disease. Am. J. Obst., N. Y., 1899, xxxix, 331-335.

Presidential address. The teaching of psychiatry. Delivered at the annual meeting of the American Medico-Psychological Association at New York. May 23, 1899. Proc. Am. Med. Psychol., Ass., 1899, vi, 79-92.

Also: Johns Hopkins Hosp. Bull., Bait, 1899, x, 205-209.

.4/so.- Am. J. Insan., Bait., 1899-1900, Ivl, 217-230.

1900

Eleventh report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1900. Bait, 1900. The Johns Hopkins Press. 114 p. 8°.

.Memorial addresses in honor of William Whitney Godding, M. D., LL. D. Delivered before the Medical Society of the District of Columbia, June 7, 1899. Nat. M. Rev., Wash., 1899-1900, Ix, 374-377.

Hospitals, dispensaries and nursing. (American philanthropy of the nineteenth century). Char. Rev., N. Y., 1900, x, 298-305; 317-331,

Hospital construction from a medical standpoint. Brickbuilder, Bost., 1900, Ix. 248.

1901 Twelfth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1901. Bait, 1901. The Johns Hopkins Press. 114 p. 8°.

Reception hospitals for cases of acute insanitv. Bull. Iowa Inst, Des Moines. 1901. lii. 3S-40.

1902

Thirteen! ii report of ihr .superintendent of The Johns Hopkins Hospital for the year ending January 31, 1902. Bait., 1902. The Johns Hopkins Press. 118 p. S\

The educated nurse and her future work. Address delivered at the graduating exercises of the Training School of the Garfield Hospital, Washington, D. C: and similarly at the Training School of the Methodist Episcopal Hospital, Brooklyn, N. Y. Baltimore [1902], Friedenwald Co.. 14 p. »'.


Psychiatry in the twentieth century. Address at the formal opening of the new hospital building at Morris Plains. New Jersey, November 20, 1901. Albany M. Ann., 1902, xxiii, 125136.

1903 Fourteenth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1903. Bait., 1903. The Johns Hopkins Press. 110 p. 8".

The future policy of Maryland in the care of her insane. Maryland M. J., Bait., 1903. xlvi, 45-54.

The duty and responsibility of the X'niversity in medical education. Science. N. Y. & Lancaster. Pa., 1903, n. s., xviii, 65-76. Also: Yale M. J., 1903-4, x, 1-17.

1904

Fifteenth report of the superintendent of The Johns Hopkins Haspital for the year ending January 31, 1904. Bait, 1904. The Johns Hopkins Press. 130 p. 8".

Is nursing a profession? Albany M. .Ann., 1904, xxv, 625-637.

1905

Sixteenth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31. 1905. Bait. 1905. The Johns Hopkins Press. 133 p. 8°.

John Howard's observations on hospitals (1773-1790). (Proc. Johns Hopkins Hosp. Med. Soc, October 23, 1905). Johns Hopkins Hosp. Bull., Bait. 1905, xvi. 412-413. Also: Tr. Ass. Hosp. Superintend.. 1905. vii, 157-166.

Response to Dr. Cheever's " Address of welcome." Tr. Ass. Hosp. Superintend., 1905, vii, 50-52.

1906

Seventeenth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1906. Bait., 1906. The Johns Hopkins Press. 125 p. 8°.

Shall training schools for nurses be endowed? An address delivered before the Training School for Nurses of Lakeside Hospital, Cleveland, May 11, 1906. Am. J. Nursing, Phila., 1905-6, vi. 843-853.

Also: Nat. Hosp. Rec. Detroit, 1906, x, 18-23.

Also: Brit J. Nursing [etc.], Lond., 1906, xxxvii, 225-227.

The medical organization of general hospitals. Tr. Am. Hosp, Ass., 1906, vlii, 72-83. Also: Nat. Hosp. Rec, Detroit, 1906, x. 14-16.

1908

Nineteenth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1908. The Johns Hopkins Press. 123 p. 8°.

The proper length of the period of training for nurses. Am. J. Nursing. Phila., 1908, viii, 671-683.

How can psychiatry assist preventive medicine? (Editorial). Am. J. Pub. Hyg., Boston, 1908, xviii, 273-278.

Psychiatry as a part of preventive medicine. Proc. Am. Med.Psychol. Ass., Bait., 1908, xv, 157-164. Also: Am. J. Insan., Rait. 1908-9, Ixv, 17-24. Also: N. Albany M. Herald. 1910, xxviil, 104108. In memoriam. Daniel Coit Oilman, 1831-1908. Address. Johns Hopkins Univ. Circ, Bait., 1908. xxvii. 20-23.

1909

Twentieth report of the superintendent of The Johns Hopkins Hospital for the year ending January 31. 1909. Bait.. 1909. The Johns Hopkins Press. 123 p. 8'.

State registration and the education of nurses In the I'nited States.

Nursing .Mirror. Lond.. 1908-9. n. s., vlll. 37-38: 53. In memoriam. William Keith Brooks. 18481908. Address. Johns

Hopkins Univ. CIrc, Bait., 1909, xxvlli. 6-9.

1910

Twenty-first report of the superintendent of The Johns Hopkins Hospital for the year ending January 31, 1910. Bait., 1910. The Johns Hopkins Press. 123 p. 8'.

Co-operation among hospitals. A paper presented to the Pittsburgh Health Conference, November 30, 1910, as a part of a symposium on " Co-operation."


373


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Memorial services for Isabel Hampton Robb, who died April 15, 1910, at Cleveland, Ohio. Remarks. Johns Hopkins Hosp. Bull., Bait, 1910, xxi, 251-252.

Florence Nightingale — a force in medicine. Address at the graduating exercises of the Nurses Training School of the Johns Hopkins Hospital, May 19, 1910. Johns Hopkins Nurses Alumna Mag., Bait., 1910, ix, 68-81.

1911 Twenty-second report of the superintendent of The Johns Hopkins

Hospital for the year ending January 31, 1911. Bait., 1911.

The Johns Hopkins Press. 109 p. 8°. The medical service of a hospital. In: Hospital management, a

handbook for hospital trustees, superintendents [etc.]

(Aikens), Phila. & Lond., 1911, 97-107. A history of Institutional care of the insane in the United States

and Canada. Am. J. Insan., Bait, 1910-11, Ixvii, 587-592.

Also: Proc. Am. Med.-Psychol. Ass., Bait, 1910, xvii, 4S3-488.

The site of the Johns Hopkins Hospital. A paper presented to the

Johns Hopkins Historical Club and repeated to the Teresians

in December, 1910. Johns Hopkins Nurses Alumns Mag.,

Bait, 1911, X, 5-20. The proper relation of the superintendent to the trustees of a

hospital. Tr. Am. Hosp. Ass., 1910, Toronto, 1911, xil, 244-248.

1912

The proper division of the services of the hospital. Read in the symposium on the relations of the hospital to the public in the section on hospitals of the American Medical Association, at the sixty-third annual session, held at Atlantic City, June, 1912. J. Am. M. Ass., Chicago, 1912, lix, 1677-1679.

[Hospital problems.] Presidential address at the fourteenth

annual conference of the American Hospital Association. In ternat Hosp. Rec, Detroit, 1912, xvi, 9-11. Also: Tr. Ass. Hosp. Superintend., 1912, xiv, 83-93. Meeting in behalf of the Isabel Hampton Robb Memorial Fund.

Remarks. Johns Hopkins Nurses Alumnae Mag., Bait., 1912,

xi, 16-19.

1913

Three-quarters of a century of institutional care of the insane in the United States. Am. J. Insan., Bait., 1912-13, Ixix, 469-481.

Extracts from the laws of Maryland and Virginia regarding the early care of the insane. Bull. Med. & Chir. Fac. Maryland, Bait, 1912-13, v, 85-88.

Early days of The Johns Hopkins Hospital and Medical School.

Johns Hopkins Alumni Mag., Bait., 1912-13, i, 105-114. The hospital as a factor in modern society. (Editorial). Mod.

Hosp., St Louis, 1913, i, 33. Hospitals and the reform of medical teaching. (Editorial). Mod.

Hosp., St. Louis, 1913, i, 182-183. Review of " A History of Nursing." Johns Hopkins Nurses

Alumnae Mag., Bait, 1913, xii, 91-94.

1914 Hospital medical statistics. (Editorial). Mod. Hosp., St. Louis,

1914, ii, 44-45. The small hospital a factor in medical education. (Editorial).

Mod. Hosp., St Louis, 1914, li, 104-105. Mental cases in general hospitals. (Editorial). Mod. Hosp., St.

Louis, 1914, ii, 172.

The human side of Florence Nightingale. (Editorial). Mod. Hosp., St Louis, 1914, ii, 364.

State registration of nurses. Mod. Hosp., St. Louis, 1914, iii, 107;

137. Dr. Rupert Norton. (Editorial). Mod. Hosp., St. Louis, 1914, Iii,

108-109.

Some of the writings of the late Eugene Pauntleroy Cordell. Bull. Med. & Chir. Fac. Maryland, Bait, 1913-14, vi, 115-119.

Relation of the general hospital to the training school for nurses. Boston M. & S. J., 1914, clxx, 333-337.


Twenty-fifth anniversary of The Johns Hopkins Hospital. 1889 1914. Address. Johns Hopkins Hosp. Bull., Bait, 1914, xxv, 355-359.

Presentation of tablets, portrait and medallion at the Hospital October 7, 1914. Remarks. Johns Hopkins Hospital Bull., Bait, 1914, X.XV, 368-369.

Hurd, H. M., McCaw, W. D. [et a!.] Johns Hopkins Historical Club. Special meeting. May 26, 1913, in memory of Dr. John Shaw Billings. Johns Hopkins Hosp. Bull., Bait., 1914., xxv, 244-253.

1915

Hospital organization and management. Ref. Handb. Med. Sc, N. Y., 3d ed., 1915, v, 299-311.

The treatment of mental cases in general hospitals. (Editorial). Mod. Hosp., St. Louis, 1915, iv, 34-35.

The general government of state hospitals. Mod. Hosp., St. Louis,

1915, iv, 244-245.

Organization and administration of hospitals for the insane. (Editorial). Mod. Hosp., St. Louis, 1915, iv, 258.

Ought training schools for nurses to be endowed? (Editorial). Johns Hopkins Nurses Alumnfe Mag., Bait, 1915, xiv, 2-3.

The early years of The Johns Hopkins Hospital. Johns Hopkins Nurses Alumnae Mag., Bait., 1915, xiv, 76-89.

Forty-five years ago and now. An address before the Training School for Nurses at the Sheppard and Enoch Pratt Hospital, May 19, 1915. Johns Hopkins Nurses Alumns Mag., Bait., 1915, xiv, 256-264.

The care of cases of mental disease in general hospitals. Tr. Am. Hosp. Ass., 1915, xvii, 455-462. Also: Mod. Hosp., St Louis, 1915, v, 33-35.


Hurd, H. M., Drewry, W. F. [et al.] The institutional care of the insane in the United States and Canada. 3 v.. Bait., 1916, Johns Hopkins Press. 8°.


Nathan Smith, Nathan R. Smith, and Alan P. Smith — a medical family. Maryland M. J., Bait., 1916, lix, 56-59. Also: Bull. Med. & Chir. Fac. Maryland, Bait, 1915-16, viii, 157-163.

Address on the occasion of the opening of the John Hubner Psychopathic Building at Springfield State Hospital, on June 9, 1915. Maryland Psychiat. Q., Bait, 1915-16, v., 29-32.

Need of segregation of imbecile women. Maryland Psychiat. Q., Bait, 1915-16, V, 64-67.

Report of committee on a history of " The Institutional Care of the Insane in the United States and Canada." Am. J. Insan., Utica, N. Y., 1915-16, Ixxii, 176-177.

Some sources of friction in the management of hospitals. (Editorial). Mod. Hosp., St Louis, 1916, vi, 30-31.

Another source of friction In hospital administration. (Editorial). Mod. Hosp., St Louis, 1916, vi, 112.

Who shall manage the training school for nurses? Mod. Hosp., St Louis, 1916, vi, 114-115.

Advantages of the budget system. (Editorial). Mod. Hosp., St. Louis, 1916, vi, 186.

1917

Hurd, H. M., Drewry, W. F. [et at] The institutional care of the insane in the United States and Canada. Vol. iv. Bait., 1917, Johns Hopkins Press. 652 p., 8°.

Johns Hopkins and some of his contemporaries. Johns Hopkins Hosp. Bull., Bait, 1917, xxviii, 225-229.

State hospitals and agricultural preparedness. (Editorial). Mod. Hosp., St. Louis, 1917, ix, 24.

Burket, W. C. Bibliography of William H. Welch, M. D., LL. D. With foreword by Henry M. Hurd. Bait, 1917, Johns Hopkins Press. 47 p., 4°.

1919

A sketch of Dr. Lyman Spalding. Johns Hopkins Hosp. Bull., Bait, 1919, XXX, 125-129. Also: Bull. Med. Library Ass., Bait, 1918-19, viii, 29-38.


I


December, 1919]


373


INDEX TO VOLUME XXX OF THE JOHNS HOPKINS HOSPITAL BULLETIN.


Abscess, postscarlatinal cervical, hiemorrhage into a. Ligation of

the common carotid. Recovery, 240. Agglutination, phagocytosis and, in the serum in acute lobar

pneumonia; the specificity of these reactions and the regularity

of their occurrence, 167. Anaesthesia and asepsis, reminiscences of two epochs, 273. Antituberculosis measures, 49.

Asepsis, antesthesia and, reminiscences of two epochs, 273. B. influciizw. the effect of different bloods on the growth of, 129. Bacteria introduced into the upper air passages, the fate of, 317. Barker, L. F., Osier as chief of the medical clinic, 1S9. Barker, L. F. and Carter, D. W., Jr., Chronic pemphigus vegetans

of several years' duration, 302. Benzine poisoning, with report of a chronic case, 309. Blogg, SI. W., Bibliography of Howard A. Kelly, 293. Blogg. M. W.. Bibliography of Sir William Osier, 219. Blood sugar, studies on. IV. Effects upon the blood sugar of the

repeated ingestion of glucose, 306. Bloomfleld, A. L., The fate of bacteria introduced into the upper

air passages, 317. Bloomfleld, A. L., The relation of spontaneous nephritis of rabbits

to experimental lesions, 121. Bloomfleld, A. L. and Harrop, G. A., Jr., Clinical observations on

epidemic influenza, 1. Bloomfleld. A. L. and Mateer, J. G., Changes in skin sensitiveness

to tuberculin during epidemic influenza, 238. Bloomfleld. A. L. and Waters, C. A., The correlation of X-ray findings and physical signs in the chest in uncomplicated epidemic

influenza. 252. Boggs, T. R , Osier as a bibliophile, 216. Books received, 139; 183; 256; 285; 315; 340. Bridgman, E. W., Notes on the group of symptoms designated as

effort syndrome, 279. Brown, T. R., Osier and the student, 200.

Brush, E. N., Osier's influence on other medical schools in Baltimore. His relation to the medical profession, 20S. Brush. E. N.. Osier's literary style, 217. Carter, D. W., Jr. and Barker, L. F., Chronic pemphigus vegetans

of several years' duration, 302. Carter. E. P., RIchter, C. P. and Greene, C. H., A graphic applica tion of the principle of the equilateral triangle for determining ^ the direction of the electrical axis of the heart in tlie human

electrocardiogram. 162. Cerebral ventricles, fluoroscopy of the, 29.

Cerebrospinal fluids of cats, analysis of, with meningeal infections, 242. Chatard. J. A., Osier and the Book and Journal Club, 211. Chorea, an electromyographic study of, 35.

Clark, Admont H., The efl'cct of diet on the healing of wounds, 117. Clark. Admont Halsey, In niemoriam, 272. Clough, P. W., Phagocytosis and agglutination in the serum in

acute lobar pneumonia; the specificity of these reactions and

the regularity of their occurrence. 167. Cobb. S., An electromyographic study of chorea, 35. Colston. J. A. C. and Waters, C. A., The r61e of the Xray In the

diagnosis of longstanding renal tuberculosis, 268. Councilman, W. T., Some of the early medical work of Sir William

Osier, 193. Cross-Ptrlatlons. the development of. In the heart muscle of the

chick embryo. 176. Crowe. S. J. and Thacker-Nevllle, W. S., Tlie influenza bacillus In

paranasal sinus Infections. 322. Cull, S. T. W., Spina bifida with associated disturbances In a

human embryo 17 mm. long, 181.


CuUen, T. S., Dr. Henry M. Hurd, flrst superintondent of The Johns Hopkins Hospital, 341.

Cullen, T. S., Dr. Howard A. Kelly, Professor of Gynecology in The Johns Hopkins University and Gynecologist-in-Chief to The Johns Hopkins Hospital, 287.

Dandy, W. E., Fluoroscopy of the cerebral ventricles, 29.

Davison, W. C. and Holm, M. L., Meningococcus pneumonia. I. The occurrence of post-influenzal pneumonia In which the diplococcus Introcellularis meningitidis was isolated. From observations at Camp Coetquldon, A. E. F., France, 324.

Davison, W. C, Holm, M. L. and Emmons, R. V. B., Meningococcus pneumonia. II. The epidemiology of postinfluenzal pneumonia in which the diplococcus intracellularis meningitidis was Isolated, 329.

Diet, the effect of, on the healing of wounds, 117.

Digitalis, observations on the clinical pharmacology of, 131.

Douglas^ B., The reaction of the leucocytes in epidemic influenza, 338.

Effort syndrome, notes on the group of symptoms designated as, 279.

Electrocardiogram, human, a graphic application of the principle of the equilateral triangle for determining the direction of the electrical axis of the heart in the human electrocardiagram, 162.

Electromyographic study of cliorea, 35.

Emmons, R. V. B., Davison, W. C. and Holm, M. L., Meningococcus pneumonia. II. The epidemiology of post-influenzal pneumonia in which the diplococcus intracellularis meningitidis was isolated. 329.

Equilateral triangle, a grapliic application of the principle of the, for determining the direction of the electrical axis of the heart in the human electrocardiogram, 162.

Felton, L. D.. Analysis of cerebrospinal fluids of cats with meningeal infections, 242.

Fluoroscopy of the cerebral ventricles, 29.

Fry, Elizabeth — Quaker Reformer, 72.

Futclier, T. B.. Osier's Influence on the relation of medicine in Canada and the I'nited States, 204.

Gastric mucosa, the occurrence of. In a case of Meckel's diverticulum producing Intestinal obstruction, 143.

Goetsch, E., The occurrence of gastric mucosa in a case of Meckel's diverticulum producing Intestinal obstruction, 143.

Granules, degeneration, and vacuoles In the fibroblasts of chick embryos cultivated in i i((0. 81.

Green, Horace, and his probang, 246.

Greene, C. H.. Carter. E. P. and RIchter. C. P.. A graphic application of the principle of the equilateral triangle for determining the direction of the electrical axis of the heart In the human electrocardiogram, 162.

Haden, R. L., Benzine poisoning, with report of a chronic case, 309.

Hiemorrhage Into a postscarlatinal cervical abscess. Ligation of the common carotlrl. Recovery, 240.

Hamnian, L., Osier and the tuberculosis work of the hospital, 202.

Hamman, L. and Hlrschman, I. I., Studies on blood sugar. IV. EITects upon the blood sugar of the repeated ingestion of glucose, 306.

Harrop, G. A.. Jr., The behavior of the blood toward oxygen In influenzal Infections, in.

Harrop. G. A., Jr.. The production of tetany by the Intravenous Infusion of sodium bicarbonate. Report of an adult caae, 62.

Harrop, B. A.. Jr., and Bloomfleld, A. L., Clinical observations on epidemic Influenza, 1.

Hlrschman, I. I. and Hamman, L., Studies on blood sugar. IV. Effect upon the blood sugar of the repeated ingestion of glucose. 306.


374


[No. 346


Holm, M. L. and Davison, W. C, Meningococcus pneumonia. I. Tlie occurrence of post-influenzal pneumonia in wliicli the diplococcus introcellularis meningitidis was isolated. From observations at Camp Coetquldon, A. E. F., France. 324. Holm, M. L., Davison, \V. C. and Emmons, R. V. B., Meningococcus pneumonia. II. The epidemiology of post-influenzal pneumonia in which the diplococcus intracellularis meningitidis was isolated, 329. Howard, S. E., Bacteriological findings in epidemic influenza, 13. Huck, J. G., Changes in the blood immediately following transfusion, 63. Hurd, H. M., Some early reminiscences of William Osier, 213. Hurd, Henry M., A sketch of Dr. Lyman Spalding, 125. Hurd, Henry Mills, first superintendent of The Johns Hopkins

Hospital, 341. Influenza bacillus in paranasal sinus infections, 322. Influenza cases, fatal, comments on the pathology and bacteriology

of, as observed at Camp Devons, Mass., 104. Influenza, epidemic, bacteriological findings in, 13. Influenza, epidemic, changes in skin sensitiveness to tuberculin

during. 23S. Influenza, epidemic, clinical observations on, 1. Influenza, epidemic, the reaction of the leucocytes in, 33S. Influenza, uncomplicated epidemic, the correlation of X-ray findings and physical signs in the chest in, 252. Influenzal infections, the behavior of the blood toward oxygen in,

10. Inoculation with blood from measles patients, insusceptibility of

man to, 257. Inoculation with blood from measles patients, insusceptibility of

monkeys to, 57. Intestinal obstruction, the occurrence of gastric mucosa In a case

of Meckel's diverticulum producing, 143. Intravenous infusion of sodium bicarbonate, the production of

tetany by the, 62. Jacobs, H. B., Osier as a citizen and his relation to the tuberculosis crusade in Maryland, 205. Kelly, H. A., Osier as I knew him in Philadelphia and in the

Hopkins, 215. Kelly, Dr. Howard A., Bibliography of, 293.

Kelly, Dr. Howard A., Professor of Gynecolog>- in The Johns Hopkins University and Gynecologist-in-Chief to The Johns Hopkins Hospital, 287. Knox, J. H. M., Jr., Dr. George Peirce, 254. Krause, A. K., Antituberculosis measures, 49. Leucocytes, the reaction of the, in epidemic influenza, 338. Lewis, M. R., The development of cross-striations in the heart

muscle of the chick embryo, 176. Lewis, W. H., Degeneration granules and vacuoles in the fibroblasts of chick embryos cultivated in vitro. 81. Lung architecture, stereoroentgenograms of the injected lung as

an aid to the study of the, 34. McCrae, T., Osier and patient, 201.

MacCallum, W. G., In Memoriam— Admont Halsey Clark, 272. MacCallum, W. G., Osier as a pathologist, 197. Macht, D. I., A pharmacological appreciation of a Biblical reference to mass poisoning, II Kings, IV, 38-41, 38. Manus meditationis, 184.

Mass poisoning, a pharmacological appreciation of a Biblical reference to, II Kings, IV, 38-41, 38. Mateer, J. G. and Bloomfleld, A. L., Changes in skin sensitiveness

to tuberculin during epidemic influenza, 238. Measles blood, the reaction of monkeys to the inoculation of, 311. Measles patients, insusceptibility of man to inoculation with

blood from, 257. Measles, the occurrence of the Pfeifter bacillus in, 331.


Meckel's diverticulum, the occurrence of gastric mucosa in a case

of, producing intestinal obstruction, 143. Meningeal infections, analysis of cerebrospinal fluids of cats with

242. Meningococcus pneumonia. I. The occurrence of post-influenzal pneumonia in which the diplococcus intracellularis meningitidis was isolated. From observations at Camp Coetquldon, A. E. F., France, 324. Meningococcus pneumonia. II. The epidemiology of post-influenzal pneumonia in which the diplococcus intracellularis meningitidis was isolated. From observations at Camp Coetquldon, A. E. F., France, 329. Meyer, A. W. and Wynne, H. M. N., Some aspects of ovarian pregnancy, with report of a case. 92. Miller, W. S., Granville Sharp Pattison, 98. Miller, W. S., Horace Green and his probang, 246. Miller, W. S., Stereoroentgenograms of the injected lung as an

aid to the study of the lung architecture, 34. Nephritis, spontaneous, of rabbits, relation of, to experimental

lesions, 121. Notes and news, 25.

Notes on new books: Carman, R. P. and Miller, A., The roentgen diagnosis of diseases of the alimentary canal, 27; — Sellards, A. W., The principles of acidosis and clinical methods for its study, 136; — Strong. R. P. (chairman). Trench fever: report of Commission Medical Research Committee, American Red Cross. 136;— Stokes, J. H., The third great plague, 136; — Aeddar, E. B., Syphilis and public health, 136; — Hartzell, M. B., Diseases of the skin, 136; — Barjon, F., Radio-diagnosis of pleuro-pulmonary affections, 136; — Prince, N. C, Roentgen technic, 136; — MacCurdy, J. T., War neuroses, 136; — Smithies, P., Quarterly Medical Clinics. A series of consecutive clinical demonstrations and lectures, 284; — Wenyon, C. M. and O'Connor, F. W., Human intestinal protozoa in the near East, 284; — Lewis, T., The soldier's heart and the effort syndrome, 284; — Wilson, R. M. and Carroll, J. H., The nervous heart, 314; — Macleod, J. M. H., Burns and their treatment, 314; — Von Hug-Hellmuth, H., A study of the mental life of the child, 314; — Macleod, J. J. R., Physiology and biochemistry in modern medicine, 314.

Noyes, M. C. Osier's influence on the library of the Medical and Chirurgical Faculty of the State of Maryland, 212.

Osier and patient, 201.

Osier and the Book and Journal Club, 211.

Osier and the student, 200.

Osier and the tuberculosis work of the hospital, 202.

Osier as a bibliophile. 216.

Osier as a citizen and his relation to the tuberculosis crusade in Maryland, 205.

Osier as a pathologist, 197.

Osier as chief of the medical clinic. 189.

Osier as I knew him in Philadelphia and in the Hopkins, 215.

Osier's influence in building up the Medical and Chirurgical Faculty, 209.

Osier's influence on other medical schools in Baltimore. His relation to the medical profession, 208.

Osier's influence on the library of the Medical and Chirurgical Faculty of the State of Maryland, 212.

Osier's influence on the relation of medicine in Canada and the United States, 204.

Osier's literary style, 217.

Osier, Sir William, bibliography of, 219. i

Osier, Sir William, some of the early medical work of, 193.

Osier, the teacher, 198.

Osier, William, some early reminiscences of, 213.

Ovum, single, twins, formation of, 235.

Paranasal sinus infections, the influenza bacillus in, 322.

Pattison, Granville Sharp, 98.


Dkckmhkk, ItM'Jj


373


Pelrce, Dr. George, 254.

I'empliigus vegetans, chronic, of several years' duration, 302.

I'feiffer bacillus in measles, the occurrence of the, 331.

Phagocytosis and agglutination in the serum in acute lobar pneumonia: the specificity of these reactions and the regularity of their occurrence. 167.

Pharmacological appreciations of a Biblical reference to mass poisoning, 11 Kings, IV, 38-41, 38.

Pneumonia, acute lobar, phagocytosis and agglutination in the serum in; the specificity of these reactions and the regularity of their occurrence, 107.

Pneumonia, meningococcus. 1. The occurrence of post-influenzal pneumonia in which the diplococcus intracellularis meningitidis was isolated, 324.

Pneumonia, meningococcus. II. The epidemiology of post-influenzal pneumonia in which the diplococcus intracellularis meningitidis was isolated, 329.

Pregnancy, ectopic, 15.

Pregnancy, ovarian, some aspects of, with report of a case, 92.

Proceedings of The Johns Hopkins Hospital Medical Society: Bloomfield. A. L. and Harrop, G. A., Clinical observations on epidemic influenza, 110: — Wolbach, S. B., Comments on the pathology and bacteriology of fatal influenza cases, as observed at Camp Devens, Massachusetts. 110; — Tliompson, W. G., A functional re-education clinic: organization and methods, 110; — MacCallum, \V. G., Malaria in the Federated Malay States. A correction. 110.

Itichter. C. P., Carter, E. P. and Greene, C. H., A graphic application of the principle of the equilateral triangle for determining the direction of the electrical axis of the heart in the human electrocardiogram, 162.

Rivers, T. .M.. Haemorrhage into a postscarlatinal cervical abscess. Ligation of the common carotid. Recovery, 240.

Rivers, T. M., The effect of different bloods on the growth of B. influcnzir, 129.

Sellards, A. W., Insusceptibility of man to inoculation with blood from measles patients, 257.

Sellards, A. W., The reaction of monkeys to the inoculation of measles blood, 311.

Sellards, A. W. and Sturn, E., The occurrence of the Pfeiffer bacillus In measles. 331.

Sellards, A. W., and Wentworth, J. A., Insusceptibility of monkeys to inoculation with blood from measles patients, 57.

Singer, C, The manus meditationis, 184.

Skin sensitiveness, changes In, to tuberculin during epidemic influenza, 238.

Smith, S., Reminiscences of two epochs — anaesthesia and asepsis, 273.

Spalding. Dr. Lyman, a sketch of, 125.

Spina bifida with associated disturbances in a human embryo 17 mm. long, 181.

Stereoroentgenograms of the injected lung as an aid to the study of the lung architecture, 34.

Streeter, C. L.. Formation of single-ovum twins, 235.

Sturm, E. and Sellards. A. W., The occurrence of the Pfcifrer bacillus In measles, 331.

Tetany, the production of, by the Intravenous infusion of sodium bicarbonate. Report of an adult case, 62.

Thacker-Neville. W. S., and Crowe, S. J., The Influenza bacillus in paranasal sinus infections, 322.

Thayer, W. S.. Osier, the teacher. 198.

Thomas, H. M., Elizabeth Fry- Quaker Reformer, 72.

Thomas, H. M.. Some memories of the development of the medical school and of Osier's advent. IS.t.

Titles of papers appearing during the year, elsewlifre than In the Bii-LETiN, by present and former members of the hospital and medical school staff, 42.


Transfusion, changes in the blood immediately following, 63.

Tuberculosis, renal, the rdle of the X-ray in the diagnosis of longstanding, 268.

Ventricles, cerebral, fluoroscopy of the, 29.

Waters. C. A., and Bloomfield, A. L., The correlatiqn of X-ray findings and physical signs in the chest in uncomplicated epidemic influenza, 252.

Waters, C. A., and Colston, J. A. C, The r61e of the X-ray in the diagnosis of long-standing renal tuberculosis, 268.

Wedd. A. M., Observations on the clinical pharmacology of digitalis, 131.

Wentworth, J. A., and Sellards. A. W., Insusceptibility of monkeys to inoculation with blood from measles patients, 57.

Wolbach, S. B., Comments on the pathology of fatal influenza cases, as observed at Camp Devens, Mass., 104.

Woods. H., Influence in building up the Medical and Chirurgical Faculty. 209.

Wynne, H. M. N., Ectopic pregnancy, 15.

Wynne, H. M. N., and Meyer, A. W., Some aspects of ovarian pregnancy, with report of a case, 92.

X-ray findings and physical signs, the correlation of. in the chest in uncomplicated epidemic influenza, 2.')2.

X-ray, the role of the. in tlic diagnosis of long-standing renal tuberculosis, 268.

ILLUSTRATIONS Two illustrations in a case of epidemic influenza — one showing

inside of mouth of patient, and the other spots found on mucosa

of check, 4. Fluoroscopy of the cerebral ventricles, 31-32. Stereoroentgenograms of an Injected lung, 35. Electromyogranis used In study of chorea, 36. Citrullus Colocynthis Arn, 39. Ecballium Elaterium. 39. Elizabeth Fry, 72. Degeneration granules and vacuoles In libroblasts of chick embryos

cultivated in vitro, 91. Gross specimens from a case of ovarian pregnancy. 96. Granville Sharp Pattison, 98. Nathaniel Chapman, 98.

Specimens of lungs from cases of Influenza, 108. Specimens of kidneys showing relation of spontaneous nephritis

of rabbits to experimental lesions, 124. Illustrations showing growth of strains of B. influcmw in human

blood meat infusion agar and rabbit blood meat infii^iion

agar, 130. Electrocardiograms showing the eflect of digitalis on the heart

waves, 134. Meckel's diverticulum, 144.

Magnified sections of muco.sa In a case of Meckel's diverticulum, 146. eland tubules in .Vleckrl's diverticulum, 148. L'mbllical polyp with central fistulous opening, remnant of

omphalomesenteric duct. In Meckel's diverticulum, 149. Omphalomesenteric duct in form of an umbilical fistula In Meckel's

diverticulum. 151. Umbilical polyp connected with Meckel's diverticulum and patent

omphelomesenteric duct with polypoid formation at umbilicus,

152. Drawing Illustrating the fundamental principle of the equilateral

triangle for determining the direction of the electrical axis of

the heart In the human electrocardiogram, 162. Drawings and electrocardiograms illustrating the principle of the

equilateral triangle for determining the direction of the electrical axis of the heart, 165-166. Photographs and drawings in a case of development of cross strlatlons in the heart muscle of the chick embryo, 178.



Spina bifida witli associated disturbances in a liuman embryo, 182.

Manus Meditationis (The Hand of Meditation), 184.

Sir William Osier in 1906. Painted by Sargent, 186.

Sir William Osier— the Saint, by Max Broedel, 192.

Sir Williarn Osier at a patient's bedside, 201.

Sir William Osier. Painted by Seymour Thomas, 206.

Bookplate of the Library of the Medical and Chirurgical Faculty of the State of Maryland, purchased through the William Osier Testimonial Fund for the Advancement of Medicine, 212.

Sir William Osier in 1901, 1902 and 1913, 214.

Dr. William S. Halsted, Sir William Osier and Dr. Howard A. Kelly taken about 1900, 218.

Formation of single ovum twins, 236, 237, 238.


Horace Green, 246.

X-ray photographs of the chest in uncomplicated epidemic influenza, 252.

X-ray photographs of the kidney and ureter in a case of renal tuberculosis, 270.

Dr. Admont Halsey Clark, 272.

Tablet in memory of Dr. Admont H. Clark, 272.

Dr. Stephen Smith, 273.

Dr. Howard A. Kelly, 288, 290.

Pemphigus vegetans, 302, 304.

Plate spreader and throat swab used in cases of meningococcus pneumonia, 331.

Dr. Henry M. Hurd at various ages, 342, 346, 364, 369.


The Origin and Development of the Lymphatic System. By Florence R. Sarin. 94 pages. Price, $2.00.

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