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the urinary organs. In this ease cocci and colon bacilli were  
the urinary organs. In this ease cocci and colon bacilli were  
associated with the gas-bacillus.
associated with the gas-bacillus.
In a case of Hr. Kelly's, of winch the full records have
been given me by Dr. Miller,' 8 there was pneumaturia deruon
K Such cases are reported by Welch and Flexner, Goebel, Dunham and Howard in papers already cited.
M These do not include some instances of very extensive postmortem emphysema of the organs with gas everywhere throughout the body.
Case XIII of our list in Journal of Experimental Medicine,
1896.
88 This case is briefly reported by Kelly and MacCallum, Journ.
strated by cystoscopic examination and ureteral catheterization to come exclusively from the inflamed left renal pelvis
and ureter. Among cocci and other bacteria were found on
coverslips bacilli morphologically resembling Bacillus aerogenes capsulatus, but unfortunately no anaerobic cultures
were made. None of the bacteria which grew aerobieally
piod need gas in lactose-agar, This case is interesting as
demonstrating that the gas may come exclusively from one
renal pelvis and ureter, but the microorganism producing the
gas was not satisfactorily demonstrated. It seems certain
that it was an anaerobic organism, and from the microscopical appearances may have been the gas-bacillus.
The subject of submucous gas-cysts will be considered subsequently; but here it may be mentioned that besides the gascysts in the renal pelves noted by Welch and Flexner in the
case already cited, Coebel found gas-blebs, containing in pure
culture Bacillus aerogenes capsulatus, beneath the mucous
membrane of the urinary bladder, without gas elsewhere in
the body, and Dunham has reported a like condition of the
bladder in a ease of emphysematous gangrene with general
invasion of the blood and organs by the gas-bacillus.
Bacteria have been found in emphysema of the bladder
(cystitis emphysematosa) also by Eisenlohr, w Camargo/" and
Kedrowsky," but it is impossible from the authors' descriptions to identify their bacteria. Kedrowsky considers that
the bacillus isolated by him is allied to Bacillus aerogenes
capsulatus, but less sensitive to oxygen. Perhaps it was
Sanfelice's Bacillus pseudo-cedematis maligni, to which I have
already referred, but Kedrowsky "s description of his cultures
hardly inspires confidence in their purity.
Welch and Flexner and Howard have reported rinding the
gas-bacillus, in association with other bacteria, in inflammatory lesions of the bladder, renal pelvis and kidneys, without
the detection of gas. Howard considers that in one of his
cases the bacillus was concerned in the etiology of suppurative
lesions of the kidneys but in this case the colon bacillus and
Streptococcus pyogenes were also present.
Infections Derived feom the Gastko-Intestinal Canal.
Mention has already been made of the frequent, if not constant, presence of Bacillus aerogenes capsulatus in the. intestinal canal, of gaseous phlegmons originating from this source,
and of the readiness with which intestinal bacteria may gam
access to the genito-urinary tract.
The intestine is by far the commonest source of the gasbacilli found together with gas-bubbles in the blood aud
organs at autopsies. This invasion may occur either with or
without definite intestinal lesions, and is probably in the
majority of cases an agonal or post-mortem event. The mode
of distribution and spread of the bacilli in these cases has
Amer. Med. Assoc, 1898, XXXI, p. 376, whose paper may be consulted for the full literature of pneumaturia.
8 " Ziegler's Beitr., 1888, III. p. 101.
"" These de Geneve, 1891.
" Centralbl. f. allg. Path. u. path. Anat., 189S, IX, p. 817.
September. 1900.]
JOHNS HOPKINS HOSPITAL BULLETIN.
201
been well described by Howard.*" whose experience has been
exceptionally large with this class of affections. Especially
demonstrative of invasion of gas-bacilli from the intestine,
usually post mortem, is the occurrence of gas-bubbles limited
to the neighborhood of the intestine, as in the intestinal wall.
within the portal or mesenteric wins, or lymphatics, in the
Subperitoneal tissues, mesentery ami omenta, around the pancreas, in the mesenteric gland, and especially in the louse
tissue near the gall-bladder and in the porta of the liver,
without gas in more remote situations. 1 bave seen examples
of each of these occurrences in very early autopsies without
ordinary cadaveric decomposition.
Local Gastro-intestinal Lesions. — Interstitial emphysema of
the gastro-intestinal wall will be considered subsequently.
Howard has described several cases with larger or smaller
areas of superficial necrosis of the mucous membrane of the
stomach and intestine, in which gas-bacilli were present in
large numbers. These areas, which may occur either with or
without gas-cysts, are found most frequently beneath the
folds of the valvular conniventes and are characterized by
absence of nuclear staining and disintegration of the cells
and tissue, usually without marked inflammatory reaction.
Bacillus aerogenes capsulatus may undoubtedly be a cause,
of meteorism. Instances of this are reported by Welch and
Flexner and by Howard.
Pneumo-peritonitis with and without Perforation. — My records include 13 cases of diffuse peritonitis in the exudate of
which Bacillus aerogenes capsulatus was found. Eleven of
these were in autopsies made either by Dr. Flexner or myself,
1 having already been published by us in 1S9C. The remaining 2 cases (both being perforations of gastric ulcers) have
been reported by Page, 8 ' and by Pratt and Fulton.'" It was
the observation of these cases which first called my attention
to the frequent presence of the gas-bacillus in the intestine.
Ten of the cases were perforative and 3 were non-perforative. Of the former 4 were the result of perforation of
typhoid ulcers, 4 of gastric ulcers. 9 '' one of strangulated, gangrenous intestine and one of a cancerous ulcer of the duodenum. In the last ease (autopsy fourteen hours after Jr.:] in
the exudate was sero-fibrinous and the gas-bacillus was Eound
in pure culture" and abundantly in the peritonea] cavity and
K Op. cit., p. 491.
" Canada Lancet, May, 1900.
" Boston Med. and Surg. Journ., June 7, 1900, p. 599.
*=■ Welch and Flexner have reported an instance of peritonitis
from perforated gastric ulcer in a rabbit, in which the gas bacillus
was found.
"The purity of the culture in this case is explicable by the
results of dishing and Livingood's interesting bacteriological and
experimental studies of the duodenal flora published in Contributions to the Science of Medicine, Dedicated by his pupils to
William Henry Welch on the 25th Anniversary of his Doctorate,
p. 543, Baltimore, 1900.
was absent from other organs and the blood. In the other
perforative eases the gas-bacillus was mixed with other bacteria, although in some instances it predominated. In all of
the eases the abdomen w a.- greatly distended with gas and
usually there was great tympanites.
I attach especial importance to the ease fully reported by
Welch and Flexner,"' in which we brought conclusive evidenci
of the occurrence of pneumoperitonitis without perforation,
the first of the kind on record in which similar proof was
obtained. The presence of gas ill the peritoneal cavity was
recognized during life. Since our publication a similar ease
has been observed by Dr. Flexner in Manila, who has kindly
furnished me the notes. At the autopsy, twelve hours alter
death, there was found hsemorrhagic infarction of the lower
part of the ileum and adjacent part of the huge intestine,
caused by the passage of this part of the intestine through
a hole in the mesentery. The peritoneal cavity was greatly
distended with gas which burnt with a pale, blue flame.
There was a large amount of frothy, bloody serum in the
peritoneal cavity together with a fibrinous exudate. The
most careful examination showed no perforation. Bacillus
aerogenes capsulatus was obtained in pure culture and abundantly from the peritonea] fluid. Gas was absent from the
blood and other organs.
We have found the gas-bacillus, mixed with other bacteria,
twice in circumscribed, gas-containing, intraperitoneal abscesses resulting from perforation of the appendix vermiformis.
Hepatic and Biliary Infections. — The development of gas
in the liver is so sinking a phenomenon in most autopsies
where the gas-bacillus and free gas are found in the blood
and organs that I'. Ernst used the. term " Schaumleber " for
the title of his art ii b the gas-bacillus, published a year
after the paper by Welch and Nuttall, in which we first
directed attention to the subject of foamy organs and the
gas-bacillus.™ I have already considered the general subject
of gas-bubbles in the blood and organs, and wish here to call
attention especially to infections of the gall-bladder and
biliary passages by Bacillus aerogenes capsulatus.
In cases of foamy liver gas may be found in the bile-duets
and gall-bladder, but my experience is that, when the gasbacilli reach tin' liver through the blood-vessels, the appearance of gas in these situations is a rather late occurrence and
met chiefly in advanced cases. In contrast to these cases are
the observations of gas in the biliary passages, associated
sometimes with definite lesions of the bile-ducts and liver.
where the evidence is that the gas-bacilli entered from the
" Op. cit., p. 35.
" Heydenreich's paper on " Emphysem der Leber " (Centralbl. f.
Bakter., 1897, XXI, p. 305) may be mentioned as a curiosity. He
had never heard of the gas-bacillus or of any other investigation
of the subject later than 1872. In contrast to this is the interesting article of P. Bernhardt on pneumathsemia and foamy organs
with full consideration of the recent literature. Deutsche med.
Woch., 1900, p. 83.
202
JOHNS HOPKINS HOSPITAL BULLETIN.
[No. 114.
intestine directly into these passages. Two such cases have
been reported by Howard." 5 and I have observed two cases.
Pratt and Fulton 100 report a remarkable ease of cancer of
the common bile-duci and pancreas in which cholecystotomy
was performed, the edges of opening in the gall-bladder being
stitched to the abdominal walls. At the autopsy the Liver
ml studded with minute abscesses with greenish translucent walls. In coverslips, sections and cultures Bacillus
- capsulatus was found in pure culture in these small
biliary abscesses, but there was no gas in the abscesses, the
liver, blood, or other organs. A somewhat similar case, in
which cholecystenterostomy for gall-stones bad been performed, was previously reported by Nicholls ™ from Adami's
laboratory. Here also multiple miliary abscesses containing
the gas-bacillus were found in the liver, but in this ease gas
was present in the liver, as well as in the blood and other organs, the autopsy being six hours after death. Larkin 10 " has
likewise reported a case of hemorrhagic pancreatitis with fat
necroses and small, multiple hepatic abscesses with gas-holes
in the liver, from which Bacillus aerogenes capsulatus was
isolated. The autopsy was eight hours after death.
Ilint/c' ha.- recorded a post-mortem observation of gas in
the inflamed bile-ducts with cholelithiasis. He cultivated
only the colon bacillus, but it does not appear that he made
anaerobic cultures.
From the foregoing cases it is to lie inferred that the gasbacillus may invade the bile-duets and gall-bladder from the
intestine, and sometimes during life, and that it may not only
produce gas hut also necroses and purulent inflammation.
The presence of gall-stones, cancer of the bile-ducts and
operations on the gall-bladder favor this mode of infection.
Etisi "" found the gas-bacillus (Bacillus perfringens), without
gas or other lesion attributed to it, in an extirpated gallbladder containing a calculus and clear viscid fluid.
[nteestitial Emphysema of the Gasteo-Intestinal,
Genito-TJbinaey and Biliary Tracts.
One of the si interesting lesions produced by Bacillus
aerogenes capsulatus is the formation of submucous or subserous gas-cysts or blebs, of which the earliest examples attributed to this organism were reported by P. Ernst, Goebel,
and Welch and Flexner. They are sufficiently common to
have been observed by nearly all investigators who have had
much experience with the gas-bacillus in human beings. My
list of cases includes '.'•"> instances of this condition, of which
.") were of the stomach, 11 of the intestine far oftener id' the
small than the large intestine), 5 of the gall-bladder ami bile
™ Contributions to the Science of Medicine, Dedicated by his
pupils to William Henry Welch on the 25th Anniversary of his
Doctorate, pp. 475 and 476, Baltimore, 1900.
'" Boston Med. and Surg. Journ., June 7, 1900, p. 599.
"" Brit. Med. Journ., 1897, II, p. 1844.
m Med. Record, 1898, LIII, p. 354.
"" Miinch. med. Woch., 1895, XLIII, p. 209.
m These, Paris, 1898.
ducts, 3 id' the urinary bladder, 1 of the renal pelvis, and I of
the vagina. The majority of the cases were observed by
Flexner, Howard, and myself, and in all the gas-bacillus was
demonstrated. The ease of emphysema of the vagina was
reported by Lindenthal.'" 5
These gas-cysts vary in size from microscopic dimensions
to large blebs. They are most common in the submucous
coat, but may be present in the mucous membrane, the muscular coat or beneath the serous covering, in fact, in any part
of the membranous wall. They may be few or in enormous
numbers, in groups or scattered. In one of our cases the
whole small intestine from the duodenum to the ileoccecal
valve was studded with small gas-cysts. Gas-cysts of the
same general character may be found in the mesentery and
omenta.
These gas-cysts are in their inception simply such gas-holes
as we are already familiar with in the liver and other organs
in eases of local or general invasion with the gas-bacillus.
They indicate a foamy or emphysematous condition of the
walls of the stomach, intestine, gall-bladder, bile-ducts, urinary bladder and vagina, due to the invasion into these parts
of the gas-bacillus.
The condition of the walls of the blebs and of the surrounding tissues varies. Some of the cavities are round and their
walls smooth, others are irregular in shape and have ragged
walls. They may correspond to dilated lymphatics, but more
frequently they do not represent dilatation of any performed
channels. There may be communication between adjacent
cavities, but oftener the cysts are distinct from each other.
The tissue in the immediate neighborhood of the cavities may
present no alteration not explicable by the mechanical pressure of the gas, or it may show necrosis in varying degree and
extent. Inflammatory changes or cellular reaction which
could be reasonably referred to the presence of the cysts or
of the gas-bacilli causing them were not noted. Sometimes
a little coagulated, homogeneous or granular material is present in sections of the cysts in hardened tissues, as indeed
may often be found in gas-holes in the organs.
In sections stained by (Irani there is usually no difficulty
in demonstrating the relation of the gas-bacilli to the cysts.
The bacilli may be in masses in the walls of the cysts, but
sometimes they are not more numerous there than in the
tissue at a distance from the gas-blebs, and occasionally it
requires some searching to find them. By anaerobic methods
the gas-bacillus can be cultivated from the cysts or the adjacent tissue.
All of the instances of submucous and subserous gas-cysts
in my list were observed post mortem. In the larger number
of cases gas-bacilli and gas-bubbles were more or less widely
distributed in the blood and organs, but without evidences of
ordinary post-mortem decomposition. There are, however,
several cases in which these gas-cysts in various situations
were the sole manifestation of the presence of the gas-bacillus
in the body. Howard has shown that if careful, systematic
'Wiener klin. Woch., 1897, pp. 3 and 35.
September. 1900.]
JOHNS HOPKINS HOSPITAL BULLETIN.
203
search is made for areas of necrosis and minute gas-cysts due
to Bacillus aerogenes capsulatus in the stomach and intestine,
these lesion? can lie found much more frequently than lias
been supposed.
It is. with our present information, a difficuli matter to say
in how many of these eases the emphysematous state existed
before death. It is certain that, at leas! in the great majority
of cases in my list, the emphysema was not the result of ordinary post-mortem decomposition. In a large numher of the
cases the autopsy was made within a few hours after death.
Howard, in one of his eases of gas-cysts, limited to the intestine, made the autopsy one hour after death. I have alreadj
emphasized the importance of great caution in interpreting
a- \ital processes the various gaseous conditions of parts and
organs not open to inspection during life, even when autopsies
are made soon after death and there is entire absence of putrefaction, and I can only repeat this caution here. Mere absence of nuclear staining around gas-holes 1 do not regard as
proof of their origin (hiring life.
, It would lead altogether too far to enter here into a discussion of the general subject of submucous gas-cysts concerning which there is a large literature, the principal references
to which will lie found in the articles of F.isenlohr."" Camargo."" Winands,'" Orlandi, 1 " 8 Dupraz 10 " and Lindenthal. 1 " 1
It would appear from a study of the records of the subjeci
that anatomically different conditions have been described
under the designation " gas-cysts " (cystides aeriferae). Some
have Keen apparently of long standing and show chronic inflammatory changes in the walls of the cysts and the surrounding tissues. The most voluminous records relate to the gascysts of the vagina (kolpohyperplasia cystica of Wmckel, emphysema vagiine of Eppinger).
At present we have no warrant to identify the more chronic
sts with thickened walls with the more acute emphysematous condition which I have described as referable to
Bacillus aerogenes capsulatus. Nevertheless the former are
probably of bacterial origin also, although I am unable to
accept the bacteriological findings of Eisenlohr, Camargo, Orlandi and Dupraz as at all convincing, for they made no use of
at lerobic methods of cultivation. It is quite possible I hat
Bacillus aerogenes capsulatus is concerned also in the etiology
of the gas-cysts of long standing; certainly it is important to
apply hereafter anaerobic cultural methods to their study.
Lindenthal lias no hesitation in identifying the emphysema of
the vagina observed by him post mortem and from which in a
single ease he cultivated what he chooses to call Bacillus
emphysematis vaginae (in reality our Bacillus aerogenes cap
sulatns) with Winckel's kolpohyperplasia cystica, hut. while
'"Zieglers Beitriige, 1888, III, p. 101.
' : These de Geneve, 1891.
"* Ziegler's Beitrage, 1895, XVII,, p. 38.
,M *Gazz. med. di Torino, 1896, XLVII, ]
"* Arch, de med. exper., 1897, IX, p. 282.
""Wiener klin. Wochenschr., 1897, pp. 3 and 35.
781.
Ic may he correct, further observations are needed before
their anatomical and etiological identification can he accepted.
The only instance in which gas-cysts of the human intestine
have been recognized during the life of the patienl is reported
by Balm, 1 " who found them in large numher upon opening
the abdomen. It is to ho regretted that no thorough bacteriological examination of this ease was made.
In my original communication on the gas-bacillus I ventured the surmise that the haeillus found by E. I'raenkel '" in
hardened sections from a ease- of gastritis emphysematosa
might he identical with Haeillus aerogenes capsulatus, and
this suspicion has gained in probability by Goebel's statements
based upon a re-examination of the sections, his work having
been done under Fraenkel's supervision.
Notwithstanding an effort at compression, so much space
has been occupied in the presentation of the foregoing subdivisions of our subject, which in less than a decade has grown
to considerable magnitude, that I shall only summarize very
briefly a few remaining topics, although all deserve fuller
treatment.
Pulmonary ami Pleural Injections. — To the two instances
of invasion of the lungs by the gas-bacillus reported by Welch
and Flexner, I can add the cultivation of this organism front
a gangrenous lung by Dr. flexner in my laboratory. It has
been found also by Guillemot"' and Hist"' in pulmonary
gangrene.
Of much importance is Levy's'" demonstration of Bacillus
aerogenes capsulatus as a cause of pneumothorax without perforation. This case and those of pneumoperitonitis without
perforation to which I have already referred have settled
affirmatively the long standing controversy concerning the
possibility of the generation of gas within closed serous sacs
during life. Nicholls "' has reported an instance of pneumothorax and pneumopericardium without perforation in which
the gas-bacillus was probably present. Rendu and Rist "' also
isolated the gas-bacillus (Bacillus perfringens) in a case of
putrid pleurisy with gas. May and Gebhart 1 " and Finley""
attribute their two cases of pneumothorax without perforation
to the colon haeillus. hut in neither were anaerobic cultures
made. It is important that in all gaseous affections anaerobeshould he searched for.
Bacillus Aerogenes Capsulatus in the BUmd during Life. —
1,1 Deutsche med. Woch.. 1899, p. 657.
'" Virchow's Archiv, 1889, CXVIII, p. 526.
1,3 These. Paris, 1899.
'" These, Paris, 1898.
1,1 Arch. f. exp. Path. u. Pharm., 1895, XXXV, p. 335.
"° Loc. cit.
1,7 Bull, et mem. Soc. med. d. hop. de Paris, 1899, 3. S., XVI,
p. 133.
°" Deutsches Arch. f. klin. Med., 1898, LXI, p. 323.
"* Philadelphia Monthly Med. Journ., 1899, I, p. 569.
204
JOHNS HOPKINS HOSPITAL BULLETIN.
[No. 114.
Extremely interesting is the demonstration by Gwyn,' "" both
by eoverslip specimens and by cultures, on repeated examinations, of Bacillus aerogenes capsulatus during life in the blood
of a patient, in the Johns Hopkins Hospital, with chorea
insaniens and acute endocarditis. 1 had the opportunity of
examining his cultures, which were entirely typical. The
patieni died but unfortunately no autopsy could be obtained.
There was no evidence during life of free gas in the blood or
tissues. The case is of importance as demonstrating that gasbacilli may be in the circulating blood for days in sufficient
number to be demonstrable both microscopically and culturally without evidence of free gas. 1 have already expressed
my suspicion that Achalme's anaerobic bacillus, which has
likewise been cultivated from the blond, as well as from the
i 3sui -. of several cases of acute articular rheumatism, is
identical with Bacillus aerogenes capsulatus.
Presence of Bacillus Aerogenes Capsulatus without Gas. — In
this connection I may say that the gas-bacillus may be presenl
and even multiplying within the human body without the
production of gas. Certain organs, above all the liver, oiler
much more favorable pabulum for the generation of gas than
do others, but even in the liver the bacilli may be present
without gas. 1 have found gas-bacilli in clumps within the
spleen and kidney, surrounded by areas id' necrosis, without
recognizable gas. 120 " I have already cited the demonstrations
by Cushing and by Pratt and Fulton of the gas-bacillus in
-mall abscesses without gas. the observation of the latter being
particularly complete and satisfactory, liist '"'' has cultivated
the gas-bacillus (Bacillus perfringens) from cases of fetid otorrhoea and of mastoid abscess. He does not mention the presence of gas in these cases. I have already cited his isolation
of this bacillus from the gall-bladder which contained no gas.
Dr. Harris in my laboratory isolated the gas-bacillus in pure
culture from an abscess containing blood and pus in the neck
of a dog. following an operation on the jugular vein. There
was no gas in the abscess. Aerobic cultures were entirely
negative. These observations, however, are not the only ones
demonstrating that the gas-baeillus may under certain circumstances and in certain situations manifest pyogenic
capacity.
'■' Bulletin of the Johns Hopkins Hospital, 1899, X, p. 134.
'-"a Cesaris-Demel's (loc. cit.) opinion that generation of gas in
the tissues is merely a putrefactive process pertaining not to any
particular kind of microorganism but to irreparable necrosis or
damage of the tissues, whereby they become the prey of indifferent gas-producing bacteria, is not proven by his own observations and is opposed by many facts described in this paper.
'-' These, Paris, 1898.
Meningitis. Pyogenic Capacity of Bacillus Aerogenes Capsulatus. — Howard,'""' in April, lsiil). reported a ease of acute
fibrino-purulent meningitis, following operation for urethroperineal fistula. Bacillus aerogenes capsulatus was found in
pure culture in the meningeal exudate. Likewise Hitschmann and Lindenthal " : ' have recorded another convincing
example of acute cerebral meningitis, following fracture of the
occipital bone, in which the gas-bacillus was found unmixed
with other bacteria. These authors call attention to the
pyogenic power of the gas-bacillus when it attacks the meninges, but. as already shown, the same power may be manifested elsewhere.
Cavities in the Brain. — Finally I would call attention to
Reuling and Herring's'" and Howard's studies of cavities in
the brain produced by Bacillus aerogenes capsulatus and to
the light which their observations shed upon certain obscure
examples of cerebral cavities previously reported.
In this excursion into pneumato-pathology I have invited
you to the survey of fields comparatively new and little
trodden. I can only hope that our journey has been not
without some interest and some profit to you. To me the
opportunity to present before such a body as the Massachusetts Medical Society the results of these investigations is one
which I highly appreciate.
I desire in closing to pay my tribute of respect and to call
to your grateful remembrance the founder of this lectureship.
Dr. George Cheyne Shattuek. That the subject of this address would not have been without interest to him may be
inferred from the title of his first Boylston Prize dissertation
on the theme propounded in 1806 and entitled: " The difference between mortification produced by an external cause and
that which is produced by a constitutional defect, the diagnostieks and proper mode of treatment of each." '"' By his
noble character, professional services and liberality Dr. Shattuck deserved well of the medical profession of his city and
state, and, indeed, of the whole country, and his memory is
worthily perpetuated not only by the foundation of this
lectureship but also by the endowment of the chair of morbid
anatomy in the Harvard Medical School.
'- Bulletin of the Johns Hopkins Hospital, 1899, X, p. 66.
,M Op. cit.
'-* Bulletin of the Johns Hopkins Hospital, 1899, X, p. 62.
,!S Published in Boston in 1808.
THE JOHNS HOPKINS HOSPITAL BULLETIN.
The Hospital Bulletin contains details of hospital and dispensary practice, abstracts of papers read, and other proceedings
of the Medical 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 XI is now in progress. The subscription price is $1.00 per year. The set of ten volumes will be sold for $20.00.
September. 1900.]
JOHNS HOPKINS HOSPITAL BULLETIN.
205
ON THE HISTOLOGY OF THE ISLANDS OF LANGERHANS OF THE PANCREAS.
By Eugene L. Opie, M. J)..
Instructor in Pathology, Johns Hopkins University.
The pancreas is much more complex in structure than the
other glandular organs which it closely resembles. Langer
buns, 1 in an inaugural dissertation published in 1869, gave
the first careful description of its histology and showed that
the organ has not the relatively simple structure oi' the salivary glands.
Langerhans studied the pancreas of rabbits which in its
essential features does not dili'er from that of other mammals.
The larger duets are lined by epithelium composed of a single
layer of high columnar cells. As the branches of the duct
become smaller, the epithelial cells become lower, cubical, and
finally flat or, as seen in section, spindle shaped, the nucleus
occupying the thicker central portion. The smallest duets
end in the acini composed of high columnar characteristically
glandular cells containing next the lumen numerous zymogen
granules. Within almost every acinus in contact with the
secreting cells Langerhans found one, two, or more cells of a
different nature, and to these he gave the name centre acinar
cells. They closely resemble the flat spindle-shaped cells
lining the very small ducts and he thinks that the epithelium
of the duct is continued over the secreting cells into the lumen
of the acinus, but he admits that he is unable to determine
with exactness the method by which the duet ends.
Distributed at intervals in the parenchyma are groups of
cells differing markedly from those of the ordinary glandular
type. Such groups are usually round and in tissue, treated
two or three days with Midler's fluid, appear with low magnification, as intensely yellow- specks. With high magnification they are found to be composed of small, irregularly
polygonal cells with a round nucleus and a refractive homogeneous cell body. Of the nature of these cell groups Langerhans declares himself entirely ignorant.
Numerous observers have described these structures which
are usually designated islands of Langerhans. Reliant." regarding them as analogous to lymph follicles, speaks of them
as -points folliculaires." Podwyssotski "' calls them pseudofollicles. They have been designated secondary cell groups,
inter-alveolar cell islets, etc.
In injected specimens Kuline and Lea' found scattered
through the organ glomerular structures composed "I' dilated
1 Langerhans. Beitriige zur mikroskopischen Anatomie der
Bauchspeicheldriise. Inaug.-Diss., Berlin, 1869.
■ Renaut. Sur les organes lymphoglandulaires et la pancreas
des vertebres. Compt. rend. d. l'Acad. d. Sciences, LXXXIX, 247,
1879.
* Podwyssotski. Beitriige zur Kenntniss des teineren Baues
der Bauchspeicheldriise. Arch. f. mikrosk. Anat, XXI. 765, 1882.
'Kiihne and Lea. Beobachtungen iiber die Absonderung des
Pancreas. Untersuch. a. d. Physiolog. Instit d. Univ. Heidelberg
II, 488, 1882.
and tortuous capillaries and showed that these glomeruli correspond to the cell groups which Langerhans described. The
islands are penetrated by numerous wide tortuous capillaries
which lie between cells forming irregular anastomosing columns. Material injected into the duct of the gland does not
penetrate the islands.
Interacinar cell islets have been studied by Harris and
(low/' and recently by Diamare," in a great variety of annual
species, including n niials, birds, amphibia ami reptiles.
Laguesse' has studied the development of these bodies in
sheep embryos and has reached conclusions which have not. I
believe, been confirmed, lie finds that at an early period of
growth the pancreas is composed of tortuous tubules formed
by a single layer id' epithelial cells. Here and there occur
cells which stain more deeply than those about them and.
like the border cells of the stomach, arc situated near the
outer surface of the tubule. These cells proliferate and form
what he calls primary islands of Langerhans. Accepting the
observations of Lcwaschcw. to be mentioned later, he thinks
that after development of the organ is completed similar
Structures, secondary islands of Langerhans, are formed from
groups of secreting acini.
Various opinions are held concerning the nature of flic
interacinar cell groups. The suggestions which have been
advanced may be classified as follows: (1) The islands id'
Langerhans. having the same origin as the secreting elements
of tin- gland, aiv formed during embryological life and persisting thereafter probably subserve some special function.
(2) They represent a stage in the embryological development
of the gland acini and those found in the adult organ are persistent rudimentary structures. (3) They are follicles of
lymphatic tissue scattered through the organ. (I) They are
modified acini, transformed as the result of functional activity
of a peculiar nature.
When throughout the gland structures are found composed
of cells differing from those of the acini, having a different
arrangement and bearing a peculiar relation to the bloodvessels, it seems probable that, formed in embryological life
they possess an anatomical identity as definite as that of the
glomeruli of the kidneys or the Malpighian bodies of the
* Harris and Gow. Note upon One or Two Points in the Comparative Histology of the Pancreas. Jour, of Phys., XV, 349,
1894.
"Diamare. Studii comparativi sulle isole di Langerhans del
pancreas. Internat. Monatsschr. f. Anat. u. Phys.. XVI. 155, 177.
1899.
' Laguesse. Sur les principaux stades du developpment histogenicnie du pancreas. Verhandlungen der anat. Gesellsch., 1897,
43.
206
JOHNS HOPKINS HOSPITAL BULLETIN.
[No. 114.
spleen. Schafer* thinks that they are similar to the small
ductless structures, the carotid and coccygeal glands and the
parathyroid bodies which are like them composed of anastomosing columns of epithelial-like cells, between which is a
network of delicate tortuous capillaries.
Laguesse" has suggested that these structures represenl a
stage in the development of the glandular acini but has subsequently abandoned this view, in support of which there is
uo evidence. A number of observers have emphasized the
supposed resemblance of the interaeinar islets to lymphoid
tissue. Kenaut '" has described the pancreas as a lymphoglandular organ composed, he conceives, of glandular structures and lymphoid tissue in intimate relation. He describes
the cell groups as " points folliculaires," in which cells of a
glandular type are situated in the meshes a reticular tissue.
Mouret " lias supported Kenaut 's somewhat ill-defined conception of a lympho-glandulax organ, but lias regarded the
cell group a.s small masses of lymphoid tissue. Kiihne and
Lea and Dieckhoff" think it probable that they are small
lymph follicles. Schlesinger 13 regards them as a variety of
lymph follicle whose cells differ from those of ordinary lymphoid tissue. Podwyssotski calls them pseudo-follicles and
states that though they resemble lymph follicles their cells
have nothing in common with lymphoid cells.
The only attempt to investigate experimentally the nature
of the islands of Langerhans has been made by Lewaschew,"
working in Heidenhain's laboratory, lie studied the pancreas of dogs ami eats, killed after having been subjected to
conditions which cause the gland to secrete actively. After
prolonged overfeeding or after the administration of pilocarpin, which stimulates the pancreas as it does the salivary
glands, he claims to have found structures representing transitions between the gland acini and the interaeinar cell group.
He observes acini containing one or more cells whose protoplasm is non-granular and stains lightly. A whole acinus
or a number of acini may be composed of such cells. In such
areas some of the cells may assume a polygonal shape and are
no longer grouped to form a central lumen. Other cell groups
consist entirely of polygonal cells without acinar arrangement, and these represent, he thinks, the fully formed islands
of Langerhans.
In order to obtain a large increase in the number of altered
acini one even maximal stimulation of the gland is not sufli
8 Schafer. Quain's Anatomy, Vol. Ill, Pt. IV p. 318.
* Laguesse Sur la formation des ilots de Langerhans dans
le pancreas. Compt. rend. Soc. de biol., 9. S., V. 819, 1893.
"' Renaut. Loc. cit.
11 Mouret. Tissue lymphoide du pancreas et cellule centroacineuse. Compt. rend. Soc. de biol., 10. S. I., 731, 1894.
'- Dieckhoff. Beitriige zur pathologischen Anatomie des Pancreas. Festschrift f. Thierfelder, Leipzig, 1895.
" Schlesinger. Die Erkrankung des Pancreas bei hereditarer
Lues. Virch. Arch., CLIV, 501, 1898.
" Lewaschew. Ueber eine eigenthiimliche Veriinderung der
Pankreaszellen warmbliitiger Thiere bei starker Absonderungsthatigkeit der Driise. Arch. f. mikros. Anat., XXIV, 452, 1886.
eient, but by the repeated administration of pilocarpin this
result is accomplished and the longer and more intense the
action of the drug the greater their number. To cause their
increase by overfeeding a very large quantity of food is necessary. Lewaschew believes that the cells composing the interaeinar groups may reassume the characters of secreting cells
and again form acini. He mentions that he has found an
unusual number of islands under conditions other than those
of increased functional activity. They were very numerous
in a dog which several days before its death had suffered with
fever.
The observations of Lewaschew have not been confirmed.
In the human pancreas one occasionally finds altered glandular cells. Xon-granular refractive cells may occur in otherwise normal acini and entire acini or groups of acini may lie
composed of such cells. Laguesse,'" regarding them as transitions between acini and interaeinar groups, has adopted the
view of Lewaschew.
It is by no means surprising that little is known concerning
the function of structures whose nature is so little understood.
Laguesse'" thinks that they represent secreting acini temporarily modified to adapt themselves to a new function, the
elaboration of an internal secretion. Schafer 1 ' and Diamare
think that the vascular islets probably furnish an internal
secretion. The only evidence in support of this suggestion is
contained in the short preliminary notice of Ssobolew." He
states that after feeding animals on carbohydrates the cells of
the islands become more granular. After ligating the duct
of Wirsung in dogs the islands of Langerhans. he finds, are
not involved in the sclerotic process which follows. He
thinks that this fact explains the absence of glycosuria after
ligation of the pancreatic ducts. In hitman eases I had observed after duct obstruction " similar resistance of the islands
to the consequent inflammation. In pancreas of two diabetics
Ssobolew was unable to discover islands of Langerhans.
I have attempted to determine the relation of the islands
of Langerhans to the other elements of the pancreas. They
have been observed in human cases under a great variety of
conditions, in cats and in dogs. Their relation to the bloodvessels has been studied in injected specimens. Finally, I
have attempted to repeat the experiments of Lewaschew in
order to test the possibility of transforming acini into interaeinar cell islets.
In the human pancreas the islands were found to be more
numerous in the splenic end or tail than elsewhere. To obtain
a numerical statement of their relative abundance, their num
15 Laguesse. Sur quelques details de structure du pancreas
humain. Compt. rend. Soc. de biol. S. 10., I, 667, 1894.
18 Laguesse. Compt. rend. Soc. de biol.. 9. S., V, 819, 1893.
17 Schafer. Internal Secretions. Lancet, 1895, II, 321.
" Ssobolew. Ueber die Structure der Bauchspeicheldriise unter
gewissen pathologischen Bedingungen. Centralbl. f. allg. Path. u.
path. Anat., XI. 202, 1900.
19 Opie. Pathological Changes Affecting the Islands of Langerhans of the Pancreas. Jour. Boston Soc. Med. Sciences, IV. 251,
1900.
September, 1900.]
JOHNS HOPKINS HOSPITAL BULLETIN.
207
ber .was determined in a sectional area of 0.5 square centimetre. Sections about 10 ft thick were made from the enlarged duodenal portion of the pancreas or the head, from
the mid-portion or body and from the splenic end or tail.
The following table gives their number in an area of 0.5
square centimetre in sections taken from the head, body and
tail of ten normal organs:
Body.
13
I
II
Ill
IV
V
VI
VII ....
VIII . . .
IX
X
Average .
The table shows that the islands are more abundant in the
tail or splenic end than in the bead and in the body, where
they are present in approximately equal number. They are
almost twice as numerous in sections from the tail as in those
from other parts. Since the number in only one plane is
recorded, in order to obtain their actual relative abundance it
is necessary to square these figures. They are then found to
be slightly less than three and a half times as numerous in
the tail as elsewhere.
The islands of Langerhans arc more numerous, as pointed
out by Kasahara/' in the pancreatic tissue of the foetus
and of very young children than in that of the adult,
Should we assume that they are formed during embryological
development and persist thereafter, this fact is readily explicable. The organ being much smaller in the foetus and in
the young child, the same number of islands, though themBelves -mailer, are closer together and therefore appear to be
more numerous in sections.
The cells composing (lie island- resemble those of the acini.
They have a large round, occasionally oval, vesicular nucleus
and a conspicuous cell body. The basal zone of the secreting
(ell. as is well known, stains deeply with nuclear dyes, for
example, hematoxylin or methylene-blue, while the central
portion which contains zymogen granules remains unstained.
The cells of the island, however, do not stain with nuclear
dyes, while with eosin their protoplasm takes ;> homogeneous
bright pink color. The nuclei differ but little from those of
in ighboring acini. They vary considerably in size and not
infrequently one finds very large round vesicular nuclei whose
diameter is two or more times that of those about. < )<
ally the cells, forming columns between which are the anastomosing capillaries, are very closely packed together and
M Kasahara. Ueber das Bindegewebe des Pankreas bei versehiedenen Krankheiten. Virch. Arch., CXLIII, 111, 1896.
nuclei are situated almost side by side; more frequently the
cells of the island are less numerous and the nuclei are less
closely crowded together.
The outline of the island is usually round or oval and is
not infrequently accentuated by a delicate circle of fibrous
tissue. In other instances the outline is less sharp and the
body accommodates its shape to that of the neighboring acini.
Occasionally one sees, apparently within the island, cells
arranged, as in the acini, about a central lumen and, indeed,
in many instances it is difficult to convince one's self that they
do not form part of it. The impression is produced that the
columns of the island are in continuity with cells having an
acinar arrangement. Since the islands and the secreting
acini have a common origin it is not inconceivable that they
may occasionally remain continuous in the adult organ. When
the foetal pancreas is affected by congenital syphilis, the
islands, I have found," retain their continuity with the secreting structures.
In the human pancreas the groups of acini about terminal
ducts are not sharply defined by connective tissue, so that
individual lobules, as in the human liver, are indistinctly
marked off and in places apparently fuse with one another.
In the pancreas of the eat the lobules, like those in the liver
of the pig, are much more sharply outlined by interstitial
tissue. Details of structure have been studied in the pancreas
id' the cat.
The parenchyma is divided by septa of fibrous tissue
into small polygonal areas varying in size and shape. When
injected with Berlin-blue a small ramification of the ducts is
found to penetrate the isolated group of acini. These subdivisions or lobules often appear completely isolated by
fibrous tissue from those nearby, but when one id' them is
traced through :i series of sections its separation may not be
uniform and in places one finds the parenchyma of adjacent
lobules in contact, the dividing septa being incomplete. That
these polygonal structures are actually independent id' one
another and represenl units of structure is readily demonstrated by causing an inflammatory increase of the interstitial
tissue. If the pancreatic <]\\i\^ of a cat are ligated and the
animal killed at the end of two or three weeks, the gland is
found to he the -eat of a chronic interstitial inflammation,
characterized by an increase of the interlobular tissue. The
Lobules are completely separated from one another by narrow
bands of firm fibrous tissue and occur in sections as rounded
triangular or polygonal areas id' parenchyma.
The islands of Langerhans occupy a position near the
centre of the lobule and in the splenic cud id' the gland each
lobule contains an island. In a given section many lobules
whose limits are more or less distinctly outlined are seen to
contain islands situated near their centre, while in neighboring lobules such structures may not be discoverable. If.
however, serial sections are studied every lobule is found to
contain an island. Its presence within the lobule is not
constant in other parts of the organ, and in the extremity
Opie. Loc. cit.
208
JOHNS HOPKINS HOSPITAL BULLETIN.
[No. 114.
of the descending arm of the gland they arc very few in
number.
The lobules are grouped about the medium sized duets.
The mam dints give off branches approximately at right
angles to their course. Brandling one or more times a dud
forms the centre of a group of lobules, which is usually elongated in form and taper.- to a point at or near the surface of
the gland. Such lobule groups arc separated from one another by relatively wide bands of areolar tissue much looser
in texture than that separating the individual lobules. The
lobule groups in the fresh state or in tissue macerated a few
Fiqi be 1. — Camera lueida tracing of the lobule boundaries in
one of a series of sections from the splenic end of a cat's pancreas.
The majority of the lobules are well defined. Those marked </, c,
f, <j and h are poorly outlined but are found to be more readily
distinguishable when traced through the series of sections. The
lobules, which are lettered (a to o), were traced through the series
and each was found to contain an island of Langerhans situated
near its centre. The section passes through the island in lobules n, e, i, / and n.
days in Midler's fluid may be separated from one another by
careful teasing. In the loose tissue lie (he larger duels.
arteries, veins, and nerves. An artery and vein penetrate
each lobule group in company with the duel and ramify between its lobules. The smallest arteries occasionally penetrate the lobules, but usually branches, diminishing in size,
give off capillaries which enter the lobule and form a close
network between the gland acini.
The capillaries id' the island of Langerhans form a glomerulus of tortuous freely anastomosing vessels, much thicker
than those between the acini. A single afferent vessel like
that of the glomerulus of the kidney does not enter this group
of dilated capillaries but numerous anastomoses make it continuous with the interacinar capillaries. When Berlin-blue is
injected through the aorta into the arteries of the pancreas,
it not infrequently happens that in portions of the gland
which are poorly injected the vessels of the island are tilled
with the injected mass, while the surrounding capillaries are
for the most part empty. If instead of soluble Berlin-blue
a granular injection mass, for example, cinnabar or ultramarine blue is used, the islands may be injected while the
interacinar capillaries contain little of the injected material.
The glomerular network is in very free communication with
the smallest arteries and apparently has a richer blood supply
than other parts of the lobule.
In the human pancreas lobules and lobule groups are not
so regularly arranged as in the cat. But both structures arc
more or less clearly definable. The lobules vary much in size
and are usually not clearly separated from one another.
Though an island of Langerhans is often situated in the
centre of a more or less clearly defined lobule, no constancy
id' position is discoverable. The lobule groups are separated by
relatively wide bands of loose areolar tissue in which are contained the medium sized ducts, the blood-vessels and the
nerves. Within the lobule group the arteries and veins which
are side by side do not, as in the cat, accompany the ducts.
In the normal human pancreas one occasionally finds small
groups of acini composed of cells differing from the typical
glandular type and suggesting a transition from the secreting
cell to that of the island of Langerhans. The cell-protoplasm
does not take the nuclear dye as does the basal portion of the
ordinary glandular cell, and when stained with eosin has a
bright pink color and homogeneous refractive appearance.
The nucleus, which shows no evidence of degenerative change.
is situated near the centre of the cell. Occasionally one or
more cells of the character described form part of an acinus
which otherwise resembles those about it. Usually, however,
a group of acini are changed, and such an area often corresponds in size to an island of Langerhans.
The presence of altered acini whose cells resemble those
of the island confirms at first sight the view of Lewaschew
that groups of acini may assume the characters of the interacinar structures. It is probable that such foci in part at
least represent what Laguesse" and Pischinger "' have described as stages of transition. The arrangement of more or
less columnar cells about a central lumen is. however, still
preserved and one does not find similar areas in which this
arrangement is lost. The lumen, indeed, is usually very conspicuous and is often considerably dilated, filled with products
of secretion which stain deeply with eosin. It seems probable
that these groups of acini are altered as the result of peculiar
functional activity, it may he. of hyperstimulation of the
gland. There is at least no evidence that they represent
22 Laguesse. Compt. rend., S. 10, I, 667, 1894.
2! Pischinger. Beitriige zur Kenntniss des Pankreas.
Diss., Miinchen, 1895.
Inaug.
September. 1900.]
JOHNS HOPKINS HOSPITAL BULLETIN.
■_•<)'. i
transitional stages between gland acini and islands of Langerhans.
Such altered acini are observed in a small proportion of
normal glands. They were found in three of twenty-seven
glands examined carefully for their presence. They were
present in three of seven relatively normal organs from diabetic patients. The occurrence of voracious appetite ami increased food ingestion in individuals so affected may explain
the occurrence of these areas which represent possibly loci of
peculiar secretory activity. They were particularly abundant
in one instance of chronic interstitial pancreatitis not associated with diabetes.
Lewaschew has claimed that he was aide to transform
groups of secreting acini into islands of Langerhans by stimulating the pancreas with pilocarpin. A single administration
of the drug does not suffice, hut by its repeated administration
an undouhted increase in the number of islands may. he says.
he obtained. Under such conditions these bodies appeared to
be more numerous than usual, but he has made no attempt
to determine their actual number. He does not record the
amount of pilocarpin used nor the frequency of its administration. T I is experiments have not been repeated.
I have attempted to confirm the observations of Lewaschew
by injecting subcutaneously pilocarpin muriate into dogs.
Since the number of islands was found to vary in different
parts of the gland, it was considered desirable to study sections
from corresponding parts of the organ. Specimens were prepared from (a) the splenic extremity, from (b) the portion
which is in contact with the duodenum, and from (V) the
d( scending portion which lies in the mesentery of the duodenum. In order to determine with accuracy the relative
abundance of the islands their number was counted in a
measured sectional area and compared with that found in the
pancreas of an animal to which pilocarpin had not been given.
Following is a summary of the experiments performed:
Dog No. 1. — The animal was given daily for nine successive
days 0.02 to 0.03 grm. of pilocarpin muriate. Profuse salivation was produced often with vomiting and diarrhoea.
Dog No. .'. — During twenty-eight hours pilocarpin muriate
0.005 to 0.0] grm. was injected subcutaneously six times.
The drug produced profuse flow of saliva.
Dog No. -:>'. — During twenty-four hours pilocarpin muriate
0.01 grm. was injected subcutaneously seven times. Profuse
salivation followed each injection.
In the table the figures represent the number of islandin 0.5 square ceni tre of sectional area. The letters refer
to the parts of the gland indicated above.
TABLE II.
Dog No. l
Average .... 56.6 37.6 6.6
Dog No. I
No. II. .
No. III.
Average
The figures show that no increase of the number of islands
was obtained in the three experiments. Transitional stages
between glandular acini and interacinar islets were not observed. The number of islands in that part of the descending
portion of the pancreas which lies in the mesentery of the
duodenum (c) is constantly much less than elsewhere. The
number in different glands and in different parts of the same
gland varies considerably. In the experiments of Lewaschew
these sources of error have apparently not been given sufficient weight.
CONCLUSIONS.
(1 ) The islands of Langerhans are composed of cells ha\ ing
the same origin as those of the glandular acini but forming
structures which are independent of the secreting apparatus
and in intimate relation with the vascular system.
(2) In the splenic end of the cafs pancreas they have a
definite position within the lobule, each of which contains one
of these structures.
(3) In the human pancreas they are more numerous in the
splenic extremity or tail than elsewhere. Similar variation
in their number is observed in cats and dogs.
(4) Prolonged stimulation of the gland does not. as claimed
by Lewaschew. transform groups of acini info islands of
Langerhans.
THE DISTRIBUTION OF CONNECTIVE TISSUE IN NEW GROWTHS.
liv W. C White, M.B.
(From the Pathological Laboratory of U" Johns Hopkins University and Hospital.)
I here report the result of the study of the distribution of
connective tissues (viz.. yellow elastic tissue, white fibrous
tissue and reticulum) in seventeen new growths, obtained in
the fresh state from the Surgical and Gynaecological Depart
ment of the Johns Hopkins Hospital through the kindness
of Dr. Cushing and Dr. Kelly.
The work was done in the Pathological Laboratory of tin
Hospital at the suggestion of Dr. L. F. Barker, and I am
much indebted to him for In- willing and valued assistance
throughout. To Dr. F. I'. Mall I am also under obligations
for many kind suggest ions.
The following methods were employed:
]. for the study of elastic tissue.
(,i) Demidessication and artificial oedema; Eresh tissue
stained w ith magenta.
210
JOHNS HOPKINS HOSPITAL BULLETIN.
[No. 114.
(6) Weigert's ' elastic fibre staining of the hardened tissue.
(c) Unna's orcein stain (hardened tissue).
2. Fur the study of white fibrous tissue and reticulum.
("I Mall's method/ Digesting the fresh frozen section in
pancreatin solution.
(b) Spalteholtz' method.' Digesting sections of hardened
tissues in pancreatin solution, alternate sections being stained
with hematoxylin and eosin for comparison.
(c) Van Gieson's picric acid fuchsin stain.
|r/i Mallory's new connective tissue stain, the use of which
was very kindly permitted by Dr. Mallory, although the formula is still unpublished.
In studying the distribution of these tissues it has been
taken for granted (1) that the tissue staining purplish with
magenta in the fresh preparations and deep blue with Weigert's stain in the hardened preparation is elastic tissue, and
(2) that the tissue left after digestion in pancreatin solution
and staining red with Van Gieson's stain and blue with Mallory's stain is either white fibrous tissue or reticulum, and I
have called them such in writing this paper.
The object has been, not to study the distribution of one
kind of connective tissue, but to study the character and
distribution of the several kinds by many methods.
It has been a great drawback that there is as yet no certain
method of distinguishing white fibrous tissue and reticulum.
Siegfried* has found in reticulum a substance which he calls
reticulin, thus distinguishing it from white fibrous tissue
which yields gelatine, but this method was not practically
applicable in the present study. Then certain structural differences, it is asserted, exist between the two substances; viz.,
the wavy more or less parallel fibrils of white fibrous tissue
running in bundles as against the very fine anastomosing and
branching fibrils of reticulum; but the two substances are s,,
intimately associated in any structure that the question arises
id' the possibility of the one being the final breaking up and
di\ ision of the other.
In the sarcomata and myomata reticular networks were
found which in structure coincided with reticulum, the fibrils
definitely branching and anastomosing, but they were here
intimately associated with bundles of wavy parallel fibres
which were just as typical of white fibrous tissue. In some
places this reticular network appeared to have Ms origin from
these bundles, while in other cases it seemed only to gain an
anchorage there, the fibrils extending only for a short distance
among the fibres of the bundles. In other places, and this
wa- very frequent in the sarcoma sections studied by Mall's
method, the filirils of the reticular network appeared to arise
from certain focal points suggesting the possibility of their
being the processes of cells which had been digested away-,
hut the most probable explanation of this appearance was to
1 Centralbl. f. alg. Path. u. path. Anat. IX, 1899.
2 Johns Hopkins Hospital Reports, Vol. I, 1896.
" Archiv f. Anat. u. Phys., Anat. Abth., 1897, Supp. Bd.
' Habilitationsschrift, Leipzig, 1892.
be found in the thickness of the sections, several fibrils overlying one another at certain points. Again, the fibrils which
presented the structural characters of white fibrous tissue
were frequently seen in the Mall preparations to break up
into much finer fibrils, suggesting the possibility of the two
substances, white fibrous tissue and reticulum, being the same
substance, the latter being the final division of the former.
So that without some method of determining the distinction or relation between the two substances the description
of what was found in the present study has necessarily been
purely objective, the two substances being included under the
one head. Still some endeavor was made to discover the relation after pancreatin digestion id' what was found in myomata to tendon and also to reticulum by the following methods
suggested by Dr. Mall.
Tendon was obtained from the human tendo-achillis;
Reticulum was obtained from the gut of a dog by drawing the
small intestine between the handles of a pair of scissors and
thus removing the muscular coats and mucous membrane,
leaving only the submucosa. A myoma was secured after
removal from the human uterus. Small sections of all three
were cut and digested in pancreatin solution. 5
They were then thoroughly washed in water and later
placed in test tubes containing (1) \ per cent hydrochloric
acid; (•,') 1 per cent hydrochloric acid; (■'!) 1 per cent solution
of caustic potash and immersed in a beaker of boiling water
and the results tabulated.
I have given also by permission the tables of Dr. Mall ' and
of Dr. Find. 7
TABLES.
Dr. Mall's Table.
Boiling KOH 1$ 30 seconds. 1.5 minutes.
Boiling HC1 }£$ 1 minute. 18 minutes.
Tissues remaining in the solution one hour before boiling.
Dr. Flint's Table.
Solution.
Time required to dissolve.
Tendon.
HC1 0.5$ 3,'{ mins. 10 mins. 11 V mins.
KOH 0.13$ 3 mins. 14% mins. 22 mins.
In Dr. Flint's work the sections remained in the solutions two hours
before boiling, and at the end of the time given the tendon was completely dissolved and the solutions clear, while the reticulum in each
case remained as a granular detritus even after boiling for thirty-five
minutes.
Time required to dissolve
Solution. Tendon. Reticulum. Myoma.
Boiling HC'l .5$ 27 mins. 43 mins. 55 mins.
" HC1 1$ 12 mins. 22 mins. 27 mins.
KOH 1%. ... 27 mins. 29 mins. 30 mins.
At the end of the different times given the tendon in each
" Pancreatin (P. D. & Co.), 5 grm.; sodium bicarbonate, 10 grm.;
water, 100 cc.
Loc. cit.
7 The Blood Vessels of the Adrenal. Contributions to the Science
of Medicine. Dedicated to Wm. H. Welch, Baltimore, 1900.
Si II 1MBER. 1900.]
JOHNS HOPKINS HOSPITAL BULLETIN.
211
i asi was completely dissolved ami the fluid remain 6
clear, but in the case of both the reticulum and tin
there remained a minute granular detritus m a verj cloudj
or turbid fluid. The appearance of tendon was also quite
differenl both from the myoma and the reticulum, which two
latter substances behaved very similarly. The edges of the
tendon section within a Eew minutes became ver\ much
swollen and assumed a gelatinous or translucent appearance,
and this gelatinous area increased ai the expense oi an opaque
centre, but at the same time dissolved awaj until all had
passed into solution. The myoma and reticulum, on the
other hand, became shreddy and granular in appearance and
gradually broke up into very minute granules which remained
suspended in the fluid. In the myoma in the I per cent
hydrochloric acid solution it was noticed a1 the end ot Eoui
minutes that there appeared some >\\ dl iti-; and translucencj
ai spots nn the surface, hut this had all disappeared a1 i he end
of ten minutes and after this n behaved \er\ similarly i"
reticulum. A longer time was taken to accomplish lie solution than in the other two tables, hut this was probably due
te the larger sections used. In the latter eases frozen sections
were used, while in this work the pieces measured probably
."> em. square. In the caustic potash experiment the section
of tendon was somewhat larger than the other two sections.
Also based upon Mall's 8 finding that tendon is much more
quickly dissolved in pepsin solution than either reticulum or
yellow elastic ti-siie. several frozen sections of my a were
digested for twenty-four hours in pancreatin solution, then
washed in water and subsequently put in pepsin solution in
the thermostat ami removed at different times, •">. In. Lo ami
30 minutes. .Mall found that tendon was completely dissolved in a strong solution of 1'. 1). & Co.'s pepsin in from
5 to 30 minutes, while elastic tissue and reticulum onlj begin
to hi' dissolved at the end of this time. In these sections all
evidence of structure was lost, even at the end of five minutes,
hut at the end of thirty minutes a considerable portion, pos
sibly amounting to -third of the original section was removed upon the slide. This experiment, however, loses
much in value from the fact that no control specimens of
p tendon or reticulum were made.
Regarding the two methods of studying white fibrous tissue
and reticulum by digestion, \iz.. that of Mall ami that of
Spalteholtz, each one gives evidence of value that is not
obtained from the other, and as Mint says, both should he
\\>ri\ together since in Mall's method owing to the thickness
of the section a suggestion of a thud dimension is obtained
and the fibrils may he traced in most cases througl t their
entire course. On the other hand, of the relation of the con
nective tissue to the cells of the growth very little can In
studied owing both to the spreading of the mount
ing and to the difficulty in obtaining a near control section.
In Spalteholtz' method, however, since alien
are easily obtained, one being digested and the otlu r stained
■Johns Hopkins Hospital Reports. Vol. I. 1896. Reticulated
Tissue.
intact, the relation of cells and connective tissue is readily
studied, but owing to the thinness of the section the fibrils
aie cut short and in in.iiu cases appear onlj as minute spirillar
forms, H nol hem:; possible to follow their course for any
distance.
The subject of elastic tissue in new growths has received a
n her of contribut - since the publication of Weigert's
elasl ic fibre stain.
MelniUw 1,'a-WMlenkow m Ziegler's Beitrage, Bd. 26, 1899,
has described the distribution of elastic tissue in various
organs in normal and pathological conditions, and states that
, lastic fibres in health^ and diseased tissues are derived mainly
from the vascular walls, and further that in tumors rj h
formation of elastic tissue occurs. In the discussion on the
paper, however, in the German Pathological Society in
Munich,' a number of observers reported cases where an
increase in amount was present. Bansemann reported a large
increase of elastin in a ease of metastatic tumor in the spleen
but had not found any, as a rule, in malignant growths.
Kchmorl reported a case where aumerous elastic fibres were
found in a carcinoma of the stomach. Orth and Nauberck
found in carcinomata cases very many elastic fibres present.
Alice Hamilton 10 has reported a case of fibro-sarcoma of
the brain in which then' was a very large amount of elastic
tissue present; the tumor presented a very peculiar rosette
arrangement and in places masses of considerable size surrounding blood-vessels, all of which masses were of a fibrillar
nature, but clastic tissue was also present as wavy fibrils running among the cells without any apparent relation to a vessel
wall or to the cells of the growth. She agrees with Melnikow
Raswedenko^ as to the origin of elastic fibres from vessel
walls but contradicts his statement that in tumors no new
formati E elastic tisst ccurs. In this case the amount
was much more than normal, but the relation was frequently
to the periphery of the vessel wall, and where this relation
was not found, the presence of elastic tissue was ascribed to
the obliteratii E the vessel or to the severance of the original
connection of the fibres.
II. W. Williams." in a paper on the new formation of
elastic- fibres, gives a report of his study of 31 case- of carcinoma: 12 in the liver, l in lymph mule-. 2 in the thoracii
duct. ? in large veins, 2 in the cerebrum, 1 in the lung, 8 in
the mammae, 1 in the skin, I in the st ach and 1 in the
rectum. The following are his conclusions:
I. \\ hen the stroma of a carcinoma is itself of new formation n i- usually free from elastic fibres.
■.'. Newly formed elastic fibres may occur in the stroma
through rarely, and they are likely to be fine in quality and
small in number.
::. Tin. tumors in which newly-formed elastii fibn
curred either contained a large an m of coi tive-tissue
"Centralbl. f. alg. Path. U. path. Anal., X. S32.
"•Jour, of Exp. Wed Vol IV. Noi - 5 and 6, 1899.
"Contributions to the Science of Medicine. Dedicated to Wm
II, Welch. Haiti nore. 1900.
212
JOHNS HOPKINS HOSPITAL BULLETIN.
CSTo. 11 l.
1 1, una or the new I y-fornied fibres were in connection with
pre-existing elastic elements of the original parts.
lie found evidence of now formation in three rases of cari of the liver. In carcinomata of lymph nodes the
stroma was usually free from elastic tissue and when present
it was ih>! possible to demonstrate its new formation. In
one carcinoma of the thoracic dud there was new formation
and in two of the venous growths, in two of the cerebral
cases, one secondary from an adeno-carcinoma of the lung
and one secondary from the stomach, there were fine elastic
fibres present possibly connected with some prolongat "I
the pia mater. In the carcinomata of the mamma nothing
was seen in |>rn\ e new formation.
Kromaver ,J found in rapidly-growing condyl ata. warts
and carcinomata of the skin no newly-formed elastic fibres.
These were present, however, in older papill ata and fibromata.
There are also a considerable number of papers on the new
formation of elastic tissue in other pathological conditions, to
which reference will be found in Dr. Williams' paper."
In seven of the seventeen case- in the series here reported.
elastic fibres were f id, the description of which will be
found under the individual cases. In all cases they apparently
had their origin fn m the vessel walls. In mil\ one case, No. 6,
a carcin a of the breast does there seem to be sufficient
ground for claiming an increase in amount or a new formation. The sections from this ease were compared with those
from three normal breasts and three other carcinomata and
contained a much greater amount of elastic tissue than any of
i he "i he: s.
The safest method of judging the amount of new formation if such exists in any case would seem to be that of comparison of sections of the growth with sections of the normal
tissue in which the growth was situated. This, unfortunately
was only done in one case (case 18). In this case a portion of
the normal breast in which the carcinoma had grown was prepared in the same way as the growth itself. A description of
the comparison will be found under this case.
Regarding the origin and normal development of elastic
fibres whether from the transformation of cells, by fusion.
into fibres or from the transformation of the intercellular
mat n\ there is still no sat isfactory answer.
< »n the subject of the study of tumors by digestion methods
u" literal ure was to be found.
Desi i;i p'i in\ of I \iii \ i iii vi Cases.
Specimen- \'o-. 1. I and 8. film. my ata of the uterus
Elastic Tissue. -In these case- there were no elastic fibres
found either in the fresh preparations or in the hardened
stained with Weigert's elastic fibre slain.
VonatFSchrift t. prakt. Dermatologie. Bd. XIX.
White Fibrous Tissue and Reticulum. — To the naked eye
these sections gave the appearance of a fibrillary structure and
under the dissect ing microscope the fibrillary nature was mure
clearly seen. The tissue remaining after digestion was collected in places in thick nias.-e- ami strands, from both of
which branches were given off and these again branched in
turn. The thicker strands presented in plate- a distinct
whorled appearance, and between the masses and strands
minute wa\y fibrils were seen running in a more or less parallel direction and passing into and becoming continuous at
mt her end with the thicker portions of the section.
Under the low power of the microscope the masses formed
nodal points from which prolongations were given off, an
infinite number of very line fibrils appearing in places.
The larger strands were composed of minute fibres in very
close apposition to one another. These strands divided and
united again and gave off branches, and from these branches
lJMt
Fig. 1. — Section of a flbromyoma digested by Spalteholz' method,
showing the bundles of white fibrous tissue and the reticular network in the meshes of which the muscle cells lay.
and Erom the sides of the strands themselves there arose ' '■
eeedingly minute, very wavy, interlacing fibrils running in a
course more or less parallel to one another, and in some places
arising from one strand and passing into and bee ing losl
in another si rand.
In other parts of the section between the strands was seen
a very fine network similar to that obtained by Spalteholtz'
thod to be described later.
"With the high power the fibrillary nature was mure clearly
seen in smne parts, the fibrils being very wavy, in others quite
straight throughout their course. The strands themselves
were composed of the wavy interlacing fibres of white fibrous
tissue while the minute network presented very much the ap
September, 1900. |
pearance of reticulum excepl thai in the
anastomosis was observed.
In the preparations by Spalteholtz' meUiod very Little could
be made < mt either with the paked eye or with the dissecting
microscope, but with the Latter very minute apertures throughout tlif section were plainly seen.
Under the Low power, however, the condition described
under the Van Gieson and Mallory preparal ions is verj i Learlj
seen; viz., a connective-tissue envelope for each muscle-cell.
The connective tissue was verj abundant and formed 1>\
far the major porti E the section. It was arranged in
two ways.
1. Running in every direction and forming a large irregular
network, Leaving meshes of varying size, were large strands
composed of wavy interlacing fibres which followed a more
or Less parallel course. In places these strands divide and
unite again, leaving spaces which are occupied by the network
in In described Later. In the midst of these strands are seen
also the apertures of blood-vessels surrounded by denser tissue,
the size of tin' vessel varying with the size of the strand.
■.'. In the meshes formed by this stroma was found a minute
network apparently formed by the division, subdh i-ion and
anastomosis "1 the branches of this stroma proceeding from
all sides of it as it surrounded the individual spaces. The
minute meshes of this second network are filled in the control
specimen with single muscle cells.
I an Gieson Preparation. — To the naked eye the general
impression of this section was red. but on holding it tip to
the light areas having a yellowish tint were seen. These
varied in size and were surrounded by a capsule id' deep red.
Besides these areas there were certain parts of the section of
a lighter and apparently Uniform red color, intimately connected with the capsules of the yellowish areas. The capsules
surrounding the yellowish areas formed an irregular network
throughout the remainder of t he seel ion.
With the dissecting microscope the darker capsules mentioned above were seen to run through the section looking
like an injected vascular network. Tin- branches from this
network ran into and divided the yellowish area- which they
surrounded into -till smaller area-.
The lighter reddish masses -ecu with the naked eye were
here not so uniform in color, but appeared a- a very close
network of red -tamed tissue, and held in the meshes of this
network were yellowish cell bodies similar to those found in
the other area-, hut here the rod -tamed material was :li
more abundant, the strands being thicker and the meshe?
smaller.
Tin- general network of red stained connective tissue was
irregular, the meshes varying in size, the larger bundles of
led surrounding the larger yellow ish ana- and branches from
these forming tin- walls of smaller areas, but even in thi
strands of red, -mall groups of yellowish cells were frequently
-cell.
With the low poue, the uniform reddish masses were een
to be composed of a dense network of comparatively thick
strands of red with small meshes containing the yellowish
JOHJ 3 HOPKINS HOSPITAL BULLETIN
id inn- no definite
213
i ed bodies. These yellowish cells were evidently the muscle
cells and will he so called in the further dtscripl
The genera] network of red could he traced with this power
io much smaller divisions, in some cases the branching and
anastomosing forming so small a network that the meshes of
the same contained only a single muscle cell.
The larger strands of red-stained connective tissue had in
places a definite whorled appearance and throughoul their
substance were seen scattered the connective-tissue corpuscles. In these strands were also seen numerous blood-vessels
the larger ones occurring in the larger strands and so on.
The muscle cells of the walls of these vessels were stained
yellow, similarly to those contained in the gem ral network.
I'nder the high power the network of connective tissue
could he traced to still liner divisions, so (hat each muscle
cell was here seen to have an enveloping capsule of its own.
very line in most instances hut comparatively thick in others.
In the midsi of the larger strand- occasional muscle cells were
also present
.Mallory'.- stain gave a very similar picture to that obtained
by Van < fieson's stain.
Specimen No. 2 was from a sarcoma of the litems, but contained so small a portion of sarcomatous tissue thai it was of
very little service for study: still in the Spalteholtz preparation a reticular network similar to that found in other sarcomata was demonstrated in one portion of the section.
Specimen No. 3 was a portion of the wall of a multiloeidai'
ovarian cyst and showed only a dense while fibrous tissue
structure in which no elastic fibres were found.
Specimen Xn. •"> was an epithelioma of the inferior maxilla.
This growth was of live and one-half years' duration, hut for
niie year previous to its removal had grown very rapidly. Il
involvi d the whole depth of the left half of the inferior maxilla from the ramus behind to a point 2 to ;; cm. hey I the
middle line in front. Il presented a lobulated appearance
with a reddish surface looking like granulation tissue I had
an act ively grow ing appearance.
No elastic lissue was found by either method excepl around
the vessels.
Mall'- preparation was very unsatisfactory for study; the
connective ti>siio remains forming a more or les> solid ma--.
from which nothing but a fibrillary construction could hi'
made out.
Spalteholtz' method showed a distribution of connective
(issue similar to that described below under Mallory's stain
the parts of il nirol seeti ccupied by the large irn gular
masses of cell- being in the digested specimen quite devoid
if ' -ounce five i issue.
The section stained by Mallory's stain gave in this ease the
best idea of the distribution of the while fibrous tissue, its
absence in the cellular areas ami its distribution* being controlled by the Spalteholtz' preparal ion
The < d win I, of lie- Section w;i- made up of evi
214
JOHNS HOPKINS HOSPITAL BULLETIN.
| No. 11 l.
strands and bay-like processes of epithelial cells joined together ly their minute protoplasmic processes winch were
very plainly visible and appealed in places as a reticular network; of this, however, nothing remained after di
These strands of cells formed a connected network bul in
certain place.- became condensed, lying much closer together
in rows surrounding larger and smaller irregular -pace- which
contained a fine loose aetwork of connective tissue, liolding
m ii- meshes numbers ol connective-tissue corpuscles and
polymorphonuclear cells.
The connective tissue in these -paces was collected in the
centre into bundles and masses of wavy fibres, and from ll e
minute fibrils radiated outward in all direction- as an exceedingly minute fibrillary network, becoming gradually looser in
texture until at the edge just inside of the rows of cells they
curved and formed an interlacing ring of tissue which, however, -cut no processes among the cells of the growth. This
latter condition was only demonstrated by (be Spalteholtz'
preparation.
In several of these spaces there were also seen small bloodvessels su mm m the network.
Besides the connective tissue in these .-pace- there were
several strands id' white fibrous tissue fibrils which divided
the section into smaller portions, but had no1 I n invaded
by epithelial cells. These strand- were evidently the origin
of the connective tissue in the spaces, as many of the latter
were found continuous with the former. The connective
tissue in the isolated spaces had apparently been shut oil' by
the invasion of the epithelial cells and had then commenced
to throw out new fibrils, for in these spaces the connective
i puseles were in a very actively multiplying condition, the nuclei dividing and undergoing mitotic changes.
The larger strands carried in their substance several large
blood-vessels. In r two places in the sections areas of
degeneration were present Idled with granular debris and
polymorphonuclear cells, and around these areas, extending
lor some distance among the surrounding cells, many polyi phonuclear cells were to be found.
Spei n No. 6 was part of a carcinoma of the lefi breasl
in a woman ."a; years oi age. The growth was of one year's
duration and al the time of removal measured 5.5x5 cm.
Besides this larger nodule there was a sec I smaller growth
box L.7 em. in size. The nipple was slightly retracted ami
there were metastases in the cervical and axillary glands.
Elastii /' ' " The fresh tissue teased out upon a slide
and lamed with magenta -bowed a considerable number of
purple stained elastic fibres varying in thickness, quite wavy
and ( tilled at their free i nds
The frozen section stained with magenta also showed
elastic Idee- a] al croup- of cell... around the 1,1
ami b nijilial ic dm t- and .,. I be connect i v e-tissile
stroma.
In the preparation hardened i i solution and
stained with \\ eigerfs i lastii Bl i In sections presented, even to the naked eye, many bltie-sta d areas, repre
senting the elastic tissue. This was distributed throughoul
the section in two ways: (1) Surrounding certain definite
areas and marking these off distinctly from the iv-i of the
section. (2) As minute lines running for short distances
through the balance of the section.
Under the low power the areas mentioned above were composed of the cells of the growth grouped together in varying
numbers from 5 or 6 up to many hundreds, and immediately
outside of these croups was an irregular or serrated encasement of elastic tissue iii single and double layers, and outside
of this again a layer of connective tissue in which were scattered many minute fibrils of elastic tissue. These were evidently the lactiferous tubules which had been invaded by the
growth. Many elastic fibres were also preseni in the walls of
the blood-vessels. There were also a number of very small
area- containing only three or four cells which were com
*
4
.
Fig. 2. — Section of carcinoma of breast No. 6. staineil by
Weigert's elastic fibre stain, showing the distribution of elastic
tissue around a large nest of cells and in the surrounding stroma.
pletely surrounded with elastic tissue and in some places these
areas themselves appeared in groups of three and four. Besides the above distribution there were also numbers of fibres
of elastic tissue running in the connective tissue strands in
double lines as if the remains of a vessel no longer patent.
It was with the high power, however, that the very large
anioimi of very fine elastic fibrils running through the -eci - could be made oui following mainly the white fibroustissue framework but often seen among the cells of the growth
with apparently no other connective tissue accompanying
them.
Many of the groups of cells were quite devoid of elastic
fibrils around I hem
There was, apparently, an increase in the amount of clastic
tissue in this growth, for in comparison with three normal
September, L900.]
JOl INS HOPKINS HOSPITAL BULLETIN.
211
breasts two from cases younger than the patienl from
the presenl growth was removed," and three other carcinomata of the mamma, this growth contained a very much
larger amount than any of the others. There were also so
many minute fibrils differing from thai around the vessels an
ducts found through the growth away from their apparenl
origin, thai the increase in amount seei I more probable.
White Fibrous Tissve and Reticulum.— Mall's preparation
showed a network of strands varying in width from the thickness of writing paper to six or seven times this width, with
meshes varying in size from a pinpoint to a pinhead: These
meshes were quite clear and appeared as open spaces throughout the section.
Fig. 3. — Section of a carcinoma of the breast No. 6, digested by
Spalteholz' method, showing a group of cell spaces outlined by
bundles of wavy fibrils and the entire absence of tissue of any
kind in these spaces.
In plaee- the c ctive tissue forming the network was
collet-ted into masses of considerable size up to an eighth o]
a sixteenth of an inch in size. In other plates the larger
strands surrounded an open space which was subdivided into
two or more -mailer meshes by threads oi the smallesl width.
The meshes were for tin mosl pari more or less circular in
outline.
Sections were examined with low power magnifical
The meshes were nearly all quite clear: some, however, had
projecting into them from the strands which surrounded
them the fn e ends of tin fibrils of which these were con
The strands forming the network were composed of minute
fibres running in a more or less parallel direction interming
ling wit] another and for the most part quite wavy. -"
1 The. elastic tis iue apparently decreases in amount
mamma atrophies after the menopause.
much so that in places, instead of running a continuous
course, certain fibrils appeared as a succession of minute
spirillse. The majority of the fibres could be traced through
out t heir course.
In many places there was a cross fibrillation, with longitudinal fibrils underlying it. both free ends of the former being
seen, evidently the fibrils of the third di nsion of the cell
-pace.
In the thinner portions of the section a bundle of fibrils
could often be traced down one side of a mesh ami curving
around a second side, then at the third side dividing some
of the fibrils, continuing around the same mesh, while otherpassed in another direction in the strand between two adjoining meshes ami so on. intimately interlacing with one another.
With the high pover the finer fibrillary nature of the str a
was much clearer hut there was no branching or anastomosis
of the fibrils, each being traceable alone its course without
interruption.
Spalteholtz' preparation showed a number of absolutely
i [ear spaces outlined by wavy fibrils in bundles which in some
places Completely surrounded them, while in others they were
continued onward between two adjoining spaces after passing
around one or two sides of a mesh. These clear spaces in the
control specimen were Idled with the cells of the growth and
evidently these had no intercellular substance between them.
The rest of the section was occupied by bundles of wavv
white fibrous tissue fibrils which frequently separated, leaving
clear spaces which were in th ntrol specimen tilled with
small groups of cells.
Mallory's and Van Gieson's stains threw no additional buhl
upon the distribution of the connective tissue in this growth
Specimen No. 1 was from a small round and spindle-celled
sarcoma removed from the thigh of a woman 59 years of age.
The tumor commenced in the adductor muscles of the thigh
and extended downward in the muscles to the popliteal space.
It diil no] involve the muscles about the knee joint, but passed
I iet ween the hones of the leg and involved the muscles on the
anterior aspect of this. There were also large glands on the
front of the thigh of similar structure. In the thigh it c
pletely surrounded the femoral vessels and extended outward
between the muscles four or five centimetres. In the popliteal space ii surrounded the popliteal vessels. Portions were
obtained from the growth in the thigh through the femoral
vessels and from tin tside of the growth.
Elastic Tissue. — The fresh specimens, both the teased and
the frozen section, stained with magenta showed considerable
n u in hers of elastic fibres varying in size and character from the
fine branching fibres similar to those in areolar tissue to the
coarser curly fibres resembling those in the ligamentum
nucha'. These fibres ran i rag the cells of the growth and
were found both in the section taken through the femoral
vessels and in that from the outside of the growth.
In the Zenker preparation, stained by Weigert's method
the blue-stajned elastic fibres were plainly visible to the nal ed
eye. I ' nder t he low power the se een to b
216
JOHNS HOPKINS HOSPITAL BULLETIN.
[No. 114.
divided into lobules of different size by strands of white
fibrous tissue ; the lobules being closely packed with the cells
of the growth with very little evidence of intercellular tissue.
The elastic fibres oei urred in the midst of the strands of white
fibrous tissue and were most abundant in the largest strands
but also in places running among the cells.
In the strands they existed as very fine straight branching
fibres with free curling ends and also as short curly fibres,
due possibly to both ends being free. They occurred also
here and there in the section as mentioned above a- curly
fibrils running among the cells.
In the section near the femoral vessels the elastic tissue
was much more abundant. With the high power the branching of the elastic fibrils was more apparent. Some of the
white fibrous tissue strands Mere quite free from the blue
fibres, and as one proceeded from the femoral vessels outward
the amount of clastic tissue grew less, although it was still
From the very large amount of elastic tissue found in this
growth and from its varying character it would seem fair
to conclude that there was considerable new formation of the
tissue.
White Fibrous Tissue and Reticulum. Mall's Preparation.
— For purposes of description the fibres forming this section
after digestion may be divided into two groups:
1. Long wavy, more or less parallel fibres running in bundles through the sections, the fibres interlacing with one another. These were evidently white fibrous tissue, and in the
control specimen this tissue divided the section into lobules.
and in the Weigerf preparation it carried the elastic fibres.
2. Exceedingly fine fibrils which formed the ground work
ami main portion of the section and lay between the bundles
of the first group. They formed a very minute meshwork
running in every direction, definitely branching and anastomosing and presenting very much the appearance of reticulum
PIG. 1. — Section of sarcoma No. 7. stained by Weigert's method
for elastic fibres, showing in dark curling lines the distribution of
the elastic fibres. At one side of the section the femoral vessel is
seen outlined by elastic tissue and surrounding this are seen
layers of elastic fibres lying among the cells of the growth alternating with layers of white fibrous tissue.
present in considerable quantity in the sections from the
outside of the .".l"W I li.
A very peculiar arrangement was present around the femoral vessels. The small round cells had encroached upon
the walls of the vessel to the endothelial lining, and from
this outward were ranged in definite order layers of small
round cells with elastic fibre ig them, succeeded bj la i rs
of white fibrous tissue with very few elastic fibres one above
the other for many layers. The fibres near the vessels were,
as a rule, much thicker than those found in th ttskirts of
the growth.
I Inna's orcein stain gave a verj imil tun to t he above
with the elastic tissue stained a silk\ brown
Pig. 5. — Section of sarcoma No. 7, digested by Mall's method,
showing the strands of wavy parallel fibrils and the groundwork
of minute reticular fibrils occupying the remaining portion of the
section. The appearance of a focal origin of these fibrils is quite
evident in certain spots.
of normal glands. In some places the fibrils appealed to arise
from focal point- spreading out in all directions and uniting
with fibrils from other points.
Under the high power the fibres of the first groups appeared as above but in the reticular network the branching
and anastomosing of the fibrils was much more evident. This
network seemed to have no direct connection with the first
group but extended a short distance among its fibres as if t<>
gam anchorage there, for in the centre of these bundles they
were not nearly so evident.
Throughout the section the apparent focal origin of these
fibrils may be due to four or five of these overlying each other
at a certain spot.
Spalteholz' Preparation. — These sections were much thinner
September, 1900. J
JOHNS HOPKINS HOSPITAL BULLETIN.
than those by Mall's method, but showed the sari
interest: the strands of white fibrous tissue dividing tl
t ton into lobules, and between these strands, and forming tin
balance of the section, an exceedingly minute network of deli
cate fibrils which branch and anastomose, the meshes of which
were in the control specimen occupied bj the r id and
spindle cells of the growth, bj single cells in mosl cases, bul in
some cases apparently by groups of two or thn ■ possibly
iv Eowever, in those spaces which were occupied bj
groups of cells there was often seen in this specimen a
jutting branch a- if it had been divided in cutting the section,
The apparent focal origin of these fibrils was also uoticed in
i bese sect ions.
Specimen No. 9 was from a carcinoma of the uterus.
Fig. 6. — Section of sarcoma Xo. 7 digested by Spalteholtz'
method, showing the reticular network with the branching and
anastomosis of the fibrils.
It showed no elastic fibres in the fresh preparations bul in
■ I ion stained l>y Weigert's stain then
-■■en in the connective-tissue stroma minute curly fibrils
extending for some distance fr the vessel's wall, from which
they had probablj arisen.
White Fibrous Tissue.— The sections studied by Mall's
method were too thick for accurate observation but the clear
spaces of the carcinomatous growth were elearlj -ecu outlined
by bundles of wavy parallel fibres of white fibrous tissue.
In Spalteholtz' preparation the cell nests and groups of cell
nests lay embedded in the connective tissi f the muscle
wall but were separated from the same by bundles d!
parallel fibres. These bundles formed a delicate framework,
enclosing large meshes which were quite clear in
section and filled with cells in the i ontrol pei i
quently the bundles after passing around i side of a mesh
would divide into two -mailer bundles which would then take
pari in the Eormation of the walls of adjoining meshes. Or
again, complete rings of lour or five »;m fibres were found
in apposition at certain points, leaving between them a clear
space, which space was also Idled with cells in l he control
section.
Tin' Van Gieson and Mallory preparations showed the
closely packed cell nests lying in the muscle wall of the uterus
surrounded by connective tissue, hut without the slightest
i \ idence of intercellular i issue.
Specimen Xo. in was from a small round-celled alveolar
sarcoma arising from the periosteum of the tibia and invading the tibialis anticus muscle in a girl thirteen years of age.
It involved the popliteal glands and also a chain of glands
extending along t he scial ic nerve.
The growth was exceedingly sofl and on cutting u a creamy
fluid was expressed.
Xo elastic tissue was found except around the blood-vessels.
In the preparation by .Mall's method the connective tissue
«;i» very abundant and disposed in a rather coarse network
with comparatively thick strands enclosing varying sized
meshes, which to the naked eye appeared quite clear.
Under the low power the section was seen to he composed
of a network id' thick strands leaving meshes of varying size
and shape. The strands were composed of bundles of minute
fibres which ran a comparatively straight course. The fibres
could often he traced curving around certain meshes, interlacing w ith li I ires going in an opposite direction and continuing on their course around and between neighboring meshes.
'fin- meshes were for the mosl pari quite (dear. Iii some,
however, there was seen a minute reticular network, the
fibrils of which branched and anastomosed.
The meshes in the control specimens were partially filled
with small round cells. In many place- the meshes were
divided by single fibres into smaller meshes, and in some
portions of the section when' the fibrous tissue was -i
abundant there was found a definite reticular network outlined \i\ bundles of wavy fibrils. This network was composed
of anastomosing ami branching fibrils similar to that desi ribed
ii ease No. '.- The -mall meshes of this network were filled
with the cells of t he grow th.
The larger meshes were so loosel} filled with cell-: in the
stained specimens thai it would seem probable that they had
contained also the creamy lliiid which was expressed on cuti nig the fresh i issue.
In Spalteholtz' preparation there was no connected network
on account of the thinness of tie- section. It was composed
of minute wavj fibrils running in various directions ami oul
lining irregular 3] - w Inch in the control specimen were
loose!} Idled with cells. The white fibrous tissue framework
was here of a \>'v\ loose texture and the interstices lefl by this
separation of its fibre ivere idled with -mall round cells in
I he eont lol -eel io||.
Iii the midsl of the clear spi frequently seen cir
218
JOHNS HOPKINS HOSPITAL BULLETIN.
| No. 11 1.
cular wavy fibrils completely enclosing small spaces which
were also filled with cells in the undigested specimen.
Numerous vessels in the undigested section were repre
sented in the digested section by small rings of connective
\ ing in the framework.
The stained specimens showed numbers of groups of muscle
fibres lying among the cells of the gro\i th.
Specimen No. 11 was taken from a carcinoma of the uterus
and contained only a very small amouni of carci latous
tissue.
\o elastin was present except around the blood-vessels.
The other preparations resembled carcinoma No. 9 in every
way.
* - 3£nz
Fn ;. 7. — Section of scirrhous carcinoma of the breast No. 12, by
Mall's method, showing the distribution of white fibrous tissue
around the small irregular clear cell spaces.
Specimen No. L2 was a scirrhous carcinoma of the breast
from a woman l!i years of age. The growth was of six
months' duration and involved also the axillary glands on
the same side. The nipple was retracted and the skin adherent to t he growth.
This growth showed both in fresh and hardened preparations considerable numbers of elastic fibres around the vessels
ami lactiferous ducts; also around certain groups of cells, and
scattered as short wavy fibrils through the abundant connec1 1\ e-1 issue -i roma.
hi the fresh digested specimen the white fibrous tissue was
very abundant in bundles of line wavy parallel fibres running
in every direction and i nclosing spaces of varying size. The
bundles were in many places very thick ami the fibres composing them very close together es< however, gradually
spread out leaving in their i [ear spaces. Or
again, branches from those larger bundles would gradually
thin out and divide to enclose clear spaces and frequently
these spaces were separated from one another by a single
fibril. There was no anastomosis of fibrils and no reticular
network. The clear spaces were filled in the control specimen by small groups of cells, the largest containing probably
fifteen or twenty cells, the smallest only two or three.
Spalteholtz' preparation gave in a thinner secti nuch
the same picture. Here the wavy fibres were present in bundles which gradually spread out and divided to enclose clear
spaei's of varying size which were occupied by the cells of the
growth in the control section.
This specimen differed from Nos. 6 and 18 (a) in the very
much larger amount of connective tissue: {!>) in the smaller
and irregular grouping of the cells, and (c) in the smaller
amount of elast ic t issue.
Fio. 8. — Section of fibro-sarconia of the liver No. 13, by Spalteholtz' method, showing the large amount of fibrous tissue surrounding the clear cell spaces.
Specimens Nos. 13 and 1-t were from carcinomata of the
liver and rectum in tin 1 same individual. The growth was
primary in the rectum, where it formed a mass ', x ti cm. in
size and Idled the whole pelvis. There were numerous secondary nodules in the liver from '.' nun. to ."> cm. in diameter.
They were firm, opaque ami yellowish ami surrounded by a
zone of greenish-yellow liver substance. The rectal growth
had eroded the sacrum and was adherent to it.
These two specimens were of so similar a nature that only
one description will lie given for both, noting any differences
thai existed.
The specimens when obtained had already been kept about
four days in the ice chest, so that the fresh preparations for
elastic tissue were not satisfactory. In the rectal growth,
however, by Weigert's slain a few scattered elastic fibres were
found running in the mid-t of the general white fibrous
stroma.
JOHNS HOPKINS HOSPITAL KULLBTIN.
219
White Fibrous Tissue — Both growths contained ;i greal deal
of connective tissue, the liver growth more than th
growth. The type was the same in both, bundles of waw
more or less parallel fibres running in every direction and
outlining clear spaces of varying size which were filled with
epithelial cells in the control section. These sections resembled very much the scirrhous growths from the breast, bu1
the fibrous t i~>m- was here even more abundant.
In Spalteholtz' preparation the section was thin, the thickness of two or three fibres. The fibres ran in many din
their further course in any one direction ceasing when iln \
■encountered bundles running in an opposite direction. In
the midst n!' the bundles minute openings were seen where
the constituent fibrils separated slightly from one another,
and in these spaces the connective tissue corpuscles were seen
to lie in the control specimen. Eere also the curving ol the
fibres around two or more sides of a clear space and onward
between two adjacent spaces was clearly seen.
Specimen No. L6 was from a scirrhous carcinoma of the
breasl of eighl years' growth in a woman forty-four years
This growth resembled very much thai described in No. 12.
It contained, however, many more elastic fibres running
through the white fibrous stroma, bul these were confined to
the stroma and to the ducts and blood-vessels, and did no! in
any rase surround groups of cells, nor were they oearly so
abundant as in case No. 6.
Specimen No. 1' was from a small round and spindle-cell
sarcoma taken from the axillary region. It had a thin translucent capsule and could so be separated from the surrounding tissues, the connection consisting only of fine branching
> 0] stive-tissue fibres and numerous small blood-vessels. Its
origin was evidently from the intermuscular connective tissue
and the growth itself was soft, elastic and lobulated, measuring I3£xl0xl8 cm. Its duration was 20 months, and H
involved also a number of glands in the supra-clavicular fossa.
No elastic fibres were funnel in either the fresh or hardened
preparations.
The digested specimens, both by Mall's and Spalteholtz'
method, showed tie same reticular network as that described
in section No. ', . and also the same white fibrous bundles
enclosing this network. Neither the Van Gieson nor Mallory
preparations showed the large amount present nor its distribution.
Specimen No. 18 was from a car< inoma of the breasl of four
months' growth in a woman thirty-seven years of age. V
;i was present as a hard regular mass freely movable
and measuring I \ 2 cm. in size.
This was an exceedingly cellular growth, thus differing
from eases No. 12 and 16, but it resembled very ram
No. 6 both in the distribution of elastic and whiti
tissue and in the type of cell of n hich it was compi
thai in the latter instance No. 18 was of a much more malignant type filled \utli young cells ami almosl resembling a
small round-celled sarc a.
Elastu Tissue. The elastic tissue here was disposed in a
very similar ua\ to No. r,. inn was not so abundant.
In tin- growth a comparison was made with a portion of
normal breast Erom the same ease with reference to the
amount and distribution of the elastic tissue with the following result: thai the elastic tissue in the growth was found to
be not so abundant a- in the norma] breast, hut differed somewhal in distribution. In the normal structure the elastic
tissue was confined to the coats of the vessels and lactiferous
ducts occasionally occurring in bundles in the stroma of the
gland, while in the growth, besides being around the vessels.
it was present surrounding large groups of cells, evidently
invaded duels, and as minute wavy fibrils was most abundanl
in the str a. hut frequently was found in among the cells
with apparently no white fibrous tissue accompanying it: also
as bundles of fibres which were infiltrated w ith epithelial cells.
t'e a. — Reticular network from sarcoma of axilla No. IS. prepared by Mall's method.
In spite of the very cellular condition of the growth il presented on digestion the distribution of fibrous tissue desi ribed
under case No. 6 of huge (ell spaces with no intercellular
network.
( lONCLl -ion-.
1. Elastic fibres are frequently presenl in new growths:
I'M in tic stroma; (b) among the cell-; (c) around the bloodvessels, and (d) iii breasl tumors around the lactiferous ducts
which have been included and invaded bj the growth.
'!. When presenl thej are usually in connection with preexisting elastic-tissue elements in the original tissue in which
t he I umor has grown.
220
JOHNS HOPKINS HOSPITAL BULLETIN.
| tSTo. 11 1.
3. N b formation probably occurs but can onlj bi deterbj a comparison of thai presenl in the growth with
that present in the norma] tissue in which the growth has
arisen.
I. Sarcomata present a large increase in connective tissue
and possess an exceedingly fine intercellular retii alar network
\.i\ similar in structure I" the reticulum present in normal
glandular tissue.
5. ( larcinomata possess a stroma of w bite fibrous tissue, outlining the cell spaces, but have no intercellular network.
6. The digest inn methods present a possible means of diagnosis between carcinomata and sarcomata in doubtful eases.
7. Uterine myomata bavea very large amount of connective
tissue both of a white fibrous and reticular nature, possessing
a connective-tissue capsule for each muscle cell; ami it would
he more correctly termed fibromyomata.
ON THE RELATION OF THE ELECTRICAL CONDUCTIVITY OF BLOOD-SERUM TO ITS
ALLEGED BACTERICIDAL POWER.
By Km ma Lootz \m> Alice Weld Tallant.
(From tin Pathological Laboratory of the Johns Hopkins I niversity and Hospital.)
A- i- well known, it i- asserted thai bl l-serum possesses
iirt. mi bactericidal properties, and many experiments tend
tn show that these properties are lost when the ser
heated t<> from 55-60° C. In a recent article Baumgarten 1
advances the theory that the bactericidal power of the serum
is due. nut tn the actual existence of bactericidal substances
in it. Imt to the fad that bacteria, in being transferred from
their natural surroundings to another medium, undergo sudden changes in assimilation ami plasmolysis.
Following the hue of thought of this article. Dr. I.. F.
Marker suggested that the writers undertake experiments to
discover whether any physico-chemical change could he
demonstrated in serum heated to the specified temperature.
Electro-chemical examination of the conductivity of the
serum was the method chosen, ami the Eollowing experiments
were carried out:
The serum was carefully obtained from dog's blood in the
pathological laboratory; the work on conductivity ua- d ■
in the Chemical Laboratory of the Johns Hopkins University.
through the courtesy of Dr. Harry ('. Jones. The apparatus
used is described bj Dr. Jones 1 ' as follows:
"J is a small induction coil, with only one or two layers
of wire. A larger coil must not he used, sine.' it does not
sharp tone minimum in the telephone. The coil
tuned to a very high pitch, should he enclosed in a bos -inrounded by a poor conductor of sound, and placed at some
distance from the bridge where the reading is to he made.
I'i" '"'I i- driven by a storage cell of medium size. A platinum wire, or better, one of manganese alloy, which has a -mall
temperature coefficient of resistance, is tightly stretched over
the meier -ink AB, which i- carefully divided into millimeters. A rheostat W. whose total resistance amounts to
1 1.1 10 ohms, is convenient. The resistance vessel R, containing the solution and electrodes — the electrodes are out from
1 P. Baumgarten. Beitrage zur Lehre von der natiirlichen Immunitat. Bert. klin. Wchnschr., No. 41. Oct. 9, 1899.
-Harry C. Jones. The Freezing-Point, Boiling-Point ami Conductivity Methods.
thick sheet platinum, ami into each plate a stout platinum
wire, about an imh in length, is welded. Mass tubes are
sealed on to the platinum wires and electrode plate-, by
means of sealing glass. . . . These tubes pass tightly through
a rubber cap, w Inch lits over the glass vessel. They are filled
to a convenient height with mercury, ami electrical connection, established by means of copper wires, which dip into the
mercury. One arm of (he telephone, T, is thrown into the
circuit between the rheostal ami the resistance, ami the other
arm i> connected with the bridge wire h\ means of a slider.
This is moved along the wire until that point is found at
which the hum of the induction coil ceases to he heard in the
telephone. Let this he some point ( '. and let us represent AC
by a. and BC by h. the resistance of the solution in the vessel
K by r. and the resistance in ohms m the rheostal by w: then,
from the principle of the bridge, we bave
wh
wb
But the conductivity of a solution, e. is the reciprocal of the
resistance, r: therefore.
September, 1900.]
JOHNS HOPKINS HOSPITAL BULLETIN.
221
wb
... A cell-constant, C, must be introduced and determined
for each cell before it can be employed for conductivity measurements."
In calculating the molecular conductivity of a substance,
its molecular concentration must be taken into account, but
in these experiments this was not considered necessary. The
results given in the tallies express the conductivity simply as
the reciprocal of the resistance, r. according to the formula
r , va
c = C
wb
The material used in the experiments was dog-serum, obtained under proper aseptic precautions. In the first experiment the serum was heated from 34 to 70 I !., and its conductivity tested at the following temperatures: 3 1 . 30 , 38 .
50°, 51°, 52°, 53°, 54°, 55°, 56°, 57°, 58°, 59°, G0°, 70°.
It was then cooled to 38°, and its conductivity again tested.
The material was kept at each of these temperatures long
enough to ensure a constant reading, and the temperature was
not raised above 70°, on account of the changes in concentration which would have occurred from evaporation.
Five more experiments were performed with serum taken
from different dogs. The conductivity was tested at 34°. the
material was then heated to 57° and kept at this temperature
for one hour, after which it was slowly cooled to 24°. and
the conductivity again tested, to discover if any change had
taken place. The results of these experiments are incorporated in the following tables. The figures in each case repre-ciit the mean of three readings.
EXPERIMENT I.
24°
11.833
55°
. .. 19.388
5<;°
19.643
:;s°
14.696
57°
19.881
50°
17.S73
58°
30.183
51°
IS. Hi
60°
18.536
.... 30.78
70°
23.253
54°
19.053
After eooling
3S°
14.743
The gradual increase in conductivity is. of course, due to
the rise in temperature.
Experiment II.
Experiment III.
Experiment IV.
Experiment V.
Experiment VI.
24°
24°
24°
Before In iiTiiil'
to 51 e
for 1 hour.
11.436
11.786
11.48
11.446
10.546
After heating to
57° C. for 1 ur. and
again cooling
to 24° C.
11.466
11.763
11 186
11.446
10.56
The results of the above experiments go to prove that the
alleged loss of bactericidal power in blood-serum heated to
57° is not due to any chemico-physical change which can be
demonstrated by the conductivity method.
A CONTRIBUTION TO THE STUDY OF MALIGNANT TUMORS ARISING IN
CONGENITAL MOLES.
By R. H. Whitehead. M. D.. Chapel Hill, N. C.
(From the Pathological Laboratory uf the Johns Hopkins I niversity and Hospital.)
In 1893 TJnna' announced his belief that melanotic malignant tumors which originate in pigmented moles should he
classed as carcinomata. He based his opinion upon an examination of some tumors of this sort, and especially upon a
study of moles obtained from newborn and very young children. According to him, the groups of pigmented cells commonly found in moles are derived from the epidermis during
embryonic life or early childhood by being cut oil' from the
interpapillary processes of the rete Malpighii, and afterwards
losing their prickles and undergoing other metaplastic
changes. He concluded, therefore, that melanotic tumors
arising in moles are not sarcomata, but carcinomata.
Since, at that time, it was generally held thai tie so-called
mevus cells were of endothelial origin, TTnna's statement
aroused considerable opposition. Green 2 denied the epider
1 I'nna, P. G. Naevi und Naevocarcinome. Bert. kiln. Wchnschr., 1S93. XXX, 14.
2 Green, L. Ueber Naevi pigmentosi. Virchow's Archiv, 1893,
CXXXIV, 331.
mal genesis of the nasvus cells, and pointed out that there is
no relation between the amount of pigment in them and that
in the epidermis — that it may lie present in either situation
while absent from the other.
Then Bauer,* a pupil of Eihhert, investigated the subject,
and reached conclusions quite the opposite of those of Unna,
even after examining Unna preparations, lie convinced himself that the mevus cells were of endothelial origin, and staled,
furthermore, that the individual cells in the groups were
separated froi le another by a line fibrous network, and
that, they were frequently branched so as to resemble stellate
connective-tissue cells.
Luliarsch* stated that he had examined a considerable
number of moles in newborn and young children, and had
■ Bauer, C. Ueber endothellale Hautwarzen und ihre Beziehungen zum Sarcom. Virchow's Archiv, 1895, CXLII, 407.
' Lubarsch-Ostertag. Ergeb. d. allg. Pathol., etc., Wiesbaden,
1896, Bd. II, S. 379.
222
JOHNS HOPKINS HOSPITAL BULLETIN.
[No. 114.
not been able to detect any correspondence between the
najvus cells and those of the epidermis.
Unna, however, did not tail to find supporters. Delbanco,*
as the result of his study of two moles, stated that the interpapillary processes of the epidermis are frequently in direct
connection with the groups of najvus cells, and that, owing
to proliferation of the stroma of the mole, numerous epidermal cells are separated off into groups and afterwards displaced into the lymph vessels.
Kromayer" rejected Delbaneo's conclusion that the nanus
cells are contained in lymph vessels, but agreed with him and
with Lima in deriving them from the epidermis. This investigator describes in the moles of infants cyst-like spaces filled
with cells containing vesicular nuclei. They are situated in
the epidermis, between the epidermis and the subjacent connective tissue, or entirely within the latter. He thinks that
all of these groups of cells become enclosed by connective
tissue later on, and that then the cells throw off fibres, until
finally little is left of the individual cells save nuclei closely
applied to fibres — that, in fine, the epithelial are metamorphosed into connective-tissue cells.
Lubarsch, 1 in a critical review of the work done up to that
time, expressed the opinion that the researches of LTnna,
Delbanco, and Kromayer were individual interpretations of
microscopic pictures rather than objective descriptions of
appearances actually observed, and that their illustrations
were susceptible of more than one interpretation. Thus, he
claimed that Kromayer's picture representing nests of naevus
cells in the epidermis could be reproduced by oblique sections
of the skin in conditions characterized by elevations of the
epidermis, as the result of growing or proliferating papilla?.
Xor was he willing to accept Kromayer's metaplasia of epithelial into connective-tissue cells, holding that the law of the
legitimate succession of differentiated cells was too well established to be surrendered on such proof as Kromayer presented. He criticized also the method with which Kromayer
worked, and was not convinced by his original preparations.
Still, he was unwilling to deny the possible existence of
epithelial naevi.
A little later Scheuber* made serial sections of several pigmented moles, and convinced himself that Unna's view as to
the origin of mevus cells was correct.
Recently Gilchrist' 1 1 as made an investigation of the subject, and. from the study of a pigmented mole in an infant,
arrived at the conclusion that the naevus cells are developed
in the waj described by Unna.
s Delbanco, E. Epithelialer Naevus. Monatsh. f. prakt. Dermat.,
1896, XXII, 105.
• Kromayer, E. Zur Histogenese der weichen Hautnaevi. Dermat. Ztschr., 1896, III, 263.
'■ Op. cit., S. 591.
8 Scheuber, A. Ueber den Ursprung der weichen Naevi. Arch,
f. Dermat. u. Syph., 1898, XLIV, 175.
» Gilchrist, T. C. On Malignant Growths Arising from Pigmented Moles. Jonrn. Cut. and Genito-Urin. Dis., 1899, XVII, 117.
Finally, Schalek "' has studied some pigmented moles and
melanotic tumors of the skin, and has satisfied himself of the
correctness of Unna's views.
In the midst of such difference of opinion one finds it difficult to reach a definite conclusion as to the nature of the
naevus cells; but the pictures of Scheuber and of Gilchrist
are, to say the least, exceedingly suggestive, and one may
fairly be permitted to hold the view that in some moles, at
Least, the groups of cells are modified epithelial cells of epidermal origin. Should a tumor spring from such cells, we
should, naturally, expect it to follow the type of carcinoma.
This expectation, however, is not always realized. Tuna."
indeed, states that all id' these tumors which he has studied
presented the structure of alveolar carcinoma (carcinoma
simplex). On the other hand, the nine tumors of this class
which I have been able to examine, had that histological
structure which most pathologists have agreed to call alveolar
sarcoma, and were so pronounced by competent observers.
While we may well hesitate to be dogmatic in such matters.
yet one is reluctant to regard as a carcinoma a tumor which
presents so many characteristics of the sarcomata.
The following rases are reported not so much with the hope
of throwing new light upon this vexed question as rather to
call attention to the fact that tumors may spring from congenital moles which represent the same processes as those
going on in the melanotic tumors, with the exception that
they totally lack true melanotic pigment.
( lse 1. — The subject of this tumor was a white man aged
47 years. He had noticed, as long as he could remember, a
" black mole " on the front of his right forearm a little above
the wrist. For the last few weeks this had been enlarging
rapidly, so that when I saw him there was in the situation
mentioned a perfectly black tumor, conical in shape, and
about 2 cm. high. The color was (\w largely to clotted
blood, with which the tumor was encrusted, owing to frequent
hemorrhages. The growth was removed by incisions carried
widely into apparently healthy tissues. Eight months afterward- 1 learned that he had died "with tumors all over him."
They were estimated as at least 200 in number, were situated
in and beneath the skin, and varied in size from that of a pea
to that of a hen's egg. Towards the end of his life he suffered
much from frequent painful micturition, and on several occasions passed in his urine fleshy masses believed by his medical
attendant to be pieces of tumor.
On section the tumor was deeply pigmented in places, and
was spongy and friable, tending to crumble to bits when
handled at all roughly. It arose by a broad, short pedicle a
little more than one cm. thick.
In longitudinal sections through the pedicle the latter is
seen to be formed by dense fibrous tissue containing sweat
10 Schalek, A. Contribution to the Histogenesis of Melanocarcinoma of the Skin. Journ. Cut. and Genito-Urin. Dis., 1900, XVIII,
145.
11 Unna, P. G., op cit.
THE JOHNS HOPKINS HOSPITAL BULLETIN. SEPTEMBER, 1900.
PLATE XVI.
;
Pig. L- Shows structure of the tumor in Case I
Fh.. 2, Casi 1.- -Shows the intraalveolar reticulum.
/3fc „ *»tiite. ^
::.-,«;
*£ 5 $K
Fig. 3, Case II.- Port ii
> ' ^ . , a: . •
a c ell-mass of the RrsI varietj
*<#»
^
*0 ss>
^
■■',
-ex .'
Fio. 4. Case II.— Portion of a cell-ma
Fh
Casi i ! '" s ' < llu ' " l: '"' ol
the econd variety.
September, 1900.]
JOHNS HOPKINS HOSPITAL BULLETIN.
223
and sebaceous glands and a few hair roots. Proceeding towards the tumor proper, many .young capillaries are encountered containing numerous polymorphonuclear Leucocytes and
surrounded, here and there, by groups of small round cells.
In this region pigment begins to appear as small masse- of a
yellow-brown color. In some cases these masses are contained in branched cells: in others I am unable to decide
whether they are intra- or extracellular in situation. Near
the pedicle the arrangement of the tumor is alveolar in character, though the stroma soon becomes very scanty, the walls
..I the alveoli being quite delicate and furnished by a lew
spindle-shaped cells. The cells within the alveoli are, in the
main, large and polygonal; their nuclei arc fairly constant in
size and appearance, being vesicular with nucleoli and grains
■ if chromatin, (.'ells with several or budding nuclei arc frequently seen. In certain alveoli fnun which some of the
tells have been removed by shaking, it can he seen that the
cells are separated from one another by a very line reticulum,
which appears t>> consist in large part of processes from the
cells themselves. Many of the cells contain pigment in the
form of yellow-brown grains. Farther towards the periphery
-I the tumor the alveolar is succeeded by what may he termed
a diffuse arrangement of the cells. Here the stroma, reduced
to a minimum, is represented only by a few parallel rows of
endothelial cells running here and there through the large
masses of cells. It is difficult in this region to detect any
intercellular substance; occasionally one sees cells with fibrillar processes. Very common are exceedingly large cells,
spherical and multinucleated, containing many granules of
pigment. The superficial portions of the tumor are inflamed
or necrotic, and infiltrated with blood. The areas still living
consisl of large vascular spaces lined by endothelium and surrounded by masses of tumor cells. The epidermis near the
pedicle is thickened, but no connection can be made oui he
t and the tumor proper. In other situations the epidermis has broken down before the invading masses of tumor
cells, which grow through and project beyond it. II has entirely disappeared from over the greater portion of the surface
of the tumor. In the thickened epidermis a few epithelial
[i arls were noticed, some of which contained pigment. The
tests i >r iron-containing pigment resulted negatively.
Here we have a typical example, in an advanced sta
ih malignant melanotic growths which spring from the
naevus cells of congenital moles — the najvocareinomata of
Tuna, or the alveolar melanotic sarcomata of most author-.
Case '.'. — This tumor was obtained, through the kindness
of Dr. ('. S. Mangum, from a white woman -">0 years old.
She consulted Dr. Mangum concerning a large mole situated
over the inferior angle of the left scapula, ft had been
present "all her life," but only recently had been enlarging.
Dr. Mangum thought best to remove the mole, especially as
there were evidences of beginning ulceration. The mbse
Mm ht history, unfortunately, could not be fully obtained.
It was learned, however, that the wound made by the opera
tion never healed, and that the lymph nodes in the left axilla
soon became enlarged. About eighteen months after the
operation she was considered by her family physician to be
dying of a malignant tumor of the uterus.
The tumor is about 2 cm. long, and 1 cm. thick. It presents the macroscopical appearances of soft papilloma, its
surface being corrugated. It possesses a short, narrow pedicle. On section it is seen to be pigmented in streaks of a dark
slate color.
In sections made through the center of the mole including
the pedicle, the latter is found composed of fibrous tissue; its
arteries are thickened, and there are some patches of small
round cells. In these sections the structure is quite suggestive
of carcinoma simplex. There are variously shaped alveoli,
for the most part long and narrow, whose walls are thick and
formed by dense fibrous tissue with scanty spindle cells. The
cells within the alveoli are packed closely without visible
intercellular substance. They are regular in size and appearance, being rather small polyhedral cells with pale vesicular
nuclei. This area, doubtless, consists of normal mole tissue.
Sections made through the other portions of the tumor,
however, present a different picture. The most prominent
feature is furnished by large, more or less round collections of
cells surrounded by capsules of dense fibrous tissue. They
are not all alike, but may be divided into two varieties. The
more numerous ones are composed, in the main, of small polygonal cells with deeply staining nuclei, though occasionally
one sees a very large cell with more than one nucleus. The
primary mass of cells is subdivided into much smaller masses
by a spindle-celled connective tissue, which runs in from the
surrounding connective tissue, and conveys vessels. In most
cases this tissue is quite scanty, and often the subdivisions
seem to be separated only by narrow cracks, the boundaries
of which are the tumor cells, though sometimes a tew spindle
cells can be seen bordering them. Xo intercellular substance
can be made out between the cells in the subdivisions. In
si ■ ol' tin' masses the thickness of the connective tissue
septa is much greater than in those just described, and then
.in appearance is produced somewhat like that described in
sections through the center of the tumor.
The cell masses of the second variety are not so numerous
as those of the first, and arc not so sharply circumscribed.
The cells composing them are, for the most part, very large
and round, and many of them contain more than one nucleus.
They are separated from one another by a delicate reticulum,
which frequently holds deeply staining nuclei; or several cells
may be shut oil' into small groups by portions of the reticulum.
As a rule, the cells towards the periphery of these masses
tend to assume the spindle shape, and gradually fade away
into the surrounding connective tissue. Areas are observed
where a mass of the first variety is passing by gradual transition into one of the second variety. Moreover, in the case of
both varieties, columns ol' cells advance into the surrounding
stroma, where they usually lend to the spindle shape.
The stroma of the tumor is furnished by a central trunk of
fibrous tissue, which gives off branches here and there to sur
round the cell masses alluded to. It conveys many blood
224
JOHNS HOPKINS HOSPITAL BULLETIN.
[No. 114.
. around which are some patches of small round cells
and many plasma cells, and contains scattered, long, narrow
spindle nuclei. In several places this tissue is losl in diffuse
of large spindle-shaped cells, for which it seems to
form an intercellular substance.
The surface of the tumor is covered everywhere by epidermis, which is necrotic over a considerable extent of the
tumor. Where the epidermis is intact, il is seen to be very
thin — it is reduced to two or three layers of cells — and is
separated from the subjacent tissue by distinct lines of connective tissue. Some epithelial pegs project from the epidermis, but they, too, are very thin, and show no connection
with the tumor cells. The pigment was found chiefly along
the course of the blood-vessels and in the most superficial
parts of the growth, where hemorrhages had occurred. Much
of it responded positively to the ferrocyanide of potassium
test, and the remainder was amorphous hsematoidin contained
largely in polymorphonuclear leucocytes.
In this case, it, would seem, the processes which occur in
the malignant melanotic tumors are undoubtedly going on —
the development of a malignant tumor from the nests of
mevus cells in a congenital mole, but with the exception that
true melanotic pigment is not present. A priori, we should
expect to find such tumors, for Green 1 " has shown that the
naavus cells are not always pigmented, nor are tumors which
arise in melanotic tissues invariably melanotic, but I have not
been able to find the records of a similar case. Unna" hints
at the possible existence of such growths, but makes distinct
mention only of melanotic tumors.
12 Green, L. op. cit.
13 Unna, P. G. Die Histopathologic der Hautkrankheiten. Berl.,
1894, pp. 746-752.
INORGANIC FERMENTS. 1
By Harry C. Jones, Ph. D.,
Associate Professor of Physical Chemistry Johns Hopkins University.
A paper bearing this title has recently appeared by Bredig
and Miiller von Berneck. 3 The authors first point out certain analogies between the action of ferments and the contact
action of metals. Alcohol is oxidized to acetic acid by the
oxygen of the air as well by finely divided platinum as by the
organic ferment mycoderma aceti. Calcium formate is decomposed into calcium carbonate, carbon dioxide and hydrogen, not only by certain bacteria, but by finely divided
iridium, rhodium, or ruthenium, finely divided platinum,
palladium, iridium, osmium, etc.. have the power of inverting
cane sugar, like invertose.
The above relations are, however, only analogies. To determine whether there is any close relation between the action
of organic ferments and finely divided metals, some reaction
effected by both classes of substances must be carefully studied.
The reaction chosen by the authors of this paper is the
decomposition of hydrogen dioxide. This reaction is effected
by all organic ferments and, also, by finely divided metals, in
the sense of the following equation:
ll ; o, = ILO +
The metal chosen was platinum, and a colloidal solution
of this substance was prepared as follows: Two platinum
wires about 1 mm. in diameter were immersed in a vessel
containing very pure water. These were placed at a convenient distance apart, and a current of from 8 to 12 amperes
and 30 to 40 volts passed between them. There was thus
formed an arc between the platinum poles beneath the surface
of the water. Platinum was torn off from the cathode in a
1 Presented to the Johns Hopkins Hospital Medical Society.
"Ztschr. phys. Chem. (Jubelband zu van't Hoff), 31, 258.
very finely divided condition, and quickly gave a blackishbrown color to the surrounding water. The liquid was then
rapidly filtered through a folded filter to remove any larger
particles of platinum which may have been torn off. The
colloidal solution of platinum is a clear, dark brown liquid,
which, when examined

Revision as of 23:53, 20 February 2020


VOLUME XI



THE JOHNS HOPKINS HOSPITAL.


Vol. XI - No. 106.1


BALTIMORE, JANUARY, 1900.


Contents - January

Contributions to the Surgery of the Bile Passages, especially

of the Common Bile-Duct. By W. S. Halsted, M. D., - - 1 Early Exploratory Operations in Tuberculosis of the Hip. By

Joseph C. Bloodgood, M. D., - jj

Gunshot Injuries by the Weapons of Reduced Calibre. By

L. A. LaGardb, U. 8. A., - - - - - . oq

A Reconstruction of a Glomerulus of the Human Kidney.

William B. Johnston, - - - -Medical Commission to the Philippines.

Barker, M. D.,


By

Ry Lewellys F.


An Apparatus to Aid the Introduction of a Catheter or Bougie. By George Walker, M. D.,

Summaries or Titles of Papers by Members of the Hospital and Medical School Staff appearing Elsewhere than in the Bulletin, ------ Proceedings of Societies :

Hospital Medical Society, - - Exhibition of Surgical Cases [Dr. Mitchell] ;— An Improved Stethoscope [Dr. Cabot] ;— The Pulmonic Second Sound [Dr. Cabot].

Books Received,


CONTRIBUTIONS TO THE SURGERY OF THE BILE PASSAGES, ESPECIALLY OF THE

COMMON BILE-DUCT.*

By W. S. H.lstkd, M. D., Baltimore, Surgeon-in-Chief to the Johns Hopkins Hospital, Professor of Surgery in the Johns

Hopkins University.


Just now I am very much impressed with the splendid results of operations for gall-stones in the common duct, for we have had of late a series of cases very desperately ill, and so transformed by their emaciation and discoloration, and so feeble in body and mind, that I could hardly picture to myself the various stages of metamorphosis toward convalescence. Every one has seen a patient whose life has been despaired of convalesce from acute disease ; they watched his rapid decline and expected an almost equally rapid recovery; but when the decline has covered a period of five or ten or perhaps twenty years the changes wrought are so great and apparently of such permanent character that the complete restoration to health is the more astonishing. The large cirrhotic liver, the dry slateyellow skin, the enfeebled intellect, the body emaciated to the last degree, seem at times almost to preclude all hopes of recovery to the practitioner who has not witnessed the changes so quickly brought about by nature as soon as the mechanical obstacles to recovery have been removed by the surgeon. What nature accomplishes without the surgeon's aid in her attempts to rid herself of the obstruction in the gall-passages and to

•Read at a Meeting of the Surgical Section of the Suffolk District Medical Society, May 3, 1899.


repair self-inflicted damage is marvelous ; but her methods are very crude and attended with much suffering and great danger, immediate and remote. I have, however, in mind at this moment two particularly creditable examples of nature's surgery.

In the first one the gall-passages were shortened to just the length of the two large stones which completely filled them. One occupied the gall-bladder, the other the pancreatic portion of the common duct; the duodenum was not only adherent to the gall-bladder, but served in place of its anterior wall, which had been destroyed; the stone in the gall-bladder, therefore, rested on the wall of the duodenum, which was pasted, so to speak, over the great hole in the front wall of the bladder. There was nothing that could be called cystic duct ; the choleductus was almost completely covered by the duodenum; the hepatic duct was much distended, admitting easily one finger. All signs of inflammation, except its results, had disappeared. The simplest conditions had been produced, and those most favorable to the expulsion of the stones in some subsequent attack ; gall-bladder and common duct were reduced to a short, wide, nearly straight tube, which bore a striking resemblance to an atheromatous aorta. The stone in the common duct was behind the duodenum and buried in its wall.


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 106.


The second patient had his first colic twenty-one years before admission to the hospital. He was never jaundiced. In the third attack, which began one month prior to operation, his temperature reached 106°. A physician aspirated pus from the distended gallbladder about twenty-four days after the onset of the third attack, or three or four days before we operated. The gall-bladder was opened in two acts. The fluid in the gall-bladder was almost clear and not bile-stained. Diagnosis : Stone in the cystic duct. Cover-slips showed few bacilli. Cultures yielded bacillus coli communis, pure. Patient applied for re-admission in eighteen months, because he had noticed a hard body just beneath the skin in the mouth of the sinus. By simply dilating the sinus I removed four large, very darkgreen, almost perfectly cylindrical stones, which were piled up upon each other in this sinus, forming a column 10 centimeters high. Nature would herself have extruded these stones which she had brought to the surface without causing the patient any discomfort.

Equally marvelous are the processes by which nature destroys all traces of her surgical handiwork. I have operated upon two cases in which perforation of the gall-passages and intestinal walls, and the expulsion of the stone, had undoubtedly occurred, but was unable in one of them to find any evidence of the perforation other than a few light and easily separable adhesions. Again, in a case of appendicitis, followed by gangrene of the greater part of the cecum and a wide preternatural anus, there were, within a year, only a few very light adhesions about a pinhole opening in the colon to tell the story. These facts are enough to make the ordinary operations for suspension of the spleen, liver, uterus, etc., seem ridiculous. Adhesions about an artificial opening fortunately never disappear. If innocent fistula? could be established, with the organs to be suspended, the problem might in a way be solved.

I wish to ask your attention to-night to a few of the unusual facts observed by us in our operations upon the bile-passages j particularly the common bile-duct. Almost every one of our common duct cases has presented us with a new fact or two which can hardly fail to interest the general practitioner, as well as those who concern themselves with the surgery of the bile-passages. To be as brief as possible, for the time is short, I will summarize at the outset some of the more noteworthy incidents observed by us in this department of surgery.

I. Dilatation of the first part of the duodenum caused by constricting adhesions ; as the result, perhaps, of tlie dilatation, an ulcer (" distention ulcer" — Kocher) on the confines of the pylorus ; the ulcer gave rise to a dissecting submucous abscess (chronic), rich in organisms because not reached by the most painstaking sterilization of the stomach. This abscess was punctured during the operation and a fatal peritonitis resulted (terminal infection), although, literally, only a drop or two escaped, and these were carefully wiped away.

II. Primary carcinoma of the duodenal papilla and diverticulum Vateri.

First operation. — Excision of portions of the duodenum (nearly its entire circumference), pancreas, common bile-duct and pancreatic duct in order to give the little growth, no larger than a pea, a wide berth ; circular suture of the duodenum and


transplantation of the stumps of the common duct and the pancreatic duct (Wirsung's) into the line of this suture.

Second operation. — Cholecystcysticoenterostomy by the writer's method* for intestinal lateral anastomosis.

III. Dynamic dilatation of the first portion of the duodenum and of the pyloric portion of the stomach, corresponding accurately to the limits of a sharply-circumscribed peritonitis; gall-stones in the gall-bladder; hydrops vesicas. Case full of interest for diagnostician. Beautiful instance of circumscribed dynamic dilatation caused by local inflammation ; no adhesions.

IV. Conditions suggesting hepaticocholecystostenterostomy (hepaticocholecystostcholecystenterostomy) as a possible operation ; common and cystic ducts reduced to fibrous cords ; dilated hepatic duct and gall-bladder. Remarkable toxic (?) renal colic resembling closely intestinal colic, associated with anuria ; colic and anuria entirely relieved by salt infusion.

V. Choledochotomy performed twice. The gall-bladder, which was shriveled at the first operation when two stones were probably in the common duct, was large and distended at the second operation when only one stone occupied the common duct (the ampulla). Hematemesis after the second operation.

VI. The densest adhesions that I have ever encountered in these operations, and probably the most difficult of my operations upon the bile passages. A small abscess in the midst of the adhesions; muscular coat of the duodenum converted into fibrous tissue; the exposed submucosa resembled gall-bladder so closely that the duodenum was aspirated and opened.

VII. Case illustrating the rapidity with which adhesions after perforation and extrusion of stone can be absorbed. Renal pains resembling intestinal colic (third observation of the kind within eighteen months). Tachycardia, believed to be due to toxemia of some kind (possibly benign embolism), suddenly disappeared during counting of pulse and while preparations were being made for subcutaneous infusion.

VIII. Discharge of pus and blood by mouth and rectum during severe gall-stone attack. Two years later, adhesions so extensive and so dense that the common duct was reached by a retroperitoneal route, over the right kidney. A stone in the ampulla had just ulcerated through the wall of the common duct and through its duodenal coverings.

Case I. — Duodenal stenosis from gall-stones ; dilatation of the stomach and of the pyloric end of the duodenum ; duodenal ulcer giving rise to a dissecting abscess. — J. S., age thirty-six, admitted February 5, 1899. Never had typhoid fever. Had malarial fever ten years ago with shaking chills. Never suffered from stomach trouble until present illness. Ever since he was eight years old has had sick headaches, lasting three to four hours, once a month ; these would be relieved by emptying his stomach. Has never been jaundiced nor had clay-colored stools. Present illness began very gradually. Three years ago, he noticed that his stomach would swell after eating and hardly regain its normal size before the next meal. Had more or less pain in the epigastrium, which was most marked about one hour after eating. No nausea or vomiting at first ; bowels regular. About the first of last October the pain became worse, and his sick headaches were more numerous and more severe. His vomiting now began. The vomiting was accompanied by colic, so severe as to double him up. Patient was obliged to stop


"Bulletin of the Johns Hopkins Hospital, No. 10, 1891.


January, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


work for two weeks. He then resumed work until Christmas, since which time he has been unable to work. Patient now vomits much more frequently. The vomiting is preceded by heartburn for about three hours and much pain in the epigastrium. Patient feels greatly relieved after the vomiting. For two weeks after Christmas he had eructations of gas ; none since then. Bowels usually constipated ; sometimes did not move for three weeks. He still suffers much from headache. His appetite is good, but he is afraid to eat. In October, 189S, patient weighed one hundred and forty-five pounds ; he now weighs one hundred and twentythree pounds, and is very weak. Neither stools nor vomitus have ever been blood-stained. Urine normal. Stools clay-colored. Patient not jaundiced.

On palpation of the abdomen no distinct tumor can be felt, but one detects an increased resistance just to the right of the umbilicus. The stomach's longest diameter is 31 cm.; its shortest diameter, 21 cm. The lowest limit of the stomach (tympanitic) is 3^ cm. below the umbilicus. Spleen not palpable. Heart and lungs normal. Glands nowhere enlarged. Pulse slow, feeble, 60 beats to the minute.

January 24th. Test breakfast (Ewald). Two hundred and sixty cc. removed one hour later ; green color ; acid. Total acidity, 5.9 cc. ; 0.1 normal NaOH. Free hydrochloric acid ; no lactic acid. No sarcinse nor Opper-Boas bacilli.

February 4th. Test breakfast. Sixty cc. removed. Total acidity, 20. No hydrochloric acid ; no lactic acid. A few Opper-Boas bacilli (?).

February 5th. Stomach tympanitic. Clapatage readily obtained. Stomach peristalsis quite marked at times. Gurgling felt over small intestines. Stomach washing with sterile salt solution, as preparation for operation, begun. Stomach holds about two liters. Cover-slip preparations show streptococci and staphylococci and numerous bacilli.

February 7th. Stomach washing continued. Cultures taken from the residual material. Cover-slips show only a few streptococci in short chains ; number much decreased since February 5th.

February 8th. Only a trace of free hydrochloric acid ; no lactic acid. Total acidity, 6.2 cc, 0.1 NaOH solution. Stomach peristalsis readily seen at times. Patient has been kept on sterile diet ever since his transfer to the surgical side. Has carbolic-acid gargle three times daily. Teeth cleansed three times daily with listerine and brush. Ingesta are boiled water, boiled milk, softboiled eggs, albumin. Micro-organisms seem to have entirely disappeared from the stomach, for the Petri plates are now sterile. Patient has shown great irregularity in amount of hydrochloric acid — at one time five per cent., at another zero.

February 9th. Operation.— Vertical incision through left rectus. This incision was made with the expectation of a possible gastroenterostomy. Stomach much dilated. In the region of the gallbladder is a mass of tissue tangled by dense adhesions. In this mass are gall-bladder and pylorus. The mass feels not unlike a new growth. Search for metastases negative, but a small, hard, dark tumor, the size of a pea, is discovered in the right lobe of the liver, near its edge, evidently an angiosarcoma. Pylorus separated from gall-bladder with the greatest difficulty. The separation had to be effected with the knife. It was impossible at first to determine accurately the relations of the gall-bladder, pylorus and duodenum to each other. In the course of the dissection a pinhole opening was made in what proved to be the duodenum. The surrounding parts had been well protected against such an accident. A drop of fluid escaped, and from these cultures were taken. The little hole was immediately sutured. The gall-bladder was next opened, and not until then could it be determined positively that the pinhole opening was not in the gall-bladder, the contents of duodenum and gall-bladder so closely resembled each other ; it was a thick, ropy, mucoid, colorless material. The gall-bladder was finally completely isolated. It was small and misshapen and


contained two or three hard mulberry-like gall-stones. The cystic duct contained no stones ami seemed to be very short and very fine. It was surrounded by numerous small vessels, two of which were tied. There was no bile in the freely opened gall-bladder, which was drained in the usual way with a rubber tube, a catgut purse-string suture sealing the bladder hermetically about the tube. Bismuth gauze was packed about the outside of the gallbladder. The peritoneum was closed with silk ; the muscles, fascia and skin with silver. Patient bore the operation very well. At G p. m , temperature 101°; respirations quiet and regular. Some distention of upper abdomen.

February 10th. Patient has been vomiting. Complains of pains in stomach and tightness across abdomen. Pulse 108 and feeble ; respirations 24 ; temperature 101°. Leucocytes at 12.30 p. m., 26,800 ; at 1.30 p. m., 34,000 ; 5.30 p. it., 36,000 ; 7 p. m., 37,800. At 6 p. m. patient drowsy, quiet ; respirations, 34 ; hands cold ; pulse barely perceptible. Cover-slips show no micro-organisms in the blood. Five hundred cc. salt solution infused under each breast. At 10 p. m. 1000 cc. salt solution infused under breasts. Pulse improved, 140 to minute ; low tension but regular rhythm. Respirations 36 ; expirations accompanied by short groans. Occasional hiccough ; no vomiting; no nausea ; no pain.

February 11th, 2.15 a. m. Patient died quietly.

Autopsy. — General peritonitis. Organisms, streptococcus pure. In the walls of the first portion of the duodenum, very near the pylorus, was an accumulation of thin mucopurulent fluid. This was held in bounds by a soft wall of granulations ; it was evidently an old abscess between mucosa and submucosa, which communicated with the lumen of the duodenum by a fine opening. A minute ulcer had perhaps been the starting point.

The first portion of the duodenum was distended, and the stomach was dilated ; the distention was due to the constriction produced by the adhesions, for which the gall-stones were responsible ; as a consequence, perhaps, of the distention and the resulting venous stasis, a minute duodenal ulcer ; and from the ulcer, the abscess, which was probably responsible for the fatal streptococcus peritonitis.

Of special interest in this case is: (1) the fact that carcinoma had been suspected — the duodenal stenosis, the dilatation of the stomach, the presence of Opper-Boas bacilli (?) justified the suspicion ; (2) the success which attended Dr. Cushing's efforts to sterilize the stomach ; the micro-organisms had apparently entirely disappeared from the stomach on the day preceding the operation, for the Petri plates, which from day to day showed fewer colonies, for that day were sterile; (3) the dissecting intramural abscess, starting probably from an ulcer which may have been due to thrombosis of a small artery, or to distention of the first part of the duodenum, or to vascular disturbances of some kind, infectious or mechanical. Although thrombosis of a small intestinal artery does not lead to infarction it may cause hemorrhages into the lumen of the intestine and slight intramural extravasations.*

Kocherf has demonstrated that in consequence of distention of the gut by retention of its contents and the resulting venous stasis, very considerable changes take place in the wall of the intestine. He writes as follows: "Arnd has proved that in strangulated hernias, when the circulation is greatly interfered with, micro-organisms make their way into the mucous mem


  • Archiv fur pathol. Anat. u. Physiol., 1875.

t Kocher : Mittheilungen aus den Grenzgebieten der Medizin und Chirurgie, Bd. iv, Heft 2, 1898.


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 106.


brane and can pass through the intestinal wall (diapedesis of the micro-organisms). On the other hand, Cassin* and Charrin f have shown how very important the normal epithelium of the intestine is as a protection to the intestinal wall against micro-organisms as well as ferments. The absence of this protection against ferments and bacteria leads to intoxication and infection. Finally, Beichel J has demonstrated that the considerable accumulation of fluid above the site of the obstruction is due in part to a hypersecretion of the mucous glands. Under the influence of the intestinal contents which, increased in amount and stagnating, are the more rapidly decomposing (the ofttimes considerable phenoluria and indicanuria is proof of the increased decomposition), the epithelium in the first place becomes destroyed because its nutrition is interfered with under the influence of the venous stasis. There result circumscribed necroses and hence ulcerations of mucous membrane, particularly in places where the venous stasis led to ecchymosis, and, finally, perforation of the serosa and peritonitis may occur. For the origin of these ulcers which, many times observed, have not been properly estimated in their relations to ileus, various explanations have been given. The most substantial explanation is the one which attributes them to the pressure of hard scybala, and it is not to be doubted that hardened fecal matter, just as foreign bodies — gall-stones, for example — can have pressure ulcers as a consequence. But the ulcers which we have pictured are certainly not dependent upon hard intestinal contents and the decubitus which they may mechanically bring about. They occur in jejunum and ileum as well as in colon by the filling up of these intestines with fluid or gas. The only factor which constantly accompanies these ulcers is overdistention of the intestine. Inasmuch as one can experimentally bring about a significant impairment of the circulation of the intestinal wall and its consequences, by overstretching of the gut, we hold to the proposition that the ulcers are best called distention-ulcers (Dehnungageschwure). Long ago I called attention to the fact that ulcers of just this kind could also in cases of strangulated hernia lead to a fatal peritonitis after constriction had been relieved, or a gangrenous loop of intestine had been resected and an entirely trustworthy suture had been made."

Case II. — Primary carcinoma of the duodenal papilla and diverticulum of the Vater, successfully removed by operation ; cyslico-enterostomy three months after the first operation. — Mrs. M. L., age sixty. Until August, 1897, patient was well. Her first symptom was itching of the skin, which came on suddenly and soon became severe. Patient says jaundice did not appear for nearly a month after the onset of the itching. Before the appearance of jaundice diarrhea set in, and there were six or seven stools a day which were watery and clay-colored. Patient has had no chills, no fever and no sweating. With the onset of the jaundice she noticed shortness of breath and an occasional swelling of the feet and legs. About the firstof January, 1898, she had persistent bleeding of the gums for three days, following the extraction of a tooth. At times the hemorrhage was profuse.


  • Mittheilungen aus Kliniken der Schweiz, Basel, 1898.

fFonctions protectrices de la muquese intestinale, Soc. de biologie, December, 1895. }Zur Pathologie der Ileus, Deutsche Zeitschrift fur Chirurgie.


Two months ago a tumor was noticed in the region of the gallbladder. This tumor does not seem to the patient to have increased in size and has never been tender. In March, 1897, she had several attacks of severe pain in the epigastrium. These attacks were not accompanied by vomiting or fever or sweating. A few weeks later she had a second but milder attack. The stools were light in color for two or three days at the beginning of these attacks, but patient recalls no change in the color of the urine or the skin at that time. The daughter of the patient states that these attacks of pain were very severe, and that her mother seemed very ill.

Examination February 14, 1898. — Patient somewhat emaciated, but fairly well-nourished. Mucous membranes pale. Heart and lungs normal. There is a distinct prominence on the right side, the highest point of which is midway between the umbilicus and anterior superior spine. The prominence descends markedly with inspiration. On palpation the prominent area proves to be pearshaped and distinctly fluctuating. The border of the liver, which reaches almost to the crest of the ileum, can be distinctly felt.

February 14, 1898. Operation. — Vertical incision through rectus muscle. A greatly dilated but not especially dense gall-bladder presented no adhesions. Liver projects five cm. below costal margin. Four silk sutures* placed in fundus of gall-bladder with French needles. Small aspirator introduced in center, between sutures; syringeful of clear fluid withdrawn. Gall-bladder opened ; contents evacuated. In the latter part of the fluid were many fine, sand-like, hard, greenish, round particles, suggesting miniature gall-stones. Common and cystic ducts were dilated to the size of one's thumb. A longitudinal opening two cm. long was made in the common duct. The same colorless fluid escaped from this incision. Duct explored with probe and finger. What seems to be a small, very hard stone is felt at site of ampulla. To determine the nature of this body, an incision was made through the wall of the duodenum. Noglandular metastases discoverable. Thestonelike body proved to be, as was feared, a carcinoma of the papilla.

Excision of the cancerous growth. — To give the growth a wide margin, a large piece of duodenum was excised, a wedge-shaped piece with the apex at the mesenteric border of the intestine. About three-quarters of an inch of the common duct and a shorter piece of the pancreatic duct were excised. The wound in the duodenum was closed in the usual way with mattress sutures. This was practically an end-to-end anastomosis of the duodenum. The common duct and pancreatic duct were transplanted into the duodenum along the line of suture. A linear incision into the common duet, which had been made for diagnostic purposes, was closed over a hammer. The gall-bladder was sutured to the peritoneum.

Abdominal wound closed in the usual way ; the peritoneum with a running silk suture, the muscles and fascia with buried silver sutures, and the skin with a continuous subcuticular silver suture. Bismuth gauze inserted to protect the suture of the intestine and common duct. Drainage tube surrounded by bismuth gauze, and gutta-percha tissue inserted into gall-bladder and held in place by a purse-string suture of catgut. Wound dressed with silver foil. Gutta-percha tissue placed between the raw edges of the skin and the gauze packing. Operation lasted three hours and ten minutes. Patient experienced apparently no shock from the operation.

February 16, 1898, first dressing. Profuse discharge of bile in dressing. Icterus less intense. Considerable abdominal distention, but no signs of peritonitis.


  • We find this a very useful procedure. The gall-bladder is manipulated by

these sutures and handling is thus avoided. These sutures are of additional service when it seems advisable to distend, subsequently, the gall-bladder with (iuid, and when it is desirable to close it temporarily during the operation.


January, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


February IS, 1898. Distention has almost completely disappeared. Tongue clean. Patient comfortable.

February 22nd. Discharge of bile into dressings still profuse. Stools becoming distinctly bile-stained. Icterus rapidly disappearing. Urine dark and gives bile reaction. Patient hungry.

February 27th. Skin sutures, tube from gall-bladder and the last of the bismuth gauze removed. Evacuations not bile-stained.

March 4th. Discharge of bile diminishing. Opening in gallbladder has been plugged for several days with bismuth gauze in order to determine, if possible, whether or not the transplanted common duct is patulous. Yesterday patient vomited 125 cc. of brownish fluid.

March 5th. Patient has had a large stool, quite dark in color. There is very little leakage from the opening into the gall-bladder, which is almost closed.

March 13th. Icterus continues undiminished. Stools are still slightly bile-stained. Abdomen somewhat distended. Active peristalsis is occasionally visible through the abdominal walls. Liver still readily palpable, the right lobe extending almost to the iliac crest. Appetite good ; tongue clean ; no indigestion.

March 27th. Attempts to plug the opening of the gall-bladder, with the hope of forcing bile into the intestine, not satisfactory, although there is some bile in the stools. Patient's general health good. Icterus has disappeared. Patient able to walk about, and is gaining strength rapidly.

April 5th. The conjunctivae are clear, but there remains still some evidence of bile pigment in the skin. No bile whatever in the stools, although the opening into the gall-bladder is almost closed ; it is barely large enough to admit a probe. Patient is beginning to have indigestion. The appetite as a rule, however, is good. The liver is diminished in size.

April 8th. Patient complains of colic and abdominal pain. Considerable abdominal distention. Dressings bile-stained. No nausea ; tongue is clear.

April 12th. Some nausea and vomiting. No distention of abdomen. Dressings very slightly bile-stained.

April loth. Abdomen soft and relaxed, but borborygmi heard by attendant and appreciated by patient. Little or no bile in dressings.

May 5th. Second operation: cholycyslduodenostomy, or eysticoduodenostomy. — Snture of fundus of gall-bladder. Complete closure of abdominal wound except for drainage. Incision alongside of old cicatrix, circumscribing fistula. Gall-bladder quite small, no larger than one's thumb. Liver about normal in size. Many fine adhesions about gall-bladder, which were easily separated. Gallbladder and ducts thoroughly exposed. The line of suture of common duct at previous operation was readily distinguishable by black-silk stitches, but it was almost impossible to find any trace of the duodenal suture. Common duct incised at site of old suture. Probe cannot be passed into the duodenum, but there is no positive evidence of the recurrence of the cancer. Unsuccessful attempts had been made before the operation to pass a probe from the gall-bladder through the common duct into the duodenum. Opening into the common duct closed in the usual way with mattress sutures over hammer. An anastomosis between duodenum and the gall-bladder or cystic duct was effected without much difficulty, although the parts to be sutured were very deeply situated and inaccessible. The duodenum was probably a little less freely movable than at the previous operation, and the gallbladder was so much reduced in size that we were compelled to pass some of the stitches into what seemed to be the cystic duct; in any event, the neck of the gall-bladder had to be used for the anastomosis. A bougie a boule, passed into the gall-bladder, was used as a darning ball to assist in the placing of the sutures. All the sutures were passed (none of them tied) before the openings into the neck of the gall-bladder and duodenum were made, the method employed being that which I described many years


ago for intestinal anastomosis. The opening in the fundus of the gall-bladder was closed with mattress sutures which inverted the wall. The abdominal wound was completely closed except for protective wicks which were passed through this line of suture into the gall-bladder. What seemed to be an enlarged gland was palpated during the operation but not removed ; it was forgotten. Patient suffered little or no shock from the operation.

May 6th, 4.30 p. m. Patient very restless, tossing about and occasionally vomiting. Ten p. m., has had occasional quiet naps and is more comfortable.

May 7th. Complains of pain in back and abdomen.

May 8th. Is very comfortable. Yellow stool, containing small particles of brown fecal matter.

May 9th. Large greenish-yellow stool.

May 11th. Patient has had daily, since last note, one or two greenish-yellow soft stools. She still complains of slight pain in abdomen.

May 12th. A large, quite well-formed greenish-brown stool. Considerable flatus expelled ; complains of gas in stomach. Slight nausea. Four p. it., vomited thick, mucus-like, chocolate-colored fluid containing milky curd.

May 29th. Patient complains of itching in the hands where the pruritus has always been the greatest when icterus was pronounced. No jaundice, however, is apparent.

June 8th. Slight chill, followed by rise of temperature to 39°. Trace of bile in the urine. Nausea, but no vomiting. No pain and scarcely any tenderness of the abdomen. Wound almost completely closed.

June 9th. Temperature normal ; patient feels well.

In the early autumn of 1898 this patient returned to the hospital too ill for operative interference, and in a few weeks died. During the summer I had corresponded with her, urging her to return to the hospital, for it was clear from her letters that the fistulous communication between the gall-bladder and the duodenum was not working well. At the autopsy it was found that the carcinoma had recurred in the head of the pancreas and duodenum closing the common duct and interfering with the perfect action of the cholecystenterostomy, or cystico-enterostomy. The anastomosis, as we had supposed, had been made between the dilated cystic duct and the duodenum ; the fistula was still perfectly pervious and should have acted nicely except for the interference, a little twisting or bending, created by the new growth.

The result in this case is not encouraging, for it was my opinion at the time of the operation that the case could not have been more favorable. But I did in this case what I never do if it can be avoided, namely, cut well down to or perhaps a little way into the new growth for the sake of diagnosis. It is furthermore a rule in myelinic that pieces shall not be excised from new growths in vivo for diagnostic purposes ; we must learn to make the diagnosis in other ways. In the case of a very small breast tumor it is occasionally impossible to make the diagnosis before operation. I have sometimes approached the tumor with the knife very cautiously, and could tell before I reached the growth, from the findings in the outlying tissues, whether we had a malignant tumor to deal with or not. I shall have more to say about this at another time, but I feel that one cannot condemn too strongly the universal practice of exploring tumors with the knife or with the harpoon or even with the needle. After investigating the subject superficially, I have the impression that amputations for the truly malignant


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[No. 106.


sarcomata have comparatively seldom been successful when preliminary exploration has been done. If I find it necessary to make an incision into a sarcoma of an extremity, I first apply an Esmarch bandage, and if the tumor is a malignant growth, the bandage is not removed until the growth has been removed. So, too, in cysts of the breast; we should not aspirate them, because (1) they may be malignant and the aspiration harmful, and (2) if maliguant, the aspiration does not tell us so. This is the first and I believe the only instance in which an operation for primary carcinoma of the duodenal papilla has been done ; moreover, I know of no other case of excision of a portion of the common duct. Heidenhain* (Worms) demonstrated last year at the twenty-seventh Congress of German Surgeons, a shriveled gall-bladder which he had removed for a small cancer of its wall ; after extracting six calculi from the bladder, a little button-like prominence on its wall caught his eye. The microscopical examination showed little or no thickening of the mucous membrane, but unmistakable alveoli in the muscular wall of the gall-bladder; furthermore, some of the lymph-vessels were plugged with cancer cells. In three months the patient succumbed to livercancer which had attained great dimensions, although at the time of the operation the liver was apparently perfectly normal. At the same session Hollander! (Berlin) reported an extirpation of the gall-bladder and cystic duct and resection of a portion of the liver for cancer, which per continuitatem involved the liver. The result he could not give, for he had performed the operation only three weeks before. There can be little doubt as to the ultimate result of Hollander's operation, although, having operated only three weeks previous to his report, he could not give it.

Case III. — Dynamic or paralytic dilatation of first portion of duodenum and of the pyloric end of the stomach correspondiyig accurately to the limits of a sharply circumscribed peritonitis. Oall-stones in gallbladder and cystic duct. Obstruction of cystic duct and hydrops vesical. — Mrs. S. G. M., age forty six. Admitted January 31, 1899. Never had typhoid fever. Headaches at intervals all her life, sometimes very severe and lasting several days; especially severe during menstruation. Digestion has been bad for sixteen years. After meals a heavy feeling in epigastrium followed by fullness and a feeling of suffocation. Belching of gas common; occasionally would regurgitate a mouthful or two of food. Rarely vomited ; never any blood in vomitus. Bowels generally constipated. Micturition frequent, occasionally twenty times a day ; generally several times at night. Menses regular. Average weight, one hundred and fifteen pounds. Has lost in weight of late. Present illness, patient states, began December 31, 1898, although she was much run down before that time. This attack came on gradually. Some distention of stomach, and in the afternoon some pain which became severe at night. The pain was in the epigastrium — a colicky pain — which, as she expressed it "went through the abdomen." Morphia exhibited. Next morning patient felt easier. Morphia continued for next two days. Pain relieved but not entirely subdued. Stools after this were very black, like tar. Physician found something in the stools which he thought might possibly be a gall-stone. Since this attack patient has never been well ; constantly in bed. Great deal of soreness through abdomen, and at times attacks of colic. These


  • Heidenhain : Verhandl. d. deutsch. Ges. f.Chirurgie, 1898, p. 126.

t Hollander, I. c. p. 131.


attacks usually came on in the evening without known cause. Much belching of gas. Bowels regular. Stools not clay-colored. No jaundice. Patient's daughter states that for many years her mother has had attacks of abdominal pain, for which the doctor gave morphia hypodermically. There were intervals of several months between the attacks.

Examination. — On palpation no tenderness except beneath the right costal margin. Here there is to be felt a rounded mass resembling a distended gall-bladder. Right rectus muscle very hard. The mass which is to be felt at the outer edge of this muscle seems lobulated.

January 29th. Attack of what patient calls "colic." She ia nervous and distressed, and complains of abdominal pain. Swallows air and belches it up again.

January 31st. Transferred to surgical side. On inspection a distended piece of gut between umbilicus and tumor, extending obliquely from the left and above to the right and below, probably six or eight inches in length. Peristalsis is to be observed at intervals ; it is not very active, but at times is quite constant. A tumor suggesting gall-bladder projects from the lower border of the liver. It seems to be nodular, or rather has a nodule on it at its upper part. This tumor descends with respiration, and is somewhat tender. The edge of the liver can be felt on each side of the tumor.

February 3d. Operation. — Vertical incision through right rectus muscle. No fluid in abdomen. Gall-bladder distended to size shown in diagram on blackboard. Its walls were thickened and white. The first portion of the duodenum and the pyloric end of the stomach were distinctly distended. Corresponding accurately to the distended portion of the bowel was a slight peritonitis, scarcely more than an injection of the serosa, and an exudate, only enough to cause very fresh adhesions between the duodenum and the gall-bladder. We should hardly call them adhesions ; the duodenum seemed rather to be lightly glued to the gall-bladder just as it might be an hour or two after an operation.

I was extremely interested to find that the vascular injection seemed to correspond accurately to the limits of the dilatation (almost ileus at times). The adhesions, if we choose to call them such, were so fresh that they were separated by very slight pressure of the finger. The general abdomen being walled off by gauze packing, the gall-bladder was opened. Its contents were colorless and in consistency like the white of an egg. Cover-slips were negative. First, one large gall-stone was found with a facet at each end. Then a second stone was detected with a probe in the cystic duct, but it could not be dislodged. Cysticotomy was performed and the stone removed in fragments. The previous attempts to dislodge it had evidently broken up the stone. Incision in cystic duct closed by mattress sutures. Gall-bladder treated in the usual way, namely, hermetically sealed about a rubber tube and protected by bismuth gauze, from the general peritoneal cavity. Abdominal wound closed in the usual way.

At first no bile escaped by the tube, but on the 10th of February, bile was abundant in the dressings.

March 2d. Wound has completely healed. Patient discharged eured.

Various diagnoses had been made in this case : (a) distended gall-bladder with adhesions ; (b) cancer of bile-ducts and liver, involving secondarily the colon; (c) carcinoma of the colon, involving secondarily the gall-bladder and gall-ducts. The distended intestine I watched with much interest several times. It seemed to me too small for colon : and no mass could be felt in the distal side of the distended gut to explain the distention. Peritonitis is undoubtedly the most common cause of paralytic ileus, and I have repeatedly observed in appendicitis that dilatation of the cecum and of the ileum may


Jaxuart, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


be caused by a very slight, perhaps merely a toxic peritonitis, but I have never before noticed such a sharp line of demarcation between the inflamed and noninflamed portion of the intestine. The dilatation corresponded accurately to the vascular injection. This was the more striking because two portions of intestine so very different were involved. That the comparatively thin wall of the duodenum should be more or less affected by inflammation of its serosa is to be expected, but that such a thick-walled gut as the pylorus and the pyloric end of the stomach should be paralyzed by such a very slight inflammation of the serosa was surprising.

Case IV. — Conditions suggesting hepaticocholecystostcholecysienterostomy as a possible operation. Common and cystic ducts reduced to fibrous cords, dilated hepatic duct and gall-bladder. Renal colic

stimulating intestinal colic; relieved by salt infusion. — Mr. ,

age sixty, had been suffering from gall-stones for several years, but not until be became persistently icteric and very ill was the first operation performed. The operator, a distinguished surgeon, found most difficult conditions confronting him. The entire common duct was impervious and reduced to a librous cord ; the cystic duct, greatly narrowed, was probably impervious ; the gall-bladder and hepatic ducts were dilated. The surgeon, very skillfully, I am told, attempted to construct a new common duct over a tube or catheter from the tissue which he had at his disposal. Just what these available tissues were I do not quite understand. For about five weeks, and until this tube was removed and the surgeon went away on his vacation, the patient was fairly comfortable and seemed to be gaining a little. Then he developed high daily fever and occasional chills, and became jaundiced again. I saw the patient in consultation with Dr. Gardner, of Providence, about one week, I believe, after the fever and the symptoms of obstruction had manifested themselves. The gall-bladder could not be felt. There was perhaps a little more muscle resistance on the right side over the region of the bile-ducts than on the left side, also perhaps the suggestion, rather indefinite, of a little induration such as might be caused by fresh adhesions. It occurred to me that in case the gall-bladder and hepatic ducts were still both dilated one might establish a fistulous communication between them, making an hepaticocholecystostomy and then, immediately, a cholecystenterostomy ; in all an hepaticocholecystostenterostomy. In any event, we thought that an operation for the relief of the symptoms was imperative. Accordingly a vertical incision through the inner margin of the right rectus muscle was made, avoiding the fistulous tract which remained after the withdrawal of the tube over which the new common duct had been constructed. I worked for two hours trying to identify and to separate the parts concerned in this operation. The gall-bladder, the ducts and the duodenum were glued tightly together and to the under surface of the liver. The gall-bladder which was finally extricated from the tangle was very small, contracted and empty ; the cystic duct was a fibrous cord. When bile was at last reached the patient was in such bad condition that the operation had to be discontinued. The parts in the neighborhood of the common and hepatic ducts were so firmly matted together that neither the latter nor the remains of the former had been demonstrated when it was necessary to bring the operation to a flose.

The patient rallied satisfactorily from the immediate effects of the operation ; but twelve or fourteen hours thereafter complained of very severe abdominal pain, which, as he indicated the location of it, ?eemed to be in the region of the colon and passing from right to left. The pain, though perhaps constant, became excessive during the paroxysms. It was never referred by the patient to his back or sides, nor did it radiate to the testicles or groin or crest or ilium. The abdomen was perfectly flat, and peristalsis could


not be observed. Nevertheless, large high enemata of hot water were given, but without appreciable relief- The urine was scanty and very dark and contained albumin and casts and a few bloodcells. Dr. Gardner promptly attributed the pains to the kidney, and related a somewhat similar case. Believing his interpretation of the pains to be correct and recognizing the fact that something must be done quickly for the relief of the kidneys, I transfused about 750 cc. under the breasts. The pulse, which was alarmingly rapid before the transfusion, dropped 40 beats within thirty minutes, and 20 beats within five minutes, and the colicky abdominal pains disappeared. Within twenty-four hours the infusion was repeated with similar results. The kidneys responded promptly to both infusions.

I report this case because (1) it suggested a new operation, hepaticocholecystostcholecystenterostomy, or hepaticocholecystosteuterostomy ; (2) it was the first of three cases of colic which I have seen associated with scanty high-colored urine ; and (3) it was, so far as I know, the first instance of subcutaneous infusion of salt solution for the relief of toxic renal colic. Soon after this Dr. Young, by salt infusions, undoubtedly saved the life of one of my patients whom I had operated upon for appendicitis, and who was suffering from perhaps the most furiously rapid toxemia that I have ever known of. This case has been reported by Dr. Young in the Maryland Medical Journal. The resemblance to intestinal colic is so great that it would undoubtedly be mistaken for it even by experienced practitioners of medicine. This was a valuable lesson for me, for since then I have twice recognized as renal colic this pain, which had been regarded as intestinal colic and treated with high injections. Our list of desperate cases of toxemia treated advantageously with infusions of salt solution is assuming large proportions.

Case V .—Choledochotomy performed twice within four and onehalf months. The gall-bladder, small and contracted at the first operation, when two stones were in the common duct, was large and distended when only one stone occupied the common duct (the ampulla). — Mrs. M. P. E., age fifty-eight, admitted May 3, 1897. October, 1892, patient began to have moderately severe attacks of pain in the region of the gall-bladder. The attacks would come ou suddenly and last several hours unless relieved by anodynes. The pain, milder at first, would gradually increase until it became very severe ; it commenced in the epigastrium and extended into the right hypochrondrium. During the winter of 1892-1893 the attacks occurred every two or three days. Occasionally there would be an interval of two or three weeks. During the remainder of 1893 and all of 1894, the attacks persisted at longer or shorter intervals, the pain always beginning in the epigastrium and radiating to the back. Sometimes during a severe attack there would be slight vomiting. Morphia generally gave relief. Patient says that the attacks were not accompanied by tenderness nor tumefaction. In the attacks observed by me there was always tenderness and, after the first operation, distention of the gall-bladder. In the spring of 1895, she went to Hot Springs, Va., where she remained several months. After this she had no pain for fifteen months, but did not seem to gain or improve in health. In September, 1896, in Italy, the pain returned. The attacks recurred with great regularity for seven or eight weeks. Most of them were attended by nausea and some by vomiting. She became jaundiced for the first time in December, 1896, and has remained more or less icteric until admission. Just after the paroxysms the icteric is deeper. For the past five months she had remained in bed most of the time. She vomits frequently, is seldom free from nausea. The bowels


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[No. 106.


have not been markedly constipated ; appetite is poor ; headaches occasional but not severe. Prior to this illness, however, she suffered very much from headaches. At no time has she had chills or sweating.

Examination. — Patient is quite deeply jaundiced ; her color is a dark slate-yellow ; tongue heavily coated ; body much emaciated ; expression rather dull, eyes lusterless. Heart not enlarged ; no adventitious sounds. Lungs negative. Urine dark, almost coffeecolored, trace of albumin, much bile-stained sediment. A few bilestained casts and epithelial cells. Red blood-corpuscles, 4,220,000 ; white, 6,000.

May 4, 1897. First operation. — Longitudinal incision through right rectus muscle ; resection of cartilages of eighth, ninth and tenth ribs, because the common bile-duct was very inaccessible. Choledochotomy ; removal of one small mulberry calculus. Exploration of duct fails to detect a second stone. Suture of duct wound. Gall-bladder atrophied and not opened. Bismuth gauze packing to suture in duct. Peritoneum sutured with fine silk, muscles and fascia with silver wire, and skin with a buried suture of catgut. Little or no shock from the operation.

On opening the abdomen the tissues were bile-stained. There was no fluid in the peritoneal cavity. The outer surface of the contracted gall-bladder was covered with new connective tissue in which were little masses of fat. The omentum was loosely adherent to the gall-bladder. The cystic and common ducts were easily isolated after division of three of the costal cartilages. No stones could be felt in the bladder or cystic duct. The stone found in the common duct could be moved quite freely up and down in this duct, but could be forced into the cystic duct, the common duct, about 1J cm. in diameter, being uniformly dilated. Bile flowed from it when opened. It was carefully explored with the fingers but not with an instrument. The gall-bladder was not opened. Two mattress sutures closed the opening in the duct, one preliminary suture being taken before the duct was opened. The sutures were passed without difficulty, the wall of the duct being about 3 mm. in thickness. No leakage occurred after the stitches were tied. The calculus, without facets, was spherical, about 1.6 cm. in diameter, and had a granular surface like a mulberry calculus.

May loth. Patient has recovered uneventfully from the operation. She is easily nauseated, however, and has very little desire for food. The stools have about the color of dark coffee and the skin has become lightened perceptibly. She complains, however, of an aching pain in the back, not relieved by posture.

May 24th. Patient has no inclination to eat; takes almost nothing by mouth. Nutritive enemata, which have been administered uninterruptedly since the operation, are still well borne. About every two days there is quite a definite attack of pain in the umbilical region and back, ushered in by nausea. Vomiting usually follows in a few hours and the distress is relieved.

May 29th. Condition little changed. Patient is fairly comfortable except for the attacks. Takes a little more food. Stools semi-solid and still quite dark. Urine has trace of bile.

June 13th. No bile in urine. Vomitus contains considerable hydrochloric acid.

June 26th. Appetite and digestion have steadily improved. Nausea less constant, often absent. Patient constipated, requires enemata; stools normal as to color.

July 4th. Much more comfortable. Nausea has disappeared ; color greatly improved, but the attacks of pain continue, although they are less frequent.

July 13th. Slight chill at 5.30 p. m., accompanied by pain in the back and head. Temperature reached 103° at 7.30 p. m.; fell to 99.2° at 5 a. m. Examination of blood for malaria, negative.

July 25th. Patient has lost one and one-half pounds in weight in the past week. The right lobe of the liver is enlarging. The spleen is palpable. Patient is having short attacks of fever accompanied by slight chills ; headache and yawning usually associated


with them. The attacks of pain continue ; they are still controlled by very small doses of morphia, one-sixtieth to one-fortieth of a grain. She sits up out of bed most of the time.

July 27th. The pain in the back has of late been accompanied by a slight rise of temperature, 99.2° to 105.5°. The urine contains no bile. The stools consist of light and dark portions sharply separated. Patient is gaining quite rapidy in weight.

August 5tb. Stools clay-colored. Temperature reached 102° last night during an attack of pain. Skin is becoming icteric ; urine contains bile ; slight pruritus. Patient's weight has increased five pounds in ten days. From August 8th to 12th no bile in urine.

Sept. 12th. The attacks of pain and the pyrexia continue. Patient is decidedly icteric after some of the more severe attacks. What we have feared ever since the operation we are now quite certain of, namely, that there is still a stone in the common duct, probably in Vater's diverticulum. The liver is considerably enlarged, but the gall-bladder has not been definitely made out.

September 13th. Second Operation. — Vertical incision near linea alba. Adhesions from previous operation separated without much difficulty. Liver much enlarged ; gall-bladder and common duct distended with bile. The wall of the common duct was much thicker; the wall of the gall-bladder, on the other hand, was probably thinner than at the previous operation. A small stone was palpated deep down behind the duodenum, presumably in the ampulla. The line of the old suture in the ductus choledochus could not be very definitely made out, but a short yellowish-white streak, evidently cicatricial tissue, corresponded, I thought, to the site of the original slit in the duct. A fine suture was placed in the common duct to serve as a handle for the subsequent manipulations. The duct was opened, and about 60 cc. of clear greenish bile escaped. A gauze plug was inserted into the proximal end of the slit to prevent the stone from slipping into the hepatic duct. Interrupted sutures were taken over a hammer of the proper size. The dislodgment of the stone was somewhat difficult. It was a little smaller than the first stone, but otherwise repeated the original exactly. The gall-bladder was opened, sewed to the peritoneum, and drained in the usual way ; a rubber tube surrounded first by gauze and then by protective being held in place by a purse-string suture of catgut. Wicks of bismuth gauze protected the line of suture in the common duct. The operation was attended with very little shock and the patient reacted very well.

Sept. 20th. There has been more or less nausea ever since the operation. Patient objects decidedly to stomach washing. Bile is draining actively from the tube. There has been little or no nausea to-day, but patient is weak and much depressed. The removal of a piece of gauze from the gall-bladder gives patient the first sensation of "heartburn," which she has had since the operation ; it lasted several hours.

Sept. 22d. Patient is thin and emaciated and alarmingly weak ; speaking is a great exertion to her. Temperature subnormal. There are no wound complications, nor any signs of peritoneal irritation or obstruction. Alimentation is almost exclusively rectal ; 6 p. m. vomited 1000 cc of fluid thick with "coffee grounds." Patient very restless. Examination of vomitus: No bile; bloodcorpuscles abundant; altered blood pigment; free hydrochloric acid ; no lactic acid.

Sept. 23d. Patient has vomited several times during the day ; in all about 2000 cm. of the same dark coffee ground vomitus. The pulse is very feeble.

Sept. 24th, 8 a. if. Pulse barely susceptible early this morning ; rallied a little after exhibition of salt solution per rectum. Still vomiting large amounts of same fluid, though nothing is being administered by mouth. 12 m. Patient is very low but still conscious. Infusions of salt solution were given under breast and in buttocks. 5.15 p. m. One drachm of one per cent, solution cocaine given by mouth. 5.30 p. m. Patient vomited 360 cc. of same dark fluid. Cocaine given again. No vomiting since second dose.


January, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


Sept. 25th, 1 a. m. Patient responds a little to the saline infusions. She is moaning and restless. Her nose and extremities are cold. She sleeps in short naps, with her eyes open and eyeballs rolled up. Complains greatly of thirst. Champagne and albumin retained and apparently relished.

Sept. 28th. Infusion again soon after midnight. Involuntary stools and small amount of dark vomitus. Is somewhat flighty at times. Pulse is thready, irregular, and cannot be accurately counted. She is sighing and seems almost moribund. Too weak to recognize surroundings or members of the family. About noon to-day I saw the patient for the first time since the third day after the operation, having returned to town as rapidly as possible in response to a telegram sent forty-eight hours ago. Dr. Cushing, house surgeon, who had attended her constantly, day and night, met me at the door of the hospital with the words, " no hope, she is dying. We went to her room ; she was cold and almost unconscious ; her eyes were open, the eyeballs rolled up ; the lower jaw had dopped. She had had more involuntary movements and could retain no nourishment. Her pulse was littre better than a flutter and could not be counted. In less than forty-five minutes I returned to the patient and found her pulse 120, and fairly regular in force and rhythm. I doubted my senses when I counted it. She was moreover not so cold, her eyes were not staring, and her lower jaw was raised. A miracle ! From that moment her convalescence was uninterrupted. She slept an hour, and on waking looked better than she had in two or three days. For twenty-four hours she was so weak that she could barely move her arms. She remembers nothing that transpired on the 23d, 24th and 25th of September.

In eight weeks, on November 22d, this patient left the hospital, not only able to walk but to take a long journey on the railroad. In one period of seven days she gained nine pounds. Her liver was rapidly diminishing in size.

In April, 1898, I had the pleasure of seeing this patient again. Her color was natural, her digestion excellent, her weight above normal and her strength steadily increasing. Her liver did not extend below the costal margin.

I have seen many cases regarded as hopeless recover, but never a being so near death as this have I known to escape it. I have speculated much as to the possible explanation of the very sudden change in her favor, but it would lead us beyond the limits of this paper to discuss the matter. In toxemias I have noted almost instantaneous drops in the pulse rate. Twice within a month I have observed a fall of 30 beats to the minute follow in less than thirty seconds the opening of an abscess. The abscesses were large and very acute ; one was a suppurating laparotomy wound and the other was a circumscribed abscess in the peritoneal cavity. The very instant that the abscesses were opened the change in the pulse was noted. A few months ago we were preparing to infuse with salt solution a patient upon whom I had operated for gall-stones and whose condition gave me not a little anxiety. His respirations were about 40 per minute and his pulse between 130 and 140. The physical signs indicated not very clearly some consolidation of the lower lobe of the right lung. While the instruments were being sterilized for the infusion, and while Dr. Cushing, the house surgeon, was counting the pulse, it fell to less than 100.

Was the hemorrhage from the stomach in the case of Mrs. R. (Case V) due simply to the prolonged vomiting; or to interference with the circulation of the portal vein (liver cirrhosis, pressure of packing) ; or to thrombosisof a small arterial branch:


or to a retrograde embolism (Recklinghausen,* von Eiselsbergt) or malposition of the pylorus or duodenum? It could hardly have been due to sepsis for there were no signs of infection. As long ago as 186?, Billroth J remarked that in septic cases we might have duodenal ulcers and fatal hemorrhages therefrom. He showed in his experiments upon animals that sepsis might cause intestinal hemorrhage, although, in his experience, it seldom did so in man; if, however, there existed an obstruction to the circulation, such as liver cirrhosis causes, little hemorrhages in the stomach plus the action of the gastric juices might lead to the formation of ulcers. The nausea began almost immediately after the operation. Whatever was the cause of this almost continuous nausea and frequent vomiting was also, probably, at least the remote cause of the hemorrhage. Von Eiselsberg has just reported seven cases of stomach and duodenal hemorrhage following operations upon the abdomen. Hematemesis occurred in six of his cases, and never later than the second, usually on the first day. The hemorrhages were demonstrated in three cases post mortem.

In my case the vomiting of" coffee grounds " was not observed until the tenth day. This patient was so carefully watched that I am quite sure that if hematemesis had occurred earlier it would not have been overlooked. In seeking for a common cause for the stomach and duodenal hemorrhages, Von Eiselsberg excludes vomiting because in two cases there was no vomiting, and in two, hematemesis occurred only a single time; he also excludes sepsis because in four of the cases there was no infection, and reaches the conclusion that " If the behavior of the wound is to be regarded as the cause of the hematemesis, then it must be assumed that in the cases which healed by first intention a retrograde embolism from a non-infected thrombus had taken place."

I wish that there was time to discuss this feature of the case more fully, but I must pass on to the consideration of another fact which this remarkable case developed. There were at the first operation almost certainly two stones in the common duct, one in the ampulla, the other more or less freely movable in the duct, although it fitted it quite snugly; but the gallbladder was small and contracted and not opened, and the liver was little if at all enlarged; the color of the skin was a light slate-yellow or ash-yellow — not the darker bronze-yellow of complete obstruction. At the second operation, however, when there was only one stone in the common duct, the gall-bladder was distended with bile and quite large, and the liver was greatly enlarged, its right lobe almost reaching the crest of the ilium. The patient's color and symptoms indicated that the stone in the ampulla did not at all times obstruct the duct completely. It sounds almost paradoxical to say that the removal of a stone should increase the obstruction, or that the one stone plugged the duct more completely than the two. I believe that a stone in the diverticulum, particularly a small


  • Die Storungen des Blutkreislaufes.

t Die Verhandlungen der duutschen Gesellschaft fur Chirurgie, 1899.

t Ueber Duodenalgeschwurebei Septicaemia. Wiener med. Wochenschr., 1867.


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[No. 106.


one, is more likely to block the duct effectually and to lead to distention of the gall-bladder than a stone, however large it may be, elsewhere in the common duct. A stone in the middle of the duct may at first occlude it completely, but the duct wall soon becomes infiltrated and thickened, it loses its elasticity, and, when distended with bile, stretches. The stone no longer plugs the duct tightly and bile trickles by into the intestine even when a second stone occupies the diverticulum, but when the proximal stone is removed, the bile instead of trickling up to the distal stone is probably jetted against it with sufficient force to hold it as a ball-valve. Furthermore, dilatation should not occur so readily in the portion of the common duct protected by the duodenal wall as in the free portion. In 1885 I operated upon a patient whose common duct contained a stone larger than the largest pecan-nut; at times one half of this stone projected into the duodenum, the other half occupied the duct; a flange had been cut on the calculus by the cicatricial ring, which engaged it and prevented it from slipping into the intestine; and yet this patient was so very slightly jaundiced that a stone in the common duct had not been suspected.

Cask VI. Miss M. H., age thirty. Transferred to surgical from medical side, January 27, 1896. Indigestion for eight years. For past four years the " gastric distress " has been very great. Patient describes a "gnawing sensation" in the epigastrium. Colicky pains radiated throughout thorax, but were at times very severe " in the back." Two years ago she had typhoid fever. For the past six months she has had frequent definite sharp gall-stone attacks with nausea, and four times with vomiting. Never blood in the vomitus. No chills, fever nor jaundice. Patient is a confirmed invalid. She suffers from headache and occasionally from vertigo.

Examination. — Abdomen flat. On deep inspiration spheroidal tumor is to be seen just below the costal margin on the right side. This tumor can also be felt. It moves with the enlarged liver, ascending and descending with the respirations. Last September patient first began to have attacks of pain in right hypogastrium, and accompanied by nausea and sometimes by vomiting. Spleen not palpable. The severe pain suffered by patient could be relieved by drawing up the knees. This pain radiated to the right shoulder-blade.

January 28, 1896. Operation. — Cholecystostomy. Vertical incision through the right rectus muscle. Elongated right lobe of liver. Very dense fibrous adhesions between the gall-bladder and duodenum. These adhesions were divided with great difficulty, and finally what appeared to be gall-bladder presented. It was aspirated, and a thick greenish fluid withdrawn. It was consequently opened with some confidence, but proved to be duodenum. It was sutured again at once, the suturing being very difficult because the muscular coat had been separated from the submucous coat during the dissection of the adhesions. The muscular coat, owing to the chronic inflammation which had existed for so many years, had become sufficiently fibrous to resemble cicatricial tissue, and consequently was unintentionally stripped from the submucosa. When the submucosa presented, it did so in the form of a little knob-like bladder, this coat resembling almost precisely the wall of the gall-bladder. The gall-bladder was finally found, deeply imbedded in adhesions, almost four cm. to the right of its usual position and far under the enlarged liver. It was opened, and one large oval stone, two cm. by one cm., removed. In the course of the operation a small abscess was discovered in the midst of the adhesions. Patient's recovery was considerably retarded by digestion disturbances, which finally disappeared completely


April, 1899. Patient says that she is in robust health and wishes to become a masseuse.

Cask VII. The history of this case cannot be published at present.

Case VIII. Discharge of pus and blood by mouth and rectum during severe gall-stone attack. Tteo years later adhesions so extensive and so dense that the common duct was reached by a retroperitoneal route, over the right kidney. — Mrs. M., age thirty-five. Admitted March, 1895. No typhoid fever. First attack of gall-stones, six years ago, began with sharp attack of pain in the right side of the abdomen. Two years ago miscarriage at seventh month ; was ill in bed thereafter four months. While in bed patient had great pain in region of gall-bladder, with high fever, for ten weeks; was continually blistered over liver. Eight weeks after the abortion she felt suddenly something "give way" ; this giving way was followed by great relief, and by horribly offensive discharge of pus and blood from the rectum and mouth. These discharges were irritating, gave her a very sore throat and mouth. She spat blood and matter for two or three weeks, and the stools during this time were very offensive. She has had pain and tenderness constantly, with occasionally severe attacks since that time ; has been jaundiced more or less ever since, but more markedly so since last July. On admission, body jaundiced and greatly emaciated; tenderness over the entire abdomen, especially in the region of the gall-bladder. Liver, in deep inspirations, extends two fingers' breadth below costal margin, and has a fairly sharp edge. Spleen palpable; stools acholic.

March 19, 1895. — Operation. Liver small, barely reaches costal margin ; its high position complicated the operation. Colon adherent to liver by rather loose bands ; gall-bladder exposed when these were divided. It was high up under the liver and no larger than the tip of the little finger; it was not opened. Adhesions were so dense over the common duct that the peritoneum was opened over the right kidney, and the common duct approached from behind under the peritoneum. A stone being felt, the common duct was the more readily exposed ; the stone was extracted through a hole made by ulceration. This hole proved to be at the junction of the duct and the duodenum, and was shut off from the peritoneal cavity by very delicate adhesions. The intestinal part of the opening was closed completely, the duct part as well as possible. The sutures were passed with great difficulty. The opening in the duct could not be completely closed, the tissues being necrotic, and bile escaped through it even after the sutures were drawn tight. Probing of the duct was carefully done. No other stones were found.

October, 1895. Six months after operation, patient is very well, She weighs one hundred pounds.

April, 1S99. Examined in my private office : patient still enjoys perfect health ; she now weighs one hundred and ninety pounds. Patient states that she has recently given birth to a healthy child.

I report the case of this woman because (1) she was so very ill when operated upon; (2) it is one of the two cases in which intestinal perforation had undoubtedly occurred prior to operation ; (3) the common duct was approached in a new way, namely, from behind the peritoneum ; (4) the stone, in the ampulla, had ulcerated through the walls of the ductus choledochus and the duodenum, and would perhaps soon have been extruded ; (5) the increase in the weight of the patient seemed phenomenal ; it was almost doubled within the year following the operation.

What the result to the patient would have been if this stone had ulcerated its way out of the common duct is quite certain, and yet I have several times found stones imbedded in adhe


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sious outside of the bile passages; they were usually close to the gall-bladder. Once I discovered a stone in the wall of a thick-walled gall-bladder; it was completely buried and was causing no disturbance, and was detected in the process of sewing in the drainage tube. This is, I believe, the only case in which I have not divided all of the adhesions encountered. If no contraindication exists, such as necessity for abbreviating


the operation, we should separate the adhesions if possible. The chance of meeting fistulous openings between bile passages and the intestine I regard as an indication for thorough exploration rather than a contraindication to it. Not infrequently adhesions alone are responsible for the symptoms which persist after the calculi have been removed by the surgeon or have escaped in other ways.


EARLY EXPLORATORY OPERATIONS IN TUBERCULOSIS OF THE HIP.

A PRELIMINARY REPORT.

(From the Clinic of Prof. Halsted, The Johns Hopkins Hospital).

By Joseph 0. Bloodgood, M. D., Associate in Surgery.


I wish to report a case of early operation in tuberculosis of the hip, and am sorry the patient is not here to demonstrate the very happy result.

Case I. — Tuberculosis of left hip, of seven weeks' duration. Operation: Capsule distended; tubercular synovitis; small tubercular focus in the neck of the femur. Result, January, 1899 (13 months), perfect. No restriction of motion.

M.K. Surg. No. 8380. Male, set. 42 years, butcher by trade, was first admitted to the hospital October 6, 1893, 5 years ago, suffering from tubercular arthritis of the left shoulder joint. The disease of the soft parts and bone was extensive ; for this reason excision was performed at once. Although 3 cm. of the shaft of the humerus were removed, the functional use of the arm is an excellent one.

It is of interest to note the possible etiology of the arthritis of the shoulder. This man had always been in excellent health. He could remember no cases of tuberculosis in his family. Eight months ago, he cut his left wrist with a dirty butcher-knife. The wound healed in about one week. One month later he noticed pain in the left shoulder, which was followed by a slight stiffness. The condition was treated for rheumatism. Five weeks ago he noticed a swelling of the upper third of the arm to the inner (medial) side of the biceps muscle.

The patient was readmitted November 30, 1898 (5 years later), complaining of pain and stiffness of the left hip joint. The following are the important facts in the history:

About seven weeks before admission, without any recollection of a traumatism, he experienced, when getting out of bed one morning, pain in the left hip. This pain has been increasing, and is now and then referred to the knee. During the last two weeks the joint has become almost immovable. He baa been able to walk some, although it gives him a good deal of pain. He limped into the hospital.

Examination. — When the patient lies flat on his back with both legs extended, the anterior superior iliac spines appear to be on a level. There is very slight apparent shortening of the


  • Read before the Johns Hopkins Hospital Medical Society. May

8th, 1899.


left leg. This, however, is due to real shortening between the trochanter and external malleolus. There is no shortening between the iliac spine and great trochanter. The hip is fixed at about 25°. There is no apparent abduction or adduction. Any attempt at motion at the hip joint gives pain, and with each motion the pelvis moves with the limb. There is no swelling about the hip joint except on the anterior surface of the thigh. This swelling is situated below the outer twothirds of Poupart's ligament, to the outer side of the vessels and extends downwards a distance of about 4 cm. It is most prominent 2 cm. within the line of the tensor vaginas femoris and 2 cm. below the iliac spine. The swelling is not very painful and on palpation seems to fluctuate. When the patient is quiet in bed and does not attempt to move the limb he suffers no pain. The leg is only painful when he attempts to walk or when some one attemps to bend it at the hip joint. The examination of the lungs was negative. The general health of the patient appears to be excellent. The patient remained under observation from November 30th to December 8th. On December 2nd, following an injection of 2 milligrams of tuberculin, the temperature rose to 100.5°. On December 4th, following 4 milligrams of tuberculin, the temperature rose to 100°. With these two exceptions, a two-hour chart shows a registration of rectal temperature between 98.5° and 99.5°. Following the injections of tuberculin the patient complained of no discomfort whatever. The only fact to be noted was that shown in the slight fever. The leucocyte count before operation was 4,000.

The arthritis was considered to be, without much doubt, tubercular, and the swelling on the anterior surface of the thigh to be due to distention of the capsule of the hip joint which had not yet ruptured.

Operation. — December 8, 1898. Anaesthetic, ether. When the patient was fully narcotized, it was demonstrated that with the exception of flexion there was but little restriction of motion in the hip joint. An incision was made in the anterior surface of the thigh, beginning at the anterior iliac spine, and the capsule of the hip joint was exposed by separating the tensor vaginaa femoris on the outer side from the rectus muscle on the medial side. As soon as the muscles were sepanih sd a tense swelling was found, which upon its surface was smooth


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and white in color. Upon its outer surface there was no exudate, nor was it adherent by connective tissue to any of the surrounding structures. When incised, it was found to be from 3 to 4 mm. in thickness, of firm white tissue, and proved to be the distended capsule of the joint. The cavity contained a large amount of viscid serous fluid containing numerous flakes of lymph and some necrotic material. The inner surface of the capsule of the joint presented the ordinary picture of tubercular synovitis. Here and there one saw cedematous hemorrhagic granulation tissue, in which were areas of yellow necrotic tissue, which could be easily scraped from its fibrous base. Between these areas of granulation tissue were smooth areas paler in color. On retracting the muscles more widely and enlarging the opening in the capsule, the head and neck of the femur were easily exposed. The examining finger at once found a small cavity on the inferior and slightly anterior surface of the neck, near its junction with the head of the bone, which about admitted the index finger (Fig. 1 «). One could also see the cavity, and in its



Case I. Fig. 1. bone removed.


Focus of tubercular osteomyelitis, b. Area of


center was a small area of yellow necrotic tissue. The bone lining the cavity was slightly hemorrhagic, but when cut with the ehisel was found not to be very soft. About 3 to 4 mm. of bone about the cavity were removed with the chisel (Fig. 1 b.) Beyond this, the cancellous bone appeared to be normal. The head of the femur was easily seen. The cartilage was not eroded. The cartilage lining the cotyloid cavity could be seen only at the rim about the head. It also appeared to be normal. The trochanter and shaft of the femur were exposed. The periosteum was not thickened. The entire surface of the capsule of


the joint was curetted. The bone cavity in the neck, and the surface of the synovial membrane after curetting were swabbed with pure carbolic. The wound was then thoroughly irrigated with 1 to 1000 bichloride, followed with salt solution. After mixing iodoform powder with the blood clot, the wound was closed, leaving a small drain extending into the capsule but not into the cavity in the bone. The entire limb and pelvis were fixed in a fully extended and slightly abducted position in plaster.

Notes after Operation. — The patient was perfectly comfortable and at no time during the convalescence experienced pain in the wound. The night after operation the temperature rose to 103.2°, falling to normal in the morning. On the second evening it rose to 104°; on the third to 103°; and on the fourth to 102°, falling to normal each morning. With this rise of temperature there was very little change in the pulse. The leucocyte count varied from 2700 to 4000. Nothing was found to explain the fever. Culture and coverslips from the serum in the wound were sterile. From December 12th to January 28th the temperature chart records no fever. The drain was removed on the sixteenth day. For four weeks the sinus communicating with the joint was irrigated daily with 1 to 1000 bichloride and injected with an emulsion of iodoformized oil. The wound at no time showed any evidence of infection and was completely closed at the end of five weeks. The patient was kept in bed in extension for six weeks, and then allowed to get up in plaster.

Note, August 14, 1899. The patient returns to the hospital walking without crutches or cane. It is eight months since the operation and six months since the plaster cast was removed. For five months the patient has been able to return to his work as a butcher. He has had no further pain. The wound is healed solidly. Careful measurements show no difference in the length of the bone or between the anterior iliac spine and trochanter, except the one noted before operation of 1 cm. shortening between the trochanter and external malleolus. Motions in the left hip joint are possible in every direction, and are but very little restricted in each (see Figs. 2, 3, 4). Forced motions are painless. Previous to operation the left leg was flexed to 25 degrees ; it now can be fully extended without change in the pelvis.

Examination. — January 10, 1900. The patient's condition is the same as that noted in August. The result so far appears to be a perfect one, not only with every evidence of an eradication of the disease, but with complete function of the joint. (See Case IX for operation in the right hip.)

Case II. — Tuberculosis of right hip, of seven years' duration. Operation: Firm fibrous ankylosis; no evidence of bone or joint tuberculosis; incapsulated extra-articular tubercular abscess. Result, Jan. 1900, 9 months, excellent.

Surg. No. 3540. There is at present (May, 1899) in the wards, a young girl who was admitted to the hospital November, 1, 1894. At that time she was suffering with tuberculosis of the right hip, the onset of which had been two years previous, when she was eleven years of age; that is, seven years ago.

Examination. — November 5, 1894, under ether. No apparent shortening. The right (affected) limb is flexed to 45 degrees,


JOHNS HOPKINS HOSPITAL BULLETIN. JANUARY, 1900.



Fig. 2. — Result lu Case I, eight months after operation.



Fig. 3. — Limit of abduction, Case I


Fig. 4.— Limit of flexion, Cum- I


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slightly abducted and slightly rotated out. Apparently do real shortening between anterior iliac spine and trochanter or trochanter and external malleolus. The measured shortening between anterior iliac spine and internal malleolus 1 cm. (due to abduction).

Examination. — April 25, 1895, after seven months. The flexion is less 20 degrees. Apparent shortening 1 cm., due to tilting up of the pelvis. Measured shortening between iliac spine and external malleolus 2.5 cm. Keal shortening between iliac spine and trochanter perhaps 1 cm. Patient is very fat, and these measurements are difficult to make. The leg is still slightly abducted. Kotation out less.

Examination. — December 8, 1896, after two years. Apparent shortening 3 cm. Keal shortening between anterior iliac spine and trochanter 1 to 1.5 cm.; between trochanter and external malleolus 2.5 cm. (about equally distributed between thigh and leg). These measurements demonstrate that within the last two years, under the best orthopedic treatment, a centimeter of real shortening has taken place, and there has been a lack of growth in the shaft of the femur of 2.5 cm.

Examination. — April, 1898. Very little if any change.

From November, 1894, up to the present time, a period of almost five years, she has been under treatment. After her first admission to the hospital she remained in the wards for two years. The treatment consisted of iodoform injections, and later of fixation in plaster. During this time her general health has remained about the same. There has been little or no loss of flesh, no fever, and no evidence of tuberculosis elsewhere. On December 6, 1896, she was given tuberculin, which was followed by no evidence of reaction. Four weeks later an abscess formed below the great trochanter. It was opened, and healed rapidly. In October, 1897, there was slight reaction to tuberculin. About four weeks ago she returned to the hospital for inspection. She was still using crutches, and suffered a good deal of pain in the hip, not only during the day when she was sitting in a chair or walking on her crutches, but also at night. This pain was generally relieved by extension.

Operation. — April 20, 1899. Ether. Under the anaesthetic it was found that the hip joint was almost completely fixed in a flexed and very slightly abducted position, with no rotation. An incision similar to that employed in the first case was made. On dividing the fascia lata about 5 cm. below the anterior iliac spine, a small cavity (2 cm. in diameter) was opened. In the center of the cavity was a mass of yellow necrotic material and a little clear serous fluid. The wall of the cavity was of smooth white fibrous tissue. No granulation tissue could be found. This cavity corresponded in position to the abscess which formed and healed a year and a half ago. It was completely excised and no communication between it and the bone or joint could be demonstrated. (A very small healed sinus, however, might have been overlooked). On exposing the joint, the head and neck and trochanter of the femur were covered with dense connective tissue. This was excised, exposing the periosteum over the trochanter and upper part of the shaft. The periosteum was slightly thickened, and on stripping it back the bone was a little rough. The outer layers of the bone of the shaft and trochanter were very thin, also that of the neck. The anterior surface of the neck, troch


anter and shaft was removed with a chisel (Fig. 5 a). The cancellous bone was very softand hemorrhagic; the marrow was also fatty and very hemorrhagic. The head of the bone and t he acetabular cavity were covered with scar tissue, in which no granulation tissue could be found. Over a small portion of the head of the bone which was exposed there was normal cartilage. No disease of the pelvic bones about the acetabular cavity could be demonstrated. About the acetabular cavity there was a narrow ridge of new bone (Fig. 5 c). The wound was thoroughly irrigated, and the small bone cavity made during the exploration was allowed to fill with blood clot mixed with iodoform, and the wound closed without drainage.



Case II. Fig. 5. — a. Area of outer table removed to expose neck, epiphysial line and head. 6. Gouge groove to explore acetabulum through head. c. New bone about rim of acetabulum.

At the operation, although the junction of the neck and the shaft was exposed, it was difficult to tell whether the angle between the neck and the shaft were more or less than normal. The neck, however appeared to be shorter than normal. Following the operation, the patient had no discomfort and the wound healed perfectly. She was discharged September 15, 1899, wearing a splint and using crutches. This supporting apparatus was used because I feared that following the removal of the bone, the neck of the femur might possibly have been weakened, and that to allow the patient to walk without some support might be followed by bending of the neck with its resultant deformity. While in the hospital, especially after the patient was up and about on crutches, the pain complained of before operation was not present.

Examination. — January 19, 1900. The patient has no pain. She walks much better but still uses the crutches and wears


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the splint. No change in measurement. Advised to discontinue crutches and later the splint.

I have reported these cases to the Society to illustrate the happy result, in the first case, after an early operation. Here, seven weeks after the beginning of the disease, we found a greatly distended capsule filled with necrotic material and lined by tubercular granulation tissue and a tubercular focus in the neck of the femur. Following the partial removal of the disease of the soft parts and the apparent complete removal of the disease of the bone, we have every evidence of the complete cure of the disease, and three months after operation the patient is able to resume his occupation as a butcher, and the functional use of the joint is almost perfect.

In the second case, after seven years of conscientious orthopedic treatment, the patient is practically in the same condition. The exploratory operation, however, demonstrated that the disease was to all appearances cured. In this latter case an earlier exploratory operation, if it had demonstrated the same condition, would have relieved the patient of a number of years of enforced rest, or, if the disease had been present, would have allowed its earlier eradication.

ADDITIONAL CASES.

Note, January, 1900. — Since the above report was made, twelve cases of tuberculosis of the hip have been subjected to operation. Nine are here reported — three cases of very recent date not being included in this report. In all, the immediate results have been very encouraging.

Case III. — Tuberculosis of left hip, of 15 months' duration. No relief of symptoms after two and a half months' treatment with extension in bed. Operation: Distention of capside ; erosion of head and neck ; no bone foci found ; immediate relief of symptoms. Residt January 1 , 1899, six months, excellent G. L. H. Surgical No. 8874. Male, at. 10. Was admitted April 19, 1899, complaining of pain in the left leg. His father died of tuberculosis of lungs, and one brother had been operated upon in this hospital for genu varum. About fifteen months ago this patient complained of pain in the left hip. The pain was intermittent, but had not prevented him from going to school or playing about ; now and then he would limp ; for different periods he would be free from pain and limping ; no history of trauma. About six weeks ago, after a well interval, he complained of sudden pain in the left hip and began to limp. The pain in a day increased so rapidly that he went to bed, being unable to walk, and that night, for the first time, cried out from pain. Being more comfortable the next day he was taken to a hospital where he remained a few days, and left with a brace. Yesterday, twenty-four hours before admission, he fell on the brace and had passed a very uncomfortable night.

Examination. — The left hip was so tender that any attempt at motion produced much pain, and an examination was made with difficulty. There was flexion (40°), abduction (45°), but no aversion. From April 20th to May 12th (22 days) the patient was placed in extension, and was more comfortable. Measurements made on the last day showed apparent shortening of .5 cm., due to slight adduction, but no real shortening. The hip was still very tender and fixed. April 29, reaction to tuberculin. From May 28th to July 2nd, although the patient was in extension, night cries increased and he was uncomfortable. From July 2nd it was noticed that there was a fullness in Scarpa's triangle. The hip was still very painful and fixed in a position of flexion and adduction. For this reason an operation was decided upon.


July 3, 1899. Operation (Dr. Cushing): Ether ; anterior incision. The joint capsule was distended and thickened ; no evidence of rupture. On incising the capsule, about an ounce of seropurulent fluid escaped. A part of the cartilage over the head was roughened and slightly elevated from the bone. The joint cavity was full of tubercular granulation tissue. In places one could see that the cartilage of the acetabulum was eroded and lifted from its base. A portion of the anterior surface of the head and neck was chiseled away, showing the epiphysial line. No focus of disease in the bone was found. The area of most marked erosion of the cartilage, and the erosion of the bone at the edge of the epiphysis, as shown in (Fig. 6, a. a. a.) were chiseled away. After disinfection



Case III. Fig. 6. — a. a. a. Areas of superficial erosion, b. Areas removed.

of the joint and bone cavity, dry iodoform was dusted in the wound, which was closed without drainage. The operation lasted one hour and five minutes.

For a few days previous to operation the pulse ranged between 90 and 100, and for three days after operation it ranged between 120 and 150 ; the temperature rose to 102°. By the seventh day pulse and temperature had reached normal. The patient was comfortable.

On August 2nd (thirty days after), a small sinus opened in the wound, discharging a clear, serous fluid, which completely healed on August 29th. Measurements made on August 30th showed a lengthening of 1 cm. and no real shortening. The flexion had disappeared, and there was a slight tendency to outward rotation. Motion in the joint was much less restricted. On August 31st, two months after the operation, the patient was fitted with a brace. On September 6th he left the hospital wearing a brace.

In this case the usual orthopedic treatment of extension and rest in bed had been given a fair trial, but did not relieve the symptoms. At the operation, tension was relieved by incision and drainage of the distended capsule, after which the patient was much more comfortable. The incision of the capsule also allowed


January, 1900.]


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correction of the flexion, and a short time after the operation all movements of the hip joint were freer and without pain.

Case IV. — Tuberculosis of left hip, of <>ne year's duration. Operation : Distended eapsuie, with purulent material ; synovial membrane convt rted into granulation tissue; sliglit erosion of head and neck and acetabulum ; wound closed ; healing per primam. Result, January, 1899, six months, excellent.

Surgical No. 9234. W. C, colored boy, aet. 2 years. Admitted July 26, 1899. One year ago the child complained of pain and tenderness in the left hip, and in a few days began to limp. The parents noticed that the leg became shorter ; the pain was worse at night, and there were night cries. The child continued to walk a little.

Examination. — The general condition was good; no evidence of rickets. The left leg was flexed to 70 degrees at the hip and 45 degrees at the knee, and adducted. Motions at the hip are restricted in all directions, but not at the knee. It was difficult to make accurate measurements, but there appeared to be no real shortening.

August 2nd (six days after admission). Operation (Dr. Mitchell): Ether: anterior incision. The capsule of the joint was thickened and ccdematous. On incising the capsule, an ounce of thin, brownish, purulent and necrotic material escaped. The synovial tissue seemed to be converted into granulation tissue. There was noticed a slight erosion on the anterior and superior surfaces of the neck at its junction with the head ; round ligaments, intact ; the rim of the acetabular cavity was covered with grayish granulation tissue ; both of these areas, as well as the capsule of the joint, were curetted. The wound was irrigated with salt solution, dusted with dry iodoform powder, and closed without drainage. The full time of the operation was fifty-five minutes.

Pulse previous to the operation was 120; during the operation, 140. The chart registers an average pulse of 120 previous to operation and one rise of temperature to 103°, which, however, followed tuberculin given on the 27th of July. Following the operation the highest temperature was 101.5°, the evening of the first day, and the pulse rose to 180, but fell that evening to' 130; up to November 27th. when patient was discharged, the average pulse was from 110 to 120. With the exception of a slight rise of temperature to 102° on October 2nd, there was no fever after August 4th, 48 hours after operation. The patient left the hospital on November 27th in plaster. The wound healed per primam.

Case V. — Tuberndosis of left hip. Subgluteal extraarticular abscess. Operation : Incision of abscess and arthrotomy ; tubercular synovitis ; erosion of head and neck ; posterior perforation of capsule. Result, January 1, 1899, two months, improved.

J. W. G.. colored boy, set. 2 years. Admitted November 9, 1899. The parents not being with the child it was impossible to get a history.

Examination. — The child is placed flat on his back. The left anterior iliac spine (the affected side) is a little lower than the right. There is a marked lumbar lordosis unless the left hip is flexed to a position of 90 degrees ; motion at the hip joint in this position is possible in all directions, but only to a few degrees. The knee is flexed to an angle of 90 degrees. Extension is only possible to a few degrees ; no rotation of thigh. If the right leg is placed in a similar flexed position at the knee and hip, there is an apparent shortening of about 1 cm., but no real shortening of the left leg. Between the anterior iliac spine and trochanter on the outer surface of the left thigh and beneath the gluteal muscles there is a fluctuating swelling.

Operation.— November 11, 1899. Ether. Under complete narcosis the leg can be veiy slightly flexed and extended. This restriction almost completely disappeared after the abscess was incised. The abscess was situated beneath the gluteal muscles and fascia


lata and contained thick, gelatinous, purulent material, with shreds of necrotic tissue, and was found to communicate with the hip joint through a small opening in the posterior wall of the capsule. The joint capsule, which was not distended, was opened through the usual anterior incision. The synovial membrane was covered with tubercular granulation tissue. On account of the youth of the child, a large incision was not made, so that the head, neck and acetabular cavity were not seen, but with the index finger erosions were felt on the anterior surface of the head and neck, which were curetted Theabscessaud thecapsuleof the joint were also curetted, swabbed with pure carbolic, irrigated with salt solution and filled with emulsion of iodoform and oil. The operation took fifty-five minutes. Very little ether was given. The condition of the patient at the end of operation was excellent.

January 15, 1900. The child is still in extension, which has reduced the flexion of both knee and hip from 90 to 35 degrees. There are no night cries. The patient appears to be perfectly comfortable. The wound is now a superficial granulating area.

Case VI. Tubercidosis of left hip, of seven months' 1 duration. No relief of symptoms after one month's treatment with extension. Operation: Tense distended capsule ; no bone focus of disease; slight erosion of the head, with loosening q) articular cartilage ; round ligaments separated ; wound closed ; healing per primam. In six weeks the wound reopened. Second operation. Result. January, 1899. after two months, excellent. Wound closed.

Surgical No. 9117. G. B.. aet. 4A years; admitted June 26, 1899. One and one-half years ago the boy fell on the ice and bruised his left hip. An area of ecchymosis over the hip remained some days. Following the injury, however, there was no special pain complained of and no limp. Eleven months later (that is, 7 months ago), the parents noticed that the child began to limp, and complain of pain, first in the calf of the leg, later in the ankle, then in the knee. About two months later the parents noticed that the affected leg was shorter and the boy walked on his toes. In about a month he began to have night cries. For the past two weeks the boy has been unable to walk on account of pain.

Examination —The left leg is flexed at the knee and thigh, with marked adduction ; no rotation ; very little motion at the hip joint. The patient was placed in extension from June 26th to July 24th. He cried a good deal at night, when asleep or awake. All attempts to overcome the flexion by extension were unsuccessful. Manipulation of the hip joint continued to be painful ; for this reason operation was decided upon.

Operation.— July 24,1899 (Dr. Cushing) : Ether: anterior incision. After separating the muscles a very tense distended capsule was exposed ; it was incised, and about an ounce of flocculent, yellow, serous fluid was evacuated. The joint, head and neck of the bone were thoroughly exposed. The round ligament seemed to be destroyed. When the thigh was flexed, one got a good view of the acetabular cavity. The lining cartilage seemed smooth. The cartilage over the head of the bone appeared to be loose. The head epiphysial line was exposed by chiseling. No focus of disease was seen. The wound was irrigated with salt solution, dusted with dry iodoform powder, and closed without drainage.

Dr. Cushing noticed that under an anaesthetic the leg could not be fully extended. As soon as the capsule was incised and the tension was relieved, full extension was possible. Time of operation about fifty-five minutes ; pulse before operation, 120 ; during operation about 140. As in the previous cases in children there was a slight tachycardia after the operation for five days, and some fever for three days. The wound healed per primam.

It was noticed on August 5th, 11 days after operation, that the leg was but slightly flexed, very little adducted, but there was slight outward rotation. On the 14th of August there was no flexion. At this time he was sent into the country in a brace.

On September 6, 1899, about a month later, he was readmitted


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to the hospital, not in as good condition as when he left. He had night cries and some pain. Twenty days after admission a sinus formed in the wound which discharged tubercular pus.

From September 28th to November 4th he was placed in extension. November 3d, measurements: Apparent shortening of 1 cm., and real shortening from trochanter to anterior iliac spine of about 1 cm. No abduction or adduction or flexion, but marked outward rotation. The hip is pretty firmly fixed in this position except that it can be slightly rotated in.

Operation, November 4, 1899 (Bloodgood) : Ether. It was found that the sinus of the previous operation passed through the rectus muscle into the joint. At this second operation the joint was exposed by an incision which separated the tensor vaginas femoris and gluteus medius on the outer side and the sartorius and rectus on the medial side. The sinus and cavity corresponding to the capsule of the joint were lined with tubercular granulation tissue. It was found that the head and neck of the bone were intact. A few pieces of partly separated cartilage were removed from the head of the femur. The outer surface of the neck was rough, soft and hemorrhagic. On extending the femur and pushing it upwards, the head of the bone moved a little in each direction. Under ether there was very little restriction of motion at the hip joint. The soft parts and bone surface were curetted, the exposed surfaces were swabbed with pure carbolic, the wound irrigated with salt solution, dusted with dry iodoform powder, and closed with a piece of protective drain into the joint cavity- No loss of blood ; no shock. Time of operation was about sixty minutes. Average pulse about 140.

Following the operation there was a slight tachycardia for a few days, but no rise of temperature. The operation in this case was a secondary one and of less extent than others. The patient was put up in plaster and later in extension, and was much more comfort able than previous to operation. The wound was irrigated, and at frequent intervals swabbed with pure carbolic and filled with emulsion of oil.

Note. — December 9, 1899, 35 days after operation. Measurements between iliac spine and trochanter and iliac spine and malleoli are about equal. Position of leg after removal of extension is as follows : The left (affected) anterior iliac spine is elevated 1 cm., the left leg is rotated out perhaps a little more than the right (this outward rotation is much less than previous to operation). The apparent shortening (1 cm.) corresponds to the elevation of the iliac spine. There is no flexion. The motions of the hip joint are about 10 degrees in flexion and extension ; adduction to a few degrees ; no restriction of outward rotation ; a marked restriction of inward rotation and abduction. Although the hip is pretty well fixed, the position could not be a better one- Attempts at motion are not painful. The wound has healed.

December 15, 1899. The patient is in the hospital, and is walking about on crutches, in a brace.

Case VII. Tuberculosis of left hip, of one year's duration. Subgluteal, extra-articular abscess and abscess beneath the adductor muscles. These abscesses developed during orthopedic treatment. Operation: Incision of subgluteal abscess; anterior arthrotomy of joint; anterior and posterior perforation of joint ; abscess beneath adductors drained through joint ; tubercular focus in neck. Result, January, 1899. two months, improved.

Surgical No. 8201. Boy, set. 8 years. Admitted October 6, 1898, one year ago. The arthritis of the left hip had been present one year, following traumatism. The limb was in a position of flexion (28 degrees) and adduction (21 degrees), with slight internal rotation. Apparent shortening, 4 cm. ; real shortening (anterior iliac spine to trochanter), 1 cm. Muscle spasm was marked. There was no evidence of abscess. The patient was placed in bed in an extension apparatus, which at once relieved the pain. He was discharged February 28, 1899 (five months), wearing a splint, and


appeared to be in excellent health. This patient was readmitted October 1, 1899, not because he was suffering any pain or discomfort, but in answer to a letter inquiring as to his present condition. He was still wearing the splint and walking with crutches. When the splint was removed and the patient placed in bed, and the anterior iliac spines fixed to the same horizontal plane, the left affected leg was so adducted that it crossed its fellow on a level with the patella. There was a large abscess behind the great trochanter in the gluteal region, and a slight fullness beneath the adductor muscles. The patient was observed in the hospital from October 1st to October 28th. There was no fever. He suffered no pain except when the apparatus was removed or when forced motions were attempted at the hip.

Operation.— October 29, 1899. Ether. The gluteal abscess was incised. It was situated between the gluteus minimus and medius and extended down to the middle third of the leg beneath the fascia lata. Passing the index finger, one could feel the capsule of the joint on its posterior surface. In this position a probe found communication with the joint cavity.

The usual exploratory incision on the anterior surface of the thigh was then made. The capsule of the joint when exposed was slightly distended, but on i:s outer surface there was no exudate and no adhesions. When incised, it was slightly thickened, and the joint cavity contained a moderate amount of seropurulent material filled with cheesy necrotic masses. The head and neck of the bone were easily felt and seen, and on the anterior and slightly inferior surface of the neck, near its junction with the head, a small tubercular bone focus was found. (Similar to Case I, Fig. 1.) This was removed with a chisel. The head of the bone seemed firmly in place in the joint cavity, and there was very little restriction of motion. The rim of cartilage which could be seen was not eroded. By pressure over the thigh in the adductor region, a great amount of tubercular pus was expressed into the joint cavity, and the finger and probe demonstrated a second opening in the capsule of the joint leading to a large abscess cavity on the lateral surface of the thigh, beneath the adductor muscles. This opening was enlarged and the cavity curetted out. The patient had a comfortable convalescence. January, 1900. Extension has corrected to some extent the adduction and flexion. The patient walks well in his brace. The wounds are almost healed. The marked adduction will need further operative treatment.

Case VIII. — Tuberculosis of right hip; orthopedic treatment for 12 months, during which time an iliac abscess, from perforation of the acetabulum, developed. Operation : Incision of abscess and arthrotomy of joint ; tubercular synovitis ; slight erosions of head and neck, with partial separation of the articular cartilage of head and acetabulum. Residt, January 1899, two months, excellent.

Surgical No. 8086. R. H., ast. 4. First admitted September 7th, 1898, with the following history : About five months ago it was noticed that the child limped; at the same time the parents noticed that the right ankle was swollen. Six weeks later the child wakened at night, crj-ing from pain in the hip ; next day was unable to walk ; this pain and inability to walk disappeared in a few days, the night cries and pain at night continuing. About eight weeks ago a slight trauma was received by the right knee; The knee became swollen and was put up in plaster by a physician. Night cries continued. The hip became more stiff.

Examination. The child walked into the hospital. The limb is flexed; slightly adducted; no rotation of foot; apparent shortening of about 1 cm; no real shortening between anterior iliac spine and trochanter; no fullness in Scarpa's triangle; adduction is impossible, and there is about 10 degrees of abduction. Patient was placed in extension September 2oth. 18 days later, he was discharged from the hospital, wearing a brace and using crutches, with a high shoe on the left foot. March 29, 1899, 7i months, patient was readmitted.


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Examination. Perfectly comfortable. Night cries have ceased. Examination reveals no muscle spasm. There is no flexion, abduction or adduction. Apparent shortening is \i cm. There is very little motion at the hip. No real shortening between trochanter and anterior iliac spine. May 6th, 37 days, discharged, wearing a splint and using high crutches and high shoe. On October 27, 1899, tive months latter, he was readmitted, not because of any pain or discomfort, but on account of swelling which had been noted for two weeks over the outer third of Poupart's ligament. Measurements : No apparent shortening; no real shortening. Leg is in a straight position, slightly rotated out. Flexion is possible to 30 degrees; abduction to 10 degrees, but adduction is impossible. There is only slight muscle spasm, associated with attempts at motion. On account of the abscess an operation was decided upon.

Operation.— November 4, 1899. Ether. Usual anterior incision, which also opened into the abscess. The abscess cavity was between the skin and fascia of the muscle. From it a sinus led below Poupart's ligament, passing between the sartorius and tensor vaginse femoris. then into the iliac fossa, anterior to the sheath of the iliac muscle. After curetting this abscess cavity the joint capsule was exposed by separating the rectus from the tensor vaginse femoris. No infiltration of the tissues outside the capsule. By pressure over the capsule a purulent material was expressed from the sinus, but on opening the capsule of the joint a direct communication could not be found. The cartilage of the head of the femur was soft and separated easily : it was removed by catching it with a clamp. The base consisted of soft hemorrhagic bone, the gross picture of tuberculosis. The anterior surface of the head and neck was chiseled. There was no evidence of disease in the neck, which seemed to be confined to the head of the bone, especially beneath the cartilage. The round ligaments had been torn and that portion of the acetabular cavity which was exposed showed evidence of disease. The cartilage was soft, and some could be pulled away, leaving a base of soft hemorrhagic bone. No attempt was made to find out the direct communication between the joint and the iliac abscess, as it would have required too much destruction of bone. The abscess cavity was traced into the pelvis between the iliac and the psoas muscle. The wounds were swabbed out with pure carbolic, irrigated with salt solution and dusted with dry iodoform. A protective drain was left into the abscess cavity and into the joint. Time of operation was about one hour and thirty-five minutes. Patient was in excellent condition.

Following the operation there was the usual tachycardia pulse of 130 to 160 for about ten hours ; no rise in temperature ; no pain or discomfort.

Examination. — December 1, 1899, twenty-seven days since operation. There is no apparent shortening. The anterior iliac spines are about even. Both legs are straight ; no outward rotation ; no real shortening ; position of the leg is perfect. Flexion, extension, abduction and adduction and outward rotation are possible only to a few degrees. Inward rotation from a position of outward rotation is possible to a greater extent than outward rotation. Attempts at motion give no pain.

Wound healed except a small granulating area and a sinus communicating with the abscess cavity. Patient is ordered brace, high shoe and crutches.

January, 1900. No change.

Case IX. Tuberculosis of right hip. Slight symptoms four months; very acute symptoms three days. Operation at once. Capsule distended, very tense; synovial membrane hyperemic; on chiseling outer table of neck, a definite bone focus found in the neck near epiphysial line. January 1, i900, six weeks, excellent result.

Surgical No. 9699. N. K.. set. 40. Admitted November 32, 1899. In July (four months ago) patient began to have pain in the right hip, and he stopped work and rested for about two weeks. Was comfortable when he kept quiet. Returning to work, he was free


from pain for a couple of weeks, but since that time he has found that he has to rest quite frequently during the day when these attacks of pain come on. He is a butcher by trade and has to stand a good deal. Three days before admission, while at work, he was seized suddenly with severe pain, so intense that he went home to bed, and sent for a physician who gave him morphia, but this did not relieve the pain. He was brought to the hospital on a stretcher in the ambulance.

The right leg was fixed in a position of flexion of about 45 degrees. Any attempt at motion was intensely painful. Extension was at once applied in this flexed position, which in a few hours relieved the patient of the pain. Next morning he was more comfortable. On examination there was a distinct fullness in Scarpa's triangle. The history and the present condition were similar to the attack in the left hip joint (Case I). There is no apparent or real shortening. The result in the left hip is a perfect one. The patient was in extension with complete relief of symptoms from November 22nd to November 27th, but any attempt at motion gave him pain. Chart records a temperature between 99° and 101° ; pulse of 70 to 80.



Case IX. Fig. 7. — a. Tubercular osteomyelitic focus, b. Area of outer table chiseled to expose aud remove a and 6. c. Area of softened cancellous bone.

Operation.— November 27, 1899. Cocaine and chloroform. The usual anterior incision was made without difficulty under cocaine, but it was found that the retraction of the muscles necessary to expose the hip joint was so painful that chloroform was given. As soon as the patient was under the anaesthetic it was still found that complete extension was impossible. The capsule of the joint was distended. On incision a fluid spurted out. demonstrating the great tension. It was a seropurulent fluid filled with coagulated lymph. On examining the capsule carefully, it was found that the synovial membrane was intensely injected and hyperemic. There was no evidence of granulation tissue. The head of the bone was easily seen in the acetabular cavity, and the cartilage, both on the head and acetabular rim, seemed normal and was not sepa


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rated. No disease could be seen at the head or neck or trochanter of the femur. The bone of the anterior surface of the neck, between head and trochanter, was chiseled ( Fig. 76) , and in the epiphysial line, between the head and neck, on the anterior and inferior surface, a small focus (about 5 mm. in diameter) of definitely tuberculous bone was found (Fig. 7 a). Surrounding this and extending into the head and neck, the bone was soft and hemorrhagic (Fig. 7c.) The tuberculous area and this softer cancellous bone were removed with the curette. The appearance of the bone lining the cavity was normal except perhaps slightly hemorrhagic but firm. The bone cavity and joint capsule were swabbed out with pure carbolic, irrigated with salt solution, and the bone cavity allowed to fill with blood mixed with iodoform. The wound was closed with a small drain extending into the capsule but not into the bone cavity. Operation required two hours and ten minutes. There was no shock, and the condition of the patient at the end of the operation was excellent.

Examination.— December 16, 1899. Wound is healed with the exception of a small sinus which was filled with iodoform and organized blood clot. Patient has had absolutely no discomfort since operation, and for about seven days has moved his right hip in every direction, and we find on examination to day that one is able to flex, abductaud adduct, rotate in and rotate the hip outwards to quite a marked degree, but not completely. These motions are without pain. January 12, 1900. The patient is up on crutches ; the wound is healed except a small superficial area. Passive and active motions with hip are but slightly restricted and give no pain.

For some years before this report, which I made to the Society in May, 1899, I had given a good deal of consideration to the subject of tuberculosis of the joints, and especially of the hip, and had been forced to the conclusion that there was much room for improvement upon the usual orthopedic treatment. I had in mind early exploratory operations in which the surgeon might be fortunate to find the focus of the disease in the bone at a period when its complete excision ; or, if the tubercular osteomyelitis were more extensive, a partial excision might be done without interfering with the continuity of the bone or function of the joint. From early experiences, especially in the knee, arthrotomy with irrigations with antiseptics and injections of large quantities of iodoform seems to have been the best procedure for treatment of the tuberculosis of the synovial membrane.

The majority of surgeons now follow the more conservative and orthopedic treatment. In the past many, and at present, without doubt, some, surgeons resort to operation, even early in the disease, but as a rule such operations have been accompanied with excision of at least the head of the femur and frequently more, of the neck and trochanter.

My first object in the early operation for tuberculosis of the hip was to avoid a complete removal of the head or of an amount of bone sufficient to interfere with the continuity of the upper end of the femur, or function of the joint, to excise the diseased bone only in small areas by a gouge and curette, trusting to antiseptic irrigation, and especially to the healing process, to check the further extension of the tubercular processes, and to encourage healing of the tissues already diseased, both of bone and soft parts. Every surgeon must have observed, especially in excisions of the knee, that tuberculous bone has frequently been left behind, but that the disease has been cured. Change of circulation, due to the operative interference, and the scar tissue of the healing process, both seem to exert a curative influence on the tubercular tissues.


The more frequently one operates, and the earlier in the disease, the more frequently he may be fortunate in finding single focus, of tubercular osteomyelitis which can be completely excised without injury to the continuity of the bone or function of the joint as in Cases I and IX. As our experience grows, I trust we will find that early operations check the disease with more certainty and in a greater number of cases than the usual orthopedic treatment. I trust also we will find that it shortens the period of treatment.

In five of these cases the joint capsule was greatly distended. It would seem beyond question that arthrotomy and irrigation in such cases are the only reasonable treatment. The symptoms due to tension are relieved, and both the infiltrated and uninfiltrated tissues, relieved of this pressure, are better able to take care of the tubercular process. In addition, the arthrotomy allows a thorough local disinfection of the surfaces of the capsule and bone, and with the aid of a small gouge one is able to explore the trochanter and neck and head of the femur without endangering the continuity of the bone. In this early exploration, any focus of bone can be completely or partly excised according to its extent. Loose articular cartilage, both on the head of the femur and on the acetabulum, can be removed and the diseased bone beneath subjected to local disinfection.

From these observations it would seem that in many cases of tuberculosis of the hip, synovitis with effusion is present early in the disease ; in a number of cases the capsule ruptures and extra-articular abscesses form. An anterior arthrotomy, if performed before rupture takes place, would effectually prevent this complication.

In three of our Cases, Nos. V, VII and VIII, extra-articular abscesses were preseut at the operation. The joint capsule in these three cases was not distended but perforation and communication with the abscess cavity were found in each case. In addition to the incision of the abscess, the joint was opened by the usual anterior incision and drained. In Case VII there were two abscesses; the one beneath the adductor muscles, on the inner lateral surface of the thigh was drained through the joint capsule. Microscopic examination of the wall of abscesses from tuberculous bone, demonstrates, especially early in the disease, that the wall of such " cold " abscesses is composed of ordinary granulation tissue. We seldom find evidence of tuberculosis. Clinical observations demonstrate that extensive excisions of the abscess wall are not necessary. The most important point in the treatment is the removal of the source of infection in the bone. For this reason in operations for tuberculosis of the hip in which extra-articular abscesses are present, I believe it is better in every case to simply incise the abscess, curetting and thoroughly disinfecting in addition, if you wish, but most important of all in every case to explore the joint and search for the focus of tubercular osteomyelitis. We however, will have to wait before forming definite conclusions, and compare the immediate and ultimate results in these cases with those in which the extra-articular abscesses have simply been incised. Kecent observations, however, have impressed me with the value of early exploratory arthrotomies in tuberculosis of the hip, not only for a confirmation of the diagnosis early iu the disease, but for treatment.


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In all the joints, especially the hip and knee, the synovial sac can be thoroughly disinfected and filled with iodoform, and with a small chisel the more common positions for the tubercular focus can be explored. To open and irrigate a normal joint, even with 1 : 1000 bichloride of mercury solution, is not followed by any restriction of motion, and Case I demonstrates that the hip joint can be drained for six weeks and yet almost complete restoration of the function result. Anterior arthrotomy of the hip is a simple operation and its dangers should be confined almost entirely to the danger of the anaesthetic. However, it must always be borne in mind that a virulent pyogenic infection of the wound at the operation or later would be a serious complication, and if we found that this occurred with any degree of frequency, it would most certainly detract from the results, even in comparison with the orthopedic treatment. More extended experience will be necessary before we can judge of the risk of infection. (There has been no iufection in our series of 12 cases.)

The anterior incision in cases of tuberculosis of the hip is not a new procedure. Mr. Barker (Manual of Surgical Operations, 1887) describes it as R. W. Parker's operation. More recently, in Treves' System of Surgery, Mr. Barker again gives this incision first place, and in addition states that Professor Hueter, of Greifswald, described asimilar method independently but at about the same date of Mr. Parker's. (Transactions of Clinical Society of London, 1880, page 105.) Bradford and Lovett (Orthopedic Surgery, second edition, 1899) describe the anterior incision for the excision of the joint, but prefer the posterior incision. As far as I am able to find in the more recent authorities, the suggestions made and the methods followed in these cases are sufficiently original to justify their publication.

To repeat, the chief object in the early operation for tuberculosis of the hip is to take the disease in its early stage, to relieve the tension of the distended capsule, to check and cure the tubercular synovitis by disinfection and drainage, to explore the bone with the hope of finding the tubercular osteomyelitis, in which case it can be partially or completely excised ; trusting also to disinfection, drainage and the healing process to check and later cure the disease of the bone without injury to its continuity. The acetabular cavity can be explored, as shown in (Fig. 55) by chiseling through the head ; more extensive operations on the acetabulum, however, could not be performed without removal or temporary dislocation of the head. It is too early to judge of the results, except in Case I, in which the patient has now a perfectly functional joint one year after operation.

In operations for tuberculosis of the joints, one must always bear in mind the possibility of disseminating the tubercle bacilli. In operations on joints where the Esmarch can be used, this danger may not be as great as in operations on the hip and shoulder. It will require, however, a number of years and careful observation to get at data for this study. The method of operation is clearly described in the details of the history of the nine cases reported. The most important anatomical point is to bear in mind the deep external circumflex vessels. Sometimes it is not necessary to divide these, but if it is found that more room is required, these vessels should


be carefully ligated. The joint can be exposed easily without dividing the muscle by separating the tensor vagina' femoris and the glutei muscles on the outer side and the sartorius and rectus to the inner (medial) side. I believe it is a better plan to lengthen the incision rather than to make a cross cut of the muscles. The separation of the muscle leaves a cleaner and a less ragged wound, and perhaps detracts much from the danger, not only of pyogenic infection but of tubercular dissemination. Through this wound, by separating the muscles, one can clearly see the capsule of the joint and the trochanter and upper portion of the shaft of the femur. On dividing the capsule, one can explore with great ease the neck and head of the femur. In these operations the head has not been dislocated from the acetabular cavity, but if one found the round ligaments destroyed, with extensive disease of the head and acetabular cavity, the head of the bone could easily be temporarily displaced to allow a better treatment of the head itself and the acetabular cavity, after which it could be replaced. This course was followed in a recent case by Professor Halsted.

Discussion.

Dk. Halsted. — To indicate what we may hope for as a final result in certain cases of hip-joint disease, even when a considerable portion of the head of the femur has been removed, and in support of what Dr. Bloodgood has said, I will refer very briefly to a case which I intend very soon to report in full with other interesting hip-joint cases. The patient, a boy, thirteen years old on admission, had an acute osteomyelitis in 1895, at the age of eleven, which involved the entire diaphysis of the right femur. Eleven months he spent in bed, and for seven months could not lie on the affected side. After walking about with a cane and without much pain for more than a month he had to take to his bed again for about a week during a second acute attack of pain in the same bone. Two or three months later two abscesses appeared, one behind the knee and one internal to the trochanter. The boy was thenceforth for nearly a year quite comfortable and considered himself sufficiently well, until the 1st of November, 1897, when he was hit in the right groin by a wagon-pole. He suffered greatly from this blow, and the following morning could not flex his . thigh. Two weeks later, November 19, 1897, he was brought to us by his physician, who stated that for several days he had been having very high fever with daily intermissions. The boy was emaciated; his expression anxious and indicative of suffering. He lay on his back; the right thigh was abducted, rotated outwards and slightly flexed ; the groove in the right groin was obliterated and there was an appreciable fullness over the head and neck of the femur. Pressure over the joint and all attempts to move the head of the femur caused pain. About the level of the top of the trochanter of the right femur, but internal and anterior to it, was a sinus from which pus escaped. Behind the inner hamstring tendons was the orifice of a second sinus discharging more pus than the other. The femur was much enlarged, and the soft parts of the thigh were swollen. An involucrum had evidently replaced the entire diaphysis. A probe in the popliteal sinus touched rough bone. The measurements, which developed a fact or two of interest, I will give at another time.


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[No. 106.


1st Operation. Nov. 2J,, 1S97.— Excision of One-Half (Anterior) of the Head, Neck and Upper Portion of Trochanter of the Eight Femuk by Frontal Section. There was a small abscess containing only a few drachms of pus just below and in front of the capsule of the hip joint, which communicated with this joint. The wall of the abscess was carefully excised. Having made the frontal section of the trochanter, neck and head of femur, the extent of the disease in these parts could be accurately determined. The upper end of the soft sequestrum was cut off. The disease had involved the neck and head and had finally, perhaps just after the blow from the pole, infected the hip joint. By some oversight no drawing was made of the lesions in the head, neck and trochanter. Nowhere were there signs of active bone disease; there was a little sequestrum near the top of the trochanter, and a little, very slender bit of sequestrated bone in the neck; the shape of the head and of the neck was not altered by the disease; the head of the bone had lost some of its cartilage, and granulations were growing from the denuded parts. The infection of the joint was probably recent, and it could be demonstrated how this might have taken place. It was not contemplated at the outset to do more at the first operation than to relieve the trouble about the hip joint, for the patient's condition contraindicated an extensive operation. The patient recovered promptly from this and from two subsequent operations upon the middle and lower thigh. As you may see in the photographs, the boy can extend his thigh perfectly, and can flex it to nearly a right angle. He walks without a cane and says that he finds the right thigh as useful as the left. The operated thigh is from 1 to 1.5 cm. longer than the other; and there are 2 cm. of apparent


lengthening on the right or operated side. This apparent lengthening is due in part to abduction and will undoubtedly disappear.

This case sheds a new light upon the surgery of the hipjoint, proving as it does that not only a useful but functionally an almost perfect joint may be obtained even when onehalf of the head and neck of the femur have been removed by, approximately, a frontal section. We may, therefore, attack tuberculous cases in the early stages in some such conservative way, taking a fine and very thin slice from the anterior surface of the neck or head, or trochanter, or from all, and having located the disease, excise only as much as may be necessary. The acetabulum can be explored in a similar manner. If the disease is operated upon early it would probably rarely if ever be necessary to remove the whole head of the femur ; and we may find that having removed a part of the disease the remainder, as in tuberculous peritonitis, may take care of itself the better for having been interfered with aud assisted.

The hip joint, a simple ball and socket joint, promises more for these conservative operations than any other joint ; large surfaces covered with cartilage do not lend themselves so readily to the formation of strong adhesions and ankylosis as the less simple joints; of all the joints the knee is perhaps the least suitable for conservative surgery. With its ligaments and reduplication of synovial membrane, with its fibro-cartilages and numerous recesses and pockets it furnishes conditions well suited to the propagation of the tubercle bacillus ; and when the crucial and lateral ligaments have been much weakened by the disease, an ankylosed joint is usually more serviceable and more comfortable than one in which motion has been secured.


GUNSHOT INJURIES BY THE WEAPONS OF REDUCED CALIBRE.*

By L. A. LaGarde, Surgeon, U. S. A.


My first acquaintance with the military weapons of reduced calibre dates from a time wheu I was pursuing studies with firearms in this institution. I am, therefore, very happy to return here to-night to talk of guns and missiles with you. .

In considering the effects of the modern arm, experimenters have generally studied it by comparison with the older weapon. I hold in my hand the Springfield rifle, calibre 45, which was used by our foot troops from 1874 to 1892. It is a single loader and in expert hands it is capable of delivering 20 shots per minute.

Its projectile has a velocity of translation of 1301 f. s., a Telocity of rotation on its long axis of 800 turns per second, and a maximum effective range of almost 2000 yards. It is made of lead hardened with antimony, cylindro-conoidal in shape, weighing 500 grains, and is propelled by 70 grains of black powder.

I will now exhibit our present service rifle — the KragJorgensen — adopted in 1892 for use by the foot troops. It is


♦Read before the Johns Hopkins Hospital Medical Society, Nov. 10, 1899.


a typical example of the reduced-calibre weapons at present in use by all the powers. It is provided with a magazine which holds five cartridges. In expert hands it is capable of delivering as many as 40 shots per minute. Its projectile weighs 220 grains, 30 calibre, composed of a nucleus of lead, enclosed iu a hard steel mantle. Its velocity of translation is 2000 f. s., the velocity of rotation 2400 turns per minute; whilst it possesses a maximum effective ran^e of 4000 yards, propelled by 37 grains of smokeless powder.

In some experiments which I conducted iu 1892 at Frankford Arseual, under the orders of the Secretary of War, my efforts were especially directed to the difference in destructive effects between the missile of the 45 calibre weapon, and that of a missile so similar to the Krag-Jorgensen bullet, that for all practical purposes they may be regarded alike.

We fired the two bullets altogether one hundred and ten times, into ten cadavers. Our aim was to traverse similar parts of the body or parts offering about the same resistance, with first one and then the other bullet at all the ranges — from 100 to 2000 yards. The ranges were not actual ; they were simulated by reducing the charge of powder so that the projectile was


January, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


21


given the remaining velocity which was common to it for any given range.

Impart. — The first thing to attract our attention at the outset of our experiment was the difference in the amount of shock imparted to a member when hit first with one and then with the other bullet. The shock was estimated by the oscillation of a limb when suspended. As might have been expected, the greater sectional area and greater weight, of the 15-calibre projectile, caused greater shock than that noted by the smaller and lighter bullet on impact with a resistant bone. Indeed, the difference was so marked that it often happened that the presence of a fracture from the latter was only noticeable upon close inspection, whereas it was invariably predicated by the motion imparted to the member when traversed by the larger bullet. The shock from either bullet as judged by the motion to the limb, was nil when soft parts alone were hit.

The minimum amount of shock from the smaller calibre bullet has been the cause of much concern among military men. The English in the Soudan, and in the Ashanti campaign were so doubtful of the efficacy of this small calibre missile to arrest the impetus of savage tribes that they resorted to the practice of making their missile explosive by filing the nose through the steel casing enough to expose the lead core. This is the famous Dum-Dum bullet which takes its name from the place of its manufacture in India. When the lead is exposed, as stated, the projectile disintegrates on impact with a resistant structure. The fragments of the steel mantle and lead core, acting as individual missiles add greatly to the destructive effects in the foyer of fracture.

Explosive Effects. — Our observations with the old and new rifles were next directed to explosive effects. We noticed these so called explosive effects with the new weapon up to 350 yards, whilst they were seldom exhibited with the old arm beyond 200 yards. Explosive effects in gunshot wounds are peculiar to rifle projectiles impressed with high velocities. Within the zone of explosive effects they are common in the experience of the military surgeon, whereas they are seldom witnessed by the civil surgeon whose experience is almost entirely confined to wounds by pistols, whose projectiles are possessed of comparatively low velocities.

In speaking of explosive effects, one should not confound the term explosive effects with explosive action. The latter term should be restricted to those wounds caused by an explosive bullet — that is, a projectile that explodes on impact. Such a projectile is hollow, charged with explosive materials which ignite when the bullet strikes against a hard substance, like bone. The bullet is thus torn asunder, causing usually an extensive lacerated wound. On the other hand the projectiles possessed of superior velocities do not explode on impact. They are solid, and at most, seldom become altered in shape. Indeed, those of the small calibre, enclosed in a mantle of the hardest steel, do not even deform when they collide with the most resistant parts of the human body; and yet they are proverbial for their explosive effects in the proximal ranges.

Explosive effects are well exhibited by firing the projectile of the old and new arm into tin cans at close range. For the


purpose of comparison, if the experiment is done by firing into tins when empty, and into another set of tins of similar capacity filled with water, the empty cans will exhibit no alteration in shape. The orifice of entrance and exit of the bullet will correspond in size to the sectional area of the projectile; on the other hand the tins that were filled with water will show great alteration in shape. The sides of the vessels will exhibit a bulging as if some interior force had exerted an outward pressure in all directions. The orifice of entrance will usually correspond to the calibre of the projectile, whilst the orifice of exit will be marked by a large irregular opening with everted edges.

If the exjieriments are continued upon a cadaver at close range, impact with a resistant bone will present certain characteristic features: The wound of entrance in the skin will correspond in size to the diameter of the bullet; the wound of exit will be marked by a bursting forth of the skin. "The track leading to the bone is conical in shape, the base of the core corresponds to the wound of exit in the skin, and the apex of the core corresponds to the seat of fracture. The bone is finely comminuted. A close inspection shows that the bony particles have been driven into the tissues at right angles to the bullet track ; it is not uncommon to find bony sand in the wound of entrance."

Five theories have been advanced to explain these explosive effects.

1. Hydraulic Pressure.

2. Compressed air, or the projectile air.

3. Rotation of the bullet.

4. Deformation of the bullet.

5. Heating of the bullet.

1. Hydraulic Pressure. — The term " hydraulic theory " has been employed by many writers to explain the highly destructive effects often found in gunshot wounds at the proximal ranges. It is based on the principle of Pascal. This principle is only applicable to a closed vessel tilled with liquid. In accordance with this principle if a certain pressure is made upon a given area of the imprisoned liquid a similar pressure will be exerted within on like areas of the vessel walls.

The experiments of Coler, Stephenson and others have effectually disproved this so-called hydraulic theory. They have shown that the highly destructive effects noted by firing into sealed vessels filled with liquid were to be noted in the same way when the vessels were unsealed. Ordinary tin buckets filled with water whether the tops were in place or not sustained the same amount of destruction.

2. Compressed air, or projectile air. — This is called the projectile air of Melsens, because it is he who recently revived this theory of projectile air in explanation of the destruction in wounds that so often suggest explosive action. Boys lias succeeded in making exact photographs of bullets in transit. He caused the bullet to cross an electric circuit. At the moment of contact with the circuit the bullet and the immediate vicinity of its trajectory are illumined by a spark which serves to throw the image upon a photographic plate. A study of the views thus obtained distinctly shows a pad of compressed air in front of the projectile. Melsens believed


22


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 106.


that this cushion of air entered the tissues at the moment the skin was penetrated or before, and that the destruction of tissues was to be accounted for by the explosion which occurred when the compressed air again regained its normal volume. The tissues fail to show any evidence of air having been forced into them, such as one might infer from the presence of emphysema, and altogether it may be said that the theory of projectile air has but little to recommend it to consideration.

3. Rotation of the bullet. — The rotation of a rifle bullet is imparted to it by the twist in the barrel. The longer the bullet the sharper must the twist be. The old Springfield 45-calibre bullet, which was but two calibres in length, and which revolved 800 turns per minute at the muzzle described one complete turn in 22 inches, because the twist in the barrel corresponded to one complete turn in 22 inches. In the present rifle the twist is sharper, viz., 1 turn in about 10 inches, and the rate of revolution is estimated at 2400 turus per minute. It is generally admitted by ballisticians that the velocity of rotation is well maintained, — that it does not diminish with the velocity of translation. Taking for granted that the projectile makes a complete turn in ten inches, we must admit that the rotation of the bullet can have but a minimum amount of effect to disjday in traversing a thigh bone which may be but one inch in diameter, because in traversing it the ball is making only T \ of a turn.

4. Defortri'ition. — The fact that the old leaden bullet became deformed when colliding with a resistant bone, especially at short range, added greatly to the amount of destructive effects. Deformation can find no plea as a cause of destructive effect in all cases since the steel-clad bullet that does not deform is proverbial for the creation of explosive effects.

5. Heating. Heating of the bullet by the act of ignition to explain explosive effects found adherents long ago, and it was not until recent years that this erroneous notion was set aside. It is not necessary to explain to an audience like this in the very institution where the significance of heat imparted to missiles was forever determined. We ware able to show in 1892 that the heat on a bullet caused by the ignition of the powder is not sufficient to destroy the ordinary septic germs. The experiments were conducted with missiles from lowvelocity rifles and the weapons of reduced calibre with the same result. To speak briefly we can truthfully say that the heat of a missile cuts no figure in gunshot wounds.*

The true cause of explosive effects is the superior energy possessed by the bullet at the moment of impact. The bone, and even the soft parts, receive a large amount of this energy and move "outwards in lines radiating from the long axis of the bullet-track with such a degree of force that they act as secondary missiles on the neighboring tissues and cause still further smashing and pulping of the tissues. Even fluid particles participate in this secondary action but it is all the more marked when fragments of bone are driven apart in this manner." (Stephenson.)

Soft Parts. — Our next experiment at Frankford with the


♦Proceedings Pan American Congress for 1893, Vol. 1. N. Y., Med. Record, Vol. 47, No. 25.


small-diameter bullet demonstrated that the wound of entrance was usually round, the size corresponding to the diameter of the bullet; the edges of the wound were at times clear cut, but more often they were rolled in and often blackened like the wound of entrance of the old leaden bullets. This, as you know, once gave rise to the idea that the edges of the wound were discolored by burning ; but thanks to the assistance of Professors Welch and Councilman, as already stated, this idea was refuted for all time in the laboratory of this institution.

The wound of exit of the small-calibre bullet was generally larger than the wound of entrance, and beyond the zone of explosive effects especially it was generally round, marked at times by a mere slit; again it was star-shaped, T-shaped, semicircular, &c; the edges were generally turned out.

Diaphyses of long bones. — Our next observations at Frankford Arsenal referred to the effects of the small-calibre bullet upon the compact substance of long bones. Here I may state that the destructive effects of the old and new bullet up to 350 yards were alike, and severe. Beyond 350 yards the lesion in the bony tissue changed perceptibly with the smaller bullet, the comminution was less, the fissures were larger, and the spiculae of bone were not so often detached. The general tendency with the little bullet between 500 and 1500 yards was to inflict a wound approaching a perforation, although a clear-cut perforation in the diaphysis itself was seldom seen. At 2000 yards the small bullet showed a tendency to again shatter the bone.

Effects upon the epiphysial ends of long bones. — Clear-cut perforations were generally observed when the small bullet traversed the spongy ends of bones. This was especially true after the zone of explosive effects and even within this zone — 350 yards — complete perforations with little or no Assuring were often seen.

Actual Conditions. — Of the wounds noticed in Cuba during the Santiago campaign I may add that they partook the general characters of the wounds that I have described as exrjerimental wounds. The wounds of the soft parts healed immediately, without an exception to my knowledge, under antiseptic dressings. The wounds of joints, including the knee, elbow, shoulder and hip were immobilized, dressed antiseptically, and they all did well. The wounds of the skull, including brain substance almost invariably suppurated, owing no doubt to the amount of dirt introduced from the scalp with the bullet.

Wounds of the lungs. — Those that survived 24 hours generally did well. In the majority of instances it was difficult to restrain the men after two or three days.

The wounds of the abdomen were generally fatal. Four or five men recovered with gunshot wounds that appeared outwardly to have perforated the intestines, but no actual proof of such perforation was obtainable. I was told that three laparotomies for gunshot injury of the abdomen were done at one of the field hospitals. The patients all died in a few hours after operation. For mauy reasons laparotomy for gunshot wound in the abdomen on the field was not considered safe or practicable. Upon the whole, the gunshot injuries by the Mauser, the reduced-calibre rifle of the Spaniards, were in keeping with those humane effects so confidently predicted by


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JOHNS HOPKINS HOSPITAL BULLETIN.


23


experimenters generally. The wounds of soft parts healed without suppuration. The lesions of bone that formerly caused such a high mortality in the statistics of wars were most successfully treated by antiseptic dressings and the proper use of immobilizing materials. Comminution, and Assuring were noticed in the diaphyses. It was, however, seldom necessary to cut down for the purpose of removing spiculse of boue, as the displacement of fragments did not require this amount of interference. The clean-cut perforations of the epiphyses, without fracture, rendered joint injuries the most favorable of all bone lesions for rapid healing, with little or no loss of function. This was especially true of gunshots of the knee.

The difference between the gunshot wounds of civil and military hospitals will be more marked in the future. The civil surgeon will continue to treat pistol-shots in which the balls often lodge. Some lesions from this source often show complete separation of fragments, which necessitates cutting down. The joint lesions are often severe, necessitating the opening of the joint, under antiseptic precautions, turning out blood clots, removing fragments, etc. Such precautions are necessary to insure against sepsis. On the other hand, it may be said that the action of the steel-clad bullets from the present military weapons and the use of antiseptics have so modified the results in the gunshot wounds of warfare that the burden of the military surgeon and the sufferings of the patient, immediate and remote, will be very much lessened.

Discussion.

Exhibition of Radiographs showing Results of SmallCalibre injuries. — Dr. W. C. Borden, U. S. A. — During the late war I was stationed at Key West with an X-ray machine, and from a study of the wounded soldiers I have arrived at some general conclusions relative to the effects of the small-calibre bullets on the human body, more particularly upon the bones. Dr. LaGarde has gone over the consideration of the theoretical effects of the bullets and these pictures will show the clinical effects as demonstrated by the Roentgen ray.

It seems to me that there are four main elements that influence the effect upon bone tissue — (1) the velocity of the bullet — (2) the part of the bone struck — (3) the angle of incidence and (4) the form of the bullet. Clinically, there is one thing above all others that affects the course of the case, and that is the presence or absence of sepsis in the wound.

When the bullet is traveling at extremely high velocity the explosive effects are produced whether the bullet strikes the bone, I mean now the shaft of the bone, at any angle or in any part. For instance, if it strikes the bone perpendicularly, it will produce a bad fracture, and it will do this equally if it merely grazes the bone. When the bullet strikes the bone laterally, merely grazing the periosteum at a high velocity, it produces a fracture that may be termed a fracture by contact. Here is an illustration (showing radiograph) ; the bullet passed across the front of the forearm, just grazing the radius, and yet, as you see, it shattered the bone completely; and here is an example showing a similar effect upon the hand at short


range. In this case the whole distal end of one of the metacarpal bones has been blown completely out, and yet the wound of exit was very little larger than the wound of entrance; the range was five hundred yards.

So much for the effect upon the human body when the velocity of the bullet is at its greatest. Now, the angle of incidence seems to me to have a marked influence. When the bullet strikes the bone in the median line with perpendicular impact, it shatters the bone as badly as if it were within the explosive range. Here is an illustration of a fractured thigh, in which the bullet went straight through, striking the femur with a median impact, and you see how badly the femur is shattered. In a little over a year after the injury I radiographed this same case; the wound had healed readily without any suppuration, and though there is a tremendous callous formed about the fracture, the position and function of the limb are almost perfect. Now as to tangential impact, when the bullet strikes the bone at an angle the fracture and Assuring are not so great, no matter what the range may be, provided it is outside the explosive zone. In this case (showing radiograph) the bullet struck the outer side of the radius, tore off a piece of bone and made a straight fracture.

Now as to the form of the bullet. Dr. LaGarde has spoken only of the bullet as it strikes after passing through the air; but in war it may ricochet, strike some object, become deformed and then strike the body. In these cases the effect of the bullet is decidedly different from that of the plain undeformed bullet. In this case (showing radiograph), for instance, the bullet struck some object before it hit the man, and the whole end of it became flattened so that it was practically like a Dum-Dum bullet. The velocity was low, for the bullet lodged in the tissues and yet because of its extreme deformity when it struck the bone it shattered it immensely. Here is an injury of the same class showing two bullets in the same limb. Both bullets were deformed and the shattering was very great. Here is a photograph of several Mauser bullets removed after X-ray examinations of the patient. All but one of them are deformed.

Here is a rather interesting radiograph showing the passing of a Mauser bullet through a phalanx. The bullet is so small and travels with such velocity that it may pass through a finger and not tear it off as would a larger bullet. Relative to this case I would say that gunshot injuries of the hand always cause some permanent loss of function. This is due to injury to the soft parts; and in regard to injury to the soft parts by the small-calibre bullet I would say that we have had a great many cases where, though the bones were markedly shattered, if the soft parts were not much torn there was not much loss of function ; but if the soft parts were greatly disturbed, the resulting cicatrizing tissues caused considerable disturbance of function.

The injury produced by these bullets to the ends of long bones is quite different from that of the shafts. In the shaft the Assuring and comminution are always greater than in the extremities. Whatever the theory of explosive effect may be it is certainly true that the dense tissue of the shaft transmits the shock more than the softer tissues and causes greater solution of continuity.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 106.


Concerning the humane effect of these bullets I should say that where they do not kill outright they are certainly much more humane than the old bullets were. I saw some cases, — one I remember in particular — where the bullet passed through


the abdomen, directly through the liver, and yet the patient was up and ran away from the hospital eleven days after receiving the injury.


A RECONSTRUCTION OF A GLOMERULUS OF THE HUMAN KIDNEY.

By William B. Johnston.

(From the Anatomical Laboratory of the Johns Hopkins University, Baltimore.) WITH SIX FIGURES.


Since the appearance of Carl Ludwig's article upon the Kidney in 1872,* in which he devotes but a few words to the structure of the glomerulus, and in which are reproduced a few drawings of the glomeruli of mammalian kidneys, other investigators have been inclined to pass over this part of the vascular mechanism of the kidney, mentioning only its afferent and efferent vessels. The difficulty of seeing anything but the exterior of a glomerulus has, of course, always obscured its intimate structure. For these reasons it has appeared advisable to make a more careful study of the arrangement of the blood-vessels of the glomerulus by means of the method of reconstruction.

The requirements for such a reconstruction are a perfect set of serial sections through a well injected glomerulus, the sections being thin enough to pass at least twice through any of its vessels which may be struck parallel to the plane of cutting, as well as a conception of the outward form of the glomerulus previous to cutting.

Preliminary injections of the dog's kidney with a variety of substances brought out the advantages of a supersaturated aqueous solution of Berlin blue over other injection masses, and the advisability of selecting and cutting a single glomerulus. Adult human kidneys from the autopsy table were usually abnormal and always failed to be well injected. In order, therefore, to obtain a good injection of a normal glomerulus, the kidney of a child three months old, dead but a few hours, was injected in situ through the abdominal aorta until the Berlin blue appeared in the renal vein. The difficulty of obtaining a faultless series of very thin sections was greater than that of selecting and cutting out a well-iujected glomerulus from clear bits of this kidney, though very many seemingly perfect glomeruli proved to be but partially injected. A chosen glomerulus from the child's kidney was imbedded in paraffin in the usual way and cut into serial sections 3 /x thick. The 3-1 sections through this glomerulus were then stained in Upson's carmine and mounted in balsam. Drawings of each of these sections enlarged 1333 diameters, the greatest convenient enlargement, were made with a camera lucida (Figs. 4, 5, 6) and the corrected drawings transferred with carbon paper to wax plates 4 mm. thick, i. e. 1333 times as thick as the original sections.


•Handbuch der Lehre von den Geweben des Menschen und tier Thiere. S. Strieker, Vol. 1.


Before beginning the reconstruction, that part of each plate representing the glomerulus proper was cut out, the line of iucision following the outer borders of the external vessels, leaving Bowman's capsule in the outer shell. The remaining wax shells thus obtained were carefully piled in order, and a plaster-of-Paris cast made of the cavity. The solid cast roughly indicated the external form of the enlarged glomerulus. As a further guide to the reconstruction, the sections of the blood-vessels appearing in each plate were cut out with the exception of wax bridges connecting them. The internal relation of these sections in wax representing the blood-vessels was thus preserved, which aided materially in piling and blending the individual sections.


XV



Fig. 1. — Was model of the glomerulus, enlarged 444 diameters, seen in profile from the left side. A F afferent vessel ; E Fefferent vessel.

From the model thus made it appears that the afferent vessel of the glomerulus, after entering the capsule of Bowman, immediately divides into five diverging branches, which with their subdivisions and with the efferent vessel form an almost spherical tuft of blood-vessels. For the sake of description we may assume that the glomerulus is suspended from its afferent vessel. The efferent vessel originates, roughly speaking, from a loop of capillaries which projects in the equatorial plane from the side of the glomerulus opposite the efferent vessel, but to the right of the median line (Fig. 2 E. V.). From this point the course of the efferent vessel is upward, inward, and to the left, grooving the superior surface of the glomerulus and dividing it into two unequal parts. This vessel leaves the glomerulus a little superior and


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25


anterior to the point where the afferent vessel divides and in a direction opposite to that of the efferent vessel. (Fig. 1.)



Fig. 2. — Wax model of the glomerulus, same enlargement and same view as in Fig. 1. The left lateral group of capillaries is separated from the median group and turned back, exposing the interior of the glomerulus, a. A short section of a capillary of the median group is removed to show the course of the deeper-lying capillaries.

Externally the upper half of the glomerulus is seen to be composed of freely anastomosing capillaries, somewhat more pronounced on the left than on the right side. The capillaries of the lower half, except on the posterior surface, are loDger and more direct. The projecting loop of capillaries mentioned above, the course taken by the efferent vessel within the glomerulus, and the tendency of many of the external capillaries to turn towards the right side, give the glomerulus the appearance of being twisted to the right. Except on the superior surface where the left half is a little above the right, the spherical form is well preserved. Lobulation where it appears at all is superficial. (Fig. 1.)



Fig. 3 — Diagram of the wax model seen from the left side. Enlarged 444 times. The right lateral group of capillaries is turned back from the main group. The group E F is a connecting loop turned over to expose deeper capillaries. The lines marked Figs. 4, 5 and 6 indicate that Figs. 4, 5 and •', are taken from those planes, representing sections 7, 17 and 30 respectively of the original series.

The capillaries of the glomerulus can be roughly divided into a right, a left and a median group, corresponding to a right branch (Fig. 3 A), a left branch (Fig. 2 B) and a median branch (Figs. 2-3 C) of the afferent vessel. Two additional branches, a right lateral branch (Fig. 3 D) and a


left lateral brauch (Fig. 2 E ), take part in the fornmtiou of the lateral group of the corresponding side and of the median group. All rive branches arise from the afferent vessel at the same time though at different angles. The distances between their points of origin are not the same. According to Ludwig, the glomerulus is composed of from 4 to 8 groups of bloodvessels.

Each main brauch from the efferent vessel subdivides almost immediately. Each of the two lateral branches (D and E) has three subdivisions which are soon lost in the three main groups. They have in general the same arrangement.




Fig 4.

In the upper half of the left group (Figs. 1-2) there is a complex network of anastomosing capillaries. In the right group (Fig. 3), which is smaller than the left group and lies at a lower level, the course of the capillaries is more direct.



Fig. 5.

FlOS. 4, r> and fl. — Camera tracings of sections 7, 17, and 30, showing the capillaries, reticulum nuclei and Bowman's capsule. Enlarged 444 diameters.

The capillaries of the median group nearest to and farthest from the origin of the median branch (C) are in general longer and freer than those of the other group. The intermediate capillaries are short and the anastomoses frequent


In addition to the many connections between capillaries of the same group, the three groups or lobules are intimately connected with one another by numerous anastomoses. The capillary connections between the median group and the right group on one hand (Fig. 2) are of the same frequency, although unlike those between the left group and the median group on the other hand (Fig. 3). At one point there is an anastomosis of all three groups (Fig. 2 d, d', Fig. 3 d, c, c', c"). The number and varied character of these connections show the impossibility of dividing the capillaries of the glomerulus completely into distinct groups.



r«:: ftC


Fig 6.

Through the divisions of the main branches of the glomerulus and their subsequent anastomoses, all the capillaries are concentrated at two distinct levels (Fig. 2 F. G) in the median plane opposite the afferent vessel. Though the formation of the efferent vessel is clearly indicated at each level in the sections, it cannot be said to actually originate until the last capillary from the glomerulus has united with it (Fig. 3 L).

It is seen that the blood in passing from the afferent to the efferent vessel has the choice of numerous paths of varying lengths. The shortest path is that from the right lateral branch of the afferent vessel just above the central point of the glomerulus and in the median line (Fig. 3 D, c). Passing outward from this point to the periphery of the glomerulus, the paths become longer and more complex. The longest path is that of the median branch and its subdivisions along the inferior surface of the glomerulus. It is three times as long as the shortest path (Figs. 2-3). Yet the shorter course is


zigzag and is composed of the smallest capillaries. As the course between the afferent and efferent vessel becomes longer and longer, the capillaries become straighter and larger, thus correspondingly favoring the blood circulation through them.

The afferent vessel is larger than its branches, especially just before the point of division ; the branches are larger than their subdivisions. The efferent vessel is of the same size as the main branches of the afferent vessel. The increased diameter of the afferent vessel and its first branches is no doubt due to the pressure in the artery when the glomerulus was injected. Excluding this factor it is probable that the diameter of the various vessels of the glomerulus is the same from the afferent to the efferent vessel.

The very fine serial sections of the glomerulus not only served as a basis for the reconstruction of the blood-vessels, but also enabled me to study more carefully the relation of Bowman's capsule to the glomerulus. Ludwig* has shown that the basement membrane of the uriniferous tubules is elastic and when treated with reagents is very likely to swell. Later Mallf showed by digesting frozen sections of various organs with pancreatin that the interstitial tissue and so-called basement membranes resolved themselves into fibrils, showing some characteristics of yellow elastic tissue, some of white fibrous tissue and some peculiar to themselves. This set of fibrils (reticulum) is widely distributed and makes up the main framework of the kidney. It is these fibrils of reticulum which form the basement membrane of Bowman's capsule.

As the afferent vessel pierces Bowman's capsule, the reticulum fibrils forming it separate as shown in Figs. 4 and 5. They are not reflected over the glomerulus, but, at the point of separation, fibrils arise which penetrate the glomerulus passing in all directions between its capillaries. The fibrils are densest at the point these vessels penetrate the capsule and gradually become less and less numerous as the periphery of the glomerulus is approached. Up to the present I have not determined the nature of these fibrils but on account of their arrangement as well as the connection with them of Bowman's capsule, I do not hesitate to class them with the other reticulum fibrils.


  • Ludwig, Strieker's Handbuch, 1871, p. 495.

fMall, Abhandl. d. K. S. Ges. d. Wiss.,Bd. 17, 1891 ; also Riihle, His's Arch., 1896, and Disse, Sitzungsber. d. Ges. z. Beford. d. ges. Naturwiss. Marburg, 1898.


MEDICAL COMMISSION TO THE PHILIPPINES.


It is matter of general belief that scientists in the retirement of the laboratory pursue their abstruse investigations oblivious of wars, revolutions, and the manifold variations in the phases of international politics, and it is, perhaps, well on the whole that there is some basis for the belief. But, as a matter of fact, it will be found that the trend of scientific research is, at times, enormously influenced by changes in the outside world; for with these changes new problems arise upon the solution of which depends the ultimate success of national undertakings. No more striking example of such


influence could perhaps be adduced than the extraordinary attention which is at present being paid to the study of the causes, prevention and cure of diseases prevalent in the tropics. While there have been, it is true, notable instances of medical research prosecuted with brilliant results in tropical fields in the past, it is only since Northern and Western nations have turned their faces resolutely towards the South and the East— faces stern in the determination to hold their own in the fierce international rivalry for conquest and control of trade — that the importance of the medical problems


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of the hotter regions of the earth has begun to be fully appreciated, and that organized bauds of skilled investigators have been seut iuto them to study the diseases to which a large mass of their fellow countrymen will henceforth be exposed.

The earlier observations on the conditions aud diseases of tropical countries we owe to missionaries and explorers, men of roving instincts and venturesome habits, who partly in self-defense, partly from desire to benefit other travelers or the natives of the regions traveled through, observed the sick and examined the methods of treatment in vogue in those lands. All such studies were necessarily fragmentary and of a desultory character, but no one with a knowledge of the subject would speak of them disparagingly, for they represent the beginnings of an important movement, and have been, moreover, attended by valuable discoveries, some of which have proved to be of the greatest benefit to humanity. It is only necessary to mention the introduction of cinchona bark into Europe in the 17th century by the Jesuits, who had seen its beneficial effects in Peru, and to recall the immense part played by its alkaloid, quinine, in the treatment of malarial diseases to-day, to realize the significance of at least one of these discoveries. Millions of lives have been saved, and whole continents made accessible to civilization, for the dangers of forest and morass have largely ceased to be prohibitive since the white man has learned to carry quinine in his blood.

Later, white traders and white soldiers, the natural successors of missionary and explorer, on entering the tropical regions took with them civil and military physicians, who by virtue of their better medical and scientific training were able to describe climatic conditions, investigate the symptomatology of diseases, and study their causes, nature and treatment far more accurately than their predecessors had done. Thanks to their efforts we are already in possession of an analysis of the more prevalent diseases peculiar to the tropics and of the many facts of importance concerning etiology, pathology, prophylaxis aud cure. Among the most fertile in results has been the work done by Fayrer in India, and in Cochin China by Calmette, on snake poison ; in Algiers by Laveran, and in India by Koss, on the malarial infections ; in Bombay by Vandyke Carter and Obermeier, on relapsing fever; in China and other countries, by Manson, on filariasis; and in the West Indies and South America, by Sternberg, Guiteras and Sanarelli, on yellow fever.

During the last thirty years, however, remarkable advauces have been made in pathological and especially in bacteriological technique. A large number of scientific investigators in all civilized countries have been gradually overcoming difficulties which had hitherto been insurmountable, but which, by the new methods at their disposal could now be satisfactorily attacked. The field of medicine has become so wide and divided into so many departments that one man can scarcely hope to cover all of them. Much as we have to thank civil and military physicians in the past for the good work they have done, we can scarcely ask in the future men who have to devote a large share of their time to the treatment of patients and to the performance of executive functions to undertake the complicated researches necessary for the


isolation of the causative agent in obscure diseases. There has to be a division of labor and the practical man must be helped out by individuals who have been especially trained in particular lines of work, and who can give all their time to such work. Accordingly, of late, European governments and educational institutions have been sending into tropical regions men especially prepared and commissioned to investigate disease, and these men have been relieved of all duties except those actually connected with their original research. In this way, Koch and Gaft'ky went to Egypt and India, in 1883, to study Asiatic cholera, an expedition which resulted in the discovery of the cause of the disease; and at Hong Kong, in 1894, Yersin isolated the bacillus of bubonic plague. That such special investigations of the causes of disease justify the education of specialists and the expenditure of the time and money required is fully evidenced by the practical results which have followed. Cholera, now that the spirillum, the growth and activity of which in human beings cause the symptoms of the disease, is known aud its habits of life and mode of dissemination have been studied, can in civilized countries be absolutely controlled; the disease can no longer gain a permanent foothold in a city in which modern methods of sanitation are employed. Plague which swept away whole populations at a breath in former times need now scarcely be feared among Western nations; for even if the hygienic precautions of the end of the century fail to keep the disease out of the West, the method of preventive inoculation which has been devised since the discovery of the causative bacillus will protect those who avail themselves of this prophylactic measure.

In the light of these facts the authorities of the medical department of the Johns Hopkins University decided in March of the present year to send two of their staff, Dr. Simon Flexner and Dr. Lewellys F. Barker, to the Philippine Islands, equipped with a complete outfit for the study of disease by modern clinical and pathological methods. They were instructed to study the diseases which prevail in the islands "with the hope not only of making contributions to the science of medicine, but also of being of service to the American forces in those islands, to the natives of the country, and to humanity at large." The expenses of the expedition were defrayed through the generosity of a few friends of the University. Two advanced medical students, Mr. Joseph Marshall Flint, of Chicago and Mr. Frederick P. Gay, of Boston, went as volunteers and at their own expense to assist in the medical work at Manila. Mr. John W. Garrett, of Baltimore, interested in the political relations of the archipelago, made a fifth member of the party.

The voyage out was made by way of Vancouver, Japan and Hong Kong. Ten days were spent in Japan and the experience there proved of great value as an introduction to the work in Manila, inasmuch as Japanese scientists have studied and. indeed, with considerable success, several of the problems which confront the investigator in the tropics. With Doctors AoyoBia and Miura in Tokyo, several cases of kakke were observed, a disease which in the Philippines and in other countries, is more generally known under the name of beri beri.


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[No. 106.


The researches of the Japanese into the nature of this malady are among tbe most interesting and important extant. Dr. Aoyoma, who when investigating plague in Hong Kong was himself attacked by the disease and for a considerable period lay in a most precarious condition, showed no ill effects of the ordeal passed through, but was as active and enthusiastic as ever in the observation and treatment of disease. In the laboratory of Dr. Kitasato, the celebrated bacteriologist, of Tokyo, opportunity was afforded for looking into the work done by Dr. Shiga, one of the assistants in that laboratory, on the cause and treatment of dysentery. Dr. Shiga, who has isolated a bacillus which he regards as the cause of epidemic dysentery in Japan, has also, by inoculation of tbe bacillus into animals, prepared a curative serum which he believes will be of value in the treatment of human cases.

At Hong Kong, the members of the Commission, through the courtesy of Dr. Lowson, had their first opportunity of studying cases of bubonic plague, clinically in the wards of the isolation hospital and pathologically in the dead-house. The disease is constantly present there, though to a varying degree, among the Chinese inhabitants, Europeans being occasionally, though but rarely, attacked. A member of the Commission, speaking of experience with plague, remarked upon the curious mental phases passed through on encountering for the first time such a world-dreaded disease. During the first visit to the morgue in which the dead bodies of plague patients were kept, great care was taken to come into no personal contact with the dead, and even draughts of air leading from the vicinity of the cadavers were avoided. On the second day, the swellings (or buboes) in the groin, axilla or neck were palpated, but with some care; and on the third day, they found themselves making post-mortem examinations of the internal organs. Though Dr. Aoyoma developed the disease as a result of his studies, and Dr. Miiller, of Vienna, died from plague contracted while attending a nurse sick of it, it is probable that pathologists, provided they take the necessary precautions to avoid infection, have less to fear than is ordinarily supposed. If one work much with the disease, however, he would be very unwise did he not take advantage of the protection afforded by Haffkine's preventive inoculation.

The members of the Commission arrived in Manila at the beginning of May and at once, thanks to letters from Surgeon-General Sternberg, and the courtesy of Colonel Woodhull, the chief surgeon of the American forces in the islands, were enabled to begin their work in the military hospitals there. The majority of the American sick in Manila are cared for in two large base hospitals known respectively as the First and Second Reserve Hospitals. In the former institution, with Major Crosby in control, are some twelve hundred patients; while in the latter, under the management of Captain (now Major) Keefer, there are perhaps onefourth as many. Assoon as the patients are convalescent, those who require further building up are sent to the pleasantly situated Convalescent Hospital on Corregidor Island. This hospital is situated on the shore snugly nestled beneath the fort which fired on Admiral Dewey's ships as he entered Manila Bay. In addition to the military institutions men


tioned, there are numerous "district" and "regimental" hosjjitals in Manila, Cavite and other places whei^American troops are stationed. It was a matter of pleasant surprise to see how efficiently large military hospitals, seven or eight thousand miles away from home, could be organized for medical and surgical work. Whatever criticisms may have been made in America with regard to the administration of military affairs, nothing but praise is to be recorded of the medical services rendered by Colonel Woodhull and his staff in the Philippine campaign.

On account of the especial facilities and material obtainable at the First Reserve Hospital, working headquarters were established there, Lieutenant Strong generously sharing his laboratory with the newcomers, and in every way possible, lending his aid to the investigations undertaken. The time at their disposal being limited, the members of the Commission decided to choose, out of the many attractive problems which immediately suggested themselves for investigation, certain only which seemed to them of the greatest importance and which could be most advantageously approached. It was found that among the American soldiers in Manila the two most fatal diseases in May and June were dysentery and typhoid fever, while among the natives tuberculosis and beri beri were common and destructive maladies. The dysenteries and tropical diseases of the liver met with were made the object of especial study, and one of the most important results of the expedition was the isolation by Dr. Flexner, from the dejecta of patients, of a bacillus which is almost certainly the cause of the acute dysentery studied. The causative agent in this disease once known, it is perhaps not too much to hope that a preventive inoculation may be devised which will render individuals going to the islands immune from attack. Such a prophylactic measure if invented would be of incalculable value, since, according to an authoritative text book, " In the tropics dysentery destroys more lives than cholera, and it has been more fatal to armies than powder and shot." Malarial fevers are frequently encountered, and in Manila the parasites of the tertian and of the asstivo-autumnal variety are easily demonstrable in the blood of patients suffering from these types of the infection. The frequency and malignancy of the cases vary with the locality and with the season of the year. The deadly calentura perniciosa is much feared in certain districts, and as soon as the country is settled this form of malaria should be thoroughly studied. The forests of the interior of Mindoro and the regions adjacent to the Rio Agusan in Mindanao are localities of unusual interest in this connection. The relation of mosquitoes to malaria, so vital a question at the moment, is one well worthy of attack in the Malayan archipelago. Not uninteresting too, in passing, is the statement in certain of the Jesuitical records of Mindanao that the natives of that island recognized as far back as two centuries ago a relation between the intermittent fevers and the prevalence of mosquitoes.

At Cavite, an outbreak of some two hundred cases of beri beri among the Filipino prisoners yielded wide opportunity for the study of this disease in its various clinical and pathological aspects. In the same town a large epidemic of what was probably Dengue fever occurred.


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The cases at the Spanish hospital of Sau Juan de Dios, those at San Lazarus, the leprosy hospital, and those at the city asylum, were made accessible to study through the kindness of Major Frank Bourns, of the Provost-Marshal's department. There were still a few smallpox cases in the city, though through the strenuous exertions of the officer mentioned, in the way of compulsory vaccination and the establishment of a carabao vaccine farm, this disease, which claimed so many victims from among the American soldiers at the beginning of the occupation, was practically stamped out of Manila. Skin diseases are very prevalent among the natives, and the affection known as dhobie itch (for the most part a form of ringworm) attacked large numbers of American soldiers.

A considerable amout of pathological material was collected by the members of the Commission especially from cases of beri beri, leprosy and dysentery, and this was brought back to America for farther study. An abundance of plague material was similarily collected at Houg Kong. Bubonic plague does not exist in Manila, and a careful search through the older records would make it appear that it has never broken out in the Philippines.

The climate, though trying, owing to the continuous heat and moisture, is believed to be supportable if Americans will take certain necessary precautions. As one genial Englishman who has lived in Manila nineteen years, and who is now in perfect health, put it, "it is not so much the climate as the glass bottle which injures people out here." The visit of the Commission to the islands was made in the hottest season of the year, and at the beginning of July the onset of the rains by increasing the moisture in the air added much to the discomfort. However, if one carefully chooses his diet, eschews iced drinks, clothes himself rationally, avoids excesses both physical and mental, keeps out of the sun during the hottest time of the day, sleeps under mosquito-netting and does not bathe in too cold water, he may live a fairly comfortable life and will probably enjoy good health. Indeed, some Americans have found themselves in better health in Manila than at home, though this is the exception rather than the rule. Diarrheal troubles are very frequent and are to be combated by rest, a simple diet and, if necessary, by wearing a woolen abdominal band. Much has been written about the drinking of boiled water by the soldiers. Outside Manila this is certainly desirable, but any attempt to persuade soldiers on the march to follow this custom will probably prove futile. The Johns Hopkins party walked one afternoon from the Bag Bag river to San Fernando, and before the end of the journey found themselves drinking any water available, some of it certainly far from pure.

Early in July, Mr. Garrett left Manila for a trip through Java, and a few days later the rest of the party returned to Hong Kong, and began the homeward voyage which was made by way of Suez and London. Two members of the Commission spent three weeks in India, and there examined as fully as possible in the time, the outbreaks of plague which existed and the plague measures adopted by English officers in the Indian Empire. In Bombay, Colonel Weir, and in Poona, Major Keid and Major Windle accompanied them to the scene of the outbreaks.


The excursion to Poona was most impressive. Traveling upward for hours through the Western Ghats, the country

was so beautiful and the air so much cooler than at the sea level, that one could scarcely believe that he was approaching, in the plain, a little lower down on the other side, the peststricken city of Poona. On arrival at the railway station, however, the first signs of distress were noticed. Train-loads of people were fleeing from the place. A drive through the town to the office of the chief plague authority showed how rapidly it was being deserted. Many of the streets were almost empty, shop doors and windows were closed and barricaded, plague notices were pasted on the wall, a preternatural stillness was everywhere noticeable, the few people encountered walking quietly along with heads bowed and faces sorrowful. A visit was made to some houses whence plague cases had just been reported with the native editor of the principal Poona newspaper, this gentlemen having volunteered his services as plague inspector. In a small hovel, scarcely larger than a ship's cabin, one might find a patient surrounded by several of his friends awaiting the arrival of the inspector. The chances for contact contamination were manifold.

At the general plague hospital, there were some eight hundred cases of the disease under the charge of Major Windle. He was assisted by eight European nurses and a number of native helpers. He complained that it was almost impossible to retain natives as workmen ; even washermen and grave-diggers could not be employed in sufficient numbers owing to the fears and prejudices of the people. Cartloads of the newly attacked were being brought into the hospital at its entrance, while a body was carried out from the wards every ten minutes to the morgue at the rear. Those who live in the West can scarcely appreciate the enormous disadvantages under which medical men fight plague in India. The people are ignorant and superstitious, the rigid caste rules prevent any successful application of modern hygienic measures, and even the preventive inoculation cannot be utilized to any great extent, owing to the fact that thus far the bacilli have been grown in beef-broth, and the natives will not countenance such a profanation of the sacred animal. Even in death, caste rules have to be observed, and it was found at the morgue that partitions had to be put up separating the low-caste Hindoos from those of high caste, from the Mohammedans and from the Parsees and Christians. The floor of the morgue presented a melancholy sight; in one of the rooms no less than thirtytwo bodies lay upon the ground as closely packed as was possible without actually piling the bodies upon one another. Mohammedans are buried, and high-caste Hindoos are burned, but the bodies sometimes accumulate so fast that they cannot be disposed of by the usual methods. Major Windle stated thai one day, a short time before, he had burned twenty-four bodies in one heap. It is absolutely impossible in Poona to employ occidental methods in the way of segregation or disinfection. The natives prefer to die rather than submit to rules which are obnoxious to them. It is no uncommon sight to see a widow, after uttering the death wail, beating her face and breasts and throwing herself violent ly upon the body of her dead husband, kissing his face and lips ; it is very strange that no more than do contract the disease. One left Poona and


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[No. 106.


Bombay thankful that in America no such unfavorable religious and social conditions prevail.

Of the results which have been obtained by the Commission, it is too early as yet to speak more than generally. The observations made in Manila have to be supplemented and controlled by further microscopical and bacteriological studies upon the material collected. It will be some months at least before a full report can be looked for.

At present the observations concerning the causation of dysentery, the differentiation of the fevers of the region, the relative prevalence of typhoid fever and malaria, the studies of the varieties of the malarial parasite there found, and the investigations of beri beri, may be specified as among the more important scientific results of the expedition. The influence of the scientific spirit and methods, with the demonstration of their practical utility, so beneficial in medical ceutres at home and exerted at so early a period in the American regime in the Philippines, can scarcely fail to be of significance in the further development of medicine there.

It is probable that in the near future other expeditions will be undertaken as only a beginning in the study of tropical medicine has been made. England and Germany are alive to


the importance of such investigations. Major Ross has recently been sent to East Africa to continue his studies upon the part played by mosquitoes in the dissemination of malarial parasites, and Dr. Wright is being sent by the English government to establish a laboratory in the Malay peninsula for the study of beri beri. Prof. Koch, of Berlin, has also lately been sent on another expedition for the investigation of the malarial fevers in the tropics. Schools of tropical medicine are being established at various English and continental ports. The time seems ripe also for undertaking instruction in tropical diseases in America. The establishment of investigating institutes, and of teaching departments in such cities as San Francisco, New Orleans, Baltimore and New York, would be an additional safeguard to the country, since these are ports most likely to be infected. Moreover, careful instruction as regards diseases peculiar to the tropics and the special character assumed by other diseases when they occur in the hotter regions of the earth would seem to be essentials for those American physicians and surgeons who comtemplate residence or practice in our tropical possessions.

Lewellys F. Barker.


AN APPARATUS TO AID THE INTRODUCTION OF A CATHETER OR BOUGIE.

By George Walker, M. D., Ohief of Clinic out-door Surgical Department, Johns Hopkins Hospital.


The accompanying cutis an apparatus which I have devised to facilitate the passage of a filiform bougie, or catheter, through a strictured urethra. The object of this instrument, is to distend the canal, and in this way to enlarge the narrowed portion, so that an instrument will pass through.

Fig. I (a) is a glass cylinder, the shape and size as seen in the cut, with three openings; the first (J) is to communicate with the urethra; the second (p) permits the entrance of oil from cylinder (rri), Fig. Ill ; the third (d) is for the reception of a rubber stopper carrying a catheter, or bougie; (/) is a pure rubber stopper, through the center of which is passed a glass tube (g) ; on the inner end of this is fitted a small ring of rubber tubing (n). Through this glass tube a catheter (e) is passed, and the rubber on the end is so fitted that it serves to prevent an outward flow of oil.

Fig. II is a rubber stopper similar to the above, with a very small opening through it, just large enough to admit easily the passage of a filiform bougie (I) and small enough to prevent the escape of oil or other fluid.

Fig. Ill (wi) is a cylindrical glass vessel for the reception of oil ; it is to be hung on wall and is connected with Fig. I, by a rubber tube (t) of varying lengths.

A rather stiff silk catheter should be used, as a soft-rubber one has a tendency to bend in the glass cylinder. The free end of the catheter is closed with a clamp or hard-rubber stopper, so as to prevent the escape of oil.

When required for use the cylinder (d) is filled with oil by slightly opening the pinch-cock (A) ; the end (b) is then introduced into the meatus and firmly held there by an assistant so as to prevent the escape of oil between the glass and


urethra. The catheter, or bougie, is then passed into the urethra as far as the strictured part; the stop-cock (A) is now



Tig. I


Ftg.JT,


opened, and the oil allowed to flow in and distend the urethra. As this is being done the catheter, or bougie, is firmly pushed


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31


inward, and as the walls are distended the stricture is slightly opened, and the instrument allowed to slip through.



Fig. IV. — An Improved Urethral Irrigating Nozzle.

I do not say that by its use all urethra can be made permeable, but certainly filiforms can be thus introduced in a num


ber of cases which without it would be impossible, and catheters passed through diseased portions that otherwise would admit only filiform. Thanks are due Dr. Andrew Stewart, of Washington, for some suggestions.

Fig. IV represents an irrigating nozzle showing an addition to the ordinary straight nozzle in the form of a disc-shaped flange attached to the body near the urethral end. The disc serves to protect one's hands and other objects in the vicinity from becoming soiled by the fluids which are ejected from the meatus during irrigation. The straight nozzle which I have used resembles in some particulars those of Valentine and Young. The complete nozzle is made in one piece; it is simple, cleanly, small and entirely efficacious.


SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.


J. Whitridge Williams, M. D. The Frequency of Contracted Pelves in the First Thousand Women Delivered in the Obstetrical Department of the Johns Hopkins Hospital. — Obstetrics, Vol. I, Nos. 5 and 6, 1899.

1. In our material, the frequency of contracted pelves (13.1 per cent.) corresponds very closely with the general average of frequency observed in Germany.

2. This is due, in large part, to the presence of a large black population in Baltimore, 469 out of our 1,000 cases being colored women.

3. Contracted pelves are 2.77 times more frequent in black than in white women, and occur in 19.83 per cent, of the former and 7.14 per cent, of the latter.

4. The statistics of Reynolds Crossen and myself indicate that contracted pelves are observed in about 7 per cent, of the white women of this country, or about once in every fourteenth case.

5. Contracted pelves, accordingly, occur in our white women about as frequently as in many German clinics, notably, Rostock, Breslau and Basel.

6. And occur quite as frequently as in Paris (Pinard and Budin) and more frequently than in Vienna.

7. As every fourteenth white and every fifth colored woman possesses a contracted pelvis, the necessity for routine pelvimetry becomes apparent.

J. Whitridge Williams, M. D. A Case of Spondylolisthesis, with Description of the Pelvis. — American Journal of Obstetrics, Vol. XL, pp. 145-171 ; also, Transactions of the American Gynecological Society, Vol. XXIV, pp. 49-79.

In this article is described the pelvis obtained from a woman dying after a symphyseotomy performed on account of a pelvis contracted by spondylolisthesis. The smallest antero-posterior diameter of the pelvis, extending from the lower margin of the third lumbar vertebra, to the upper and posterior margin of the symphysis pubis, was 6yi cm.

The article is accompanied by numerous illustrations, which clearly illustrate the deformity, as well as its mode of production. This is the first American case which has been described anatomically, though such cases have been observed clinically by Blake, Lombard, Flint, Gibney and Lovett.

A full list of the literature on the subject accompanies the article.


J. Whitridge Williams, M. D. Report of the Committee of the American Gynecological Society, of which Dr. Williams was Chairman, "On the Value of Antistreptococcic Serum in the Treatment of Puerperal Infection." — American Journal of Obstetrics, Vol. XL, pp. 289-314 ; and Transactions of the American Gynaecological Society, Vol. XXIV, pp. 80-110.

I. A study of the literature shows that 352 cases of puerperal infection have been treated by many observers, with a mortality of 20.74 per cent.; where streptococci were positively demonstrated the mortality was 33 per cent.

II. Marmorek's claim that his antistreptococcic serum will cure streptococcic puerperal infection, does not appear to be substantiated by the results thus far reported.

III. Experimental work has cast grave doubts upon the efficiency of antistreptococcic serum in clinical work, by showing that a serum which is obtained from a given streptococcus may protect an animal from that organism, but may be absolutely inefficient against another streptococcus, and that the number of serums which may be prepared is limited only by the number of varieties of streptococci which may exist.

IV. Thus far the only definite result of Marmorek's work is the development of a method by which we can increase the virulence of certain streptococci to an almost inconceivable extent, so that one hundred-billionth of a cubic centimeter of a culture will kill a rabbit.

V. The personal experience of your committee has shown that the mortality of streptococcus endometritis, if not interfered with, is something less than 5 per cent., and that such cases tend to recover if Nature's work is not undone by too energetic local treatment.

VI. We unhesitatingly condemn curettage and total hysterectomy in streptococcus infections after a full-term delivery, and attribute a large part of the excessive mortality in the literature to the former operation.

VII. In puerperal infections a portion of the uterine lochia should be removed by Di'ulerlein's tube for bacteriological examination, and an intra-uterine douche of four to five liters of sterile salt solution given just afterward. If the infection be due to streptococci, the uterus should not be touched again, and the patient be given very large doses of strychnia and alcohol, if necessary. If the infection be due to other organisms, repeated douchings and even curettage may be advisable.

VIII. If the infection extends toward the peritoneal cavity,


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[No. 106.


and in gravely septicemic cases, Pryor's method of isolating the uterus by packing the pelvis with iodoform gauze may be of service. IX. The experience of one of the members of the committee with antistreptococcus serum has shown that it has no deleterious effect upon the patient, and therefore may be tried if desired. But we find nothing in the clinical or experimental literature or in our own experience, to indicate that its employment will materially improve the general results in the treatment of streptococcus puerperal infection.

Howard A. Kelly, M. D. A Curette for Cervical Cancer.— American Journal of Obstetrics, Vol. XL, 1899, p. 829.

The author has devised a toothed curette for the removal of redundant carcinomatous material in cases of cancer of the


cervix, which he considers much more satisfactory than any of the dull or sharp scoops now in use.

The instrument consists of a stout handle 9i cm. long, a shank 114. cm., tapering to an ovoid bowl which is 4 cm. long, 17 mm. wide, and 14 mm. deep. The essential feature of the curette is the series of crenations, each 2 mm. in height and 2\ mm. wide at the base, surmounting its blunt margin. These little teeth are very effective in removing the diseased tissue. A smaller instrument, two-thirds the size of the one described, is also used.

W. H. Welch, M. D. Thrombosis and Embolism. — Albutt' s System

of Medicine, Vol. VII, 1899. The Material Needs of Medical Education. — Journal of the

Alumni Association of the College of Physicians and Surge ni,

Vol.11, No. 4, 1900.


PROCEEDINGS OF SOCIETIES.


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY. Tuesday, December 5, 1899. Exhibition of Surgical Cases.— Dr. Mitchell.

We have to show three cases that have been treated in the service of Dr. Halsted, during the last few months, all traumatic and all having been serious accidents.

Case I. — The first man, a miner, aged 28 years, was admitted in August with the history of an injury received 32 hours previously, haying been crushed under a mass of falling coal. He was unable to walk after the accident on account of pain, though he had perfect motion of the limbs and could stand. He had retention of urine and was catheterized by a physician at the mines aud the bladder was later aspirated. The urine obtained by catheterization contained a great deal of blood, but the aspirated secretion was clear. He was operated upon immediately after his entrance to the hospital.

On examination, the patient was unable to stand, the bladder was much distended, reaching almost to the umbilicus; the perineum was infiltrated with blood. A perineal incision was made, opening a cavity beneath the symphysis pubis, which was filled with blood clots and urine ; the bladder still remained distended. A catheter passed through the meatus entered this cavity in the perineum, thus locating one end of the ruptured urethra. Suprapubic cystotomy was then done and retrograde catheterization showed the proximal end of the urethra, which had been ruptured just beneath the symphysis pubis. The urine in the bladder was perfectly clear. There was a fracture of the ascending and descending ramus of the left pubic bone, and a separation of the symphysis pubis. By attaching a piece of silk to a soft-rubber catheter, we were able to pass it through the entire course of the urethra. The urethra was not sutured because of the wide separation. A Bloodgood suprapubic tube was fixed in the bladder, and the perineal wound packed with gauze. The patient did very well. The bladder could be irrigated through the catheter and there was no trouble from infection. The catheter was allowed to stay in until September, when it was removed because blocked with salts, and a new one introduced. This was finally removed, nearly two months after the


operation, but the urethra still opened in the perineum. On October 23rd, the suprapubic tube was removed and the wound allowed to close, and from that time he has been voiding partly through the meatus and partly from the perineal wound, the latter having closed only within the last few days. The urethra has been dilated from time to time and a number 27 sound can be introduced with ease. He walks without evidence of trouble. The pubis is evidently firmly united.

Uase II. — This is a case of recovery after very great shock. The man was admitted ten days ago, about 6.30 p. m., in very bad condition and with the history of an injury to his right arm a short time before. He was working in a guano factory wheu his arm was caught in the machinery, and the forearm and hand very badly crushed. The skin of the arm was torn from the shoulder, down just as you would tear out the sleeve of a coat. His pulse was 80 aud very weak, respiration 40, temperature 97.5°, and he was crying with pain aud begging to have the arm taken off. He was immediately put to bed, the arm dressed with sterile gauze, the foot of the bed elevated and he was infused with 600 cc. of salt solution in the breast, and given i gr. morphia and a hot enema of coffee and salt solution. Up to 10 o'clock he improved, his pulse had become much stronger, he was quiet, his respiration slower and altogether he seemed better. After that time he began to go down again rapidly and there was considerable oozing from the dressings. He was in very bad condition when put on the table at 11 p. m., and though he was under ether only 10 minutes his condition became much worse during that time. He was given strychnia hypodermically and salt solution infusion during the operation. The foot of the table was elevated and his legs tightly bandaged. The operation itself lasted only 5 minutes. Dr. Bloodgood controlled the vessels by digital pressure in the axilla and the arm was amputated just below the shoulder. The vessels were quickly tied and the wound packed with gauze. At the end of this brief period, however, the radial pulse could not be felt, and the heartsounds were so weak that the second sound could not be heard after the operation. The foot of his bed was kept elevated, he was infused again with salt solution and given


January, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


33


hypodermics of strychnia and morphia with hot enemata of coffee and salt solution. His condition remained very alarming during all that night, the pulse being rapid and weak. the temperature rising to 103.6° and he became delirious, attempting to bite and scratch the assistants. Towards morning, however, he became quiet and from that time on has made a rapid convalescence. The wound was inspected a few days after the operation and everything was found clean and in good shape. His blood-count has been somewhat interesting. The night of the operation it was practically normal, although there had been a great deal of hemorrhage — red corpuscles 5,000,000, leucocytes 23,000, and hemoglobin 70 percent. Thirty-six hours later it showed reds 3,000,000, leucocytes 12,000 and hemoglobin 50 per cent.

Case III. This case has been very interesting to us in connection with the question of nerve regeneration. He is a German, 38 years of age, and was admitted on the 10th of November with an injury of the inner and posterior part of the left arm, having been in contact with a buzz-saw. He was admitted in fairly good condition and kept quiet for two hours before operation, when he was put on the table and the arm cleaned very thoroughly. No anesthetic was used and although the operation lasted two hours or more, no bad effect was produced so far as we could see. There were three main cuts with numerous lacerations extending from them. The upper cut exposed the musculospiral and ulnar nerves and divided the internal cutaneous. The second cut divided the ulnar, made a large ojjening into the bone and divided the musculospiral just where it winds around the bone, while the third cut divided the median nerve just above the elbow, without exposing the artery. The triceps muscle was extensively lacerated and the ulnar nerve was hanging in this mass of lacerated muscle which was torn entirely from the bone at one point. The biceps was also partially divided and there was extensive laceration of the skin. We identified the peripheral portion of the nerves by pinching the ends slightly and getting a corresponding contraction. The central portions could be identified by pain when they were seized. A hasty examination for anesthesia was made and it was thought to be complete, but since then we find that we were mistaken. Tbe nerves were sutured, the muscles brought together with buried silver and catgut sutures, and the skin approximated loosely over the wound. The man has made a perfect recovery and everything has healed per primam except the portions where there was no skin and these are covered by healthy blood clot. At the first dressing we found complete anesthesia of those portions supplied by the median, ulnar and musculospiral nerves. The only sensitive area was that supplied by the external cutaneous and some filaments of the musculospiral that came off above the injury.

Discussion.

Db. Thomas. — Was there any difficulty in bringing the ends of the nerves together ?

Dr. Mitchell. — They were very far apart at the time, but we had no difficulty in approximating them and suturing without tension.


Dr. Thomas.— It will be very interesting to watch his recovery and note where regeneration first takes place, since all the nerves were completely divided.

An Improved Stethoscope. Dr. Cabot. — I have with me a stethoscope that I have used on about 40 cases adav for five months and which pleases me so much that I thought it worth while to bring it before you. It was invented by a gentleman in Boston, not a physician, who had seen the ordinary stethoscope and who thought he could make an instrument that would combine the advantages of this with those of the phoueudoscope. It consists of a simple diaphragm of metal like that of the telephone connected with the chamber into which the tube of the stethoscope enters. It magnifies all sounds and it might be said to bear the same relation to the ordinary stethoscope that the high power of the microscope does to the low power. With it you can, I think, also hear sounds deeper in the chest than those heard with any other stethoscope. I have used it constantly for examination of the lungs and heart and find it exceedingly valuable for both. It enables you to hear cardiac murmurs, especially those of aortic regurgitation that can not be heard in any other way and this seems to me to be a point of great importance. The murmurs of mitral stenosis are not always, however, heard as well as with the ordinary stethoscope; that fact I can not account for.

A very obvious advantage of the instrument is that in listening to cases of pneumonia of the posterior lobes where the patient is very weak and you do not want to turn him, you can slip this flat edge under the back and hear the sounds with ease. I have known of an instance of a consultant being called from New York to Boston in such a case and feeling that he had not the right to turn the patient or raise him no examination of the lungs was made for two days. With such instrument as this such a delay could not occur.

I think also it is not an exaggeration to say that you can hear as much of the heart-sounds through the clothes with this instrument as you can with any other instrument next the skin. You should not listen to the lungs through the clothes, because the friction sounds of the clothes are so much like those of the lungs.

There are certain things that you can not do with it. If the patient has a very thin bony chest you do not get good effects, and it is not always good for very superficial sounds. I always carry the bell of the ordinary stethoscope to slip on for such cases. I don't think I should want the instrument alone without this arrangement, but I certainly should not want ever to be without this instrument again. I feel sure that any one who ever tries it will not give it up until something better is invented.

The Pulmonic Second Sound. Dr. Cabot.— About one year ago, in reading Gibson's recent work on the heart, I noticed some observations concerning the second sound in health that disturbed me a great deal. I had always been taught that in health the pulmonary second sound was not so loud as the corresponding sound from the other side. Dr. Sarah li. (,'reightou went over one thousand cases


34


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 106.


this summer in my clinic with reference to this point, throwing out all cases where there w r as anything wrong with the heart. She showed that in each decade, there is a rising percentage of aortic and a diminishing percentage of pulmonic accentuation as compared with the preceding decade. In other words, unless these one thousand cases are very deceptive, the accentuation of the aortic sound is a matter of age, the pulmonic sound being louder in the young and the aortic in older persons.

One other point that has struck me in the last two years in the examination of the normal chest is the presence in healthy persons of fine rales at the base of each axilla. If you listen in persons over 40 years of age, you will hear in a large proportion of cases these fine crepitant rales at the end of inspiration. They are heard over a very small area, frequently not larger than half the size of your palm. The explanation of this phenomenon is entirely dark to me. I thought it might be due to the formation of pleural adhesions, but I find it in connection with Litteu's phenomenon so frecpaently that I can not see how that explanation can be accepted, so that I leave the observation as a purely clinical oue without explanation.


BOOKS RECEIVED.



VOLUME TO COMMEMORATE THE 25TH YEAR OF DR. WELCH AS A TEACHER AND INVESTIGATOR.

It is customary in Germany for the pupils of a great teacher to express their appreciation and gratitude by dedicating to him a volume of their contributions to learning. The pupils of Dr. Wm. H. Welch, of Baltimore, have decided to give expression to their regard for him in a similar way and the publication of a volume to mark his twenty-fifth year as a teacher and investigator is now in progress.

During the past twenty-five years some seventy-five persons have undertaken investigation under Dr. Welch's leadership, and nearly half of these will contribute to the volume mentioned. The edition will necessarily be limited by the number of subscribers. An early announcement of the publication is made to give opportunity for subscription so that the committee can decide upon the number of copies to be printed.

The volume will be royal octavo in size and will contain at least five hundred pages of printed matter. It will, in addition, be illustrated with many lithographic plates and text figures. The price has been fixed at five dollars. The book will contain contributions to pathology and to correlated sciences agreeing in scope with that of the leading scientific medical journals.

The Committee of publication consists of :

A. C. Abbott, University of Pennsylvania, Philadelphia, Pa.

L. F. Barker, Johns Hopkins University, Baltimore, Md.

Wm. T. Councilman, Harvard University, Boston, Mass.

Simon Flexner, University of Pennsylvania, Philadelphia, Pa.

W. S. Halsted, Johns Hopkins University, Baltimore, Md.

A. C. Herter, University and Bellevue Hospital Medical College, New York.

Wyatt Johnston, McGill University, Montreal, Canada.

F. P. Mall, Johns Hopkins University, Baltimore, Md.

Walter Reed, Army Medical Museum, Washington, D. C.

Geo. M. Sternberg, Surgeon General's Office, Washington, D. C.

All communications and subscriptions should be addressed to Dr. F. P. Mall (Secretary), Johns Hopkins University, Baltimore, Md.

Baltimore, November 11, 1899.

MONOGRAPHS.

The following papers are reprinted from Vols. I, IV, V, VI and VIII of the Reports, for those who desire to purchase in this form:

STUDIES IN DERMATOLOGY. By T. C. Gilchrist, M. D., and Emmet Rixford, M. D. 1 volume of 164 pages and 41 fullpage plates. Price, bound in paper, $3.00.

THE MALARIAL FEVERS OF BALTIMORE. By W. S. Thayer, M. D., and J. Hewetson, M. D. And A STUDY OF SOME FATAL CASES OF MALARIA. By Lewellys F. Baker, M. B. 1 volume of 280 pages. Price, in paper, $2.75.

STUDIES IN TYPHOID FEVER. By William Osler, M. D., and others. Extracted from Vols. IV and V of the Johns Hopkins Hospital Reports. 1 volume of 481 pages. Price, bound in paper, $3.00.

THE PATHOLOGY OF TOXA.LBUMIN INTOXICATIONS. By Simon Flexner, M. D Volume of 150 pages with 4 full-page lithographs. Price, bound in paper, $200.

THE RESULTS OF OPERATIONS FOR THE CURE OF INGUINAL HERNIA. By Joseph C. Bloodgood, M. D. Price, in paper, $3.00.

Subscriptions for the above publications may be sent to

The Johns Hopkins Press, Baltimore, Md.

HOSPITAL PLANS.

Five essays relating to the construction, organization and management of Hospitals, contributed by their authors for the use of The Johns Hopkins Hospital.

These essays were written by Drs. John S. Billings, of the U. S. Army, Norton Folsom, of Boston, Joseph Jones of New Orleans, Caspar Morris, of Philadelphia, and Stephen Smith, of New York. They were originally published in 1875. One volume bound in cloth, price $5.00.


January, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


35


THE JOHNS HOPKINS MEDICAL SCHOOL.


FACULTY.


Danibl C. Oilman, LL. D., President.

William H. Welch, M. D., LL. U , Professor of Pathology. Ira Kh.sisEN, M. D., Ph. D , LL. D.. Professor of Chemistry. WILLIAM Oslbr, M. D., LL. D., F. R. C. P., Professor of the F

.Medicine, and Dean of the Medical Faculty. Hknrv M. Hi'KD, M. H., LL. D., Professor of Psychiatry. William S. Halsteo. M. D., Professor of Surgery. Howaki> A. Kbllv, M. D., Professor of Gynecology. Franklin P. Mall, M D.. Professor of Anatomy. John J. Abel, M. D-, Professor of Pharmacology. William H. Howell, Ph. D., M. D., Professor of Physiology.


Thomas B. Futchi Joseph C. Bl


iples and Practice of


R, M. B., Ass

ioi>, M. V., A

n, M. B., Assoi

N, Ph. D., Assc

.. _,Ph. L>., M. D., Assc JohnG. Clark, M.L)., A


Ross


ASS. CUL


Willia.i K Bkooks, Ph. D., LL. D J. Whiiruigb Williams, M. D., Pro'fes: John- S. Killings, M. D., LL D., Lectu Albxanubk C. Abbot., M. D., Lecturer Chakles Wari Rolbkt Flbtc


of Comparative Anatomy and Zobloev of Obstetrics. B>

on the History and Literature of Medicine Hygiene. Ph. D., M. S . Lecturer on Medical Zoology. , M li , M. R. C. S. (Eng.). Lecturer on Forensic Medu


I.RI



vs F. Bar


Wi


LLIAl


1 S. Tha'


lot


-. M


. T. Finn


(Ski



P. Drbvi


Wi



■ W. Rus


Ko


ISB 1


L. Rand.


. M. D., Clinical Professor of Pediatrics

kbnzie, M U., Clinical Professor of Laryngology and Rhinology.

jbald, M. D . Clinical Professor of Ophthalmology and Otology. HOMAS. M. D., Clinical Professor of Neurology.

Lord, M- D , Clinical Professor of Dermatology and Instructor in Anatomy. ilchrist, M. R C. S., London, Clinical Professor of Dermatology. rklby, M D., Clinical Professor of Psychiatry.

r, M. B , Associate Professor of Pathology.

, M D., Associate Professor of Medicine.

i\l. D., Associate Professor of Surgery.

Ph. D , Associate in Physiology.

l, M. Ii, Associate in Gynecology.

•H, M. D.. Associate in Ophthalmology and Otology.


iatein Medicine,

iociate in Surgery, ate in Gynecology.

iate in Pharmacology. — jn Gynecology. Charles R. Bardbbn, M. D., Associate in Anatomy. Harvey W. Lushing, M. D., Associate in Surgery. George W. Dobbin, M. D., Associate in Obstetrics.

Walter Jones, Ph. D., Associate in Physiological Chemistry and Toxicology Frank R. Smith, M. D., Instructor in Medicine. Hbnrv B. Jacobs. M. D., Instructor in Medicine. Hugh H. Young, M. D , Instructor in Genito-Urinary Diseases Otto G. Ramsav, M.D., Instructor in Gynecology. Thomas McCrae, M. B., Instructor in Medicine Albert C. Crawford, M. D., Assistant in Pharmacology Sidney M. Cone. M. D., Assistant in Surgical Pathology. Norman MacL. Harris, M. B., Assistant in Bacteriology. Jesse W. Lazear, M. D., Assistant in Clinical Microscopy. Stewart Paton, M. D., Assistant in Clinical Neurology.


Lee W


Hi


Percy M. D..

Louis P. H»> Melv.n T. Si Norman B. G


Ph. G.. eth Hukdon, M. D., Assis O. Reik, M. D., Assistant m G MacCallum, M. D. hology.


n, M. D., Ass

GER, M. D., (

r, Ph. D., As. , M. B.. Demi


ant in Gynecology.

n Ophthalmology and Otology.

Assistant in Pathology and Curator of the Mu


1 Clinical Microscopy.


GENERAL STATEMENT.


The Medical Department of the Johns Hopkins University was opened for the instruction of students October, 1893. This School of iMedicine is an integral and coordinate part of the Johns Hopkins University, and it also derives great advantages from its close affiliation with the Johns Hopkins Hospital. The required period of study for the degree of Doctor of Medicine is four years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter. Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and in the Dispensary and Wards of the Hospital While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in the Laboratories of Anatomy, Physiology Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and' Dispensary and in the Clinical Laboratories. Especially advantageous for thorough clinical training are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and surgical dressers in the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Medicine the school receives:

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

2. Graduates of approved colleges or scientific schools who can furnish evidence : (a) That they have acquaintance with Latin and a good reading knowledge of French and German; (b) That they have such knowledge of physics, chemistry, and biology as is imparted by the regular minor courses given in these subjects in this university.

The phrase "a minor course," as here employed, means a course that requires a year for its completion. In physics, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room exercises and five hours a week in the laboratory in each subject.

3. Those who give evidence by examination that they possess the general education implied by a degree in arts or in science from an approved college or scientific school, and the knowledge of French, German, Latin, physics, chemistry, and biology above indicated.

Applicants for admission will receive blanks to be filled out relating to their previous courses of study.

They are required to furnish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry and biology. If such certificates are satisfactory, no examination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass at the beginning of the session in October, the matriculation examination for admission to the collegiate department of the Johns Hopkins University (2) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B. degree in this University, and (3) to furnish satisfactory certificates that they have had the requisite laboratory training as specified above. It is expected that only in very rare instances will applicants who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO ADVANCED STANDING.

Applicants for admission to advanced standing must furnish evidence (1) that the foregoing terms of admission as regards preliminary training have been fulfilled (2) that courses equivalent In kind and amount to those given here, preceding that year of the course for admission to which application Is made have been satisfactorily 1 completed, and |3i must pass examinations at the beginning of the session in October In all the subjects that have been already puraued by the class to which admission Is sought. Certificates of standing elsewhere cannot be accepted in place of these examinations.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

Since the opening of the Johns Hopkins Hospital in 1889, courses of instruction have been offered to graduates In medicine. The attendance upon these courses has steadily Increased with each succeeding year and indicates gratifying appreciatl >u of the special advantages here afforded, with the completed organization of the Medical School, it was found ueceesary to give the courses Intended especially for physicians at a later period of the academic year than that hitherto seleoted It Is however, believed that the period now chosen for this purpose is more convenient tor the majority of those desiring to take the courses than tho former one The special cour.es of Instruction for graduates in medicine are now given annually during the months of May and June. During April there Is a preliminary course In Normal ■ — s are In Pathology. Bacteriology. Clinical Mlcl Medicine. Surgery, Gynecology. Dermatology. Diseases of Children Diseases of the

Nervous System, Genlto-Urlnary Diseases, Laryngology and Rhinology, and Ophthalne logy and Otology. T he instruction is Intended to meet tho requirements of practitioners of medicine, and Is almost wholly of a practical character. It Includes laboratory courses, demonstrations, bedside teaching, and clinical Instruction In the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses are open to those who have taken a medical degree and who give evidence satisfactory to the several Instructors that they are prepared to profit by the opportunities here offered. The number of students who can be accommodated In some of the practical- , . irUy limited. For these the places an ' i ng to the date of application.

During October a select number of physicians will be admitted to a special clas-» for the study of the important tropical diseases mot with In this region. The Annual Announcement and Catalogue will be sent upon application. Inquiries should be addressed to the

REGISTRAR OF THE JOHNS HOPKINS MEDICAL SCHOOL, BALTIMORE.


36


JOHNS HOPKINS I OSPITAL BULLETIN.


[No. 106.


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report In Pathology.

The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction; ^ HeaUng of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By F. P. Mall, M. U. a Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Berkley, M. D. „.. ,. „„ „ „

Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, M. D.

Report in Dermatology. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T C Gilchrist, M. D., and Emmet Riiford, M. D. A Case of BhXmycetic Dermatitis in Man; Comparisons of the Two Varieties of

P?otozoa7lnd the Blastomyces found in the preceding Case, with the so-called

Sites found in Various Lesions of the Skin etc.; Two Cases of Molluscurn

Fibrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhnng). By

T. C. Gilchrist, M. D.

Report In Pathology. An Experimental Study of the Thyroid Gland of Dogs with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, M. D.

Volume II. 570 pages, with 28 plates and figures.

Report in Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks C n Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin. By H. A. Lafleur, M. D. Cases of Postfebrile Insanity. By William Obler, M. D. A^te Tuberculosis in an Infant of Four Months. By Harry Toulmin, M. D. Rare Forms of Cardiac Thrombi. By William Osler. M. . D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in Medicine. Tubercular Peritonitis. By William Osler, M. D. A Case of Raynaud's Disease. By H. M. Thomas, M. D. Acute Nephritis in Typhoid Fever. By William Osler, M. D. Report in Gynecology.

The KSS X-o fXZoXZTU; «chV-1890. By Howard The1ie^t L ;^he D Auto^i H Jfn E Tw R o C B ase i U D yin g in the Gynecological Wards without Operation ; Composite Temperature and Pulse Charts of Forty Cases of Abdominal Section. By Howard A. Kelly, M. D. ne Management of the Drainage Tube in Abdominal Section. By Hunter Robs,

TheGonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 16, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. n „_.„„

Report of the Urinary Examination of Ninety-one Gynecological Cases. By Howabd

A. Kelly, M. D., and Albert A. Ghriskby, M. D. Lhrature of the Trunks of the Uterine and Ovarian Arteries as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D.

Myxo-Sarcoma of the Clitoris. By Hunter Robb, M. D. „,„.„.

Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report in Snrgery, I. The Treatment of Wounds with Especial Reference to the Value of the Blood Clot

in the Management of Dead Spaces. By W. S. Halsted, M. D. Report in Neurology, I. A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D.

Haematomyelia. By AU0U6T Hoch, M. D. ... , iV o_t i r, • ».

A Case of Cerebrospinal SyphiliB, with an unusual LeBion in the Spinal Cord. By

Henry M. Thomas, M. D.

Report in Pathology, I. Amosbic Dysentery. By William T. Councilman, M. D., and Henri A. Lafleob, M. D.

Volume III. 766 pages, with 69 plates and figures.

Report in Pathology.

Papillomatous Tumors of the Ovary. By J. Whitriooe Williams, M. D.

Tuberculosis of the Female Generative Organs. By J. Whitridoe Williams, M. D. Report in Pathology.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Fleiner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugata Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele- Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diag nosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A Kelly, M. D. . . , . . .. ___ . _ -.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mary Sherwood, M. D.

Intestinal Worms as a Complication in Abdominal Surgery. By A. L. Stavely, M. p

Gynecological Operations not involving Coeliotomy. By Howard A. Kelly, M. 1>. Tabulated by A. L. Stavely, M. D.


The Employment of an Artiflcial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina with Haematokolpos and Haematometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anaesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howarr A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5. 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.

Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.

By William Osler, M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetson, M. D.

Report in Neurology. Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of Mut mtuctdus; The Intrinsic NerveB of the Thyroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley, M. D.

Report in Surgery. The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology. Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. Cullen, M. B. Report in Pathology. Deciduoma Malignum. By J. Whitribge Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thayer. M. D., and J. Hewetson, M. D. A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Blumer, M. D., Simon Fleiner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.


Volume VI. 414 pages, with 79 plates and figures.

Report in Neurology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory.— Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part i. — Alcohol Poisoning. — Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol); Part II. — Serum Poisoning.— Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part III.— Ricin Poisoning.— Experimental Lesions Induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia.— Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V.— Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Pathology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S. Cullen, M. B.

Pregnancy in a Rudimentary Uterine Horn. Rupture. Death. Probable Migration of Ovum and Spermatozoa. By Thomas S. Cullen, M. B., and G. L. Wilkins. M. D.

Adeno-Myoma Uteri DirTusum Benignum. By Thomas S. Cullen, M. B.

A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By William D. Booker, M. D.

The Pathology of Toxalbumin Intoxications. By Simon Fleiner, M. D.

Volume VII. 537 pages with illustrations. (Now ready.)

I. A Critical Review of Seventeen Hundred Cases of Abdominal Section from the standpoint of Intraperitoneal Drainage. By .1. <■. (lark. M. 1>. II. The Etiology and Structure of true Vaginal Cysts. By James Ernest Stokes, M. U. III. A Review of the Pathology of Superficial Burns, with a Contribution to our Knowlr.lj the Pathological changes in the organs in cases of rapidly fatal burns. By

CUARLES RUSSELL RARDEEN, M. D.

IV. The Origin, Growth and Fate of the Corpus Lutemn. By .1. G. Clark, M. D. V The Results of Operations for the Cure of Inguinal Hernia. By Joseph C. Blood,M.D.

Volume VIII. About 500 pages with illustrations. (In

press.)

Studies in Typhoid Fever.

By William Oslkr. M. I>.. with additional yaper! M.D., I. P. Lyon. M. D„ L.P. Rambir Mitchell. M.D.

Tltc price of a set bound hi cloth [Vols. I-1'II] of the Hospital Beports is $35.00. Vols. I. II noil III ore not sold separately. Tin- price of Vols. IV, V, VI noil VII is $3.00 end,.

Subscriptions for the above publications may be sent to


The Johns Hopkins Press, Balti;


Md.


The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured from Messrs. CUSH1NQ & CO. and the BALTIMORE NEWS COMPANY. Baltimore. Subscriptions, $1.00 a year, may be addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE; single copies will be sent by mail for fifteen cents each.


BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. Xl.-No. 107.1


BALTIMORE, FEBRUARY, 1900.


[Price, 15 Cents.


C01TTEliJ"TS.


Report upon an Expedition Sent by the Johns Hopkins University to Investigate the Prevalent Diseases in the Philippines. By Simon Flexner, M. D., and Lewellys F. Barker, M.B., - - - - 37

A Case of Multiple Gangrene in Malarial Fever. By William Osler, M. D., ----- - 41

Benjamin Jesty : A Pre-Jennerian Vaccinator. By Thomas McCrae, M. B., - 42


Haemophilia in the Negro- By Walter R. Steiner,

Summaries or Titles of Papers by Members of th

and Medical School Staff appearing Elsewh

Bulletin, ------------ Proceedings of Societies :

Hospital Medical Society,

Exhibition of Medical Cases [Dr. Futcher].|

Notes on New Books,



REPORT UPON AN EXPEDITION SENT BY THE JOHNS HOPKINS UNIVERSITY TO INVESTIGATE THE PREVALENT DISEASES IN THE PHILIPPINES.


To President Gilman, Doctors Welch and Osler,

Philippine Committee of the Johns Hopkins University Medical School.

Gentlemen : — We have the honor to submit to you a brief account of our work and movements in carrying out your commission to study the prevalent diseases in the Philippine Archipelago. Your commissioners, consisting of Dr. Simon Flexner and Dr. L. F. Barker, to whom were voluntarily attached Messrs. J. M. Flint and F. P. Gay, of the Medical School, the latter having given their time and paid all their own expenses, sailed from Vancouver on March 29th, 1899, and arrived in Manila, May 4th, where they immediately established themselves for the purpose of the work mentioned. Owing to the military situation it was found impracticable to visit other ports in the Archipelago or to penetrate into the interior of the Island of Luzon. The entire time of the commission, therefore, was spent in the study of disease existing among the natives and American troops in Manila and at Cavite.

Work in Japan and Hong-Kong.

As transport sailings were uncertain, and the passage out by them slow, it was decided to save time and go by fast steamer, the Canadian Pacific Railway giving special rates to the commission on tickets around the world.

The original plan of your commissioners was to proceed directly to Manila by way of Hong-Kong, at which latter port


it was intended to stop only long enough to outfit for the tropics and to catch the earliest steamer sailing for Manila. After consideration of the probability that certain new kinds or phases of disease, not occurring in temperate regions, might be encountered in the Archipelago, and of the fact that the diseases of the Philippines would probably have much in common with those of Japan, it was decided to spend one week in Japan, where modern hospitals could be visited and advantage taken of the results of the study of tropical disease by highly trained and eminent Japanese physicians. The decision proved to be valuable in many ways ; and we especially desire to express our obligations to Professors Aoyama, Mitsukuri, Miura and Kitasato, who showed us many courtesies. The opportunity to see in the Japanese hospitals pure and mixed examples of beri-beri assisted us greatly in our subsequent studies, as did also the observations on dysentery made in the Institute for Infectious Diseases at Tokio.

While outfitting at Hong-Kong we improved the opportunity to study the bubonic plague, which was still prevailing at that port. This study was made easy by tin.' generosity and courtesy of the English Civil Physician, Dr. James Lowson, in charge of the Plague Hospital and Mortuary. The study, begun in this way, was extended when two months later we returned to Hong-Kong, en route to America. At this time a considerable exacerbation of the disease had taken place, and within a week or ten days we saw several scores of cases and performed many


38


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 107


autopsies. The several forms of infection : inguinal, axillary, tonsilar, cervical and pulmonary, were thus encountered. Bacteriological examinations were made and tissues collected for future study. Two of the party (Dr. Barker and Mr. Flint) spent ou the return journey three weeks (at their own expense) in India, where the great epidemics of plague there raging were observed.

Arrival in Manila.

Immediately upon our arrival in Manila, quarters were sought at the " Hotel de Oriente." Very insufficient accommodations were secured for a limited time, as the sudden accession of families of Army and Naval officers had strained the hotel to its fullest capacity. Having been forewarned of the conditions of living in Manila, we took the precaution to bring with us from Hong-Kong a group of Chinese servants, intending to set up housekeeping if practicable. After much difficulty a small house was secured in San Miguel, where, by hiring parts of the furnishings and buying what could not be rented, a temporary establishment was secured.

Within a few hours after our arrival, the credentials and private letters brought were presented to Colonel Woodhull, Surgeon-in-Chief to the 8th Army Corps, and to General Otis. Colonel Woodhull afforded us every opportunity to prosecute our work in the military hospitals. Although no special introduction was in our possession, we quickly met Dr. Bournes, chief health officer of Manila, who opened to us the hospitals under his charge. Somewhat later we met Dr. Pearson, Chief Naval Surgeon, who opened to us the Naval Hospital at Cavite.

Hospitals in Manila.

Civil Hospitals. These consist of a large hospital within the walled city, San Juan de Dios. It has a capacity of from 250 to 300 beds, and accommodated, during our stay, both natives and Europeans. The number of European patients was small. When the military hospitals were much crowded a certain number of wounded prisoners of war were accommodated. The hospital contained chiefly native medical cases of both sexes. The San Lazaro or leper hospital, in the outskirts of Manila, contained from 80 to 100 lepers during our stay. These had come from Luzon, almost exclusively from Manila and its immediate surroundings. The two sexes are provided for in separate, large and airy wards. One wing of the building, having a private entrance, is devoted to native prostitutes who apply regularly for examination, and are incarcerated here and treated medically when found to be suffering from venereal disease.

Military Hospitals. These consisted, besides the regimental hospitals which were virtually detention camps, of three Eeserve Hospitals — the 1st, 2nd and 3rd Reserve Hospitals; a convalescent hospital on Corregidor Island and the Hospital Ship Relief, which was anchored in the bay. The First Eeserve Hospital, under the control of Major Crosby, had been originally the Spanish military hospital. It has been from time to time, by the erection of tents over platforms raised a foot or two from the ground, increased in capacity until in July it contained 1200 or more beds. The Second Reserve Hospital, under the control of Major Keefer, was a transformed


modern school- building, and because of its limited capacity (250 beds), high ceilings and wide corridors it made a model hospital. The Third Reserve Hospital had just been established towards the end of our visit, and was smaller than the others and intended as a convalescent hospital. The hospital at Corregidor is a temporary structure and intended for convalescents. It is especially well adapted for its purpose because of the high and hilly character of the island and its complete investment by the sea. The Relief was used as a hospital for acute cases ; but some time before we left, the acute cases were transferred to the Reserve Hospitals, and the Relief sailed for San Francisco with invalided men.

The Reserve Hospitals accommodated especially American sick and wounded ; but a ward in the First Reserve Hospital was set aside for the Filipino wounded.

After the outbreak of beri-beri at Cavite, a hospital under military control was established at San Roque in the remains of the Spanish Marine Hospital which had been wrecked by the insurgents.

Naval Hospital. A small hospital for sick seamen and marines was established at Cavite. Through the courtesy of Dr. Pearson this was open to us for clinical studies.

Clinical, Pathological and Bacteriological Laboratory. Through the kindness of Colonel Woodhull and of Major Crosby, the officer-in-chief of the First Reserve Hospital, a small Filipino house, situated on the banks of the Pasig, was given us in which to establish a laboratory. This was done on the second floor of the house. The expense of putting up workingtables was kindly borne by the Medical Corps of the Army. The laboratory equipment was set up in this building, and within a very few days after our arrival work was begun. We desire to speak of the co-operation of the Medical Staff of the hospital who afforded us every opportunity to visit the wards, and many of whom joined or assisted us in clinical and pathological work. We wish especially to acknowledge the co-operation and assistance of Lieut. Richard P. Strong, a graduate of the Johns Hopkins University Medical School, who had on our arrival already begun to do laboratory work and who gave up much of his valuable time in furthering our interests. It was found unnecessary to establish laboratories in the other hospitals, in the first place, because all were connected with the First Reserve by the Signal Service telegraphic system of which we had free use; and next, because all the dead were carried to the morgue in conjunction with the First Reserve Hospital. We went or were frequently called to the other hospitals to make clinical and bacteriological examinations.

With few exceptions, all the dead were subject to autopsy. Post-mortem examinations were made at the Civil Hospitals upon natives, and at the Military Hospital upon all that died. Exceptions were made only in the cases of those dead from gun-shot wounds, when, if pressed for time, necropsies were sometimes omitted.

Prevailing Diseases.

The subject of the prevalent diseases may be considered as they affect (1) the natives, and (2) Europeans and Americans, especially the American garrison.


February, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


39


Diseases affecting Natives, (a) Skin Diseases. Of the skin diseases prevailing among the natives, aside from small-pox and other specific exanthemata, may be mentioned (1 ) of the scalp, which are very frequent; (2) dhobie itch; and (3) an affection which resembles closely, and which is probably identical with, Aleppo boil (Delhi boil, Biskra button, epidemisehe Beulenkrankheif). (b) Small-pox. This disease has been so generally prevalent in Luzon that the natives have, to a large extent, lost fear of it. All evidence points to the greatest carelessness in preventing its spread during Spanish times. Isolation of the sick and disinfection of the habitations seem not to have been attempted; and vaccination, even among the Spanish garrison, had not been carried out. Under these circumstances it could be no surprise that after the American occupation the disease should appear and even become epidemic. The epidemic which appeared early last year was promptly met by Dr. Bournes, who caused the Spanish garrison still in Manila, and natives and Chinese within the city to be vaccinated. In order to insure satisfactory results he found it necessary tore-establish a vaccine farm in which young caraiao were used for the preparation of the virus. Under the influence of this measure and by the aid of isolation of the sick, the disease had, in May, practically disappeared within the military liues about Manila, (c) Leprosy. A definite focus of this disease exists in Luzon. The cases, in the neighborhood of 100, which are confined in the San Lazaro Hospital, came from Manila and the country immediately surrounding that city. The disease affected both sexes, being more frequent in adults, although also present in half-grown boys and girls. The commonest forms were the tubercular and mutilating. Autopsies were performed upon several cases that had died during our stay, (d) Ttiberculosis. Accurate statistics of the extent of the prevalence of this disease are difficult if not impossible to obtain. That the disease is a common one is indicated by several facts. It is frequently met with in the native hospitals, where it may have been recognized duriug life or is disclosed at autopsy. Many cases of supposed beriberi which we autopsied at San Juan de Dios proved to be tuberculosis. It is possible that the two diseases had co existed, for we found such combinations freely recognized by •Tapanese physicians in the hospitals in Japan. Tuberculosis of the lungs was also found as a common complication in leprous individuals that came to autopsy. Not very infrequent spectacles met with on the streets are much emaciated and weak natives affected with suggestive coughs and free expectoration. While it is not certain that these individuals were examples of tuberculosis, there is strong probability that this explanation of their condition is the correct one. (e) il Diseases. Syphilis, by general agreement (statistics not available), does not prevail unduly. Chancroids and gonorrhoea are, on the other hand, very common. The majority of the prostitutes confined in the San Lazaro were victims of these two diseases. A very common complication of the soft sore, owing to lack of cleanliness, is swelling and suppuration of the inguinal glands, (f) Beri-Beri. This disease is well known among the natives. It would appear to be epidemic and endemic in Luzon. It is, judging from cases met with in San Juan de Dios Hospital and the statements of native phys


icians, constantly appearing in a sporadic form. During our stay an epidemic appeared among the Filipino prisoners confined at Cavite. Some 200 cases developed in a few weeks ; the mortality ranged from 20 to 30 per cent. The several recognized forms of the disease— cedematous, paralytic, and mixed — were encountered. Clinical and bacteriological studies were made upon the living, and the dead were subjected to autopsy and bacteriological examination. The difficulty of getting to and fro between Manila and Cavite, on account of the impossibility of land communication, made this part of our work difficult and time-consuming. A considerable collection of pathological material and other data has been made. This material is now in process of study and arrangement.

Diseases affecting Americans. The chief causes of disability among American land forces are the enteric diseases. These are diarrhoea, dysentery, typhoid fever, and gastro-intestinal catarrhs. Many of the diarrhoeas are merely preliminary to the symptoms of dysentery. Other infectious fevers are relatively infrequent. A small number of cases of scarlet fever and diphtheria only were encountered. The malarial fevers prevailed but not seriously during the months of .May, June and July, (a) Dysentery. This disease is responsible for the greatest amount of invalidation and the highest mortality. It appears in acute, sub-acute, and chronic forms. The chronic form is sometimes attended by secondary abscess of the liver. The acute form may end in 24, 48, or 72 hours. In it the whole of the large intestine and usually the lower portion of the ileum are involved. The mucous membrane of the gut is swollen, congested and cedematous, in places hemorrhages have taken place into the mucous membrane, and the submucosa is swollen and its blood-vessels greatly dilated. No ulcers existed in such cases. Amoebae were absent or very difficult to find in the fresh stools and in the intestinal contents immediately after death. In the sub. acute and chronic forms ulcers are present in the mucosa; the coats of the intestine are greatly thickened ; at times large sloughs of mucous membrane, partly detached, occur, and t lie lesions are confined to the large intestine. Amoebae are more commonly present in these cases, but are variable as to actual occurrence and numbers. Large hepatic abscesses, usually single, were encountered in a number of these cases. Amoebae were variable in the contents of the abscesses. In one very large abscess, occupying both right and left lobes of the liver, no amoebae were seen, but a pure culture of the Staphylococcus pyogenes citreus was obtained. The clinical studj of the cases of dysentery with reference to amoebae was equally unsatisfactory. In cases with marked symptoms both in patients confined to bed and those beginning to go about but still with persistently loose bowels, these organisms were frequently missed : while in instances ready to be discharged, they might, at certain examinations, be found to be very abundant. In morphology, the amoebae studied corresponded with the amoebae coli found in Egypt and in this country. The bacteriological study of cases of dysentery was carried out upon the fresh stools of acute and chronic cases, and with the intestinal contents, mesenteric

glands, liver, etc., of can dyi i subjected to autopsy.

The intestinal flora was studied in its entirety by means of plate cultures. Varieties of micro-organisms were separated.


40


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 107.


Many of these were well-known species or occurred normally in the situations in which found. Tests with blood sera for agglutination were made, and those organisms giving positive reactions were separated for further study. Two groups of bacilli were thus differentiated : (1) Having affinities with the group of bacillus coli communis. The agglutination was variable, being constant and sensitive with the blood-serum of the same individual (host), and inconstant, and active in relatively strong solutions only, in serums from other individuals. (2) Having affinities with the group of bacilli of which the bacillus typhosus is the type. Agglutination was constant and sensitive with blood-serum of host as well as the sera of other individuals suffering from dysentery. Inactive with normal serum and serum from cases of typhoid fever, malaria and beriberi. A bacillus belonging to the second group, which is still under study, would seem to agree with the bacillus dysenteriae isolated by Shiga from cases of endemic dysentery occurring in Japan. It is regarded by us as an important factor in the causation of the dysentery of the Philippine Islands. Experiments in immunization of animals and the production of vaccine are in progress, (b) Typhoid Fever. The total number of cases of typhoid fever in the hospitals during May, June and July was far below that of dysentery ; the number of deaths also was less. It was, however, a frequent affection among Americans. The examination of the blood, microscopically and with the Widal test, was of the greatest help in diagnosis. The disease came to autopsy presenting the classical intestinal lesions and also in atypical forms. In the small number of autopsies made upon those dead of this disease, several instances of slight intestinal involvement or even entire escape were met with. These cases would have remained very obscure or even undetermined except for the Widal reaction and bacteriological examination. In some instances the typhoid bacillus was found widely disseminated throughout the body, the autopsy being made immediately after death, (c) Malarial Fevers. A large proportion of the cases were sent in from the field and outlying military stations where examinations had to be hastily made, as instances of " malaria " or " intermittent fever " turned out to be cases of other diseases (typhoid fever, dysentery, etc.). A number of true cases of malarial fever were, however, met with, and in the blood of these the characteristic parasites, identical with those occurring in other places in which studies of the blood have been made, were found. No quartan parasites were met with, but cases of quartan affection doubtless exist. Typical infections with the " tertian " and "aestivo-antumnal " varieties of the parasite were encountered by us, and by microscopists among the Army physicians in the Reserve Hospitals and on the Relief. One of the fatal cases of malaria was complicated with acute lobar pneumonia. The cases of " calentura perniciosa" which occur in Mindoro, Mindanao and in certain parts of Luzon should be studied as soon as these regions are accessible. The Archipelago is favorable also for the study of the relation of mosquitoes and other insects to malarial infection. Some of the malarial cases were undoubtedly recidives, imported from Cuba or elsewhere. A very small number of deaths were referable to malaria. Two instances of acute malarial infection came to us for autopsy.


On the other hand, several instances of malarial pigmentations of the organs, in persons dying from other diseases, were encountered. Parasites in the latter cases were absent. These men had, as a rule, been in Cuba or Porto Rico during the Spanish war.

(d) Tuberculosis. A number of cases of pulmonary tuberculosis developed among the soldiers in the American troops. A definite history of exposure to wet and various hardships was elicitable iu many of these cases.

(e) Dengue. At Cavite there occurred a large outbreak of an epidemic fever of short duration (a few days), known locally as Cavite fever. Almost all who remained in Cavite for any length of time were attacked. Second and third attacks were common. Muscular pains were severe in some cases and not in others. A slight exanthem was present in many of the cases. Flushing of the face, restlessness and general malaise accompanied the fever and rapid heart action. Malarial parasites were not present in the blood, nor did the serum from such cases agglutinate cultures of the typhoid bacillus. The epidemic is regarded as one of Dengue.

(f) Tropical Ulcers. A number of the American soldiers suffered from a form of indolent ulceration, locally known as " tropical ulcer." These ulcers occurred singly sometimes, but were more often multiple. They began as small pustules, which gradually extended. They were most frequent among those who had been compelled to make long marches through swampy districts, and the patients themselves attributed the ulceration to " poisoning " in the marshes.

(g) Wound Infection. Our experience with wound infections was rather limited. The other problems undertaken, regarded as more important as bearing on the general question of disease and its causation in the Islands, left but little time and opportunity to attack this interesting subject. Certain observations of interest were made. Pyogenic infections due to the common pus cocci occurred. In a small number of gun-shot wounds causing compound fractures emphysematous gaugrene occurred and the bacillus aerogenes capsulatus was isolated. In oue instance of compound fracture of the tibia, a spore-bearing bacillus was associated with the bacillus aerogenes capsulatus. It was found in cover-slip preparations from the original wound and in the first set of cultures. It could not be further transplanted and hence was not identified. In two other cases was the bacillus aerogenes met with, one a case of jDeritonitis following infection of the intestine from an incarcerated hernia, and the other also a case of peritonitis but secondary to perforation of a typhoid ulcer of the intestine. The army surgeons were enthusiastic as to the adequacy of the "First-Aid Package" in limiting the number of wound infections.

Clihatological and Hygienic Conditions. The climate is that of continual summer. There is a wet season (S. W. Monsoon) and a dry season (N. E. Monsoon). The hottest period is at the end of the dry aud the beginning of the wet season — precisely the period of our visit. The climate from November to March is said to be delightful. In the worst season of the year the climate is very trying, and especial precautions are to be taken if Americans are to keep


Fig. 3. \ Fn

To illustrate Dr. Osier's Ca -i Mu" ' gangrene in Malarial Fever


February, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


41


well there. The extremes of temperature are not great, but the constancy of the high temperature, together with a high degree of humidity, makes the climate peculiarly enervating. We were interviewed at length while in Manila, officially by the l". S. Philippine Commission, with regard to climate and the hygieuic precautions to be observed, as well as with regard to other medical problems in the Islands. The climatic conditions and the hygienic precautions to be taken will form the subject of a fuller report to be made later.

The above represents, briefly stated, the results achieved by your expedition sent to the Philippines. As will be patent to you. Dot a little yet remains to be done before the scientific portion of the work is completed. This portion of the report is for the present only hinted at or withheld until it shall have been finished. It is the intention of your commissioners to make careful studies of the material relating to beri-beri, dysentery, malarial and typhoid fevers, leprosy, and the bubonic plague, which has been collected. These studies, with the exception of that relating to dysentery, will be carried out upon preserved material, and the labor involved, which has been divided between Baltimore and Philadelphia, will necessitate that some time must elapse before the finished report is forthcoming. The task of completing the study of the bacillus isolated from cases of dysentery has been assigned


to Dr. Flexner, who was principally engaged with that- theme during the residence in Manila. In order to carry out the experiments as designed, an outlay for experimental animals and their maintenance will need to be made. It is known to you that the original sum so generously contributed by friends of the University and appropriated for the use of your commission, has been exhausted, and that private means have been drawn upon to defray a part of the expense involved. We would respectfully draw attention to this fact and to the further expenses to be incurred, and request direction as to your wishes regarding these matters.

We wish to express our deep gratitude to Messrs. Flint and Gay, whose untiring efforts during our residence in Manila made it possible to accomplish far more than we could have done unaided. It is a pleasure to acknowledge also many kindnesses on the part of Mr. John W. Garrett.

That we are deeply indebted to the officers in the Medical Service of the U. S. Army and Navy for opportunities and aid, is evident from the report preceding. Courtesies and kindnesses extended by various citizens of Manila, European and native, are here also gratefully acknowledged. Very respectfully,

Simon Flexner, Lewellts F. Barker.


A CASE OF MULTIPLE GANGRENE IN MALARIAL FEVER.

(with illustrations.) By William Osler, M. D., Professor of Medicine, Johns Hopkins University.


There are three groups of cases of multiple gangrene:

(1.) Raynaud's disease. — There have been previous wellmarked vascular disturbances in the extremities (syncope, asphyxia or hyperasmia), the gangrene is very often symmetrical, is usually slight in extent and limited to the fingers or toes, more rarely to the ear-tips or nose.

(2.) Multiple spontaneous gangrene of limbs. — In young or middle-aged persons, without any obvious cause, massive gangrene of one, two or three extremities occurs. Many illustrations of this are recorded in the literature.

(3.) Multiple spontaneous gangrene in association with the acute infections. — In measles, typhoid fever, typhus fever, scarlet fever, diphtheria and malaria, local gangrene may occur. There are multiple patches, not symmetrical, and the skin and subjacent tissues are more frequently affected than the extremities. While of course the phenomena of Raynaud's disease may occur as a sequence of any of the specific fevers, a large proportion of all the cases of local gangrene occurring during or after one of the fevers have nothing whatever U< do with this affection.

The relationship between malarial fever and Raynaud's disease is believed to be very close. Many references are given to cases (a majority from French sources) by Barlow in his article in Allbutt's System, and more fully by Monro in his excellent monograph on the disease. (Glasgow, James Maclehose & Son, 1899.) Altogether, in the cases he has col


lected, there were only 8.3 per cent, with malarious antecedents. I have looked over the notes of cases of Raynaud's disease which I have seen in Baltimore, nine in number, and I do not find malaria to be related as an etiological factor in any one of them, nor, so far as I know, in our very large series of cases of malaria during the past ten years has there been a single instance of Raynaud's disease.

The following case is a very remarkable illustration of multiple gangrene occurring in a case of aastivo-autumnal malaria. Similar cases have been reported in the literature, and are referred to by Monro in his monograph (page 96), but they seem to be exceedingly rare.

Clinical Summary. — Malaria when six years old — typhoid fever twice — last attack four months before onset of present illness — illness in the middle of October, supposed to be influenza, but more probably malaria— on November 2nd, onset of spots of gangrene in various parts— rapid extension— condition on admission as shown in the figures — complexion muddy — spleen enlarged — blood showed very many cestivoautumnal organisms —temperature slightly elevated at first— subsequently no fever — rapid recovery.

V. W. B., aged 23, bar-tender, admitted to Ward E, Thursday, November 29, 1899, complainiugof sores on various parts of his body.

Family history.— Mother died of consumption. No history of rheumatism or of any special disorders of the skin.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 107.


Personal his fori/. — As a child he had measles, mumps and whooping cough. When six years old he had malaria. Five years ago he had a very severe attack of typhoid fever, after which he had an abscess in the abdominal wall, which opened spontaneously and discharged for two mouths, leaving a large scar. lie had at the same time many boils. Last year he went south with the Fifth Regiment, and in August he had a second attack of typhoid fever, and was ill for two months. He has had gonorrhoea twice; has never had lues. He has used tobacco freely ; whiskey and beer in moderation.

Present illness. — -The patient has been living in Baltimore this autumn, and has been very well until the middle of October, when he was ill in bed for nearly two weeks with pains in the back and general weakness; no fever, no chills, no herpes. The doctor called it influenza. The patient got up and was about for a few days, when, on November 2nd, just twenty-seven days ago, he noticed blebs about half an inch in diameter on both hands, which were slightly swollen. The nest day a mottled area appeared on the instep of the left foot. It had a bruised appearance. A similar one appeared on the buttocks and on the dorsum of the right foot. Other spots came iu the situation to be subsequently mentioned.

The hands and feet became very much swollen. The blebs broke and discharged a dark fluid ; the skin around the affected areas was very red. There was no itching. He had some pain at night. Ten days ago he had slight chilly feelings. There had been no redness, nor swelling, nor blueness of the fingers or toes, and there had been no numbness or tingling. The urine had been clear. Dr. Futcher made the following note on the day after his admission.

"The patient is a large-framed, well-nourished man; complexion rather sallow. The skin of whole body is pigmented, markedly so about nipple and umbilicus, to slight extent about geuitalia; no increase in either axilla. The lips and mucous membranes are of fairly good color ; no pigmentation of mucous membranes. Over dorsum of left hand, just behind knuckles, there are four whitish scars, the result of healing vesicles. Over the ring, middle and little fingers there is a brownish-yellow discoloration of the skin which is gradually peeling off where the blebs are healing. On palmar surface of same fingers the skin is raised in large blebs. The skin has a brownish-yellow color, and over the ring finger is quite gangrenous, and there is involvement of the subcutaneous tissue. The thumb aud index finger are not involved.

" Right hand. — The dorsum of baud is unaffected. On the


dorsal surface of first and second inter-phalangeal joints of index, middle and ring fingers the skin is thickened, brownish in color, no vesicles. Over the hypothenar eminences on palm is a large area, measuring 5x6 cm., in which the skin is loosened from the subjacent tissue, markedly discolored, and at one point a serous fluid is exuding. The palmar surface of all four fingers shows a gangrenous condition of the skin with vesiculation and oozing of fluid, most extensive on ring finger, where the process invades the palm of the hand.

" Right foot. — Over dorsum of foot, below ankle, is an area, 5x3 cm., in which the skin is gangrenous and exceedingly black; slough still adherent to adjacent tissue; surrounding skin, slightly pigmented. Over the heel there is an area of brown, discolored, thickened skin, measuring 5x6 cm.: this area is sensitive to the touch.

" Left foot. — Below external malleolus is an area, 5x3 cm., of gaugrenous and sloughing black skin.

" Left buttock. — Just over the spine at the junction of the dorsal and lumbar regions there is a patch of dry gangrenous skin l*x2 cm. Over left gluteal region there is an irregular gangrenous patch, quite dry, measuring 4$x2 cm., slightly sensitive to pressure.

"Occiput. — Over the lower part of occiput, on each side, there are two areas in which the scalp has a gangrenous appearance, slight oozing of fluid causing matting of hair.'"

Though the history did not suggest malaria, as in the routine examination of the abdomen the spleen was found to be considerably enlarged, the blood was at once examined, and very large numbers of aistivo-autumnal organisms were found. The crescents were in unusually large numbers. Cultures taken from the blood proved negative. There was no leucocytosis, and the differential count was practically normal. The eosinophiles were only 2 per cent. The patient was at once given quinine in full doses, and he began to improve rapidly. The larger sloughs were treated with linseed poultices made with bichloride solution. Crescents and ovoids persisted in the blood for some time, though by December 15th they were rapidly disappearing. On December 14th, the gangrenous patches on both hands had healed. On the feet the sloughs had separated, leaving deep ulcers, the sheaths of the tendons being exposed. The urine examinations were negative throughout. The patient had a slight rise of temperature (100°) at first; subsequently none at all. The figures from photographs, by Dr. Brownell, illustrate the condition on admission.


BENJAMIN JESTY: A PREJENNERIAN VACCINATOR.

By Thomas McCrae, M. B., {Tor .), Instructor in Medicine and Physician in charge of the Clinical Laboratory,

Tlie Johns Hopkins Hospital.


"That a disorder communicated to the human animal from one of the brutes should protect the former against the contagion of small-pox, is one of the most interesting facts in the whole history of medicine. How glimpses of a truth so remarkable were first revealed to the casual observation of certain peasants, and how the result of this chance observation was gradually ' matured into a


rational and scientific form by a mind deeply imbued with the best principles of sound philosophy,' I have not leisure to tell you in detail."— (Watson's Practice of Physic.)

Tradition has it that there were many instances of the "glimpses" of the truth of vaccination referred to by Watson,


JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY.


Copy of print in the Fi ft i i ction. ot the Johns Hopkins Hospital.



PAINTED BY M. W. SHARP


TO I UK PRESIDENT, VICE-PRESIDENTS, TREASI REKS IIMSTKKS. AND

MEDICAL OFFICERS OF Mil. ORIGINAL VACCINE INSTITI TION,


This Print of Mr. Benjamin Jesty, from a Picture in the possession of the institution, i- respectfullj inscribed by their devoted Serv't,

WILL" SAY.

Mr. B. Jesty, Farmer of Downshay, Isle ol Purbecl ' who inoculated his Wife and Two Sons for the Vaccim Pocl

1774, from his Cows al thai time disorder'd bj the ( ind who ubscquently, from the raosl rigorous rrial

found unsusceptible of the Small Pox Having rations Example of Vaccine Inoculation from his own knowledge ol the

fact of [Insusceptibility of the Small Pox after casual I oh P k in Iiis own person and in thai of others, and from knowing the

ssness of the Complaint. To commemmorate thi I r ol these historical truths the Vaccine In titutiou have procured

this Portrait. Extract from tht Minutes oj tht Original I ■■< tilution, Broad Street, Golden Square, Seplembi r, 1805

London, Publishi i Dec l'. 1805, bj the Engraver, 92 S on St.. Marylebone. 1731 1816


February, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


43


long before the great work done by Jenner. But the majority of these lack certain proof as cases of the employment of the inoculation of cow-pox as a preventive of small-pox. 11* the evidence regarding the subject of this sketch seems thoroughly authenticated, and there can be no doubt of Jesty having performed vaccination in 1774. The date of Jenner'a Bret vaccination was 179»5. although for many years before he had been making observations regarding it. The material relating to Jesty has been very fully collected by Crookshank in his work on " The History and Pathology of Vaccination," from which much of my information is obtained. Jenner appeals to have regarded the account of Jesty as au invention likely to from the credit due to himself. But it can in no way lessen Jenner'a fame. The early instances were only isolated occurrences without influence further than their own surroundings, while Jenner introduced vaccination and gave it to the world.

Benjamin Jesty was born at Yetminster in Dorset, and was a fanner. Subsequently he moved to the farm of Downshay in the Isle of Purbeck, in Dorset, situated not far from Swanage. Judging from what has come down to us concerning him, he appears to have been au eccentric man, full of quaint ways of action and speech, but with a good share of the power of observation and of sensible reflection over what he had observed. In 1774. small -pox was prevalent in his locality. He was thought to be in no danger of it himself, having had the cow-pox previously by taking it casually from the cows. This was a matter of tradition through the countryside. Some of his family were not so protected, and the fact that two of his maid-servants, who had previously had the disorder from the cows, attended patients suffering from small-pox without infection, seems to have determined Jesty to inoculate the cow-pox into his own family as a preventive of small-pox. The farmer is said to have argued thus : " For his part he preferred taking infection from an innocuous animal like the cow, subject to so few disorders, to taking it from the human body, liable to so many and such diseases, and that he had experience on his side, as the casual cow-pox was not attended with danger like the variolous infection; and that beside there appeared to him little risk in introducing into the human constitution matter from the cow, as we already eat the flesh and blood, drink the milk and cover ourselves with the skin of this innocuous animal." ( Extract from the communication of Rev. Dr. Bell).

Accordingly, Jesty carried out his ideas and inoculated his wife and two sons, aged two and three years, with the cow-pox. The patients went into the fields, and the virus was taken on the spot from the teats of the cows. A stocking-needle was the instrument used; Mrs. Jesty being inoculated under the elbow, the sons above. The latter had the disorder in a favorable way, but in the course of a week Airs. Jesty's arm was much inflamed. She had fever, and was so ill that a neighboring surgeon, Mr. Trowbridge of Cerne, was called. He said " You have done a bold thing, but I will get you through it if 1 can." She soon recovered perfectly. Dr. Bell states that the boldness and novelty of the attempt produced no small alarm in the family and no small sensation in the neighborhood. Fifteen years later, in 1789, the sons were inoculated for the small-pox by Mr. Trowbridge, along with others who had nol


had the cow-pox. At this time the inoculation of small-pox was a common procedure. The arms of the Jestya inflamed, but this soon subsided, and no fever or other variolous symptoms were observed. The unprotected individuals went through the usual course of inoculated small-pox. Subsequently -Mrs. Jesty and her sons were often exposed to small-pox without taking it, while in 1805 one of the sons was inoculated for small-pox with a negative result.

It is a wonder, as Dr. Bell notes, that nothing of these cases was known to Jenner, as they would have been valuable evidence in support of his doctrines of the value of vaccination. But when one considers the means of communication of the (lav. it is easily understood why this experiment of a south-ofEnglaud farmer should have only become known to a very local district. Statements regarding these facts were drawn up in 1803 by Dr. Bell and Mr. Banks, the member for Corfe Castle, which is close by. These came before a committee of the House of Commons and the Jennerian Society. In 1804, the Society endeavored to get Jesty to come to London in order that they might see him and investigate the matter, but an attack of gout j>reveuted. The following year the secretary of

the society wrote : —

London, July 25th, 1805.

Sir : — I am desired to propose to you that, provided you will come to town at your own convenience, but as soon as possible, to stay not longer than five days unless you desire it, for ttie purpose of taking your portrait as the earliest inoculator for Cow Pock, at the expense of the institution, you will receive 15 guineas for your expenses and the members of the establishment will be happy to show you any civility during your stay in London, on which account it is hoped you will be put to little or no expense. I have the honor to remain, Sir.

Your obedient humble servant,

Will Sancho.

Mr. Jesty accepted the invitation and journeyed to London, taking one of his sons with him. It is seated that they met with great attention from the members of the Jennerian Society who were much amused by Jesty's ways. Some idea of his characteristics is given by various incidents reported. His family tried to induce him before coming to dress more fashionably, but he said ;i he did not see why he should dress better in Loudon than in the country." Mr. Colson writes that on his return he gave a very unfavorable account of the metropolis, but said there was one great comfort there, viz., that he could be shaved every day. While there he was inoculated for the cow-pox, and his son for the small-pox, but neither took effect. This was done by the Society probably for the sake of their investigations. Mr. Jesty was presented with a pair of very handsome gold-mounted lancets, and his portrait was taken by Mr. Sharp; but he proved an impatient sitter, and it is said would only be kept quiet by Mrs. Sharp's playing on the piano for him. The portrait was presented to the Vaccine Institution, and is said by Crookshank to be now in the possession of Jesty's great grandson. There is an excellent copy of it in the Fisher collection of medical portraits in the Hospital.

The members of the Jennerian Society drew up a statement which among other things testified— " that Jesty had given decisive evidence of having vaccinated his wife and two sons in 1774, who were thereby rendered unsusceptible of the small


44


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 107.


pox as appears from their frequent exposure and inoculation. He was led to this from knowing the common opinion regarding the protection of cow-pox against small-pox and that he himself for the same reason was incapable of taking small-pox and from observation of the same thing in others. He believed that cow-pox was free from danger and that by it he should avoid various human diseases, such as the evil, madness, lues and many bad humors as he called them." The year after his visit to London, Jesty seems to have suggested an application for some pecuniary reward, but as the secretary of the Vaccine Institution considered any grant improbable, the matter was dropped.

Last summer, in company with Dr. Osier, a visit was made to the locality where Jesty lived. To-day, the ordinary native of the district does not know the name of Jesty. His farm, Downshay, is in the Isle of Purbeck in the county of Dorset. It occupies a delightful situation in a valley between the Purbeck Hills and Nine Barrow Down, a few miles from Corfe Castle. Leaving the Kingston road, the house is reached by a rough way through the fields with many steep descents. It is not seen at first, indeed we did not look for it, as our whole attention was centred on the superb outlook. To the left, in the setting sun, were the ruins of Corfe Castle guarding the gateway to the Isle of Purbeck; to the right, Swanage and its bay, with far off on the horizon the white cliffs of the Isle of Wight (The Needles) ; while across the valley was the fine sweep of the Nine Barrow Down. Encircled by trees and in a depression, we did not see- the house until we reached the barnyard, when we were greeted by a jolly looking dairy-man who was just driving out his herd. The entrance to the garden was through a fine old stone gateway with pillars of a quaint design. The house was of a type common on the island, of two stories


and well built, looking very fresh and clean after its more than 250 years. The date of building, 1635, was carved on the side of the house.

From the farm-house, a drive of a few miles brings one to the village of Worth Matravers where Jesty is buried. This is situated on the point of land known as St. Alban's Head. Here, in the parish church, a picture of Jesty with a suitable inscription is found hung up in the vestry. In the church-yard adjacent is his grave with that of Mrs. Jesty alongside. His tombstone bears this inscription: —

SACRED

TO THE MEMORY

OF

BENJ N JESTY (OF DOWNSHAY)

WHO DEPARTED THIS LIFE

April lGth, 1816 Aged 79 years.

He ivas born at Yetminster in this County and was an upright honest man, particularly noted for having been the first person (known) that introduced the Cow Pox by inoculation and who, from his great strength of mind, made the experiment from the cow on his wife and two sons in the year 177 Jf.


One feels that Jesty was in advance of his generation, and a man who saw probably better than he knew. He did his little to blaze out the path which has since become a highway. That he could do but little to advance vaccination, his circumstances decided. To another was the honor of giving vaccination to the world.


HEMOPHILIA IN THE NEGRO.

By Walter E. Steiner, M. D.


Although the disease haemophilia appears to have been known since the time of Albucasis,' the great Arabian physician, yet the two, or possibly three, cases reported before FordyceV short article appeared, contain no real contribution to the study of this disease. In the year 1784, its hereditary character was pointed out by Fordyce. Nineteen years later the term "bleeder" was given by Otto 5 to those who had haemophilia, and in addition to this he showed the general immunity of the females and their tendency to transmit the bleeding disposition to their offspring. Following these writers a number of American and German physicians did much in contributing to the knowledge of this disease. Schonlein' named it " haemoph ilia " about 1828, and gave it a place in his text-book on " Pathology and Therapeutics." Its later history is closely associated with the name of the British physician J. Wickham Legg. 5

The first attempt to collect all of the reported cases was made by Naas," in Germany, in a paper published in 1820. He also endeavored to give a systematic description of the affection.


This work was followed by other statistical articles by Lange, 7 Grandidier, 9 and Dunn, 9 the last appearing in 1883.

Many cases have been reported among different races. The Anglo-Germanic race has furnished most of them, followed by the Latin, Scandinavian and Teutonic races. Individual instances have also been given by Heymann '" in a Mohammedan family from Palembang, on the Island of Sumatra, where this diathesis was found in three generations, and by Koch " in a possible case of haemophilia in a Creole from Port of Spain, Trinidad. But in all the literature on the subject there is but one well-defined case in the negro mentioned.

This case was reported by Dr. Hadlock ,= before the Academy of Medicine of Cincinnati, on November 16, 1874. The patiept was a mulatto boy, aged seven years, who was found, on the doctor's visit, to be bleeding from the mouth. On examination Dr. Hadlock considered the hasmorrhage due to a decayed snag of a tooth which had become loosened. The tooth was accordingly extracted with the result that the haemorrhage became alarming in character. A compress steeped


February, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


45


in a solution of the persulphate of iron checked it for a time, but on the next day it seemed to be more violent than ever. The ig point was then cauterized and astringents were also given, all of which succeeded in arresting the hemorrhage temporarily. It recurred again, however ; all efforts to check it were in vain, ami the boy diet', in forty-eight hours. "On inquiring into the history of the boy's family" Dr. Hadlock found -that many of its members had died from haemorrhage from slight wounds. An uncle had cut himself with a scythe and died in consequence. His father had received a slight

i from a briar and bled to death."

The following case, which was admitted to the Johns Hopkins Hospital on April 10, 1899, is consequently the second to be recorded in the negro race.

Alverta W., aged 14 years (Medical History, No. 9764), complains of haemorrhage from the nose and mouth, and headache.

Family history (obtained mostly from patient's mother). — Father, mother and two brothers, alive and well; a sister died of throat trouble, aged 6 years. No history of tuberculosis, rheumatism, or any neoplasm in the family.*

HmmophiUc history. — Patient's great-grandmother was a bleeder from early childhood till her death, June 8, L898, from old age and la grippe. Her doctor frequently told her the bleeding was due to the fact that she had " too much blood." Patient's mother (Alverta S.) says she can distinctly remember the doctor coming about twice a year to remove some of

oo-much blood," by cupping or leeches. The greatgrandmother had fourteen children, ten boys and four girls.

Of these, the patient's mother remembered the names of eleven only, seven boys and four girls. (See family tree.) The seven known personally to the patient's mother were all of them bleeders, and are now all dead but William T. One

.died from hemorrhages from the no mouth in 1895, in Philadelphia, at the age of thirty-four years. He had had luemorrhages from early childhood, but during his last five years they were more severe. The doctor told his wife he did not have consumption, but what diagnosis was made of the case is unknown. The patient's grandmother used to bleed from the nose occasionally. She died December 30, 1898 (aged 60), of -asthma, dropsy, Bright's disease and heart disease."

Patient's mother frequently bled from the nose till her sixteenth year. She has had no attacks since.

Patient's brothers have occasional attacks of epistaxis. and bleed considerably from the slightest cuts and bruises. /' • history. — As a child, had measles, mumps and ing cough. Ulcerated sore throat" of two weeks' duration


  • One brother, William W. iSurgical History, Xo. 9080), was later

admitted tc the Johns Hopkins Hospital, on the surgical side, complaining of a swollen right ankle. He gave the history of an attack of gonorrhoea one month previously. The swelling in the ankle seemed located in the tissues about the joint, tie n apparently no effusion in the joint itself. The diagnosis of gonorrheal arthritis was made. Patient left the Bospita

advice, being only slightly improved. In view of the occurrence of joint troubles in haemophilia, added interest is given to this case.


one year ago. She gives a somewhat indefinite history of malaria in the spring of 1896. No chills, but thinks she had chilly sensations and fever. Was living in Baltimore at the time.

She has been a sufferer from severe frontal headaches ever since she can remember.

Menstruation has not yet been established.

HmmophiUc history. — Has bled easily from the slightest scratches since early childhood, but the amount of blood lost


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at


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- = 3 ■a & o £

! -a = a, a *> ~> "


a s £

"f o '=»

«5.


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46


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 107.


has been very slight in every instance. No attacks of epistaxis till present illness.

Present illness.— About two and a half months ago, she woke up one morning and found her pillow and night-dress bathed in blood, which came from her nose. By eating some salt, she checked the haemorrhage after she had bled about a cupful. Since then she has not enjoyed her customary good health, but has felt very weak and drowsy. Five days prior to her admission to the Hospital, she was awakened by an attack of epistaxis. It started with a sudden gush of blood, but soon amounted to only a slight ooze, and so continued for three days. Salt was also used on this occasion, but to no purpose. Two days after this, she found she had had her third nosebleed, during the night. It was very slight, however, and she was not awakened by it. In all, she thinks she lost about " half a wash-basin of blood."

Her only symptom in these attacks has been constant frontal headaches.

No bleeding from, or swelling of her gums, has ever been noticed, nor has any blood ever been detected in her urine or faces. On admission, temperature, 100.4°; pulse, 104; respiration, 24.

Physical examination— Patient is a quite well-developed, dark-skinned negro girl. Lips and mucous membranes are rather pale. Her tongue has a reddened, glazed appearance. The gums are swollen, and inflamed, but no bleeding points can be seen, nor can the gums be made to bleed on pressure. Thorax.— Negative on examination. Pulse 100 to the minute, regular in force and rhythm, good volume and tension. . Abdomen.— Negative. Extremities.— Negative. No petechia? or purpuric spots seen anywhere. Blood examination negative for malarial parasites. Leucocytes, 10,500. The day following admission, a small herpetic area was noted on her lower lip. The nose examination was negative. Four purpuric spots, about 2 mm. in diameter, were seen about the right clavicle.

Blood examination.— Coagulation time, between 3-4 minutes; red blood corpuscles, 5,088,000; white blood corpuscles, 4,500 ; haemoglobin, 60 per cent. ; blood platelets, 212,000.

On the third day a few additional purpuric spots were seen about the flexor and extensor surfaces of both arms and legs, at the elbows and knees. For the past two nights there has been slight bleeding from her gums.

On April 14th, the following note was made by Dr. Futcher: Patient's gums are still distinctly swollen, but less so than on admission. They bleed easily on pressure.

Seven days later the gums were considerably less swollen, and could not be made to bleed on pressure. At the time this note was made, patient had been up and about the ward for four days.

Blood examination, April 23.— Red blood corpuscles, 5,020,000 ; white blood corpuscles, 6,000 ; haemoglobin, 47 percent.; blood platelets, 280,000.

The patient improved wonderfully during her stay in the Hospital, and was discharged April 24th. No more petechial spots were noted after those seen April 12th, and those then seen quickly vanished.


Urine.— On entrance the urine was straw-yellow in color, clear, 1021 in specific gravity, faintly acid in reaction, negative for sugar, but contained a trace of albumen. There was a white flocculent precipitate. Microscopically a few hyaline and granular casts were seen as well as a number of epithelial cells, and calcium oxalate crystals. Mucous strands were also seen. The urine gradually cleared up, and on the last examination (April 21), no casts nor albumen were found. Her temperature nine hours after admission rose to 101.2°, but gradually fell till the next day, when it was 99.8°. From this time on there were daily elevations, the highest point reached being 100.7° on April 14th.

Treatment.— Patient was given calcium chloride (grs. xv t. i. d.), a drug which was first introduced by Wright ,3 for the treatment of this disease. It was given in the following prescription, as advised by Wright:


Oalcii chloridi, Aquae chloroformi Aquae aurantii fiorum, Aquae q. s. ad. M. S. §ss. t. i. d. p. c.


3iii.

3iigiv.

5vi


It is interesting to note that both the cases of haemophilia were not in patients of pure negro blood.

In a study of the family tree of the second case we find :

(1.) The extraordinary fertility of bleeder's families (a fact first pointed out by Wachsmuth ,, ) is well shown in the family of our patient's great-grandmother. Five of her children died early, and none of the others, save one, now survives.

(2.) Of these, three children out of the six known to patient's mother died young. This accords with the fact that a large percentage of the bleeders die early.

(3.) Contrary to the usual statement, both the males and the females seem to have been bleeders, but only one (a male) died from the effects of haemorrhages.

(4.) The preponderance of the males is seen in two of the families named. This excess of sons over daughters has been given as a reason for the rarity of this disease.

(5.) The bleeding tendency in each instance was transmitted through the females.

In conclusion, I wish to thank Or. Osier for allowing me to report this case.

References.

1 Liber Theoricae nee non Practicae Alsabaravii ; the reference is found in Tractatus XXXI, Sectio II, Capitulum, XV, Folio, CXLV. " De Passione fluxns sanguines a quocumque

locorum."

2. Fordyce: Fragmenta Chirurgica et Medica, L,onu.

1784, p. 41.

3. Otto: Medical Repository, N. Y., 1803, \ I, 1-4.

4 J. Wickham Legg: Article on Haemophilia in Allbutt's System of Medicine, Vol. VI, p. 548. Schonlein's account of the disease first appeared in his "Vorlesungen" which afterwards formed his text-book on pathology and therapeutics.

5. J. Wickham Legg : (a) A Treatise on Haemophilia, Lond., 1872 158 pp.: (b) Report on Haemophilia, St. Barth. Hosp. RepJ Lond., 1881, XVII, pp. 303-320; and other articles.


February, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


47


6. Naas: Archiv. f. med. Erfahr., Berl., 1820, 1, 385-434.

7. Lunge: Zeitschr. f d. ges. -Med., Bamb.,1850, XLV, 145-231.

8. Grandidier: Schmidt's Jahrb., Leipz., 1863, CXVII, 329 341. Ibid., 1872, CLIV, 81-102. Ibid., 1877, CLXXII, 185 L93.

9. Dunn: Am. .Tourn. of Med. Sc, Jan., 1883.


10. Heymann: Archiv f. path. An;il., etc., Berl., 1S59, XVI, 182-183.

11. Koch: Brit. M. J., Lond., L890, I, 1301.

12. Hadlock: Clinic, Cincin., L874, VII, 241.

13. Wright: Brit. M. J., L891, II, 1306.

14. Wachsnmlli : Zeitschr. d. deutsch. Chir. Ver., Magdeb., 1849, III, 459-517.


SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.


Robert L. Randolph, M.D. Acoin: A New Local Anaesthetic— The Ophthalmic Record, Chicago, August, 1899.

Acoin in solutions of 1 : 100 and 1:300 produces satisfactory anaesthesia in an unirritated eye in about tbe same length of time as cocaine.

2. In more than one case where the eye was congested, repeated instillations of acoin were inadequate to produce satisfactory anaesthesia.

3. Inspection of the cornea with a high-power lens failed to show any defects in the epithelium after its use.

4. Acoin has no effect upon accommodation.

5. It has no effect upon the size of the pupil.

6. It does not increase the intraocular tension.

7. Several experiments demonstrated that the staphylococcus pyogenes albus did not grow in agar which contained acoin in the proportion used in the clinic, and, furthermore, that exposure of this organism to the action of acoin for twenty-four hours was followed by death of the organism. This would look as though acoin were not only an inhibitor of the growth of this organism, but that it also killed this organism after a certain length of time. It is evident that conclusions drawn from this limited experience with acoin may have to undergo more or less modification with further trial.

Expulsive Intra-ocular Hemorrhage after Preliminary

Irideccomy for Cataract. — TJie Ophthalmic Review, London, December, 1899.

The case reported was an old lady of 76. She was exceedingly nervous ami refused to enter the hospital, but preferred remaining at hume and being nursed by members of her own family. From the uniformly favorable results attending preliminary iridectomy for cataract, this operation was first performed with intention of removing the lens a few weeks later. The operation was perfectly smooth. On the morning of the third day, it was found that the anterior chamber was almost completely obliterated, and that the lens was pressed so far forward as to force the iris against the posterior surface of the cornea. The condition grew worse, till the lens was almost forced through the old wound, when it was thought remove the lens. This was done and immediately there was a flow of bloody vitreous. Oozing kept up for four days. Light perception was gone, and in six months the eye had shrunken tc half its original size. Six months later glaucoma appeared in the other eye. She was unwilling for iridectomy, and with the history of the fellow eye it was thought best not to urge such a measure. The development of glaucoma in this eye justifies us in concluding that the same condition was present, in aless advanced stage, in the right eye at the time of the preliminary iridectomy. The case is of exceptional interest inasmuch as the haemorrhage followed iridectomy, for, as a rule, such catastrophies are seen only after removal of the lens. It is interesting to note the fact that intra-ocular bleeding did not commence till hours after the iridec


tomy. The nature of the trouble was not suspected till the morning of the third day, when the evidence of pressure behind the lens was unmistakable, so that bleeding must have been going on intermittingly fordays before the lens was removed . The constant reduction of intra-ocular tension caused by the yielding of the eyeball at the point of the wound would explain the persistent character of the haemorrhage. It is needless to add that we undoubtedly had in this case senile degeneration of the bloodvessel walls— so strong a predisposing cause to such results.

P. H. Verhoeef, Ph. B., M. D. Shadow Images on the

Retina. — Psychological Review, January, 1900.

The usual pin-hole experiment is produced by pricking a small hole in a card, which Is then held before the eye, but within the point of distinct vision. Under these conditions, if a pin is held between the hole, which serves as a source of light, and the eye, it casts an erect shadow upon the retina, and this shadow is projected as an inverted image of the pin. This experiment was described and explained by Le Cat in 1740. It is possible, however, that he was not the first to describe it, for he does not, in his work, claim that the experiment was original with him.

To show the dependence of the position of the projected image upon the relative position of the pin-hole, the experiment may be modified in the following interesting way. If, for instance, the eye is focused for the near point and the pin-hole is held beyond this point, the shadow of an interposed pin will appear erect. Under these conditions, if the pin-hole is gradually brought closer to the eye, the image of the pin becomes more and more blurred and finally disappears when the hole is at the near point, that is, when the eye is accommodated for the source of light. If the hole is brought still nearer, the original experiment is reproduced, the image of the pin again appears but is now inverted. This experiment is rendered easier if the accommodation is assisted by a convex lens, one of about ten diopters being very convenient. The lens is held close to the eye and the pin in front of the lens, or better, immediately behind it. Then if the pin-hole is placed beyond 10 cm. from the supposedly emmetropic eye, it will appear out of focus and the shadow will be upright. As it is brought closer, the phenomenon just described takes place.

If a sheet of white paper or a piece of ground glass is taken, and a small black spot is made upon it about the size of a pin-head, and this spot is used in place of the pin-hole in the above experiment, a white streak will be seen crossing the black spot. The phenomenon is best obtained without a lens, and is not an easy thing for most persons to see, since it requires that the accommodation shall be relaxed at will. This white shadow behaves in exactly the same manner as does the black shadow in the pin-hole experiment —under the same conditions it may be seen upright, inverted, or be made to disappear. The experiment should be conducted in a good light, and a piece of white paper about five centimeters square should be used. This phenomenon may also be obtained with a photographic camera.


L8


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 107.


The explanation of this phenomenon lies in the fact that the black spot, under the conditions mentioned, produces only a blurred image upon the retina, and while the interposed pin reduces the illumination of the margins of the spot, it has no appreciable effect upon the middle of the latter, the resulting difference in illumination thus producing the appearance of a white streak.

If a sufficiently large spot is used, it will be noticed that on relaxing the accommodation, the center (of its image) appears much darker than the rest of the image. This is due to the fact that as the spot is made larger it cuts off more and more rays which otherwise would have reached the center of its image, and when it is as large as the pupil, it cuts off all the rays parallel to the primary axis, thus producing a small spot in the center of its image totally devoid of light. But even when the spot is much less than half the size of the pupil, the image appears darker in the center, since many rays will even then be cut off from the center of the image. This circumstance explains the fact that if a moderately large black spot is used for the shadow experiment, the white shadow of the pin is broken by a dark central spot into two white lines, somewhat resemblins crescents. If a large black spot with a small white one in the center is used, the appearance of these two crescents may be obtained, and in addition the usual black shadow is seen over the central white spot.

If, in place of a spot, a black line is used, the pin will produce a white line running down the middle of its image ; the shadow in this case is more marked and more easily obtained than when a small black spot is used. Two lines drawn at a slight angle to each other, will give a bend in the white shadow at their intersection, but the shadow leaves one or both of the lines at a certain distance from this point. When a narrow red line is used instead of a black one, and a lens is employed to aid the eye, the white shadow takes on a greenish or bluish color. By the use of a lens a narrow line may be so blurred as not to be seen, but a pin in front of the eye decreases so much the amount of light reaching the lateral portions of the image on the retina, as to produce the appearance of a well-defined white shadow. The same thing is also true for a point.

Scheiner's experiment in which two pin-holes placed close together are held before the eye and a double image of a pin is produced, may be explained in the same way as the white shadow just considered, since the two images obtained of the pin may be regarded as one image with a white shadow down its middle produced by the portion of the card-board between the two pin-holes.

When simply blurring a line by relaxing the accommodation, it can be noticed that if the line is not too large, one can always


obtain a white line running down its middle, and within this line a faint dark line. In the case of a small black spot, a white spot is obtained in the center of its blurred image. This is probably due in most part to the denser and probably less transparent nucleus of the crystalline lens shutting off more rays than the rest of the refractive apparatus of the eye- This appearance is not produced by a photographic camera and hence must be mainly due to some such peculiarity of the eye as that suggested. It is possible, however, that the positive aberration of the eye may play some part in its production.

Thomas R. Brown, M. D. Recent Work iu Typhoid Fever. — Maryland Medical Journal, January, 1900.

Arthur W. Elting, M. D. The Antitoxin Treatment of Tetanus.— Albany Medical Annals, January, 1900.

T. Caspar Gilchrist, M. D. Progress in Dermatology. — Maryland Medical Journal, January, 1900.

William G. MacCallum and Thomas W. Hastings, M. D. Acute Endocarditis caused by Micrococcus Zymogenes (Nov. Spec), with a Description of the Micro-Organisms. — Journal Experimental Medicine, September-November, 1900.

William Osler, M. D. The Home Treatment of Consumption. — Maryland Medical Journal, January, 1900.

A Rhode Island Philosopher (Elisha Bartlett.)— The

Boston Medical and Surgical Journal, January, 18 and 25, 1900.

Stewart Paton, M. D. Certain Essential Points iu the Technic of Staining Nerve-Cells. — Philadelphia Medical Journal, January 13, 1900.

Robert Reuling, M. D. Pathology and Bacteriology. — Maryland Medical Journal, January. 1900.

William R. Stokes, M. D. Recent Advances in the Study of Tuberculosis. — Maryland Medical Journal, January, 1900.

Hugh H. Young, M. D. Recent Reports on the Operative Treatment of Hernia.— Maryland Medical Journal, January, 1900.


PROCEEDINGS OF SOCIETIES.


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Exhibition of Medical Cases.— Dr. Futcher.

During the past three or four months we have had a number of interesting cases of embolism and thrombosis in the medical wards. A brief report of these cases may be of interest.

Case 1. Thrombosis of the left external jugular subclavian and axillary veins, associated with mitral stenosis, with subsequent embolism of the left popliteal artery.

One of these cases was referred to, at a previous meeting, by Dr. Welch when speaking of thrombosis of the veins of the upper extremity associated with heart disease. The patient, a woman aged 35, had had an attack of chorea when seven years


old, and previous to admission had several attacks of acute articular rheumatism. There were marked signs of mitral stenosis with a rapidly-acting heart and cardiac hypertrophy. The first point of interest in the case was the development of some swelling over the left side of the neck, first seen on January 19th, 1899, two weeks after her admission. She complained of slight pain in the left side of the neck and down the inner part of the arm. The pain and swelling gradually increased, so that within a week there was very marked swelling over the left side of the neck, shoulder, arm and dorsal surface of the fore-arm. There was marked tenderness over the sternocleido-mastoid muscle and along the course of the external jugular vein. There was no special elevation of temperature


February, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


49


du ing the attack. There was no doubt that the patient was Buffering with thrombosis of the external jugular vein and, also, apparently, of the subclavian and axillary veins.

Thrombosis of the peripheral veins in cardiac disease is more common in the upper than in the lower extremities. According to Bouchut. the ratio of thromboses of the veins of the upper extremity to those of the lower is placed at 1 to 50, but in cardiac disease- the ratio is decidedly reversed. Dr. Welch was only able to find 26 cases in the literature of venous thrombosis of the peripheral veins in association with heart disease, and of those, 1? were in the veins of the neck or upper extremity, and it is interesting to note that the left side is much more frequently involved than the right.

To return to our case, by March 13th all the local symptoms had subsided and nothing of special importance developed until November "24th, 1899. when, at 12 o'clock, the patient suddenly complained of intense pain in the left foot, associated with a feeling of the pricking of pins or needles and some numbness. I was in the ward at the time the pain came on, and examined the foot, but nothing could be made out by the examination. The pain continued very severe during the afternoon, and at 4.30 P. M. the foot and leg still showed no changes on inspection. The next morning there was marked cyanosis of the left lower extremity as high as the tubercle of the tibia; the foot was cold, and there was great tenderness over the dorsum of the foot and about the shin. Dr. Osier saw the patient and made a diagnosis of embolism of the popliteal artery. The femoral artery pulsated, but there was no pulsation of the popliteal. The next day, November 26th, contrary to expectations, the cyanosis had largely disappeared, and the foot had become almost as warm as that of the other side. From that time on the symptoms gradually subsided, though she still has paroxysms of acute pain at times. The point of interest in connection with the case is the recovery without local gangrene. A great many of these cases result in gangrene of some portion of the extremity. In embolism of the arteries the onset of pain is usually very sudden, differing in this respect from thrombosis, where the pain is more gradual in its development.

Case 2. Thrombosis of the left femoral vein in a case of pulmonary tuberculosis. This condition is not so very uncommon in tuberculosis, usually occurring in the veins of the lower extremities. The patient, a man 55 years of age, was admitted Oct. 22nd, with marked signs of advanced pulmonary tuberculosis. About two weeks after admission, he began to complain about midnight of severe pain in Scarpa's triangle. The next morning his leg was definitely swollen, being 3 cm. larger than the other leg at the calf. The superficial veins were distinctly dilated, and the temperature on that side was, if anything, a little higher than that of the other leg, though there was no change in its color. The pain persisted for about ten days. Tne swelling has gradually diminished, and at present there is a definite thickening to be made out along the course of the femoral vein. Thrombosis in tuberculosis is generally held to be due to the development of marantic bhrombi. Dodwell and others think that they are of infectious origin due to various pyogenic micro-organisms. Arterial thrombosis in tuberculosis is a rare event. It occurs most commonly as a thrombosis of the pulmonary artery or its branches in tuber


culosis of the lungs. Very rarely it occurs as a result of tuberculous involvement of the intima of the arterial walls.

Case 3. Thrombosis of the right axillary and brachial veins, occurring in the course of a malarial nephritis. The patient, a man aged 39 years, was admitted Oct. Kith, 1899, suffering from malarial nephritis. He had a marked amount of albumen in the urine, with numerous casts. He was distinctly anaemic, showing less than 3,000,000 red blood corpuscles, and about 50 per cent, of haemaglobin. .Estivo-autumnal malarial parasites were found in the blood. On Oct. 18th, it was noticed that the right arm was somewhat swollen, and this condition increased during the next three or four weeks to such an extent that it was deemed necessary to make incisions in the skin to let out the fluid. Considerable relief followed this procedure. The swelling eventually diminished, and, although suspicion was entertained of a venous thrombosis, it was not until the oedema had markedly disappeared that a marked thrombosis of the right axillary and brachial veins was found to exist.

Just what the cause of the thrombosis was in this case is hard to say. It is doubtful whether malaria had anything to do with it. French observers have claimed that malaria does, at times, cause a thrombosis of the veins, but Dr. Welch is inclined to believe that there is really no relationship between the malaria and the thrombosis in these cases. In over 2000 cases of malaria in Dr. Osier's department, no instance of thrombosis was found. It is probable that the thrombosis in this case was due either to the nephritis or to the anaemia.


NOTES OX NEW BOOKS.


Hints on Elementary Physiology. By Florence Haig-Brown. (Philadelphia : P. Blakiston, Son & Co., 1897.)

This is an excellent little primer for nurses ; and the introduction, by Dr. William M. Ord, is a recognition of its merit. He says: "As an evidence of earnest diligence in preparation for what is one of the most responsible and certainly the very hardest possible occupation in life (nursing), it calls for all praise and respect. The qualities of the hook will, I am well assured, command the success which I most heartily wish for it." It is abundantly illustrated, and the plates are for the most part good, but some should be changed in a second edition, especially that one illustrating the mucous surface of the ileum, on page 79. We do not desire to be hypercritical, but on page 101 the author states that the tongue " is composed of muscle, fat, the hyoid bone, and the lingual vessels and nerves." In such an elementary treatise as this, is it not a little misleading to consider the hyoid bone as a portion of the tongue? Under the title of ventilation, we find the temperatures, given as suitable for dwelling rooms, surgical and medical wards, etc., very low — much lower than is the custom here in America to keep such rooms, and we believe too low for health in many cases. This little book is, in spite of any small deficiencies, far superior to many larger works on this subject written for nurses, and it is to be hoped it may have a wide circulation.


MONOGRAPHS.

The following papers are reprinted from Vols. I, IV, V, VI and VIII of the Reports, for those who desire to purchase in this form:

STUDIES IX DERMATOLOGY. By T. C. Gilchrist, M. D., and Emmet Rixpord, M. D. 1 volume of 164 pages and 41 fullpage plates. Price, bound in paper, $3.00.

THE MALARIAL FEVERS OF BALTIMORE. By W. S. Thayer, M. D., and J. Hewetson, M. D. And A STUDY OF SOME FATAL CASES OF MALARIA. By Lewellys F. Baker, M. B. 1 volume of 280 pages. Price, in paper, $2.75.

STUDIES IN TYPHOID FEVER. By William Osler, M. D., and others. Extracted from Vols. IV and V of the Johns Hopkins Hospital Reports. 1 volume of 481 pages. Price, bound in paper, $3.00.

THE PATHOLOGY OFTOXALBUMIN INTOXICATIONS. By Simon Fleaner, M. D. Volume of 150 pages with 4 full-page lithographs. Price, bound in paper, $2 00.

THE RESULTS OF OPERATIONS FOR THE CURE OF INGUINAL HERNIA. By Joseph C. Bloodgood, M. D. Price, in paper, $3.00.

Subscriptions for the above publications may be sent to

The Johns Hopkins Press, Baltimore, Md.


VOLUME TO COMMEMORATE THE 25TH YEAR OF DR. WELCH AS A TEACHER AND INVESTIGATOR,

It is customary in Germany for the pupils of a great teacher to express their appreciation and gratitude by dedicating to him a volume of their contributions to learning. The pupils of Dr. Wm. H. Welch, of Baltimore, have decided to give expression to their regard for him in a similar way and the publication of a volume to mark his twenty-fifth year as a teacher and investigator is now in progress.

During the past twenty-five years some seventy-five persons have undertaken investigation under Dr. Welch's leadership, and nearly half of these will contribute to the volume mentioned. The edition will necessarily be limited by the number of subscribers. An early announcement of the publication is made to give opportunity for subscription so that the committee can decide upon the number of copies to be printed.

The volume will be royal octavo in size and will contain at least five hundred pages of printed matter. It will, in addition, be illustrated with many lithographic plates and text figures. The price has been fixed at five dollars. The book will contain contributions to pathology and to correlated sciences agreeing in scope with that of the leading scientific medical journals.

The Committee of publication consists of :

A. C. Abbott, University of Pennsylvania, Philadelphia, Pa.

L. F. Barker, Johns Hopkins University, Baltimore, Md.

Wm. T. Councilman, Harvard University, Boston, Mass.

Simon Flexner, University of Pennsylvania, Philadelphia, Pa.

W. S. Halsted, Johns Hopkins University, Baltimore, Md.

A. C. Herter, University and Bellevue Hospital Medical College, New York.

Wyatt Johnston, McGill University, Montreal, Canada.

F. P. Mall, Johns Hopkins University, Baltimore, Md.

Walter Reed, Army Medical Museum, Washington, D. C.

Geo. M. Sternberg, Surgeon General's Office, Washington, D. C.

All communications and subscriptions should be addressed to Dr. F. P. Mall (Secretary), Johns Hopkins University, Baltimore, Md.

Baltimore, November 11, 1899.


HOSPITAL PLANS.

Five essays relating to the construction, organization and management of Hospitals, contributed by their authors for the use of The Johns Hopkins Hospital.

These essays were written by Drs. John S. Billings, of the U. S. Army, Norton Folsom, of Boston, Joseph Jones of New Orleans, Caspar Morris, of Philadelphia, and Stephen Smith, of New York. They were originally published in 1875. One volume bound in cloth, price $5.00.


THE JOHNS HOPKINS HOSPITAL BULLETIN.

The Hospital Bulletin contains announcements of courses of lectures, programmes of clinical and pathological study, details of hospital and dispensary practice, abstracts of papers read and other proceedings of the Medical 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 X is now in progress.

The subscription price is $1.00 per year.

The set of ten volumes will be sold for $20.00.


54


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 107.


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report In Pathology.

The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction; ^Xg o. Intestinal Sutures 6 ; Reversal of the Intestine; The Contortion of the

Vena Portae and its Influence upon the Circulation;!?? F. P. Mall, u. «• A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Berkley, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, M. D.

Report In Dermatology. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organ*. By

T C Gilchrist, M. D., and Emmet Riiford, M. D. ...—_»■ « »

A Case of Blastomyces Dermatitis in Man; Comparisons of the Two Vsnetie. of

Protozoa, and the Blastomyces found in the preceding Cases, with the so-called

Parasites found in Various Lesions of the Skin, etc. ; Two Cases of Molluscum

FibroBum; The Pathology of a Case of Dermatitis Herpetiformis (Duhnng). By

T. C. Gilchrist, M. D.

Report In Pathology. An Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, M. D.

Volume II. 570 pages, with 28 plates and figures.

Report In Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with Gallstones. By William Osler, M. D.

Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D.

On Pyrodin. By H. A. Lafleur, M. D.

Cases of Post-febrile Insanity. By William Osler, M. D. _,„„, ., „

Acute Tuberculosis in an Infant of Four Months. By Harry Toulmin, M. D.

Rare Forms of Cardiac Thrombi. By William Osler, M. . D.

Notes on Endocarditis in Phthisis. By William Osler, M. D. Report In Medicine.

Tubercular Peritonitis. By William Osler, M. D.

A Case of Raynaud's Disease. By H. M. Thomab, M. D.

Acute Nephritis in Typhoid Fever. By William Osler. M. D. Report In Gynecology.

The Gynecological Operating Room. By Howard A. Kelly, M. D.

The Laparotomies performed from October 16, 1889, to March 8, 1890. By Howard A. Kelly, M. D., and Hunter Robb, M. D.

The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of forty Cases of Abdominal Section. By Howard A. Kelly, M. D.

The Management of the Drainage Tube in Abdominal Section. By Hunter Robb,

The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. ,_,,-, „ „

Report of the Urinary Examination of Ninety-one Gynecological CaBes. By Howabd

A. Kelly. M. D., and Albert A. Ghriskey, M. D. Ligature of the Trunks of the Uterine and Ovarian Artenes as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Clitoris. By Hunter Robb, M. D. ....

Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report In Surgery, I. The Treatment of Wounds with Especial Reference to the Value of the Blood Clot

in the Management of Dead Spaces. By W. S. Halsted, M. D. Report in Neurology, I. A Case of Chorea InsanienB. By Henry J. Berkley, M. D. Acute AngioNeurotic Oedema. By Charles E. Simon, M. D.

Haematomyelia. By AuausT Hoch, M. D. . ,..„,.'.„

A Case of Cerebrospinal Syphilis, with an unusual Lesion in the Spinal Cord. By

Henry M. Thomas, M. D.

Report in Pathology, I. Amaibic Dysentery. By William T. Councilman, M. D., and Henri A. Latleui, M. D.


ures.


Volume III. 766 pages, with 69 plates and fig

Report in Pathology.

Papillomatous Tumors of the Ovary. By J. Whitridoe Williams, M. D.

Tuberculosis of the Female Generative Organs. By J. Whitridqe Williams, M. D. Report in Puthology.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Flexner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By W». T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugata Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A Kelly, M. D. .

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mary Sherwood, M. D.

Intestinal Worm! as a Complication in Abdominal Surgery. By A. L. Stavzlt, M. D

Gynecological Operations not involving Coeliotomy. By Howard A. Kelly, M. D Tabulated by A. L. Stavelt, M. D.


The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina with HaematokolpoB and Hsmatometra. By Howabd A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anaesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.

Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.

By William Osler, M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetson, M. D.

Report In Neurology. Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of J/"s muscuhts; The Intrinsic Nerves of the Thyroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley. M. D.

Report in Surgery. The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology. Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; TuberculosiB of the Endometrium. By T. S. Cullen, M. B. Report in Pathology. Deciduoms Malignum. By J. Whitridoe Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever.

By William Osler, M. D., with additional papers by G. Blumer, 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.

Report in Neurology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory.— Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I.— Alcohol Poisoning.— Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol); Part II. — Serum Poisoning.— Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part III.— Ricin Poisoning.— Experimental Lesions in duced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia.— Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V.— Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report In Pathology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S. Cullen, M. B.

Pregnancy in a Rudimentary Uterine Horn. Rupture, Death. Probable Migration of Ovum and Spermatozoa. By Thomas S. Cullen, M. B., and G. L. Wilkins, M. D.

Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. Cullen, M. B.

A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By William D. Booker, M. D.

The Pathology of Toxalbumin Intoxications. By Simon Flexner, M. D.

Volume VII. 537 pages with illustrations. (Now ready.)

I. A Critical Review of Seventeen Hundred Cases of Ahdominal Section from the standpoint of Intraperitoneal Drainage. By J. G. Clark, M. 1). II. The Etiology and Structure of true Vaginal Cysts. By James Erne.- i Stoker, M. 1). III. A Review of the Pathology of Superficial Burns, with a Contribution to our Knowledge of the Pathol igical I Ihanges in the Organs in cases of rapidly fatal burns. By Charles Russell Bardeen, M. I). IV. The Origin, Growth and Fate of the Corpus Lnteum. By J. G. Clark, M. 1). V. The Results of Operations for the Cure of Inguinal Hernia. By Joseph C. Bloodgood, M.D.

Volume VIII. About 500 pages with illustration?. (In

press.)

Studies In Typhoid Fever.

Bv William Osler. M. D., with additional papers by J. M.T. Kinney. M.D., S. Flexner, M. D.. I. P. Lyon. M. I)., L. I'. Hamburger, M. D., II. w.< ushing, M.D., and J. F. Mitchell, M.D.

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BULLETIN


OF



THE JOHNS HOPKINS HOSPITAL.


Vol. Xl.-No. 108.]


BALTIMORE, MARCH, 1900.


LPrice, 15 Cents.


COK-TENTS.


Notes on an Improved Method of Removing the Cancerous Uterus by the Vagina. By Howard A. Kelly, M. D., - A Preliminary Report on the Surgical Treatment of Complicated Fibroid Tumors of the Womb, with a Description of Two Methods of Operating. By Howard A. Kelly, M. D.,

Observations upon the Neural Anatomy of the Inguinal Region Relative to the Performance of Herniotomy Under Local Anesthesia. By Harvey Cushino, M. D.,

The Pathological Findings in a Case of General Cutaneous and Sensory Anesthesia without Psychical Implication. By Henry J. Berkley, M. D.,

Congenital Malformations of the Heart as Illustrated by the Specimens in the Pathological Museum of the Johns Hopkins Hospital. By W. G. MacCallum, M. D.,


Summaries or Titles of Papers by Members of the Hospital and Medical School Staff appearing Elsewhere than in the Bulletin, ----- 71

Proceedings of Societies :

Hospital Medical Society, .-72

Exhibition of Patients [Dr. Platt] ; — Changes in the Cells of the Nucleus Dorsalis resulting from Pressure upon the Upper Portion of the Spinal Cord ; Area of Necrosis in Internal Capsule in Typhoid Fever [Dr. Barker] ; — Poisonous Snakes [Dr. Kelly].


Notes on New Books,


Books Received,


NOTES ON AN IMPROVED METHOD OF REMOVING THE CANCEROUS UTERUS BY THE VAGINA.

By. Howard A. Kelly, M. U., Gynecohgist-in- Chief, the Johns Hopkins Hospital.


My ideas upon the subject of the extirpation of the cancerous uterus (cervical cancer) bare undergone considerable change within the past year. A careful examination of my material and reports from other clinics have shown that we dare not reason too closely upon a supposed analogy between cancer of the uterus and cancer of the breast ; in other words, glaudular metastases, which play such an important part in the extension of mammary cancer are relatively unimportant, and as a rule, only observed in the latest stages of uterine cancer.

More careful histological studies show that the uterine cancer extends progressively through the tissues from its cervical focus. The great aim of the operation for the extirpation of cancer, becomes, therefore, that of giving the diseased cervix the widest possible berth, instead of being, as before supposed, the removal of the uterus plus the extirpation of the pelvic glands.

In the first place the frequent recurrence of the disei the scar tissue of the vaginal vault points to the importance of commencing the enucleation on the vaginal side at a point far below the manifest limits of the invasion, not less than 2-2 J cm. distant or even more.


In order to give the diseased cervix the widest possible berth in the direction outwards into the bases of the broad ligaments, I would again insist upon the necessity of catheterizing the ureters in every case as a preliminary to the radical operation. This can be done by putting the patient in the knee-breast position, and introducing my open vesical speculum, and carrying one of my renal catheters up into one kidney and then catheterizing the other. The patient is then turned on her back and the air allowed to escape from the bladder through a vesical catheter, and the enucleation proceeded with.

If this preliminary catheterization is not done, the operator is forced to adopt one of two courses, both of which are bad ; either he must skin out the cervix for fear of including the ureters in his ligatures, or he must consume a long time in a difficult dissection of the ureters not marked out by the bougie. Tin' latter alternative many feeble patients will not stand. I insist, therefore, with the utmost earnestness and emphasis that the surgeon who proposes to give his patient the besi possible chance of recovery is under the absolute necessity of learning to catheterize the ureters.

After this most important preliminary and after a thorough


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curettage of the diseased area, I cut through the vagina on all sides and proceed to strip it loose from the bladder, so as to expose the vesico-uterine peritoneum, and to open the peritoneum as widely as possible at this point. If the bladder is diseased, the base of it may be cut off and left sticking to the cervix.

The peritoneum is now also opened posteriorly into the recto-uterine pouch so that the uterus remains attached by its broad ligaments alone.

A gauze pack is then put into the pelvis behind the uterus and the cervix is thrust back against it, while the anterior uterine wall is caught with museau forceps step by step and drawn down through the anterior incision until the fundus appears at the vaginal outlet.

The next step now is to bisect the uterus from above downward ; this is not attended with any serious bleeding.

The surgeon now proceeds to remove the uterus in the following manner: one half of the body of the uterus is caught by a stout museau forceps, while the other half is allowed to retract within the vagina; then, catching the cervix of the same side with the forceps, the body is completely severed from the cervix by dividing from within outward. As soon as the division is completed, the uterine vessels are clamped in the exposed cellular tissue, and the detached body is now pulled further out and the round ligament clamped, and lastly the uterine cornu. In this way one quadrant of the uterus is removed. The body of the uterus on the opposite side is next removed in like manner.

Ligatures are then applied in place of the clamps. The ovaries and tubes are removed after the body of the uterus. It is, as a rule, much easier to remove the ovaries and tubes in this way when there is more room secured than to take them out with the body of the uterus. The removal of the body of the uterus in this way affords so much room that it now becomes an easy matter to take out the cervix on the side which is least implicated, under all circumstances giving it the widest possible berth, and keeping the rigid catheterized ureter under touch all the time during the enucleation.

The steps of the operation as thus far described, which have been rapidly and easily conducted, may be looked upon as more or less preliminary; three-quarters of the uterus have been removed and the remaining quadrant, that half of the cervix which is on the side where the infiltration of the broad ligament is most marked, now remains to be extirpated also, completing the operation.


In reality so important is this last step that the operation may at this point be looked upon as only having just begun. All the skill of the operator must be concentrated upon this step, upon securing the most thorough, wide extirpation of this remaining piece.

In order to do this as effectively as possible, the extirpation of the three portions indicated has afforded a maximum space, and the operator is not now embarrassed by the presence of the uterine body in the pelvis. He holds in the grasp of his forceps a small nodule, one-half of the cervix, and his desire is to get it out with perfect control of the vessels giving it the widest possible berth. This may be done in some cases by ligature, but will be better done in other cases by cautery clamps such as have been devised by Dr. Skene, of Brooklyn, or by igniextirpatiou as extensively practised by Mackenrodt of Berlin (see Martin's Festschrift, 1895, p. 100).

If the ureter lies clearly beyond the diseased area and- is unaffected, it may be dissected out and left intact; in many of these cases, however, the operator must not hesitate a moment in cutting off the ureter above the diseased area, and proceeding with the wide enucleation of the nodule as if the ureter did not exist. After the enucleation is over, the ureter may then be readily turned into the denuded bladder and stitched there (uretero-cysto-neostomy).

The anterior and posterior peritoneal surfaces are then drawn down and attached to the vagina, and are again sutured together in the middle line, so as to leave but two small openings up into the pelvis which are loosely stuffed with gauze.

While the cases operated upon are still too recent to he offered in evidence, there can be no doubt whatever that this plan of operating, like any other plan which gives the disease a wider berth, must give a better percentage of permanent recoveries.

Cases: F. J., Nov. 7, 1899, Gyn. No. 7351.


S. S., Nov. 14, 1899, E. J., Nov. 14, 1899, S. T., Nov. 18, 1899, K. -M.. Nov. 29, 1899, K. H., Nov. 30, 1899, M. J., Dec. 21, 1S99, M. H., Jan. 10, 1900, I. B., Feb. 24, 1900,


7370. 7371.

7384. 7405. 7411. 7428. 7495. 7582.


A PRELIMINARY REPORT ON THE SURGICAL TREATMENT OF COMPLICATED FIBROID TUMORS OF THE WOMB, WITH A DESCRIPTION OF TWO METHODS OF OPERATING.

By Howard A. Kelly, M. D., Gynecologist-in- Chief, the Johns Hopkins Hospital.


It is now four years and a half since I described before the Southern Gynecological Association, at a meeting in Washington, November 12, 1895, a new method of performing a supravaginal myomectomy for fibroid tumors of the uterus.*


! See Bulletin of the Johns Hopkins Hospital, Feb., 189G.


This new method of enucleation was by means of a continuous incision through first the ovarian, then the uterine vessels of one side, down under the tumor, cutting across the cervix, and catching the uterine vessels of the opposite side as they are exposed, and up the broad ligament to the round ligament, and last of all the corresponding ovarian vessels. By means of this rapid plan of enucleation the tumor and


March, 1900.]


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the part of the uterus involved with it are rolled out and all the vessels controlled within three or four minutes.

Complications on the part of the tubes and ovaries, in the form of adhesions, hydrosalpinx and pelvic abscesses, are also more easily dealt with under this plan of enucleation than under any other. It is always easier to attack an inflamed tube and an ovary from the front of the broad ligament which is opeued up in this way, than to attack the same inflamed structure from the posterior part of the pelvis before enucleating the tumor.

The large experience which I have gained since publishing tlie paper above referred to has only served to confirm my conviction that no other plan of operating can rival this one in simplicity, in rapidity, and in affording complete control of the complications referred to.

While this plan is the best for the vast majority of cases, occasionally a complicated case turns up in which it can only be applied with difficulty. I have in mind several cases which have recently passed through my hands where neither the common method of performing hysteromyomectomy, that of tying down on both sides to and including the uterine vessels, and then amputating the cervix, nor my own method of the continuous transverse incision epitomized above was applicable without great difficulty and considerable risk to the patient.

The first case in which I found it necessary to make a radical departure in the method of enucleation belonged to the group of cervical myomata. In this instance there was no cervix to be felt by the vagina, and on opening the abdomen the bladder was found raised half way up the umbilicus by an ovoid tumor choking the pelvis, with its long axis vertical. The body of the uterus containing a few small nodules sat high up in the abdomen above the umbilicus like a cap on top of this tumor and on the right and on the left sides the displaced uterine and ovarian vessels were spread out in a network. I began the enucleation by trying to tie off these vessels wherever I could catch them on the left side. There was a great deal of hemorrhage from the surface of the tumor, and as soon as I commenced to detach the ligated vessels and to push them down the hemorrhage increased. It was evident that the patient, who was already feeble and anaemic, could not survive the operation if there was to be any additional considerable loss of blood. I then at once resorted to the following plan which promptly overcame the difficulty and speedily terminated the operation without further loss of blood:

I took two long-jawed pedicle forceps and controlled all the vessels on each side of the uterus on top of the tumor by thrusting one of the open jaws of the forceps through the capsule of the tumor on one side at about the level of the round ligament from the front of the broad ligament until the point appeared on the posterior surface of the tumor behind the broad ligament; I then clamped the forceps powerfully down on the uterine and ovarian vessels, entirely controlling the circulation. Both sides were treated in this way.

I then took a long-bladed knife, and grasping each uterine cornu with stout short-toothed museau forceps and pulling


in opposite directions, I bisected the uterus and cut on down into the tumor as far as the vesical peritoneum, which was freed and pushed down, when the tumor was completely bisected.

The next steps were the enucleation of the left and the right halves of the tumor. Grasping the left half of the tumor at a convenient point and pulling it away from its bed with a pair of museau forceps it was rapidly enucleated from its uterine bed by means of a blunt cremated spatula, which I always use in the enucleation of myomata. The right half was then enucleated in the same way. All these steps were carried out without a particle of hemorrhage, in remarkable contrast to the beginning of the ojteration.

With the enucleation of the large cervical tumor the tissues surrounding it collapsed, and the uterine artery was easily reached and tied at a selected point below the body of the uterus, and all the difficulties of the situation vanished and the case became a simple one. The two halves of the uterus were enucleated separately and the bed of the tumor closed by buried sutures and the vesical peritoneum drawn over and attached to the posterior peritoneum concealing the wound and the operation finished.

The enucleation of the bisected uterine body may be done after the removal of the tumor in one of two ways — either by tying the ovarian vessels, now easily reached, and the round ligaments and lastly the uterine vessels and then amputating, or by severing first one then the other half of the uterus from the cervix below, cutting from within outwards, from the centre of the cervix towards the broad ligament, and so exposing and catching the uterine vessels, after which they are divided and each half is pulled up in turn by its cervical extremity and the round ligaments of the ovarian vessels tied in order. The direction of the enucleation in this case is from below up, the reverse of the direction ordinarily taken ; the extirpation in this way is facilitated by the sagittal bisection of the uterus.

The patient made an excellent, uninterrupted recovery, and has returned to her home and duties in the country.

I would urge this plan of dealing with fibroid tumors of large size occupying the lower uterine segment, and elevating the uterine as well as the ovarian vessels, and choking the pelvis; in these cases the vessels cannot be tied in mass, but require numerous separate ligatures, and the operator is constantly embarrassed by hemorrhage if the ordinary plan is pursued.

The other case in which still a different plan of operating was found necessary was that of a fibroid tumor filling the pelvis and reaching as high as the umbilicus. The patient, when put on the table, had a rapid small pulse which speedily ran up to 140.

I opened the abdomen, and after releasing some omental adhesions, found the large tumor firmly fixed in front of the vertebral column behind the umbilicus by extensive dense adhesions. The colon was so intimately attached to it that it soon became evident as I tried to detach it that a continued dissection would necessitate an extensive resection of the bowel. I then resorted to a plan successfully adopted in a previous case, January 24, 189J (See Gym Reports, No. 2, p.


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[No. 108.


582), that of leaving a thin layer of the tumor upon the bowel, that is, of sacrificing the tumor for the sake of the bowel. As soon, however, as I cut into the tumor it began to bleed freely, and I did not dare to go ahead on account of the condition of the patient.

I then turned to the lower pelvic pole of the tumor, hoping to be able to free it by tying off the vessels from above downwards and amputating the cervix ; I found it attached to the whole anterior surface of the uterus above the cervix, pushing the fundus of the uterus down to the pelvic floor out of reach. I was able to place two clamps on the tops of the broad ligaments controlling the ovarian vessels, but this was not a necessary step in the following procedure then adopted, which met the complications in a satisfactory manner.

The cervix which could be felt at the vesical reflection was caught by stout short-toothed museau forceps and pulled up within reach; the vesical peritoneum was detached and pulled down, exposing more of the cervix, which was caught with a second pair of forceps.

A knife was then plunged through the cervix in an anteroposterior direction between the two pairs of forceps, and the cervix was cautiously divided from side to side (that is to .-:i\ coronally or transversely) by pulling the divided cervix apart. The cellular tissue to the left of the cervix was first exposed, and the uterine vessels, not yet seen, clamped with a short, stout forceps; the uterine vessels on the right side were next controlled in the same way.

When these important vascular trunks were thus secured, the upper forceps was forcibly used to drag up the tumor and uterine body, rotating them on a transverse axis, exposing first the round ligaments and then the ovarian vessels of the left and the right sides, respectively; these structures were clamped and the whole mass disconnected from its j^elvic attachments. The tumor now only remained adherent by the dense adhesions at its upper pole. The next step was the rupture of an enormous abscess lying behind it and extending from the centre of the tumor into a sac bordered posteriorly


by the lumbar vertebra? and above by the mesocolon and discharging through a large opening into the transverse colon. The tumor now rolled out, being enucleated from behind forward without added injury of the bowel, other than was rendered necessary by the opening into its lumen. The contaminated abdominal cavity and the abscess cavity, containing at least a litre of thick yellow pus, were cleansed, the opening in the bowel sutured and the long abdominal wound closed, leaving a large iodoform gauze drain about the umbilicus into the remainder of the sac under the colon.

The patient has made an excellent recovery with a small rapidly closing fistulous tract.

This type of operation is, I think, the very best that can be adopted for those cases in which there are dense adhesions to the upper pole of the tumor which cannot be dealt with without great risk by attacking them in a direction from before backwards.

I have tried the first plan of operating by bisecting the fibroid uterus in eight cases in all; it has so happened that several complicated cases of tumor developed in the cervical region have recently come into my hands. In the other cases I simply made the enucleation in this fashion in order to demonstrate its feasibility. The continuous transverse incision must always remain the operation of elective choice.

The second plan of operation has been followed in but one case (K. H.).

Cases: A. W., December 10, 1899, No. 7438.

C. W., December 21, 1899, No. 7460. T. B., January 1, 1900, No. 7474.

A. S., January 3, 1900. (Sanatorium.) M. B., January 27, 1900, No. 7537.

D. 0., February 4, 1900, No. 7552.

E. H., February 24, 1900, No. 7583. M. K., February 26, 1900, No. 7597.

K. H., February 1, 1900, No. 7549. (Myoma with abscess opening into colon.)


OBSERVATIONS UPON THE NEURAL ANATOMY OF THE INGUINAL REGION RELATIVE TO THE PERFORMANCE OF HERNIOTOMY UNDER LOCAL ANESTHESIA.*

By Harvey Cushing, M. D., Associate in Surgery, the Johns Hopkins University.


Introduction.

During the past two years in a considerable percentage of the large number of herniotomies performed in Dr. Halsted's clinic recourse has been made to methods of local anaesthesia. In thirty of these cases definite contraindications to the employment of general narcosis have been present, and from this number two definite groups may be recognized:

i I I Those cases in which immediate operative intervention is demanded, as in strangulation, and in which ether is contraiudicated from the shock and vomiting associated with ileus;

And (II) the cases in individuals advanced in years who desire to become rid of an annoying hernia, and who a few

  • Extracted from The Annah of Surgery, Vol. XXXI, 1900, p. 1.


years ago were uniformly refused operation, since associated cardiovascular lesions, chronic bronchitis and emphysema with other senile changes made them submit to the administration of general anaesthesia with notorious uncertainty.

When there exists no apparent contraindication to the administration of ether or chloroform, however, it may safely be said that the anaesthesia of the operator's choice will continue to be a general and uot a local one. Nevertheless, during the past few months observations upon the nervous anatomy of the inguinal region to be reviewed in this paper, have so greatly assisted us in the development of a painless operation that this statement may be qualified to a considerable degree. Since August of 1899 thirty-two herniotomies with cocaine or eucaine ,5 have been performed upon young

men who might without risk have taken a general anaesthetic, and in manv instances absolutely without the infliction of pain other than that incidental to the first insertion of the needle. Daring the fall this procedure became so popularized in the

ward where our hernia cases were admitted that the operation under the local anaesthetic became the method of the patient's choice. An individual awaiting operation needed to remain in the ward only long enough to compare the convalescence of an ether case with that of one done under cocaine to choose the latter for himself. Such patients usually regard the shaving and skin preparation as the most trying part of their operative ordeal, and most of the original observations on cutaneous anaesthesia were made on these cases during the operation and immediately after closing the wound. It has been found also that the patient can assist not a little in certain steps of the operation, as, for example, when the neck of i he sac is closed, in making negative abdominal pressure to prevent the omentum, or bowel, from being pushed down between the peritoneal sutures.

Observations prom Cocaine Operations upon the Neural Anatomy of the Hernial Region.

The application of an anatomical familiarity with the peripheral distribution of the spinal nerves, which since the introduction of ether and chloroform has fallen into abeyance, has become once more of interest and importance to the surgeon in extensive operations under local anaesthesia. Furthermore, no condition has ever afforded similar opportunities for the accurate investigation of the sensory distribution of these uerves, since methods of dissection are necessarily gross, and physiological experiments upon animals naturally present variations from the human type.

The principles of cocainization of main trunks of nerves, introduced as early as 1885, have since heen utilized ill operations on the extremities for minor and even major amputations,* for the anesthetization of areas on the thigh preliminary to the removal of Thiersch grafts and like procedures, but I tun unaware that heretofore similar methods have been made use of in operations on the trunk. To insure success in any major operation attempted under local anaesthesia, an accurate knowledge of the course and situation of the nerves likely to be encountered is most essential, since the accidental division of an unexpected sensory nerve-trunk is often sufficient to overcome whatever preliminary inhibition to pain the patient may have had. and thus to make recourse to complete narcosis necessary in eases where it should, perhaps, be specially avoided. In our earlier hernia operations pain was not infrequently inflicted where now none is occasioned, owing to greater familiarity with the course and distribution of the • concerned.


•Absolutely painless amputations cf the lower extremity for senile gangrene in individuals to whom it seemed unwise to administer ether have on two recent occasions been performed at this hospital after preliminary exposure and cocainization of t fie sciaticnerve in the thigh (under cocaine). This procedure is free from the objections which seem to attend Bier's method {Deutsche Zeittchriftfur Chirurgie, 1899) of cocainization of the spinal cord.


Ill the accompanying sketch (Fig. 1) an attempt has been made to show diagrammatically the usual cutaneous distribution of the inguino-scrotal nerves as well as the deeper situation of the main trunks. Through the kindness of Dr. Bardeen I have been able to compare with my results a great number of sketches made in the anatomical department for an unpublished report on the peripheral nervous system, ami though there is considerable variation in the situation and anastomoses of the particular nerves of this region, as may be seen by consulting Griffin's article (Journal of Anatomy and Physiology. 1891), we have taken what may represent tin average.


Lateral Cutan's of 12 O



Fig. 1. — Showing inguino-scrotal nerves, their peripheral distribution and relation .if the main trunks to the hernia incision, f. iliohypogastric; If. [lio-ingninal ; III. Genito-crural ; IV. Genital branch; V. Crural branch.

Superficial Nerves encountered by the Incision. — The skin incision, as ordinarily made, passes in a line which separates the ventral and lateral cutaneous branches of the twelfth dorsal and lirst lumbar nerves. The lower angle of the incision, however, quite uniformly overlaps the at branches of the first lumbar (ilio-hypogastric) nerve, as they sweep downward and outward from their point of em through the aponeurosis, about five centimetres above the external ring. The upper angle of the incision, depending


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somewhat on its distance from the median line, and also upon the variable and complementary length of filaments of the



Fig. .'. — Areas of anesthesia after double cocaine herniotomy. Anaesthesia lies to the inner side of left incision, which was made nearer Poupart's ligament and has divided lateral cutaneous branches of twelfth dorsal. It lies to the outer side of the right incision made farther from Poupart's and dividing fibres from the anterior division of twelfth dorsal. This was one of our earlier cases in which no attempt was made to preserve the nerves, and the anesthesia is permanent.

ventral and lateral branches of the twelfth thoracic, ma} 7 divide fibres from one or the other of these sources, and thus lead to a subsequent area of anaesthesia to the inner or outer side of this upper angle of the incision. This is well illustrated by the accompanying photograph (Fig. 2) of a double



Fig. 3. — Showing small post-operative area of anaesthesia to the inner

side of the incision, consequent to the division of lateral cutaneous branches of the twelfth dorsal. In this case the ilio-inguinal and genital branch of the genito-crural had been divided with loss of cremasteric reflex, but without producing any cutaneous amesthesia.

herniotomy, in which the incisions were made at different distances from the median line. This bordering anaesthesia, on one side or other of the skin incision, may occasionally represent the entire area of post-operative cutaneous anaes


thesia, even when the ilio-inguinal and the genital branch of the genito-crural have been divided or cocainized, as is shown in photograph (Fig. 3). Presumably in such instances the crural branch of the genito-crural supplies the area on the inner side of the thigh (cf. Fig. 4) usually innervated by the former two nerves. (Such an arrangement occurs not infrequently in Dr. Bardeen's diagrams. On several occasions there has been no resulting post-operative area of cutaneous anaesthesia whatever.

Deeper Nerves met in the Operation. — The ilio-inguinal nerve emerges from the external ring, and near by, or also through the ring, the genital branch of the genito-crural appears. In the canal they frequently are found anastomosed as one trunk, the early cocainization of which at the deeper part of the canal, after splitting the aponeurosis beyond the internal ring, is perhaps the most important step of the operation. As has been stated above, this may result in no additional cutaneous anaesthesia. The usual anaesthetic sequel, however, is represented bv a complete loss of sensation of the entire scrotal contents, cord, hernial sac, and testicle, with the possible exception of its lower vascular supply (superficial perineal),



Fig. 4. — Area of anaesthesia of ilio-hypogastric, ilio-inguinal, ami genital branch of genito-crural in a unilateral cocaine case, following operation. This began to fade by the tweuty-tirst day, with return of cremasteric reflex. This represents the most complete type of anaesthesia in unilateral cases, and is the same even after division of the cord and castration, and consequent section of all possible cutaneous filaments of the genital branch of the genito-crural and the ilio-inguinal.

and by a cutaneous area of anaesthesia which occupies the inner side of Scarpa's triangle, spreading over the adductor tendons. Division of the nerve is uuassociated with any surface anaesthesia of the scrotum whatever (cf. Fig. 4). It is ordinarily stated, to the contrary, that these nerves are a source of cutaneous supply to the scrotum; for instance, Professor Thane says (Quaiu's "Anatomy," Vol. iii, Pt. II, p. 341, 1895), " The root of the penis, on its dorsal aspect, and a part of the scrotum anteriorly are supplied by the ilio-inguinal and genito-crural nerves." It was of extreme interest, consequently, to find that the ilio-inguinal, supplying most of the contents of the scrotum, was not represented by any cutaneous distribution to the same. The inferior pudendal branch of the


March, 1900.]


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61


small sciatic and superficial perineal of the internal pudic, therefore, supply in most cases, at all events, its en tirecutaneous surface. Jt is possible that, on the principle of Sherrington's observation concerning the overlapping of sensory areas, we might account for the failure of anaesthesia after division of the single nerve to appear over the whole territory innervated by it. but as will be seen by comparing segmental spinal lesions such an explanation will not hold, and probably the whole scrotal cutaneous supply is from the sacral and not the lumbar plexus. A case of fracture-dislocation of the spine at



Fig. 5. — Areas of cutaneous anaesthesia result from ;i compression fracture of the twelfth dorsal vertebra, producing a total transverse

lesion at the tifth lumbar segment. Scrotal and penile anaesthesia are complete, though the lesion lies below the first lumbar (ilio-inguinal) segmental level.

the twelfth dorsal vertebra, with transverse lesion of the cord, entered the hospital at the time these observations were being made, and offered confirmatory evidence of what has jusl bei □ stated. The anaesthetic areas resulting from this injury, and which are shown in the accompanying diagrams plotted by Dr. Yates (Fig. 5), offered an interesting negative of the anaesthesia following the hernia cases. Though tin penis and scrotum in this case were devoid of sensation, the transverse lesion of the cord was situated at the fifth lumbar segment, — that is, between the level of origin of the ilioinguinal (first lumbar) and that of the small sciatic and


internal pudic (second and third sacral) nerves. If the ilioinguinal normally overlapped the latter nerves, the root of the penis and upper part of the scrotum would naturally have retained sensation. A similar condition is shown in one of Kocher's diagrams of a case of fracture-dislocation at this level. (Die Lasionen des RuchenmarJcs u. s. v., S. o-. 1 ; i. In another of his cases {Ibid., S. 631), in which the segmental lesion is at the 3-4 sacral level, the upper portion of the scrotum has retained sensation as the inferior pudendal i 1-2 sacral) has escaped injury.

Furthermore, in this spina! case, as would be expected, the cremasteric reflex was retained, whereas we have observed that after division or cocainization of the ilio-inguinal andgenitoerural nerves, this reflex is. temporarily, at all events, lost on the side of division.* On the other hand, the vermicular movements of the dartos, supplied together with the skin by the sacral nerves, are preserved after divisions of the ilioinguinal, but were lost in the spinal case together with the cutaneous anaesthesia.

The ilio-hypogastric, as will be seen in the diagram (Fig. 1). may be twice encountered in the operation ; its superficial filaments by the sktu incision, as has been described, and its deeper trunk, as it lies upon the muscle-fibres of the internal oblique at a varying distance from the lower edge of the muscle (Fig. 6). Cocainization of the edge of this muscle, consequently, before its division as in the Halsted operation, is very necessary, especially since, in addition to this main trunk, which may usually be easily recognized after exposure of the internal oblique, there are, contrary to Griffin's observations, offshoots to the muscle itself from this nerve, given off dorsad to the portion exposed by the iucision. There are fibres from the genito-crural (Thane) as well, which are similarly distributed to this lower border of the internal oblique. The ana of cutaneous anaesthesia, which follows ansesthetization or division of this main stem id' the iliohypogastric at its point of exposure, surrounds the lower angle of the incision, and extends from a level about seven centimetres above the root of the penis to within one or two centimetres of that organ. No anaesthetic area has ever been found corresponding to Macalister's described branches reaching up towards the umbilicus. In unilateral cases this ilio-hypogastric anaesthesia does not extend to the median line, owing to the overlapping of fibres from the opposite side, so that in bilateral cases alone, such as are illustrated by Fig. 2, can its limits be definitely made out.

The Anesthetic, and Application of Anatomical Observations to the Operation.

It is not within the scope of this paper to discuss the relative merits of various local anaesthetics; suffice it to say that we have found the combination advocated by v > ("Schmertzlose Operationen," L899) to be as efficacious as any with which we have experimented. His solution >>"o. taining the following ingredients:


  • It is important, therefore, to guard against division of these

nerves in varicocele operations in which it is desirable to preserve cremasteric tone


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Cocainas mur., 0.1

Morphine mur., 0.02

Sodii chlor., 0.2

Aqua destillata, ad 100.00

has best served our purpose, and has been without the objections usually accredited to cocaine solutions, — viz., toxicity and dissolution when sterilized. Solutions in strength of 1 to 20,000. Scbleich claims to be efficient for infiltration, and capable of producing anaesthesia winch is free from the prodromal hyperesthesia, the "anaesthesia dolorosa," which accompanies aqueous and saline infiltrations. Amounts of the 1 to 1000 solution, however, greatly in excess of what is needed for the longest operation, have failed to give toxic symptoms, and, contrary to the experience of many, we have found that one or two sterilizations fail to diminish its efficiency. Experience with eucaine ( 3, which Braun (Archiv fur Jclinische Ghirurgie, 1898) and Hentze (Archir fur pathologische Anatomie und Phi/siologie, 1898) have so strongly advocated, has failed to demonstrate in our hands that it possesses any superiority over the 0.1 percent cocaine solution of Schleich. In fact, we have been impressed by the fleeting nature of the anesthesia and by its tardy appearance.

On several occasions long skin incisions have been made through a linear area of anaesthesia, produced half with sterilized Schleich's solution and half with the eucaine ,5 combination, which Braun advocates. If the operation is prolonged over an hour, pain is occasioned on placing the subcuticular suture of closure in the eucaine area, while none appears in that which had been infiltrated with cocaine. The fact that its toxicity is five times greater than that of eucaine does not argue in its disfavor, provided one uses solutions weak enough to avoid toxic effects. For anesthetization of the individual nerve-trunks I have used a •> to 1 per cent sterilized solution usually of cocaine which is injected directly into the nerve sheath.

Steps of the Operation. — Individuals — and it is especially important for those advanced in years — are usually kept in bed for a day or two preliminary to the operation, to give an indication of their ability to endure recumbency and for the purpose of training them to void their urine in this position. Evacuation of the bladder is usually accomplished by the aid of an enema if any postural difficulty is experienced, and it is a matter of satisfaction that but one of the cases reported in which these precautions were taken required post-operative catheterization, an old man, sixty-eight years of age, who had symptoms of prostatic hypertrophy.

It has been the custom to administer hypodermically a tenth or an eighth of a grain of morphine, three- quarters of an hour before, and to repeat this shortly before the operation. Ceci has emphasized the efficiency of this morphia-cocaine combination, and I have found it most satisfactory. The drug must be used with caution, however, since occasionally even small doses of morphine in old people may confine the bowels and lead to distention, which may be troublesome, as one of our cases illustrated. Similarly, in old people with tardy bladders, it may inhibit the proper evacuation of the urine, though we have never had the misfortune to observe this.

Patients past middle age also are usually shaved and cleaned


on the operating-table, to avoid any exposure incidental to an open-ward preparation. The skin in the line of proposed incision is infiltrated with Schleich's cocaine solution, and the incision may be immediately made through the linear wheal thus produced. It is common experience to find the infiltrated tissues more vascular than usual, and it is important that all bleeding points be immediately clamped, since a dry and unstained field is essential to the success of the dissection.*



Fig. 6. — Sketch showing usual situation of nerves as exposed after reflection of the divided aponeurosis.

It is unnecessary and useless to attempt to anesthetize the panniculus. As Schleich has shown, only tissues which can be " cedematized " are fitted for the infiltration method, and in the panniculus, at the upper angle of incision practically no nerves are encountered. If, however, throughout its whole length, this incision is carried down to the aponeurosis, unanesthetized fibres of the ilio-hypogastric will be encountered in the superficial fat at the lower angle, together with one or two large veins, division of which is painful, so that anesthetization of the panniculus layer would here he necessary. A much better method is to carry the incision only at


  • A good index of one's skill and familiarity with the hernia operation can be drawn from the condition of the tissues at the time of

closure, for they should be as free from blood-staining as when first incised. This, of course, is the most important factor in obtaining perfect healing, and for the accomplishment of this a good assistant is indispensable. A perfect hernia operation is not a " one-man " operation.


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the upper angle down to the aponeurosis, which is then opened in line of fibres from the external ring, and the ilio-hypogastric and inguinal nerves immediately cocainized with a 1 per cent solution as they are thus exposed. After this procedure the lower angle of the incision may be painlessly carried down to the external ring, and the remaining intercolumnar fibres of the aponeurotic insertion divided. Reflection of the pillars of the ring then gives the view shown in the accompanying sketch (Fig. 6). In the Halsted operation at this stage the internal oblique fibres are divided, preliminary cocainization of the edge of muscle being necessary for the reasons given above. There is, under ordinary circumstances, no further need of the anaesthetic, as we are working in an area freed from all sensation. The combined ilioinguinal and genital branch, which has been cocainized at the outer limit of exposure, is now reflected usually to the outer side, care being taken not to divide it, since this leads apparently to a more or less permanent paralysis of the cremaster, which is to be avoided. I believe the accidental division of this nerve leads to the great relaxation of the scrotum so often seen after hernia and varicocele operations. In the latter operation, especially, it would be detrimental to the best interests of a successful result to interfere with the cremasteric function in any way. I think it not impossible also that the division of these nerves and interference with the sympathetic plexus about the cord may be responsible for the occasional atrophy of the testicle which has followed the great denudation of the vas deferens in some operations. The remainder of the operation, the exposure of the sac and cord after a longitudinal division of the infundibuliform fascia, the amputation of the sac at its neck, and closure of the peritoneal opening, the excision of the fundus of the sac, division of the cord and castration — if deemed advisable in senile cases— may now be done practically without pain. Occasionally, however, some stray fibres of the genito-crural may be encountered about the neck of the sac, and also during castration I have found that ligation of the veins at the lower pole of the testicle may be painful, though division of the cord above is not. Possibly the superficial perineal branches which have been unanaesthetized furnish nerves to this lower blood-supply.

The closure of the parietes by any of the more commonly employed methods may now be painlessly accomplished. Not infrequently in these cases, in old people with large hernias of long standing, the two rings have become concentric, and the falciform expansion of the conjoined tendon is no longer present. It is in such cases that Bloodgood has advocated transplantation of the rectus fibres after opening of the sheath and exposure of this muscle, so that a muscle-lined wound may be formed throughout the whole length of the inguinal canal. Xo additional cocainization is necessary for this step, since innervation of this portion of the rectus comes by the nerves already cocainized. Tightening the deep sutures in closing the wound may elicit a dull sensation of pain, which the patient usually describes as an uncomfortable sensation of " pressure" and it is occasionally possible that the upper one of the deep sutures must be placed above the field which is completely anaesthetized and thus be painful. For this reason it should be left to the last. The subcuticular


silver suture, used in closing the skin, does not pass beyond the limits of the original area of cutaneous infiltration, and consequently it may be placed without pain. Interrupted " through and through " cutaneous sutures, of course, must be avoided, as they would emerge outside of the limits of original cutaneous infiltration.

It occasionally happens during the operation, whether from slight ability on the patient's part to endure discomfort or from the accidental division of some sensory fibres, that what inhibition towards pain he may have at first possessed becomes exhausted, and recourse must be had to a general anaesthetic. Under these circumstances we have found that a few inhalations- of chloroform — not enough, however, to make the patient lose consciousness — are sufficient to tide him over the most difficult parts of the operation. It is remarkable, under such circumstances, how small an amount of the general anaesthetic is requisite to benumb sensation. We may justly speak, therefore, of the method of anaesthesia which is employed as a morphia-cocaine-chloroform combination, the first and last drugs being merely adjuvants of the local anaesthetic, which in most cases suffices alone.

An assistant in these cases, who takes the place of the anaesthetist, occupies by no means an unimportant position. The usual record of pulse and respiration is kept, and by occupying his attention and by timely encouragement the patient may be tided over the more trying periods of his operative ordeal; duties which otherwise devolving upon the operator may be distracting. Lilienthal {Annals of Surgery, 1898, p. 58) speaks of this position as that of a "moral anaesthetist."

Patients have never complained of post-cocainization pain in the region of the incision, and healing seems to have been absolutely unaffected by the local infiltration. In none of these cases has there been other than primary union. It is very unusual for the large, starched, or plaster dressings, immobilizing thigh and pelvis, to be cut down before the tenth or twelfth day, when the suture is removed.

Advantages of the Local Anmsthetic. — There is an avoidance of unpleasant or dangerous post-etherization secpuelae. There is no vomiting or retching to put strain upon the recent sutures. Urinary disturbances are much less apt to occur, and catheterization is rarely necessary. The diet may practically be continued as before the operation. There is no backache, since there is no narcosis to induce relaxation of spinal muscles, and thus put strain upon the ligaments. The dressings may be applied originally to suit the comfort of the patient — which is of especial importance in old people — and there is no subsequent disarrangement of them. Above all is the advantage gained in being able to operate with comparative safety in patients who would incur immediate risk in submitting to general anaesthesia.

Disadvantages. — These seem trivial in comparison. More time is consumed in the operation, and there is necessarily some distraction to the surgeon. In two exceptional instances there has been some post-operative nausea for a few hours — possibly from an idiosyncrasy toward cocaine. The operation is doubtless more difficult and some pain is inflicted. The degree of this depends entirely, however, upon the surgeon's familiarity


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with the use of local anaesthetics in abdominal work, as well as with the steps of the hernia operation and also upon his knowledge of the anatomical distribution of the sensory nerves of the region concerned. On many occasions no actual pain whatever need be experienced, and should there be some, it is small in comparison with the discomforts of an ether convalescence;


and the greater difficulties which confront the surgeon at the operating-table are more than compensated for by his subsequent freedom from the anxiety which, in this particular class of cases, attends the administration of, and convalescence from, general anaesthesia.


THE PATHOLOGICAL FINDINGS IN A CASE OF GENERAL CUTANEOUS AND SENSORY ANESTHESIA WITHOUT PSYCHICAL IMPLICATION.

ABSTRACT PAPER. By Henry J. Berkley, M. D., Clinical Professor of Psychiatry.


The detailed clinical history of this case can be found in Brain, Vol. XIV, Part IV, 1891. A careful search of the medical literature has disclosed no similar instance occurring either before or since the date of its publication.

A synopsis of the clinical record as then published shows:

(1) A strong hereditary tendency to nervous instability; the mother, two maternal uncles, two brothers and two sisters having been insane. The father had died of tuberculosis.

(2) A syphilitic infection acquired from her husband at the age of twenty-nine years, subsequent to which the patient had several abortions, sore throat and falling out of the hair.

For twenty-two years after the subsidence of acute symptoms due to the syphilitic process there was fair health. Then came an attack of acute arthritis, after which the patient never fully recovered her former physical condition. Within a few months thereafter, her eyesight began to grow dim, there were sudden flashes of light before the eyes, and vision was gradually extinguished, only sufficient remaining to enable her to distinguish light from darkness.

In the early summer of 1889, nearly six years after the rheumatic attack, the patient began to experience a general tingling and formication in the skin of the entire body, which was shortly followed by several spells of uncontrollable vomiting.

A consensus of the numerous examinations made during the years 1889 and 1890 showed a total loss of thermic, pain, olfactory, gustatory, equilibrium, pressure and weight sensations; almost total of the visual sense; and a partial loss of tactile and muscular imjiressions, muscular sense and auditory perceptions. None of the special senses, or cutaneous sensations remained wholly uninvolved.

Besides these disturbances of the sensory apparatus several other symptoms of almost equal prominence were recorded.

The musculature while responding to the will did so in such a feeble manner that the patient was incapacitated from helping herself to any extent. Thus the dynamometer when taken in the hand and squeezed was so feebly compressed that the indicator showed no movement on the dial, though the woman exerted every effort in the trial. Despite this fact, however, both nerves and muscles responded promptly to the galvanic and faradic currents, nor was there anything abnormal noticeable about the quality or time of the reaction,


The cutaneous reflexes were all abolished. The faucial and pharyngeal reflex movements were absent, and a sound could ■ be passed over the epiglottis into the larynx withoutelicitinga sensation of discomfort or inducing cough. During the attacks of emesis there was no sensation of nausea.

When first examined the knee jerks were present and normal. The biceps jerk could also be elicited with some little trouble. The reaction of the abdominal muscles was lost, and the ankle beat was feeble. By the middle of July, 1890, the right knee reflex had disappeared, and the left one was weak. All other reflexes, deep and cutaneous, had been completely abolished. A year later the jerk of the left patella tendon was found to be extinguished.

Furthermore, with auditory perceptions a progressive dulling could be noted. When the woman was first admitted to the hospital, the sense of hearing was fairly acute in both ears. Gradually the difficulty in receiving auditory impressions increased, until finally the voice could not be heard except with strenuous effort.

The ophthalmoscopic examination showed an extensive choroiditis pigmentosa with atrophy of the optic nerves. Only a few vessels could be seen in the retina, aud these were of minute size. In both lenses there was a beginning cataract.

Whether the optic nerve atrophy should be considered part of the general disease-process, beginning as it did long before the other symptoms, is somewhat problematical, though in tabes the same trouble is not infrequently noted as a forerunner of definite symptoms of the disease.

The pupils were at first in a state of mid-dilatation, and responded slowly to light, direct or reflected. They did not dilate on irritation of the cervical sympathetic. At a later stage the pupils became somewhat narrower, but remained sluggish to stimuli.

There were a number of interesting disturbances of the glandular secretions. During the fall of 1889 the mouth was found to be almost absolutely dry, the tongue heavily cracked, the epithelium eroded from its tip and sides, while the entire buccal surface was red and congested. At the same time the secretions of the lachrymal glands had almost ceased, the surfaces of the conjunctivae being dry and injected. The skin was also dry aud devoid of odor. After a course of potassium iodide these phenomena slowly abated, and the secretions returned to a more normal state.


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Various unusual sensations troubled the patient at times. Tramps of the gastrocuemii, sensations of burning h the scapula?, a girdle feeling around the abdomen and neuralgic twinges in the nerves of the extremities were often complained of. Occasionally there were clonic fibrillary spasms of the small muscles of the thumbs.

Attacks of diarrhoea, refractory to treatment with drugs, though yielding to a continued milk diet, occurred in the latter part of the winter of 1890. These were on several occasions followed by a protracted vomiting without pain or nausea.

Trophic symptoms in the form of a bulbous appearance of the finger tips and ridgiug of the nails, together with purpuric spots, developed late in 1891.

Throughout the long course of the illness there was never the slightest departure from normal mentality on the part of the patient; no hysterical attacks, no pathological depression or exaltation, and no delusions or hallucinations were ever noted. A slight apathy was the only perceptible change in the mental phenomena, but this was not greater than is frequently noticed in those who have become blind and helpless.

In discussing the etiology of the sensory phenomena in the previous article, three possibilities were suggested : (1) that the malady was functional, an opinion largely influenced by the pathological findings in the three autopsies on cases of general cutaneous and sensory anaesthesia, reported by Von Ziemssen, Krukenberg and Schiippel respectively. This view was held to be hardly consistent with the presence of an optic neuritis, loss of the reflexes and the trophic manifestations ; (2) that the case was an obscure instance of syringomyelia ; or (3) that the terminal end-apparatus of the peripheral nerve fibres was diseased.

Though many points are not cleared up by the autopsy, and subsequent microscopic examination of the tissues, the results obtained are sufficient to show that none of these explanations would hold good, the nearest approach to a correct diagnosis being found in the last conjecture — disturbance of the peripheral nervous system.

The patient's condition did not materially alter after the record of the case was published. The anaesthetic and other symptoms, from the reports of the House Physicians to the Hospital, remained about stationary, and on the rare occasions on which I saw her, there were no additional phenomena to he noted other than a steady though slow decline of the vital powers. Late in the year 1893, another ophthalmoscopic examination was made by Dr. H. Friedenwald, who found in the left eye an extensive and typical retinitis pigmentosa, the papilla being blurred and of a dirty yellow color. Fewvessels could be seen. In the right eye the clouding of the lens was so profound that the retina could not be seen.

About the middle of May, 1898, Mrs. R. became slightly lethargic, a condition that slowly increased to coma, in which state she died on the 25th of the month.

The autopsy, performed ten hours after death, was distinctly negative, all portions of the central and peripheral nervous systems showing an apparently natural condition. 'I Inlarger vessels of the thorax, abdominal and cranial cavities,


showed scattered atheromatous plaques, but were not considerably thickened. The right middle cerebellar and both posterior communicating arteries of the circle of Willis were congenitally rudimentary. There was some gelatinous thickening of the pia over the central regions of the hemispheres. The optic nerves showed but faint signs of a diseased condition, although the left nerve was a little smaller than the right one. Both kidneys were atrophic, weighing 100 grams each, the loss being principally in the cortex.

After proper hardening for the various Nissl, Weigert, Marchi, and other stains, sections of the entire nervous system were made and studied. The results obtained were to a degree remarkable, and for the sake of convenience may be separated into three categories. (1) Lesions appertaining to the blood vessels, (2) those of the proper nerve elements, and (3) those belonging to the membranes surrounding the encephalon and cord.

There being some difference in the intensity of the vascular lesions in the several portions of the nervous system, it is perhaps better to describe the appearances in the several sections in detail. Those of the arteries of the cord being the best defined will be first studied.

The arteries and veins contained in the pia mater are all immensely thickened, but the morbid process varies considerably in its histological characters in different vessels. In the largest arteries, for example, in the arteria spinalis anterior, the iutima is approximately normal, while the middle lamina is greatly hypertrophied. In this latter layer the nuclei are too numerous, though few of them correspond in morphological characters to the nuclei of smooth muscle cells. The adventitia shows no alteration either in respect to its nuclei, or to the connective-tissue fibres.

In a few arteries running longitudinally in the cord's envelope the endothelium and fenestrata have separated from the muscularis — probably a post-mortem change — while the latter layer has assumed a coarsely fibrous aspect, and holds but few nuclei of any kind. The fibres making up the former muscular layer are arranged in a convoluted fashion, resembling to some extent the iufoldiugs of a fenestrata, and on a superficial examination the whole layer might be taken for a multiplied membrana elastica. That such is not the case is readily determined by the fact that a perfect lamina is often found internal to the fibrous middle layer.

In a few of the medium-sized arteries, the lumen is completely closed, solely from an overgrowth of the middle layer. The fibrous tissue composing this media shows no evidence of a hyaline degeneration.

The contents of the lumen of such vessels as are not obliterated are interesting. With eosin hematoxylin or the Van Gieson stain, the whole canal is seen to be filled with a material containing no blood cells, and homogeneous except for a faint granulation. In preparations by other stains, this homogeneous substance is found to contain a few epithelioid cells with round nuclei. Naturally, vessels that are entirely obliterated, or have their lumen filled by a partly organized mass, were in the minority, the greater number having sufficient blood-carrying capacity to perform a portion of their vital functions.


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The smaller arteries also present considerable variation in their structural conditions. A majority have walls thickened in the same manner as is present in the larger ones, while with others there is a minor though distinct degree of hyaline degeneration of the middle coat— it now assuming a yellowbrown tint with picric-acid fuchsin. When this hyaline condition is preseut, the nuclei are sparse and deformed. In a few arteries the elastica is reduplicated, or even quadruplicated, while at the same time the lumen is so narrowed as to be obliterated here and there, or the small opening internal to the intima is filled with a mass of epithelioid cells, in which stainable nuclei are uncommon.

The walls of the larger veins are almost as thick as those of the arteries, but the lumen is dilated rather than narrowed, and often with an irregular outline.

The root fibres of the entire cerebrospinal axis contain numbers of thickened vessels, some patulous, some obliterated. Many of these vessels show a considerable degree of hyaline alteration of the muscularis. Nowhere, however, do the nerve bundles present any considerable augmentation of the connective-tissue elements.

At one point surrounding an artery coursing longitudinally in the meninges, just outside of the external margin of the left Burdach column, lies a nodule of disintegrated round cells, which bears much resemblance to a gummatous neoplasm, which after growing a certain extent had degenerated. The size of this new formation was very small.

The walls of the vessels within the substance of the cord were also greatly thickened, some of those in the anterior horns being visible to the naked eye. Others in the medullated regions are almost equally large. Everywhere there is hypertrophy of the vascular walls, principally of the middle layer and at times it is difficult to distinguish between vein and artery.

The vessels appear to be unduly numerous everywhere; there is no actual new formation of vessels, but the smallest arterioles, even the capillaries, are so thickened as to be unusually prominent in the microscopic field.

This condition of affairs is more especially true for the gray horns than for the medullary tracts. The horns seem to be everywhere strewn with vessels of all sizes, from those noticeable by the unaided eye to enlarged capillaries. The region containing the greatest number of diseased vessels lies lateral, on both sides, to the gray commissure and in Clark's columns.

There was considerable variation in the intensity of the vascular disease in the several regions of the cord and bulb. In the lumbar and cervical levels, while the morbid process was distinct, it had not the same severity as in certain regions of the medulla, and especially in the lower levels of the dorsal cord, where the lesions seemed to have reached their acme of intensity.

The diseased arteries and veins within the nervous tissues have now only one type of alteration. The intima is but slightly affected, a little thickening of the subendothelial tissue being now and then visible, but it is upon the media that the greatest stress of the pathological condition has fallen. This layer is greatly thickened, and presents either a


hyaline or fibrous appearance, according to the intensity and duration of the process, the hyaline degeneration apparently preceding the fibrous change. In some of the vessels the peculiarly shaped nuclei of the muscular structures are to be seen at infrequent intervals, distorted and shrunken to such an extent as to be hardly recognizable. In others no nuclei at all are to be found, and the lamina though fibrous is homogeneous in character. With the Van Gieson stain, the media of a number of vessels takes on a red coloring, but this is diffuse over all the layers, and not confined to the middle one. In still others, the stain acts differently; the intima and adventitia are tinged red, while the muscularis takes only the yellow of the picric acid, and appears not striated but homogeneous.

Externally to the muscularis, lymph spaces are often noted corresponding to local dilatations of the intravascular space. These sometimes contain a few leucocytes. In the adventitia around the altered vessels there is little or no morbid change. It is not unduly thick or fibrous in character, and contains a moderate number of round and oval nuclei. In eosin-hsematoxylin preparations a greater degree of intimal involvement is noticeable. There is distinct though slight hypertrophy of the layer, with multiplication to a limited degree of the endothelial cells. The lamina are nowhere closed, though there may be great thickening of the media. The regular ring-like appearance of the lumen is rarely disturbed.

Vascular lesions in the cortex and ganglia of the brain are not nearly so profound as in the cord, though here and there a vessel considerably thickened may be noted, the alteration affecting principally the middle layer.

In the meninges of the encephalon fairly numerous thickened arteries are to be seen. They are not equally distributed everywhere, but occur locally. The points of selection in the basal regions for the most altered vessels are in the nerve roots, and especially in the arteries lying between the nerve bundles. In nearly all of the cranial nerves several of these pathological vessels are to be seen, though it is only rarely that a degenerated nerve fibre is to be discovered near them, with the exception of the optic nerve tracts where all the fibres have atrophied.

The arteries of the integument showed precisely the same lesions as those of the cord and meninges. In some the morbid process is more extensive than in others, and pronounced hyaline changes in the media are noticeable. The muscular nuclei have for the most part disappeared. The endothelial and subendothelial structures are slightly hypertrophied.

Lesions of the nerve elements varied in direct concordance with the severity of the vascular disease, reaching their acme in the lower portion of the dorsal cord and in the medulla. There was a subsidence of the acuity of the process in the upper region of the cord and in the cortex cerebri. All the changes of a pathological nature were strictly of an atrophic order, and of these the fatty pigmentary degeneration of the cells was the most prominent. Of secondary importance was a condition of simple atrophy of the entire nerve body with shrinkage of the protoplasm and nucleus. The lesions of the conducting fibres were also entirely of a degenerative type.

Throughout the cord, but especially in the dorsal region,


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many of the cells in the gray horns were completely filled with

coarse yellow pigment grains, among which a shrunken nucleus is now and then discernible. No nucleolus is visible in the atrophied vesicles. In rather infrequent instances the nucleus is pushed to the periphery of the cell. The cells of the columns of Clark seem to have suffered more severely than elsewhere.

in those cells in which the accumulation of pigment is not BO considerable, the Xissl bodies are coarse, do not retain their regular arrangement in the protoplasm, but are irregularly distributed throughout the substance. At times these granula also show a tendency to group themselves together at the periphery of the cell-body. leaving a clear ring of considerable extent around the neighborhood of the nucleus. In still other nerve bodies there are scattered clumps of granula in the protoplasm, with large spaces in between devoid of any staiuable substance. Lying among these better preserved cells are others that are shrunken to a mass of fine granular material in which neither nucleus nor nucleolus is visible.

The state of the nucleus varies considerably in the least damaged cells. In a majority the caryoplasm and chromatin particles are natural, but there are also a variable number in each section in which the vesicle has the appearance of being swollen, aud the nuclear substance is unstainable. In a very few instances there is a double nucleolus marking the presence of an irritative process.

In the upper cervical enlargement and medulla the state of the cells was almost precisely similar to that at the lower levels, though a larger proportion shows a normal arrangement by the Nissl methylene blue. In a considerable number the protoplasm is filled with masses of yellow pigment, which sometimes covers and obscures the nucleus. The irregular disposition of the Xissl bodies in some nerve elements is shown with great distinctness, but in others the granula are diffused throughout the cytoplasm, and their ordinary appearance is (oat. Quite a number of the nuclei exhibit a shrinkage of their volume and irregularity of contour. The vesicle also has a tendency to retire to the periphery of the protoplasm.

In the medulla, there were cells among the scattered nuclei on the floor of the ventricle that showed displacement and distortion of the cell-nuclei, but pathological cells on the whole are not common, and few of the nuclei of origin of the cranial nerves contain any considerable numbers of them.

In the higher regions of the medulla oblongata the cell-nuclei are much more frequently displaced than lower down, and the bodies of the cells show greater atrophy. In the region lateral to the V-shaped point of the ventricle there are numerous heavily pigmented cells. The entire cytoplasm is now filled with it, and the nucleus is no longer visible. Some of the nerve elements are in process of disintegration, and double nucleoli are by no means infrequent within the nuclear ring. The morbid process is most marked in the nuclei of origin of the .\, XI and XII cranial pairs. Corresponding with the degree of cellular degeneration there is here an advanced degree of arterial disease.

In the anterior portion of the medulla the superior olivary bodies show a pathological state, in that their cells contain heavy masses of pigment equally diffused through the bodies.


Elsewhere the accumulation of metaplastic material can hardly be said to be greater than is ordinarily found in persons of

somewhat advanced age. The Xissl bodies are fairly well stained in such cells as are not considerably pigmented. The cells of the glossopharyngeal nucleus have less pigment in them than any other nerve elements of this region.

At the level of the pons the cells of the nucleus acusticus dorsalis are filled with metaplastic granules; all others are freer from the accumulation of grains than in the medulla. The nuclei in the cells of the acusticus are displaced, and the outlines of the vesicles are indistinct.

Few changes can be determined among the nerve bodies of the cerebellum, and the vascular lesions are correspondingly slight.

In the cortex the quantity of the pigment granules in the pyramidal cells was not above the normal, and is not diffuse but confined to one corner of the cell. The nuclei and nucleoli are perfect. The cells of the corpora striata and lenticular bodies were a little more pigmented than those of the cortex owing to the more extensive vascular implication.

Taking into consideration the severity of the vascular lesions and the degree of pigmentary atrophy of the protoplasm of the nerve bodies consequent thereto, there is singularly little degeneration of the medullated portion of the neurone, aud when it does occur, it is only where the vascular disease has reached its maximum of intensity. But two of the cranial nerves showed any varicosity or atrophy of the nerve fibres. The gray degeneration of the optic nerves had apparently long antedated the other lesions, being far more advanced. Few medullated tubes in the tracts showed any blue-black coloring with the Weigert stain, aud all were atrophied; yet there was a very trivial thickening of the interstitial connective tissue between the bundles of fibres, and uo multiplication of the fixed nuclei. The degeneration of the fibres among the bundles of the hypoglossal nerve was limited to a single strand, and was probably a direct consequence of the occlusion of an artery that ran longitudinally through it.

The examination of the root fibres of the superior portions of the spinal cord was negative. In the dorsal region a greater number than usual of small medullated tubes were discovered, and some of these were blackened by the Marchi stain, but altogether the number was inconsiderable. No varicose fibres were to be seen anywhere.

Within the substance of the cord, two sclerotic tracts, both of small size and among the ascending fasciculi were found. The lumbar cord was free from any trace of medullary degeneration, and it was not until the level of the ninth dorsal vertebra was reached that any disease of the white columns became manifest. At this level, a small area of degenerated fibres first becomes visible, situated in the right column of Burdach in close proximity to that of Goll. The area occupied is very small. It was at first entirely separated from the pia, but soon approached it more closely, and finally touched the margin. The form of the degenerated tract was irregularly pyramidal, the base broad, lying upon the external margin, the apex, sharply defined, penetrating more deeply. Nearly all of the nerve tubes within this area are atrophied,


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with here and there an enlarged axis cylinder among them. This degenerated zone disappeared entirely before the cervical enlargement was reached.

A few millimetres above the beginning of the first degenerated tract (at the level of the lowermost border of the seventh dorsal vertebra), a new area of degeneration was noticed, this time in the left postero-lateral column. At first it appears under a magnification of 80 diameters, as a circular patch not larger than the head of a pin, lying close to the Lissauer zone though not within the indirect pyramidal tract, and well separated from the external border of the cord. Very shortly it enlarges, and assumes a wedge-shaped form, having its broad base on the external border of the cord, and its apex turned towards the deeper regions. It now lies well within the direct cerebellar fasciculus.

Tn the lower cervical region, the sclerotic area broadens, and at the same time moves from the posterior part of the column to a position almost in the middle of the lateral region, now occupying a place along the posterior edge of the Gower's tract. The irregular wedge-shape is retained throughout this region, the borders of the degenerated being sharply defined from the normal tissue.

In the uppermost region of the cervical cord, the sclerotic zone again moves slightly forward (ventrally) until it comes almost directly into the Gower' tract, then at the level of the lower portion of the pyramidal decussation it decreases perceptibly in size, and at length becomes reduced to a narrow band along the anterior border of the cord, completely within the Gower's bundle.

The sclerotic tract now rapidly decreases in size until it is finally lost at the level of the uppermost portion of the decussation, no degenerated fibres being found in the direct cerebellar tract or extending in the direction of the nucleus lateralis. The cells of this nucleus are numerous, not atrophied in the least, and do not differ in any way from those in the adjacent nuclei of origin of the nerve roots. Sections carried through the medulla aud pons failed to show any further degenerated tracts. Prom the lowermost dorsal to the level of the lower cervical enlargement, the fibres contained in the posterior commissure were much less numerous than usual.

Except in the sclerotic fasciculi, an examination of the neuroglia cells failed to show any participation on their part in the morbid process. While in places about the root fibres of the nerves or origin, the pia was to some extent thickened, this alteration was never considerable, aud w hat thickening there was of the membrane was dependent upon an hypertrophy of the fibre elements aud not upon multiplication of round cells.

To recapitulate: — The fundamental pathological basis for the various nervous phenomena described in the clinical history of the case is as follows: (1) A hyaline-fibrous degeneration of the arterial system existed, which was not confined to the central nervous regions, but was equally evident in the roots of the spinal nerves and iu the skin tissues. The degree of alteration varied from slight thickening of the muscular layer to complete closure of the lumen from hypertrophy of the middle coat of the vessel walls. The morbid change was


accordingly not uniform, but reached its maximum of intensity in the vessels of the lower dorsal cord, the meninges of the bulb and cord, aud also in certain of the root bundles of the cerebro-spinal nerves. (2) As a consequence of the vascular lesions there were degenerations of an atrophic order in the nerve cells of the gray horns of the cord, more particularly in those of Clark's column, and in the medulla oblongata. To this alteration in the central nervous substance at least a portion of the various symptoms must be attributed. Besides the principal lesions there were others of considerable, though minor importance.

The degeneration of scattered fibres in the bundles of the spinal and bulbar nerves played some part in the general symptomatology, being shown during life by the lowering of tone as regards the innervation of the muscles, as well as by disturbances of the functions of the nerves extending from the terminal apparatus.

The sclerosis of a portion of the outer zone of Burdach's column would siguify that fibres ascending through the posterior root zones were degenerated, though the small area involved shows that their numbers were inconsiderable. The lesion of the tract itself has but little significance, the fibres involved belonging to short inter-connecting bands.

The lesion of the direct cerebellar tract is not only of more importance, but presents some rather peculiar features. The absence of the majority of the medullated fibres from the posterior commissure, over considerable regions of the medulla spinalis, favors the view that a portion of the cerebellar bundle is formed from the fibres of this commissure. The gradual change of position in the sclerotic area shows also that the fibres — at least in this instance — do not proceed directly upward in the column, but are gradually diverted as other fibres enter, and assume a more and more anterior position ; and, furthermore, that a portion of the fibres are lost in the upper cervical and lower regions of the medulla and do not proceed to higher levels. This ending of the ascending fibres has been ascertained for a part of Gower's bundle, but is not usual in the case of the component medullated fibres of the direct cerebellar tract. At its beginning, the degenerated area almost touched the left posterior root zone, while iu the upper cervical region it verged upon, if it did not enter, the area assigned to Gower's bundle. The total disappearance of the degenerated area at the lowermost level of the medulla may be considered to have sufficient anatomical value upon which to base the theory that in the so-called direct cerebellar tract other fibre bundles, which are at present unknown, enter into its formation, and that these correspond more closely, in their manner of termination, to the bundles of the Gower's system than to those of the cerebellar paths. The deportment of the sclerotic fasciculus may also give rise to the supposition that we have to do more here with an undescribed bundle, running from the dorsal to the uppermost cervical region.

As an explanation of the numerous symptoms of the case, it would appear most reasonable to suppose the existence of a disease-process affecting simultaneously both the peripheral and central nervous systems. Assuming that the arterial lesions were of late specific origin — and of this there can be


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but little reasonable doubt — a chronic progressive involvement of the nutrient channels, here and there leading to marked narrowing or even to closure of isolated vessels, might certainly have produced just such a train of symptoms as was present. Of primary importance would be the involvement of the arteries of the anterior and posterior nerve roots of the bulbo-spiual system, though the direct lesions of the nutrient supply to the terminal nerve apparatus — which have to be inferred as they could not be definitely determined — would be of equal value. This inference of the implication of the end-apparatus is justifiable, since the arterial degeneration in the skin was quite extensive, and whenever there is starvation of a nerve tissue there result pathological reactions which may be manifest in a multitude of ways.

The slowly progressive character of the symptoms is also consistent with the theory of tissue-starvation. All the lesions of the nerve cells of the cord and bulb are of this type — atrophy and pigmentary degeneration from malnutrition. Whenever nutrition is at a low ebb, metaplastic granules accumulate in the protoplasm of the cell.

The condition of the optic tracts — in which the lesions are identical with those of other nerve roots except that they are more advanced— would argue that the thickening of the blood-vessels was of long standing, and that only when the process had advanced to an extreme degree did any definite symptoms show themselves. This is exemplified more particularly in the state of the cortex cerebri. Though in this


region vascular disease was manifest and diffuse, it had not advanced nearly to such an extent as in the gray matter of the dorsal cord or in the adjacent meninges. As a consequence, the functions of the cortex, while not as perfect as in youth, were not reduced to the same low level as those of the cord and bull).

One pathological fact should be remembered in considering the clinical symptoms, namely, that it is not necessary for a vascular lesion to proceed to such a profound degree as to cause the entire shutting off of the nutrient supply before a nerve tissue will show signs of deviation from its normal functions. With a reduced supply of nutrient plasma, definite manifestations of nervous exhaustion are brought about, and these are not due to a degeneration of the component portions of the neurone which is visible in the tissue after death, by our present methods of preparation, in the form of morbid alterations of the cytoplasm, axone or myelin. Long before this stage is reached the entire neurone is incapable of performing its natural functions in an efficient manner, and as a consequence, anaesthesias, parasthesias, diminution or exaltation of the reflexes, and dulling of the special senses can be noted. Almost precisely similar results are encountered in advanced stages of progressive paralysis, especially in the syphilitic cases in which, when vascular lesions of the arteries of the cerebrum and cord have advanced to a profound degree, there is a gradual but progressive dulling of cutaneous sensibilities and special sensations.


CONGENITAL MALFORMATIONS OF THE HEART AS ILLUSTRATED BY THE SPECIMENS IN THE PATHOLOGICAL MUSEUM OF THE JOHNS HOPKINS HOSPITAL.


By W. G. MacCallcm, M. D., Assistant in Pathology.


The literature on the congenital malformations of the heart is very extensive, but is well represented by the works of Eokitansky,* Peacock,f Bauchfuss % and Vierordt§ That of Eokitansky, dealing with the defects of the septa, is, perhaps, the foundation of our accurate knowledge of these anomalies, while Rauchfuss, Peacock and others have added greatly to the observations of anomalies of the heart in general, and have done much to determine their relations to one another. Vierordt, writing in the light of the more recent embryological work of His and Born, presents the whole subject in the most concise and lucid way.

The following is intended to be a brief synopsis of the various malformations to serve as the legend to the photographic illustrations which are taken from the specimens iu the pathological museum, and also in a way as a catalogue of those specimens:


•Rokitansky: Die Defecte der Seheklewiinde des Herzens. Wien, 1875.

t Peacock : On malformations of the human heart, with original cases. London, 1853.

X Rauchfuss : Die angeborenen Entwicklungsfehler des Her/ens. Gerhardt's Handb. d. Kinderkrankh. Tubingen, 1878. Bd. IV, 1 abth.

\ Vierordt : Die Angeborenen Herzkrankheiten. Wien, 1898.


A. — Open foramen ovale. This is perhaps to be considered a malformation only when the defect is large, as it is so extremely common to find a small interauricular opening well guarded by the valvnla foraminis ovalis. Even when widely open in persons who have reached adult life, the symptoms it produces are indefinite or none. It may occur pure or in association with a variety of other defects. The symptoms are more definite when it is associated with mitral insufficiency, for there is then pulsation of the veins of the neck. The so-called paradoxical embolism is the result of the passage of the embolus through the open foramen into the systemic arteries, by which means the sifting-out action of the pulmonary circulation is avoided.

Fig. 1 allows a glass rod passed through the foramen ovale. The fossa ovalis in this case is deep and the valvula foraminis ovalis hulged into the left auricle. It was, however, able to completely close the opening.

B. — Defects in /lie septum ventriculorum. Rokitansky considered the pars membranacea as derived from the ventricular wall, while more recent writers trace its origin to the aortic septum; defects in the septum are most commonly in this small area, the " undefended space" of English writers. They may, however, be at other points in the septum, seldom near the apex. The defect seldom occurs pure, but is oftenest associated with narrowing of the pulmonary orifice. Cyanosis


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appears wheu the pulmonary is narrowed (Roger's disease), and there is generally a single, loud, constant murmur in the upper median precordial region, beginning in systole and covering both sounds. The absence of a murmur in diastole is explained by the covering of the defect by the tricuspid and mitral valves.

Aneurismal dilatation of the membranous portion of the septum may occur, the saccular projection appearing in the right ventricle underneath the tricuspid leaflet to which it is often attached. This sacculation may be actually perforated, hut neither of the two specimens in this collection shows this perforation.

The origin of this condition is variously explained as being due to arteriosclerosis, differences in intracardiac pressure, and traction by the adherent tricuspid leaflet.

Fig. 2. The pars menibranacea septi is pierced by a round hole about 1 cm. in diameter. The pulmonary orifice in this case was narrowed by a thickening and contraction of the valves.

Fig. 3. The pars membranacea septi is in this case bulged into the right ventricle, forming a saccular projection beneath the tricuspid valve. The mouth of this sac is seen just below the aortic valves.

C. — Stenosis of pulmonary. This is the commonest of the malformations of the heart. It is explained as due either to abnormal division of the truncus arteriosus or to congenital inflammatory disease. The narrowing may occur in or above the valves, by the constriction of a fibrous ring in the artery or lastly by a constriction in the conus.

It is often associated with defects in the septa. The right ventricle is hypertrophied unless the pulmonary is completely atresic and the septum ventriculorum closed.

Clinically there is cyanosis with various sounds on auscultation, none of which are typical. Often there is a loud systolic murmur in the 2nd and 3rd left interspaces. The 2nd pulmonary sound may be weak, but is strong if the ductus arteriosus is widely open.

The so-called " Eechtslage " is a condition in which extreme narrowing of the pulmonary orifice is associated with a wide defect in the septum ventriculorum and a shifting of the aortic orifice so that it opens directly over the septum and thus communicates with both ventricles.

Figs, i and 5. " Rechtslage." A, stenosed pulmonary orifice; B, aorta opening into each ventricle; C, mitral, and D, tricuspid orifice. In Fig. 5 a rod is passed through the left ventricle from its apex into the aortic orifice. The figure shows the aortic orifice as seen through the right ventricle.

As regards the general idea that tuberculosis of the lungs is especially frequent in cases of pulmonary stenosis, it is found by a consideration of the statistics that while tuberculosis is frequent in these cases it is not relatively more so than in the other conditions (of heart and general) that produce a predisposing depression of the nutrition of the pulmonary tissues.

D. — Anomalies in the division of the truncus arteriosus.

1. Persistence of truncus due to a failure of division.

2. Stenosis or atresia of the pulmonary from the defective course of the dividing septum.

3. Transposition of the arterial ostia.


Rokitansky's classical work on the transposition of the arterial trunks has lent a great theoretical interest to this group; but as the collection contains no representative, no illustration is given. With transposition of vessels we may have the vessels opening from their proper ventricles or from the opposite ventricles, this depending on the behavior of the septum membrauaceum, which by a change in its relations may correct the anomaly. There is generally extreme cyanosis, but this may be prevented by a widening of the bronchial arteries.

E. — Anomalies in the semilunar valves. Anomalies in the semilunar valves occur more often at the pulmonary orifice than at the aortic. At either orifice there may be but two segments, or on the other hand there may be four or five. They have been explained as due to an excess of the endothelial cushions which go to form the valves.

F. — Anomalies in the aorta. The ductus arteriosus may persist as an open communication between the arterial trunks with hypertrophy of the heart. No cyanosis and sometimes a systolic murmur in the 2nd left interspace.

Stenosis or obliteration of the aorta near the entrance of the ductus arteriosus is not uncommon. The stenosis assumes various forms and relations to the position of the ductus — the point of predilection is in the isthmus aortas. The pulmonary is dilated and the arch of the aorta and the arteries springing from above the structure greatly widened. Collateral circulation to the lower portions of the body is effected by anastomoses between the internal mammaries and intercostals. The pathogenesis of the condition is rather obscure. The process is by some thought to be an extension of the obliterative changes going on in the ductus.

There is seldom cyanosis; sometimes cedema: the superficial arteries become tortuous and pulsate visibly, there is inequality in radial and femoral pulse and often a systolic murmur varying in its location.

Fig. 6. Stenosis of aorta (B) just below entrance of ductus arteriosus (C). A is placed upon the widened pulmonary artery. The specimen shows great dilatation of the arterial branches and arch of aorta above the stricture.

G. — Anomalies in the auricular ventricular valves. The remaining anomalies are chiefly those affecting the tricuspid and mitral valves, and these cases are so rare that it is difficult to make auy general statements concerning them.

The representative of this group in the collection is so curious that it seems to deserve to he reported in some detail.

The case was that of an artist who had always been blue and who died at the age of 30 of pulmonary tuberculosis. At the autopsy there was found to be a chronic tuberculosis of the lungs, with chronic passive congestion of the viscera. The heart was enlarged, the enlargement being especially in the right side. The Eustachian valve is found to persist as a large apparently functional valve. The valvula foraminis ovalis also persists, but is not competent to close the foramen ovale, which is open to a width of about 1 cm. The very huge appendix auriculas opens by two mouths into the auricle, which is somewhat constricted near its middle by a muscular ring.


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The tricuspid valves are ballooned out into the right ventricle and have apparently become closely grown together with the ventricular wall. Two of the segments are visible against the interventricular septum and toward the left — these are wrinkled and folded membranes, which are very soon fused with the ventricular wall and are apparently f unctionless. The remaining segment seems to furnish the whole membrane which lines the ventricular wall and septum ; and below, roofing the trabecular, forms the floor of a sort of intervalvular chamber. This chamber opens into the ventricle through a round opening, situated toward the left, just below the conns arteriosus and guarded by a flap-like fold of the chamber wall. It further opens through several small openings, each guarded by tiny valves which are furnished with chorda; tendineae and papillary muscles. The pulmonary artery is slightly narrowed, and the ductus arteriosus persists as a cord, but otherwise the heart is approximately normal.

Ebstein * has reported a case in which the malformation of the heart coincides in every detail with this one, and although no other such cases are reported the recurrence of the malformation in every detail suggests in a way that cannot be ignored the existence as a cause of a definite sequence of events. A possible explanation is as follows: The valves are, of course, formed on the medial side by a prolongation from the septum intermedium — on the lateral side by an involution of the wall of the auricular canal. If in an early stage these endothelial cushions reach a greater extent than normal, and retain their attachment to the muscular trabecular, they would in time become a membrane, supported by muscular trabecular. This might occur only on the lateral side, the


  • Ebstein. Arch. f. Anat. and Phys.,'1866, S. 238.


valves produced from the septum, developing in part normally. The free edge has possibly lost its muscular attachment as a result of the inefficiency of muscular action in the direction in which the blood stream affects it.

The association of pulmonary tuberculosis with this malformation (also observed in Ebstein's case) is interesting in connection with what was said above as to pulmonary stenosis. Naturally the effect of such an insufficiency of the tricuspid — for the mere presence of a large inner chamber, acted upon by the contraction of the ventricle, but not guarded from the auricle constitutes an insufficiency — is the same as that of the pulmonary stenosis in producing a poor nutrition of the lung tissue. The compensating persistence and development of the Eustachian valve is also to be noted.

Figs. 7 and 8 illustrate this malformation. Fig. 7 shows the right auricle and ventricular portion of the heart laid open. The open foramen ovale (A), and the two mouths of the auricular appendix are readily seen ; B points to the large round opening into the ventricle ; C, the apical portion of the functional ventricle; D, the medial leaflets of the tricuspid valve.

In Fig. 8, the conus arteriosus pulmonalis is laid open, showing the larger portion of the functional right ventricular cavity with the opening B just below the pulmonary orifice and guarded by the flaplike valve.

In connection with several malformations, it may be stated that the theories as to their origin, ascribed them formerly either to a true congenital malformation, or to a fcetal endocarditis. The majority of authors, however, now lean to the view that the role of foetal endocarditis is relatively unimportant, and that the vegetations so often seen on malformed valves, on the edges of septal defects, etc., are to be explained as the result of the predisposition of such malformed parts to inflammatory processes.


SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE H0S1TAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.


Thomas R. Brown, M. D. Internal Medicine. — Maryland Medical Journal, February, 1900.

Robert Reuling, M. D. Pathology. — Maryland Medical Journal, February, 1900.

Hugh H. Young, M. D. Surgery. — Maryland Medical Journal, February, 1900.

William Osler, M. D., and Thomas McCrab, M. D. Latent Cancer of the Stomach. — Philadelphia Medical Journal, February, 1900.

Henry J. Berkley, M. D. General Pathology of Mental Diseases. — American Journal of Insanity, January, 1900.


Henry J. Berkley, M. D. Transitory Alienation Following Distressing Pain. — American Journal of Insanity, January, 1900.

William Osler, M. D. After Twenty-Five Years. — Montreal Medical Journcd, November, 1899.

Patrick Cassidy, M. D. Report of a Severe X-Ray Injury. — Medical Record, February 3, 1900.

Irving Phillips Lyon, M. D. The Inoculation of Malaria by the Mosquito. — Medical Record, February 17, 1900.

Lewellys F. Barker, M. D., and Joseph Marshall Flint. A Visit to the Plague District in India. — The New York Medical Journal, February 3, 1900.


THE JOHNS HOPKINS HOSPITAL BULLETIN.

The Hospital Bulletin contains details of hospital and dispensary practice, abstracts of papers read and other proceedings of the Medical 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 XI is now in progress. The subscription price is $1.00 per year. The set of ten volumes will be sold for $20,00.


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PROCEEDINGS OF SOCIETIES

THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.


Monday, February 5, 1900.

The meeting was called to order by the President, Dr. H. M. Thomas.

Exhibition of Patients.— Dr. W. B. Platt.

Case 1. — Infant, seven months old, came to the Garrett Hospital when five months of age with a sinus just below the right eye and a history that pus occasionally escaped from the right nostril. An examination showed an empyema in the right antrum with necrosis of the bony wall in at least two places. The sinus above had caused contraction of the lower eyelid. There is also an opening into the nose apparently one-eighth inch in diameter. I removed a molar tooth as the best way of getting a free opening into the antrum to clean it out. The child improved immediately, the sinus above healed up, and the discharge was not more than a drop a day, and the child was sent home. A small piece of necrosed bone was also removed from the alveolus.

The child returned in seven weeks with the history of a recurrence. Pus now escapes through the right nostril and from the sinus below the right eye. I do not find any record of cases similar to this in infants, and the exact cause is not clear. It may be an osteomyelitis. The probability is that there was an abnormally large opening from the antrum into the nose which became infected during child birth, with subsequent involvement of the delicate bone wall.

Case 2. — This boy, seven years old, has a curious defect, a hole J inch in diameter in the palatoglossus muscle of the left side. There is every reason to believe that it is a congenital defect. Of course, one may suppose it a case of congenital or inherited syphilis, but in view of the frequent defects in the development of the soft palate, it is probably one of this kind.

Case 3. — This is a case of congenital hip-joint dislocation. The girl, six years old, was sent to the Garrett Hospital from Virginia, with the history that she had always limped, and became fatigued on prolonged exertion. An examination of the right limb will show you that it is not hip-joint disease. She has perfect mobility, not the slightest hampering of the movements of the limb and no bowing up of the lumbar region on flexion of the thigh on the pelvis. On first looking at it I thought of infantile paralysis, because the whole limb is somewhat atrophied in appearance as compared with the other. The distance from the right anterior superior spine to a horizontal line drawn through the right trochanter is three-quarters of an inch less than corresponding measurements on the left side. On drawing down the right thigh limb and letting it go we get a distinct, though slight, telescoping.

What is to be done with children of this sort? If the telescoping amounts to three or four inches, if the gait is very bad, or fatigue or pain follows moderate exertion, an operation must be done. Statistics show that after two or three years the hip in many cases again telescopes. A man of large experience has said that fifty per cent, of the operated cases relapse. This little girl walks and runs so well that we


have tried only massage to increase the strength of the gluteal muscles. Some cases have done well by use of the ordinary hip-joint apparatus to keep the hip extended and pressed into the socket for some months. A certain number of these cases never have anything more than a slight limp.

Changes in the Cells of the Nucleus Dorsalis resulting from Pressure upon the Upper Portion of the Spinal Cord. —

Dr. Barker.

The specimen is from a case of compression of the upper part of the thoracic cord, the section being taken from the lower part of the thoracic portion. It will be recalled that the thoracic portion of the cord is characterized by the presence of a column, or nucleus, of gray matter on each side called Clarke's nucleus, or the nucleus dorsalis. The cells in this nucleus, give off axis-cylinder processes which run out into the dorsolateral region of the cord and then turn upward, ascending through the cord to the cerebellum, the whole bundle being known as the fasciculus spinocerebellaris dorsolateralis, or direct cerebellar tract. If one cuts through a medullated axoue, there result changes in the whole neurone. If the axone of a neurone be cut anywhere between its cellbody of origin and the end of its axis-cylinder process, the nucleus becomes displaced in the cell-body, assuming an eccentric position, usually very close to the axone hillock; in addition to this change the tigroid masses, or Nissl bodies, break down into very minute granules, like fine dust, which become diffused through the cell. If the ulnar nerve, for example, be cut, one finds in the spinal cord that all the cells which give origin to the fibers of the ulnar nerve show this peculiar form of degeneration — so-called "reaction at a distance." If then the cells of Clarke's nucleus send their axones to the cerebellum, we should expect, in compression of the upper thoracic cord, to find this change below the lesion, in all the cell-bodies which send their axis-cylinder processes to a part of the cord above the lesion. Accordingly sections from this cord below the lesion ought to show degeneration of the cells of Clarke's nucleus. The specimen under the microscope illustrates the alterations well. The cells show the change described in varying degrees of intensity. I have before pointed out the occurrence of similar changes in the nucleus dorsalis in inflammations of the soft meninges {Brit. M. J., Loud., 1897, ii, pp. 1839-1841). The superficial position of the fibers of the direct cerebellar tract makes it especially liable to injury.

Area of Necrosis in Internal Capsule in Typhoid Fever. —

Dr. Barker. It was not easy to make out the lesion when the brain was first cut up. The brain was put into formaline immediately after its removal and was divided by the method of Petri some days later. On cutting through the brain it was found that the formaline had not penetrated the whole substance of each hemisphere, there being a large area that was soft. No definite area of necrosis was made out. In view of the marked clinical symptoms it seemed necessary to keep the tissue of


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the right side for microscopic examination. These pieces were put back into the formaline in order to complete the hardening.

The hardening has now become complete and the lesion is perfectly well-defined and easily visible. It is an ana of softening in the upper part of the right internal capsule, ahoul the size of a small hickory nut, situated just lateral from the caudate nucleus a little medial and slightly dorsal from the upper border of the cortex of the island of Reil.

The necrosis must have involved practically all of the fibers of the pyramidal tract on the right side, and is undoubtedly due to a plugging of a branch of the artery supplying the area. The tissue is to be thoroughly worked up microscopi dally, but it seemed to be worth while before cutting the pieces into sections that the gross lesion should be presented to the Society.

Poisonous Snakes. — Dr. Kelly.

Dr. Kelly concluded his demonstration of the poisonous snakes of North America by exhibiting: 2 specimens of Elaps fulvius, one of which had caused the death of a man by biting him in the hand ; 1 boa constrictor (young) showing remarkable difference from native snakes in the fine bead-like appearance of the body due to the scales in S3 rows, and the peculiar pear-shaped head also covered with minute scales; 1 Sistrurus miliarias, or ground rattlesnake ; 2 large diamond-back rattlesnakes ; 1 living moccasin, Trigonocepkalus piscivorus ; 1 mountain blacksnake, Bascanium constrictor ; and casts of snakes made by Mr. John W. Thompson, of the Philadelphia Zoological Gardens, one finely colored Texas copperhead, one very large diamond-back rattlesnake, and one very large moccasin.


NOTES 03V NEW BOOKS.

An Experimental Research into Surgical Shock. By George W. Chile, A.M., M. D., Ph.D. Svo. pp. 160. (Philadelphia : J.

B. Lippincoll Company, 1S98.)

Due mainly to the leadership of the German and French schools of pathology, the research work of most surgical laboratories in this country to-day is devoted largely to the investigation of problems which the comparatively modern subjects of pathological histology and bacteriology have offered for solution. In consequence it has gradually come about that the methods of investigation best known to the physiologist have fallen into abeyance in spite of the valuable data relative to surgical principles which may be obtained by their employment. Prompted by some preliminary research conducte 1 in the laboratory of his quondam preceptor, Mr. Victor Horsley, Dr. Crile, making use of physiological methods of experimentation, has undertaken an investigation concerning the nature of surgical shock ; a subject which has always been somewhat nebular in its indefiniteness and offering problems the solution of which can only be approached by employing these methods.

The results of this excellent piece of work are comprised in a small volume of 160 pages which received the Cartwright Prize in 1897.

The essay represents the results of entirely personal observations, and in this lies, perhaps, the chief occasion for congratulation ; and yet, on the other hand, for criticism of the author's published work, the value of which, considerable a3 it now stands, would have been


greatly enhanced as a book of reference had the bibliography of the subject been given, and the comparative results of other investigators in the same direction been cited. A cursory review of the theories of shock advanced by various writers is contained on the introductory four or five pages of the volume without references to the articles which have evidently been consulted.

After a brief description of the "Modes of investigation and annotation " which, though original with the author, are those commonly employed in the physiological laboratory, the chief part of the essay (100 pages) is given up to the detail of the individual protocols of the 148 experiments upon anesthetized dogs.

In these experiments, observations were made of the effects upon the respiratory, cardiac and vascular mechanism of all conceivable forms of traumatism upon the individual tissues and organs of the body, somatic, splanchnic and neural. These experiments evidence the author's thoroughness and ingenuity, and though their record, from necessary repetition, makes the protocols uninteresting reading, an excellent index renders it possible to abstract data from them, otherwise buried in the mass of material, which will be of value to those pursuing similar lines of investigation.

The author has given an interesting summary of bis experimental findings in the latter part of the volume, with 35 composite charts of manometric readings, illustrating the effects produced upon the blood pressure by the various experiments. These included procedures showing the rise in blood pressure consequent upon burning the skin, injuries of the periosteum, dilatation of the sphincter ani, etc.; procedures showing the negative effect of certain manipulations, as upon the joints: procedures showing the great "depressor" effect of cutting away the cerebral hemispheres, of manipulation of the larynx, the testicle, the parietal peritoneum, the intestines, etc. It was furthermore demonstrated that when an animal was exhausted, as late in an experiment, and with shock present or pending, the application of stimuli, ordinarily producing a temporary rise in blood pressure, under these circumstances would be followed by a fall.

Possibly, from a practical standpoint, the most valuable suggestions from Dr. Crile's work originate in the results of his observations upon the "blocking" effect of the preliminary local administration of cocaine as a preventive measure toward shock in anticipation of those peripheral manipulations which ordinarily have a marked depressor effect. This is most strikingly shown in one of the composite charts (near page 127. These charts unfortunately are not numbered) which illustrates the great fall in blood pressure which ordinarily follows upon manipulations of the larynx, and the inhibitory effect of preliminary cocainization of the mucosa upon this fall.

As prophylactic measures toward shock the author emphasizes the necessity of careful hsemostasis under all circumstances ; of atropine in operations on the larynx or in procedures which might cause mechanical stimulation of the vagi ; of a proper respect for tissues and the avoidance of tearing or finger dissections unfortunately used by many operators. Precautions toward over anesthetization, especially with chloroform, are dwelt upon as most likely to occur in those operative procedures which are associated with an acceleration of the respiratory rate, and in abdominal, anal and other operations. Emphasis is also laid upon the likelihood of shock, in consequence of operations in the gall-bladder or pyloric region, due to pressure on the venous trunks, diaphragm and splanchnic nerves. He truly says, "The severity of shock produced in abdominal operations is in direct ratio to the distance from the pelvis."

Dr. Crile offers nothing new in the matter of treatment, believing that small and frequently repeated hypodermic injections of strychnia and intravenous saline infusions to he the most efficacious measures, with elevation of the lower extremities, application of heat, etc. Emphasis is rightly given to the fact that intelligent prevention is more valuable than treatment.


74


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[No. 108.


In the etiological factors producing shock the author does not seem in his views to differ widely from the theories proposed by Fischer, Goltz and Seabrook. An attempt is made to differentiate collapse and shock, the latter being regarded as especially dependent upon " vasomotor impairment or break down," the degree of shock being proportionate to the failure of the pressor action. Factors, cardiac, respiratory and hemorrhagic, may add to shock, or, if their effects are severe and immediate, may produce collapse. Certain widespread vasomotor action, as that following section of the splanchnic nerves, may, however, produce the same condition.

Dr. Crile's work is important in the effect it will have in stimulating investigation of surgical problems on physiological lines. It is to be hoped that observations by the methods of Nissl will be made upon the histological changes in the medullary nerve centers and ganglia responsible for these vasomotor disturbances, and also that mercurial manometers, constructed so as to be applied to the extremities, may be employed in surgical operating-rooms for the purpose of recording vasomotor effects and changes in blood pressure, and to indicate impending shock more definitely than at present is possible through the medium of the anasthetizer's finger on a peripheral artery. Cushing.

Essentials of Diseases of the Skin, including the Syphilodermata, arranged in the form of Questions and Answers prepared especially for Students of Medicine. By Henry W. Stelwagon, M. D., Ph.D., Clinical Professor of Dermatology in the Jefferson Medical College, etc. Fourth Edition, thoroughly revised. Illustrated. (Philadelphia: W. B. Saunders, 1899.) In the present edition, the whole book has been subjected to careful scrutiny and revision, and the text has undergone numerous small but important changes in order that it may reflect the present state of knowledge of cutaneous diseases. The rarer affections like hydroa vacciniforme, blastomycetic dermatitis, and erythema induratum are briefly but adequately described. The book is extremely useful to students of medicine who wish to review the subject.

A Text-Book of Embryology for Students of Medicine. By J. C. Heisler, M.D. (Philadelphia: W. B. Saunders, 1899.) The work thus presented to us is an attempt to supply the real need of a concise text-book of embryology, written in the English language, and planned especially for the average medical student who is learning anatomy.

A few words will characterize the book. It is not a new account, but a condensed familiar one. It is a fairly straightforward statement of human development, such as one might write who was acquainted with anatomy, and who wrote the embryological story from a reliable knowledge of four or five well-known textbooks ; as, for instance, Mark's translation of Hertwig's work (the influence of which is very strongly manifest) ; the American text-book of obstetrics; Minot's embryology ; Piersol's histology, etc.

The press-work is good, and large-type headings are convenient for reference. Comparative references and discussions are eliminated wherever possible ; making it easy to quickly find the main facts of development as here given for any special structure.

The weakest portion of the book is that devoted to the earlier phenomena : fertilization, the ovum, maturation, the sperm, cleavage, germ-layers, foetal appendages, etc.

On reading these pages (and the same is true of other sections), we wonder how the writer of a text-book to-day can be satisfied with such an antiquated and incomplete resume\ Certainly, there has been no lack of remarkable discoveries and well-founded generalizations by the embryologists and cytologists of the last ten years, from which to formulate a modern and comprehensive statement, however brief. In all fairness to the science it attempts to treat, a good text-book


should be at least up to date, representing the most recent advances in all lines of investigation. The book before us would be greatly improved by the incorporation of what is found to be valuable, after a judicial sifting of the original contributions of recent embryological research.

We must not, however, be too severe on those who seek to adapt the good work of others to a special need— a difficult task. Even if the result be little more than a fairly clear restatement of the conceptions of two or three master minds, who have already brought together the main threads of research, those who may be introduced to the subject in this indirect manner, will, at any rate, receive many valuable and reliable facts. H. Mc. E. K.

Essentials of Anatomy, including the Anatomy of the Viscera, arranged in the form of Questions and Answers prepared especially for Students of Medicine- By Charles B. Nancrede, M. D., Professor of Surgery, etc., in the University of Michigan. Sixth Edition, thoroughly revised by Fred. J. Brockw ay, M. D., Asst. Demonstrator of Anatomy, Columbia University, New York. (Philadelphia : W. B. Saunders, 1899.) This is a thoroughly revised sixth edition of a useful little book which has been approved by long service in medical schools and training schools for nurses. It is concise without the sacrifice of clearness, and the excellent illustrations assist the text.

The Hygiene of Transmissible Diseases ; their Causation, modes of Dissemination and methods of Prevention. By A. C. Abbott, M.D., Professor of Hygiene and Bacteriology, and Director of the Laboratory of Hygiene. University of Pennsylvania. Illustrated. (Philadelphia: W. B. Saunders, 1899.) As the title indicates, this volume of 300 pages gives an account of transmissible diseases with details, more or less complete, as to their proper and successful management. The section on the causation of disease is probably the most satisfactory and philosophical of the whole book. It treats of the influence of age, sex, race, occupation, density of population, heredity and season, upon diseases in general ; and also of chemical, physical, mechanical, parasitic and bacterial agencies as exciting causes of the actual development of diseases. This section is well illustrated by tables, charts and diagrams. The following section, on the causation, modes of dissemination and prevention of special diseases, contains much information as to diseases which are transmitted from one person to another. The account which is here given of the bacteriology of transmissible diseases is full and extremely satisfactory, as would naturally be expected from so accomplished and skillful an observer. The sections on prophylaxis and disinfection are also valuable, and the directions which they contain are sensible and practical. The book is well calculated to meet a want which has long been felt by physicians and nurses.

The Bulletin of the Ohio Hospital for Epileptics, Vol. I, Nos. 2 and 3. Gallipolis, O. The Hospital, 1898. The volume consists of a number of papers by Dr. A. P. Ohlmacher, with an introductory statistical report by H. C. Butter, manager of the hospital. The first two of Dr. Ohlmacher's papers form an account of the autopsies in cases of epilepsy performed during his service, which he prefaces with a somewhat detailed description of a rather ordinary autopsy technique. In these cases, special attention has been directed to the association of the lymphatic constitution with epilepsy, and throughout the report the effort is made to show that "idiopathic" epilepsy may perhaps be the direct result of the presence of the " constitutia lymphatica." It is sometimes difficult to follow the chain of arguments which connects the lymphatic constitution with epilepsy, rhachitis, tetany and exophthalmic goitre on the one hand and with the causation of gliomata on the other.


March, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


75


Two other papers are concerned with the description of various tumors of the central nervous system, with secondary epileptic symptoms. It is to be regretted that amid the profusion of illustrations there are no drawings of the microscopical appearances of the tumors to supplement the descriptions. In the fifth paper, there is described the case of an idiot child with immense thickening of the skin and subcutaneous tissues in association with atrophy of the thyroid, and another case in which there was a localized area of thickening of the skin without thyroid atrophy. Finally, the last paper is devoted to the description of tumors occurring in various animals.

The report is marked by a diffuseness which seems unfortunately common in neurological literature, but the suggestions contained are very worthy of confirmatory work. It seems especially desirable, too, that such work on comparative pathology as is embodied in the last paper should be more extensively carried out.


A Manual of the Practice of Medicine. By A. A. Stevens, M. D., of Philadelphia. (Philadelphia : W. B. Saunders, 1900.)

This is the fifth edition of this work, which shows its popularity. Any extended notice regarding the book is unnecessary. Dr. Stevens has succeeded in condensing much into 500 small pages. The material chosen, and the method of its arrangement, make it one of the best books of its kind.


The American Year-Book of Medicine and Surgery, edited by George M. Gould, M. D. Medicine. (Philadelphia : W. B. Saunders, 1900.)

The current volume of the Year-Book is a welcome addition to the library shelves. In these days, unaided by the Index Medicus, the gleaning of the fields of literature has become a heavy and often well-nigh impossible task. In this the series of volumes of the Year-Book is of valuable help. The work is too well-known to require any description of its characteristics. This yearsees a new departure in the division of the work into two volumes, which will be found most convenient. In one volume it was growing beyond the bounds of easy handling. Dr. Gould, in the preface to the volume on Medicine, notes some changes in the editorial staff. Dr. Riesman takes charge of the section on Pathology in place of Dr. Guiteras. Drs. Wilcox and Stevens edit the department of Materia Medica and Therapeutics, while Dr. Abel is succeeded in Physiologic Chemistry by Drs. Hunt and Jones of Baltimore. The present volume sustains the previous high character of the work. Not the least useful feature is the complete index. "We hope the work is having the pecuniary recognition that it deserves.


Letter, Word and Mind-Blindness. By James Hinshet.wood, M. D., of Glasgow. (London : II. K. Lewis, 1900.)

These are lectures delivered before the Glasgow Medico-Chirurgical Society which appeared in the Lancet and are now published in a book of 85 pages. The writer takes up the general subject of visual memory and then discusses the various groups of cases designated in the title. He is able to report several cases of bis own, which were unaccompanied by derangements of the auditory and speech-motor centers. From the study of bis cases and those in the literature, the writer considers that there are separate cerebral areas for the usual memory of numbers, letters and \\ ords. The lectures are well and clearly written, and the study of the cases given throws light on an exceedingly interesting subject. Dr. Hinshelwood shows how much may be made out of a few cases by thorough analysis.


BOOKS RECEIVED.

Archives of Neurology and Psychopathology. Vol. II. Nos. 1-2. 1899. 8vo. 319 pages. State-Hospitals Press, Utica, N. Y.

Transaction* of the Clinical Society of London. Volume the thirtysecond. 1899. 8vo. LVII-f- 296 pages. Longmans, Green & Co., London.

Transactions of the Texas State Medical Association. Thirty-first annual session held at San Antonio, Texas, April 25-28, 1899. 8vo. 347 pages. Von Boeckman, Schutze & Company, Printers, Austin, Texas.

A Manual of Modern Surgery, General and Operative. By John Chalmers Da Costa, M. D. Second edition. With 386 illustratious. 1898. 8vo. 911 pages. AV. B. Saunders, Philadelphia.

A Text-Book of Materia Medica, Therapeutics and Pharmacology. By George Frank Butler, Ph.G., M. D. Third edition, thoroughly revised. 1899. 8vo. 874 pages. W. B. Saunders, Philadelphia.

A Text-Book of the Practice of Medicine. By James M. Anders, M. D., Ph.D., LL. D. Third edition, revised. Illustrated. 1899. 8vo. 1292 pages. W. B. Saunders, Philadelphia.

A Manual of the Diagnosis and Treatment of the Diseases of the Eye. By Edward Jackson, A. M., M. D. With 178 illustrations and 2 colored plates. 1900. 12mo. 604 pages. W. B. Saunders, Philadelphia.

A Manual of the Practice of Medicine. Prepared especially for students. By A. A. Stevens, A.M., M. D. Fifth edition, revised and enlarged. Illustrated. 1898. 12mo. XV + 519 pages. W. B. Saunders, Philadelphia.

A Text- Book of Diseases of Women. By Charles B. Penrose, M. D., Ph.D. Third edition, revised. Illustrated. 1900. 8vo. 531 pages. W. B. Saunders, Philadelphia.

Hints on Elementary Physiology. By Florence A. Haig-Brown. With twenty-one illustrations. IGmo. 1897. XII + 121 pages. P. Blakiston, Son & Co., Philadelphia.

The Medical Annual Synoptical Index to Remedies and Diseases. For the twelve years, 1887 to 1898. 12mo. 411 pages. [1899.] John Wright & Co., Bristol. Simpkin, Marshall, Hamilton, Kent & Co., Ltd., London.

Progressive Medicine. A Quarterly Digest of Advances, Discoveries and Improvements in the Medical and Surgical Sciences. Edited by Hobart Amory Hare, M. D. Volumes I, II, III, IV. March, June, September, December, 1899. 8vo. Lea Brothers & Co. Philadelphia and New York.

A System of Medicine. By Many Writers. Edited by Thomas Clifford Allbutt, M. A., M. D., LL. D., F. R. C. P., F. R. S., F. L. S., F. S. A. Volumes VI, VII, VIII. 1899. 8vo. The Mac-MilIan Company, New York.

Transactions of the American Ophthalmologic^ Society. Thirty-fifth annual meeting, New London, Conn. 1899. 8vo. 469-592 pages. Published by the Society, Hartford.

Saint Bartholomew's Hospital Reports. Edited by Norman Moore, M. D., and D'Arcy Power, F. R.C.S. Vol. 35. 1900. 8vo. 356 and 246 pages. Smith, Elder & Co., London.

Transactions of the Louisiana State Medical Society. Twentieth annual session held at New Orleans, La., May 16, 17, 18, 1899. 8vo. 173 pages. New Orleans.


76


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 108.


Practice of Medicine. A manual for students and practitioners. (Lea's Series of Pocket Text-Books) by George E. Malsbary, M. D. Series edited by Bern B. Gallaudet, M. D. Illustrated with forty-five engravings. 1S99. 12mo. 404 pages. Lea Brothers & Co., Philadelphia and New York.

The American Year-book of Medicine and Surgery. Collected and arranged with critical editorial comments by S. W. Abbott, M. D., Archibald Church, M. D., e! al. Under the general editorial charge of George M. Gould, M. D. Two Vols. 1900. Svo. W. B. Saunders, Philadelphia.

Annual and Analytical Cyclopmdia of Practical Medicine. By Charles E. de M. Sajous, M. D., and one hundred associate editors, assisted by corresponding editors, collaborators and correspondents. Volume IV. 1S99. 4to. 622 pages. The F. A. Davis Co., Philadelphia, New York, Chicago.

Proceedings of the New York Pathological Society. For the years 1897 and 1898. Svo. XVIII + 289 pages. 1899. Printed for the Society.

Seventh Report of the Slate Veterinarian of Maryland. December 1, 1899. Svo. 249 pages. Baltimore.

Essentials of Anatomy, including Anatomy of the Viscera. Arranged in the form of questions and answers. Prepared especially for students of medicine. (Saunders' Question-Compends, No. 3.) By Charles B. Nancrede, M. D. Sixth edition, thoroughly revised by Fred. J. Brockway, M. D. 1899. 12mo. 419 pages. W. B. Saunders, Philadelphia.

Essentials of Medical Chemistry, Organic and Inorganic. Containing also questions of medical physics, chemical philosophy, analytical processes, toxicology, etc. Prepared especially for students of medicine. (Saunders' Question-Compends, No. 4.) By Lawrence Wolff, M. D. Fifth edition, thoroughly revised by Smith Ely Jelliffe, M. D., Ph. D. 1899. 12mo. 222 pages. W. B. Saunders, Philadelphia.

Essentials of Diseases of the Skin, including the Syphilodermata. Arranged in the form of questions and answers. Prepared especially for students of medicine. (Saunders' QuestionCompends, No. 11.) By Henry W. Stelwagon, M. D., Ph. D. Fourth edition, thoroughly revised. Illustrated. 1896. 12mo. 276 pages. W. B. Saunders, Philadelphia.

MONOGRAPHS.

The following papers are reprinted from Vols. I, IV, V, VI and VIII of the Reports, for those who desire to purchase in this form: STUDIES IN DERMATOLOGY. By T. C. Gilchrist, M. D., and Emmet Rixford, M. D. 1 volume of 164 pages and 41 fullpage plates. Price, bound in paper, $3.00. THE MALARIAL FEVERS OF BALTIMORE. By W. S. Thayer, M. D., and J. Hewetson, M. D. And A STUDY OF SOME FATAL CASES OF MALARIA. By Lewellys F. Barker, M. B. 1 volume of 280 pages. Price, in paper, $2.75. STUDIES IN TYPHOID FEVER. By William Osler, M. D., and others. Extracted from Vols. IV and V of the Johns Hopkins Hospital Reports. 1 volume of 481 pages. Price, bound in paper, $3.00.

THE PATHOLOGY OF TOXALBUMIN INTOXICATIONS. By Simon Flexner, M. D. Volume of 150 pages with 4 full-page lithographs. Price, bound in paper, $200.

THE RESULTS OF OPERATIONS FOR THE CURE OF INGUINAL HERNIA. By Joseph C. Bloodgood, M. D. Price, in paper, $3.00.

Subscriptions for the above publications may be sent to

The Johns Hopkins Press, Baltimore, Md.


VOLUME TO CELEBRATE THE 25TH YEAR OF DR. WELCH AS A TEACHER AND INVESTIGATOR,

It is customary in Germany for the pupils of a great teacher to express their appreciation and gratitude by dedicating to him a volume of their contributions to learning. The pupils of Dr. Wm. H. Welch, of Baltimore, have decided to give expression to their regard for him in a similar way and the publication of a volume to mark his twenty-fifth year as a teacher and investigator is now in progress.

During the past twenty-five years some seventy-five persons have undertaken investigation under Dr. Welch's leadership, and nearly half of these will contribute to the volume mentioned. The edition will necessarily be limited by the number of subscribers. An early announcement of the publication is made to give opportunity for subscription so that the committee can decide upon the number of copies to be printed.

The volume will be royal octavo in size and will contain at least five hundred pages of printed matter. It will, in addition, be illustrated with many lithographic plates and text figures. The price has been fixed at five dollars. The book will contain contributions to pathology and to correlated sciences agreeing in scope with that of the leading scientific medical journals.

The Committee of publication consists of :

A. C. Abbott, University of Pennsylvania, Philadelphia, Pa.

L. F. Barker, Johns Hopkins University, Baltimore, Md.

Wm. T. Councilman, Harvard University, Boston, Mass.

Simon Flexner, University of Pennsylvania, Philadelphia, Pa.

W. S. Halsted, Johns Hopkins University, Baltimore, Md.

A. C. Herter, University and Bellevue Hospital Medical College, New York.

Wyatt Johnston, McGill University, Montreal, Canada.

F. P. Mall, Johns Hopkins University, Baltimore, Md.

Walter Reed, Army Medical Museum, Washington, D. C.

Geo. M. Sternberg, Surgeon General's Office, Washington, D. C.

All communications and subscriptions should be addressed to Dr. F. P. Mall (Secretary), Johns Hopkins University, Baltimore, Md.

Baltimore, November 11, 1S99.


HOSPITAL PLANS.

Five essays relating to the construction, organization and management of Hospitals, contributed by their authors for the use of The Johns Hopkins Hospital.

These essays were written by Drs. John S. Billings, of the U. S. Army, Norton Folsom, of Boston, Joseph Jones of New Orleans, Caspar Morris, of Philadelphia, and Stephen Smith, of New York. They were originally published in 1875. One volume bound in cloth, price $5.00.


THE JOHNS HOPKINS HOSPITAL BULLETIN.

The Hospital Bulletin contains announcements of courses of lectures, programmes of clinical and pathological study, details of hospital and dispensary practice, abstracts of papers read and other proceedings of the Medical 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 XI is now in progress.

The subscription price is $1.00 per year.

The set of ten volumes will be sold for $20.00.


The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by TEE FRIEDENWALD CO., Baltimore. Single copies may be procured from Messrs. CUSH1NO & CO. and the BALTIMORE NEWS COMPANY, Baltimore. Subscriptions, $1.00 a year, may be addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE ; single copies will be sent by mail for fifteen cents each.


BULLETIN


OF



iBRAj^:



c MAYS 1900 c>


THE JOHNS HOPKINS HOSPITAL.


Vol. Xl.-No. 109.1


BALTIMORE, APRIL, 1900.


[Price, 15 Cents.


CONTEISTTS.


An Unusual Method of Performing Hysteromyotnectomy. By Otto G. Ramsay, 51. D., -77

A Squamous-Celled Carcinomatous Degeneration of an Ovarian Dermoid Cyst ; also an Adenocarcinoma of the Ovary Associated with an Ovarian Dermoid Cyst. By Lindsay Peters, M. D., - • 78

Pulmonary Tuberculosis, with Diffuse Pneumonic Consolidation, in a Lion. By W. G. MacCallum, M. D., and A. W. Clement, V. P., 85

Arsenical Pigmentation and Keratosis. By Louis P. Hamburger. 51. D.. - 87


PAGE

Uncontaminated Urine. By Howard A. Kelly, M. D., - - 91

Summaries or Titles of Papers by Members of the Hospital and Medical School Staff appearing Elsewhere than in the Bulletin, ----- 92

A Note on a Series of New Vesical Specula. By Howard A. Kelly, M. D.,

Proceedings of Societies :

Hospital Medical Society, The Pathological Findings in a Case of General Cutaneous and Sensory Anaesthesia [Dr. Berkley] ; — Specimens of False Porencephalia [Dr. Berkley] ;— On a form of Conjugation of the Malarial Parasite [Dr. Ewing].


93


93


AX UNUSUAL METHOD OF PERFORMING HYSTER0MY0MECT0MY.

By Otto G. Eamsay, M. D., Instructor in Gynecology, Johns Hopkins University, Baltimore, Md.


An article in the Johns Hopkins Hospital Bulletin of March, 1900, by Dr. Kelly, entitled "A Preliminary Report on the Surgical Treatment of Complicated Fibroid Tumors of the "Womb, with a Description of Two New Methods," describes two unusual methods of performing hysteromyomectomy in difficult cases, which reminds me of a somewhat similar operation I performed for the removal of a myomatous uterus on September 23rd, 1898.

The patient, admitted to The Johns Hopkins Hospital complaining of " tumors of the womb," was 29 years of age, and had been sick for about seven years, beginning at that time to complain of abdominal pains. The abdominal tumor was first noticed by her six years ago, and it had increased in size considerably since then.

On examination, the abdomen was found distended, especially in its lower portion, by a symmetrical tumor, which, on palpation, was found to be composed of several nodules, the largest measuring about 15 by 15 cm.

By vaginal examination, a rounded tumor was felt lying in the cul-de-sac behind the cervix and extending downward between the rectum and the vagina nearly to the vaginal outlet. The cervix could not be found by the vagina, even under ether, being displaced above the symphysis, and the tumor itself was lying quite firmly pressed against the symphysis, giving the impression that the tumor was adherent in the


cul-de-sac. This rounded tumor was connected directly with the masses felt through the abdominal wall, and on pressure through the vagina the abdominal mass could be moved slightly. It was, however, impossible to move the growth much by making pressure either through the vagina or through the rectum. (See Fig. 1.)

Operation. — The usual median incision was made, taking the precaution to enter the peritoneal cavity high up rather than in the usual position, so as to avoid an elevated bladder. (Kelly.) On entering the peritoneal cavity, the bladder was found displaced upward, and when the incision was lengthened, it was seen bulging out above the symphysis pubis. On examining the relations of the tumor-mass and the surrounding structures to decide in what manner it might be best attacked, it was found that it could not be delivered through the incision usually made in a hysteromyomectomy, and, on further examination, the reason for this was discovered to be the extension of the growth into the cul-de-sac.

As the usual transverse operation could not be made, the next question was, by what new plan the growth might be removed. The tubes, with the broad ligaments and ovaries, were found raised up but lying somewhat anterior to the main mass of tumor, and on tracing them to their origin, the tumor was found to have arisen entirely from the fundus and posterior surface of the uterus, and the cervix and lower por


78


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 109.


tion of the body of the uterus could be recognized lying covered by the bladder on the anterior surface of the tumor proper. (See Fig. 2.)

In the first place, the vesical peritoneal reflection onto the uterus, which was much higher than usual, was definitely recognized and the peritoneum at this point incised, the bladder was then pushed down for a distance of 5 or 6 cm., exposing the lower portion of the body of the uterus and the cervix. When this had been accomplished, the uterine vessels on each side could be felt pulsating distinctly where they passed to the cervix. The plan of the operation which I then determined to follow was to tie the uterine vessels on both sides, then to cut across the cervix, and after that, to deliver the tumor from the cul-de-sac, thus reversing the usual steps in the operation. I first freed the ovaries from the tumor by a series of ligatures near the uterine cornu, as it was my iutention not to remove them ; this was easily accomplished, as their relations were not much distorted from the normal. The uterine arteries were tied just at the point where they curve up to reach the cervix. Then, as previously determined, the uterus was cut across from side to side, thus loosening the tumor entirely from its cervical and broad ligament attachments. The tumor was then fixed in the abdominal cavity only by its extension into the cul-de-sac; on attempting to raise it from this position, it was found densely adherent to the whole cul-de-sac and to the rectum posteriorly. These adhesions were carefully separated by raising the tumor slowly and dividing them with the Angelas they came into view. The densest adhesions were found between the rectum and the tumor, and here some difficulty was experienced in the detachment, though a slow removal prevented any injury to the rectal coats. After removal of tin- tumor the remainder of the operation was carried out in the usual manner, the amputated cervix was closed in with catgut sutures, and the bare area on the floor of the pelvis cov


ered by drawing the anterior and the posterior layers of the peritoneum together with catgut sutures. The large overdistended bladder was left puckered over the cervix, and the wound appeared as usual after a normal hysteromyomectomy. Several oozing points on the rectum were checked by fine catgut sutures, the peritoneal cavity was cleansed and the abdominal incision closed in the usual manner.

The convalescence was normal, save for a slight collection of blood above the stump of the cervix between it and the bladder, which was easily evacuated by dilating the cervical canal, otherwise the patient recovered in a perfectly satisfactory mauuer.

Remarks.

The chief points of interest in this case are the peculiar developments of the myomatous tumor from the posterior surface of the uterus and its extension into the eul-de-sac ; the upward displacement of the bladder covering the whole anterior surface of the uterus, and the method of attacking such a tumor.

Such a growth is rarely seen, and, therefore, this method of operation will only be useful in a certain number of abnormal cases. The principle, however, would seem to me to be a good one, and it might also be applicable in other conditions besides cases of posterior myomatous development. Thus, for instance, in densely adherent pelvic structures, or in cases with large pelvic abscesses, it would be easier to separate the bladder from the uterus anteriorly where there are usually but few adhesions, and to tie the uterine arteries on each side before any attempt is made to remove the adherent masses, thus obviating one of the chief difficulties in such an operation, namely, hasmorrhage from the misplaced or with difficulty accessible uterine artery.

The cervix, in these cases, could be cut across after tying the vessels, and a point of leverage obtained to remove more easily the adherent structures.


A SQUAMOUSCELLED CARCINOMATOUS DEGENERATION OF AN OVARIAN DERMOID CYST;

ALSO AN ADENOCARCINOMA OF THE OVARY, ASSOCIATED

WITH AN OVARIAN DERMOID CYST.

By Lindsay Peteus, M. D.


(From the Gynecological Department of The Johns Hopkins Hospital.)


Out of 7,600 patients admitted to the wards of the Gynecological Department of the Johns Hopkins Hospital since September, 1889, (there being 42 cases of dermoid cysts among that number), only two cases of carcinoma associated with a dermoid cyst have been observed. There was one case of dermoid cyst of the ovary coexisting with squamous-celled carcinoma of the cervix uteri, the latter extending out into the broad ligaments and to the tubes, not, however, involving the dermoid cyst. The combination of carcinoma and dermoid in the same tumor in any manner is rare, and carcinoma developed primarily from epithelial structures in a dermoid is very seldom seen.


In discussing the relations of carcinoma to dermoid cysts it is necessary to bear in mind the various possibilities, which are: First, a carcinomatous degeneration of the dermoid tumor itself; second, the carcinomatous degeneration of a part of an ovary, another part of which contains a dermoid cyst; third, the original association of a multilocular cyst with a dermoid cyst, followed by a carcinomatous degeneration of the multilocular tumor, (Gessner), and fourth, the possibility of a dermoid cyst of the ovary being invaded by a carcinoma from some contiguous organ.

The first case to be described in this report is one of carcinomatous degeneration of an ovarian dermoid cyst. Dr. Kelly


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL, 1900.


Bladder



Fig. 1.— Shows tlie relations of the tumor to the rectum, bladder, and symphysis pubis and its extension into the cul-de-sac.


Top of



Fig. '.'. — Tom I appear through the domlnal wall, showing ■

surrounding structures. Th'- relations ol the bladder to the cervix and bodj "I the uterus can be well seen.


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has already reported this case briefly before the Medical Society of the Johns Hopkins Hospital,* and I shall, therefore, not dwell upon the points which he has brought out, but shall endeavor to add to what he has reported something of the subsequent history of the case, and a more detailed description of the pathological findings. 1 am indebted to Dr. Kelly for placing the case in my hands for thorough description and publication.

Case I. (Gynecological No. 7394).— Mrs. H. T., white, aged 46 years, was admitted to the Johns Hopkins Hospital, Nov. 24, 1899.

Complaint, pain in bowels."

The patient has had 10 children, no miscarriages. There is nothing of interest in the history of her labors except that she had puerperal septicaemia after the birth of her 9th child, 14 years ago. and that the birth of her last child, 10 years ago, was induced at the 8th month on account of haemorrhages which began in the 6th month of gestation and ceased soon after delivery.

Menstruation has always been regular and normal. The last menstruation before operation was on Nov. 4, 1899.

She has had slight leucorrhcea, from time to time, for many years.

Her family history is good, excepting that her mother died of heart disease.

Her past history is good.

The history of her present illness is as follows. Since the birth of her 9th child, 14 years ago, she has suffered with soreness in both inguinal regions, and with distressing bladder symptoms— a sensation of weight or pressure on the bladder and, at times, incontinence of urine, at other times prolonged and painful retention of urine. Seven or eight years ago she noticed for the first time a tumor low down in the left side of the abdomen. This was freely movable and changed its position whenever the patient assumed certain postures. She thinks that the tumor remained the same size from the time she first noticed it until about three months ago, when it seemed to rise and cause" knots" or "lumps" in the abdomen. About this same time (three months ago), having previously been able to go about and attend to her duties, she took to her bed on account of the severity of the bladder symptoms mentioned above, and has remained in bed ever since. For the past two weeks she has been unable to void urine, except a very little at a time, and that only while standing.

Physical examination on admission. — The patient is emaciated ; her cheeks are sunken, the complexion is sallow, the eyes watery, the mucous membranes pale, the tongue clean.

The pulse is regular in force and rhythm, of fair volume, but rather low tension, 96 per minute. The vessel-wall is palpable.

The lungs are negative.

The heart is also negative.

Vaginal examination. — The external genitalia are normally developed, but somewhat atrophic. The vaginal outlet is markedly relaxed. The posterior vaginal wall presents at the vulval orifice over an area of about one square inch. The cervix cannot be distinctly outlined, but is apparently pushed upward an inch or two above the upper border of the symphysis, and to the right side. Here a small polyp can be felt. Filling the whole of the pelvis and extending to within 1J in. of the vulval orifice, pushing forward the posterior vaginal wall, is a tumor mass. This is in places hard and firm, in other places fluctuant. It is apparently firmly fixed in the pelvis, especially on the right side. The rectum is pushed well to the left side of the pelvis and its lumen is encroached upon by the mass. The uterus is apparently situated upon the anterior face of the tumor, its fundus being about 10 to 12 cm. above the upper border of the symphysis. The


•Philadelphia Med. Journ., 1S'J«, Vol. IV, No. 36, p. 1208.


bladder is greatly distended, extending to the top of this mass which we consider to be the uterus. During examination urine passes freely from the meatus. The tumor, which apparently springs from the right side of the pelvis, extends to the umbilicus above. It is irregular in outline, somewhat nodular. It is fluctuant and tense over most of its surface and is apparently firmly fixed in the pelvis. Slight crepitation can be felt over the left anterior surface of the tumor.

Operation (Cystectomy by Br. Kelly). — A median incision, IS cm. long, was made, exposing the uterus flattened against the anterior abdominal wall. Several small, hard nodules in the bladder peritoneum were excised, and others were seen over the peritoneal surface. The tumor was densely adherent to the sigmoid, rectum and pelvic walls. A large leash of blood-vessels running in the infundibulo-pelvic ligament on the left were ligated and cut. The tumor contents (dermoid) were drawn off by a large trocar. The peritoneal coat of the tumor was incised and the tumor-wall separated, by blunt dissection along the surface of cleavage, from its adhesions to the intestines, pelvis, etc. There was moderate oozing until, on detachingthe tumor from the rectum and vagina, low down on the posterior wall of the pelvis, near the anus, a carcinomatous mass was encountered, which bled freely and was curetted away. After curettage, removing about 12 cc. of friable material, resembling an advanced cervical cancer, an opening into the posterior vaginal vault was made with the end of blunt forceps and stretched the full width of the vagina for drainage. Washed-out iodoform gauze was laid in the pelvis and brought out into the vagina. The question then was, how to protect this cancerous area, sure to break down immediately, from the peritoneal cavity above. This was done by taking the large, somewhat plastic uterine body, with its right tube and ovary amputated, but with the left tube and ovary intact, and drawing it back into retroflexion, when it snugly and exactly filled the opening at the pelvic brim. The uterus was then sewed to the brim of the pelvis by continuous catgut suture, beginning with the right round ligament and suturing it for about 2 cm. to the brim and then continuing on around the fundus on a line between the tubal ends, anterior to the amputated surface on the right, over to the opposite tube and ovary and beneath them, leaving them projecting up into the abdominal cavity. The rectum was protected from sutures by a thick fold of membrane left from the capsule of the tumor. After extirpation, the rectum just had snug room at the brim of the pelvis. The left round ligament was not sutured, as the suturing ended with the infundibulopelvic ligament. Several bleeding points on the sac-wall were ligated. The abdomen was flushed out with normal salt solution and closed with interrupted silkworm-gut and catgut sutures.

Description of the Tumor.— Gynecological-pathological No. 3647.

Gross description. — The specimen consists of a cyst, a Fallopian tube and numerous small scraps of tissue of irregular shapes, which were removed by curettage from the posterior wall of the pelvis.

The cyst is 13 cm. in diameter. Exteriorly it is pinkishyellow in color and for the most part smooth, though in places, especially towards the base, dense adhesions are seen. Also near the base, on the right, postero-inferior portion of the outer surface, is a circular, rough excrescence, about 5 cm. in diameter and raised about 5 to 7 mm. above the surrounding surface. This is composed of pale-pink, somewhat hard, coarsely granular tissue, some parts of which are quite friable, other parts firmly held together by a stout fibrous


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network. At about the centre of this circular area there is a small opening, 5 mm. in diameter, into the cyst-cavity, apparently made by tearing of the cyst-wall in removal of the tumor. There is another small opening, about 2 5 cm. long, in the upper wall of the cyst, made during the operation for the purpose of evacuating the contained fluid. The thicknpss of the wall varies from 1 to 4 mm., except in one part of the cyst near its base, where long, high, narrow ridges of tissue, to which wisps of long, fine, blonde hair are attached, project into the cyst-cavity. The thickness of these ridges from side to side varies from .5 to I cm. They rise from 1 to 2.5 cm. above the surrounding surface and are from 2 to 4 cm. long. The wisps of hair are matted together by a large amount of greasy, sebaceous secretion. In the wall, beneath the base of the highest of the ridges of tissue just described, there is found a mass of hard bone, about 2 cm. in its greatest diameter, of very irregular shape. There are also, on various parts of the inner surface, smooth, slightly elevated ridges which represent the remains of previously existing septa. The remainder of the inner surface has a puckered or rugous appearance and, in general, is of an opaque, yellowish-white color. But there are numerous areas from 3 mm. to 2 cm. in diameter which are very sligh ly (scarcely .5 mm.) elevated, of a reddish-brown color and have sharply defined, circular or irregular outlines. They have a somewhat velvety appearance owing to numerous minute, columnar and papilla-like projections of which they are composed. The inner surface of the cyst opposite the rough, circular area on the outer surface is comparatively smooth, except immediately around the small opening at the centre of the rough area, where there is a border about 2 to 3 mm. in diameter, composed of slightly raised, coarsely granular tissue.

The Fallopian tube is 5.5 cm. long, having a practically uniform diameter of 6 mm. It is enveloped by dense adhesions. The fimbria? are matted together, the ostium abdominale occluded. Just below the tube, betweeu the layers of the broad ligament, 1 cm. from its outer extremity, are three small, thin-walled, translucent cysts, side by side, 3 to 5 mm. in diameter.

The irregular pieces of tissue removed by curettage are firm in consistency, dark red in color, for the most part very friable, and have many slender projections on their surfaces. They vary from 1 to 2.5 cm. in greatest diameter.

With the exception of the scraps of tissue removed by curettage from the posterior wall of the pelvis, which were preserved in a 5 per cent solution of formalin, the gross specimen was preserved in Mi'iller's fluid and afterwards washed in running water, then placed in 95 per cent alcohol. Sections were cut for microscopic study from (re) the ridges of tissue from which the wisps of hair took origin ; (b) various parts of the wall, not including the rough excrescence on the outer surface; (c) the portion of the wall occupied by the rough excrescence; (d) from the scraps of tissue curetted from the posterior wall of the pelvis ; (e) from the Fallopian tube. These, after being properly hardened by the usual method, were embedded in celloidin. Microtome sections were then cut and were stained with hematoxylin and eosin.

Microscopic description, (a). Sections through the ridges


of tissue from which the wisps of hair took origin are seen to have very uneven surfaces, presenting alternate, irregular projections and depressions. Upon the surface is a layer of stratified squamous epithelial cells, which varies from 2 or 3 to 6 or 7 cells in thickness. The most superficial of these epithelial cells have degenerated and have been cast off from the surface either singly or in homogeneous, deeply eosinstained bands formed by the coalescence of the superficial cells. Definite prickle-cells are seen in the deepest stratum of the layer. In many places the epithelium covering the surface is degenerated throughout the thickness of the layer, being converted into a mass of retractile, disintegrated, deeply eosin-stained tissue. In the stroma beneath the layer of surface epithelium there are many cross and oblique sections of hair follicles and numerous normal sebaceous and sudoriparous glands. Some of the hair follicles contain hairs, others do not. The stroma is composed of dense, wavy fibrous tissue, poor in nuclei, and running through it are many thin-walled blood-vessels. There are also many masses of colored bloodcorpuscles in the stroma, some of which are free in the tissues, others contained in the walls of congested blood-vessels. The tissues, in many places, show beginning hyaline change. Scattered through all the tissues of the wall are fairly numerous small round cells and a few polymorphonuclear leucocytes. The degree of the leucocy tic invasion varies very much in different parts of the specimens, being quite dense in many places near the inner surface.

(b~). On examining many sections from various parts of the wall (not including the rough excrescence on the outer surface), it is found to be composed for the most part of dense fibrous tissue which, iu mauy places, shows hyaline degeneration. In a few places, small bundles of non-striated musclefibres are seen. The fibrous tissue is densest next to the outer surface, where, in some places, its appearance is suggestive of ovarian stroma. The outer surface is generally smooth and even, but here and there thick, non-vascular tags of adhesions are seen. There are also a few slit-like spaces just beneath the outer surface lined by a single layer of flattened, endothelial cells. Blood-vessels of considerable size aie scattered in moderate abundance through all parts of the wall.

The inner surface is, for the most part, devoid of any epithelial lining, although in some places it is covered by layers of stratified epithelium from 2 or 3 to 15 or 20 cells in thickness. The cells in the thickest layers are, in general, flattened from side to side instead of from above downward, as in the stratified squamous epithelium of normal structures such as the cervix uteri, vagina, skin, etc. In the thinnest layers they are flattened from above downward, and in the layers intermediate in thickness they are much less compressed, i. e., more polyhedral in form Some of the cells in the deepest strata are prickle-cells. No definite papilla? are formed beneath the epithelium. The portions of the inner surface not covered by epithelium are wavy in outline and composed of fibrous tissue, which, iu many places, resembles chronic granulation-tissue, containing many very small, wellformed, congested blood-vessels. The tissues, a short distance below the surface, are permeated by extravasated blood.

The reddish-brown, slightly elevated areas on the inner surface, noted in the macroscopic description, are seen in the microscopic specimens to have very uneven surfaces, presenting many irregular depressions and processes. They are composed of loosely disposed cells, which are exceedingly multifarious in size and structure. Some of the cells are of moderate size, polyhedral in shape, containing single, spherical or oval nuclei, which stain homogeneously. There are a few elongate cells with spindle-shaped nuclei, but the most conspicuous feature in the tissues of these areas is the presence of immense giant-cells, some of which occur in groups of from 2 to •">, and appear to be partly fused with one another. They are seen sometimes on the surface, sometimes a short distance below it. Each giant-cell contains from 3 or i to 40 or 50 small spherical nuclei, which are grouped around the periphery in some of the cells, towards the centre in others. Numerous minute blood-vessels, many of them engorged with blood, run in and out among the cells, and in the interstices of the tissue are large numbers of small round cells, polymorphonuclear leucocytes and colored blood-corpuscles. The protoplasm of the cells containing single nuclei, as well as that of the giant-cells, is deeply stained with eosin, and has an homogeneous, cloudy, blurred appearance, the outlines of the cells being as a rule ill-defined. The deepest portion of this tissue is continuous with underlying hemorrhagic areas in the cyst-wall. Its cells show no evidence of abnormally active proliferation, nor any tendency to strike downward into the subjacent tissues.

(c). Sections through the part of the wall occupied by the circular excrescence on the right, postero inferior portion of the outer surface have the following appearances :

The distance from the inner to the outer surface in the sections varies from .5 to 1 cm. The outer portions of the wall are composed mostly of masses of epithelial cells. These masses are very irregular in shape, of various sizes, and are separated from one another by dense fibrous stroma. The epithelial cells in the masses are very variable in form and size, the average-sized cells being about as large as the cells seen in the stratum granulosum of the skin. In general, the cells on and near the margins of the masses are smaller, more closely packed together, and contain more deeply stained nuclei than the cells uearer the centres of the masses. The cells near the central portions of the masses are very large and their nuclei are somewhat more palely stained than those near the margins. All of the nuclei vary greatly in intensity of staining. They also, like their containing cells, are very variable in size, some of them being as much as 5 or (3 times larger than the averagesized nucleus. They are, as a rule, spherical or ovoid in shape, consisting of an outer, narrow, homogeneous, pellucid, lightly hagmatoxylin -stained rim or capsule and a large, central mass of coarse, highly refractile, deeply hsematoxylinstained granules, in a few of them a central, spherical or ovoid nucleolus being seen. The protoplasm of the cells is finely granular and stains deeply with eosin. In some places, where the outlines of the cells are distinctly seen, prickles are observed around the margins of the cells. There are many large, necrotic areas in which no cellular elements are


found. Small areas of necrosis are often seen in the central portions of the epithelial masses.

The masses of epithelial cells just described have the arrangement and other characteristics of carcinoma; they are, in fact, "carcinoma cell-nests." The new growth, although involving chiefly the outer layers of the cyst-wall, is found (in sections through the wall made in such a way as to include the rough margins of the small opening on the inner surface, opposite the centre of the circular excrescence on the outer surface) to extend through the entire thickness of the wall, in one place a transition from the lining epithelium into the carcinomatous tissue beiug seen. The only carcinomatous portion of the inner surface is that covered by the rough margins of the small opening opposite the centre of the excrescence on the outer surface. The carcinomatous tissue is seen undermining the lining epithelium as well as growing downward from the inner surface. The growth spreads more and more laterally as it approaches the outer surface.

The portions of the sections not invaded by the carcinoma are composed of dense fibrous tissue. All of the tissues are diffusely infiltrated with leucocytes — chiefly polymorphonuclear. The infiltration is most marked in the fibrous stroma around the cell-nests.

In these sections no karyokinetic figures are found. There are, however, a considerable number of tumor-cells, in each of which a pair of nuclei is seen. Each nucleus in every pair has the form of one-half of an ovoid which has been divided at a right angle to its long axis, the divided ends facing each other and being almost, if not quite, in contact. Except for their form and their position relative to each other, these twin nuclei do not differ in appearance from the nuclei of the tumor-cells in general, nor is any difference between the appearance of the protoplasm of the cells containing the twin nuclei and that of the cells containing single nuclei detected. In addition to the twin nuclei, one occasionally sees a nucleus with a faint, indefinite, light line running across its middle. Some cells are found in which there are three distinct, well-formed nuclei, which are closely adjacent to one another, their adjacent edges being flattened as if from pressure against one another, and a few cells are seen in which there are indistinct lines of cleavage (?) in each nucleus, dividing it into four parts. Still another type of cell is seen which is always mononuclear and is noteworthy, not on account of any peculiarity of its nucleus, but because there are light lines radiating from the margins of the nucleus through the protoplasm to the borders of the cell-wall. These cells are always nearly exactly circular in outline, and their protoplasm stains deeply with eosin in a narrow zone immediately around the nucleus, from which the color gradually shades into a very pale pink at the margins of the cell.

Occasionally one finds a group of cells arranged in concentric layers around a central cell, all the cells in the layers being flattened towards the centre of the group. They have the appearance of" carcinoma pearls" in au early stage of formation.

(d). In the sections from the scraps of tissue curetted


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away from the posterior wall of the pelvis, the same tissueelements are found as were described for the outer part of the wall in the third group of sections (c), and the tissues have the same general arrangement into epithelial masses surrounded by dense fibrous stroma. The epithelial cells, however, differ from those described under group (c) in the following respects: the former have a smaller average size than the latter, their protoplasm stains a faint pinkish-violet color instead of taking an intense eosin stain and their nuclei, instead of being composed of coarse granules are vesicular, having very thin walls containing fine, loosely scattered granules of chromatin. Many of the cells in these sections contain karyokinetic figures showing various stages of indirect celldivision, some of the figures being symmetrical, others asymmetrical. Also many cells are found containing 2 or sometimes 3 well-formed nuclei within a single cell-wall which shows no evidence of beginning division. All of the tissues are diffusely infiltrated with polymorphonuclear leucocytes and small round cells, the infiltration being most marked in the fibrous trabecular between the epithelial masses. There is no suggestion of a glandular arrangement of the cells.

(e). The folds of the mucosa of the tube are normal in size and are not adherent to one another. They are covered by a single layer of normal, low-columnar, ciliated epithelial cells, which contain spherical or oval, evenly stained nuclei. The stroma of the folds has the normal ajipearance and is free from leucocytic infiltration. The muscular coats are atrophied, appearing in small, scattered strands of non-striated muscle-fibres just exterior to the tubal mucosa. Between the scattered strands of muscle-fibres is dense, wavy, fibrous tissue, poor in nuclei. The outline of the outer surface is generally slightly wavy and is partly covered by small cells, in a single layer, which have large, oval nuclei, flattened from above downward, which almost completely fill the cells. These are endothelial cells of the peritoneum. There are a few tags of old, slightly vascular, fibrous adhesions projecting from the outer surface.

Deductions from Description of Specimen. — From the above description it is evident that we are dealing with a squamous-celled carcinomatous growth in the wall of a dermoid cyst. As a transition from the lining epithelium of the cyst into the carcinoma is demonstrable in the microscopic specimens and, moreover, there being no discoverable carcinoma in any other part of the body, there can be no doubt that the origin of the growth was from the lining epithelium of the cyst. The fact that the growth at its point of origin covers such a small area and projects so slightly into the cavity of the cyst is remarkable, and we offer as an explanation thereof the suggestion that the pressure exerted by the contents of the tensely distended cyst may have prevented the growth of the tumor into the cavity.

Concerning the peculiar appearances in some of the tumorcells noted in the description of group (c) of the microscopic specimens, it is impossible to arrive at any conclusions, the tumor not having been placed in the fixing fluid until several hours after its removal from the body. However, we think it possible that the appearances are due to changes in the cells which have taken place after extirpation of the tumor, the


nuclei in groups of 2, 3 and 4 being possibly the result of the completion of the cycle of division by nuclei which, at the time of removal of the tumor, had already begun to divide. The appearance of some of the multinuclear cells is, however, very suggestive of direct division of the nuclei.

The giant cells noted in the description of group (b) of the microscopic specimens have the same appearance as the giant cells which are often met with on the inner surfaces of dermoid cysts free from any malignant new growth. These have been described (Hildebrandf) as foreign-body giantcells, supposed to be due to the presence of hairs in the walls of the cysts ; but we have often observed them in parts of the walls of dermoid cysts in which there were no hairs to be seen and also in simple dermoids in which no hairs were found in any part either by macroscopic or microscopic examination ; they are, therefore, as suggested by Cullen, more probably a form of embryonic epithelium from which the lining epithelium of the cysts is developed. In the case which we now have under consideration the giant-cells are found in parts of the tumor remote from the ridges of tissue to which alone the hairs were attached.* The tissue in which some of our giant cells are embedded is, in all probabilty, granulation tissue formed as a result of long-standing inflammation of and hemorrhage into the tissues upon and immediately beneath the surface of the cyst-wall.

Post-operative History. — The patient had practically no nausea after operation, but pain during the first 3 days was sufficiently severe to require morphia. During the 5th, 6th and 7th days the gauze drain in the pelvic cavity was gradually pulled out, a small piece of it being clipped off each day, until on the 8th day all that remained of the drain was removed, after which a considerable amount of sanguinopurulent fluid escaped. The cavity in the pelvis was then carefully cleansed by douching with a saturated solution of boracic acid and again filled with clean gauze. From this time on dilatation of the opening into the cavity and douching and repacking of the cavity were repeated every day. On the 9th day the abdominal wound was inspected and found to have healed perfectly. Alternate silkworm-gut sutures were removed. On the 12th day all remaining sutures were removed from the abdominal incision, and the following uote was made. "By examination with one finger in the cavity and another finger in the rectum, it is ascertained that the cavity lies entirely to the right of the rectum and is separated from it by a septum of firm, indurated tissue, about .5 cm. thick, which extends upward (along the side of the rectum) to a point just within the reach of the examining finger. The lumen of the rectum is considerably encroached upon."

The patient was allowed to be out of bed in a wheel-chair on the 24th day, and was able to walk several days before her discharge from the hospital on the 36th day.

During the entire convalescence there was considerable


  • Cullen says that in very early dermoids of the ovary, where no

epithelium is as yet present and where no sebaceous nor sudoriparous glands are found, the diagnosis can be made, with almost absolute certainty, from these characteristic giant cells. (Personal communication).


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sanguino -purulent discharge, which at times had an offensive odor. The patient complained repeatedly of pain in the right hip and back, chiefly at night. There was also, at times, severe pain in the rectum, which was, however, relieved by defecation.

During the first 3 days after operation the temperature chart showed a range of temperature between 100° and 101°F., the pulse ranging between 90 and 108 per minute. After this time the temperature continued very slightly above normal until the end of convalescence, except on the 19th and 24th days, when there were slight rises to 100.5°F. The pulse, after the 3rd day, ranged between 88 and 104 per minute.

The following is a note made on the discharge of the patient from the hospital on the 36th day. "The cavity posterior to the vagina has decreased in size. It holds about two ounces. The new growth has increased markedly and extends down to the anal orifice. The opening into the cavity admits the index finger. The uterus is felt in adherent retroflexion. The patient's general condition is only fair ; she suffers considerable pain in the hip and back; she also requires codeia at night for sleep, and suffers with constipation."

Id a letter written thirteen weeks after operation, the patient states that she notices very little change in her geueral health since leaving the hospital, but that she now has a very offensive discharge, "like decayed blood," from the rectum. It is, therefore, highly probable that the carcinoma has now extended through the rectal wall. The fact that the patient is still alive and notices very little change in her condition, except that which can be explained by local extension of the growth, shows that the efforts to protect the abdominal cavity by suturing the uterus to the pelvic brim have been successful.

Review of the Literature. — The first indubitable case of carcinoma developed from epithelial elements of a dermoid cyst is that reported by Bierman, 3 in 1885. Before that time other cases had been published by Heschl, 3 von Wahl,* Colin,' \ eit'- and Pomorski, 7 in which carcinoma and dermoid cysts were said to be associated in the same tumor; but none of these will be discussed, some of them being too inadequately reported to establish their authenticity, others undoubtedly deserving to be considered as " mixed tumors " and not as dermoid cysts which have undergone carcinomatous degeneration. In 1884, Babinski" reported two cases which he considered to be carcinoma "probably" derived from dermoid cysts, but his descriptions are meagre and his conclusions are uncertain. After the publication of Bierman's case, Himmelfarb," in 1886, Krukenberg, 10 in 1887, and Tauffer," in 1895, each reported an authentic case of squamous-celled carcinomatous degeneration of a dermoid cyst. In 1897, two other cases were published, one by Thumin,' 2 another by Yamagiwa.' 1 Clark," while, working in the laboratory of Chiari, at Prag, published, in 1898, the case of a dermoid cyst which had been discovered among a large collection of museum specimens and which proved, on microscopical examination, to have undergone carcinomatous change in one part. The tumor had been extirpated by abdominal section, in May, 1885, from a woman aged 29 years. At the same operation a metastatic nodule the size of a walnut was removed from the left axilla.


The patient made a good recovery from the operation, but no further history was obtainable. Clark was able to trace, in the microscopic specimens, a transition from the normal epithelial lining of the cyst into the carcinomatous tissue. He also described giant-cells similar to those which we have noted in our case. Tauffer gives very full abstracts from the descriptions of the cases of von Wahl, Heschl, Bierman, Himmelfarb and Krukenberg, and Clark also gives a very satisfactory summary of all the cases published prior to his own.

Since the report of Clark's case, we find only one other observation of carcinomatous degeneration of a dermoid cyst of the ovary, that reported by Lockhart and Anderson," in 1899. In their case the patient was an unmarried woman, 50 years of age. At operation, the tumor was punctured and "120 ounces of thick, grumous fluid, containing caseous material and hair," escaped, revealing the dermoid nature of the tumor. It was learned that the tumor had originated in the left ovary, and that its pedicle, consisting of the uterus and broad ligament, was twisted half way around. Many dense adhesions of the cyst to the upper part of the left wall of the abdomen, to the omentum, to the under surface of the right lobe of the liver, to the right anterior abdominal wall and to the intestines, were encountered. The patient did well for the first four weeks after operation, and was discharged from the hospital on the 31st day, but died one week later. The tumor is described as a " large, irregular-shaped mass, measuring 18x15x14 cm., weighing 1,570 grins." Its peritoneal covering was " thickened and hemorrhagic." On section it was found to be composed of a "series of large cysts whose walls were markedly thickened, in some places measuring 5 cm." The cyst contained a " thick, oily, flocculent fluid, as well as two large, rounded masses of hair, about the size of large apples." Three teeth, embedded in the wall and projecting into the cyst-cavity, were also found. The following is a copy, in full, of the description of the microscopic specimens: "The tumor is seen to be composed mainly of epithelial elements, which infiltrate extensively the fibrous tissue stroma. Multiple pearl-nests are found in these areas. At other points the epithelial cells are arranged in alveolar and tubular forms, as in carcinoma, with large bands of fibrous tissue surrounding them. A large amount of adipose tissue is also present. The vessels throughout are numerous, and engorged with blood, and in places surrounding these are a large number of small, round cells." They then conclude:

" The tumor is, therefore, an ovarian dermoid cyst, with cpitheliomatous, and, in some places, carcinomatous infiltrations. It also shows evidences of acute, and, in some places, sub-acute inflammatory reaction."

Cone," in 1897, described a dermoid of the lower jaw which showed squamous-celled carcinomatous degeneration, and referred to similar cases observed by Franke, Czerny and Briddon. Cone also noted in his case the presence of giantcells. These were of two kinds, one of which were found around the roots of hairs and thought to be "foreign-body giant-cells," the other kind being seen in the centres of typical tubercles and considered as " tubercle giant-cells."

In 1897, Yamagiwa published, with his case, which we have


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already alluded to, another case which he believed to be one of adenocarcinoma, developed from a nipple-like growth or anomalous, misplaced mammary gland on the inner surface of the dermoid cyst. That is the only case of adenocarcinomatous degeneration of a dermoid of which we are able to obtain record.

As yet, no case of carcinoma, thought to be derived from the sudoriparous or sebaceous glands of a dermoid cyst, has been reported.

The secondary changes, other than carcinomatous, which have been observed in dermoid cysts, are rather limited in variety. Friedlander" has reported an instance of cystic degeneration of glands in the wall of a dermoid, Biermau" an instance of primary sarcoma and Faquet' 9 an instance of endothelioma in a dermoid. Papillary growths in multilocular ovarian cysts, which were only partly dermoid, have also been reported.

The remaining case which we have to report is interesting as an example of the second class of possibilities which we have mentioned, /. e., a carcinomatous degeneration of a part of an ovary, another part of which contains a dermoid cyst. On looking through the literature we do not find any similar case previously reported.

Case II. {Gynecological No. 5164.}— Mrs. K., white, aged 36 years, was admitted to The Johns Hopkins Hospital, April 6, 1897.

The patient has had 6 children and 1 miscarriage. Puerperal

fever followed her last confinement, six years ago, and at the

same time she had "milk leg," affecting the right lower extremity.

Her menses began at 16 years. They are always regular and

last 3 to 4 days.

She had profuse and offensive leucorrhuea for two years after the birth of her last child.

Two uncles died of phthisis. The family history is otherwise negative.

The patient has had only the usual diseases of childhood, and has always been strong and well.

Her present illness began in August, 1896, with fever which her doctor pronounced typhoid. She was in bed two weeks and since then has had fever "off and on," and at recent menstrual periods has suffered exquisite pain in the left ovarian region, with great nausea and vomiting.

Operation (Double Cystectomy , with removal of the uterus, by Dr. Kelly). — The right ovary is found converted into a lobulated and nodular tumor about 10 cm. in diameter. This is slightly bound down by adhesions, and at its inner and upper pole is a subperitoneal cyst, 4 cm. in diameter.

Enucleation was commenced on the right side on account of adhesions of the left ovary, which was twice the normal size and was occupied by a growth similar to that on the right. The uterus was amputated at the cervix, and the operation was then completed in the usual way. Small, secondary nodules were seen in the omentum.

Over the region of the left kidney there was a lobulated, nodular mass about 8x7 cm. This was probably infiltrated omentum. The abdomen was washed out with salt solution. In closing the wound, catgut was used for the peritoneum, and interrupted, through-and-through silkworm-gut and catgut for the other layers.


Description of the Specimen. No. 1645.


Gynecological-pathological


Gross description.— -The uterus measures 6.5 x 4.5 cm. The posterior surface and fundus are covered by adhesions. On section the uterine cavity is seen to be 4 cm. long, and 4 cm. broad at its fundus. The uterine mucosa is pale and looks (edematous. In the cervix is a dilated follicle 4 mm. in diameter.

Right side.— The ovarian tumor, which resembles a cystic kidney in contour, measures 10x5.5x4 cm. The surface is nodular, and on one side is a bunch of 8 or 9 cystic or partlysolid nodules, some of which resemble hemorrhagic Graafian follicles, others contain clear fluid. On section, the tumor is found to be of a yellowish color and to consist of a somewhat friable, homogeneous or fibrillated tissue, which here and there, around the periphery, presents small cystic areas into some of which haemorrhage has occurred. In the hilum of the tumor is a cyst 2.5 x 1.5 cm. which contains a buttery material resembling dermoid contents.

The Fallopian tube is bound down to the surface of the tumor, but is apparently patent.

Left side.— The ovary is converted into a small, nodular tumor, 4x3 cm., resembling the one on the opposite side. On its upper surface, at the inner pole, is a corpus luteum 1 cm. in diameter.

Microscopic examination. — The uterine mucosa has an intact surface epithelium. The glands are abundant and a few slightly dilated. Frequently a gland is seen extending a short distance into the muscular coat, but the glands are perfectly normal. The stroma of the mucosa is rarefied.

Right side. — The ovarian elements are almost entirely replaced by neoplastic tissue. This consists of narrow, branching processes of epithelium penetrating the stroma in all directions. These processes often consist of but two rows of cells, which may present a narrow central lumen. Frequently, however, the cells form solid cylinders, sometimes of considerable thickness. On cross-section, solid nests of epithelial cells are found or a minute cavity, lined by one layer of cells. The individual cells vary in size and form, but are usually large, oval or cuboidal, and contain large, round, oval, crescentic or irregular nuclei, which in general take an intense, solid stain. Nuclear figures, both symmetrical and asymmetrical, are abundant, and there is slight karyorhexis, but, on the whole, nuclear fragment ion is not notable, and cell degeneration of all kinds is practically absent. The cell-masses are separated from one another by delicate strands of connective tissue, but the tumor is further irregularly divided into lobules by broad bands of connective tissue, and by practically unaltered ovarian stroma, which, in some portions, especially around the periphery of the tumor, is present in considerable amount, though in every part showing, here and there, small epithelial masses.

The cystic portions appear to have originated in Graafian follicles or degenerated corpora fibrosa. In one section a corpus fibrosum is found. Scattered through the stroma are a moderate number of small round cells. The vascularity of the tumor is moderate, the vessels usually of small size. The cyst found in the hilum of the tumor presents the usual appearances of a simple dermoid. It is lined by stratified squamous epithelium, and in its wall are a few sebaceous


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glands. No hair follicles are seen. For the most part the cyst is surrounded by a narrow band of connective tissue or ovarian stroma, but at some points the epithelial cells have penetrated to the surface and cell-masses are found in the mesosalpinx aud even between the Layers of muscle-bundles in the tube-wall. The broad ligament also contains metastases, cell-nests being found in the lymph-spaces, and, in one place, in a large vein. The tubal mucosa is normal and no tumor elements are found on the upper surface of the tube wall.

Left side. — The tumor is similar to that ou the opposite side. The corpus luteum observed macroscopically presents the usual features and shows commencing organization.

Diagnosis. — Carcinoma ovarii duplex associated with a small dermoid cyst in the right ovary. Corpus luteum in the left ovary. Practically normal uterine mucosa. Perisalpingitis. Subperitoneal cysts.

Keferences.

1. Hildebrandt: Ziegler's Be.itr. z. path. Auat., 1890, Bd. VII, S. 169.

2. Bierman: Prager med. Wochenschr., 1885, No. 21, S. 201.

3. Heschl: Prager Vierteljahrsschr., 1860, Bd. LXVIII, S. 57.


4. von Wahl : St. Petersb. med. Wochenschr., 1883, S. 70.

5. Colin: Zeitschr. fur Geburtsh. und Gvnakol., 1886, Bd. XII, S. 36.

6. Veit: Zeitschr. fur Geburtsh. und Gvnakol., 1S90, Bd. XIX, S. 329.

7. Pomorski: Centralblatt fur Gynakol., 1889.

8. Babinski: Progres Med., Paris, 1884, XII, p. 29.

9. Himmelfarb: Centralblatt fur Gynakol., 1886, S. 569.

10. Krukeuberg: Archiv fur Gynakol., 1887, S. 241.

11. Tauffer: Virchow's Archiv, 1895, Bd. CXLII, S. 389.

12. Thumin : Archiv fur Gynakol., 1807. S. 547.

13. Yamagiwa: Virchow's Archiv, 1897, Bd. CXLVII, S. 99.

14. Clark: Amer. Jour, of Obstet., 1898, Vol. XXXVIII, No. 3.

15. Lockhart and Anderson : Montreal Med. Jour., 1899 Vol. XXVIII, p. 116.

16. Cone: Johns Hopkins Hos. Bull., 1897, Vol. VIII, p. 208.

17. Friedlander: Virchow's Archiv, Bd. 56, S. 365.

18. Bierman: Prager med. Wochenschr., 1S85, No. 21.

19. Faquet : Archiv. de Toe. et Gynecol, 1895, Vol. XXII, p. 629.


PULMONARY TUBERCULOSIS, WITH DIFFUSE PNEUMONIC CONSOLIDATION, IN A LION.

By W. G. MacCallum, M. D., and A. W. Clement, V. S., Baltimore, Md.


While in Birmingham, Ala., in November, lfc99, one of the lions belonging to the Hagenbeck menagerie, a large adultmale of the black-maned sort, which had been captured in South Africa and had been in captivity ten years, fell ill. The keeper noticed that the lion was not well and frequently refused food. On the removal of the menagerie to Baltimore it grew worse, developed a slight grunting cough, became very much thinner than normal, and, after an illness of about four weeks altogether, died.

The autopsy was performed the next day. The body was that of an adult male lion, said by the keeper to be about fourleen years old. The subcutaneous and omental 1'at were very much wasted. There was no accumulation of fluid in either peritonea] or pleural cavities, and the peritoneal surfaces at least were Bmooth and glistening.

For the sake of brevity, the description of the heart and abdominal viscera will be omitted, as they were apparently quite normal. The lungs appeared somewhat collapsed, and seemed to contain much less air than normal. Their pleural surfaces were not quite smooth, but had lost their gloss. There were, however, no adhesions between the layers. The left lung, which consisted of three lobes, was found to contain very little air, small portions of the upper lobe only being insufflated ; the middle and lower lobes were quite solid. On cutting through the lung, the cut surface of the upper lobe presented, in general, a translucent appearance, being densely studded with small translucent nodules which projected from the surrounding surface ; these hardly exceeded a pin-head in size, and never showed any central area of necrosis. The


intervening lung-substance was gray or grayish-yellow, and somewhat gelatinous and translucent. The lower lobes were more firmly aud uniformly consolidated, the firmness being due to a diffuse consolidation rather than to the translucent nodules which were more sparsely scattered throughout these lobes. The cut surface was, as in the upper lobe, grayish-yellow and somewhat translucent. In the posterior portion of the lobe, there were two well-detined cavities communicating with one another by a narrow channel, and marked off from the surrounding lung by the fibrous thickening of their walls. These cavities communicated with the bronchi; their walls were fairly smooth and covered with a purulent material. Obliterated arteries crossed from side to side.

The right lung was much more voluminous than the left, the upper lobe being insufflated and containing only a lew of the translucent nodules described. The lower lobes, as in the left lung, were consolidated. They were riddled w 7 ith tubular cavities, which correspond with the bronchi, and which, for the most part, were filled with a yellowish purulent material.

The bronchial glands were slightly enlarged and deeply pigmented, but showed no areas of caseation.

Hardened sections of the upper lobes of the lung show the presence of small areas of consolidation here and there. These consist of rounded or oval tubercle-like masses of cells, sometimes close to the bronchi but more often in relation with the small blood-vessels. They are not entirely without a blood supply, for minute blood-vessels may be seen in their interior. They are made np for the most part of epithelioid cells, with vesicular nuclei arranged in an irregularly concentric manner,


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often about several centres. There are very few lymphoid cells, but a considerable number of cells resembling polymorphonuclear leucocytes; and these, with the epithelioid cells, which are often much distorted and of bizarre form, make up the nodule. Very rarely is there any central giant-cell. These nodules are often very sharply outlined on account of the fact that they may fill an alveolus without disturbing the epithelium of the adjacent alveoli. The alveoli adjacent to the tubercles contain a gelatinous exudate consisting almost entirely of coagulated fluid and desquamated epithelial cells. There are a few polymorphonuclear leucocytes, but scarcely any fibrin ; occasionally a little is shown by Weigert's fibrin stain.

Sections of the lower lobes show a great increase in the connective tissue throughout the lung, associated with the tubercle nodules, which are here much conglomerated. Giant-cells are seen in these matted tubercles, although so rare in the discrete nodules in the upper lobes. The alveoli of the intervening substance are completely obliterated by the fibrous tissue which is often much pigmented by coal-dust. In other portions of the lower lobes there are areas of gelatinous pneumonia, and also areas in which the walls of the alveoli, together with the exudate, have become completely necrotic and caseous.

The more densely consolidated portions often show definite bronchiectatic cavities, with thick fibrous walls and a content of cellular debris.

The giant-cells described above very commonly contain welldefined tubercle bacilli, as shown in sections stained by the method of Mallory. Stained by Weigert's method no other organisms can be demonstrated. Cultures from the lung were sterile, and two guinea-pigs, inoculated subcutaneously and intraperitoneally with emulsions of the lung substance, unfortunately died from intercurrent infections, so that no propagation of the organism was effected.

The demonstration of bacilli, identical in morphology with the tubercle bacilli in the giant-cells which formed the centres of nodules in the lung, morphologically like tubercles, seems conclusive enough evidence that the lesion was really tuberculosis of the lungs.

Sections of the other organs showed no tubercles and no other noticeable abnormality.

The exclusive localization of the process in the lungs is interesting in connection with the similar case reported by Straus,* in which, although there were large caseous masses in the lungs, there were no other viscera involved.

Straus' case is the only one in the literature which is


  • Straus: Arch, de med. exper., 1894, VI, 645.


described in detail. Tuberculosis in lions does not seem extraordinarily uncommon, however, for Jensen mentions two cases, Haughton another, and Eayer, quoting Pirrault, two others. It is well known from the work of Jensen,* Eben,f Froehner,J Bollinger§ and others, that dogs and cats are more commonly subject to tuberculosis than is generally thought to be the case.

The localization of the tuberculous lesions in these more or less closely related animals is of interest in connection with this case. Dogs, as reported by these authors, most frequently suffer with pulmonary tuberculoses, and tuberculosis of the serous surfaces is with them more common than in cats, in which, while pulmonary tuberculosis predominates, lesions in the digestive organs are especially frequent.

It is not within the scope of this note to review the literature on tuberculosis in animals, of which good summaries are given by Nocard|| and Leray,** Rayerff and others.

Lebert,JJ in writing of the tuberculosis of apes, states his opinion that they probably suffer in wild life as well as in menageries, and that they live no better in the tropical menageries than in the more northern ones. General opinion, however, seems to favor the view that confinement so lowers the resistance of wild animals, and especially those transported from tropical countries, as to predispose them to the invasion of the tubercle bacilli.

The most important result of a study of this case is apparently the evidence in favor of the view that a diffuse pneumonic consolidation can be caused by the tubercle bacillus alone. Cultures were sterile, and coverslips and sections showed no organisms except the tubercle bacilli, a condition not often found in the human lung, the seat of so extensive a change.

Whether the peculiarities of the bacilli, so much discussed of late,§§ or the differences in the tissues of the beasts, are to be given as the causes of the slight morphological differences in the tubercles in different animals, must be left undecided here.


  • Jensen : .1. comp. path and therap., 1891, IV, 103.

tEben : Dtsch. Zeitschr. f. Thiermed, 1892, XIX, 129. {Froehner: Monatsch. f. prakt. Thierheilk., Bd. VI, Heft 9, p. 385. § Bollinger: Virch. Archiv, 1872, LV, 290. | Nocard : Animal tuberculoses, etc., 1895.

    • Leray : Gaz. de Hop., Paris, 189S, LXIX, 1425.

ft Bayer : Arch, de Med. compar., 1843, I, 189-219. tt Lebert : Dtsch. Archiv fur klin. Med., 1873, XII, p. 42. §§Th. Smith : Journ. of Experimental Med., 1898, Vol. III. p. 451. Mafassi: Ztsch. f. Hygiene, 1S92, Bd. II, p. 445.


THE JOHNS HOPKINS HOSPITAL BULLETIN.


The Hospital Bulletin contains details of hospital and dispensary practice, abstracts of papers read, and other proceedings of the Medical 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.

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April, 1900.]


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ARSENICAL PIGMENTATION AND KERATOSIS.*

By Louis P. Hamburger, M. !>.. Assistant in Medicine, Johns Hopkins University.


This patient, who has been kind enough to appear before the society to-night, is a clerk, forty-two years of age. He entered the Johns Hopkins Hospital Dispensary on the first of November 1899, complaining of swelling of the feet and abdomen. The family history is negative. As a child he had measles and scarlet fever. He has used neither alcohol nor tobacco. To that which is of importance in his past history I shall refer later. His illness began about eight months ago with a"cold"aud a cough. About a month thereafter his abdomen began to swell, and he noted that at the end of the day's work his legs were swollen. The cough soon disappeared but the swelling of the abdomen continued. He has had no shortness of breath, nausea, "fainting spells" nor symptoms of weakness. His bowels have been regular. He presented about the same condition when I first saw him that he exhibits now. He is a sparely nourished man, the visible mucous membranes are of good color and present no unusual pigmentation. What immediately attracts one's attention is the condition of his skin. There is a more or less deep-brown discoloration over almost the entire body. The pigmentation as it appears over the abdomen may be taken as a type of this discoloration ; differences in degree are presented by the skin in various localities. The skin in this situation is of a mottled yellowish-brown color; the mottling is due to small rounded areas of less pigmented, almost white skin, alternating with similar areas more deeply colored. Here and there are little dark, almost black, mole-like spots. The skin feels natural and is at points a little scaly. The face is slightly involved ; it is freckled, the complexion is muddy. On the neck, particularly at the back and the sides, the discoloration is marked, being less punctate and more diffuse than over the abdomen. Still more diffuse is the coloring of the axillary folds; they are uniformly colored a deep-browu. The punctate arrangement is resumed over the shoulders and arms, being more marked over the posterior and internal aspects of the limbs. The discoloration is slight over the forearm and practically absent over the hands. The chest and upper part of back are slightly involved; the areola?, however, are of a dark chocolate-brown color. The abdomen and lower half of back are markedly pigmented. The inguinal folds, buttocks and internal aspects of the thighs are strikingly dark. Toward the lower thirds of the thighs the pigmentation fades ; the skin of the legs is only dotted here and there with spots of pigment; the feet are free from the discoloration.

The skin of the hands is rough and dry. Over the palms it is diffusely thickened. Here, as well as over the dorsal


•Presentation of the patient before the Johns Hopkins Hospital Medical Society, December 18, 1899.

[Note. — Since this paper has been in press my attention has been called to the excellent article by Dr. Hartzell on " Epithelioma as a Sequel of Psoriasis and the Probability of its Arsenical Origin," which was published in the Am. J. of Med. 8c. of September, 1899. Some of the ground here independently traversed is covered by his contribution. — L. P. H.]


surfaces and between the fingers, are numerous small and large dirty-gray warts and callosities from the size of a pinhead to that of a pea. Some of them look like ordinary warts; others are smaller and more like little fine local thickenings. There is a "wart" on the ulnar border of the right wrist. The nails look natural. Projecting from the left elbow for a distance of about a centimetre is a curious conical wartlike thickening recalling somewhat the heaped-up scales of psoriasis.

The soles present even a more remarkable appearance than the palms. Here too is a diffuse thickening but particularly along the outer border, the heel and area corresponding to the metatarsophalangeal articulations. Over these parts and extending a little way up the posterior aspect of the heels there are numerous yellowish horny excrescences of all sizes, discrete and confluent. The nails are unaffected. From the anterior surface of right shoulder there projected a yellowish- brown, lobulated round wart. It was excised, and, examined microscopically, shows the structure of a papilloma.

Below each internal malleolus is a reddened scaly patch having a diameter of about a half centimetre. They bleed from minute points on removing the scales (psoriasis).

The lungs are clear. The point of the heart's maximum impulse is in the 5th 1. i. s. in the nipple line. At this point as well as in the axilla a blowing systolic murmur is heard. The pulse is regular, 62 to the minute.

The abdomen was distended, bulging a little at the flanks. In these regions the percussion note was flat, but became tympanitic on one side when lying on the opposite.

The liver dulness began at the sixth rib in the right parasternal line. Palpation of the abdomen was unsatisfactory owing to the distention. The skin over the shins pitted a little on pressure. The urine contained neither albumin nor sugar.

Under a course of purgation the complaint for which he sought treatment has been a good deal relieved. The abdomen is not so distended, the feet are not so much swollen.

The cutaneous changes had come on so gradually that the patient had paid little attention to them. The warts had been annoying and he had had some of them removed from time to time.

When I saw this combination of extensive pigmentation and keratosis, I made inquiry at once as to the use of arsenic. The patient was much surprised by the question, replying that he had been taking Fowler's solution in doses of from five to eight drops three times daily off and on for a period of ten years. During this time he suffered from a cutaneous eruption which first appeared as a patch on the antero-external aspect of the right knee. It was red, dry and scaly. Other patches of varying sizes appeared from time to time over the body. The eruption itched, bled on scratching, and resembled the "spots" now present on the ankles. Arsenic was prescribed and the skin disease was benefited. After three or four weeks he would discontinue the use of Fowler's solution, only to resume it as a rule in another fortnight; at times because of the


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appearance of a fresh patch of eruption, often because of a fear of its return. Just when the present cutaneous manifestations made their appearance he does not know, but he is quite sure that it was subsequent to the use of arsenic.

To recapitulate: This man, suffering from some chronic cutaneous affection (probably psoriasis), began taking arsenic in the usual doses ten years ago and has continued its use off and on ever since. He took the last dose three weeks before his first visit to the dispensary. Then he had ascites and presented the cutaneous lesions which we have just considered.

It is more than probable that there is a causal relation between the ascites and the use of the arsenic. In this patient no other etiological factor is available. Mr. Hutchinson* has described a similar but more severe case in which paracentesis was performed on three occasions, complete recovery following only on discontinuing the drug. And in Geyer's report f on the endemic arsenicism of Keichenstein, due to the arsenical drinking water, several similar cases are quoted. However, it is not to this condition of our patient that I wish to call particular attention, but to the combination of widespread pigmentation and keratosis of the hand3 and feet. It is a clinical picture of prolonged arsenical medication. So characteristic is it that, in this case, the diagnosis can be made de visu without the assistance of the patient's statements.

It is right interesting to know how the relation between these dermatoses and the use of arsenic has been established. I shall begin with a consideration of the melanoderma.

Thomas Hunt is probably the first observer to call attention to arsenical pigmentation. In a communication on the administration of arsenic, published in 1847, he wrote: "The trunk of the patient first, and subsequently all those parts of the body which are by the dress protected from the access of light and air, become covered with a dirt-brown, dingy, unwashed appearance, which under a lens reveals a delicate desquamation of the epidermis, and is, in fact, a faint form of pityriasis." % He viewed this change as an effect of the drug's action.

In spite of this early account of arsenical melanoderma the condition was not generally recognized for many years thereafter. It was well known that any chronic inflammation of the skin might leave its mark in the shape of a pigmentation at the site of an old lesion, llebra, in his well-known textbook, spoke of this fact in connection with cases of psoriasis, and particularly those treated with arsenic, recommending a reduction of the dose as soon as the pigmentation appears. § No more definite statement regarding the relation between the arsenic and the discoloration is made. Before Hebra's book was published, Devergie had expressed the opinion that the pigmentation in such cases is in all probability due to the arsenic, and the term " taches arsenicales " is applied to the

Archives of Surgery, 1895, Vol. VI, p. 389.

f Ueber die chronischen Hautveriinderungen beim Arsenicismus u. Betrachtungen uber d. Massenerkrankungen in Eeichenstein. Arch. f. Derm. u. Syph., 1898, Bd. 43, S. 221.

{ Further observations on the administration of arsenic. Lancet, 1847, I, p. 92.

§ Lehrb. d. Hautkrankh., 1874, 2 Aufl., S. 345.


discolored areas.* But this view was not so readily accepted, and discussion continued as to what share the disease took and what role the arsenic played in the causation of the melanoderma. In time, however, there accumulated many dermatological observations, in which the pigment was said to appear at points unaffected by the original cutaneous disease, so that there could be no doubt as to its arsenical or inflammatory origin. Finally, when clinicians began to report numbers of cases, chiefly of chorea and accidental poisonings where discoloration of the skin followed the ingestion of the drug, arsenical pigmentation was accepted as au established fact and came to take its place in the list of arsenical dermatoses. f That list is a long one; besides the eruptions which we are now considering, it includes representatives of all the elementary cutaneous lesions from the cedematous to the pustular. In this connection it is of interest to note that a certain chronological sequence in the appearance of these eruptions can be observed. Some represent an acute intoxication, as it were; others, a chronic. At one end of the series stands the oedema which may come on after a day or two's administration; at the other end are the melanosis and keratosis. As a rule, the melanosis appears after a period of some weeks or months of arsenical medication. It matters not what preparation of the drug is used; arsenious acid, sodium arseniate, Fowler's solution — all have caused it.

The localization of the discoloration, as our patient presents it, may be taken as typical. The pigment appears in small yellowish-brown macula;, which coalescing may come to cover a large area of skin, giving to it a rather characteristic mottling. But it is not always characteristic enough to be distinguished from the bronzing of Addison's disease. Like the pigmentation of this disease, it is more intense in localities exposed to friction or where there is normally more or less pigment. In this patient you see how dark the axillary and inguinal folds and the areolae are. Unlike the coloring of Addison's disease, the exposed parts do not tend to suffer, nor are the visible mucous membranes involved. The shade of the pigment does not help in the differentiation from " bronzed skin," for in both conditions all shades of brown may be represented. Indeed, a case of arsenical pigmentation has been reported in which the skin, from the groins to the toes, was " absolutely black." J When one considers that these patients may present the gastro-intestinal symptoms of arsenic poisoning, the differentiation between arsenical intoxication and Addison's disease becomes worthy of consideration. There is a case of so-called arsenical melanoderma on record which, by its subsequent course, proved to be an example of suprarenal disease.§

The error might have been avoided had the pigmentation of the mucous membranes been rightly interpreted.

In phthisis and exophthalmic goitre pigmentation of the


  • Traite pratique des Maladies de la Peau, 1S57, p. 137.

t For literature, see Geyer, loc. cit.

t Barthelemy : quoted by Rasch, Contribution a l'etude des dermatoses d'origine arsenicale, Ann. de Derm, et de Syph., 1893, t. IV, p. 160.

§ Audry, Ann. de Derm, et de Syph., 1S96, t. VII, p. 1415. For "note rectificative," see tome IX, 1898, p. 538.


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skin is sometimes seen. It is possible, as has been suggested, that in some of these cases the discoloration may have an arsenical origin, for in both diseases arsenic is often administered for long periods of time.

What are the minute changes in the pigmented skin? Our patient, grateful that the cause of his trouble had been discovered, volunteered to give us a bit of tissue for microscopical study. Accordingly, a small piece of skin was excised from bhe lumbar region.

In this specimen the epidermal cells are not hyperpigmented; the corium is the seat of the discoloration. The pigment is distributed almost exclusively about the bloodvessels. Hence, it is seen in the papillae, but it is most abundant about the basilar layer of capillaries from which the papillary vessels arise. It presents itself in the adventitia of the vascular wall as little brown granules, which lie heaped up to form fine lines, or more frequently very dark ovoid and spindle-shaped groups of about the size of a connective-tissue cell. In many of these collections of pigment nuclei are risible, so that their cellular character is undoubted. The nature of the pigment granule itself is quite obscure. Mr. Hitzrot has kindly made some microchemical tests in the present case, with the same negative results that other observers report. The pigment failed to turn blue when treated with hydrochloric acid and potassium ferrocyanide, and remained unchanged on the addition of ammonium sulphid, or of a five per cent solution of neutral hematoxylin. There does not exist the analogy between arsenical pigmentation and argyria that Devergie claimed, for from these experiments it is clear that the pigment contains neither arsenic nor iron. Perhaps, suggests, it is hsematoidin. It is a fact that the longcontinued use of arsenic is attended in some individuals by a decided decrease in the haemoglobin and red blood-corpuscles. The metal itself in chronic poisoning is deposited not only in the liver and spleen, but also in the marrow of the bones ; therefore, at tbe very fountainhead of blood-formation. These observations, added to the microscopical picture, the perivascular deposition, leave little doubt that it is from the disintegration of the blood that the pigment results, but the intimate mechanism of its formation and deposition is entirely unknown.

As to the treatment of arsenical pigmentation, the essential indication is clear. Withdrawal of the drug is usually followed in the course of months by a disappearance of the discoloration. In a few cases the pigmentation has been permanent.

Although melanoderma is a late lesion of arsenical intoxication, keratosis is a still later manifestation, and, in point of time, stands last in the series of arsenical skin eruptions. It is only within the last few years that its arsenical origin has been established beyond dispute. I say beyond dispute in face of tlie statements made less than two years ago by such eminent dermatologists as Kaposi and Neumann, to the effect that they had never demonstrated with certainty a single case of arsenical keratosis.* After examining this patient and reviewing with me the literature, I will leave you to judge if these statements are warranted by the facts !

Many years ago Romberg wrote of a palmar and plantar


  • Ann. de Derm, et de Syph., 1898, t. IX, p. 481.


affection in association with the use of arsenic. He Btated that he had seen exfoliation of the skin iu these regions in individuals who had taken the drug.* But, probably the first definite allusion to an undoubted case of arsenical keratosis is male by Erasmus Wilson, in 1868. In discussiug the effect of fifteen months' use of the drug on his patient, he writes: " Hut the most striking evil resulting from the action of the arsenic next to the melasma is the state of chronic erythema of the palmar and plantar surfaces of the hands and feet. These surfaces are red, hot and swollen; the cuticle is dry, harsh, desquamating and covered with hard, dry points, corresponding with the apertures of the sweat-glands, which resemble minute corns, and which she designates by that name."!

In a report of the terrible epidemic at Hyeres, in France, in 1887, where more than four hundred people were poisoned by wine containing arsenic, mention is made of a case in which the epidermis of the soles, particularly about the heels and balls of the toes, became hard and dry and horny. J In the same year, at a meeting of some brauches of the British Medical Association, held at Gloucester, Mr. Jonathan Hutchinson called attention to several cases of keratoses of the palms and soles, due, he thought, to the ingestion of arsenic. He thought it probable, too, that the drug might cause a peculiar form of cancer.§

The whole subject received important contributions in 1891 by the publication and discussion of three English observations on palmar and plantar keratoses. || The third of this series was reported by Pringle as one of '"Keratosis of the palms and soles probably of arsenical origin." The patient was a young woman, suffering from psoriasis, who took Fowler's solution for one year. It was then noted that the epidermis of the palms and soles was thickened and keratotic in patches, varying in size from that of a pin's head to that of a pea, so that the skin presented a warty appearance. The affection extended along the lateral borders of the fingers. The description tallies in the main with the case before us. Pringle presented his patient before the Dermatological Society of London, where Mr. Hutchinson gave it as his opinion that the case was one of arsenical keratosis. Considering all of this evidence, there can be at present no doubt as to the existence of such a condition.

The lesion appears after some months or years of arsenical medication, either as a diffuse hypertrophy of the epidermis, or there arise local thickenings of all sizes, giving to the skin a warty appearance. Most frequently, perhaps, the two conditions are combined. Rarely is there any erythema, a circumstance which distinguishes it from the hereditary palmar and plantar keratoses. The palms and soles are usually involved, though, as in this patient, the dorsal and lateral aspects of the fingers and elbows may be affected. As it appears on the


  • Klin. Wahmehmungen u. Beobachtungen, Berlin, 1851, P. 228.

t Jour, of Cut. Med., 1868, Vol. I, p. 355.

I Barthelemy : quoted by Rasch, op. cit., p. 153.

§ An address on the study of skin diseases as illustrating the doctrines of general pathology. Brit. Med. Jour., 1887, II. p. 230.

II Brooke: Brit. Jour, of Dermat., 1891, p. 19. Crocker: ibid., p. 169. Pringle: ibid., p. 390.


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elbows it recalls the condition of psoriasis, hence Mr. Hutchinson's term " arsenical psoriasis."

By what mechanism the lesion is produced is far from clear. Excessive sweating of the palms and soles has been observed during the long-continued administration of arsenic. It may be that, owing to this hyperhidrosis, arsenic is excreted in the sweat in an unusual amount and that the prolonged contact of the drug in these regions may determine the localization of the lesion. The appearance of the "corns" about the apertures of the sweat-glands has been noted in a few instances.

When the arsenic is withdrawn the keratosis usually remains stationary or slowly diminishes. Active treatment with such preparations as salicylic acid should not be undertaken without bearing in mind a third and less fortunate termination of these keratoses, to which Mr. Hutchinson* drew attention at a meeting of the Pathological Society of London, in 1887. Here he elaborated the proposition which he had made at Gloucester that the internal administration of arsenic could be the cause of a "peculiar form of cancer." He presented notes and drawings of three cases in which, following the use of arsenic, not only palmar and plantar keratosis developed but also malignant growths. His thesis drew forth some opposition, but Sir James Paget, who occupied the chair, remarked that he " had seldom heard an argument founded on clinical and pathological evidence more definitely suggesting the conclusion advanced." Mr. Hutchinson's first case was that of a man suffering from psoriasis who had taken arsenic for many years. "Corns" developed on his hands and feet. A corn on the sole of the foot ulcerated, resembling at first a perforating ulcer. According to Sir James Paget's opinion, " the disease was cancerous." Microscopical examination was inconclusive. The growth was removed ; the patient recovered.

The second case was one of unusual interest. An American physician had taken arsenic for psoriasis for a long period. The psoriasis was cured, but the skin of the palms and soles became rough. Fungous ulcerations appeared on both hands. Ultimately both hands were amputated. Eighteen months later the patient died. Metastases of epithelioma were found in the left axillary glands, in both lungs, in the suprarenal glands, and in a rib. I shall refer to this case later on.

Finally, the case of a clerk, aged 34 years, who had taken arsenic for a long time for psoriasis, was cited. When he appeared at the Skin Hospital the palms and soles were dotted with " corns." Then an epithelioma of the scrotum appeared. It was excised, but the subsequent movements of the patient could not be followed.

Now, the facts which were thus brought forward were not unknown, but Mr. Hutchinson's interpretation was novel. Thus, in 1874, an epithelioma taken from the foot of an individual suffering from psoriasis is exhibited before the Anatomical Society of Paris. f A few years later, Cartaz J reports to the same society the case of a man forty years of


  • Brit. Med. Jour., 1887, II, p. 1280.

f Pozzi, Bullet, de laSoc. Anat., 1874, p. 587

t Bullet, de la Soc. Anat., 1877, p. 549.


age, suffering from psoriasis, in whom a cancerous ulceration developed over the palmar surface of the right ring finger.

Both patients showed keratoses. They had presumably been treated with arsenic as is practically every case of psoriasis though no mention is made of this fact.

In 1885, Dr. J. C. White,* published an article with the title : " Psoriasis, Verruca, Epithelioma, a sequence." Two cases are reported. The first patient was a man who had had psoriasis of many years' standing. He had taken arsenic in considerable doses. For ten years he had had keratoses on his hands. Three years previous to his examination by Dr. White in 1884 one of these " warts " on the anterior aspect of the right palm ulcerated and a similar but less extensive change took place on the left palm between the fore and middle fingers. The ulcers were viewed as epitheliomata, but before resorting to a radical operation, the patient sought the advice of Mr. Hutchinson and others in Europe. Mr. Hutchinson has pictured the patient's hands in his Archives of Surgery.| To his opinion and the subsequent history of the patient I have already alluded in referring to his second case. Let it be added that microscopically the growths proved to be epitheliomata. Dr. White at the same time reported the case of another man, 52 years of age with psoriasis of long standing, warts on the hands and an epitheliomatous ulcer on the anterior aspect of the right wrist and palm. He, too, had been subjected to an arsenical treatment. White considered the psoriasis as a cause of carcinoma through an intermediate lesion, the wart. At that time arsenical keratosis was not recognized. Even now in hearing the reports of these cases of "arsenical cancer," to use Mr. Hutchinson's term, the fact that all the patients were subjects of psoriasis must draw the critic's attention. It may be true that psoriasis with its hyperplasia of the epidermis predisposes to the formation of epithelioma in individuals submitted to continued arsenical medication, but that it is not a necessary condition is illustrated by a case of Ullman,J presented to a society of physicians in Vienna in 1898. The patient, a young woman, had been taking Fowler's solution seven or eight years for a facial acne. A palmar and plantar keratosis followed. During the preceding year an epithelioma appeared on the face. It was extirpated. Six months later, another epithelioma which had developed on the thickened skin of the heel, was removed. Here the cutaneous disease, the acne, can have played no role, not even that of a predisposing factor, in the development of the new growth. Still more conclusive are the reports of the cases from Eeichenstein.§ The three individuals whose histories, Geyer gives had all been saturated with the arsenical drinking water; had acquired the "Keichensteiu complexion," and keratosis of the hands and feet. Each suffered from an epithelioma of the right hand.

In a majority of the cases I have now reviewed, the cancer has appeared either on the hands or feet, regions peculiarly susceptible to arsenical keratosis. Indeed, where the details have been carefully observed, it has been noted that the


  • Am. Jour, of Med. Sc, 1885, Vol. LXXXIX, p. 163.

1 1891, Vol. II, plate XX.

t Ann. de Derm, et de Syph., 1898, t. IX, p. 481. § Op. cit.


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL. 1900.



F 1 1 ; . I, — Shows the diffusely thickened skin of the palm, the deepening of the cutaneous furrows and the scattered keratosis.



Fig. 2. — Shows the horny excrescences on the ile of the Co a determining factor in their localization


distribution suggests t In' pressure of the shoe as


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epithelioma most often arises directly from these keratotic patches.

This fact is not remarkable, knowing how frequently the keratoses of old age undergo a similar change. Nor is it surprising that the " arsenical warts " of the right hand, constantly exnosed to trauma and irritation, most often suffer these changes.

In one of Mr. Hutchinson's cases, the scrotum was the seat of the epithelioma. This localization is of interest in view of the fact that it is an old observation, that the external genitalia are points of predilection of arsenical lesions. Dr. Pari,-; writing in 1825 concerning the poisonous effects of arsenious acid on plants and animals states that "the smelters are occasionally affected with a cancerous disease of the scrotum similar to that which infects the chimney-sweeps."* You see that the very localization of the epitheliomata in these cases favors Mr. Hutchinson's proposition that arsenic may be the cause of cancer."

To sum up: The present case has given us an opportunity to review a number of interesting and important facts in connection with the administration of arsenic. We have seen that its prolonged use is at times attended with wide-spread pigmentation or keratosis chiefly palmar and plantar, or both pigmentation and keratosis. Associated together, they form a picture which can scarcely be mistaken. The keratosis may in rare instances undergo epitheliomatous changes and lead to a fatal termination. The possibility of such a serious outcome, let alone other accidents of arsenical intoxication, emphasizes once more that arsenic is no indifferent drug. The occurrence


  • Quoted in Butlin's Lectures on Cancer of the Scrotum. Brit.

Med. Jour., 1892, Vol. II, p. 67. See also, Brouardel, Troubles de l'appareil cutane dans l'arsenicisme. Gaz. hebd. de Med. et de Chir., 27 juin, 1897, p. 603.


of these dermatoses, however, is not to be viewed as the result of a medical error in its administration. Its use continued for months, and at intervals even for years, is the only relief on which many sufferers from psoriasis can rely.

As with other drugs the range of individual susceptibility is wide. While one will develop a keratosis after a few months of arsenical medication, another may take the drug for years with impunity. Mr. Hutchinson has recorded a life-long use of arsenic for the relief of psoriasis in a man sixty years old.* Speakiug generally, it had not interfered with his health.

Strange to say, too, I can find no record of these cutaneous accidents we have been considering among the Styrian arseniceaters. That arsenic may be habitually used without deleterious effects, and tolerance to large doses established, is illustrated by Mr. Hutchinson's case and the experience of the Styrian peasants, but such an immunity in medical practice is not the rule. Even Mr. Hutchinson's patient suffered from passing, but nevertheless profound, disturbances which might very well be attributed to the drug. From all of which I conclude that without a definite indication prolonged treatment with arsenic is an error.

A common acne may be combated by simpler and less serious measures than years of arsenical medication ! On the other hand, as I have just said, for certain cases of psoriasis and let me add, of lichen ruber, chorea, some grave ana?mias, and occasionally for retarding the growth of various malignant tumors, the prolonged use of arsenic is a veritable boon. But in these instances its administration must be under medical supervision and not determined, as in the case of the patient before you, by his fears and opinions. " Virtue itself turns vice, being misapplied."


  • Arch, of Surgery, 1892, Vol. IV, p. 104.


TJNCONTAMINATED URINE.

By Howard A. Kelly, M. D., Gynecohgist-in- Chief, The Johns Hopkins Hospital.

THE BEST WAY TO SECURE UNCONTAMINATED URINE FROM THE BLADDER AND FROM THE KIDNEY, AND HOW TO MINIMIZE

THE RISKS OF CATHETERIZATION IN WOMEN.


The question of catheterization is ever a burning one, whether in the large clinic after important pelvic operations, where it is conducted on a wholesale scale, or in the case of the single patient at her home after confinement. In view of the frequeDt immediate untoward results of catheterization and their distressing sequela?, I think we might almost reckon this procedure among the major gynecological operations, until the question as to the safest method is finally solved.

The first query of importance is, "Who shall catheterize the patient — shall the doctor or the nurse?" A little consideration will show that it would be practically impossible for the doctor, often at a distance and otherwise engaged, to add this to his already burdensome duties, and it must therefore !»• looked upon as distinctively a nurse's duty. (See Fig. 1. 1

To this end the nurse must be especially trained; she must


be warned of the unusual risks and taught each step with great exactitude. The method I have adopted for some years past in my own clinics is the following:

I prefer to use a glass catheter, which I firs! tried in 1884, when I made one extemporaneously for an urgent case out of the glass tube of a baby's feeding-bottle; the glass is easily kept clean, and can be introduced without, touching the end which nilcrs the bladder. (See Amer. Jour. Obs., February, 1889, p. 184.) (See Kuestner Centralb. f. Gyn., 1890, No. 33.) (See also an excellent article by Prof. Kuestner, on glass catheters, as a means of prophylaxis against cystitis in women, Deutsche med. Woch., 16 May, 1883.)

Each patient has her own catheter for her exclusive use as long as she needs one. It is sterilized by boiling live minutes in a soda solution and then placed in an open-mouth bottle


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[No. 109.


filled with 5 per cent carbolic solution, or 1-1000 bichloride of mercury with some cotton on the bottom to protect the end of the catheter.

Just before using it may be boiled again in the soda solution.

The nurse then scrubs her hands carefully and places the patient on a bed-pan and exposes the vulva and separates the labia so as to expose the urethral orifice.

She now takes up a pledget of cotton, saturated with a boricacid solution, in the grasp of a forceps, and with this thoroughly cleanses the urethral orifice. This is repeated with another pledget when the patient is ready for catheterization. (See Fig. 2.)

She now draws two sterile finger-cots over her thumb and index finger of the right hand, and thus well protected grasps the catheter by its (inter end and removes it from the receptacle, rinses it off with sterile water, or if it has just been boiled lifts it directly from the pan, and gently introduces it into the urethra, allowing it to take its own way into the bladder and never under any circumstances using force.

I desire here to point out the fact that the catheter nevir completely empties (he bladder when the patient is lying down ; and if there is any cystitis it is best to wash it out, using a large catheter with a strong curve at its vesical end. After the irrigation the curved end is turned downwards towards the base of the bladder, when the sediment often escapes first.

Uncontaminated urine maybe obtained from (he bladder for bacteriological study in the following manner:

The catheter is sterilized with a piece of rubber tubing covering an inch or more of its outer end and projecting about 2 inches beyond it. It is then introduced, preferably


by the physician, with the precautions described, and the urine allowed to escape for a few seconds, after which the rubber sleeve is pulled off and the urine now running over the sterilized end of the catheter is collected in a test-tube. Iu my investigations of several hundred specimens in this way conducted with my associate, Dr. Thos. R. Brown, we have had no cases of accidental contamination, In twenty instances sterile urine was taken as a control experiment and in every case it remained sterile. (Fig. 3.)

In securing uncomtaminated urine from the kidney, I proceed in a similar manner. The bladder is washed out and emptied, and the patient is put in the knee-breast posture and the ureteral orifice exposed. This may now be cleansed with a little pledget of boric-acid solution and the catheter introduced.

The catheter is sterilized with a rubber sleeve protecting and projecting beyond the end. The operator draws on the. hand which grasps the catheter a sterilized half-glove, which I have had made for this purpose, and grasping the catheter, protected also if need be by a sterile towel on his shoulder, he introduces the end into the ureter and pushes it on up into the kidney. The patient is then allowed to lie down on her side or on her back, the sleeve is pulled off, and the sterile end of the catheter is put in a sterile test-tube held in place by the cotton plug.

I have done this not less than sixty times and have never yet seen an accidental contamination.

It is evident, therefore, that by this procedure, when the ureter is catheterized by my method through the open speculum in an air-distended bladder, we possess a method of securing cultures from infected kidneys which is impossible in any other way short of a surgical operation.


SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE HOSPTAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.


Arthur W. Elting, M. D. The Bacteriology of Gonococcus Infections. — Albany Medical Annals, March, 1900.

Harvey Cushing, M. D. Exploratory Laparotomy Under Local Anesthesia for Acute Abdominal Symptoms Occurring in the Course of Typhoid Fever. — Philadelphia Medical Journal, March 3, 1900.

Norman B. Gwyn, M. D. The Examination of the Urine for Typhoid Bacilli. — Philadelphia Medical Journal, March 3, 1900.

Robert Keuling, M. D. Changes in the Skin in Paralysis Agitans.— Maryland Medical Journal, March, 1900.


Robert Reuling, M. D. Pathology and Neurology. — Maryland Medical Journal, March, 1900.

George Walker, M. D. Electrolysis as a Means of Curing Chronic Glandular Urethritis. — Maryland Medical Journal, March, 1900.

Thomas R. Brown, M. D. Internal Medicine. — Maryland Medical Journal, March, 1900.

Hugh H. Young, M. D. Surgery. — Maryland Medical Journal, March, 1900.

Geo. W. Dobbin, M. D. Obstetrics and Gynecology. — Maryland Medical Journal, March, 1900.


MONOGRAPHS.


The following papers are reprinteil from Vols. I, IV, V, VI and VIII of the Reports, for those who desire to purchase in this form: STUDIES IN DERMATOLOGY. By T. C. Gilchrist, M. D., and Emmet Rixpord, M. D. 1 volume of 164 pages and 41 fullpage plates. Price, bound in paper, $3.00. THE MALARIAL FEVERS OF BALTIMORE. By W. S. Thayer, M. D., and J. Hewetson, M. D. And A STUDY OF SOME FATAL CASES OF MALARIA. By Lewellys F. Barker, M. B. 1 volume of 280 paees. Price, in paper, $2.75. STUDIES IN TYPHOID FEVER. By William Osler, M. D., and others. Extracted from Vols. IV and V of The Johns Hopkins


Hospital Reports. 1 volume of 481 pages. Price, bound in paper, $3.00.

THE PATHOLOGY OF TOXALBUMIN INTOXICATIONS. By Simon Flexner, M. D Volume of 150 pages with 4 full-page lithographs. Price, bound in paper, $2-00.

THE RESULTS OF OPERATIONS FOR THE CURE OF INGUINAL HERNIA. By Joseph C. Bloodqood, M. D. Price, in paper, $3.00.

Subscriptions for the above publications may be sent to

The Johns Hopkins Press, Baltimore, Md.


THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL, 1900.


^^5=



Fig. 1. — The sterilized glass catheter, protected by a rubber sleeve. When first introduced, a little urine is allowi • ! In escape into the vessel A ; then the rubber sleeve is pulled off, and nncontaminated urine runs directly from the end of the glass tube into the sterile tube B.



Fig. 2.— Shows the nurse holding the catheter with fingers protected by sterile rubber finger cots, while the urine escapes from the sterile end into the glass tube upon removal of the rubber protecting sleeve.


Urtter HinalcaOuUr



3HBBB



Fio. :',.- The renal catheter protected by the rubber sleeve On Introduction, the sleeve is palled off and the end of the catheter, marked bv the arrow, inserted in a sterile tube and uneontamlnated urine collected.


April, 1900.]



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A NOTE ON A SERIES OF NEW VESICAL SPECULA.

l'.v Howard A. Kelly, M. D.



Tubus


The new vesical speculum in use, showing the wide area open to inspection on the vesical wall (paries vesicalis). The cylindrical portion (tabus) occupies the urethra and projects into the bladder lost, vesicalci; the conical portion (conns] with its ocular end occupies the vulvar cleft. By making the cone as indicated on the dotted lines, a much larger Held is secured for inspection and for instrumentation. The tube in some cases may with advantage be mad.' 2cm. longer, when it projects further into the bladder and serves to push up the base of the bladder in inspecting it.


The open cylindrical vesical speculum when in use is topographically divided into a urethral and a vulvar portiou.

The calibre of the urethral portion is limited by the degree of safe or convenient distention of the urethra, and in the average specula ranges from No. 9 to No. 12 (the numbers in my scale representing millimetres in diameter); in the larger sizes, used for operations, the calibre may even be carried as high as 20 mm., the limit of a safe degree of dilatation, as shown bv Simon.


The vulvar portion, however, has no such necessary limi tations and may, as I have found, be expanded with great. advantage into a broad funnel. The best form of funnel is one in which the angles formed by the lines of the slanting sides meet exactly in the middle of the tubular portion. This gives a maximum area of inspection and a maximum room for treatment, especially in using instruments with crossed blades. The length of each of these parts of the speculum should be 5 cm.


PROCEEDINGS OF SOCIETIES.


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Monday, February 19, 1900.

The Pathological Findings in a (use (if General Cutaneous and Sensory Aiiipsthesia.— Dr. Berkley. (See Buli. f.tin for March.)

M'kcimens of False Porencephalia. Dr. Berkley. — The person from whom this specimen was obtained was a medium-grade imbecile, who had lived to reach the age of 58 years. He was tall, with fairly developed musculature, and without marked cranial deformity. At the autopsy, the brain weighed 950 grammes. The convolutions on the external aspect of the hemispheres were without any marked asymmetries, but the right half of the brain was considerably smaller than the left, and when taken out of the bony envelope, flattened perceptibly. On closer examination, a defect was found on the median-inferior aspect of the hemisphere, measuring four centimetres in its greatest length by two in its greatest


width. The anterior margin lay considerably forward of the splenium of the corpus callosum, the posterior end stopped three and a half cm. before the tip of the occipital lobe. The defect was separated from the ventricle by a leathery substance, from 1.50 to 1.75 mm. in thickness. This showed no trace of cerebral matter. The lesion formed a pocket beneath tingeneral level of the surrounding brain-tissue, which was filled with a gelatinous mass. The convolutions involved were portions of the posterior end of the convolution of the corpus callosum, the anterior and middle parts of the lingual convolution, the innermost aspect of the occipitotemporal gyrus, and a large part of the convolution of the hippocampus. The cuneus was not disturbed. The foot of the hippocampus was not entirely destroyed, its anterior portion retaining some of the nerve elements. In the posterior portion of the hippocampus the traces of an old hemorrhage were found, showing that the lesion had originated in the rupture of a blood-vessel. The corpus callosum throughout its whole extent was poorly developed, but the posterior half was especially thin, an evi


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dence that the injury to the cortex had taken place in early life, and that the hemispheres had not fully developed thereafter. When the right and left sides of the corpus callosum were compared in the cross-sections, the left side was seen to be thinner than the right. There were no indications of localized brain lesion during life.

On a Form of Conjugation of the Malarial Parasite.— Dk.

EWING.

In four cases of tertian infection the writer has encountered appearances in the blood which seem to admit of no other explanation than that of conjugation of malarial parasites. In a considerable number of other cases similar appearances were found, but much less frequently.

The blood in these cases showed a large number of young rings and many half-grown and full-grown forms. A great many cells showed double infection with young rings. In many instances these rings were entirely separate, each exhibiting a single large granule of chromatin. Many cells, however, contained two rings, which were clearly fused together along one segment of the ring, and two large chromatin granules were then invariably found at different points in the rings. The fused parasites usually differed in appearance. One was a large delicate ring with a thin bow, and chromatin grauule of moderate size, while the other was a coarser body with thickened bow, enclosing little or no hemoglobin, and exhibiting a large chromatin granule.

Among the single rings, these two forms of young parasites were often distinguished, but no single rings could be found containing two equally large chromatin granules, while every red cell that exhibited two large and equal chromatin granules contained also two distinct rings. It appears, therefore, that the bodies of many parasites had become fused together, while their nuclei remained separate.

On examining the parasites in later stages of development, most of them were found to have lost the ring form and to have spread out into a large number of threads, with nodal thickenings variously curled in the red cell. These threads evidently represented the pseudopodia of a very active amoeboid stage. The chromatin masses were now subdivided into ten or twelve granules ; but, in the majority of the cases, these masses were far apart and showed no tendency to unite. In many cells, however, the amoeboid figures were less marked, and the masses of chromatin lay side by side, united by a little achromatic substance. Later some parasites were found in which the two groups of rather large chromatin granules lay in immediate apposition, surrounded by achromatic substance. This phase was marked by a distinot reduction in the length of amoeboid figures.

Many older spheroidal, hyaline forms, belonging to this same brood, were found in these cases, but all the older hyaline forms were single, and exhibited a single large group of fine chromatin granules. Not one cell harboring two fullgrown parasites could be found in prolonged and repeated searches through several slides. Whatever interpretation may be placed upon this peculiar absence of older twinned forms, the finding of all stages of union, first of the bodies and later


of the nuclei, likewise appears to admit of no other explanation than that of conjugation.

Dk. Welch. — I have been greatly interested in Dr. Ewing's paper, and consider that the Society is to be congratulated upon this opportunity to listen to his personal presentation of these important observations. There can be no question as to the accuracy of these observations, whatever difference of opinion there may be in their interpretation. Most of the questions which had occurred to me in the course of Dr. Ewing's remarks, he answered before their conclusion.

The most important question seems to me whether the conjugation of parasites described by Dr. Ewing, is to be looked upon as something essential, really pertaining to the life history of the organism, or as merely a more or less accidental coalescence, or fusion, of two cells. Of such fusion of cells we have some examples in normal and pathological processes, and if this latter be the proper interpretation, there may be some question as to the propriety of the designation " conjugation," which has a special meaning among biologists. I do not know that Dr. Ewing is in a position to express himself more definitely upon this point.

Dr. Thayer. — We all, I am sure, feel grateful to Dr. Ewing for the very interesting communication which he has made. I regret extremely that Dr. Lazear is not here to take part in the discussion, inasmuch as he has for the past year been making careful studies in this line. Unfortunately, he has gone to Cuba, and his specimens and the paper which I had expected to have in time to read to-night have not been recei ved.

Dr. Ewing's interpretation of his interesting observations is extremely suggestive. I recognize many of the pictures which have been described, but I must confess that their possible importance had escaped me. I have, without much thought, always assumed that the reason why twin parasites were relatively common in the early stages of development of the organism and so infrequent later on was that with the growth of the several contained organisms the red blood-corpuscle was eventually ruptured, both parasites escaping and meeting the fate which apparently inevitably befalls extracellular bodies at this stage of development. But, after all, this is a pure hypothesis, and in view of Dr. Ewing's careful studies I should surely feel called upon to thoroughly restudy the question before venturing to dispute his conclusions.

A rather interesting point in connection with this matter, if we are to regard the process as one of fusion, is that at a certain stage the structure of the organism might justify the term plasmodium, the biological inaccuracy of which as applied to the ordinary parasites has been so generally recognized.

In connection with the possibility that this process might be a true conjugation, a rather inviting, though I fear improbable, explanation of its possible significance suggested itself to my mind.

In the sestivo-autumnal parasite, for instance, beside the organisms pursuing the ordinary cycle of development, there soon appear other bodies morphologically distinct from these, the crescentic and ovoid forms. These forms, Mannaberg


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contends, are the result of conjugation of two elements belonging to the ordinary cycle.

Only from the bodies belonging to the crescentic group do the sex-ripe forms (macrogametes and microgametocytes)

develop.

In a recent communication Bastianelli and Bignami assert that the sex-ripe forms in the tertian parasite likewise develop from elements morphologically distinguishable from those belonging to the ordinary cycle.

What causes the differentiation of the crescent group in the aestivo-autumnal parasite and of the group destined to develop into sex-ripe forms in the tertian parasite? May it be that these sex-ripe forms in both instances develop only as a result of conjugation of two bodies, each of which alone would be capable of pursuing only the ordinary asexual cycle — that the process observed by Dr. Ewing is a necessary stage in the production of elements destined to develop into flagellate forms ^microgametocytes) or macrogametes ?

I am, however, unaware whether there is any analogy to justify such an hypothesis — and what is more important the fact that the crescents are formed as a result of conjugation is by no means settled. Indeed, we are iuclined to believe, with the Italians, that this is not the case.

Dr. MacCallum. — I would like to ask one or two questions of Dr. Ewing. 1st, Whether he has seen any actual fusion of the chromatin bodies, or whether they simply lie side by side as he has pictured them ; and, 2d, What happens after this — whether there is any difference between the conjugated forms and the others. As I understood him, they both go on to sporulation : and it struck me as an occurrence which has its parallel in certain lower animals, that conjugation should take place in these young immature cells. I would also like to know whether he has observed this only in one cycle or in several successive cycles.

Dr. Ewisg. — When I made up my mind to read this paper in Baltimore, it was with the idea that I could obtain more information here than anywhere else on a point which concerns the minute morphology of the malarial parasite. This decision seems to have been justified, and I feel that I am now in a better position to consider the importance of this process.

Dr. Welch has hit the nail on the head in regard to the significance of the process. I am fully convinced that all the stages I have described actually occur, but it is a totally different thing to ascribe to such a process its proper interpretation. I am inclined to think that this process has not the full significance we find it to have in certain lower animals where conjugation is a necessary preliminary to sporulation. It is certainly not so of the malarial organism. I only claim that it occurs frequently, and is a real fusion of parasites, undergone for convenience, perhaps, but is not an essential preliminary to sporulation. I thank Dr. Welch very much for making the suggestion that clearly places the process in its correct position.

I confess that I had not had in mind the possibility that when two parasites conjugate the result might be the rupture of the cell and death of both parasites. I had suspected that some one might claim that one parasite, gaining the upper


hand, had destroyed the other, but it had not entered my mind that both might be thrown out.

Now, what can be said as to the possibility of such a process occurring? It seems to me that if it does occur with any frequency, it would occasionally be observed in some specimen; and it seems, on general principles, extremely unlikely that if such a rupture and extrusion occurs, we should examine hundreds of specimens and fail to find any trace of such a process. I have been over these slides until my eyes hurt, and have not found any traces of the rupture of cells and extrusion of twin parasites. The suggestion is an extremely good one, however, and I shall hereafter bear it mind. I am somewhat surprised that I did not think of it before, and I want to thank Dr. Thayer for the suggestion.

In regard to Dr. Thayer's suggestion concerning the relation of this process of conjugation to the life history of the parasite and preparing it for growth in the mosquito, I have not allowed myself to draw any conclusions whatever on that point. I am inclined to think, with Dr. Welch, that it is a mere fusion taking place when they are very numerous, and has probably nothing to do with the development of flagellate bodies or of any form especially adapted to growth in their new host. It seems rather to increase the numbers of young parasites produced in the human host. I was unable to trace the full development of some of the single parasites. This, also, is an extremely important point, and is the one I had foremost in mind in discussing the subject. I have noticed in these conjugating specimens that 1 can hardly ever get any flagellate bodies.

Dr. MacCallum wishes to know if I have actually seen fusion of the nuclei. I have not. I do not see how it is possible in the fresh specimen to accurately follow the process of union of masses of chromatin, such as we are dealing with here. My experience is that only the grosser processes can be identified with certainty by such means, and I feel that the identification of the nuclear bodies in the fresh specimen, as concerned in this process, would be unreliable in my hands. I should prefer to leave that to some one more familiar with the study of fresh-blood specimens. I do believe very firmly, however, that such union of nuclei does occur, from study of stained specimens. The same answer applies to his last question: Have I followed the development through several generations or only in one? I have not been able to follow up more than one generation, because we are in New York seldom able to follow these cases long. In the cases of the soldiers at Montauk, I had to take many specimens within a few minutes and usually saw the patient but once.

HOSPITAL PLANS.

Five essays relating to the construction, organization and management of Hospitals, contributed by their authors for the use of The Johns Hopkins Hospital.

These essays were written by Drs. John S. Billings, of the U. S. Army, Norton Folsom, of Boston, Joseph Jones of New Orleans, Caspar Morris, of Philadelphia, and Stephen Smith, of New York. They were originally published in 1875. One volume bound in cloth, price $5 I 0.


96


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 109.


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report In Pnthology.

The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

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Endocardial


Tubercular Peritonitii


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Report in Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

GallBtones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin. By H. A. Laeleur, M. D. Cases of Postfebrile Insanity. By William Osler, M. D. Acute Tuberculosis in an Infant of Four Months. By Harry Toulmin. M. D. p„r» Forms of Cardiac Thrombi. By William Osler. M. 1). n Phthisis. By William Osler, M. D.

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The Gynecological Operating Room. By Howard A. Kellt, M. D.

The Laparotomies performed from October 16, 18811, to March 3, 1890. By Howard A. Kelly, M. D.. and Hunter Robb, M. D. _

The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty CascB of Abdominal Section. By Howard A. Kelly, M. D.

The Management of the Drainage Tube in Abdominal Section. By Hunter Robb.

The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D Report of the Urinary Examination of Ninety-o:


By IIowabd of Checking


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A." Kelly, M. D.,"and Albert A. Ghriskey, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Mean

Hemorrhage from the Uterus, etc. By Howard A. Kelli. M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams. M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D Myxo-Sarcoma of the Clitoris. By Hunter Uobb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. Dy

Howard A. Kelly, M. D.

Report in Surgery, I. The Treatment of Wounds with Especial Reference to the Value of the Blood Clot

in the Management of Dead Spaces. By W. S. Halsted, M. D. Report in Neurology, 1. A Case of Chorea Insaniens. By Henry .1. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. liaematomyelia. By August Hoch, M. D. A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By

Henry M. Thomas, M. D.

Report in Pathology, I. Amcebic Dysentery. By William T. Councilman, M. D., and Henri A. Laeleur, M. D.

Volume III. 766 pages, with 69 plates and figures.

Report in Pathology.

Papillomatous Tumors of the Ovary. By J. Whu

Tuberculosis of the Female Generative Orga

Report in Pathology.

Multiple I.ympho-Sarcomata, with a report of Two Cases. By Simon Flexner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr.. M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugata Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diag' nosis; Operation for the Suspension of the Retrotlexed Uterus. By Howard A Kelly, M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mary Sherwood, M. D.

Intestinal Worms as a Complication in Abdominal Surgery. By A. L. Stately, M. D

Gynecological Operations not involving Celiotomy. By Howard A. Kelly, M. D Tabulated bv A. L. Stavelt. M. D.


The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howabd A. Kelly, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina w-ith Haematokolpos and HaMnatometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anaesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.


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Report on Typhoid Fever.

By William Osler, M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetson, M. D.

Report in Neurology.

Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of M«- musculm; The Intrinsic Nerves of the Thyroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley, M. D.

Report in Surgery.

The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology.

Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. Cullen, M. B. Report in Pathology. Deciduoma Malignum. By J. Whitridoe Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D A Study of 6cme Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever.

By William Osler, M. D., with additional papers by G. Bluuer, M. D., Simon Fleiner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.


Volume VI. 414 pages, with 79 plates and figures.

Report in Neurology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory. — Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I. — Alcohol Poisoning. — Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol); Part II. — Serum Poisoning. — Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part III. — Ricin Poisoning. — Experimental Lesions induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV. — Hydrophobic Toxaemia. — Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V. — Pathological Alterations in the Nuclei and Nucleoli of Nerve CellB from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Pathology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S. Cullen, M. B.

Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of Ovum and Spermatozoa. By Thomas S. Cullen, M. B.. and G. L. Wilkins, M. D.

Adeno-Myoma Uteri Ditfusum Benignum. By Thomas S. Cullen, M. B.

A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By William D. Booker. M. D.

The Pathology of Toxalbumin Intoxications. By Simon Fleiner, M. D.


Volume VII. 537 pages with illustrations. (Now ready.)

I. A Critical Review of Seventeen Hundred Cases of Abdominal Section from the standpoint of Intra-peritoneal Drainage. By J. G. Clark, M. D. II. The Etiology and Structure of true Vaginal Cysts. By James Ernest Stokes, M. U. 111. A Review of the Pathology of Superficial Burn?, with a Contribution to our Knowledge of the Pathological Changes in the Organs in cases of rapidly fatal burns By

I'UABLES RUSSELL BABDEEN, M. D.

IV. The Origin, Growth and Fate of the Corpus Luteum. By J. G. Clark, M. D. V. The Results of operations for the Cure of Inguinal Hernia. Bv Joseph C. Blood QOOD, M. D.


Volume VIII. About 500 pages with illustrations. (In press.)

Studies in Typhoid Fever.

Bv William Osler, M. P.. with additional papers by J. M.T. Finney. M. 1> ., S. Fiexner. M. I'.. I. P. Lyon, M. D., L. V. Hambubc.br, m'. D., h. w. Cushing, M. D . and J. F Mitchell, M.D.

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.




BULLETIN


OF



THE JOHNS HOPKINS HOSPITAL.


Vol. XL- No. 110.]


BALTIMORE, MAY, 1900.


[Price. 15 Cents.


COZtTTEHsTTS.


Urinary Anomalies. By Thomas R. Brown, M. D., - - - - 97

Acute Leuksemia in Childhood, with Report of a Case. By Thomas McCrab, M. D., - - - - 102

Personal Experience in Operations for Stone in the Bladder. By A. T. Cabot, A.M., M. D., 107

Summaries or Titles of Papers by Members of the Hospital and Medical School Staff appearing Elsewhere than in the Bulletin-, •-- - -Ill


Proceedings of Societies :

Hospital Medical Society. 112

The Inheritance of Deafness [Professor W. K. Brooks] ; — The Exhibition of a Three-months Infant with a Caudal Appendage [Dr. Watson] ;— Specimens of Cystic Kidneys [Dr. MacCallum] ; — Idiopathic Dilatation of the Colon [Dr. Futcher] ; — Report of Gynecological Cases [Dr. Miller].

Notes on New Books, 116

Books Received, 117


URINARY ANOMALIES.

I. SIMULATIVE NEPHRITIS. II. POST-OPERATIVE GLYCOSURIA. III. MALINGERING MELITURIA.

By Thomas R. Brown, M. D.


I. Simulative Nephritis (after Nephrotomies and Nephropexies).

The exact etiology of nephritis is still such an unsolved problem that anything that has the least bearing on even the smallest part of this problem should, we think, prove of some interest.

Besides the fact that a nephritis may be brought about by exposure to cold or by the action of various poisons — as those of the specific fevers, various chemical substances, and the toxines produced by skin-burns — very little is known of the cause of the condition.

I wish in this brief communication to report an interestii g form of urinary anomaly, which I have designated by the name of "simulative nephritis," occurring after certain simple operations upon the kidney.

These operations of nephropexy, or stitching the kidney in place, have become quite common within recent years, due to the work of Glenard and his school, and the demonstration by them of the characteristic and distressing symptom-complex noted in those suffering with a falling, or ptosis, of the kidneys, or "nephroptosis;" while we may also have a falling of many of the abdominal organs, usually associated with symptoms of a similar nature to those seen in cases of nephro


ptosis, Glenard designating these conditions as "gastroptosis," " hepatoptosis," "splenoptosis," according to whether the stomach, liver, or spleen is displaced, while a general displacement of all the abdominal viscera is known as "enteroptosis."

My attention was first called to the urinary peculiarities, after operation for floating kidney, by a case (Case I) — seen for the first time last year — in which the patient complained of severe pain in the left renal region, and, as nothing seemed to relieve it, an exploratory nephrotomy was decided upon.

The urine had been examined on four occasions previous to the operation, and was found to be perfectly normal, except for a number of red blood-cells and the amount of albumin one would expect with such a degree of hematuria, brought about by catheterization of the ureter, on the last two examinations. The operation consisted of an exploration of the kidney, an artery forceps being forced through the renal tissue into the renal pelvis to determine whether or not a stone was present; and, after the negative results of this examination, the closure of the renal wound and the stitching of the kidney to the posterior abdominal wall.

On the day following the operation the urine, of specific gravity 1.022, besides containing many red and some white


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[No. 110


blood-cells and epithelial cells, contained enormous numbers of casts of all kinds— hyaline, finely and coarsely granular, blood and some epithelial — the microscopic field being simply crowded with them. The urine contained a considerable amount of albumin, but no sugar.

In sis days the urine, of specific gravity 1.026, had cleared up considerably and contained but a trace of albumin and few blood and epithelial cells, but there were still a number of hyaline casts, and a few granular, blood and epithelial casts; while ten days later the urine, now of specific gravity 1.017 and showing but a faint trace of albumin, still showed a few hyaline casts and now and then a granular or epithelial cast, with a few red and white blood-cells and epithelial cells.

A bacteriological examination of the urine made at the height of the condition showed that it contained no microorganisms. The urine was obtained under the most careful aseptic conditions and cultures made upon the various media, but the results were all negative.

The patient leaving at this time, the urine was not again examined for several weeks, when it was found to contain neither albumin, blood-cells, nor casts; and again, ten months after the operation, the urine was found to be absolutely normal.

Associated with this urinary condition there had been absolutely none of the symptoms of a nephritis, no edema of the legs, no ascites, no retinal symptoms, no more headache and nausea than would be expected after ether anesthesia; while the quantity of urine voided was about the same as is usually seen after the administration of ether by inhalation.

The most striking characteristic of the urine was the marked disproportion between the number of casts and the amount of albumin present, the latter being so much less than one would expect from the great number of the former.

Since this case, which was regarded as being of peculiar interest, I have followed, as carefully as the circumstances would allow, all the cases of nephropexy that came within my reach.

In all, four such cases have been followed carefully, while in two other cases the urine was examined at a quite considerable time afterwards; but, as we shall see shortly, the results of this late examination are of slight interest, as the study of the other four cases has demonstrated that an early examination is absolutely essential.

In two of these four cases, in which the urine was examined immediately after operation, it was found to be normal except for a trace of albumin and a few blood-cells as one would naturally expect after the operation performed; no casts were seen after a most thorough search.

In the other two of the four cases carefully studied, however, the conditions found were, I think, of sufficient interest to warrant their being described at greater length. In the li -t of these the urine on the day before the operation was acid, of specific gravity 1.018, containing neither sugar nor albumin, while a microscopic examination showed only a few uric acid crystals and threads of mucus. On the day following the operation — a simple nephropexy— the urine contained a small amount of albumin, but an enormous number of casts, mostly hyaline, some granular, and an occasional


blood-cast, with some red and a few white blood-cells and epithelial cells.

On the next day, there was but a trace of albumin, a few red blood-cells and very occasional white blood-cells and epithelial cells, but still hyaline casts in moderate amount, while two days later both albumin and casts had entirely disappeared.

The patient was in a rather poor general condition, and her blood contained but sixty-one per cent of hemoglobin.

The second case was very similar, showing on the clay preceding the day of operation a normal urine of specific gravity 1.020 with no sugar, no albumin, and a few epithelial and puscells (voided specimen), while on the evening of the day of operation, the urine of specific gravity 1.016, while showing but a trace of albumin, showed enormous numbers of casts, hyaline, finely and coarsely granular, and blood-casts with a few free red blood-cells and epithelial cells.

On the following two days the urine contained but a trace of albumin, the specific gravity was 1.020 and 1.028 respectively, while on the first of these two days the sediments still showed enormous numbers of casts though not in quite so great abundance as the night before (mostly hyaline and granular with a few blood and epithelial casts), with a few red blood-cells and epithelial cells and occasional white bloodcells, while on the second day the only casts present were the hyaline and finely granular, which w : ere still quite numerous, with an occasional red blood-cell, white blood-cell and epithelial cell.

Five days later the albumin and casts had entirely disappeared, and the only things seen in the sediment were occasional red and white blood-cells.

In the other two cases, the urine was not examined until the fourth and seventh day respectively after the operation, and neither casts nor albumin were found in either, but only an occasional red and white blood-cell.

These latter cases, however, as mentioned before, are of little interest because of the lateuess of the urinary examination. Thus, of five cases in which the kidney was stitched in place, in three we have found in the urine what would lead one on microscojnc examination to make a diagnosis of acute nephritis, and yet associated generally with but a trace of albumin, and having none of the clinical signs and symptoms of such a disease.

In all the cases the urine was perfectly normal before the operation and after this trausitory cylindruria. We have, evidently, four factors distinctly involved in the production of this condition: 1st, the handling of the kidney, usually quite slight, except in the first case, in which a nephrotomy was also performed, and where the cylindruria and albuminuria persisted for a much longer period of time; 2nd, the taking of the stitches through the renal substance, and, in the first case, the trauma necessary in an exploration of the renal pelvis; 3rd, the irritation of the renal tissue by the ether that is, in part, eliminated by means of the kidneys — a well recognized condition as shown by the fact that a definite nephritis occasionally develops after protracted operations under ether anesthesia, this point having been gone into in detail very recently by Galleazi and Grilo (Gior. d. R. Acade


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JOHNS HOPKINS HOSPITAL BULLETIN.


99


mia di Torino, 1899, p. 293); 4th, the diminution in the elimination of fluids which is almost invariably seen after ether anesthesia, and which undoubtedly subjects the kidney to a greater chance of becoming diseased.

Probably in the development of this "simulative nephritis," all these factors play a part, although the stitching and handling are probably of most importance as evidenced by the fact that the urinary condition was so much more marked and persistent in the case where the trauma and handling were greatest, viz : the first case, where both a nephrotomy and a nephropexy were performed.

In connection with the effect of trauma upon the kidneys a recent article of Professor Stern, of Breslau (Monatscbrift fiir rnfallheilkunde, 11, 1899), is of interest.

llf considers in this article the definite relation between trauma aud the development of nephritis, and after mentioning the extreme rarity with which nephritis develops after injuries, blows, falls, or contusions in the kidney region, describes the following conditions which may arise after such injuries: — 1st, cases which either rapidly end fatally or are rapidly cured, in which the urinary picture is that of an acute nephritis, but with more albumin than one would expect from the number of red blood-cells; in the cases that came to autopsy an extensive renal necrosis was to be made out, but no nephritis; 2nd, cases of long-lasting albuminuria with casts in the urine, without the general symptoms of a diffuse nephritis; the condition may last for more than a year but is extremely rare, aud, so far, no autopsy records are to be had of such cases; probably these are cases of circumscribed inflammatory processes following the renal trauma; 3rd, typical casee of diffuse nephritis after trauma; in the literature a number of such cases are to be met with, with the characteristic urinary picture, and also the oedema, retinal changes, anemic manifestations, etc; certainly in some of these cases, at [east, a latent chronic nephritis was probably present before the injury.

While the number of our cases is small, it is probable that here also we may have analogues to the post-traumatic phenomena described by Stern, the extent of the condition probably depending upon the amount of trauma and handling which the kidney sustained during the operation, the amount of ether used, the general condition of the patient and the local condition of the kidney before operation.

Thus, in some cases we will only have the presence of a few red blood-cells and a trace of albumin rapidly clearing up; in others a urinary picture resembling a nephritis but less albumin than would be expected from the number of casts and cells present (differing in this respect from Stern's observations after trauma) and no other symptoms, the condition clearing up in a few days; in others a cylindruria and albuminuria of higher grade and longer duration, often lasting several weeks, but unaccompanied by other symptoms and finally clearing up entirely (examples of these cases are to be found in our five cases); while a longer persisting cylindruria with some albuminuria, and even a typical diffuse nephritis, must be considered as possibilities.


II. Post-Operative Glycosuria.

Since the original experiments by Claude Bernard, the subject of the disorder of metabolism, known as glycosuria, has been one of surpassing interest.

Certain experiments and discoveries have thrown some light upon the etiology of this condition, notably Bernard's celebrated piqtire diabetiqur, by which he showed that by puncture of a certain spot in the floor of the fourth ventricle polyuria and glycosuria could be produced; Lancereaux's, von Mering's and Minkowski's demonstration of the relationship which existed between certain pathological conditions of the pancreas and glycosuria; and the more recent work on alimentary glycosuria in various conditions, notably diseases of the liver, kidney and cerebrospinal apparatus, in which the organism is unable to appropriate the amount of sugar usually given (100 grammes) and some therefore jiasses into the blood, raising its sugar-content, and causing hyperglycemia and glycosuria.

It would be obviously unprofitable in an article of this kind to do more than touch upon some of the conditions in which glycosuria has been noted.

According to Abeles, Wedenski, Schilders, Moritz, Baisch and Kleen, there is a faint trace of glucose in normal urine, while Brim ton has recently shown that after breakfast, the meal richest in carbohydrates, traces of sugar can usually be demonstrated in the urine.

Besides diabetes mellitus, the alimentary glycosuria and the physiological glycosuria just described, glucose has been found in the urine in a variety of diverse conditions, the condition usually being of low grade and transitory. Many cases of this nature have been reported, and to describe all the conditions in which glycosuria has been found would take me beyond the limits of this paper ; it is of interest, however, to note some of the more important of these transitory glycosurias.

For convenience these cases may be divided into three groups: (1) the toxic; (2) those associated with diseases and injuries of various kinds, although probably in many cases of the latter group, a toxemia of some kind plays a considerable role in the etiology of the condition ; and (3) puerperal glycosurias.

(1). Toxic. — Transitory glycosuria has been described after the use of amyl nitrite, mercury, hydrocyanic acid, sulphuric acid, alcohol, strychnia, glycerin, nitro-benzol, thyroid extract, lead, phloriazin, caffein, diuretin, phosphorus, arsenic, carbon monoxid, morphia, tuberculin, pancreatin, while of the analgesics and anesthetics, a transitory glycosuria has been described after chloroform, chloral, amyl nitrite — in the case of the last-mentioned drug the sugar sometimes reaching two per cent — while Harley, Kleen and Von Jaksch describe the appearance of small quantities of sugar in the urine after ether, and Andral describes a case of true diabetes developing after ether anesthesia.

Of course, in some of these the only tests used were Fchling's or Trommel's tests, and recent work has shown that occasionally we find other reducing substances in the urine, especially glycuronic acid.


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[No. 110.


Thus, undoubtedly, in f ae of the cases described above the reducing substance was not glucose but glycurouic acid, as Marchot has shown with chloralamid; Ewald, von Mering and Magnus-Lew, with nitrobenzol and nitrotoluol; aud Hoppe-Seyier with orthonitrophenylpropionic acid; thus, before we definitely prove the presence of glucose in the urine, besides Fehling's or Trommer's tests, the fermentation test, the polariscopic test, and the pheuyl-hydrazin test should also have been made.

(2). Associated with diseases or injuries. — Transitory glycosuria has been described as occurring during the course of cerebrospinal meningitis, cholera, typhoid fever, relapsing fever, diphtheria, tetanus, phthisis, many of the exauthematous fevers, hepatic fibrosis and rickets. Frerichs has described it in gastritis; Da Costa in old age; Burdel during the malarial paroxysm; Rotch in scarlatinal nephritis; Ord ir angina pectoris and chronic interstitial nephritis; Exner in cholelithiasis, though Rausch vigorously denies this ; Marchot in syphilis; while after pertussis, asthma and a variety of other diseases, a faint trace has been occasionally found.

Of especial interest are those cases of transitory glycosuria found af fo r injuries to the cerebrospinal apparatus and in various .ental and nervous diseases. Thus, it has been described in cerebral, bulbar aud pontine hemorrhage; after concussion of the brain or spinal cord ; in cerebral tumor, abscess, softening and parasitic disease; in disseminated sclerosis; in epilepsy and epileptic insanity; in neuralgias of various kinds, especially sciatica; in exophthalmic goitre; in " a fatal case of myxedematous condition with tachycardia, melena and mania (by Osier); in Friedreich's disease (by Best); in sexual neurasthenia (by Peyer); while it has been frequently seen in some of the functional neuroses, as Charcot's grand hysteria, the traumatic neuroses, neurasthenia, severe psychical derangements, and after great emotion.

Kleeu has given the name "functional nervous glycosuria" to those cases where sugar appears in the urine in cases of acute or chronic "functional " nervous disturbances, and mentions several interesting cases where a transitory glycosuria was noted after grief, anger, excitement and other emotions of various kinds.

(3). Puerperal glycosurias.— Recent work has shown that a puerperal lactosuria is much more common than a puerperal glycosuria, although the latter is found in a certain number of cases.

Roque (Les glycosuries nou diabetiques, Paris, 1899) makes the following divisions of the subject:

A. Intermittent glycosurias of arthritics, while as subheadings, are put the hereditary form in the young, the gouty form in the adult and old man, that of the obese, and the azoturic.

B. Digestive glycosurias, subdivided into that form seen after eating excessively of sugars, or carbohydrates ; and that form seen in digestive disturbances.

0. \ervovs glycosurias made up of those seen in the systemic affections of the nervous system, those seen in the neuroses and psychoses, and the traumatic glycosurias.

O. Puerperal glycosurias.

Hofbauer makes a somewhat different division of the trans


itory glycosurias, dividing them into the neurogenic, febrile. toxicogenic and -puerperal.

The cases I wish to report, three in number, are examples of transitory glycosuria after ether anesthesia. The first case was in a white woman of fifty-nine, who was successfully operated upon for carcinoma of the uterus, aud hemorrhoids, and who had always been healthy, having had only whoopingcough, measles, chicken-pox, malaria and rheumatism, who had had eleven children and no miscarriages, and whose history and physical examination showed that the patient was not nervous at the time of her admission to the hospital and had never been so during her life.

For twenty years she had had a double pulsating goitre which had been associated with no symptoms whatsoever.

Owing to her pelvic trouble, she had had some frequency of micturition, but a careful urinary examination made on the day preceding the day of operation showed that the urine was absolutely normal, with neither albumin nor sugar present, of acid reaction and with only a few epithelial cells in the sediment.

On the day after the operation the urine was found to be of specific gravity 1.021; it showed some red blood-cells (due to the catheterization of the ureters); aud, besides some albumin, contained between 2 and 3 per cent of sugar, tested for, qualitatively, by Fehling's and the phenyl hydrazin test ; and, quantitatively, by the polariscopic and fermentation tests. On the next day about 1 per ceut of sugar was present, while after the third day, on which a trace was found, no sugar was found in the urine during her subsequent stay in the hospital, although a daily urinary examination was made.

The convalescence was extremely uneventful, the temperatui'e never rising above 99.(5° F., and the patient showing rather fewer symptoms of nervousness than one would expect after an operation of such magnitude.

The condition was such a rare one that all the urinary records of the Gynecological Department were carefully examined to see if any other cases of like nature could be found.

Unfortunately iu most operative cases there is but little need for a post-operative urinary examination, and there were comparatively few cases in which the urine was examined after the operation.

Two cases of very similar nature to the one I have described were found, however, as the result of this examination.

One of these was a colored woman of forty, who had a large myoma, which had been associated with much hemorrhage aud pain, and which had left the patient in extremely poor condition ; the expression was very troubled, the patient was very nervous at times, had a poor appetite, aud slept very badly. Up to the beginning of the hemorrhages, however, the patient had been very healthy, pleurisy and inflammatory rheumatism ten years before being the only serious illnesses she had ever had.

The operation was merely an exploratory incision, the myoma being found to be absolutely inoperable; the patient was given three hundred aud fifty grammes of ether iu sixty minutes. The patient had suffered with burning frequent micturition for a long while, due to the pressure of the tumor,


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but the urine examined twenty-seven times previous to the exploratory incision was absolutely normal except for a faint trace of albumin : there was never any sugar present.

The day after the operation, the urine, of specific gravity 1.020, besides containing a trace of albumin, showed a large amount of sugar (the exact percentage not given), tested for by the fermentation and Fehling's tests.

The next day. however, the sugar had entirely disappeared, nor was ever a trace of it again found during the patient's convalescence, which was slow hut uneventful, the temperature never rising above 100° P.

The other case was a young woman with an unimportant previous history except that she hail always been very nervous, and ou examination she was found to be of an extremely neurotic temperament. The operation performed was the suspension of a retroflexed uterus aud the repair of a relaxed vaginal outlet.

The urine, examined on the day previous to the operation, was found to lie absolutely normal, while in the urine voided directly after the operation, 0.8 per cent of sugar was found (tested for by the Fehling's and fermentation tests); no trace of sugar was subsequently found in the urine.

None of these three patients gave any history to suggest that a glycosuria might have been present previously, as polyuria, eczema of the genitals, etc.

The exact cause of the transitory glycosuria in these three cases -'■•ins to have been, undoubtedly, the inhalation of the ether. i. e., a toxicogenic glycosuria, while certainly in the last - the highly nervous character of the patients may have aided materially as a contributory cause, i. c, there was probably a neurogenic as well as a toxicogenic factor.

When we consider, on the one hand, the enormous number of patients that undergo anesthesia, and, on the other, how man] of theseare nervous, neurotic aud hysterical individuals, in all of whom the thought of operation would be associated with the most intense emotions, it would seem that this condition should not be so extremely rare, and probably a careful urinary examination made after every operation would result, in some cases, in the discovery of a post-operative glycosuria.

III. Malingering Melitoria.

The third urinary anomaly I wish to report is one which, for want of a better name, I have called "malingering melitnria."

The case was admitted to the private ward with the diag

diabetes, made by the physician attending her at her

home. The patient was a young girl of extremely neurotic

iment: in fact she had had several attacks of what was

probably hvstero-epilepsy, the patient apparently becoming

i] i scions and assuming remarkable poses.

In many respects she did not have the usual symptoms of diabetes, but the urine seemed characteristic ; between 4,<hid and 7,000 ccm. of a pale urine of a specific gravity between 1.030 and 1.050 being passed during the twenty-four hours.

The urine showed sugar by the Fehling's reaction, although the reaction did not coincide at all with the quantity one would have supposed to be present from the high specific gravity: with phenylhydrazin hut few crystals of phenyl


glucosazon were obtained, white' ' =e quantitative determinations made by the polariscope and the fermentation tube differed markedly ; by the latter test the gas was formed extremely slowly, but, after standing a considerable length of time, the amount of carbon dioxid formed showed that there was between one per cent and two per cent of sugar present.

On other occasions in which the urine was examined, the phenylhydrazin aud Fehling's tests were negative; by the fermeutation test gas-bubbles were formed extremely slowly, while the polariscopic test was positive as before.

The urinary condition was such as to make one suppose that the variety of sugar present was not glucose, at least except for an occasional trace, aud the absence of phenylmaltosazon crystals with phenylhydrazin and the dextrorotatory polariscopic reaction showed that it was neither maltose nor levulose respectively.

It was therefore thought probable that the sugar present might be the ordinary cane-sugar, CisELnOn, with occasional traces of glucose mixed with it (due either to a slow inversion in the acid urine, or to the commercial introduction of small ' I nan ti ties of glucose). To determine this definitely, chemically, before attempting to discover its source, the tbllowi experiments were performed: The urine was concenth. ,ed and boiled with dilute hydrochloric acid for from twenty to forty minutes, when the resulting fluid, after being neutralized with bicarbonate of soda, gave the following reactions: By Fehling's test the reaction was extremely marked and instantaneous, differing in this respect from the much -slower and less characteristic reaction or the complete absence of reaction noted before; by the pheuylhydrazin test the precipitation of the phenylglucosazon crystals was profuse; by the polariscopic test on the other hand, the plane of polarization was turned slightly to the left; while in the fermentation tube the gas-formation was much more rapid than before aud the reaction was more marked than with the original specimen.

All these tests showed conclusively that the sugar present was cane-sugar, the reactions just given depending, of course, upon the fact that cane-sugar when boiled with acids is converted into a mixture of glucose aud levulose (one dextro-, the other levo-rotatory), aud the reactions given above are exactly those that would occur in such a mixture, while the extreme slowness of fermentation of the original urine is explained by the fact that cane-sugar, in the presence of the yeast-ferment is first converted into glucose and levulose, the former of which then undergoes fermentation. As the girl was extremely hysterical and neurotic, and as the passage of such large quantities of cane-sugar in the urine is practically unknown, it was thought that she herself probably introduced the sugar into the urine.

All sugar was therefore carefully kept off her food-tray, and for a time the sugar entirely disappeared from the urine ami the specific gravity dropped to between 1.006 and 1.010, although the polyuria continued.

In a few days, however, the sugar reappeared, although not in such quantities as before; a nurse was then detailed to watch the patient most minutely, when it was found that the patient would slyly remove the lumps of sugar from her tea or coffee and deposit them in the urinary ve


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[No. 110.


When this source was also eliminated, the melituria entirely disappeared, and the patient on being confronted with the evidences of her deception, left the ward in high dudgeon, after absolutely denying what the nurse had plainly seen.

This case, I think is quite unique of its kind, the especially interesting feature, besides the presence of the sugar, being the marked polyuria, a very prevalent urinary condition in very neurotic and hysterical individuals, as well as in diabetics.

In these days when the advertising column of every newspaper is a treatise on diagnosis, and every hillside and vacant lot a manual of therapeutics, it is no wonder that the little and often the distorted knowledge that is so dangerous has proven a fruitful source of hypochondriasis, neurasthenia and malingering among the <n -»/./.<>!'; but so far as I know, this is the first case in which it has brought about a malingering melituria.

The cases in the first and second portions of my article were in the service of Dr. Kelly, and the third in the service of Dr. Osier; both of whom 1 wish to thank sincerely for allowing me to work up and report these cases of " urinary anomalii s."


Discdssion.

Dr. Futcher. — Dr. Brown's cases of post-operative glycosuria following ether administration, call to mind those cases in which the urine contains copper-reducing substances after the administration of certain drugs. In 1875, von Meringand Minkowski found that, after the administration of chloral hydrate to an individual, the urine contained a substance which had the power of reducing alkaline copper solutions. They found that the substance which gave this reaction was urochloralic acid in combination with glycuronic acid. Since that date it has been discovered that a large number of medicinal substances administered internally, either themselves, or in some modification, combine with glycuronic acid and are excreted in the urine, giving rise to a reduction of copper solutions simulating the reaction of glucose. The more important of these substances are chloroform, morphine, camphor, phenol, resorcin, thymol, menthol and others.

The report of the examination of the urine in Dr. Brown's case indicates, however, that the patient had a transitory glycosuria.


ACUTE LEUKEMIA IN CHILDHOOD WITH REPORT OF A CASE.

By Thomas McCrae, M. B. (TV.), Instructor in Medicine, The Johns Hopkins University, and Physician in Charge of the Clinical Laboratory, The Johns

Hopkins Hospital.


The question of the condition of the blood in the anaemias of early life is such an unsettled one, and cases of acute leukaemia in childhood are so rare that every such case is worthy of report in detail. The present case is as follows:

Male; aged 'i\ years : anaemia ; fever; purpuric rash; Hood pticture of leukcemia; hosmorrhagi s ; convulsions; death; duration about one month.

J. L., male, aged 3 years, was admitted to the service of Professor Osier, in The Johns Hopkins Hospital on May 11th, 1898. The symptoms to which his parents drew attention, were a slight cough and a peculiar area over the sacrum which had almost a gangrenous appearance. The circumstances connected with his admission to the hospital were rather peculiar. His sister was a patient at the time with a surgical complaint, and he was brought from out of the city to see her. He had some cough and interference with his breathing, probably due to adenoids. For this he was admitted, but at the time it was not thought that he had any serious condition.

Family history. — One uncle on the father's side had died of tuberculosis; otherwise the history was negative. There was no history of lues nor anything suggesting it.

Previous history. — He was a large healthy child at birth. He was not breast-fed, but brought up on various artificial foods, combinations of milk, etc. For two months after birth he did not thrive, but afterwards did well until two years old, when he had fever for some time, the nature of which was unknown. Chicken-pox was the only disease of infancy that he had had. In February of 189.S — three months before admission — he caught cold and had some bronchitis. With this it


was noted that there were numerous ulcers over the mucous membrane of the mouth. Since this attack he had some cough and obstruction to his breathing. He did not snore at night, but frequently woke up complaining of being choked. About the same time a peculiar bruised area was noted over the sacrum, which was slightly tender. This was thought to have been due to injury. The area did not increase in size, and there were no others like it elsewhere. Otherwise the boy had seemed to be perfectly well, with good appetite and digestion.

Present illness. — There were no special symptoms of this and only the previous conditions were mentioned. To these his parents had given but slight attention, as the boy was thriving and seemed hearty and strong. It was thought, however, that for a clay or two previous to admission he had been more easily tired than ordinarily and was rather peevish. He had also complained of some slight pains in the neighborhood of the joints. The boy's father — who was a physician — was positive that until a few days before admission, the patient had been as well as usual ami played about with his ordinary vigor.

Examination showed a very stout boy, large for his age. but with a generally pale flabby look which was very striking. He was very bright and intelligent and showed a lively interest in his examination. The mouth was kept open, and the breathing was noisy. The tonsils were much enlarged and there were numerous adenoids present. The gums and mucous membranes were very pale. The shape of the thorax was normal. There were no rickety nodules. The percussion

note whs clear throughout. The breath sounds were everywhere harsh and accompanied by numerous sibilant and sonorous rales. No tubular breathing was heard. The hear! sounds were clear and of normal relative intensity. The abdomen was full and prominent. The edge of the liver was felt about 3 cm. below the costal margin. The spleen was palpable and hard, although not enlarged beyond the costal margin. There was do tenderness over the abdomen. There was no glandular enlargement. No oedema or signs of rickets were present. Over the sacrum was an area about 5 cm. in diameter, dark purple in color and with a bruised, almost gangrenous look. It felt indurated, was slightly tender and was not adherent to deeper structures No fluctuation could be mad.' out.

The patient remained in the hospital until .May 24th, during which time his general condition was as follows:

May loth. Frequent coughing and constant mouth breathing. His appetite was good and he took his food well.

May 18th. The general condition was worse. There were great irritability and restlessness. At times complaint was made of pains in the legs. A small petechial rash appeared ou the legs. It was most marked about the knees.

May 20th. He was very fretful aud could only be got to take nourishment with difficulty. At times there were severe paroxysms of coughing. There were periods when he became collapsed with great pallor and a very feeble pulse. The purpuric rash persisted. There were many coarse rales every where over the the chest. The liver and spleen were as before. No enlarged glands were felt.

May 22d. The patient was much weaker. There was no pain.

May 24th. The condition was worse. He was very weak and took but little nourishment. In view of his grave condition his parents decided to take him home to Indianapolis. It was learned that he stood the journey well and seemed better for a day.

His subsequent history was obtained from Dr. F. B. Wynn, of Indianapolis, to whom I am also indebted for the account of his blood examination. Dr. Wynn writes as to his condition : "The temperature was from W° to 100°, pulse 1 10 160 and very weak, respirations 40-50 with considerable d\ petechial haemorrhages, 3everal attacks of epistaxis, and on two days nausea and vomiting." Death occurred on May 30th with convulsions which were thought to be due to cerebral haemorrhage. There was no autopsy.

While in the hospital, his temperature was elevated, usually to 100° and 100.5°. On May 21st it rose to 103.3° falling gradually to 99° on the morning of the 24tb. The pulse varied from 120 to 160, aud the respiration usually about 40. Dyspnoea was most marked after the <f aghing. He did not lose any weight while in the hospital. The urine had a specific gravity of 1.015 to 1.017. The reaction was acid and there was neither albumin gar present. The diazo reaction was not given. Misroscopically urates and uric acid were found.

Blood. — The first examination after admission was on May 12th. The haemoglobin was 35 per cut <\. Fleischl), the red corpuscles 1,680,000, and the white cells 26,000 per cmm.


(a ratio of 65 to 1). A differential count of 1000 leucocytes in specimens stained with Ehrlich's triple stain showed :


Polymorphonuclears . . 13.3 per cent.

Lymphocytes, Small. 41.5 1

, ' , ,- ^86.5 do.

do. Large. 4.). J

Large mononuclears ... .2 do.


The red cells did not show any special variation from the normal in either shape or size, and but slight polychromatophilia. No nucleated red cells were seen in counting 2000 leucocytes nor in careful additional search. The lymphocytes showed all variations in size from the smallest up to some which were fully 15 microns in diameter. So many cells were ou the border line that the division into small and large is only approximate. The depth of nuclear staining varied much in cells of the same size but the general staining was pale. This was more marked in the larger forms ; still, there were hut few small lymphocytes with a typical deeply staining nucleus. Cells with nicked or divided nuclei were very rare. The protoplasm about the nucleus was unstained in the majority of the larger forms. One myelocyte was seen. In this, as in the later specimens, there was a marked tendency for the lymphocytes to disintegrate and appear in the stained specimen as shapeless blotches with a pale blue stain. The polynuclear cells in the same specimen would be quite normal. It was found that by making the specimen rather thick, and drawing the covers apart as rapidly as possible, this disintegration could be prevented. Both the small and large lymphocytes showed the tendency to break up.

May 15th. The differential count of 1000 leucocytes showed — ■

Polymorphonuclears ... 4.4 per cent. Lymphocytes, small. 78.9 \ _ , ) - iJ . ()n large, 16.7 J

The general characters of the cells were much as on May 12th. There were still all variations in size between the largest aud smallest lymphocytes. No nucleated red cells or myelocytes were found.

May 19th. The haemoglobin was 32 per cent, red corpuscles 1,760,000, and white cells 60,800 per cmm. (a ratio of 39 to 1). The differential count of 1000 leucocytes gave:


Polymorphonuclears . .


. .4


pe


r cent.


Lymphocytes, small, '.•<;.(; \


99.2



do.


large, 2.6 J





Large mononuclears, . .


. .3



do.



. .1



do.


The red cells were much the same. No nucleated red cells were found in counting 2000 leucocytes, aud in additional search. The lymphocytes were much smaller on the .-i and many of them were of the typical small type. No myelocytes were seen.

May 21th. The haemoglobin and red cells were practical!] the same as on the 19th, hut the white corpuscles hail fallen to 21,800 per cmm. (a ratioof si t,, i i. The differential count of 1000 leucocytes showed :


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[No. 110


Polymorphonuclears, . .

Lymphocytes, small, 89.2 1

large, 9.4 J


. .9 per cent 98.6 do.


Large mononuclears, . .


. .4 do.



. .1 do.


The general characters of the cells were as before, but the red cells showed somewhat greater variation in staining. No nucleated red cells or myelocytes were seen.

Dr. Wynn very kindly sent me his count taken a few days later in Indianapolis. The haemoglobin was 30 per cent (Gowers), red corpuscles 1,800,000, and white 36,000 per ciimi.

In considering this case a striking feature is the rapid course. The patient was admitted to the hospital almost accidentally — if one may so term it — on May 11th, and beyond the presence of enlarged tonsils and adenoids he seemed, on superficial examination, to be in ordinary good health. Had it not been for the results of the blood examination, no suspicion of leukaemia would have been entertained. There were no symptoms pointing to acute disease, and his father was sure as to his having been in his normal condition up to a few days before. From the time of admission to the hospital until death was less than three weeks. Including the few days of malaise previously the whole course was not over four weeks. Even when the first blood examination was made, the possibility of the case being one of extreme lymphatism was considered, although the high percentage of lymphocytes (86.5) suggested leukaemia. In his condition any attempt to remove the adenoids and enlarged tonsils was thought unadvisable, even though they caused considerable obstruction. About May 18th the geueral condition changed and the symptoms were more severe. The blood showed 99.2 per cent of lymphocytes and the hsemorrhagic rash had appeared. The temperature ranged higher and from this to the time of discharge the downward course was rapid. I >eath, as already noted, occurred on May 30th.

In regard to the blood condition a relatively high proportion of the haemoglobin to the red corpuscles is seen. The color index on the first examination was slightly over 1, falling a little below it subsequently. A high-color index, while usually characteristic of pernicious anaemia, occurs not infrequently in other blood conditions. In a recent case of lymphatic leukaemia in this hospital the color index was always about 1 during observations extending over a period of two months. In two recent cases of splenic anaemia the same ratio was observed. It will be noted that there was practically no diminution in the number of red cells during the course of the disease. In the stained specimeus they showed but little variation from the normal throughout. Variations in the staining were rather more marked. No nucleated red cells were found at any time, although special search was made for them. In all the specimens the same difficulty was found in obtaining satisfactory slides. Unless the covers were drawn apart very rapidly, the majority of the lymphocytes were irregular masses without any definite outline. They took the stain exactly as the nuclei in the better specimens. This tendency to disintegration may be a feature of the lymphocytes in acute cases. So far as known there are


not sufficient observations to speak with certainty on this point. The staining of the nuclei of the lymphocytes showed great variation, although the prevailing stain was a pale one, and this was most marked in the larger forms. The lymphocytes showed increase both absolutely and relatively. The polymorphonuclears showed an absolute reduction. On admission they were 3400 per cmm., but fell later to 240 and 180 per cmm. The eosinophils were absent in the earlier counts, and 60 and 21 per cmm. were found in the later ones.

Leukaemia is a relatively rare disease in the first decade. Cassel' states that among 3000 autopsies in Friedrichshain there were only two instances of leukaemia below the age of ten years. Considering acute leukaemia, however, there seems ground for thinking that it occurs in a somewhat larger proportion. Theodor collected 45 cases of acute leukaemia of which 6 were in the first decade. There were 5 between the ages of 10 and 15 years. Fussell and Taylor 5 have published a series of 56 cases, among which 9 were in this period. Morse 4 in reporting a case in 1898 collected 7 from the literature. There is doubt expressed as to cases reported some years ago, but apparently 13 previously reported cases may be accepted. A recent case in an infant reported by I'ollniann is not included, as the condition appears to have been considered congenital. Bloch and Hirschfeld 6 report a case in a boy aged eight months, which was probably acute, but the exact duration was not known. The present case is the fourth to be reported within a year. The previous eases are asfollows:

I. Keating'. Female, aged 4* years; epistaxis. fever, hemorrhagic rash, cervical glands and spleen enlarged. The blood was examined by Dr. Osier. The red cells were normal, no nucleated cells being seen. The whites were very numerous, there being 50 or 60 in one field. They were largely lymphocytes. Duration 9 weeks; type probably lymphatic.

II. Wadham". Male, aged 5 years; no haemorrhages, slight fever, cervical glands enlarged, abdominal pain and distention. The type can not be decided from the description given. Duration 8 weeks. Autopsy.

III. Guttmann". Male, aged 10 years; a previous history of enlarged tonsils and adenoids, haemorrhages, hsemorrhagic rash, no fever, hemiplegia, priapism, spleen and liver enlarged. The blood showed whites to reds as 1 to 1.4. Type was probably lymphatic. Duration 4J days. At autopsy the thymus was found much enlarged.

IV. Eichhorst'". Male, aged 8 years ; onset sudden with precordial pain, haemorrhages, fever, enlarged spleen and liver; no swelling of the lymph-glands. ' The blood showed 88,000 whites. No nucleated reds were seen. Duration 2 weeks. Autopsy. Lymphatic in type.

V. Muller". Male, aged 4 years ; haemorrhages, ulceration of throat and only the cervical glands enlarged, liver and spleen enlarged, fever. The blood showed 109,000 whites of which 97 per cent were mononuclear, with an acute staphylococcus infection. Shortly before death the leucocytes fell to 6800. Duration 5 weeks. Lymphatic in type. Autopsy.


.May, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


105


VI. Mfiller". Male, aged 4 years: haemorrhages, hemorrhagic rash, fever, liver and spleen enlarged. The blood showed 209,000 white cells of which 98 per ceut were mononuclear. Duration 4 weeks. Type lymphatic. Xo autopsy.

VII. Goldschmidt". Male, aged 2 £ years ; cervical glands enlarged, liver and spleen enlarged, fever, nephritis. Blood picture of ieuksemia. Nucleated red cells present. Duration

5 weeks. Autopsy. Lymphatic in type.

VIII. Theodor. Male, aged 4 years; luetic family history, haemorrhages, cervical glands enlarged, spleen enlarged, liver not: no fever. The white cells were to the reds as 1 to 9. Nucleated red cells were present. Duration 6 weeks. Lymphatic in type. Xo autopsy.

IX. Cabot 13 . Infant; lymphocytes over 98 percent, duration

6 weeks, lymphatic in type.

X. Morse*. Female, aged 3 years ; haemorrhages, enlarged tonsils, liver and spleen enlarged, general glandular enlargement. The duration was not more than 7 weeks, and probably less. Tlie type was lymphatic. Xo autopsy.

XI. Bradford and Shaw". Male, aged 7 years; haemorrhages, fever, swelling and ulceration of the mouth, cervical glands enlarged, spleen enlarged, liver not. Duration probably 7 or 8 weeks. Autopsy. Lymphatic type.

XII. Haushalter and Bichon". Male, aged 7$ years ; hemorrhagic rash, no fever, glands and spleeu enlarged, blood cultures yielded streptococci. Duration 8 weeks. Autopsy. Lymphatic type.

XIII. Bradley". Male, aged 8 years; haemorrhages, haemorrhagic rash, liver and spleen enlarged. The white cells were 85,000, of which 97 per cent were lymphocytes. There were a few nucleated red cells present (personal communication from Dr. Bradley). Duration 7 weeks. No autopsy. Lymphatic type.

It is of interest to compare the symptoms in this series of A.8 in case IX only the blood features and duration are known, it is not considered in the figures given for various other symptoms.

Family history. — There is nothing of any importance under this heading. In ouly one case was therea luetic history, and two had a tuberculous family history.

Previous history. — Various infections are noted in the previous histories of the cases. One had had meningitis, one suppurating cervical glands, and three had suffered from some affection of the tonsils. This last is of some importance in connection with the number of instances in which the disease was accompanied by acute tonsillitis.

-A large proportion of the cases were in male-, namely 11 out of 13. This is true of acute Ieuksemia at all In the series of Fussell and Taylor, among 55 acute Here the sex was known, 33 were males. The same is found in leukaemia generally in childhood. Thus, BirchEirschfeld, among 39 cases below the age of 15 years, found 25 males and 14 females. This applies to cases from the earliest years.

Otuet.—TMe was sudden in many of the cases as might be

expected from the rapid course. In one case, Xo. VIII, the

mptom was haemorrhage following a fall from a horse.

In four cases haemorrhage was the first prominent symptom.


Hemorrhages. — These occurred in 10 cases. The bleeding was from the nose, mouth, stomach, bowels and kidney. In no case did the bleeding seem to have beeu sufficient to cause death directly. A hemorrhagic rash was present in 10 cases, of which 9 had also bleeding from a surface.

/' ver. — This was noted in 8 cases, its absence in 4. and in 1 there was no note. The temperature was usually not extremely high. The highest was in No. X I. where it rose to 105.4°. In this ease blood cultures taken at this time were negative.

Glandular Enlargement. — General enlargement was noted in 4 cases, enlarged cervical glands only in 5 cases, no enlargement in %, and no note in 2 regarding it. In the cases with enlargement of the cervical glands only, this was usually associated with local throat or mouth conditions such as enlarged tonsils, adenoids or ulceration.

Spleen. — This was enlarged in all the cases. The degree was not great, the edge usually being 3 to 4 cm. below the costal margin.

Liver. — There was enlargement in 8 cases, none in 3, and in 2 the condition was not noted. In no case was the enlargement extreme.

Miscellaneous Symptoms. — Pains in the joints and bones were noted, hemiplegia, priapism, etc., but none in any large proportion of the series.

Blood. — There was marked anaemia in all the cases in which blood examinations were made. Among the eight cases in which the corpuscles were counted the highest count was in No. VI, viz., 2,350,000 and the lowest of 1,000,000 in No. IV. The percentage of haemoglobin varied from 40 in No. V to 18 in No. II. The degree of anaemia in these acute cases is striking. It suggests the possibility of the development of the disease in children already anaemic. The red corpuscles did not show auy rapid fall while the cases were under observation. If such low counts were suddenly brought about by the disease, it. would seem probable that the rapid fall would continue with the advance of the other symptoms. If the onset of the disease were attended with such rapid blood destruction, why not the terminal stages? An explanation may be that these children had been suffering from leukaemia iu a more chronic form for some time and that what we consider the whole course was only an acute exacerbation at the termination. The histories of these cases and the consideration of the marked general features do not support this view The question is an interesting one, and may be answered when cases have been observed with blood counts taken prior to the onset of auy symptoms.

The high-color index in the present case has already been commented on. A color index over 1 was shown in 4 cases of the series, Xos. IV, V, XIII. XIV. When the color index was below one, as in three cases, Xos. VI, X, XII, it was only about .5. This relation of the haemoglobin to the red cells divides the cases into one class with the blood of a pernicious anaemia type, and into a second with the characters of a secondary anaemia: As already stated a similar point has been noted in a series of cases of splenic anaemia. So far as can be gathered from the description- given, no difference wi served in the shape and size of the red cells in these two groups. In spite of the severe anaemia the red corpuscles as a


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[No. no.


rule showed little variation from the normal in their characteristics. This may be due to the acuteness of the condition as in a case of pernicious anaemia at present under observation in which the symptoms developed with great suddenness. It was fully two months after the onset before the red cells showed any special variation in size, shape or staining. In 10 cases of this series it was noted that the red cells showed no marked changes from normal in their general characters. In the remaining 3 cases there was no note on this point. The occurrence of nucleated red corpuscles is an interesting question. The statement is made by some writers that cases of leukaemia in children show more abundant nucleated red corpuscles and that megaloblasts are usually equal in number to normoblasts. The cases of this series do not seem to support the view that nucleated red cells are common in acute leukaemia in childhood. Thus among 11 cases in which full descriptions are given, no nucleated red cells were found in 7, and in the 4 cases where they were found the numbers do not seem to have been large. In only one case, No. VIII, was the occurrence of megaloblasts noted. In this instance their number increased while the patient was under observation.

White corpuscles. — The number of the leucocytes shows wide variation. There are counts in 8 cases, the highest being 209,000 in No. VI, and the lowest 21,000 in the present case. The characteristics of the white corpuscles are much the same in all the cases. In some only a general account is given but sufficient to recognize the prevailing type of cell. In all there is an absolute and relative increase in the mononuclear elements. The proportion of large to small cells varies in the different cases. There does not appear to be any relation between the varying proportions of large and small forms and the relative acuteness of the disease. The mononuclears in all the described cases showed great variation in their staining. The largest absolute number of mononuclear cells was in No. VI, where they numbered 204,800 per emm. The absolute number of the polymorphonuclear leucocytes was about normal in most of the cases. The highest number per cmm. was in No. XI, where they were about 15,000 on one occasion and 8800 on another. The lowest number was in the present case, where on admission they were 5400 per cmm., falling later to 240 and 180. Myelocytes were rarely seen and were only noted as of very occasional occurrence.

Type of Leukcemia.—Th.'\s is apparently lymphatic in 13 cases, and in the remaining case no note regarding the blood is given. This is in accordance with the acute course of lymphatic leukaemia generally as compared with the splenomyelogenous type. There are instances of the latter variety in children.

Duration. — The period of nine weeks has been generally accepted as the limit of time within which a case should be considered acute. While the general features of the case should also be considered in classing a case as acute, still it will be found that nearly all cases with acute features terminate in this time. Muller," in reporting the two cases noted before, has also described a case with a duration of 13 weeks, which, in its general features, might be termed acute. The duration in 4 cases of this series was less than one month, and in 10 was between four and nine weeks.


General features. — These cases show some agreement in their features beyond the acute course. The disease occurs usually in a male with no special feature in his family or previous history except perhaps a history of throat trouble. This was marked in some instances and suggests possibly something of a causal relationship. In one, No. XII, emphasis is laid on the presence of carious teeth. Possibly, if this condition had been more often looked for, it might have assumed more importance as a possible causal source of infection. Hunter" has recently raised the question of a possible association between foci of infection in the mouth — such as carious teeth — and pernicious anaemia, considered as a chronic infective disease. A possible relationship to the socalled "Lymphatic Constitution" must also be considered. This has been discussed by Ewing'" who considers that there is no direct indication of connection between that condition and leukaemia. That children with the lymphatic constitution are more apt to develop leukaemia we can not say. One of the series, No. Ill, showed a much enlarged thymus at autopsy.

The onset is usually with moderate suddenness ; fever is present in a majority of the cases with haemorrhages and a haemorrhagic rash. General glandular enlargement is found in less than half of the cases ; in more the cervical glands alone show enlargement. The spleen was enlarged in every case where there are notes of an examination and the liver also in more than half of the series. In all, the anaemia is a striking feature, and the symptoms of the disease may be summed up as a severe anaemia with frequent multiple haemorrhages, fever, enlargement of the spleen and frequently of the liver. In some cases general glandular enlargement, but in others only of the cervical glands, enlarged tonsils, ulceration of the mouth, pains in the bones, etc., are present. With these is a downward course to a rapidly fatal termination. Guinon and Jolly' 9 in discussing the subject divide the cases into three classes:

1. Typical forms: swollen glands; anaemia; terminal haemorrhages.

2. Haemorrhagic form : features of an infectious purpura.

3. Pseudoscorbutic: lesions of the mouth, gums and tonsils predominate.

Diagnosis. — This can only be made with certainty through the examination of the blood. In nearly all the cases emphasis is laid on the striking anaemia. This with the severe general symptoms and the occurrence of haemorrhages should suggest a blood examination. Probably the conditions with which it is most apt to be confounded are: (1) an acute infection with specially marked throat symptoms, and (2) a haemorrhagic purpura. Bradford in referring to his cases has laid emphasis on the probability of considering an acute leukaemia to be merely an infection unless a blood examination be made. Probably, with more frequent routine work on the examination of the blood, cases will be found more often.

Treatment. — This can only be symptomatic with our present knowledge. In no case does any treatment appear to have been of any service.

In conclusion, emphasis may be laid on the necessity of careful study of the anaemias of early life. The subject at


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present is in a rather chaotic state, and only through careful blood examinations can we hope to have the lines drawn more satisfactorily.

References.

1. Cassel : Ein Fall von lieno-medulliirer Leukamie bei eineu achtjahrigen Miidchen. Berl. klin. Wochen., 1898,

p. ;:.

•-'. Theodor: Acute Leukamie in Kindesalter. Archiv f. Kinderheilk.. 1897, XXII, II. 12, p. 47.

3. Fussell and Taylor: Acute Leukaemia. The Philadelphia Medical Journal, 1899, III, p. 39.

4. Morse: Acute Leukaemia in Childhood. Archives of Pediatrics, 1S98, XV, p. 130.

5. Pollmaun : Ein Fall von Leukamiie beim Neugeborener. Munch, med. Wochen., 1898, I, p. 44.

(i. Bloch aud Hirschfeld: Zur Kenntniss des Veranderangen un Oentralnervensysfcem bei Leukamie. Zeit. f. klin. Med.. 1900, XXXIX, H. 12, p. 32.

7. Keating: Lymphatic Leukaemia in Children. Amer. Jour, of Obstetrics, 1886, p. 160.

8. W'adham: . Case of Leucocythsemia in a Child. Lancet, 1884, I. p. 158.


9. Guttmann : Uebereinen Fall von Leukaemia acutissima. Berl. klin. Wochen., 1891, XXVIII, p. 1109.

10. Eichhorst: Ueber acute Leukamie. Virchow's Archiv, 1892, CXXX, p. 365.

11. Muller: Zur Kenntniss der acuteu Leukamie im Kindesalter. Jahrb. f. Kinderh., 1896, Bd. XLI1I, p. 130.

12. Goldschmidt: Acuter Leukamie. Munch, med. Wochen., 1896, XLII1, p. 714.

13. Cabot: Clinical Examination of the Blood. 3rd edition. New York, 1S98, p. 397.

14. Bradford and Shaw : Five cases of acute Leukaemia. Medico-Chir. Trans., 1898, LXXXI, p. 343.

15. Haushalter and Richon : Leucemie aigue chez un enfant. Archiv de Med des Eufants, 1899, June, p. 356.

16. Bradley: A case of acute Lymphatic Leukaemia. New York Med. Jour., 1899, p. 923.

17. Hunter: Further observations on Pernicious Anaemia; a chronic infective disease; its relation to infection from the mouth aud stomach. The Lancet, 1900, I, p. 221, et seq.

18. Ewing: The Lymphatic Constitution. The N. Y. Medical Journal, 1897, II, p. 37.

19. Guinon and Jolly : Un cas de leucemie aigue. Rev. mens, des Mai. de l'enfance, 1899, June, p. 262.


PERSONAL EXPERIENCE IN OPERATIONS FOR STONE IN THE BLADDER.*


By A. T. Cabot, A. M., M. D.


Not many years ago, a leading surgeon of the West, going through the Massachusetts General Hospital, pointed to the Bigelow instruments and asserted that in a few years litholapaxy would be an operation of the past.

I would ask you to contrast with this opinion the experience and practice of English surgeons in India. Those men, who see more stones in a year than many of us do in a lifetime, are earnest and enthusiastic advocates of litholapaxy. Indeed, it was an Indian surgeon who extended the scope of the operation to the treatment of children.

Which of these opinions is most in accord with the facts? Is litholapaxy being superseded by other methods of stoneremoval and becoming obsolete or not? Ought it to be so ■ led ? These are the questions that I wish to discuss with you in the light of what experience I have had.

In considering the comparative value of these operations, we have to take account of the death-rate which accompanies each, of the injury to important structures which each involves, and of the liability to a recurrence of stone-formation which follows each.

A statistical study of these questions from cases reported by other operators is difficult and of little value. Many surgeons use litholapaxy for their easy cases, where the stone i? small, and cut for their larger stones, in which a longer duration and severity of the disease has presumably led to serious secondary changes in the urinary organs. Such a practice

•Read at the meeting of The Johns Hopkins Hospital, April 2d, 1900.


would give litholapaxy an unfair showing over the operations resorted to in the more serious cases.

Again, in many of the cases of suprapubic incision for stone, the operator removes a portion of the prostate or digs the stone out of a pocket, so that the operation ceases to be a simple lithotomy.

When we come to an examination of the question of injury to the parts about the neck of the bladder, it is often impossible for the surgeon who operates to follow his patient in after life and ascertain the extent and remote consequences of such injury. Cases occasionally come to the notice of all of us in which an incision made in childhood has led to impotency, not discovered until after puberty was established, or even much later. I have met with at least two cases in which a perineal lithotomy has been followed many years later by a narrowing of the urethra sufficiently close to cause symptoms of stricture, and in one of these a pachydermia vesicae, and, finally, a carcinomatous condition of the bladder, developed.

Lastly, in judging of the frequency of stone-recurrence, the difficulty is even greater; and one is constantly compelled to revise his own statistics, as cases supposedly cured reappear with a return of symptoms. How often this recurrence occurs in cases reported by others, it is difficult to say; but, judging from my own experience, it must happen more often than published statistics would lead one to suppose.

For these reasons I propose to depend, as far as possible, on my own experience for the facts from which I draw the conclusions I shall present. I shall endeavor to give this experi


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[No. 110.


ence in a sufficiently explicit manner to enable others to judge how far my deductions are supported by reliable observation. The stones I have met with in my practice have been,as a rule, secondary to enlargement of the prostate. Many of them, in fact the majority, have been phosphatic stones, dependent upon the cystitis set up by the enlargement of the prostate. Even the uric-acid stones which have occurred in these cases have usually been in part due to the incomplete emptying of the bladder, owing to the obstruction.

The average age of these patients has been somewhat over sixty year?. The material, therefore, from which I have derived my experience, has been as unfavorable to success in stone-treatment as is possible; for most of the operations have necessarily been done in bladders already diseased, often too, in cases where the kidneys were more or less affected.

Litholapaxy has been the operation of choice in all of my cases, irrespective of the size of the stone or the condition of the patient, except in a few instances when, for some reason, it could not be used or when some other condition compelled a cutting operation and the removal of the stone was merely an incident in this. Thus, in operations for stone I have done litholapaxy 122 times, suprapubic lithotomy 12 times, and perineal lithotomy once.

The suprapubic operations were selected in two cases because the lithotrite would not enter the bladder without an undue exercise of force. In six cases the operation was primarily a prostatectomy, and in one case the coexistence of a myoma of the bladder-wall compelled us to make the suprapubic incision. In two cases the stones were sacculated and could not be reached by the lithotrite. In one case the stone was so large that the lithotrite, when grasping it, would not lock. I find that out of the one hundred and twenty-two litholapaxies six patients have died within a comparatively short time after the operation. In order that you may judge of the degree in which the operation was responsible for the deaths, I will briefly report these cases.

The first death occurred in a man sixty-nine years of age, upon whom I operated in 1885. The patient was feeble and had a weak pulse. The condition of the urine, however, was reasonably good, showing nothing beyond alkaline fermentation, and it was passed in good amount. The patient, however, had a troublesome cough with profuse purulent expectoration. The stone was small and soft, weighing only 98 grains and the operation was in no way difficult. The patient was wholly relieved of his urinary symptoms by the removal of the stone, the urine became acid, and almost wholly cleared of pus-. In the meantime, however, his cough became much worse. On the fourth day after the operation he began to have considerable dyspnoea, and presently an examination of the lungs revealed the presence of pneumonia, secondary to the bronchitis which had existed previous to the operation. He died on the tenth day following the operation.

The second patient was an old man who had complete obstruction of the prostate so that for some time the urine had been drawn by suprapubic aspiration. The aspirating needle touched a stone and I was then called to the patient. At the time that I saw him the urine was suppressed, so that the contents of the bladder at the operation consisted almost


wholly of stringy mucous. The operation was done as a desperate effort, without much hope of its success. A large oxalate-of-lime stone was crushed and pumped out. The kidneys never resumed their function after the operation and the patient died about twenty-four hours later.

The third patient was a broken down man of sixty years who had a chronic bronchitis, with a feeble heart. He entered the Massachusetts General Hospital on account of extreme pain in the bladder and frequency of urination. A stone had previously been touched before he was sent in. The condition of his lungs and heart was so wretched that he was kept in the Hospital two months while everything possible was done to improve his condition and get him to the point of bearing the operation. The urinary difficulty and pain, however, were so excessive that he got little sleep and did not regain any . strength. A quick litholapaxy was, therefore, finally done under ether. The operation did not take long and was not especially difficult. The patient, however, developed a great increase of difficulty of breathing immediately following it and died three days after the operation.

The fourth case was that of a woman sixty-two years of age. A hard stone weighing a little over an ounce was removed by litholapaxy and at the same time, some glands in the neck, which were extensively tuberculous, were curetted. The patient did very well for a time. The temperature fell to normal and recovery seemed assured, when she gradually began to fail and died six weeks after the operation, death being due to the tuberculosis and not in any way to the operation on the bladder.

Case 5 was a man eighty-four years of age who had suffered for a long time from urinary symptoms, believed to be due to enlargement of the prostate. A catheter, which was tied in his bladder was so worn upon one side that it became evident that there must be a stone there pressing upon it. I etherized and examined him. There was a large stone, in fact I thought there were several stones, in the bladder, which were crushed and pumped out. This operation relieved his pain in great measure, but for three weeks following the operation the temperature was irregular and the general condition of the jiatient rather unsatisfactory. This was ascribed to pyelitis and possibly pyelonephritis. Finally, on the twentieth day after the operation, the temperature fell to normal and remained so until the twenty-seventh day. The patient was now suddenly taken with severe dyspnoea with symptoms pointing to the chest, and quickly died. Aii autopsy was not allowed, but it seemed quite clear that the final cause of the death was pulmonary embolism, which came at the time when he was practically recovered from the immediate effects of the operation.

The sixth case was that of a feeble man of seventy who entered the Hospital with a history of having had symptoms of stone for six months. The operation was an easy one and thi' patient seemed to be reasonably well after it. Death occurred suddenly and unexpectedly on the third day. The autopsy showed a condition of pyelitis and pyelonephritis, although no cause for the suddenness of the death could be discovered.

It would be certainly a contradiction of fact to ascribe the death in the fourth case to the operation.


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In Cases 1 and 3, the fatal outcome did not in any way result from the manipulations of the operation, but was probably dependent on the irritation to the lungs of the anaesthetic employed.

Cases 2 and t'> died, in spile of the operation, of the condition of the kidneys which already existed at the time of the litholapaxy.

In Case 5, the pulmonary embolus may have come from the pelvic veins and have been, therefore, an indirect result of the operation. I remember one fact bearing upon this point and that is. that in one case, which subsequently recovered, I saw a phlebitis of one leg following a secondary washing of the bladder, done ten days after a litholapaxy. This shows that the pelvic veins may occasionally become inflamed from the irritation caused by the use of urethral instruments.

If all of these cases, except the one that died of tuberculosis, be counted as deaths from litholapaxy, we have a mortality of 4 per cent.

Every one of the patients who died was in a seriously damaged state before the litholapaxy and the outcome was to be ascribed to an aggravation of antecedent conditions rather than to any damage inflicted by the operation.

As far as this experience goes, then, we have the right to feel that a litholapaxy on a tolerably healthy subject has practically no risk.

Further than this, a study of my cases shows that among them were a number of patients who were passing large quantities of urine of low specific gravity and several that had shown digestive disturbances suggestive of mild uraemic conditions.

Such patients are, according to my experience, very unfavorable subjects for lithotomy or any extensive cutting operation, and yet, with one exception (Case fi just reported), they did well after litholapaxy.

Could any of the patients who died have had a better chance by any other operation ?

I think that possibly this question should be answered in the affirmative, in regard to two of them ; for, at the present time, instructed by some excellent work, done here at Johns Hopkins Hospital, should I again have a case of stone in a man suffering from serious bronchitis, 1 should be inclined to prefer a suprapubic lithotomy, done under cocain anaesthesia, to a litholapaxy.

My friend, Dr. Chismore, of San Francisco, would doubtless in such a case do litholapaxy under cocain aiuesthesia ; but I have had such difficulty in producing a satisfactory aiuesthesia of the prostate and bladder in this way, that I should prefer the quick cutting operation.

DIFFICULTIES MET WITH IN THE OPERATION.

I have had two cases, already mentioned, in which the enlarged prostate so resisted the passage of the lithotrite that I was obliged to resort to a suprapubic operation. These are the only instances in which I have had to abandon an attempt at litholapaxy.

A strictured urethra adds little difficulty to the operation. If it yields readily to divulsion, the canal thus enlarged can


be easily traversed by the litholapaxy instruments, and I have done many operations in this way.

When a tight stricture exists in the perineum, urethrotomy may be done and the opening thus made may be utilized for the litholapaxy. A perineal litholapaxy is an easier operation than where the instruments have to traverse the whole length of the urethra. With the patient in the lithotomy position the stone rolls back towards the fundus of the bladder where it is easily reached, and through the distensible deep urethra large instruments can be readily used.

In the whole series of litholapaxies I have had but one serious accident. This was a rupture of the bladder and has been fully reported. I will here only say that the bladder was very intolerant and spasmodic; so much so that 1 introduced but two ounces of fluid before using my lithotrite. The stone was a very small one, and was caught and crushed at once without any difficulty. During this procedure the water was kept in the bladder by a rubber band around the penis. A constant oozing of fluid through the interstices of the instrument showed how great the pressure in the bladder was. When the tube was introduced it was at once found that the water, which went in without resistance, did not return, and it was, therefore, evident that the bladder had ruptured itself. An immediate laparotomy showed that the rupture was extraperitoneal, and that the effusion was under the peritoneum on the left side of the pelvis. This collection of fluid was drained by an incision similar to that for tying the iliac artery, and a drainage tube was also introduced into the bladder through the perineum. The patient recovered, but always continued to have an excessively irritable bladder.

As it is well known that the bladder has been frequently ruptured when distended in a suprapubic operation and that even the rectum has been similarly damaged by the Peterson's bag, it will be seen that this accident is in no way peculiar to the operation of litholapaxy. In fact, the introduction of fluid in litholapaxy is so constantly under the control of the surgeon's hand that he is able to accurately judge of tindegree of distention. It is, therefore, an accident which must occur but rarely, and then only when extremely thinwalled diverticula exist.

The fear that many surgeons have of nipping the bladderwall with the lithotrite has little, if any grounds.

When the bladder contains a proper amount of fluid, its walls are gently stretched, and it is almost impossible to catch them with the instrument, even if the effort is made to do so. The dauger may be wholly avoided by operating in the centre of the base of the bladder. When the heel of the instrument rests at this point, the bladder-walls do not fall into the blades and sufficient space is given for easy manipulation of the instrument without touching them.

INJURY DONE BY OPERATIONS.

I have known of no serious or lasting injury following a litholapaxy. The irritation following the operation quickly subsides, and leaves the patienl nowise worse for the operation.

Suprapubic lithotomy avoids important structures, but occasionally leaves an annoying and obstinate fistula. Perineal lithotomy, by which I mean the lateral incision, has the dis


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[No. 110.


advantages, already alluded to, of occasional impotency, occasional stricture, and rarely of fistula following it. I have seen instances of all of these sequelae, so that litholapaxy has Led advantage in the avoidance of injury.

RECURRENCE OF STONE.

Among these patients are two instances in which a uricacid stone has re-formed in consequence of the persistence of the diathesis that led to its original formation. On one of these patients I operated twice, and upon the other three times.

There are nineteen instances in which a phosphatic stone has appeared some months or years after the removal of a primary stone. In two or three instances the primary stone was a uric acid calculus; in all other cases it was phosphatic.

In six of these cases, the previous operation had been done by some other operator.

This recurrence of a phosphatic stone may be due to the persistently alkaline condition of the urine. Several instances of this sort have come to my notice, the most striking of which was a case of multiple calculi iu which, within a fortnight of a thorough washing out, the bladder would contain from fifty to one hundred little, separate, well-formed stones. This tendency was finally overcome by frequent pumping out of the calculi, combined with medical treatment directed to making the urine acid.

In two or three cases the recurrence may perhaps be regarded as the result of an incomplete operation, leaving a fragment to serve as a nucleus for a new stone. This accident has usually been avoided by care in. washing out the bladder with the evacuator ten days or a fortnight after the litholapaxy. In some eases several washings have been necessary before the bladder was found to be entirely free from calcareous matter.

In one case, of a woman, the projection into the bladder of two stitches put in by two other surgeons, for the closure of the opening made in doing a vaginal lithotomy, led to the repeated recurrence of calculi until the stitches were found ami removed.

In two cases sacculated stones which lay concealed in pockets in the vesical wall gave rise to repeated stone-formation in the Madder-cavity. The removal of the stones loose in the bladder was followed in each case by such a cessation of symptoms that the presence of the encapsulated calculus was not suspected, but it was finally found by a cystotomy done for the purpose of discovering the condition to which the recurrence of the stone was due.

Finally, certain local conditions of the bladder-wall favor the formation of stone and lead to constant recurrences until they are removed.

It is notorious that tumors and granulating surfaces within the bladder are prone to be encrusted with salts. The crystallography of stone-formation is interesting in connection with these cases of calcareous deposit on granulating surfaces.

The crystals that exist in the urine do not tend to cohere and form a stone except in the presence of albuminous material. Rainey showed many years ago that the presence of colloid or albuminoid substances in a solution causes crystalline materials to become spheroidal in shape and to coalesce


in rounded form. This is the law of molecular coalescence which has a very decided bearing upon stone-formation in the bladder.

As long as the urine is non-albuminous, crystals of uric acid or oxalate of lime may form in the urinary passages, be washed along and discharged with the urine without forming a stone. But when albumin is present, either in the pus thrown out in consequence of some irritation or in the serum exuding from a granulating surface, we have conditions favorable to " Molecular Coalescence."

It has frequently been urged by advocates of cutting operations that recurrence of stone is especially prone to occur after litholapaxy, owing to incompleteness in the operation. My experience does not coincide with this view; for the cases of recurrence after litholapaxy have, with one or two exceptions, been shown to be due to a general diathesis or to the local conditions described above. The suprapubic operation, too, is far from being exempt from the opprobrium of failure to prevent recurrence of calculous formation.

I have had one case in which a stone followed a prostatectomy, and in four instances have seen stone-recurrence after suprapubic removal.

But why, it will be asked, should a suprapubic operation. which gives opportunity for the most thorough cleansing of the bladder, leave behind it a tendency to stone formation ?

I thiuk the reason for this is that wounds of the vesical wall do not heal immediately by first intention, but are very apt to leave a granulating spot for a greater or less time : and such a surface, as we have seen, is prone to become encrusted with calcareous material and so serve as the nidus for a new stone.

On one or two occasions after a suprapubic operation, I have washed out the bladder with the result of obtaining a little calcareous matter which presumably had been deposited upon such granulating spots.

In 1889, writing upon the Choice of Operation for Stone in the Bladder, I stated as my belief that litholapaxy should be employed except iu the presence of one of the following conditions :

1. A very large and hard stone may resist every attempt at crushing, especially if it is tightly grasped by the spasmodically contracted bladder.

2. A stone may have as a nucleus a foreign body, such as a piece of necrosed bone or a bullet, too hard to crush and too large to pass out through a tube.

3. An encysted stone may be out of reach of the lithotrite.

4. False passages may exist, which so interfere with the introduction of instruments that the dangers of the operation are greatly enhanced, and the question of lithotomy is to be entertained.

5. The hip may be anchylosed in a position which interferes with the use of urethral instruments.

6. A stone may be so lodged in the prostatic urethra, that it cannot be pushed back into the bladder where it can be seized by the lithotrite.

7. When the constant recurrence of the stone makes it seem probable that an ulcerated patch exists in the bladder


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and is leading to a calcareous deposit, the suprapubic operation is required for the removal of this local condition.

8. In the presence of an obstructing prostate the suprapubic incision will sometimes be advisable, with the object of removing the obstruction. The removal of the stone is merely an incident in this operation.

I have seen no reason, with added experience, to change I bis opinion except as far as is set forth in this paper, in relation


to cases of coincident bronchitis or other condition making etherization dangerous.

I feel that a mortality of four per cent, in a series of cases averaging sixty years of age, is considerably less than could lie expected from suprapubic lithotomy in a similar class of patients, and that the avoidance of fistulas and the shortened convalescence add decided advantages to this method of operating.


SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.


Samuel Theobald, M. 1>. A Case of Extensive Detachment

of the Retina in a Myopic Eye, in which Complete Recovery followed Rest in Bed and the Administration of Pilocarpin. — Archives of Ophthalmology, Vol. XXIX. No. 1, January, 1900.

The treatment was begun within four days of the occurrence of the detachment, and to this fact the successful outcome of the case is, perhaps, in considerable measure, to be attributed. The detachment was so extensive as to preclude an ophthalmoscopic view of the papilla, and sight was reduced to ability to detect movements of the hand in the upper and outer portion of the held. Pilocarpin muriate was given by the mouth in increasing daily doses, beginning with gr. J for nineteen days, the maximum dose reached being gr. j. The patient was confined to bed for two weeks, and kept in the hospital for five weeks. The administration of the pilocarpin was followed by five-grain doses of potassium iodid. Within five weeks of the commencement of the treatment the retinal detachment had markedly diminished, and at the end of three months it had en tirelv disappeaied. ^gradually improved

20 to ,„ +. 'W hen last seen, fourteen months had elapsed since the

reattachment of the retina, and there were no siyns of a recurrence of the trouble.

Diseases of the Lachrymal Apparatus. — Ainerii m

Text-Book of Diseases of the Eye, Em; Nbseand Throat, 1899.

Affections of the External Ear. — American Tt


oj Diseases of the Eye, Ear, Nost and Throat, 1&99. Report of One Hundred Consecutive Cases of Cat


aract Extraction. American Journal of Ophlhah Vol. XVI, No. 12, December, 1899, pp. 353-:;;:..

The cases were in no sense selected, but included two eyes which had previously been iridectomized for glaucoma, two in which there was dislocation of the lens of traumatic origin, one in which t hei e was myopia of high grade with detachment of the retina, three in which the cataract was secondary to syphilitic iridochoroiditis, one in which the lens was shrunken and the iris adherent to its capsule, and one myopic eye in which there had occurred previously an attack of iridochoroiditis.

The operations were divided as follow s :

Extraction with iridectomy 52

Extraction after preliminary iridectomy

(usually accompanied by trituration of lens). 26

Simple extraction 20

Extraction of dislocated lens in capsule. 2

100


The results obtained are summarized as follows : 20 20 \

TT to


Successes Vz


xm/ Successes ( Knot recorded)

Total Successes

Partial Successes f 7=. — to


11


Partial Successes ( V not recorded) 2

Knot improved (though recovery from operation was smooth ) 2

Lossestfrom suppuration) 2

100

Of the two eyes lost by suppuration, one was a highly myopic eye, in which the operation was completed without accident ; the other an eye previously iridectomized for glaucoma, in which the lens capsule was very tough, and the vitreous humor the consistency of water, and in which during the efforts to extract, the lens the whole contents of the vitreous chamber escaped, and the eye collapsed. There were five other cases of escape of vitreous, but in these the loss was inconsiderable, and the success of the operation was not impaired. There were seven well-marked cases of iritis. In 27 cases a secondary operation (discission of capsular opacity) was performed (and in three of these a repetition of the discission was required). In no instance was it necessary to perform a secondary iridectomy or iridotomy.

There were no losses among the 20 cases of simple extraction, and, as to visual results, all were successes except one, in which

the rather poor sight obtained I - ) was due to retinitis hsemor rbagica. There were among them, however, 3 cases of prolapse of the iris, and, while only 2 of these were so extensive as to require abscission, they induced, the author tells us, "A lack of confidence in the method, the outcome of which has been an adherence, for some time past, to the modified Graefe extraction— a section throughout in the sclerocorneal juncture, a narrow conjunctival flap, and a small iridectomy made by a single snip with the scissors."

Thomas 1!. Brown, M. D. Cystitis Due to the Typhoid Bacillus Introduced by Catheter in a Patient not Having Typhoid Fever. — Medical Record, March 10, 1900.

Arthur W. Elting, M. D. Intermittent, Gastric, Hypersecretion, with a Report of a i3ase.— Boston Medical and SurgicalJournal, March 22, 1900.

Howard A. Kelly, M. I>. What Precaution Shall We Take to Avoid Leaving Foreign Bodies in the Abdomen after Operations? — New York Medical Journal, March "J I. 1900.


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[No. 110.


John G. Clark, M. D. A Critical Summary of Recent Literature on the Localization, Diagnosis, Prognosis, and Treatment of Gonorrhoea in Women. — American Journal of the Medical Sciences, January and April, 1900.

Andrew II. Whitridge, M. D. Bradycardia with Intermittent Albuminuria. — Boston Medical and Surgical Journal. March 39, 1900.


George Blumer, M. D. Infectious Character of Tuberculosis and the Prognosis of Incipient Pulmonary Consumption. — Albany Medical Annals, April, 1900.

Thomas McCrae, M. I). Spleno- Myelogenous Leukaemia with Disappearance of the Spleen Tumor and of the Myelocytes from the Blood. — British Medical Journal, March 31, 1900.


PROCEEDINGS OF SOCIETIES.


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY. Monday, March 5, 1900.

In the absence of the President, the meeting was called to order by Dr. Hurd. The Inheritance of Deafness.— Professor W. K. Brooks.

Some of you know, perhaps, that Professor A. Graham Bell, who is identified in the public mind with the invention of the telephone, has never regarded anything of so-called practical value, like the telephone, as his important scientific work. His life has been devoted to a subject that will appeal to us as more important, but which is not so regarded by the public. He has devoted his life to the amelioration of the condition of the deaf.

Many years ago, Professor Bell's attention was attracted to the fact that deaf people marry much more frequently in this country than they do abroad, the easy conditions of our life enabling them to do so to better advantage here than in foreign countries. These marriages are also increasing very rapidly, and he pointed out that this was accompanied by a very rapid increase in the number of deaf; they are increasing much more rapidly than the population at large. He attributed the tendency of deaf people to marry deaf people to our methods of teaching the deaf. We bring together in the community all the deaf children, as well as the hearing ones, and keep them there during the period when acquaintanceships are formed and they naturally learn a sign-language which separates them from the rest of the community. Believing, then, that this tendency of deaf people to marry deaf people might be due to our method of education, he has advocated teaching the deaf children regular speech in the common schools so that they will not be cut off by language or sympathetic fellowship from their associates, and he has thus made a good many bitter enemies among those whose business is the vested industry of teaching the old sign-language. He has been very successful in his efforts, and this method of teaching has been growing successfully, so that while more deaf children are still taught by the old method than by the new one, the latter is steadily gaining ground. Undoubtedly this will to some extent tend to do away with this tendency of deaf people to marry deaf people.

Professor Bell has endowed the Volta Bureau for the Amelioration of the Condition of the Deaf, an institution with a good equipment, and Professor Fay, one of the prominent educators of tiie deaf, has made use of it for gathering statistics


concerning the marriages of deaf people, and he has just published a volume of data which contains more statistical information than has ever been published on this subject before.

One interesting result of his study is to show that the influences that cause deaf people to marry deaf people are much deeper seated than Professor Bell supposed. These new statistics show that of the pupils of the asylums who marry, some two-thirds marry deaf persons. Of the deaf persons taught regular speech by the new method who have married, two thirds have married deaf persons. Of the deaf persons who have been to no institution and who have married, twothirds have married deaf persons. The classes from which these statistics were taken were not of the same size, it is true, but they indicate that there is some psychological influence at work aside from that referred to by Dr. Bell. This report, however, accomplishes another purpose so successfully that it enables us to control the inheritance of deafness by giving deaf persons who contemplate marriage advice that is scientific, and Professor Fay can now advise them how to marry without the danger of transmission of deafness.

The book contains some 600 or 700 pages of statistics and percentages, and some three months ago I had them well in mind, but my mind is very leaky for figures, and I find the percentages are nearly all gone. I cannot, I fear, present them properly now and you must take such figures as I give with a grain of salt, though they will be, I think, substantially accurate. To show how much need there is for care in handling statistics, I may be allowed to tell an anecdote. I published, a little while ago, a review of this very book, and said that it contained a record of 5000 deaf persons who had married. I received a letter from the author saying I was wrong — that the book contained a record of 5000 marriages of deaf persons in which 8000 deaf persons were concerned.

This study, then, of 8000 deaf persons who have married, shows, in the first place, that deaf people are very much more likely to have deaf children than are hearing people, although they are much more likely to have hearing children than deaf children. Taking deaf people on the average, those who marry must expect to have one deaf child if they have eleven children, so that there are ten chances of a hearing child to one of a deaf child, while normally hearing people need not expect one deaf child in ten thousand children. Of course, this one may be the first or it may be the last of the ten thousand children, and the deaf child may be an only child, while the 9999 may be in other families. The liability to deaf children is not equally great with all deaf persons, the character of the


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parental deafness having a great deal to do with it. Some deaf persons who have married deaf persons having large families with no deaf children, while all the children in others were deaf children.

Deaf persons are popularly divided into the congenitally deaf and the adventitiously deaf, the first never having shown any evidence of hearing, the second class having heard, but having lost the ability to hear. Now. when classified m this way there is a probability of transmission in, I think, 30 per cent for the congenital group, and less than 5 per cent for the second group. If it were possible to draw this line with rigorous exactness, if it admitted of any scientific restriction, it would always be highly imprudent for the congenitally deaf to marry, while much less hazardous for the adventitious deaf to do so ; but this line cannot be drawn with exactness. Deafness is never discovered until the child has reached the age when normal children begin to talk. Then, too, many people who lose their hearing through disease, after having once heard, have deaf relatives, which shows that they had a susceptibility to deafness, that it was not purely adventitious, and that possibly from the scientific side it might really have been a congenital deafness. As a matter of fact most persons reported as congenitally deaf can only be said to be supposed to be congenitally deaf, and vice versa. You cannot divide the two classes on that line.

It has been known for a long time that deaf persons frequently have relatives who have deaf children; and Professor Kay has divided these 5000 marriages into two groups, those concerning people known to have deaf relatives, and those not known to have had such. Here the result is remarkable indeed, for deaf persons who have deaf relatives will have nearly 40 per cent of deaf children, while deaf persons without deaf relatives, who marry, will have only 1.2 per cent of deaf children. In a country like this, where very few persons know all their relatives, and where it is possible that it may be very difficult to trace collateral branches thoroughly, perhaps some of these deaf people that are reported to have had no deaf relatives simply had no known deaf relatives, and Professor Fay has stated that in some of his cases this was found later to have been the case. lie thinks that where they have no deaf relatives there is really little more danger of deaf children than happens to normal people; that is, deaf persons without deaf relatives may many with as much safety as ordinary people. Even there we cannot be sure, for deaf persons may have no deaf relatives, because they are not yet born, and deaf persons may have unborn brothers or cousins who will be deaf. As deaf people do not marry, however, until mature, as a rule, that danger is very slight, and it is pretty safe to advise them that they may marry provided they do not marry a mate with deaf relatives. On the other hand, deaf persons with dial relatives should be advised not to marry underany consideration.

It did not fall within the province of Professor Fay to consider, statistically, the hearing persons who have married : but he shows clearly that a hearing person with deaf relatives h just as likely to transmit deafness as is a deaf person ; and it is a little more unsafe fir a hearing person with deaf relal marry than for a deaf person without deaf relatives; so il really becomes a question of the deaf relatives that cause the


danger. Neither deaf persons nor hearing persons with deaf relatives should marry, and they certainly should not marry persons with deaf relatives.

One of the peculiar points brought out is a little difficult to state. It is that deaf persons who marry hearing persons are more likely to have deaf children than those who marry deaf persons, lie says that if all the deaf persons in this list had married hearing persons, the number of deaf children would have been increased 50 per cent. That fact had been suspected for a good while, and Darwin refers to it in his Variations of Animals and Plants Under Domestication, and says that it is very puzzling and cannot be explained at present. An English writer says that intermarriage of the deaf carries the inheritance to such a point of perfection that it topples over of its own weight. That is perhaps only a paraphrase of what Darwin says.

Now, if you look through the whole list of these 10,000 names — for there were 5,000 marriages, though only 8,000 deaf people — you find that many more deaf persons have married hearing persons with deaf relatives than have married deaf j^ersons with deaf relatives. Deaf persons who marry hearing persons, then, tend to marry hearing persons with deaf relatives. and it is no more than you should expect, that the deaf persons who have married hearing persons should have more deaf children than the deaf persons who have married deaf persons ; it is the deaf relatives, remember, that are the index of danger, This result which so puzzled Darwin has received a clear explanation.

One other matter I should like to speak of in this connection. Some twelve years ago I was asked to prepare a discussion on the conditions necessary to produce a deaf variety of the human race. The paper was presented to the Royal Commission for Investigating the Condition of the Deaf in England and was jmblished along with a number of others. I asserted that the only condition necessary was that persons with deaf relatives should marry and continue to marry generation after generation, and that is exactly the result that Professor Fay has arrived at. I was in a hopeless minority at that time. All the other scientific men who prepared papers on this subject holding that all that was necessary was that deaf persons should marry dial' persons for successive generations. Professor Fay's study shows that they were wrong, and my conelusion, reached some twelve years ago, turns out to be exactly what this very great volume of statistics proves, and leads to Professor Kay's advice. Deaf persons who are sure they have no deaf relatives, may marry other deaf persons without deaf relatives, or may marry hearing persons without deaf relatives with impunity; but those who have deaf relatives, whether hearing or deaf themselves, should be discouraged from marrying either deaf or hearing persons who have deaf relatives.

The cases in which the transmission of deafness is greatest and where it rises above 50 per cent is where the parties having deaf relatives, marry these relatives; that is, when the marriages are consanguineous marriages between persons with deaf relatives. The intermarriage of people with deaf relatives is almost sure to result in deaf children, more than half of the children being deaf whether the marriage is between deaf or hearing people.


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[No. 110.


I' lie Exhibition of a Three-months Infant with a Caudal Appendage.— Dr. Watson.

This infant has a peculiarity which I think is of sufficient rarity to be of interest to the Society. It has a tail. Its parents are not proud of it and want it amputated this week, so I exhibit the child to-night without having had time to look up the literature of the subject further than to ascertain that the i t ion is quite rare, although not unique.

It is a healthy male child a little over three months old. The tail springs from where a tail should, just posterior to the anus, and consists of two segments, a longer, thicker, more fleshy proximal segment, and a distal segment which is shorter, thinner and more fibrous. It is covered with normal skin. The length of the tail, when the child was three weeks old, was one and three quarters inches. Forty days later it was two inches and now it is two and a quarter inches long, having grown one half of an inch inside of three months;— apparently out of proportion to the growth of the rest of the body. It seems to have no connection with the coccyx, although it springs from the skin right over its tip. There seems to be no bony or cartilaginous tissue in it. It is well supplied with muscular tissue, and, in fact, the infant seems to express its emotions wiili the tail, for when the child is crying the tail shrinks up one half an inch in length, the distal portion partially telescoping within the proximal one. At other times it lies relaxed at full length or curls out upon the buttocks.

Dr. Harrison and I have secured some excellent photographs of the appendage. When it is amputated, Dr. Harrison will study it anatomically and we will make a further report.

Discission.

Professor Brooks.— The South American Indians say that

the white men wear clothes to cover up their tails. It is the

mi to cill abnormalities of this kind reversions, but it

ns to me very doubtful whether you can regard them as

anything like harking back to an ancestral type. Man, like all

mammals, has a well-developed caudal region in the embryo,

and its persistence is, I should think, simply a retardation of

lopment. Normally, the tail stops growing at a very early

■■: and. becoming very small and insignificant, forms the

rudimentary coccyx. If that does not take place, there is a

retention of the normal embryonic condition.

In this particular case you would have to go very far back to prove that there was harking back. The anthropoidal apes have no more tail than man, and you would have to go back considerably beyond the primitive condition of these apes to find anything like a tail. It does not look possible that that could be the explanation when we have at hand such a simple explanation as the one I have given. You do not suppose that a hairlip is a throwing back to the condition of rodents; it is simply a persistence of embryonic conditions.

Specimens of Cystic Kidneys. -De. MacCallum.

Dr. Osier asked me to show one or two specimens from the museum. Cystic kidneys fall into two groups as he has mentioned, one like those passed around and one that occurs congenially. The appearances as you see are rather different. The cysts as seen in childhood usually contain clear contents


and are of a different color. In connection with this, too, one usually finds some other changes. Here is the child from whom these kidneys were taken. There was a condition of hydrocephaly, and there were seven or eight fingers or toes on each hand or foot. The kidneys may be large enough to cause obstruction to birth, and in this case they had to be removed before the child could be delivered.

There are two theories as to their origin — the inflammatory, as described by Virchow, who thought the cyst-formation really the result of retention due to marked interstitial nephritis about the pillar of the kidney, and the noninflammatory theory advocated by those who consider the cyst due to constriction of the tubules higher up as the result of chronic troubles; other authors think that the mere weakness of the walls of the tubules allows of the retention.

The French authors usually adopt the neoplastic theory, believing that it is simply due to proliferation of tissue bringing about the cystic growth. They describe them as adenocystoma.

Shattuck ascribes the formation of the cyst to the malposition of portions of the Wolffian body in the kidney, but some work recently done tends, I think, to rather disprove that. Rindfleish ascribes it to failure of union of the cortical tubules with those of the medulla.

In connection with the cystic kidneys found in adults, as Dr. Osier stated, we sometimes find cysts in the liver, and here is a specimen which illustrates it. This is the kidnev from a case seen by Dr. Thayer, which came to autopsy some time ago, and is almost exactly like the one passing around, but the liver in that case showed numerous small cysts.

Monday, March 19, 1900.

The meeting was called to order by the President, Dr. Thomas.

Idiopathic Dilatation of the Colon.— Dr. Fitcher.

This case is one of considerable interest. Usually rare cases come in pairs. Some time ago we had in the Hospital a case of dilated colon, which is now followed by this child with the following history: He is four years of age, and was born in Massachusetts. There was nothing especiallv remark'able about the child in the first few months. He seemed to be mentally a bright child for his age. At one year of age it was noticed that the abdomen was very large and its appearance soon became the talk of the neighbors. In 1898, he was taken to the Holyoke Hospital, where he remained under observation for a considerable time. Previous to that the child had been very constipated, going for six or seven days without a movement, and then such periods would be followed by severe attacks of diarrhoea. The movements were usually of a drab or whitish color. When constipated the child was especially dull, but at other times did not suffer and seemed quite bright mentally. Fortunately for the little fellow he was well taken care of by a nurse who became interested in the case, and up to the present time he has been carefully attended to, and has not been suffering. He has been getting irrigations twice a day.

Tie boy has a markedly distended abdomen, but not so


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much now as when he came to us a week ago. There was then a very striking distention of the upper part of the abdomen, particularly above the level of the umbilicus. The abdomen is fairly symmetrical, and you see the child is well-nourished, and intelligent-looking. If you look at the child from the side you will see how pendulous the abdomen is, and how the distention is greater above the level of the umbilicus than il is below. No definite peristalsis can be made out even by stimulating with a cold towel. While under treatment during the last week he has been getting daily irrigations, and with each a fairly large constipated stool was passed. He seems quite comfortable except that the irrigations occasionally cause some irregular contractions, and at such times he complains of pain. The abdomen is now a little softer than on admission, and no fecal concretions can be made out by palpation, but that is not an indication that none are present, because the same condition was noticed in our other case, which was eventually found to have a large amount of fecal concretion in the colon.

The case is one of so-called idiopathic dilatation of the colon. There are three or four different types of colon dilatation. In the first class may be placed those cases in which there is simple gaseous distention. In the second group come those cases in which there is distention of the colon from contents of some form, either fecal, or foreign bodies introduced from without and more rarely by gall-stones. In the third group are those cases which result from organic obstruction in front of the distended bowel. Then there is the fourth group of so-called idiopathic dilatation of which this is the type.

Some believe that in these so-called idiopathic cases there is some actual constriction or stricture of the bowel in the region of the sigmoid flexure. Treves, I believe, holds this view and believes that it is always present. The colon becomes very markedly hypertrophied, that is, the muscular tissue of the wall is very much increased in thickness, but in the majority of cases no change has been observed in the mucosa.

One of the most remarkable cases is that reported by Formad in the University Medical Magazine, Vol. i. It was a case of a dilated colon in a man 23 years of age. He was known as the " balloon man," which was an appropriate name as shown by the illustrations which I show you. The colon in this case was of enormous size, being as large as that of the ox, and when removed, weighed 47 pounds.

As to treatment there is not very much that can be done, and the cases generally terminate fatally early in life. If kept under careful observation, they may live with comfort for a considerable number of years. Surgical interference is advisable in some cases. Treves had a case in which he excised the greater part of the colon with a successful result. The operative procedure usually performed for relief of the symptoms is that for an artificial anus.

I will pass around photographs of the colored boy whom we had in the wards recently. In his case there was pronounced peristalsis which is usually a marked feature. This boy had an enormous abdomen. Passing up over the left half of the abdomen, crossing its upper part and occupying the right


hypochondrium was an enormously distended portion of the bowel which we believed was the sigmoid flexure, and which proved at operation to be such. This patient had the condition since he was eight years of age, and was fourteen years old when operated upon. He, too, gave the history of alternate constipation and diarrhoea. When he entered the hospital he had not had a movement for fourteen days. He was operated upon, the sigmoid flexure being excised, but unfortunately peritonitis set in and the boy died. The colon was enormously dilated, measuring -19 cm. at its greatest circumference. It contained large quantities of semifluid feces. At autopsy the colon contained about eight quarts of semisolid feces.

The advisability of a colotomy in this case is being considered.

Report of Gynecological Cases. — Dr. Miller.

Case 1. — Acute gonorrheal peritonitis. The patient was a young woman married just two months whose husband gave a history of having been treated in the dispensary here for two years for gonorrhoea. He had been pronounced cured by a competent assistant after repeated examinations of the slight discharge that still existed. Two months after marriage, at the menstrual period, the patient developed severe pain in the pelvis and the discharge was more profuse than usual. The pain occurred especially on the right side. In a few days the abdomen became distended and she had nausea, vomiting, elevation of temperature, and in fact all the signs of general peritonitis. She was sent into the hospital and operated upon by Dr. Kelly.

The entire picture and operation was that of peritonitis and the infection had evidently come through the tubes both of which contained pus which was discharging into the abdominal cavity. Both tubes were removed and she made an uninterrupted recovery. Although coverslips were negative and cultures on ordinary agar proved negative, I think it was a gonorrheal infection. The infection came through the tubes. and to a woman who has never been pregnant there are practically only two kinds of infection through the tubes; first, gonorrheal, and second, tubercular. I believe if we had had the proper media we should have grown the gonococci.

Case 2. — Ovarian abscess with general peritonitis. In this case there was general peritonitis with pockets of pus in either flank, and free pus in the peritoneal cavity. She recovered after washing out the peritoneal cavity and removing the uterus and both tubes. She had always been healthy, but her periods had been irregular and painful. She had three miscarriages, the first two giving no trouble, but the third was the beginning of the present illness. Tenderness was excessive in both groins. No swelling had been noticed, but when she came in we found a lump in the lower part of the abdomen. Examination showed a pelvic mass on left side about the size of a large orange and intimately connected with the uterus. At operation the peritoneal cavity contained pus and there was a fibrinous deposit on all the intestines. There was a large abscess of the tube and ovary of the left side, which contained a yellowish brown offensive pus. The right ovary \\-.\and adherent. Enucleation was done in the usual manner, but the patient's condition became so bad on the table that the pus


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[No. 110.


was imperfectly removed from the peritoneal cavity and a drain had to be placed in the pelvis. The pulse was so rapid aud weak that she had to be infused repeatedly for the first night, but after that her recovery was satisfactory. The offensive odor of the pus led me to believe it was a colon-bacillus infection, but coverslips aud cultures were both negative.

Case 3.— Suppurative Ovarian Cyst with Forma/ion of Gas in.-iile the Cyst. The patient was a woman forty-three years of age, who had been admitted ten years previously on the medical side, but having refused operation for the removal of the cyst was discharged. She had severe pains at times, but kept her health pretty well until the last four months. When she came in she looked septic and was very weak. The elevation of temperature was uot very marked. A tumor mass could be made out extending down into the pelvis and up into the abdominal cavity. It was tympanitic over nearly the whole of its surface. This complicated the diagnosis very much. At operation the tumor was found to be an ovarian cyst densely adherent to the abdominal wall and intestines and having a very thick wall. Incision was made into the cyst and there was an immediate escape of gas and a very offensive brownish necrotic material containing some pus. Coverslips showed a bacillus that was thought to be too small for the gas bacillus, and cultures were negative. Five days alter the operation cultures were again made and showed the colon bacillus, but probably that was not the nature of the original infection. She has improved greatly in general health, and the whole interior of the cyst- wall is gradually sloughing away.

NOTES ON NEW BOOKS.

Thirtieth Annual Report of the Massachusetts State Board of Health. (Boston : Wright & Potter Printing Co., 1899.)

This report contains about nine hundred pages of matter describing the work done under the direction of the Board for the year ending September 30, 1898.

The general contents and arrangement of the report are similar to those with which the many who appreciate the work of this Board have been familiar in past years.

It is a commendable characteristic of New England that the membership of efficient government boards is left unchanged from year to year in recognition of their services- The death of Dr. Charles P. Worcester, Chief Analyst in the Food and Drug Department, after ten years' service must lie chronicled with regret.

The year 1898, in Massachusetts, was characterized by the greatest freedom from epidemics with one or two exceptions in the last half-century.

The typhoid death-rate has been reduced from 8.2 in 1871-75 to 2.5 during 1808. In this connection it may be noted that the work of Mark \V. Richardson, in confirming for Massachusetts the observations of earlier investigators elsewhere, has called renewed attention to the transmission of typhoid fever through the urine of otherwise recovered typhoid patients. Richardson found typhoid bacilli in the urine in such cases in about 2-5 per cent of those examined, the bacilli persisting sometimes for considerable periods. The fresh urine may be even cloudy with organisms. It is a simple matter to " plate out," and to test the colonies thus isolated with typhoid serum or blood. This is worth the consideration of health officials in districts where typhoid is prevalent and water supplies are not well guarded indicating a possible method of cultural release from isolation on the same general principles as the release of diphtheria cases.


In diphtheria, the fatal ty for the pre-antitoxin, four-year period (1891-1894), was 28.3 per cent of cases ; for the antitoxin period (1895-1S98) 15 6 per cent.

In consumption it is gratifying to note a steady decrease. The classification of this disease, now universally regarded as distinctly infectious, under the " zymotics" is justly criticized, but is nevertheless retained in Massachusetts. Still this classification is not quite so bad as the retention of "alcoholism" under the same heading — a classification which seems crude if not absolutely barbarous— and only recently abolished. A State hospital for consumptives has been established. As illustrating the progress of sanitation in this disease, it is not out of place to note that Boston has now (1900) joined the list of cities in which the reporting of pulmonary tuberculosis is compulsory and in which disinfection is performed by the Board of Health after the death or removal of the tubercular patient. Combined with the supervision of tuberculosis in schools, these advances should contribute powerfully to the further reduction of cases in the future.

An outbreak of dysentery was investigated by O. Richardson, with the result that an organism regarded as B. coli com., but unusually virulent, was isolated and considered as the pathogenic organism.

Under Filtration of Sewage, a good account of experimental work on the '"septic tank" method for purification is given. While acknowledging that the present firm establishment of an unfortunate nomenclature in the literature of this subject makes it now somewhat difficult for isolated writers to introduce more appropriate terms, we think that the State Board of Health of Massachusetts carries sufficient weight in the scientific and sanitary world to make it well worth while for that Board to suggest a new phraseology. For instance, "septic" tank as a name for the receptacle in which bacterial decomposition of the sewage takes place might better be changed to '" decomposition " tank. We feel particularly disposed to criticize the use of the term " toxin " in the statement made on page 442 to the effect that the formation of toxins in sewage is illustrated by the formation of gas under certain circumstances. Certain products of bacterial activities are classed as ptomains. Only such ptomains as are capable of producing toxic effects on animals are designated as toxins. It may be that the products of the bacterial decomposition of sewage are toxic to animals, but the experiment described certainly fails to illustrate or demonstrate such toxicity.

Mr. H. W. Clark contributes a paper describing a large number of experiments on the action of various waters on lead pipe, designed to determine the relation between the substances originally in solution in the water and the degree of action on the lead. It was shown that in general the active agents are oxygen and carbon dioxid, and that the purer the water, the greater the action. In waters showing high hardness, the action of the oxygen and carbon dioxid was reduced. Waters high in organic matter may not attack lead until the organic matter is decomposed and carbon dioxid thus set free Iron, galvanized iron, zinc and block tin were also experimented with.

The engineers of the Board contribute a paper reviewing the working of the sewage filtration plants at present in operation in the State.

Under Food and Drug Inspection, the comforting assurance is given that the staples are almost never adulterated, and that the adulteration, when it is found, is rather commercially fraudulent than physiologically harmful. For instance, one hundred and forty-five samples of wheat flour tested yielded adulteration in only five instances, consisting only of a small percentage of corn flour. The cost of this inspection was about $11,0(10 for the year. As the daily ration of the State is estimated to cost $625,000 and for the year therefore $228,125,(00, it will be seen that the very valuable supervision of the supply costs but .005 per cent of the value of the material supervised. The articles most liable to adulteration are


May, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


117


milk, butter, spices, coffee, syrups, molasses, cream of tartar, honey, vinegar, jellies, jams, olive oil and certain kinds of canned goods. Preparations of foods for diabetic patients, advertised as starch-free or nearly so, showed in the majority of cases a larger percentage of starch than the limit claimed and sometimes as much as is present in ordinary wheat flour.

The report of the bacteriological laboratory is restricted to an account of the antitoxin results for the year and of the diagnostic work on diphtheria, tuberculosis and malaria. By an oversight in proof-reading, the tables (pp. 73S-740) giving the results of the diphtheria cultural examinations have been made to show the doubtful results as reaching about one-third of the total cultures. The figures given under the heads of " Doubtful Cultures," and " Cultures Examined for Release from Quarantine," should be transposed, thus making the doubtful results only about 1 per cent.

Dr. S. W. Abbott contributes an exhaustive Life Table for Massachusetts.

The Series c-f Annual Reports from this Board are of such a uniformly high order that one can find but little to criticize. Compared with similar reports from other sources, these stand almost or quite at the head. Compared amongst themselves, however, we detect in the last two or three years a distinct dropping off in the contributions on original investigation which made former reports so valuable to others than statisticians, as well as to the latter. AVe should be glad to have a detailed account of the making of the various antitoxins carried out with such success by Dr. Theobald Smith. We think that a bacteriological investigation of the waters of the State, so thoroughly worked over on the chemical and " biological " sides, would furnish much information. With the improved technique, and the clearer conception of bacteriology developed of late years, a great deal of the disheartening confusion which exists in the present records of water bacteriology might be cleared up by a prolonged systematic and carefully worked out examination of the species to be found.

In ridding the State of typhoid-polluted water a great advance has been made, but doubtless there still remain some minor sanitary questions in the same line. The epidemic of dysentery already referred to suggests one of these.

In conclusion, we may again congratulate the Board upon this continued evidence of the excellence of their work.

HlBBERT WlNSLOW HlLL.

The Anatomy of the Brain. A Text-book for medical students. By Richard H. Whitehead, M. D., Professor of Anatomy in the University of North Carolina. Illustrated with forty-one engravings. (The F. A. Davis Co., 1900, pp. 1-96.) Dr. Whitehead has done a real service to the medical students of America in preparing this volume. The surface anatomy of the various parts of the brain is first described, the classification of His and the nomenclature of the Basel Commission being adhered to. This is followed by a description of the internal anatomy of the same parts, the text being everywhere illustrated by somewhat schematic but accurate drawings. A section on the various conducting paths in the brain terminates the volume. The language is everywhere clear and simple, and the descriptions are systematically arranged. The student will find in this volume the simplest and at the same time the most accurate and concise introduction to the study of the anatomy of the brain in English.


BOOKS KECEIVEI).

A System of Medicine. By many writers. Edited by Thomas Clifford Allbutt, M. A., M.D., LL. D., D. SC, F. R. < . I'.. F. R.S., F. L. S., F. S. A. Volume IX. Mental Diseases and Diseases of the Skin. 1900. 8vo. XII +998 pages. The MacMillan Company, New York. MacMillan & Co., Ltd., London.


The Journal of Experimental Medicine. Edited by William H.

Welch, M. D. Volume IV. AVith thirty plates and seventeen

figures in the text. 1899. 8vo. XII+ 654 pages. D. Appleton

and Company, New York. The Johns Hopkins Hospital Bulletin. A'olume X. 1899. 4to. 240

pages. The Johns Hopkins Press, Baltimore. Refraction and How to Refract, including sections on Optics,

Retinoscopy, the Fitting of Spectacles and Eye-glasseB, etc.

Two hundred illustrations, thirteen of which are colored.

1900. Svo. XII +301 pages. P. Blakiston's Son & Co.,

Philadelphia. Transactions of the Washington, Obstetrical and Gynecological Society.

A'olume A'. October 4, 1895 to June 16, 1899. 8vo. 456 pages. The International Text-Book of Surgery. By American and British

Authors. Edited by J. Collins AA r arren, M. D., LL. D., and A.

Pearce Gould, M.S., F. R. C. S. Volume I. General and

Operative Surgery, 947 pages. A'olume II. Regional Surgery,

1072 pages. 1900. Svo. AV. B. Saunders, Philadelphia. Surgical Pathology and Therapeutics. By John Collins Warren,

M. D., LL. D. Second edition, with an appendix. Illustrated.

1900. Svo. S73 pages. W. B. Saunders, Philadelphia. Saint Thomas' Hospital Reports. New series. Edited by Dr.

Hector Mackenzie and Mr. G. H. Makins. A'olume XXA r II.

1899. Svo. 483 and 120 pages. J. & A. Churchill, London. Catalogue of the Anatomical and Pathological Preparations of Dr.

William Hunter, in the Hunterian Museum, University of Glasgow. Catalogue prepared by John H. Teacher, M. A., M. B., C. M. Two volumes. 1900. Svo. LXXA'II + 943 pages. James MacLehose & Sons, Glasgow.

A Pocket Medical Dictionary giving the Pronunciation and Definition of the Principal Words used in Medicine and the Collateral Sciences, etc. By George M. Gould, A. M., M. D. Fourth edition, revised and enlarged, 30,000 words. 1900. 16mo. 837 pages. P. Blakiston's Son & Co., Philadelphia.

Twentieth Century Practice. An International Encyclopedia of Modern Medical Science by Leading Authorities of Europe and America. Edited by Thomas L. Stedman, M. D. In twenty volumes. A'olume XIX. Malaria and Micro-organisms. 1900. Svo. AVilliam AVood and Company, New York.

Elements of Clinical Bacteriology. For physicians and students. By Dr. Ernst Levy and Dr. Felix Klemperer. Second enlarged and revised edition. Authorized translation by Augustus A. Eshner, M. D. 1900. 8vo. 441 pages. AV. B. Saunders, Philadelphia. '

Report relating to the Registration of Births, Marriages and Deaths in the Province of Ontario for the year ending 3\sl December, 1898. Printed by order of the Legislative Assembly of Ontario.

1900. 8vo. 50 + CCXXII pages. Warwick Bros. & Rutter, Toronto.

Essentials of Surgery. Together with a full description of the Handkerchief and Roller Bandage. Prepared especially for students of medicine. (Saunders' Question Compends, No. 2.) By Edward Martin, A. M., M. D. Seventh edition, revised and enlarged. AA'ith an Appendix. Illustrated. 1900. 12mo. 312 pages. W. B. Saunders, Philadelphia.

An Essay on the Nature and the Consequences of Anomalies of Refraction. By F. C. Donders, 31. D. Revised and edited by Charles A. Oliver, A.M., M. D. (Univ. Pa.). 1S99. Svo. VIII + 81 pages. P. Blakiston's Son & Co., Philadelphia.

Diseases of the Nose and Throat. By J. Price-Brown, M. B., L. R. C. P. E. Illustrated with 159 engravings, including 6 full-page color-plates and 9 color-cuts in the text, many of them original. 1900. svo. XX -471 pages. The F. A. Davis Company, Philadelphia, New York, Chicago.


118


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[No. 110.


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS' HOPKINS HOSPITAL REPORTS. Volume I. *23 pages, V9 plates.

Report in Pathology- \

The Vessels and Wallsof the Dog's Stomach; A Study of-the' Intestinal Contrset.on;

HeXg of Internal Sutures; Reversal «l the Intestine; The Contraction of

Vena Portae and its "Influence upon the Circulation. By F. P. Mall, m. u A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

Re.4u!a?e P d hy Tissue'a H nfl t s , Re^tTon E \o M the 3 -Connecti T e tissue Fibrils. By F. P.

Mall, M. D. Report in Derruaitology.

Two Cases of Protozoan (Coccidioidal) infecttoiTor the Skin and other Organs. By T. C. Gilchrist, M. D., and Emmet Rixford, M. D. Varieties of

A Case of Blastomyces Dermatitis in Man; Comparisons of the Two v "ieries <* Protozoa, and the Blastomyces found in the preceding Cases with th so called Parasites found in Various Lesions of the Skin, etc.; Two Cases of Momisc urn F?b™sum; The Pathology ofja Case of Dermatitis Herpetiformis (Duhnng). By T. C. Gilchrist, M. D. >

Report in Pathology.

An Experimental Study of the Thyroid Gland of Dogs, with especial consideration of Hypertrophy of this Gland. By W. S. Halsted, M. D.

Volume II. 570 pages, with 28 plates and figures.

Report in Metlicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with Gallstones. By William Osler, M. D.

Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D.

On Pyrodin. By H. A. Lafledr. M. D.

Cases of Post-febrile Insanity. By William Osler, M. D.

Acute Tuberculosis in an Infant of Four Months. By Harrt Toulmin, M. U.

Rare Forms of Cardiac Thrombi. By William Osler. M. D.

Notes on Endocarditis in Phthisis. By William Osler, M. D. Report in Medicine.

Tubercular Peritonitis. By William Osler, M. D.

A Case of Raynaud's Disease. By H. M. Thomas, M. D.

Acute Nephritis in Typhoid Fever. By William Osler, M. D. Report in Gynecology.

The Gynecological Operating Room. By Howard A. Kei.lt, M. D. „„„.„„

The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard A. Kellt, M. D.. and Hunter Robb, M. D. ,_.„,«,_>. „i»».

The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of Abdominal Section. By Howard A. Kellt, M. D.

The Management of the Drainage Tube in Abdominal Section. By Hdnter Robb,

The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kellt, M. D. Report of the Urinary Examination of Ninety-one Gynecological Cases. By Howard

A. Kellt, M. D., and Albert A. Ghriskey, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kellt, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kellt, M. D. Myxo-Sarcoma of the Clitoris. By Hunter Robb, M. D. Kolpo- Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kellt, M. D.

Report in Surgery, I. The Treatment of Wounds with Especial Reference to the Value of the Blood Clot

in the Management of Dead Spaces. By W. S. Halsted, M. D. Report in Neurology, I. A Case of Chorea InBaniens. By Henrt J. Berklet, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By August Hoch, M. D. A Case of Cerebrospinal Syphilis, with an unusual Lesion in the Spinal Cord. By

Henrt M. Thomas, M. D.

Report in Pathology, I. Amoebic Dysentery. By William T. Councilman, M. D., and Henri A. Laflece, M. D.


Volume III. 766 pages, with 69 plates and figures.

Report in Pathology.

Papillomatous Tumors of the Ovary. By J. Whitridoe Wi..liams, M. D.

Tuberculosis of the Female Generative Organs. By J. Whitridoe Williams, M. D. Report in Pathology.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Fleiner, M. D.

The Cerebellar Cortex of the Dog. By Henrt J. Berklet, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugdta Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A Kellt, M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mart Sherwood, M. D.

Intestinal Worms as a Complication in Abdominal Surgery. By A. L. Stavely, M. D.

Gynecological Operations not involving Celiotomy. By Howard A. Kellt, M. D, Tabulated by A. L. Stately, M. D.


The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kellt, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina with Haematokolpos and Haematometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anaesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kellt, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.

Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.

By William Osler, M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetbon, M. D.

Report in Neurology. Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of Mus musculus; The Intrinsic Nerves of the Thvroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley, M. D.

Report in Surgery. The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology. Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. Cullen, M. B. Report in Pathology. Deciduoma Malignum. By J. Whitridoe Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetbon, M. D. A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Blumer, M. D., Simon Fleiner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.


Volume VI. 414 pages, with 79 plates and figures.

Report in Neurology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory.— Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I.— Alcohol Poisoning.— Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol); Part II.— Serum Poisoning.— Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part III.— Ricin Poisoning.— Experimental Lesions Induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia.— Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V.— Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Pathology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S. Cullen, M. B. , „

Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of Ovum and Spermatozoa. By Thomas S. Cullen, M. B., and O. L. Wilkins, M. D.

Adeno-Myoma Uteri Diifusum Benignum. By Thomas S. Cullen, M. B.

A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infanta. By William D. Booker, M. D.

The Pathology of Toxalbumin Intoxications. By Simon Flexnir, M. D.

Volume VII. 537 pages with illustrations. (Now ready.)

I. A Critical Review of Seventeen Hundred Cases of Abdominal Section from the standpoint of Intra-peritoneal Drainage. By -I. G. Clark, M. D. II. The Etiology and Structure of true Vaginal Cysts. By James Ernest Stokes, M. I). III. A Review of the Pathology of Superficial Burn- with a Contribution to our Knowledge of tin- Pathological changes in the organs in cases of rapidly fatal burns By Charles KT/SSELL Bardben, M. 1>. IV. The Origin, Growth and Fate of the Corpus Lutenm. By .1. G. Clark, M. D. V. The Results of Operations for the Cure of Inguinal Hernia. By Joseph C. Bloodgood. M. 1).

Volume VIII. About 500 pages with illustrations. (In

press.)

Studies in Typhoid Fever.

Bv William Oslsr, M. I'.. with additional papers bv J. M.T. Finney. M.D., S. Flexner, M. D.. I. P. Lyon. M. D., L. P. Hamburger, m. D., H. W. Cushing. M. D., and J. F

Siitchkll, M.D.

The price of a set bound in cloth [Vols. I-TII] of the Hospital Reports is $35.00. Vols. 1. II ami III are not sold separately. The price of Vols. IV. V. VI and Til is $5.00 each.

Subscriptions for the above publications may be sent to

The Johns Hopkins 1'kkss, Baltimore, Md.


The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured from Messrs. CUSH1NG & CO. and the BALTIMORE NEWS COMPANY, Baltimore. Subscriptions, §1.00 a year, may be addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE ; single copies will be sent by mail for fifteen cents each.


BULLETIN


OF


THE JOHNS HOPKINS H



AL


Vol. Xl.-No. MM


BALTIMORE, JUNE, 1900.


[Price, 15 Cents.


CONTBH'TS.


Notes on the Plague in China and India. By Joseph Marshall Flint, 119

A Study of Christian Science. By Harry T. Marshall, M. D., 128

Twenty-fifth Anniversary of Dr. Welch's Graduation, .... 135

Contributions to the Science of Medicine Dedicated by his


Pupils to William Henry Welch on the Twenty-fifth Anniversary of his Doctorate, 138

Summaries or Titles of Papers by Members of the Hospital and Medical School Staff appearing Elsewhere than in the Bulletin, 147

Notes on New Books, 147

Books Received 147


NOTES ON THE PLAGUE IN CHINA AND INDIA/

By Joseph Marshall Flint, The Johns Hopkins University.


Aside from the recent outbreaks of Bubonic Plague which have attracted such widespread interest in themselves, there is something in the historical associations of the disease that has lent to them an added interest. Probably no other medical subject has been so extensively used for literary material as the Pest, for the dramatic and harrowing episodes of the great epidemics have afforded ideal material for descriptive writers who have availed themselves of its riches again and again. Thus Boccaccio, Defoe, Gibbon, Hodge, and othersf have described the havoc it played in Europe when it was known as the Black Death. Accordingly, when, with the Philippine Commission, in Hong-Kong and later in Didia we had an opportunity of seeing the disease, it was evident that the facts of its epidemiology and environment were quite as interesting and certainly more dramatic than the clinical and pathological features of the disease itself.

The last recorded epidemic of note was that which occurred in Egypt in about 1825, and from that time to the outbreak in


  • I wish to express my indebtedness to Prof. Simon Flexner and

to Prof. L. F. Barker for permission to report these notes on the plague which were made while the Philippine Commission was on its trip.

f Boccaccio: The Decameron. Introduction. Defoe: The Journal of the Plague Year. Defoe: Due Preparation for the Plague. Hodge: Loimologia. Vincent: God's Terrible Voice in the City. Boghurst : Loimographia. Pepys : Diary. June 7th, 1665, to Jan. 19th, 1666.


Hong-Kong, the disease has been endemic in the central portion of China. Not much attention was paid to it, however, until HopperJ noted its existence in Yunnan. He says : " Despite of such a favorable climate, Meng-tzu, in common with other parts of Yunnan, has suffered annually for a period of years from the plague, a kind of malignant fever, fatal in a few days, having as one of its symptoms a hard swelling in the neck, in the armpits, or in the groin, which has carried off a number of its inhabitants. On approach of the epidemic, the first victims are rats, which, fearless of human beings rush madly into their presence, and after capering around the room fall dead at their feet." From Yunnan the disease traveled to Pakhoi by one of the common trade routes, where according to Lowry and Horder, it has been endemic for over twenty years. In 1891, it broke out in Kao-chao, later in towns situated on the West River, and finally in 1894, a severe outbreak occurred lower down in Canton. Now, the infection of HongKong proceeded either from Pakhoi or Canton ; but inasmuch as Pakhoi is more than three times as far from Hong-Kong as Canton, and the Hong-Kong commerce with the latter port is hundredsof times greater than t hut with the former, it is probable that Canton was the source of contagion. Supporting this view is the following significant fact : On the second of March, 1894, a large Chinese procession was held in Hong-Kong, which was attended by over 40,000 Cantonese coolies of the lower class.


J Imperial Maritime Customs, Annual Report, 1889.


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[No. 111.


At this period, tens of thousands were dying of the plague in Canton, and accordingly it is not improbable that the Island of Hong-Kong was inoculated then.

The first cases appeared in the district of Tai-ping-shan where the sanitary conditions are worse than in any other part of the city. (Properly speaking the city is called Victoria and the island Hong-Kong, but the latter name is now commonly used for the city as well.) In the native and European quarters of the city, Hong-Kong presents a strange contrast, for the European districts, from a sanitary point of view, are probably unexcelled in any city in the Orient; but the native quarter, notwithstanding some fairly broad, clean streets and new buildings, is really a whitened sepulchre. Here, in the tenements and side alleys, the coolies live in indescribable filth ; the segregation and overcrowding being so great that at night the overflow sleeps in the streets. Many of these in the native districts are so narrow that one walking with outstretched arms cau almost toueh the buildings on opposite sides of the road. The houses are three or four stories high and originally contained fairly large-sized rooms. The Chinaman, however, with his naturally frugal mind, subdivides them by cheap wooden partitions, and makes four rooms for one. With the decrease in the size of the rooms goes an increase in the number of their occupants, so that in one poorly ventilated tenement from 30 to 40 natives are huddled together, with less than 150 cubic feet of air-space per capita. As yet the coolie has not learned even the rudiments of personal hygiene, and the Chinese enjoy the unenviable distinction of being one of the filthiest peoples on the face of the earth. Apropos of this trait, some one has fitly called them practical Malthusians. One day in Hong-Kong we counted 14 coolies pulling and pushing a meat-cart that could have been drawn easily by a single horse; so, in a country where man and the horse show in a commercial ratio of 14 to 1, little in the way of civilization or personal aesthetics can be expected. As a rule the common coolie never cleans either himself or his houses.

In speaking of these questions Lowson* says : "At the beginning of the outbreak a majority of the houses were in filthy condition. When to a mixture of dust, old rags, ashes, broken crockery, moist surface soil, etc., is added faecal matter, and the decomposing urine of animals and human beings, a terribly unsanitary condition of affairs prevails; and that this is no overdrawn picture of what was to be met with in Tai-ping-shan, many Europeans now know to their cost." One must recall, moreover, that Hong-Kong is Europeanized China, and that the conditions prevailing there do not compare with those found in Canton, for example — a typical Chinese city like those in other parts of the celestial Empire. Indeed, in comparing it with Canton, there is something almost Utopic about the sanitary condition of the native quarters of Hong-Kong.

Once begun, the epidemic was fought by the following general sanitary measures : (1) Removal of the sick and dead. (2) Temporary segregation of those exposed while the premises were being disinfected. (3) Cleansing and disinfecting of "infected premises." (4) Disinfection of clothing. (5)


  • Lowson: J. The Epidemic of Bubonic Plague in 1894.

Medical Report, Hong-Kong, 1895.


General cleansing and limewashing of all tenement houses. (6) House-to-house visitation. (71 Disinfection of public latrines. These measures were all carried out with a considerable degree of success — much more success than attended the similar ones established later in India. This is due partly to the fact that the Chinaman is more easily bullied by sight of power than the Hindu, and partly because the customs offended by the plague regulations are, in China, for the most part merely personal and are neither national nor religious.

During the height of the epidemic the medical staff had more to do than it could accomplish, but by the aid of a number of British soldiers, especially assigned to plague duty, managed to keep up the routine work necessitated by the sanitary plague regulations. In this work the greatest opposition came from the unwillingness of the Chinese to send patients into the hospitals and the resistance they made to house-to-house inspection. In the secretion of cases, moreover, they often went to unheard-of extremes, and the district inspectors in their search for patients often saw sights that it seems almost impossible to believe. Dr. Lowson says, for example: "To overpaint the pitiable surroundings associated with plague work at the commencement of the epidemic would be impossible. I have entered a long, low cellar, without any window opening, and with air entering only by a square open shaft from the level of the roof three or four stories high. Down one side of the shaft ran a broken earthenware drain-pipe, leaking freely, the contents streaming down the wall of the air-shaft to a shallow pool of filth which crossed the undrained floor of earth. Although it was broad daylight outside, a lantern was necessary to see one's way. On a miserable sodden matting, soaked with abominations, there were four forms stretched out. One was dead, the tongue black and protruding. The next had the muscular twitchings and a semicomatose condition heralding dissolution. In searching for a bubo we found a huge mass of glands extending from Poupart's ligament to the knee-joint. This patient was beyond the stage of wild delirium. Sordes covered the teeth and were visible between the blackened and parted lips. Another sufferer, a female child about 10 years old, lay in the accumulated filth of apparently two or three days, unable to speak owing to the presence of enlarged cervical glands. The fourth was wildly delirious and was constantly vomiting. The attendant — the grandmother of the child — had a temperature of 103° F. and could only crawl from one end of the cellar to the other. She was wet through and was herself doomed. This is no fancy sketch but a true picture of how we found some of the patients at the outbreak of the scourge in Hong-Kong. No one unfamiliar with the horrors of the coolie accommodations in China, could credit how the poor live in Hong-Kong, or could imagine how the horrors of their everyday life were intensified by the plague." In disinfecting some infected premises one day Dr. Lowson told us that in one room the inspectors were forced to dig through two feet of dirt and human excreta to reach the floor.

The mortality from plague in Hong-Kong among the Chinese varies between 91 and 93 per cent, so that almost all of those afflicted, no matter what their treatment, die. Naturally, in view of these facts it is not astonishing that the


June, 1900.]


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coolies rebel against sending their sick into the hospitals, for there the tremendous mortality is emphasized much more than it would be in cases that remained at home. Both in the Tung-Wah Hospital and Kennedytown Hospital for infectious diseases, wards are set aside where those who elect may receive native treatment. Of course, this practically amounts to a recognition of the quackery of the Chinese doctors on the part of the government, which thus officially assumes the responsibility for their treatment. This practice is now being strenuously opposed by the Colonial medical men.

During our visit to Hong-Kong, the plague was quiescent and there were only from 16 to 20 deaths a day from the disease. The house to house visitation at this time had been given up, so that the majority of these cases were found dead on the streets and were carried by the inspectors to the mortuary. On entering the morgue each morning the sight was a ghastly one, for t he bodies were lying about on the



DR. JAMES A. LOWSON, CHIEF PLAGUE OFFICER AT HONG-KONG, IN FRONT OF THE KENNEDYTOWN HOSPITAL.

tables waiting until the hasty autopsies, necessary for burial, could be performed. Many that had not been discovered promptly were fly-blown, while other cadavera that had for several days been lying undiscovered in obscure places were half-eaten by maggots before they were carried to the mortuary. The disposal of cases that die after successfully eluding the vigilance of the district inspectors is facilitated by the habit which the coolies have of sleeping on the streets during warm nights. In Hong-Kong, during the hot season, night shows many weird and picturesque sights. The little narrow streets in the native quarters, lighted dimly by the flickering street-lamps are simply covered by the sleeping coolies who are drawn from the crowded and poorly ventilated houses by the stilling heat. They are so crowded that one cannot walk for any distance without stumbling over the half-naked sleepers who lie stretched out on little pieces of matting. So when a secreted plague patient dies, he is carried out by relatives and laid in the


street among the sleeping forms. Most of these rise at dawn to go to work, and those that do not are usually taken later to the mortuary by the plague inspectors.

The mortuary is situated half-way up the hill on the outskirts of the city toward Canton, and consists of a modern deadhonse, an office for the government medical officer, and quarters for the native care-taker. The first striking thing about the plague bodies was the presence on many of two parallel rows of deep purple spots about the size of a Spanish dollar extending from the sides of the neck down on to the chest. At first sight these appeared to be a new manifestation of the disease until Dr. Lowson told us that these purpuric spots were the result of the Chinese method of counter-irritation. This consists in firmly pinching the skin between the thumb and forefinger until it is bruised. As there is. in plague,a general tendency to hemorrhagic extravasation into the skin and serous membranes, the blood oozing from the torn vessels into these traumatic areas soon turns black, and gives the appearance which we first noted. Mosquito and flea bites behave in much the same manner. Likewise the slightest scratch or



SMALLPOX WARD AT THE KENNEDYTOWN HOSPITAL.

bruising of the skin is apparently always followed by a pink blush, and later by a subcutaneous hemorrhage which soon changes to a dark purple-colored spot. In many cases we observed extensive bullae filled with blood-stained serum, and in one or two instances the idiopathic hypodermic hemorrhages which gave the disease its mediaeval name of the Black Death. The main plague hospital in Hong-Kong is now at the old Kennedytown Barracks, in the extreme outskirts of the city, which have been converted into a hospital for infectious diseases. Here principally plague and smallpox cases are received. The hospital occupies a commanding position at the foot of Mount Austin, from the base of which the grounds extend to the water's edge. The main building, a substantial stone structure overlooking the mouth of the West River towards Kowloon, is covered by stucco, and contains the laboratory, offices and a few wards. The major part of the hospital. however, consists of rude matsheds made of palm-tha walls and roof stretched over bamboo frames. They have rough board floors, and are lined by coarse matting. On the whole they make a fairly hygienic hospital, except that thorough disinfection of the wards is impossible. A fen


122


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 111.


supported on piles over the water's edge are perhaps more sanitary than the rest, because they get air and sunlight in greater abundance. As a rule these wards are large enough for four or five patients, their small size being a decided advantage, as convalescents and those in the early stages of the disease are thus kept from witnessing the depressing scenes



A ROW OF PLAGUE WARDS IN THE KENNEDYTOWN HOSPITAL.

that often occur when patients are in the delirious stages of the malady. Plague patients do not have beds or cots but lie on a platform made of boards, supported by ordinary carpenter's horses, over which is spread a small oblong piece of matting. They have no bedding, and their heads rest on the peculiar Chinese pillows which look more like bamboo rat-traps than



MATSHEDS AT THE KENNEDYTOWN HOSPITAL, WHERE NATIVE TREATMENT IS GIVEN.

anything else. When patients get in the maniacal delirium that often accompanies the acute stage of the disease, they are tied down on their rough litters by cloth thongs. A patient so controlled can be seen in the accompanying photograph. In the male wards there are coolie attendants while the women


are nursed by amahs. Besides the Kennedytown Hospital, there were during the days when the epidemic was at its height several other temporary hospitals established in the city, and a floating hulk, the Hygeia, nicely fitted up and anchored off the Kennedytown Hospital, was used for European and Japanese patients. Aovama. the Japanese physician who was infected from an autopsy wound, was treated on this ship.

Epidemics begin in the bubonic form, and when the epidemic is at its height and the mortality is greatest, changes to pneumonic plague, and finally in the defervescent stage dies off again in the bubonic type. This has occurred regularly in HongKong, and has been noted in the many epidemics that have occurred in India by the plague authorities there. Atmospheric conditions do not seem to have much influence on the disease, except that during the rains, people are driven into the crowded, dirty houses, where they are more exposed to infection ; and the bacilli, moreover, are protected under these circumstances from the dessicating and bactericidal action of the sun's rays. This, Kitasato has shown, is one of the most potent agents in the destruction of the plague bacillus.



PLAGUE PATIENT UNDER RESTRAINT IN THE HONG-KONG PLAGUE HOSPITAL.

exposure for an hour usually being quite sufficient in temperate climates to destroy the germ. Epidemics are usually heralded, by a great mortality among the rats, which seem, when affected with plague, to lose all fear of human beings and run boldly about the houses. In part, at least, the infection of the rats can be accounted for by the ingestion of septic material, i. e., sputum and dejecta of plague patients, but by far the most prolific cause of its spread is by fleas. It is well known that fleas soon leave the bodies of rats dead of the plague, and it is supposed get on to other healthy uninfected rats. The agency of these insects as transporters of the disease has been shown by Simond* and by Lowson who put fleas from plague rats on healthy rodents, and found that they died of the disease in about three days. Flies and mosquitoes, however, do not seem to play such an important role in the transmission of plague to human beings, for both infest the wooded area about the Kennedytown Hospital, and yet no one of the attendants there


  • Simond: "Propagation de la peste " Annates de

Pasteur, Oct., 1898.


was ever infected. By far the most important atria of infection for human beings are through abrasions of the skin, through the mucous membranes of the respiratory tract, and to a lesser degree through the alimentary tract. Plague, like any infectious disease, thrives where sanitary conditions are poor ; and in China and India finds naturally ideal conditions for its spread among the hordes of natives whose lives of misery and squalor form the dark side of the human picture in the Far East. The symptoms and bacteriology of the pest have already been well described in the translations of the papers of Kitasato and Aoyama which appeared in this journal some years ago* so reference will be made only to some of the more important points which were brought to our attention in India and China. It appears that the disease may exist in any of its forms alone, or two or even more may simultaneously complicate each other in the same patient. In the simple bubonic type the location of the bubo indicates that the portal of entry of the infection occurred in the area drained by that set of lymph-glands, but it is also not uncommon to find glands enlarged en echelon. Thus, in one of our Hong-Kong autopsies the femoral, inguinaliliac and lumbar groups were all enlarged and hemorrhagic. From the observations made at the Arthur Roads Hospital in Bombay, based upon the study of a large number of cases, the site of the buboes occurred as follows:

Femoral, 33.12 per cent.

Femoro-inguinal. . . . 23. 36 " '■

Axillary, 16.35 " "

Inguinal, 12,38 " "

Cervical, 5.25 " "

.Multiple, 4.67 " "

Total .... 94.13 " "

The frequency with which the buboes occur in the lower sets of lymph-glands is explained by the fact that both in India and China, natives of the lower classes go barefoot. But in this connection it is worthy of note that all of the men in the Shropshire segment in Hong-Kong who were attacked with the plague while on inspection duty had femoral or inguinal buboes, even though they were well-booted. Their trousers, however, were open at the bottom, admitting dust particles laden with plague bacilli. While on similar duty in India, the soldiers always wore puttees, and not a single case was reported among them.

In most cases the buboes are exquisitely tender and generally require local applications to relieve the pain. For this purpose the ice-bag has been used with good effect in India. Between the portal of entry and the enlarged glands, there is often a well-marked lymphangitis and at different points multiple lymphatic abscesses may occur. This was particularly marked in Aoyama's case. When we met him in Japan, he showed us the scars of the numerous incisions made to relieve the condition about which there was a slight tendency to the formation of keloid. This has been repeatedly observed in


  • Flexner : Bulletin of The Johns Hopkins Hospital, Vol. VII,

Oct., 1896.

Bulletin of The Johns Hopkins Hospital, Vol. V, Oct.,

1894.


Hong-Kong among the Chinese who have recovered after a complication of suppurating buboes or lymphatic abscesses. Most of the buboes do not suppurate, but the fact that the great majority of cases die within two or three days after the onset undoubtedly bears a relation on this point. Likewise, it seems that mixed infections have a very important influence on the question of suppuration as the following figures show. In the pus of 29 suppurating btiboes examined by the several continental commissions working in Bombay, the following results were obtained:

Bacillus pestis, 8

Staphylococci, 9

Streptococci, 5

Sterile, 7

Total, 29

A suppurating plague bubo forms a most indolent ulcer and the granulations at the base sprout with such reluctance that it may take months for them to heal. Fortunately in these old chronic ulcerations the pus is usually sterile. In one case in Hong-Kong, followed by recovery, the femoral vessels lay exposed in the base of a large slough about a suppurating bubo.

The incubation period in plague varies between three and nine days, but in the majority of cases averages about five or six. It seems that there are no constant prodromata, and the onset, as a rule, is sudden, marked by headache, fever, backache, and a general feeling of malaise. Vomiting of a blood-stained fluid has been observed not infrequently at the onset, a phenomenon due to the action of the plague toxin in the mucous membrane of the stomach which, at autopsy, is nearly always injected and ecchymotic. In Hong-Kong, they were in the habit of speaking of the plague facies. which Lowson believes is often of assistance in the diagnosis of the disease. It consists of a mixture of anxiety, cyanosis, and dyspncea, and in mentioning it Lowson says: "Generally speaking, there is something indescribable in the face of the plague-stricken which seems to help your diagnosis — an expression as if the sufferer himself knew all about it, and his inner consciousness had left its mark upon his features." There is something quite characteristic about the plague tongue, which has a heavier coating than in typhoid fever and is considerably clearer about the margins. Soon the coating turns black and sordes often cover the teeth and lips. After the onset the fever usually rises rapidly and reaches its maximum in from 12 to 24 hours. The common temperature ranges from 103° to 105° F., but cases with a fever as high as 108° are not infrequently observed.

The patient soon after the onset shows evidence of great prostration. The pulse, at first, is full and bounding, and later becomes feeble and collapsed. Dicrotism is very common, and the heart, in the majority of cases, needs repeated stimulation to overcome the cyanosis. The cardiac symptoms observed clinically in plague cases conform in general to the results obtained experimentally by the injection of the toxic nucleoprotein of the Pest bacillus into animals. Lustig and Galeotti have also shown! that the subcutaneous injection of


i Lustig and Galeotti : Lo Sperimentale, It


124


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 111.


large amounts of the plague toxin into animals is followed 03 a local thrombosis at the point of inoculation, and 1l1.it the blood-pressure in dogs falls rapidly to 10-15 mm. of mercury, accompanied by a progressive diminution in the force and rhythm of the heart-beats soon resulting in death.

On the second or third day, the cerebral symptoms usually appear: these consist of a general apathetic condition on the part of the patient, coma or delirium of varying degrees. During this period it is often difficult to get the patients to take nourishment, and the attendants must resort to strategy or rectal feeding. This was notably the case with Doctor Aoyama, who could only be tricked into taking nourishing draughts by appealing to his politeness, on the one hand, and his patriotism on the other, by alternately toasting Queen Victoria and the Mikado in champagne, milk and other nourishing and stimulating beverages. During this period of the



ONE OF THE PLAGUE STREETS, POONA.


disease symptoms of meningeal involvement and cerebral hemorrhages were sometimes observed.

The respiratory symptoms in most cases consisted of a marked hypostasis owing to the marked cardiac weakness; but when the pneumonic type of plague was present, the condition was more often of a lobular type. In uncomplicated cases the plague bacillus can be found in the sputum, bat oftentimes there is present a mixed infection with the pneumococcus. (Edema of the glottis and extensive laryngitis were also found in some of the Bombay cases. During the course of the disease, as well as at the onset, vomiting occurs and the vomitus in such cases is stained with both bile and blood. The spleen is palpable and remains so during the course of the disease. There is always some albumin in the urine, but it is small in amount; likewise casts, epithelial debris, and occasionally Plague bacilli are also found. In general the disease runs its course in five or


six days, but the fever may remain elevated for weeks especially in cases where there is a secondary pyaemic infection. Death in most cases occurs from heart failure. No cases of reinfection above suspicion have been reported, but relapses are not uncommon during convalescence and result usually from local extension from the original focus of the disease.

Between the plague in China and India there are many points of difference which depend, it seems, partly on the character of the natives. In China the pest is more fatal than it is in India, the death-rate among the Chinese being 93 per cent, and only about 82 per cent among the low-caste Hindus, who are the heaviest sufferers from the disease in India. The general standards of life and personal hygiene are much lower among the Chinese than they are among the Hindus ; but for some reason the epidemics are so much greater in India that the terrible effects of the disease are more obvious and its many horrors are impressed on the observer by the magnitude of the sufferings of the natives. Since the first outbreak in India, in 1896-7, the death-rate has constantly increased each year, until, in 1899, more than 50,000 people died of plague in the City of Bombay alone. Moreover, the disease has now spread in a



PLAGUE FUNERAL IN INDIA.


large part of India and has appeared in Bengal. Madras and many points in the Bombay Presidency. The really serious part of the question is that apparently it is still on the increase, and precisely what the end will be no one at present can foretell. The Colonial Covernment. however, is doing all in its power to stamp out the disease, and no experiment is left untried that oilers the slightest hope of solving this very serious question.

The plague measures in India are much like those in HongKong except that they are, perhaps, not quite so thorough. In India the plague authorities have had to fight against the bigotry, opposition and animosity of the native who gives far more trouble to the sanitary authorities than his celestial neighbor. Here exist the ideal conditions for the spread of any disease; namely, overpopulation, overcrowding, malnutrition, unhealthy environment and crude and unclean methods of living. Under these conditions the energy required to fight the plague in India has been tremendous because of the inertia of the vast population, which even looked with disfavor on the measures meant for its good. In Bombay alone, the plague


June, L900.


JOHNS HOPKINS HOSPITAL BULLETIN.


125


expenses for the first year of the epidemic amounted to over fifteen lakhs of rupees.

< lertain facta concerning the plague epidemics of India have been more fully described in another place ; * but the methods of treatment employed in India and the results obtained in their use are of the greatest importance. No effort or expense has been spared bv the Indian government to try any method that offers any hope of relieving the distressing com! it urns. To this end, the Bombay Presidency has fitted up the old government house at Parel as a plague laboratory, and lure the plague prophylactic of Haffkine and Lustig's Heilserum are manufactured. Yersin, it appears, was the first to manufacture a serum supposed to act as an antitoxin to the poisons produced by the plague bacillus. Like the diphtheria antitoxin it was made on the assumption that the plague toxins were soluble products of the growth of the pest bacillus and could be obtained from filtered fluid cultures of the organism. The first cases treated by the antitoxin were in China and the results, it is stated, were very satisfactory. Somewhat later



WARD IN POONA PLAGUE HOSPITAL. THE PATIENT COVERED WITH A BLANKET IS DEAD

several plague patients at the Arthur Roads Hospital in Bombay were inoculated with the antitoxin, but the results were practically negative; so, from lack of both results and material, further experiments with Yersin's serum were not undertaken. In the Oporto epidemic Calmette f used 5 serum and reports excellent results with it. Two facts, however, should be noted, i. >•.. that the number of cases treated in India was too small to allow any conclusions as to the real value of the antitoxin as a therapeutic agent to be drawn, and, on the other hand, that the cases occurring in Portugal were by no means as severe or fatal as those among the natives of Bombay.

Then some time later Haffkine. % making experiments along

  • Barker and Flint. " A Visit to the Plague Districts of India."

New York Medical Journal, Feb., 1900.

t Calraette : Presse Medicate, 1899.

% Report on the Outbreak of P.tibonic Plague, 1896-97. Bombav, 1897.


the same line reported to the health commissioner that his

efforts to obtain an antitoxin for plague by methods similar to those used by Behring, Kitasato and Rous for diphtheria were unsuccessful and that his experiments resulted negatively. At a later period Lustig and (ialeotti§ had a similar experience, but they found, however, that the essential toxin was situated in the body of the plague organism and wasof the nature of a " nucleoprotein toxique." They succeeded in isolating this toxin by the following method: A three days' growth of the plague bacillus on large agar plates is scraped off and dissolved in 1 per cent KOII. This solution is filtered and acidulated with dilute acetic acid, whereupon it yields an abundant white precipitate which is washed and dried and in this state can be kept indefinitely. It is prepared for use by dissolving in a dilute solution of sodium bicarbonate [0.5 per cent]. This )niclc<>prolein toxique\\ is soluble in alkalis and insoluble in dilute acids. In general it gives the proteid reactions and by artificial digestion can be split up into peptone and an insoluble nuclein. When injected experimentally it produces the symp


LOW-CASTE HINDU DEAD, POONA MORTUARY.

tonis which we have already described. It is from this mccleoprolehi toxique that the antitoxin is manufactured by injecting it into a horse. The quantity used naturally depends a good deal on the condition and strength of the animal. Tin- injection is followed byaviolenl reaction at the site of inoculation ; an area of localized oedema half as large as a man's head may persist at the point of inoculation for many days. We saw that condition in one of the horses at the Parel Laboratory in Bombay. These large injections are repeated as often as the condition of the horse permits until the required degree of immunity is produced. Then the serum is withdrawn and prepared in the usual way. As yet the number of antitoxic units hae not been determined by animal titration, ami the preparation of the serum in large quantities has only just begun. The complete reported results thus far include 175 inoculations, with 100 deaths, and 75 recoveries, or a mortality of 57.30 per


^ Lustig and Galeotti : Lo .Sperimentale, 189S.

I Galeotti : Arch, des Sciences Biologiques. Tome VIII, 1899.


J 26


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 111.


cent. Thus, the mortality for plague averages about 73.70, so that, at present, the serum saves about. 1 6 per cent of the cases. In these inoculations the cases were not selected but were taken as they came, and included IS in which dissolution was imminent. After the injection a hypothermic action was noted which seems in plague cases to be a specific reaction, as it was never obtained when people who were not suffering with plague were inoculated. At times considerable prostration seemed to follow the injection and a slight increase in the cardiac weakness so that caffein, camphor or ether were often given with the antitoxin. After the second injection there was an amelioration of the conditions. The antitoxin, according to Galeotti, acts in a manner exactly opposite to the nuchoprotein toxique. The pulse becomes less frequent and the dicrotism disappears; there is an augmentation in the force of the heartbeat, while the buboes, at the same time, become less painful, and any tendency to suppuration is arrested. Bacilli, moreover, tend to disappear from the blood. In pneumonic cases and in the severer gastro-intestinal infections, the antitoxin in its present strength apparently has no effect.


' • * JSP


S3ygl^^r~


t ' 1


•*■'"



ms:


CHILD DEAD OF PLAGUE, POONA MORTUARY. PREPARATION FOR FUNERAL.

Soon after the outbreak of plague in India M. Haffkine, formerly of the Pasteur Institute, who had been at work in India on some problems concerning cholera, began the preparation of a prophylactic against plague.* The principle involved in the preparation of that fluid is similar to that followed by Lustig somewhat later in the manufacture of his Heilserum ; namely, that the plague toxin resides in the body of the pest bacillus, and cannot be obtained from the soluble products of its growth. The preparation of the Haffkine prophylactic fluid is now carried on, on a large scale, in Bombay ; and it is shipped all over India and to many other parts of the world. At present the prophylactic meets with great opposition from the natives, especially the Hindus, who will not submit to inoculation because the fluid contains meat, and thus offends one of their most cherished religious principles. To meet this


  • Haffkine : Ttie plague prophylactic. Ind. Med. Gazelle, June

1897.

Remarks on the plague prophylactic fluid. Brit. Med.

Jour., 1897, Vol. II.


objection an effort is being made to procure a medium on which to grow the organisms from a substratum gluten and other substances free from meat extracts.

The manufacture of the prophylactic is quite simple, and through the kindness of Dr. Melne, who had charge of the Parel Laboratory in Haffkine's absence,we were able to follow the prophylactic through the various stages of its preparation. A kilogram of finely chopped goat's flesh, after macerating in hydrochloric acid, is placed in an autoclave and heated for six hours under a pressure of three atmospheres. This is then filtered and neutralized with KOII and diluted up to three litres, when it becomes the medium in which the plague bacillus is grown. Some plague material is put into these flasks and the bacillus is identified by what Haffkine has described as the stalactitic growth. If such cultures rest absolutely undisturbed for five or six days, after being inoculated on the surface, fine delicate thread-like processes can be seen hanging from the surface into the depths of the bouillon which have a very strong resemblance to the stalactites that hang from the



MOHAMMEDAN GIRL BEING BURIED BY THE HOS


AUTHORITIES.


roof of a grotto. This growth, according to Haffkine, is pathognomonic of the plague bacillus, and the purity of such a culture can be tested microscopically. The culture is put into a Pasteur flask, from which a large series of 3-litre flasks are inoculated after it is certain that the original culture is uncontaminated. These are grown in a huge, darkened room, containing long tables on which hundreds of these 3-litre flasks rest. Owing to the high mean temperature thermostats are unnecessary in India. To make the prophylactic it is necessary to get repeated crops of the stalactites in each flask and to keep the surface inoculated ; a small amount of sterile '•ghee," a sort of clarified butter, which floats on the surface and always contains after the original inoculation a few bacilli, is added so that after repeated shakings the surface of the culture is always reinoculated. In this way five or six crops of stalactites are obtained before the serum is finished, and this takes, as a rule, about six weeks. After agitating the flasks, the little clumps of bacilli sink slowly to the bottom and anew surface growth slowly appears. The culture is killed by immersion in a constant water-bath at


June, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


127


70° C. for three hours when some carbolic acid or thymol is added, and while care is taken to keep it well shaken the prophylactic is decanted into small bottles and is then ready for use. The usual dose of the plague prophylactic was about 2 cm., but at Hubli. where it was used most extensively, Leumann * was in the habit of using a greater quantity at each injection, lie always took into consideration, however, the age and physical condition of the patient in making the inoculations. An ordinary antitoxin syringe is used for this purpose and the injection made well into the subcutaneous tissue. Injections into the skin are apparently more painful than those made well below the coriuin. After two inoculations with tinplague prophylactic the blood of the patient usually gave the YVidal reaction. This, however, is not obtained so readily after a single protective injection. Leumann allows from 14 to 20 days to elapse between the first and second injections, and regards the constitutional reaction of headache, fever and malaise as more important than the agglutination test. Extremes of age do not seem to affect the value of the inoc


BURNING GHAT, POONA PLAGUE HOSPITAL.

ulation, as on one occasion a child 10 days old was inoculated while on another, a woman of 90 was protected against the Women as far advanced in pregnancy as the seventh month were inoculated without the occurrence of any unfavorable symptoms, a fact which is rather interesting when one considers that all pregnant women taking the disease itself abort. To avoid, as far as possible, the injection of the protein in the incubation stage of the disease, it was regarded a safe rule not to inoculate any one with a temperature of 100° F. until it was certain that he was not suffering from the plague.

Since it has now been generally recognized that, under the conditions which obtain in India, the hygienic and sanitary measures have little or no effect in influencing the course of the epidemic or lessening the mortality from the disease, the results obtained at Hubli have been most successful and gratifying. In all some 78,000 inoculations were done in ;i of four months in Hubli. in the province of Dharwar, many of

  • Report No. 7569, of 1898.


which were, however, on the inhabitants of the outlying districts and villages. It seems that the double inoculations have a greater protective power against the disease than single injections of the prophylactic, which statistically is shown to amount to 10 per cent of the total mortality among the inoculated. But in Dharwar the results were even better than at Hubli; for there were, among 4,926 single inoculations, 45 cases and 15 deaths; and in 3,387 double inoculations, 2 cases and 1 death.

Moreover, among these inoculations were undoubtedly included some cases where the prophylactic was given to those in the incubation period of the disease. Hubli, where the Haffkine serum received its first large and comprehensive test, is a mercantile town of about 50,000 inhabitants. It was attacked by the pest at the beginning of the monsoon rains, and the average monthly rainfall between October and April reached 28 inches. Although a large health camp was established, and as many plague regulations as possible were put in force, it was evident that the authorities could not cope with the epidemic, so they determined to make a thorough test of the prophylactic. Mr. Cappell, the collector of Dharwar. says : '•If this experiment had failed, the mortality, judged by the actual mortality among the uninoculated, would have been appalling. All possible sanitary measures in the shape of disinfection, unroofing of houses, and segregation were applied concurrently with the inoculation as the government is already aware; but the rate of mortality among those who held back from inoculation rose at one time to a height which, 1 believe has never been approached elsewhere— standing in the third week of September at the figure of 657 per thousand per week."

The duration of the protection afforded by the serum could not be definitely determined, although the majority of the citizens were protected for at least 5 months. In 69 households, all of the inoculated members escaped the disease while some of the uninoculated in the families succumbed to the disease. Perhaps a more conclusive idea of the scopie of the enormous experiment may be gathered from the appended table, which shows that at only one period did the non inoculated have a percentage advantage over the inoculated in the mortality tables and that was when the epidemic was not severe and the number of the inoculated was low.


A STUDY OF CHRISTIAN SCIENCE.

Bv Harry T. Marshall, M. I) , Fellow in Pathology, The Johns Hopkins University.


TWENTY-FIFTH ANNIVERSARY OF DR. WELCH'S GRADUATION.


On the evening of May 4, Prof. Councilman of Harvard University, in behalf of the students and coworkers of Dr. Wm. H. Welch, at a complimentary dinner held at the Maryland Club, Baltimore, presented him, in honor of the twentyfifth anniversary of his doctorate, a volume of contributions to the science of medicine, containing 38 papers, all embodying original research. (See page 138.)

Address of Professor W. T. Councilman.

On this occasion, 25 years after your entrance into the medical profession, we, your students, present to you this volume. It contains a number of articles written by us, each of which contributes to the advancement of medical knowledge. We have chosen this method to tell you of our esteem and affection, for we feel that it is the highest and most enduring tribute we could lay before you. For, unlike any tribute wrought in stone or metal, it has the quality of increase. The results of the investigations here set forth will stimulate further investigations and lead to still greater increase of knowledge. It is the work of men you have taught, who have come under your influence and who have received from you the inspiration which has enabled them, often amid great difficulties, to continue in the path along which you first led them.

It is one thing to tell a man what is the right way ; it is better still to show him ; but it is quite another thing to take him by the hand and lead him along it. This you have done, and it is this which has made you the great teacher which you are, for a teacher to be great must be a leader among men. You have taught us what is known. In your lectures you have presented to us, with a clearness that has never been surpassed,


the known facts of medical science and the deductions to be drawn from those facts. We have learned from you the importance not of theory, but of definite knowledge. You have further showed to us that merely to acquire what is known is not the true aim, but that he who would himself advance and contribute to the advancement of his fellows must seek to enlarge the bounds of knowledge. By your own work you have led us. The importance of the work you yourself have done is recognized by the world. It has been marked by your characteristic clearness, thoroughness and fairness. In the work which you have inspired, there has been absolute freedom in the worker. You have always sought to turn their investigations into the development of truth.

The work has been in a broad field, and the workers have had a clear sky above and fresh breezes around them. All branches of medical science have been enriched by this work. The breadth of the work is shown in the subjects treated in this volume. We feel that you are a part of it, that our work is due to your inspiration. But your work as a teacher ami leader has not been confined to those who have felt your presence ; it has been far wider. Your influence has been felt in every part of the country, because each man who has gone from you has been a missionary burning to lead others into the light.

One year after your graduation, The Johns Hopkins University opened its doors. The central idea of the university, the idea with which it started, which distinguished it from other institutions of learning in this country at that time ami gave n at once its high position in the world, is that it is the duty of a university both to impart knowledge and to increase knowl


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edge by original research. In the medical education at that time there were no high ideals. There were numerous schools in which the medical art was taught, but in no place had the university ideal, which aims at the advance of knowledge, entered into medical education. Not that there were not a few great teachers, but the principle was not there.

The creation of the Medical School of the University was slow. First physiology and then pathology were established as departments of the university. Sixteen years ago, Dr. "Welch, you were called to the chair of pathology in the university. There was no hospital to furnish material, no students to teach. You began your work, and before the hospital was opened you had grouped around you an earnest band of workers. Those of us whose fortune it was to have been with you in those early days can never forget them.

When the Medical School was opened, the ideals of the university had been established in its most important departments and were a controlling power. There sprang up at once that close union between the university and the medical school to which, more than anything else, the marvelous growth and influence of the medical school has been due. The medical school was founded in the laboratories of physiology and pathology. There has been in the medical school and in the hospitals a close union between art and science, an appreciation of their mutual dependence, which in its fullness was new to America.

We have ourselves tried to do what we could to advance knowledge and to extend to others the ideals which we learned from you. Your spirit lives in us, and we extend to you in this work the best expression of our affection, our esteem ami our gratitude.

Address of Professor Welch.

On accepting the volume. Dr. Welch replied as follows:

M;i friewh and fellow students: — I have no words adequate to express my appreciation of this demonstration of your affection and loyalty. With a heart full of thanks I accept this magnificent volume of contributions to medical science by my pupils and coworkers, now and in the past.

I thank you, Dr. Councilman, for your generous words in presenting this volume, even if I must believe that your estimate has far exceeded my merits. Although I have been kept in ignorance of the details of this undertaking, I know that my especial thanks are due to Dr. Mall and Dr. Flexner for its inception and conduct, as well as for the incentive to several of the contributions. Turning the pages, I see how much is due to the marvelous artistic skill of Mr. Broedel, and I am not surprised to hear of the unselfish devotion of Dr. Hurd in the editorial work, nor that my old friend and colleague, Dr. Ilalsted, has been active in arranging for this occasion. To all who have honored me by their contributions to this volume I am deeply grateful, and the kind messages from many other pupils and associates have gladdened me.

Nothing could afford me livelier pleasure and satisfaction than to have my name associated in this way with a volume of contributions, which cannot fail to interest all workers in scientific medicine. I recognize among the contributors not only the names of those who have gained distinction as inves


tigators, but also of those who are beginning their careers and will now win their first spurs. To me the most significant feature of this occasion is that the time has come in America when a group of investigators, more or less closely connected through common teachers, can bring together so large a number of important, original contributions to medical science. Twenty-five years ago this would not have been possible. That I should have been permitted to participate with others in bringing about this advance is to me a source of much gratification.

When Dr. Prudden and I first started our small laboratories in New York, he at the College of Physicians and Surgeons, and I at the Bellevue Hospital Medical College, the outlook was not eucouraging for a young man to select pathology for his career. The contrast between then and now in this respect is indeed a striking one. To-day, pathology is everywhere recognized as a subject of fundamental importance in medical education and is represented in our best medical schools by a full professorship; at least a dozen good pathological laboratories, equipped not only for teaching but also for research, have been founded ; many of our best hospitals have established clinical and pathological laboratories; fellowships and assistantships afford opportunity for the thorough training and advancement of those who wish to follow pathology as their career; special workers with suitable preliminary education are attracted to undertake original studies in our pathological laboratories; students are beginning to realize the benefits of a year or more spent in pathological work after their graduation, as a foundation for future success in practical medicine, surgery, or the specialties; and as a result of all these activities the contributions to pathology from our American laboratories take rank with those from the best European laboratories. While we realize that we are only at the beginning of better things and that far more remains to be accomplished than has been attained, nevertheless, the progress of pathology in America during these twenty-five years has surely been most encouraging.

When I look back over this quarter of a century I realize how favored I have been by my opportunities, and here you will r>ermit me to be somewhat personal. My interest in pathologic anatomy was awakened in my student and hospital days by Delafield and Janeway, who are among the best pathologic anatomists whom I have ever known. I received also a strong stimulus toward scientific work from Jacobi, whose seventieth birthday will be celebrated to-morrow night in New York by well-earned honors. I owe more than I can tell you to my teachers in Germany, to Cohnheim. Weigert, von Eecklinghausen and Wagner, and through them to the great master, Rudolph Virchow. Upon my return to this country, my association with Dr. Austin Flint, the elder, was to me an inspiration, and in many ways of the greatest advantage.

While the prospects for earning a livelihood and for advancement in a pathologic career may not have seemed encouraging in New York, 22 years ago, in reality the circumstances were fortunate. About that time there were introduced great improvements in histologic technic, which led to a deeper insight into the structure and activities of cells and opened the way for new directions of development. Above all, it was the begin


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uing of the bacteriologic era marked by the great discoveries of Koch, of whose earliest work I saw something while studying in Cohuheim's Laboratory in Breslau, and whose personal teaching I later enjoyed. To have begun one's work as a teacher of pathology at such a period and after intercourse with such masters of the science, and to have been permitted to continue it during these years of unparalleled progress, must be considered a circumstance fortunate for the teacher.

The time was fully ripe in this country for the introduction of laboratory teaching and investigation in pathology, and it is certain that if one had not appeared to undertake it, another would have done so. It was an easy matter under such circumstances to demonstrate the value of the pathologic laboratory in medical education. I have every reason to feel grateful for the encouragement and support accorded the little laboratory at Bellevue College and the opportunities there afforded to me. Prudden's Laboratory, founded about the same time at the College of Physicians and Surgeons, has developed under his masterly direction into a large and splendidly equipped laboratory, surpassed by none in its influence upon the advancement of pathology in this country. I need not speak here of the wider opportunities, so well known to you, which I found in Baltimore, of the liberal policy of the Trustees of The Johns Hopkins University and Hospital in the establishment and support of the Pathological Laboratory, of the advantages derived from the intimate association of the Medical School with this great University and Hospital, of the stimulus received from my colleagues, and of the attraction of our high standards of education in drawing to us highly trained students.

Above all, most fortunate have I been in those who have worked with me as pupils and associates, and to these coworkers is due in the first instance whatever of success has attended my efforts as a teacher and student of pathology. I am delighted to see here to-night my old friend and co-worker in the New York Laboratory, Dr. Meltzer, and also Dr. Beyer. To have had such a coadjutor in the early organization and conduct of the Baltimore Laboratory as Dr. Councilman, such an original investigator as Dr. Mall for the first fellow in pathology, such special workers in the early days of the laboratory as Sternberg, Halsted, Herter, Abbott, Bolton, Nuttall, Booker, Miller, Barkley, Clement, Howard, Russell, Blachstein, Thomas, Williams, Randolph, Gilchrist, and others — all of this I count as the best of good fortune. I call to mind on this occasion with affectionate regard many others who have followed these earlier workers, but the list is too long to enumerate. I must, however, give expression of my indebted


ness to Dr. Flexner, who since the opening of the Medical School until the end of the last academic year has been my closest associate in the work of teaching and in the supervision of the laboratory.

While it has been hard to part with such associates, it is a matter of pardonable pride that so many have been called to important chairs in other institutions — Councilman to Harvard ; Abbott, Flexner and Clark to the University of Pennsylvania ; Wright to the Laboratory of the Massachusetts General Hospital ; H.U.Williams to the University of Buffalo ; Blunier to the Bender Hygienic Laboratory in Albany; Bolton to the Hoagland Laboratory and subsequently toother institutions; Howard to the Western Reserve University ; Nuttall to the University of Cambridge, England ; Russell to the University of Wisconsin ; and now we are to lose Barker, most scholarly, versatile, inspiring of teachers and profound in his studies, who has been called to an important position in the University of Chicago. That we shall retain with us young men of great promise is evidenced by such contributions as those of Cullen, Cushing, Young, Bardeen, the MacCallums and Opie in this memorial volume. I rejoice to see in this book in connection with Cushing's, the name of our muchloved Livingood, whose career of unusual promise was cut short by an ill-timed fate.

1 should like to be able to speak of the value of the contents of this volume which you have dedicated to me, but I see it for the first time to-night. A glance through the pages assures me that here are gathered together papers with which any medical teacher in the world would be proud to have his name associated. I may be permitted to call attention to the importance of the contributions from our women students; and it will not, I trust, be invidious if I mention the superb work of Miss Florence Sabin, done under Dr. Mall's and Dr. Barker's direction, and so beautifully illustrated by Mr. Broedel.

As I have already said, I see in this volume of studies an iudex of the great advance during the last quarter of a century in the material conditions surrounding pathological teaching and investigation in this country, brought about especially through the establishment of laboratories. It is also a significant token of the greater things which we may assuredly expect in the future, when America will take her place in the front rank with those countries which contribute most to the progress of the medical and biological sciences. If my name shall ever be mentioned among those who in those earlier days have helped to promote our science in this country, I shall owe it above all to you, my pupils, colleagues, and fellow workers.


MONOGRAPHS.


The following papers are reprinted from Vols. I, IV, V, VI and VIII of the Reports, for those who desire to purchase in this form: STUDIES IN DERMATOLOGY. By T. C. Gilchrist, M. D., and Emmet P.ixford, M. D. 1 volume of 164 pages and 41 fullpage plates. Price, bound in paper, $3.00. THE MALARIAL FEVERS OF BALTIMORE. By W. S. Thayer, M. D., and J. Hewetson, M. D. And A STUDY OF SOME FATAL CASES OF MALARIA. By Lewellys F. Barker, M. B. 1 volume of 280 pages. Price, in paper, $2.75. STUDIES IN TYPHOID FEVER. By William Osler, M. D., and others. Extracted from Vols. IV and V of The Johns Hopkins


Hospital Reports. 1 volume of 481 pages. Price, bound in paper, $3.00.

THE PATHOLOGY OFTOXALBUMIN INTOXICATIONS. By Simon Flexner, M. D. Volume of 150 pages with 4 full-page lithographs. Price, bound in paper, $2 00.

THE RESULTS OF OPERATIONS FOR THE CURE OF INGUINAL HERNIA. By Joseph C. Bloodqood, M. D. Price, in paper, $3.00.

Subscriptions for the above publications may be sent to

The Johns Hopkins Press, Baltimore, Md.


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CONTRIBUTIONS TO THE SCIENCE OF MEDICINE DEDICATED BY HIS PUPILS TO WILLIAM HENRY WELCH ON THE TWENTY FIFTH ANNIVERSARY OF HIS DOCTORATE.


TITLES AND ABSTRACTS.


A Contribution to the Study of the Pathology of Early Human Embryos. By Franklin P. Mall, Professor of Anatomy, Johns Hopkins University. With 6 plates and 29 figures in the text. (Pages 1 to 68.) The paper is based upon the study of 50 pathological human ova which have been collected by the author during the past six years. Nearly all of the embryos were cut into serial sections, thus permitting of a more careful study than is possible from that of the external appearances alone. As far as possible, additional data were obtained from the physicians from whom the specimens were obtained, and these prove to be of much value. The paper discusses the following subjects :

1. Arrested development of the embryo with continued growth of the ovum.

2. Degeneration of the embryo, leaving only the umbilical cord.

3. Ova, normal in form, without embryos and uterine moles.

4. Vesicular forms of pathological embryos.

It is followed by an appendix giving the main data of all of the normal embryos known as well as a detailed description of each of the pathological specimens discussed in the communication.

II.

On Urea in Some of its Physiological and Pathological Relations. By C. A. Herter, Professor of Pathological Chemistry, University and Bellevue Hospital Medical School, New York. (Pages 69 to 109.) The physiological portion of this paper deals (a) with experiments which were undertaken with a view to comparing the capacity of different types of kidney in the excretion of urea, and (b) with the experiments relating to the nature of the cell activity concerned in the excretion of urea.

The pathological section is devoted to a record of experimental observations on the following subjects: (a) the toxic action of intravenous infusions of watery solutions of pure urea, especially in dogs and monkeys, (S) the action of urea upon experimentally damaged kidneys, (c) double nephrectomy and its effects upon the urea content of the blood, muscles, liver and brain, (d) insufficiency of urea in the course of renal disease, (e) the relation of an excess of urea in the blood (literal uraemia) to uraemic states. Evidence is brought forward in this section of the paper which indicates that a large excess of urea in the blood is capable of giving rise to disturbances which manifest themselves clinically, although in some examples of conditions included by clinicians as uraemic it is quite clear that urea can play no part in occasioning the symptoms.


III.

The Direct Action of Nicotin upon the Mammalian Heart. By Henry G. Beyer, M. D., Surgeon U. S. Navy. With 9 figures in the text. (Pages 111 to 134.)

This paper gives an account of some experiments made upon the isolated heart of the cat with nicotin in blood in different degrees of strength ; it also describes the effects of nicotin on the dog's apex on which two experiments were made; finally, several experiments are recorded in which nicotin in blood was allowed to run through the coronary vessels while the heart was in a state of fibrillation.

The experimental evidence brought out seems to warrant the following conclusions, namely: — (1) Nicotin acts as a powerful stimulant on the vagus nerve endings as well as on the accelerator or augmentor nerve endings in the heart; (2) it increases both the tonus and the irritability of the muscular fibres of the heart and, lastly, causes the contraction of the coronary vessels.

IV.

The Effect of Shaking upon the Bed Blood-Cells. By S. J. Meltzer, M. D. New York. (Pages 135 to 151.) The conclusions reached are as follows:

1. Shaking of even a very short duration has a detrimental effect upon the red blood-cells, which manifests itself by an early separation of the haemaglobin followed by a rapid breaking down of the stromata into dust.

2. The process of defibrination is invariably very injurious to the life of red blood-corpuscles.

3. Prolonged shaking of the blood with a granulated insoluble substance turns the red blood-cells into fine dust. Cells of different animals show different degrees of resistance. The destruction is due to a molecular shock and not to a gross injury. The continual shaking beats together again the fine dust into large granules and dust. Possibly the molecular destruction is characteristic of organized elements.

4. Certain degrees of shaking can also prolong the life of the red cells, but the degree which is favorable to the life of the cells of one species of animal may be detrimental to the cells of another species.

These relations present a special instance of the general law formulated by the writer for the relations of vibration to all living organisms; for each individual form of life there is a minimum degree of vibration which is indispensable and another degree which presents the maximum limit.

V.

The Blood- Vessels, Angiogeuesis, Organogenesis, Reticulum, and Histology of the Adrenal. By Joseph Marshall Flint, Baltimore. With 8 plates and 28 figures in the text. (Pages 153 to 228.)


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The adrenals are situated in what may be termed the vascular crossroads of the abdomen, for within a few centimetres of them the large trunks which supply almost all of the abdominal viscera are given off. Most of these contribute to the circulation of the glands which may be divided into three systems of vascular units, supplying respectively the capsule, cortex and medulla. In the capsule, there is an arterial and a well marked venous plexus. From the former the branches which supply the entire organ are derived. The blood-vessels of the cortex consist in the main of parallel capillaries with transverse anastomoses which empty into the venous tree of the medulla; while the arteries supplying the medullary substance pass entirely through the cortex to ramify in the medullary portion of the gland, giving off in their course arterioles and capillaries which empty finally into the branches of the venous tree, or into medullary veins which join them. The venous tree itself Mows into the lumbar vein at the hilus of the gland.

This complex vascular system, following partially known laws, can be traced by means of injected embryos in its gradual evolution from the simplest to more complex stages, until finally the adult arrangement is reached. Curiously enough, the medulla is developed outside of the cortex and grows into it after the latter is well formed, the various steps in this transposition being beautifully shown in stained or injected adrenals of embryo pigs. Of especial interest is the fact that simple mechanical misplacements may lead to anomalies of structure in the adult gland, occurring during the migration of the medulla, which are unintelligible in the adult organ unless viewed in the light of their formation.

The framework of the adrenal is made up of reticulum which can be studied best by some of the destructive methods. The reticulum fibrils have a delinite arrangement in relation to the cells and blood-vessels, which they support and hold in position. Finally, the architecture of the adrenal is described most fully from the conditions found in the dog, where such variations of structure as transposed cortex or misplaced medulla are explained by the ingrowth of the medulla as followed in the organogenesis of the gland in a series of embryo pigs.

VI. Specific Degenerations of the Cortical Arteries. By Henry J. Berkley, M. D., Clinical Professor of Psychiatry, The Johns Hopkins University. (Pages 231 to 230.)

VII.

The Regeneration of the Crystalline Lens. (Alvarenga Prize Essay, L899.) By Robert L. Randolph, M. D., Baltimore.

With 6 figures in the text. (Pages 237 to 203.) The subject attracted the attention of investigators seventylive years ago. Since then several have busied themselves with the problem, but within the past thirty years nothing of note has appeared in connection with it. It is surprising to see that a histological problem of such importance finds no mention in either works on anatomy or ophthalmology. The object of this work is to ascertain whether the lens of the rabbit is regenerated after its extraction — whether, in other words, a new lens is formed. The conclusions are as follows:


1. Regeneration of the lens in the rabbit's eye occurs only when some portions of the lens arc left behind at the extraction.

2. Removal of the lens in capsule is followed by a negative result. 3. Panophthalmitis is followed by a negative result. 4. The volume of the regenerated lens may be equal to that of the original lens. 5. The regenerated mass is lenticular, though sometimes it is ring-shaped and at other times it is semilunar. 0. 'The reason why positive results occur so much less frequently than negative ones, is because we are unable to protect the animal from infection after the operation. 7. Theoretically one would suppose that the longer the animal were allowed to live the greater would be the volume of the regenerated mass. This, however, was not the case in these experiments. In one instance where an animal was killed fifteen months after the extraction of its lens, the regenerated lens was about equal in size to that seen in another case where the rabbit was killed after six weeks. It may be added that there was no apparant reason for this. 8. A mild iritis, lasting for a week or ten days after the operation, is conducive to a successful result. This may be explained by the increased vascularity of the parts which lie next to the lens.

The second portion of the paper is devoted to a consideration of the works of Wolff and Erik Miiller. The former made the statement that the lens of the tritou (salamander) is regenerated from the iris epithelium and Miiller confirmed Wolff's results. The author made fresh observations and reaches the following conclusions: 1. In the case of the newt, extraction of the lens is followed by its regeneration. 2. Regeneration occurs even when the lens has been removed in its capsule, so that the new lens must take its origin from tissue having a different physiological value; and. as the experiments of Wolff have shown, this structure is the iris.

VIII. The Histology of Acute Lobar Pneumonia. By Joseph II. Pratt, M. 1)., Boston. With 1 plate. (Pages 205 to 277.)

Early in the disease the alveoli contain many cells almost, identical in appearance with the so-called transitional cell of the blood. They are usually slightly larger than the polynuclear leucocyte, and contain an irregular vesicular nucleus, surrounded by a rim of protoplasm, containing either a few granules or none at all. In a case in which death occurred eleven hours after onset, there were great numbers of these cells in the exudate and no polynuclear leucocytes.

Large phagocytic cells are found in all stages of the disease, but in greatest number in gray hepatization. The inclusions consist chiefly of polynuclear leucocytes and lymphocytes, more rarely of red blood-corpuscles. These phagocytic cells probably play an important part in resolution. Similar cells are found in the lymphatics, in the pleural exudate, and in the bronchial lymph nodes.

The fibrin is not formed by a degeneration of the alveolar epithelium, but comes exclusively from the exuded blood plasma.

The lymphatics are involved late in the disease. There is proliferation of their endothelium, and they become distended with cells, serum and fibrin.

Early in the disease there is no infiltration of the interstitial


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1 11 cases 'lying during the second week, there is often infiltration with lymphoid and plasma-cells. As a' rule the longer the duration of the disease the greater the number of plasma-cells.

These results are based upon a study of fifty cases of typical lobar pneumonia.

1\. Bilateral Cholesteatomatous Endotheliomata of the Choroid Plexus. By George Blumer, M. D., Director of the Bender Hygienic Laboratory, Albany, N. Y. With 1 plate. (Pages 279 to 280.)

X. Concerning the New Formation of Elastic Fibres, Especially in the Stroma of Carciuomata. By Herbert U. Williams, M. D., Professor of Pathology and Bacteriology, Medical Department, University of Buffalo. (Pages 291 to 296.) Our knowledge of the condition of the elastic fibres in normal and pathological tissues has recently been much improved by the discovery of selective staining processes. Weigert's method was used by the writer with most satisfactory results. A review of the literature of the subject shows that newly formed elastic fibres have been found in the intima of the arteries in arteriosclerosis and endarteritis, in chronic productive inflammations of the serous membranes, in cirrhosis of the liver, in chronic interstitial nephritis, and in certain scars and tumors of the skin.

The writer endeavored to determine whether newly formed elastic fibres constituted a part of the stroma of carcinoma. Thirty-seven carciuomata growing in various organs were studied, with the following conclusions:

1. When the stroma of carcinoma is itself of new formation it is usually free from elastic fibres.

2. Newly formed elastic fibres may occur in the stroma, though rarely, and they are likely to be fine in quality and small in number.

'■'). The tumors, in which newly formed elastic fibres occurred, either contained a large amount of connective-tissue .stroma, or the newly formed elastic fibres were in connection with preexisting elastic elements of the original parts.

XI. Cirrhosis of the Liver of the Guinea-Pig Produced by a

Bacterium (Bacillus Coli Communis) and Its Products.

By George II. Weaver, M. D., Assistant Professor of

Pathology, Hush .Medical College, Chicago. With 2

figures in the text. (Pages 297 to 305.) The injurious agents which act acutely upon the liver affect the cells of the liver and bile-ducts, the character and strength of the agent determining the degree of injury produced. Only two substances which act in a chronic manner stimulate the growth of connective tissue. An imrjortaut factor in determining the effects of injurious agencies upon the liver is to be found in the peculiarities of the tissues of the individual. The organism studied belongs to the group of colon bacilli. The live cultures and those which had been devitalized by heat when injected into guinea-pigs produced exten


sive cirrhoses in the liver of the animals. The early changes were in the form of necrosis, the connective-tissue proliferation following a little later.

XII. On the Muscular Architecture and Growth of the Ventricles

of the Heart. By John Brdxe MacCallum, Baltimore.

With 24 figures in the text. (Pages 307 to 335.) By the study of embryonic hearts of various ages, macerated in nitric acid, the organ was found to consist of several layers of muscle, the course of which is described in some detail. Nearly all the fibres begin in the auriculoventricular ring of one ventricle, and end in the papillary muscles of the other. Those fibres which begin near the outside of one ventricle end near the inside of the other ventricle. The thin superficial layers being removed, the left ventricle can be unrolled so that its cavity and papillary muscles are exposed. This shows it to be a flat baud of muscle continuous with the muscle fibres that cross over in the septum from the right ventricle. Grouping these layers together it is clear that the heart in the embryo is a scroll-shaped band of muscle with tendons at each end. As it grows older the layer of muscle passing over in the septum remains comparatively thin, while the ventricular walls increase greatly in thickness. The growth takes place mainly near the inside of the ventricular walls, as shown by the presence of karyokinetic figures near the endocardium and by the fact that the muscle-cells in this situation are younger in an actively growing heart than those near the surface of the organ. These growing points must therefore be at the two ends of the unrolled heart. The heart, then, resolves itself into a flat band of muscle with a growing point at either end.

XIII.

Some Observations upon the Anatomy of the Gall-Bladder and Ducts. By George E. Brewer, M. D., Assistant Demonstrator of Anatomy, College of Physicians and Surgeons, New York. With 5 plates and 50 figures in the text. (Pages 337 to 354.) In this paper are given the results of 160 dissections of the gall-bladder region in the adult human subject, which were carried out during the years 1898-99 at the auatomical laboratory of the College of Physicians and Surgeons (Columbia University), New York. These observations were originally undertaken by the writer with a view to familiarizing himself with the normal relations of the structures in this vicinity, and of perfecting his technique in handling and suturing them. Noting numerous variations from the normal, and certain rather striking abnormalities which were of decided surgical interest, the writer extended his studies far beyond the limit originally intended. In addition, numerous observations were made on the size of the gall-bladder, the length and calibre of the ducts, the surgical relations of the duodenal orifice of the common bile-duct, and an effort was made to establish certain landmarks by which it may be rapidly located through an incision in the duodenum. Observations were also made with a view to establish landmarks by which the operator could rapidly locate and accurately mark out


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the position of the principal nerve-trunks likely to be injured

by an incision through the abdominal wall in this region. In this paper are also included observations upon the distribution of the hepatic artery, which are illustrated by fifty figures of actual dissections, showing numerous variations ami many anomalies of interest to surgeons who are accustomed to operate in this region.

XIV. A Case of Plexiform Neuroma of the Eyelid (liankenueuron). By Harry Friedenwald, M. 1)., Associate Professor of Ophthalmology. College of Physicians and Surgeons, Baltimore. With 2 plates. (Pages 355 to 357.) The patient, female, was 16 years of age. The abnormality was first noticed when she was a few months old. Two operations had been performed when she was a child. The right upper lid was greatly hypertrophied, especially in its temporal part : the lower lid but slightly affected. There was almost complete ptosis and the thickness of the lid was greatly increased. Firm, round and corded masses could be felt under the skin and could be followed back into the orbit.

At the operation fine white threads characteristic of the growth were found and removed. The growth was easily freed from the orbit with a blunt instrument and was found to extend much deeper into the orbit than was expected. The tumor was found to consist in great part of masses of whitish fibres varying greatly in thickness and weighing seven grammes. Sections showed the characteristic appearance of neuromata. Everywhere there were found smaller and larger nerve bundles imbedded in a framework of connective tissue. Some — for the most part smaller — bundles showed nothing abnormal. Others again presented varyiug degrees of hyperplasia of the endo- and perineurium with the nerve elements placed more or less centrally, or with a few scattered axis cylinders in the periphery. There were other bundles again in which the hyperplasia was still greater, and in which it was difficult to recognize any nerve elements whatever.

XV.

A ( ase of Multiple Myeloma. By James H. Wright, A. M., M. I)., Pathologist to the Massachusetts General Hospital, Boston, Mass. With 3 plates. (Pages 3o9 to 366.)

XVI. The Development of the Musculature of the Body- Wall in the Pig, including its Histogenesis and Its delations to the Myotomes and to the Skeletal and Nervous Apparatus. By Charles Bussell Bardeen, M. D., Associate in Anatomy, The Johns Hopkins University. With 10 plates. "(Pages 367 to 399. The investigation considers the development of the intrinsic thoraco-abdominal musculature from the myotonies in the pig's embryo. The histological changes taking place in the mii-culature are described, as well as the early relations of the musculature to the nervous and skeletal apparatus.

Three periods are recognized in the development of the musculature:

1. The period during which the myotomes expaud dorsally and send ventral processes into the membrana reuniens. The


cells, both of the mesial and the lateral plates of the myotomes

are shown to lie converted into musele-til'ivs.

2. The period during which the tissue of the myotome, becomes utilized in the formation of the muscles characteristic of the adult. Segmentation is shown to persist only where the muscle-tissue remains throughout united to the vertebras or to the ribs. The peripheral nerves are shown to develop independently of the myotomes, and to become associated directly with the musculature only after the muscles have become differentiated.

3. The period during which the muscles expand, become perfected in internal structure and are shifted into the relative positions characteristic of the adult.

Cell-multiplication takes place during the first two periods and during the early part of the third. Cell-division takes place by mitosis in round undifferentiated "myoblasts." From these the muscle-cells are developed by elongation of the cell-body, nuclear multiplication by direct division, and fibrillar differentiation of the protoplasm. The differentiated muscle-cells do not divide to form new cells. During the third period, however, many of the muscle-cells undergo retrograde metamorphosis.

XVII. A Bare Variety of Adenocarcinoma of the Uterus. By Thomas S. Collen, M. B., Associate in Gynecology, The Johns Hopkins University. With 3 figures in the text. (Pages 401 to -107.) In the uterus we have three distinct varieties of epithelium : the squamous epithelium of the vaginal portion, the very high cylindrical pale-staining epithelium lining the cervical canal and the racemous glands, and the cylindrical ciliated epithelium of the body. From these three distinct kinds of epithelium three definite varieties of carcinoma develop. And, in fact, nearly all carcinomata of the uterus may be classified under one of the three varieties :

(1) Squamous cell carcinoma of the cervix.

(2) Adenocarcinoma of the cervix.

(3) Adenocarcinoma of the body of the uterus.

The accompanying case differs materially from any that we have yet seen. Clinically, it is interesting to note the advanced age of the patient, who was 76 years old. There had been no haemorrhages at any time and notwithstanding the ex tent of the growth the symptoms wereof onl] one year's duration. On examining Figure 1, one is immediately impressed with the uniform involvement of the entire uterine cavity, the body being equally as much implicated as the cervix. The surface also presents dome-like elevations instead of the papillary or tree-like growths so common both in adenocarcinoma of the cervix and body. Another marked feature is, that notwithstanding the advanced age of the patient, the uterus is the size of a three-mouths pregnancy.

On histological examination the growth is found bo be glandular in type. These glands are large and lined by one layer of high cylindrical epithelium, the nuclei of which rest directly on the basement membrane and the gland-cavities contain a homogeneous material thai takes the hematoxylin


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stain. Iu other words, both the glands and their contents resemble those found in the cervix.

XVIII. A Bacteriological and Microscopical Study of over Three Hundred Vesicular and Pustular Lesions of the Skin with a Research upon the Etiology of Acne Vulgaris. By T. Casper Gilchrist, M.D., Clinical Professor of Dermatology, The Johns Hopkins University. With 1 plate. (Pages 409 to 430.)

Stained smears were examined from every lesion. A summary of the results is as follows :

Impetigo Contagiosa. — Prom every one of the 17 cases examined the streptococcus pyogenes was obtained, and in ten cases it was in pure culture. In 7 cases the staphylococcus pyogenes aureus also grew. The disease was reproduced in three cases by inoculating with a pure culture of the streptococcus obtained.

Ecthyma. — Two cases yielded pure cultures of streptococcus pyogenes.

Staphylococcia or Folliculitis Staphylogenes. — Sixteen cases examined: two cases yielded pure cultures of streptococcus pyogenes; in five cases the S. pyogenes al bus was also present; in seven patients the S. pyogenes aureus was present in pure culture.

Tricophytosis. — In a case of tinea barbae one culture yielded a pure growth of tinea megalosporon ectothrix, whereas in the second culture the S. pyogenes aureus was also present. By inoculation experiments on two men it was proved that the fungus was pyogenic and that therefore the pustular lesions of tinea barbae may be produced by the fungus alone without the presence of the ordinary pus organisms. The same results were proven in a case of tinea circinata where pustules were present and a pure culture of the tinea magalosporon endothrix was obtained. It was also shown that the same fungus was the cause of pustular lesions on a boy's scalp.

Furunculosis. — Prom 20 cases pure cultures of the S. pyogenes were obtained in every case.

Scabies. — Nine cases; the staphylococcus pyogenes grew in pure culture in 4 cases; in 2 cases the S. pyogenes aureus was also present; the albus being present alone in the ninth case.

From beneath scales of pediculosis capitis and corporis, cultures of streptococcus pyogenes and S. pyogenes aureus and albus usually combined.

The S. pyogenes aureus grew in pure culture from 3 cases of sycosis vulgaris.

The pustular lesions of syphilis were shown, with two exceptions, to be due to mixed infectious of the streptococcus and S. pyogenes aureus and albus.

Cultures were negative in 10 cases of herpes zoster (vesicles), 2 cases of sebaceous cyst, 15 cases of dermatitis venenata (vesicles), 4 cases of pernio (vesicles), 3 cases of erythema multiforme (vesicles), and one case of pemphigus pruriginosus.

Eczema. — Nineteen cases; in cultures from G vesicles, 5 were sterile, while one showed the S. pyogenes albus. In 13 cases of eczema madidans, 5 gave the staphylococcus pyogenes aureus alone, 4 yielded the albus, and 2 were sterile after


wiping the surface of the lesions. Out of 10 cases of pustular eczema, 2 gave the S. pyogenes aureus, 4 showed the albus, 2 cases yielded both aureus and albus, and one was sterile.

Acne Vulgaris. — This yielded the best results. 96 lesions from 54 patients were examined. 54 cultures were sterile; 31 showed from one to many colonies of staphylococcus pyogenes albus ; 11 cultures gave pure growths of a bacillus in glycerin-agar. All the smears from the jms showed bacilli. This bacillus grew slowly en masse in glycerin agar. The colony at first was creamy white, later it became pinkish, then almost black in one very old culture. It grew on glucoseagar without forming gas; grew in bouillon; invisibly on potato; grew fairly well on blood-serum, but not in Dunham's or milk. It did not decolorize by Gram's stain, was motile and branched. It killed mice and guinea-pigs. Bacillus acnes was the name suggested for this micro-organism.

XIX.

The Frequency and Significance of Infarcts of the Placenta, Based upon the Microscopic Examination of 500 Consecutive Placenta 1 . By J. Whitridge Williams, M. D., Professor of Obstetrics, The Johns Hopkins University, and Obstetrician-in-Chief to The Johns Hopkins Hospital. With 3 plates. (Pages 431 to 460.)

XX.

A Contribution to the Knowledge of the Bacillus Aerogenes Capsulatus. By W. T. Howard, Jr., M.D., Professor of Pathology, Western Reserve University, Cleveland, Ohio. With 1 plate. (Pages 461 to 495.)

After a review the author reports thirteen cases of gasbacillus invasion, which he divides into three groups:

Group I. Bacilli entering the body through the genitourinary tract — two cases. In one there were cerebrospinal meningitis and brain abscesses, both containing gas-cysts and general gaseous emphysema due to B. aerogenes capsulatus. In the second case, with abscess of the prostate, chronic cystitis, pyonephritis and gaseous emphysema, the bacillus was concerned in the renal lesions.

Group II. Bacilli entering through the biliary tract — two cases. In one the gas bacilli were limited to the gall-bladder and liver, and in the other — a case of typhoid fever — there was general gaseous emphysema, best marked in the liver and biliary tract.

Group III. Bacilli entering through lesions of the stomach and intestines, — nine cases, comprising the following lesions as the portal of entry: strangulated hernia ; necrosis of the stomach with gas blebs (typhoid fever); crushing injuries, involving the gastro-intestinal tract; intestinal ulcers (typhoid, two cases, lymphosarcoma, one case); and post-mortem disintegration of the stomach and ileum (four cases).

In the last four cases, microscopically, there were no gascysts found in the gastro-intestinal tract, which on microscopical examination showed both cysts and bacilli.

The author next discusses the various modes of invasion, the destruction of the bacilli in the body and their effect upon the lesions.


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XXL

The Intravascular Growth of Certain Endothelioma^. B\ W. G. MacCallum, Associate in Pathology, The Johns Hopkins University. With 1 plate audi figures in the text. (Pages Wi to 510.)

The writer, after reviewing the records of several similar cases in the literature, give3 the clinical history and autopsy protocol of a case which occurred at The Johns Hopkins Hospital. The tumor of the testicle was incompletely extirpated and at tin' autopsy, several months later, the extension along the spermatic vein could be traced into the vena cava. filling it with translucent papillary masses which extended into the heart. Large metastatic nodules were found on lungs, liver and elsewhere. The tumor was shown to spring from spaces with endothelial lining thought to be the lymphatic spaces. The proliferation of these cells produced not only cyst-like cavities but complicated cell masses. Especial interest attached to the relation of the tumor to the bloodvessels, as the intravascular papillary masses generally hung free in the blood, and were overgrown by the endothelium of the vessel.

XXII. The Cultivation of Amoebae. By Casper 0. Miller, M. D., New Market, Va. (Pages 511 to 523.)

Cultures were made in sterilized Erlenmeyer flasks with water containing a small percentage of organic matter, in all of the cultures living bacteria were present.

The fact that encysted amoebae withstand drying was taken advantage of to eliminate from the cultures those protozoic forms which do not withstand drying. Algae were eliminated by excluding the light from the cultures.

The amoebae were gathered from various sources; of these some have been cultivated since 1889. Some cultures containing encysted amoebae have been dried for six years without killing the amoebae. Some of the amoebae cultivated did not encyst. Of those encysting, two varieties have been studied: one forming spherical cysts — A. Sphaerocystis ; and the other forming irregularly shaped cysts — A. Irregular i a.

In the culture of A. Sphaerocystis, oval cysts resembling coccidia? in many respects are found at times, and there are also occasionally present sharply defined, consecutive bodies.

Although it is not proven, at the same time it is questioned whetla-r Amoebae Sphaerocystides, coccidiae and the crescents, are not phases in the development of the same organisms. Those who have cultivated amoebae on solid media only describe them as muliplying by division, but in the fluid cultures there are appearances which seem to indicate thai amoebae also multiply by segmentation.

XXIII.

The Bacillus Pseudo-Tuberculosis .Murium ; Its Streptothrix Forme and Pathogenic Action. By DoEOTHl M. ; Baltimore. With 1 plate. (Pages 525 to 541.) A study of the l>. pseudo-tuberculosis murium first i by Dr. Welch in 1894 : described by Kutscher in Germany in L806; recovered in Baltimore in 1897, from a spontaneous case of pseudo-tuberculosis in a mouse.


This paper deals with the cultural properties of the organism, previously undetermined, with the study of the conditions •under which the organism varies from its usual form of a simple rod in giving off side branches, and with the nature of the pathological lesions on the animal body. It is shown that the bacilli branch in the body and in artificial media; and that in the body aggregations of bacilli appear, which resemble the " Driisen "of actinomyces. In the tissue lesions the nodules differ from true tubercles, in being composed of bacteria and not of proliferated or emigrated body-cells.

AX IV. Experimental and Surgical Notes upon the Bacteriology of the Upper Portion of the Alimentary Canal, with Observations on the Establishment There of an Amicrobic State as a Preliminary to Operative Procedures on the Stomach and Small Intestine. By Harvey Gushing, M. D., Associate in Surgery, The Johns Hopkins University, and Louis E. Livingood, M. !>.. Late Associate in Pathology, The Johns Hopkins University. With 8 figures iu the text and 1 diagram. (Pages 543 to 591.) From numerous clinical observations upon the character of the peritonitides consequent to perforating wounds of the alimentary canal it seemed probable that the severity of the infection bore a distinct relation to the situation of the perforation and that the favorability of the prognosis was proportionate to the nearness of the lesion to the stomach.

This suggestion, originating from clinical data alone, was the occasion of a series of experimental observations upon animals and human beings relative to the bacteriological features of the alimentary canal, especially of its upper portion. A great scarcity of micro-organisms was found to he the invariable rule iu the neighborhood of the duodenum of the 35 dogs and rabbits which were examined under varying dietary conditions. With certain precautionary measures, such as sterilization of the ingesta and a fast of a few hours, a condition of amicrobism could almost without exception be brought about in the stomach and upper portion of the intestine of a healthy animal.

Adaptation to surgical procedures of the principles established by this experimental work has shown the feasibility, under a certain dietary regime, of rendering the upper portion of the alimentary canal practically free from micro-organisms in anticipation of operative work on the stomach and upper intestine, so that exposure of the lumen of the canal is unattended by risks of ensuing peritonitis.

X X V.

The Origin, Development and Degeneration of the Bloodvessels of the Human Ovary. By JOHN G. Clark, M. D., Professor of Gynecology, University of Pennsylvania. With •"> plates and 11 figures in the text. (Pages 593 to 676. The author contributes a special research upon the ovarian

circulation, in which the normal distribute f the arteries

and veins of the ovary and their relationship to each other

have been studied. At lirst sight the solution of this qu

did not appear to present greater difficulties than those encountered in the ordinary course of any research. A review of the sections of a few injected adult ovaries, however, at once demonstrated the futility of attempting to draw any conclusions from this source; for the close crowding together of the parallel vessels of the medullary portion, and the markedly irregular course of those in the cortex, or follicle bearing zone, rendered impossible any accurate observations concerning the relative number and distribution of the veins and arteries and the exact course followed by each system.

With a view, therefore, of securing ovaries possessing a simpler scheme, a study was made of the lower animals, such as the dog, rabbit, guinea-pig, sheep and pig, but with unsatisfactory results, and only after the injection of the generative organs of a monkey was a suggestive clue secured. Beyond this point, however, it was difficult to proceed; and only after the injection of a very large series of ovaries from individuals, ranging in age from a six-months foetus to a woman many years beyond the menopause, were final conclusions reached.

In the search for this normal scheme through an extensive number of serial sections, various questions directly dependent upon the circulation presented themselves for solution, which widened the scope of this work until it developed into a composite anatomical and physiological research.

Thus, the various vital phenomena have been considered which transpire within the follicle from its embrvological origin and progressive growth to the time of its disappearance, either through an obliterative process or through its rupture, organization as a corpus luteum, and final retrogression as a corpus fibrosum. In this connection the author has advanced theories concerning the development of the ovary ; the differential signs of sex; the descent of the ovary; the cause of ovulation ; the synchronism of ovulation and menstruation ; the mechanism of the rupture of the mature follicle, and the final cessation of ovulation ; which have been based upon observations made in the study of a very large number of section.-.

Soon after beginning this work he was struck not only with the difficulty of arriving at a definite knowledge of the scheme, but also of determining the age at which this scheme may be taken as a standard for comparison.

This is certainly not possible after active ovulation is established ; for the constant changes in the vascular system, induced through the maturation, rupture and organization of the follicle, introduce an element of variability into the circulation of this organ which occurs in no other.

Failing to reach any satisfactory starting point in the adult, the author next studied the ovary of a girl approaching puberty, but with little more success, for it was found that almost as constant variations occur in the follicular circulation before as after the inauguration of ovulation. In the hope of finally Qg a period in the life of the female individual at which a definite standard for comparison might be found, numerous specimens from children of various ages were injected and closely studied. Finally, the ovary of a six-months foetus was obtained, which furnished a definite clue to the arrangement of the vessels; but as the follicular apparatus was still in process of development, a new-born child in which the tunica albuginea was well formed was selected as the standard. Even here the solution of the question was not easy, for in


order to trace the ramifications of the vessels from the point of their entrance into the ovary to their ultimate termini the study of the serial sections of many ovaries was necessary.

XXVI. The Gonococcus. A Report of Successful Cultivations from Cases of Arthritis, Subcutaneous Abscess, Acute and Chronic Cystitis, Pyonephrosis and Peritonitis. By Hugh H. Young, M. D., Instructor in Genito-Urinary Diseases, The Johns Hopkins University. (Pages 677 to 707.)

This report represents a study of unusual infections of the gonococcus occurring at The Johns Hopkins Hospital during the past four years.

Gonorrhceal arthritis is first considered, and a complete tabulation is given often cases in which pure cultures of the gonococcus have been obtained from diseased joints.

Five cases of subcutaneous abscesses due to the gonococcus are presented, together with a careful review of the literature showing the great rarity of such cases.

A case of general suppurative peritonitis, in which the gonococcus alone was grown from the peritoneal exudate, being the only case on record, is detailed.

In the discussion of gonococcus cystitis, a review of the literature shows that only two cases of acute cystitis in which the organism of Neisser was obtained in pure culture, and one case where by aspiration of the bladder pure cultures of the gonococcus were obtained from the urine, are recorded. In others it was found on coverslip preparations.

A case of chronic alkaline cystitis of four years' duration, due to the gonococcus alone, is presented as the first case in the literature, and the occurrence of a double pyonephrosis in the same case, due to the same organism, and likewise the first recorded instance, is mentioned.

The literature of kidney affections following gonorrhoea is reviewed at length, and a historical resume of the successive demonstrations of the widespread infective powers of the gonococcus is appended.

A XVII. The Histogenesis of the Cellular Elements of the Cerebral Cortex. By Stewart Paton, M. D., Assistant in Clinical Neurology, The Johns Hopkins University. With 7 figures in the text. (Pages 709 to 741.)

XXVIII. Experimental Pancreatitis. By Simox Fi.kxxek. M. D., Professor of Pathology, University of Pennsylvania, Philadelphia. (Pages 743 to 771.) The study upon which this paper is based consists of a series of experiments carried out upon dogs in which injections of acids, alkalies and other chemicals, as well as bacterial cultures, have been made into the duct of Wirsung and the interstitial tissue of the pancreas. By the several procedures employed, hemorrhagic, suppurative, necrotizing and chronic indurative pancreatitis have been produced. There has been frequently associated with these conditions fat-necrosis both in the peritoneal cavity and in the distant fat. The several forms of pancreatitis produced have been considered in their relation

to pancreatitis in human beings. The histology of the lesions is also described and a comparison is drawn between the changes found in the experimental cases and those described in similar lesions in human beings. Attention has been paid to the cause of fat-necroses with the determination that in all of them the fat-splitting ferment in quantities demonstrable by chemical test existed.

XXIX.

Chronic Hypertrophic Gastritis of Syphilitic Origin, Associated with Hyperplastic Stenosis of the Pylorus. By John C. Hemmetkr, M. D., Clinical Professor of Medicine, University of Maryland, and Wm. Royal Stokes, M. D., City Bacteriologist, Baltimore. With 4 figures in the text. (Pages 773 to 794.)

The most important pathological changes noted in cases of gastric syphilis are ulceration, necrosis, and atrophy of the mucous membrane of the stomach, with a marked chronic interstitial increase of the connective tissue of the submucous coat. Large fibrous bands also extend into the muscular coat of the organ.

The case which the authors of this article report, gave a typical history of syphilis. The patient showed an absence of free and combined HC1, and pyloric stenosis was suspected. A surgical operation was performed for relief of the symptoms, and the patient died one month later.

An autopsy showed general infection with the bacillus pyocyaneus and staphylococcus aureus, and the stomach was found shrunken to about one-third of its natural size. There was marked pyloric obstruction, without tumor or ulcer. The submucous coat was thickened and the mucous membrane coarsely granular in appearance.

A microscopic examination showed atrophy of the glands of the mucous membrane, with the formation of villous-like projections, or diffuse formation of young fibrous tissue. The submucosa shows a marked thickening due to the presence of fibrous tissue with many areas of lymphoid cells, especially about the smaller veins.

This fibrous tissue extended to the muscular coat, and in places the peritoneum was thickened. The blood-vessels showed multiplication of the intimal cells but no other marked changes. These changes were more marked at the pylorus, bur were apparent in sections taken from various portions of the organ.

The history of the case and the changes described justify the belief that the entire pathological process in the stomach was syphilitic in character.

XXX.

A Case of Adenocarcinoma which Originated in the Submucous Glands of a Trachea-Like Formation, Found in a Sacral Teratoma. By William H. Hudson, M. J)., La Fayette, Ala. With 2 plates. (Pages 795 to 804.) A case of adenocarcinoma which developed from the submucous glands of a trachea-like formation found in a sacral teratoma is reported.

Among the fcetal structures found in the teratoma were the trachea, the oesophagus, the posterior spinal ganglia, and other structures resembling normal physiological tissues.


The special interest in this communication centres in the malignant changes which were found to exist in the tumor. Reported cases of malignancy in teratomata are exceedingly rare, by far the largest number of such cases being of the epidermal type. The case here reported, and one other, are all the reported cases of teratomata in which malignancy has originated from glandular structure.

The surgery of teratomata is also considered, and the removal of these tumors is advised in every case, where such operations can be performed with safety to the patient,

XXXI.

On Hydromyelia in Its Relation to Spina Bifida and Cranioschisis. By E. Bates Block, M. D. With 3 plates. (Pages 805 to 858.)

XXXII.

Experimental, Disseminated Fat-Necrosis. By Eugene L. Opie, M. D., Assistant in Pathology, The Johns Hopkins University, Baltimore. With 1 plate. (Pages 859 to 876.)

The relation of fat-necrosis to lesions of the pancreas was studied experimentally in cats. If the outflow of pancreatic secretion is completely obstructed by ligating both pancreatic ducts, foci of fat-necrosis are produced and may be widely disseminated. In two instances, in which the animals lived twenty-five and twenty days after the operation, almost the entire abdominal fat was opaque-white and necrotic, and loci of necrosis were found in the subcutaneous and pericardial fat. The presence of a fat-splitting ferment was demonstrated in the necrotic fat. In other instances, in which the animals lived a shorter time, less extensive necrosis resulted. Assuming that after duct-ligation a gradual diffusion of pancreatic juice or of the fat-splitting ferment occurs, the attempt was made to hasten the diffusion by stimulating, after ligation of the ducts, the secreting activity of the gland with pilocarpin. After the death of the animal extensive necrosis of the abdominal fat with foci in the pericardium was found. To test the ability of the fully formed pancreatic juice to cause necrosis of fat the duodenal end of the organ was transplanted in such a way that the secretion was poured into the subcutaneous tissue of the abdominal wall; typical fat necrosis resulted.

The condition essential to the production of focal fatnecrosis is the penetration of the fat-splitting ferment of the pancreas into living fat, and the lesions of the pancreas associated with fat-necrosis are such as permit this diffusion into the surrounding tissue. The widespread necrosis occasionally observed in man and in animals may be reproduced experimentally by conditions which favor diffusion of the ferment.

XXXIII. Multiple Hyperplastic Gastric Nodules Associated with Nodular Gastric Tuberculosis. By Claribel Cone, M. D., Professor of Pathology, Woman's Medical College, Baltimore. (Pages 877 to 890.) The report is of a case of tuberculosis of the stomach occurring in the course of a general miliary turberculosis, which came to autopsy in the pathological laboratory of The Johns


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Hopkins Hospital in October, 1808. Besides the tuberculous infection of the stomach, gastric lesions of unusual character were also found.

From the surface of the stomach projected numerous .small granules and occasional larger rounded nodules, varying in size from that of a pin-head to that of a pea.

Upon microscopic examination these nodules presented several histological types. There were (1) nodules due to connective-tissue overgrowth or to irregular fibrous contraction; (2) atypical glandular nodules; (3) nodules specifically tuberculous.

The connective-tissue nodules are doubtless a feature of chronic gastritis which was present. The atypical glandular nodules possess in part the features of a neoplasm ; in part, the features of a simple hyperplastic growth.

Glandular hyperplasia seems more probable because there are present in the same mucous membrane simple proliferating gastric tubules, irregular groups of two, three or more tubules, larger irregular collections, and the circumscribed nodules themselves, all having a similar general structure, and all, no doubt, an expression of the same pathologic process.

The tuberculous nature of some of the nodules has been shown beyond question by both the histologic and the bacteriologic examination.

Between the tubercles and the hyperplastic glandular nodules no direct relation can be traced.

XXXIV. On Serum Substitutes with Special Reference to Asiatic Cholera. By Arthur Blachstein, B. A., M. D. (Pages 891 to 901.)

XXXV.

Endocarditis Due to a Minute Organism, Probably the Bacillus Influenza?. By Mabel F. Austin, Baltimore. (Pages 903 to 911.)

In three cases of endocarditis which have come to autopsy, a minute bacillus was found which differs from any of the bacteria previously described as the cause of the disease.

The bacillus is identical in its peculiar morphological characteristics with the B. influenza? of Pfeiffer. Cultures were not obtained. The organism is very minute. It stains with the basic auilin dyes, but rarely uniformly; usually the poles of the bacillus take the stain more intensely, giving the appearance of a diplococcus. When treated by Gram's method the bacillus is readily decolorized. Great numbers of the organisms were found in the coverslip preparations made from the diseased valves, and in sections of the recent vegetations, and in one case clumps of bacilli were found also in the lung alveoli. No other microorganisms were present.

While the failure to obtain cultures forbids definite conclusions as to the nature of the organism, it seems very probable from the evidence obtained that the bacillus is the Bacillus influenza?. This is of especial interest in connection with the many clinical reports of endocarditis occurring as a complication of influenza. The clinical histories of the three cases are given with the histological and bacteriological studies of the tissues obtained at autopsy. A brief review of the literature bearing on the subject is presented.


XXXVI. On a Case of Chronic Nephritis Terminating with Symptoms of Landry's Paralysis. By Lewellys F. Barker, Associate Professor of Pathology,- The Johns Hopkins University. (Pages 913 to 923.) The paper records a case of chronic diffuse nephritis which for two weeks before death presented the symptoms of acute ascending paralysis. At autopsy there were small red granular kidneys; an acute terminal hsemorihagic colitis due to the streptococcus pyogenes was present. The microscopic examination of the spinal cord and brain revealed lesions in the nervecells and in the blood-vessels. The lumbar cord was most affected, but there were alterations as high as the cerebral cortex. Not only were the motor-cells involved but alterations were also met with in the nerve-cells of the nuclei of the dorsal funiculi in the medulla oblongata.

XXXVII.

Model of the Medulla, Pons and Midbrain of a New- Born Babe. By Florence R. Sabin, Baltimore. With 8 plates and 52 figures in the text. (Pages 925 to 1045.)

The article contains a description of a model of the medulla, pons and midbrain of a new-born babe made after the waxplate method of Born. It was prepared from a series of horizontal sections stained by the method of Weigert-Pal, and it reproduces in three dimensions, the various structures of the region so magnified that they can be seen and easily handled. The model, moreover, can be taken apart completely.

The model illustrates the form and position of each tract, the course of development being thereby suggested. The fact that the medial and lateral lemnisci which form the mam sensory tracts are closely related in form to the other structures, while the pyramidal tract has but little or no influence in moulding the other parts, is emphasized.

The cerebral nerves and their nuclei are described and grouped according to their position and form, and these groups also illustrate the course of development. The most curious and interesting form, perhaps, met with in the model is that of the inferior olivary nucleus, its gyri and sulci being clearly indicated. The relation of the medulla oblongata to the spinal cord is also illustrated. The mode in which the white and gray matter continue into the medulla, the changes these undergo and the intrinsic structures of the medulla, pons and midbrain are in turn considered.

XXXVIII. A Contribution to the Surgery of Foreign Bodies. By William S. Halsted, Professor of Surgery, The Johns Hopkins University. With 3 plates and 1 figure in the text. (Pages 1017 to 1059.)

DESCRIPTION OF THE JOHNS HOPKINS HOSPITAL.

By John S. Billings, M. D., LL. D. Containing 56 large quarto plates, phototypes, and lithographs, witli views, plans and detail drawings of all buildings, and their interior arrangements — also woodcuts of apparatus and fixtures ; also 116 pages of letter-press describing the plans followed in the construction, and giving full details of heating-apparatus, ventilation, sewerage and plumbing. Price, bound in cloth, $7.50.


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147


SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.


Thomas McCrae, M. B. Spleno-Myelogenous Leukaemia; with Disappearance of the Spleen Tumor and of the Myelocytes from the Blood. — The British Medical Journal, March 31, 1900.

The patient, whose case is reported, came under observation twice in one year, with typical signs of spleno-myelogenous leukaemia. On each occasion the spleen tumor gradually disappeared, the leucocytes returned to normal and the myelocytes disappeared. He ultimately died, apparently of cerebral hemorrhage. No similar case was found in the literature, although instances of disappearance of one of these conditions named are not uncommon.

Hugh H. Young, M. D. The Present Status of the Appendicitis Question, as Shown by the Recent Literature and Society Transactions of France, Germany, England, and the United States.— Maryland Medical Journal, April, 1900.

Thomas R. Brown, M. D. Progress in Pediatrics.— Maryland Medical Journal, April, 1900.

Andrew H. Whitridge, M. D. Can Beginning Pulmonary Tuberculosis be Diagnosed Through a Shirt?— The Medical Examiner and General Practitioner, April, 1900.

Hunter Robb, M. D. A Clinical and Pathological Report of Two Cases of Genital Tuberculosis.— Cleveland Medical Gazette, March, 1900.

Thomas R. Brown, M. D. Cystitis due to the Typhoid Bacillus Introduced by Catheter in a Patient not Having Typhoid Fever. — Medical Record, March 10, 1900.


XOTES Otf XE« BOOKS.

Diseases of the Stomach. By John C. Hemmeter, M. D., of Baltimore. (P.Blakiston'sSondk Co. Philadelphia, 1900.) This is the second edition of this work which originally appeared in 1897. To the first edition a number of illustrations and nearly one hundred pages have been added. The general plan of the work has not been changed. Among the new material the articles on Hypertrophic Stenosis of the Pylosus, Obstruction of the < Irifices, and Hemorrhage from the Stomach are specially noticed. Recent work and literature have been carefully used. The bibliography given is a very valuable feature of the book, but many readers would prefer to have fewer references inserted in the text. In using the book we have often found the lack of orderly arrangement rather a drawback. The exact whereabouts of all the points on a given subject are often found with difficulty. The work has been found very useful and we congratulate Dr. Hemmeter on his second edition.

The Anatomy of the Brain. By Richard H. Whitehead, M. D. {The F. A. Davis Company, 1900.) This is a book of 96 pages which aims at giving a short and concise account of the anatomy of the brain without too many minor details. It is divided into four chapters dealing with the divisions, the surface anatomy, the internal anatomy and the conducting paths of the eneephalon. The text is clear and the giving of the terms adopted by the German Anatomical Society in addition to those commonly used in this country is a helpful feature. The illustrations are good and are not too complicated. Altogether the work should be of great use especially to students, as it is probably the best short description of the brain that we have in English.


John G. Clark. Two Cases of Extrauterine Pregnancy.— American Journal of Obstetrics, April, 1900.

Henry C. Coe, M. D. Pain as a Pathognomonic Symptom of Ectopic Pregnancy.— Medical X,„s, April 21, 1900.

William Osler, M. D., and Thomas McCrae, M. B. (Tor.). Cancer of the Stomach in the Young.— New York Medical Journal, April 21, 1900.

Simon Flexner, M. D., and Lewellys F. Barker, M. D. Prevalent Diseases in the Philippines. — Science, April fi, 19U0.

T. Caspar Gilchrist. Two Unusual Cases of Annular Syphilides in Negroes.— Maryland Medical Journal, April, 1900.

Thomas R. Brown, M. D. Cystitis Caused by the Bacillus

Pyocyaneus. Progress in Medicine.— Maryla7id Medical

Journal, May, 1900. Harry T. Marshall, M. D. A Study of Christian Science.

— Md. Med. Jour., May, 1900. H. O. Reik, M. D. Some Interesting Cases of Mastoiditis.—

Md. Med. Jour., May, 1900. Robert Reuling, M. D. Pathology and Neurology.— Md.

Med. Jour., May, 1900. Hugh H. Young, M. D. Progress in Surgery.— Md. Med.

Jour., May, 1900.


BOOKS RECEIVED.

Transactions of the College of Physicians of Philadelphia. Third series. Volume the Twenty-first. 1899. 8vo. XLVIII + 197 pages. Printed for the College. Philadelphia.

Proceedings of the Philadelphia County Medical Society. Vol. XX. Session of 1899. Joseph M. Spellissy, M. !>., Editor. 1899. 8vo. XVIII + 368 pages. Printed for the Society, Philadelphia.

The British Guiana Medical Annual. Edited by J. F. S. Fowler, M. B. Eleventh year of issue. 1899. 8vo. 23 + XXXVII pages. Printed by Baldwin and Co., Georgetown, Demerara.

Injuries to the Eye in their Medicolegal Aspect. By S. Baudry, M. D. Translated from the Original by Alfred James Ostheimer, Jr., M. D. Revised and Edited by Charles A. Oliver, A. M., M. D. With an Adaptation of the Medico-legal Chapter to the Courts of the United States of America, by Charles Sinkler, Esq. 19(10. 12mo. X+ 161 pages. The F. A. Davis Co., Philadelphia, New York, Chicago.

The Medical Annual and Practitioner's Index. Eighteenth Year. 1900. 12ino. LXXX + 871 pages. John Wright & Co., Bristol.

The Pathology anil Surgical Treatment of Tumors. By N. Senn, M. D., LL. D. Second edition, revised. Illustrated by 478 engravings, and 12 full-page plates in colors. 1900. 8vo. 7)8 pages. W. B. Saunders, Philadelphia.

Essentials of Diagnosis. Arranged in the form of Questions and Answers. Prepared especially for Students of Medicine. (Saunders' Question-Compends, No. 17). By Solomon SolisCohen. M. D., and Augustus A. Eshner, M. D. Second Edition, revised and enlarged. Illustrated. 1900. 12mo. 417 pages. W. B Saunders, Philadelphia.


148


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[No. Ill,


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report In Pathology.

The Vessels and Walls of the Dog's Stomach; A Study ol the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of toe

Vena Portae and its Influence upon the Circulation. By P. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Berkley, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By *. v.

Mall, M. D.

Report In Dermatology. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. D., and Emmet Rixford, M. D. A Case of Blastomyeetic DermatitiB in Man; Comparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, with the so-called

Parasites found in Various Lesions of the Skin, etc.; Two Cases of Molluscum

Fibrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhnng). By

T. C. Gilchrist, M. D.

Report In Pathology. An Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halbted, M. D.

Volume II. 570 pages, with 28 plates and figures.

Report in Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Obler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin. By H. A. Lafleur, M. D. Cases of Post-febrile Insanity. By William Osler, M. D. Acute Tuberculosis in an Infant of Four MonthB. By Harry Toulhin, M. D. Rare Forms of Cardiac Thrombi. By William Osler. M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in Medicine. Tubercular Peritonitis. By William Osler, M. D. A Case of Raynaud's Disease. By H. M. Thomas, M. D. Acute Nephritis in Typhoid Fever. By William Osleb, M. D.

Report in Gynecology. The Gynecological Operating Room. By Howard A. Kelly, M. D. The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kelly. M. D., and Hunter Robb, M. D.

The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By Hunter Robb,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinary Examination of Ninety-one Gynecological Cases. By Howard

A. Kelly, M. D., and Albert A. Ghriskey, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the NegreBS. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Clitoris. By Hdnter Robb, M. D. Kolpo- Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report In Surgery, I. The Treatment of Wounds with Especial Reference to the Value of the Blood Clot

in the Management of Dead Spaces. By W. S. Halsted, M. D. Report in Nenrology, I. A Case of Chorea lnsaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By August Hoch, M. D. A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By

Henry M. Thomas, M. D.

Report in Pathology, I. Amoebic Dysentery. By William T. Councilman, M. D., and Henri A. Lapleor, M. D.


Volume III. 766 pages, with 69 plates and figures.

Report in Pathology.

Papillomatous Tumors of the Ovary. By J. Whitridoe Williams. M. D. Tuberculosis of the Female Generative OrganB. By J. Whitridoe Williams, M. D.

Report in Pathology.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Fleiner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By \Vn. T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugata Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A. Kelly, M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mary Sherwood, M. D.

Intestinal WormB as a Complication in Abdominal Surgery. By A. L. Stavely, M. D.

Gynecological Operations not involving CcBliotomy. By Howard A. Kelly, M. D. Tabulated by A. L. Stavely, M. D.


The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina with Haematokolpos and Hannatometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anaesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howarh A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.

Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.

By William Osler, M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetbon, M. D,

Report in Neurology. Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of Mux musailus; The Intrinsic Nerves of the Thyroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley, M. D.

Report in Snrgery. The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halbted, M. D.

Report in Gynecology. Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. Cullen, M. B. Report in Pathology. Deciduoma Malignum. By J. Whitridoe Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever.

By William Osler, M. D., with additional papers by G. Blumer, M. D., Simon Flesner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.


Volume VI. 414 pages, with 79 plates and figures.

Report in Neurology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (StudieB Nob. I to V). By Henry J. Berkley, M. D.

Introductory.— Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I.— Alcohol Poisoning.— Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol); Part II. — 8erum Poisoning.— Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part III.— Ricin Poisoning.— Experimental Lesions induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia.— Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V.— Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Pathology.

Fatal Puerperal SepBis due to the Introduction of an Elm Tent. By Thomas S. Cullen, M. B.

Pregnancy in a Rudimentary Uterine Horn. Rupture, Death. Probable Migration of Ovum and Spermatozoa. By Thomas S. Cullen. M. B., and G. L. Wilkins, M. D.

Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. Cullen, M. B.

A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By William D. Booker, M. D.

The Pathology of Toxalbumin Intoxications. By Simon Fleiner, M. D.

Volume VII. 537 pages with illustrations. (Now ready.)

I. A Critical Review of Seventeen Hundred Cases of Abdominal Section from the standpoint of Intra-peritoneal Drainage. By J. <;. Clark, M. D. II. The Etiology and Structure of true Vaginal Cysts. By .Iambs Ernest stokes, M. D. 111. A Review of the Pathology of Superficial Burns, with a Contribution to our Knowledge of the Pathological i nanges in the Organs In eases of rapidly fatal burns By Charles Russell F.aiideex, M. 1). IV. The Origin, Growth and Kate of the Corpus Lutemn. By J. G. Clark, M. D. V The Results of Operations for the Core of Inguinal Hernia. By Joseph C Bloodid, M. D.


Volume VIII. About 500 pages with illustrations. (In

press.)

Studies in Typhoid Fever.

Bv William Osler, M. I")., with additional papers by J. M. T. Finney. M. p., S. Plrxkee, mil. I. P. Lyon. 51. D„ L. P. Hamburger, M. n., H. W. Ctjshikg, M. D., arid J. F Mitchell, M.D.

The price of a set bound in elnth [Vols. I-V1I] of the Hos2>it<il Reports is $35.00. Vols. I. II and in are not sold separately. The 2'iiee o; I ■•Is. IV. V. VI nn,l VII is SS.OO each.

Subscriptions for the above punlicatio


The Johns IIopHns Hospital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured from. Messrs. CUSH1NO & CO. and the BALTIMORE NEWS COMPANY. Baltimore. Subscriptions, 81.00 a year, may be addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE ; single copies will be sent by mail for fifteen cents each.


BULLETIN


OF



THE JOHNS HOPKINS HOSPITAL.


Vol. Xl.-Nos. 112-113. 1


BALTIMORE, JULY-AUGUST. 1900.


[Price, 30 Cents.


COWTEWTS.

PAGE HAOE

On the Present Status of Therapy and Its Future. By r. I> r i„ l:l ry Carcinoma of the Appendix Vermiformis; II. Car Lewellys F. Barker, M. B 149 cinoma of the Appendix Secondary to Carcinoma of the

A Comparative Study of Some Members of a Pathogenic Ovaries. By Elizabeth Hurdon, M. D 175

Group of Bacilli of the Hog Cholera or Bac. Enteritidis A Case of Transient Spastic Con nt strabismus. Bv

(Gartner) Type, intermediate between the Typhoid and Samuel Theobald, M. D .178

Colon Groups. With the Report of a Case resembling'

Typhoid Fever, in which there occurred a Post-Febrile Summaries or Titles of Papers by Members of the Hospital

Osteomyelitis due to such an Intermediate Bacillus. By and Medical School Staff appearing Elsewhere than in

Harvey Gushing, M. D., 1"'<; the Bulletin, 180

Charles Frederick Wiesenthal, Medicina? Practicus, the Notes on New Books 181 Father of the Medical Profession of Baltimore. By

Eugene F. Cordell, M. D 170 Hooks Received 181


ON THE PRESENT STATUS OF THERAPY AND ITS FUTLRE.

By Levvellts F. Barker, M. B., Tor., Associate Professor of Pathology, Johns Hopkins University.


The only means we have of judging what the future has in store is to review the history of the past and to view accurately the present tendency or drift. The history of therapy is the history of medicine, for medicine began with therapy. It is not my purpose in the time allotted to rue to undertake a recital of this history; I shall have to be content simply with an enumeration of epochs and perhaps a hint at the periods of progress.

Historians are gradually collecting for us the data concerning the earliest therapeutic efforts. The history of the earliest medicine shows of what a jumble these efforts consisted. With the dawn of intelligence the sympathy which was gradually evolved through the sense of pain led the primitive man to attempt to relieve the pain of his fellows. You recall the lines of a literary medical man:

" The hunt is o'er; the stone-armed spears have won: Dead on the hillside lies the mastodon. Unmoved the warriors their wounded leave: The world is young and has not learned to grieve.


•Address in medicine delivered before the Ontario Medical Association, Toronto, June 6th, 1900.


But one, a gentler sharer of the fray, Waits in the twilight of the western day, Where 'neath his gaze a cave-man, hairy, grim, Groans out the anguish of his mangled limb. Caught in the net of thought the watcher kneels, With tender doubt the tortured member feels, And, first of men a healing thought to know, He finds his hand can check the life-blood's flow."

Disease is as old as man — it is only the knowledge of disease that is recent. In the fiercer physical struggle for existence which must have characterized the life of our primitive forefathers, external wounds and manglings, as well as physical injuries due to exposure to the weather, to extremes of cold and heat, must have been common. Crude surgical procedures evolved by herdsman or shepherd began to be applied to man. The diseases peculiar to the female sex were first treated by the wise old women who had lived through the mysteries of the life of that sex. Of the nature of disease in general and particular the ghost of a true idea did not exist. Obscure diseases were regarded as instances of demoniacal possession. Prayers, chants and sacrifices to healing gods were universal. Devils were exorcised chiefly through the medium of priests. The priestly art and that


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[Nos. 112-113.


of the physician were often combined. In China, in India, in Chaldea, in Egypt, the development of early medicine followed the same fundamental principles, though each country manifested special peculiarities.

The medicine of the Greeks interests us as much as any. Philosophers all. with an intense longing for the good, the true and the beautiful, they have left behind them records which in many respects make modest even the reader of to-day. In Heraclitus. Democritus and Empedocles and. above all, in Hippocrates we meet with much that is practically good in modern medicine and philosophy, especially as concerns the individual life, the ideal development of the personality. Though infants in anatomy and physiology and almost entirely ignorant of the nature of specific diseases, the Greek physicians had accumulated an account of symptoms and conditions and a therapeutic armamentarium that surprises the modern who for the first time reads his Hippocrates. The treatment of fractures and dislocations, the trepanning of the skull, the tapping of the abdomen and chest, the mode of dealing with hernia show us how daring they were in surgical measures. Had they known how to control hemorrhage, who can tell what operations these cool-headed Greeks might not have devised. They were far less happy in the more difficult field of internal medicine. Most of their ideas about internal diseases were wrong, but some of their descriptions of individual cases are magnificent. Concerning the therapy of internal diseases, Hippocrates bad many sound principles, and described some good practice. He recognized the healing power of nature and urged his followers to aid and follow nature — "quo natura vergit, eo tendere opo'rtet." In Hippocrates can be found the tenets of many of the famous schools which have followed him. The principle of " contraria contrariis " and that of " similia similibus" are both in his pages, but wiser than some who came after him he limited himself to neither. " According to its kind and the circumstances underlying it, a case must sometimes be treated byagents acting unlike the disease, sometimes, on the other hand, the treatment must be undertaken by agents acting similar to the disease. The reason for this lies in the weakness of the human organism." Perhaps the strongest part of the therapy of that day was in the emphasis laid upon diet, gymnastics, bathing and mode of life in general. Who but has read and appreciated the Charmides of Plato, that exquisite dialogue in which the principles of Greek temperance are embodied. For a long time after Hippocrates this personal hygiene was accentuated. The visits of young men to the temples of /Esculapius, there to be instructed as to how to live, were long continued. Walter Pater's appreciation of a visit of this sort described in Marius the Epicurean will be recalled by many of you.

In Galen's time theory and gross empiricism reigned supreme. The idea of the four elements, heat, cold, dryness and moisture influenced the giving of drugs. These elements in a sense corresponded- to the four cardinal juices of the human body, blood, mucus, yellow bile and black bile. The


therapeutic ideas of Galen, like his medical ideas in general, dominated medicine for a thousand years.

With the advent of Vesalius and the development of human anatomy one might have hoped for rapid improvement in therapy, but this improvement was not immediately forthcoming. Even Harvey's discovery of the circulation of the blood and Malpighi's studies of physiology and pathologywere not immediately fruitful in a therapeutic way. Paracelsus alone stands out as a reformer in internal medicine and therapeutic effort. He bravely opposed the authority of Galen, recognized the fallacy of trusting to knowledge obtained from books and relied rather upon personal observation and experience. Analysis shows, however, that even Paracelsus did but little to advance the actual knowledge of therapy.

About this time there was a wide-spread awakening in all the natural sciences. Descriptive natural science and systemization ruled the thought of the day. During the period which followed a series of medical systems developed, based upon one-sided theories and badly based generalizations; Haller's doctrine of irritability. Brown's doctrine of stimuli. Hahnemann's homoeopathy, Gall's phrenology, along with many other schools came at this period to their development.

Real progress in therapy dates from the time when natural science became an exact study. Rigidly accurate observation followed by mature reflection has led to experimentation. Medicine of this sort is only a century old. It was almost synchronous with the widening of chemical discovery and of the working out by physicists of the principles which underlie many natural phenomena which up to the time had been entirely obscure, that microscopic studies began to be prosecuted seriously. Histology developed with Bichat; the cell doctrine with Schleiden and Schwann, pupils of the celebrated Johannes Midler. The French and the Germans became enthusiastic for pathological anatomy. Rokitansky counted his autopsies by thousands. The older physicians like Sydenham and Bcerhaave, found worthy successors in Louis, Schonlein, Traube, and Wunderlich.

Virchow's cellular pathology established an entirely new view-point whence disease-processes could be observed. Charles Darwin's work on the " Origin of Species," Herbert Spencer's philosophy and Huxley's researches in comparative anatomy stimulated investigators in all sciences to examine into the evolution of phenomena, to consider the order of events in organic processes. Enormous strides continued to be made in physics and chemistry, and the new facts discovered in these branches permitted of the development of physiology by Ernst Briicke, Carl Ludwig. Emil Du Bois Reymond, Helmholtz and Claude Bernard. Caspar Fr. Wolff, Karl von Baer, Balfour, and His unravelled the mysteries of embryonic development. Improvements in the microscope and in microscopic technique led to a deeper penetration into the mysteries of histology and microscopic anatomy, normal and abnormal, than the most enthusiastic could have hoped for a few years earlier. New instruments of all sorts were


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151


devised. Auenbrugger's percussion and Laennee's auscultation revolutionized physical diagnosis. The ophthalmoscope, the laryngoscope and the speculum, had much to do with the establishment of the specialties of ophthalmology, laryngology and gynaecology.

In the fight against infectious diseases a great victory had been won in the discovery of vaccination by Edward Jenner. Later on Henle's ingenious speculations concerning the nature of contagious diseases set many great minds in motion. With Pasteur and Koch came illumination. The infectious agent in the majority of infectious diseases is now known, ean be cultivated in pure culture and can be utilized in animal experiment.

Physiological and pathological chemistry have been unveiling the mysteries of the fluids and solids of the body; pharmacology and toxicology arc investigating the influences of drugs and poisons upon these. The application of Lister's happy idea with regard to wound infection, aided by the Americanborn boon of anaesthesia and a bloodless technique, totally changed the aspects of surgery. Wound infection, if not entirely an event of the past, has been enormously reduced. The holiest places of the body are to-day invaded by the surgeon's knife; the abdomen, the thorax, the joint cavities and even the brain are frequently and fearlessly explored. The heart, the last organ of man to be made accessible to surgical treatment, can now be sutured with success.

But more time must not be spent in glancing at the past; it is necessary at once to look at the present and to divine, if it be possible, whither we are being led.

As a result of development along so many diverging lines the study of modern medicine is concerned with a field so wide that he who glances over it, cannot fail to be appalled by its magnitude. No single intelligence can in these days be familiar with the details of growth in all its parts; no single individual ean hope to work efficiently in more than one or two of its subdivisions. The complexity of the work demands a division of labor, and most is gained from the efforts of men who, familiar with the general trend of progress in the whole field, concentrate their activities upon some one corner of it. Individual workers in the special medical sciences are pushing their investigations at the moment with unwonted zeal. Anatomists are ever devising new technical methods; the cells formerly believed to be very simple " elements " are found to be highly complex organisms; parts of the body as, for example, the nervous system, are having their true cellular nature for the first time revealed; the structural basis of the intrinsic mechanisms of individual cells is in process of demonstration; the relations of the basis in one cell to that in other cells are being found out. Physiology, so long interested in the hydraulic principles of the circulatory apparatus and the muscle-nerve preparation, is being diverted into new channels of research, utilizing in its experiments the newly discovered principles underlying chemical and physical phenomena. The oxygenating and reducing processes which occur in the body, the various stages of anabolic and cata


bolie metabolism, the phenomena of secretion and excretion, the interrelations of the various bodily activities, the functions of the different neural complexes, the mechanisms of defence and adaptation — these are some of the subjects with which physiologists are now busying themselves.

In pathological anatomy and physiology just as strenuous efforts are being made as in the other fundamental departments. Our ideas concerning inflammation have been so much modified that we are advised by some of the ablest pathologists to give up the term altogether. The nature of inflammatory exudates is still under discussion; what elements are of haemic and what of local origin are disputed; the great cleft between the acute inflammations and the chronic processes associated with production of new connective tissue is still unsatisfactorily bridged. The aetiology of tumors, as yet unsolved, stimulates the embryologist on the one hand and the parasitologist on the other to renewed exertion. New tumors are being discovered; old ones are being regrouped; finer and finer distinctions between benignancy and malignancy are being drawn with results eminently satisfactory for the practical surgeon.

The therapeutic hopelessness that pathological anatomy inspires is more than compensated for by the faith in the future of therapy and prophylaxis directly derivable from a consideration of the teachings of pathogenesis. As pathological processes are traced further and further back to the earliest stages when function begins its deviation from the normal and the causes underlying those deviations gradually become recognizable the means of prevention and the indications for treatment become obvious.

Bacteriology appears to have done for us the greatest work of which it is directly capable; further advances in a similar direction promise to be made rather through the aid of chemistry and physics. The study of protozoan invasions is yet in its infancy and may have surprises in store for us. One cannot help but feel that we are on the brink of the discovery of the infectious agent in syphilis and the infectious fevers, but who can prophesy what the nature of the agent will be — animal, vegetable or less highly organized " ferment."

We have some reason to be proud of the present status of public hygiene. There never was a time when the general public was more industriously educated concerning the importance of hygienic measures than at present — never a time when the laity was more thoroughly exercised over this topic. .Sanitary associations are innumerable; public health departments are everywhere demanded. Meat, milk and vegetables are inspected; impurities in food and drink are more and more excluded through the vigilance of the law. Contagious diseases are diagnosed early and isolated by city officials. Governmental sanitaria are in sight. Quarantine and disinfectant measures are more rigidly and fortunately more intelligently employed than ever before. Great epidemics are being choked at their starting places, the only mode in which they can satisfactorily be combatted. A fire can be extinguished by a fire department in its incipient stage — once well


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under way it is beyond the control of human interference. There is good prospect that ere long the world will be through with those tremendous outbreaks of contagious disease of bacterial origin which from time to time have so devastatingly swept over both Western and Eastern civilizations. Thanks largely to Anglo-Saxon enterprise the back yards of the world in which the embers of epidemics smoulder are being rapidly cleaned up; this together with the rendering ever more infection-proof of the materials to which the flame of infection spreads bids fair to make the whole subject if not entirely, at least largely, a matter of history.

The present position of personal hygiene is a subject upon which we have less reason to congratulate ourselves. In principle we know much, in practice we do but little. Concerning climate, fresh air, diet, clothing, bathing, work, rest and recreation there is perhaps less dearth of information than negligence and inattention in performance. We behave hygienically when we are forced to do so, but not as a well planned order of life. Above all on this continent we have as yet to learn how to live and the problem here is less simple than elsewhere, for life here, especially in the great centres, is life at its most complex. Nowhere else is the strain so great — nowhere else does it so rapidly increase in tension. It must be a nervous system other than that which has been and that which is that will stand it. That nervous system may be now evolving, but in the meantime the unfit are succumbing in numbers ever more alarming. Moderation in all things and elimination of the non-essential from our lives would do much to tide us as a race over the transition period.

Perhaps the most significant movement at present observable in medicine is the beginning of the application of the newer ideas of physics and chemistry to the solution of biological questions. One has ever to be on his guard lest he expect too much from the introduction of new methods of approaching problems, but in this instance the principles underlying are so fundamentally important and have already worked such marvelous transformations in the mode of thought and activity of chemists that we are justified in expressing great hope for the future in their use by medical investigators. The doctrines of van't Hoff and Arrhenius are pregnant with great possibilities, van't Hoff's brilliant generalizations with regard to the behavior of solutions are found to hold good by a whole series of workers — the laws of osmotic pressure appear to be strictly analogous to the laws of Boyle, Gay-Lussac and Avogadro concerning gases. The theory of the dissociation of electrolytes — salts, acids and bases — into their components, the ions (cations and anions), which we owe to Arrhenius, affords a satisfactory explanation of an enormous number of facts hitherto unintelligible. These newer doctrines not only correlate facts hitherto unconnected, but they have shown the way to new lines of experimentation and have acted as a most powerful stimulus to original research. While it is probably not true that chemical activity is due solely to ions and never to whole molecules, yet the number of chemical reactions which according to the physical chemists are purely


ionic is very great, including certainly the majority thus far investigated. The studies of Kahlenberg and True on the toxic effects of acids and bases on plant life indicate that it is the hydrogen ion of the acid and the hydroxyl ion of the bases which is the active constituent. The significant experiments of Loeb on the power of muscle to absorb water in the presence of acids suggest the value of the physical-chemical method of thought in physiology. The work of Kronig and Paul upon the effects of disinfectant substances has made probable the ionic nature of this influence. The introduction by Dreser of the conception of the osmotic work done by the kidney and a calculation of the same in foot pounds is of the deepest interest, even if his interpretation of his results, as it would appear, has to be somewhat modified. The practical results in sight from the clinical studies by the method of physical chemistry undertaken by Hamburger, Kbppe, Koranyi and others are being thankfully received by clinicians all over the world. Loeb of Chicago has recently interested us by proving the poisonous effects of pure solutions of common salt, and though his experiments have been upon lowly organisms, I should consider the medical man rash who continued to give a patient of low vitality large doses of ordinary salt solution when he can just as well introduce a solution in which the holding in a variety of salts corresponds more nearly to that of normal serum. Almost startling, too, is the assertion of Loeb that the eggs of echinoderms can be fertilized in the absence of spermatozoa by magnesium ions. If the phenomenon of fertilization — that sanctum sanctorum of physiological processes begins to be invaded by physical chemistry — what may we not expect from that science in the future. It would take too long to refer to other work in this field — to the constant reciprocal relation existing between chlorides and achlorides of the blood and urine, to the newer ideas on the occurrence of oedema, to the speculations concerning so-called ion-proteids. Suffice it to say, that the promise for the future in pathogenesis and in pharmacodynamics is much brightened by the advent of physical chemistry. Were a medical student, suited by heredity and environment to look forward to the higher things in medicine, to ask me the question, " How can I best fit myself to make real advances in knowledge in medicine and therapy during the next twenty-five years? " I should say, " In addition to a thorough medical course, arm yourself with sufficient mathematics and gain a thorough theoretical and practical training in the methods of physics and chemistry and especially in the principles and methods of what is called ' physical chemistry.' After this turn your attention to the solution of medical problems." Not that the doctrines of van't Hoff and Arrhenius will be able to clear up all difficulties — the doctrines themselves may even be found to be only helpful hypotheses and later be supplanted by others less faulty,* but all our knowledge is but relative, and at present new knowl


  • Some physicists are inclined to believe that the "corpuscular"

doctrine advanced by J. J. Thomson seriously threatens the position of the ion-conception.


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edge can probably be easiest readied by working witb the methods referred to.

The conviction is not infrequently expressed that surgery having gone so far cannot have many great conquests still before it, but when we review recent progress it would seem hazardous to deny the possibility of still more interesting advances. The extensive use of local anaesthesia since the introduction of cocaine in 1884 has led to striking modifications in surgical technique. The general narcosis produced by ether and chloroform together with perfected haemostatic methods had a tendency to encourage slow operations. With cocaine anaesthesia and infiltration of the tissues with nearly indifferent fluids surgeons have again been compelled to operate more quickly and with greater efforts at precision. The discovery of the X ray has made bone surgery much more accurate work than it could ever have been before. Most noteworthy, perhaps, in modern surgery, are the operations which are now undertaken upon the liver, gall-bladder and bile ducts. These together with gastrointestinal surgery have elevated abdominal surgery to even a higher rank than that attained by pelvic surgery through the activity of the gynaecologists. Progress can certainly be expected still in the treatment of surgical diseases. Max Broedel in Kelly's service has just shown us by a study of its blood-vessels the safest way to cut into the pelvis of the kidney.

The sharp line between medicine and surgery is breaking down. The two domains overlap at their boundaries and the importance of medical men and surgeons working together is becoming more and more appreciated. The establishment of a journal, the Mittheilungen aus dem Grenzgebiete der Chirurgie und Medizin, is an indication of the feeling which exists. The surgery of the future aside from emergency cases will be largely done in hospitals. Surgeons, to attain the necessary technical skill and familiarity with normal and pathological living tissues, must stand for years over an operating table. A trained corps of assistants and nurses is essential for the more difficult problems which now fall to the lot of the surgical specialist.

Compared with the brilliant achievements of the surgeon the therapeutic efforts of the physician are felt by most medical men as well as by the laity to be somewhat disappointing. In spite of the extraordinary keenness of diagnostic power which has been developed in internal medicine the painfully exact studies in pathological histology and in physiological and pathological chemistry, the wide-spread activity in pharmacological and pharmacodynamical experiment and the indefatigable efforts of the manufacturing chemist to supply new drugs, the view is prevalent and rightly so that in the treatment of internal diseases " we have more to hope for the future than to entrust to the present." The explanation is obvious. The age is one of doubt. Authority now less than ever before counts for anything. There is a lively fear of empiricism, an insatiable desire for rational explanation. Pathological anatomy stimulated to brilliant diagnosis, but, for a time at least, it encouraged therapeutic pessimism.


Skoda, the type of a therapeutic nihilist even went so far as to say " we can diagnose disease, describe it and get a grasp of it, but we dare mil expect by any means to cure it." In such a temper drugs of unknown physiological action cannot conscientiously be set to act upon bodily tissues in disease in which we are ignorant of the deviations from the normal of the chemical and physical processes going on in the cells. The death blow came first to polypharmacy; to-day, with many physicians, pharmacotherapy, as a whole, is almost moribund. Ask the prescription chemist how his work now compares with that of fifteen or twenty years ago. He will tell you that he is lucky if he fills ten recipes to-day, where he formerly filled a hundred. The druggist in the village or small town may still receive an occasional prescription which orders ten or fifteen varieties of herbs, but the fine old concoctions know to our fathers have almost entirely disappeared. It is seldom in this day that more than one or two drugs are prescribed at one time and these too often because " the patient must have something." A dozen drugs altogether suffice for the pharmacotherapeutic armamentarium of some of the most eminent physicians on this continent.

The reaction against the use of drugs, together with the development of the expectant method of treatment, permitted of a more accurate study of the natural cure of the disease than was before possible. Consistent homoeopathists who pushed their minimal dosage to such a degree that any conceivable drug effect was prevented did much, though unintentionally, to illustrate the healing power of nature unaided. Dietl's studies of pneumonia, treated without blood-letting, convinced him and the world that the effects of therapeutic interference in this disease had been greatly over-estimated.

Marked as have been the advantages derived from these therapeutic revolutions I cannot help but feel that the time has come for a more hopeful outlook for therapy in internal medicine. More thought among the best men might with advantage be given to it. Not that a whit less attention should be given to diagnosis or to pathological study — only through these is a successful therapy thinkable — but may we not interest ourselves more in the therapeutic measures of proven value which are really at our disposal. I am fully aware that some practitioners fail to properly diagnose their cases, that there are those who have but little scientific knowledge of disease, and it is these usually who possess the largest magazines of misplaced confidence in drugs. It may even be said to be certain that the majority of men in practice who leave it temporarily to undertake post-graduate work, would be benefited more by instruction in the wealth of diagnostic aids recently put at our disposal than by a course in therapeutics. That the skilled diagnostician, however, can be of greater service to his patients if he put the same keen, welldirected intelligence into motion with regard to treatment that he uses in diagnosis instead of stopping short at the diagnosis and shrugging his shoulders when therapeutic effort is mentioned, must be patent. A- Leyden puts it: " The task of therapy is to help the patient as far as is possible with the


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means at its disposal at the time; it dare not postpone the treatment to future discoveries. Specific therapy, long looked upon as that alone which is safe and worth striving for, is deprived of its ahsolute dominion; instead of ' curing diseases,' our task is altered to ' making patients well.' "

1 cannot help but think that one of the causes of therapeutic pessimism among the better men in the profession lies in the fact that when therapeutics is spoken of most men call pharmacotherapy disproportionately into mind. It is because they are insufficiently known and appreciated that dietotherapy, climatotherapy, hydrotherapy, kinesiotherapy, electrotherapy ami psychotherapy are not ranked with pharmacotherapy, and yet, in the majority of cases with winch physicians deal, one or more of these is of far greater importance than treatment with drugs. Psychotherapy especially has a great future. Not until physicians become better psycholo-. gists and learn better how to apply psychic methods in the treatment of disease can we hope for the disappearance of such psychic epidemics as that represented by Christian science. In the near future psychopathogenic mechanisms should be carefully studied in order that psychoprophylaxis can have a wider field.

What the future of pharmacotherapy will be who will be rash enough to judge? That it will be great seems certain. That it cannot soon be great seems sure. Synthetic chemistry has supplied us with a host of new bodies for experimentation. Only a very small percentage of these have thus far been found to be of value. Antipyretics, analgesics and hypnotics especially are being multiplied. They have to be slowly tested on animals, then on healthy human beings and last of all on human beings in diseased conditions before their actual value can be ascertained. The effects of drugs like acetonechloroform and urethane astonish us, however, and whet the appetite for further discovery.

No single system of therapy is likely soon again to hold general sway. Contraria contrariis and similia similibus have ceased among scientifically cultivated men to be a universal guide of therapeutic action. The biologically fundamental principle of Pfliiger and Arndt, namely, that " minute stimuli, excite to vital activity, stimuli of medium strength favor it, strong stimuli inhibit it, strongest abolish it, it being, however, always an individual matter whether a given stimulus will prove to be feeble or one of medium strength or maximal," associated with the Ritter-Valli law that " diseased organs are in a state of heightened excitability " has been made by Oscar Schulz the basis of his " organ-therapy." Very valuable as the concept appears to be, medical men, with a caution born of experience, will be loath to accept it or any other generalization as an all-sufficient maxim.

The revival of organotherapy or opotherapy, as the French designate it, is a marked feature of present treatment. One of the oldest methods, having been employed long before the Christian era, opotherapy began with an attempt to producean aphrodisiac effect by administering the genital organs of the respective sex to the individual who desired stimulation.


It is rather curious that the present revival was inaugurated by Brown-Sequard, the composition of whose elixir vitae you know. Organotherapy has, however, this time a rational basis in the conception of an internal secretion, deduced by BrownSequard from the studies of Claude Bernard. The production of experimental cachexia thyreopriva and the bringing of the proof that the transplanted thyreoid would save an animal from the disease suggested the possibility of the use of thyreoid substance in myxcedema and cretinism witli the marvellous results which most practitioners have by this time been permitted to observe. The chemical analyses of Baumann showed that an iodine compound in the normal thyreoid is an important clement in the gland.

This " Parenchymsaftherapie," as Virehow designates it, is obviously a substitution-therapy — a restoration to the diseased body of chemical substances, the removal of which from the normal body gives rise to symptoms of disease. It is in atrophic conditions of the gland that the therapy is valuable. Myxcedema and cretinism are diseases which correspond to the "altruistic atrophy" of Hansemann, while Basedow's disease is thought by many to be an example of " altruistic hypertrophy." Had the principles underlying thyreoidtherapy been earlier recognized we should not have expected benefit from the administration of thyreoid extract in hypertrophic conditions of the gland.

The French are busy testing the effects of thyreoid-therapy on the healing of fractured bones. The experimentation is still in progress and it is too early yet to say much regarding it.

Ponfick's remarkable case, which makes it appear possible that the hypophysis and the thyreoid may be compensatory glands, will doubtless stimulate to further study.

With the advent of a successful thyreoid therapy, the notoriety hunters soon introduced organic extracts of the most various sorts. Cardin, cerebrin, heparin were launched and vaunted. Examination of the manufacture of a certain prostate extract showed that it was being prepared from female animals! Such empirical attempts were worse than useless. They represent a return to the primitive.

With certain of the organs we are, however, provided with a rational basis for experimentation. Mering and Minkowski proved the disastrous effects upon the animal of extirpation of the pancreas. The diabetes which followed extirpation could be prevented by transplantation of pieces of pancreas. Yet for reasons not satisfactorily understood pancreas therapy has not been made practically useful.

Again, the effects of removal of the adrenals have been carefully studied. Addison's disease is believed to be largely the result of loss of adrenal substance. Unfortunately, the administration of adrenal extract, while it may alleviate some of the symptoms of Addison's disease, has no effect on the others. The attention paid to the adrenal of late by physiological chemists has, however, been most fruitful. The studies concerning the blood-pressure raising constituents are extremely valuable. The active substance has been isolated


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and its chemical nature studied. The work of Aliel and others upon epinephrin is furnishing most interesting data for future use.

Rhinologists are using adrenal extract as a vaso-constrictor in the nose. Fresh from the German press comes a careful paper by Stoelzner (in Heubner*s clinic), detailing a large series of cases of rickets, markedly benefited by adrenal extract. He finds that the cranio-tabes. the sweats, the delayed coming of the teeth, the irritability of the vaso-motor system. the general restlessness and excitability, the curious smell of the urine, are all very markedly improved by the treatment. The softening of the thorax is frequently benefited. The spasm of the glottis and other symptoms of tetany, however. generally appear to remain uninfluenced by the adrenal extract. The improvement can frequently be made out during the first week of treatment. An amelioration of the symptoms goes on rapidly for a few weeks, later on more slowly.

The spleen and bone-marrow extracts which have been introduced increase the white and red corpuscles of the blood, possibly owing to the nuclein which they contain. That hypophysis extract is of no value in acromegaly would not be surprising, if acromegaly should turn out to be, as some investigators believe, rather an instance of " altruistic hypertrophy " in the sense of Hansemann than one of " altruistic atrophy."

One of the most recent advances claimed in opotherapy is the feeding of ovarian substance as a substitution-therapy in cases (1) where the ovaries have been removed at operation. and (2) at the climacteric to relieve the phenomena characteristic of that period.' The substance is given in Germany in the form of Landau's oophorin tablets. Loewy and Eichter report that this ovarian substance has a remarkable capacity for increasing the oxygenating power of the body-cells in n which the ovaries have been removed. Their protocols arc very convincing. Whether or not the therapy will be useful in preventing the obesity so characteristic of so many such cases we must wait to see, but the Germans feel confident that it will.

The advances along the lines of opotherapy are sufficiently indicated by the foregoing experiences. Physiology, experimental pathology, physiological chemistry, pharmacology and pharmacodynamics must lead the way.

In the struggle against infectious diseases a rapid extension of the powers of the physician is observable. The resistance of human beings as a whole is being increased not only by the

Blow method of natural selection, but by a more rapid i I

through personal hygiene. Prophylactic inoculations have been multiplied since the work of Pasteur. The cholera inoculation, that for pesl and thai for typhoid, appear to be valuable. Flexner m Philadelphia is now experimenting with a prophylactic against tl dysenteriaa so deadlj in

its effects in the Philippine Islands and Japan. The introduction of Behring's serumtherapy in diphtheria has undoubtedly greatly reduced the mortality of that disease, indeed, diphtheria is now scarcely a disease to be dreaded. Aside


from the serum against diphtheria, however, there is as yet little of practical value to acknowledge from this side.

The antidiphtheric serum is an antitoxic serum. That introduced against tetanus is also an antitoxic serum. To be ranked with these two is probably also Calmette's serum against snake poison. Tetanus serum is only preventive, not curative, possibly owing to the fact that the antitoxine injected subcutaneously or into the blood cannot reach the toxine when once the latter has combined with the protoplasm of the nerve cells. Even intracerebral introduction of the antitoxine is not fully satisfactory for obvious reasons. All the other sera which have been introduced, namely, those against cholera, the streptococcus, pneumococcus. the bacilli of plague, anthrax and typhoid fever are not antitoxic sera but antibacterial sera. They do not neutralize the poison which the bacteria produce but have the power of killing the bacteria in the body of the patient and of dissolving them up. Not a single one of these sera is as yet practically useful as a therapeutic measure.

Ehrlich's studies make it probable that with these antibacterial sera at least two bodies are necessary for successful action; (1) the interbody or immunizing body, and (2) the end-body or complement (formerly called addiment by Ehrlich). The latter is present in normal serum and is the true dissolvLng body, but it can act only when it is bound to the bacterial cell by means of the immunizing body. The antibacterial sera are rich in the immunizing body. Tt may be possible that they are insufficient owing to there not being enough of the end-body present. Wassermann is now making experiments in this connection. He hopes that by increasing the amount of end-body or complement available that the antibacterial sera may be rendered valuable in the treatment of disease in human beings.

Had not this paper already become too long it would have been interesting to refer to the progress making in the treatment of conditions of autointoxication and of the so-called constitutional diseases, but I must forbear.

From what has been said it is obvious that we have no reason to be discouraged as regards the future of therapy, but rather cause for hope and enthusiasm. We have learned the secret of progress and some formula; for daily action. The secret of advance lies in the consciousness of the tact that it is the orderly application of the well-trained intelligence to medical problems that alone yields valuable results— not the haphazard guess work of the ignorant and untrained mind. Prolonged teclmical education and systematic research lead to therapeutic advance. In daily life, in the application of discoveries already made, the quack and the routinist physician, with the healing power of Nature behind them, will cure many cases, but we can be sure thai "renter 3UCCess and especially greater mental satisfaction will attend the efforts of the physician well educated in the various medical scienci thinking all around and through his case, arrives at thi accurate diagnosis possible and gives the patient the benefit of a well-planned conscientious treatment, utilizing every means


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which will tend to his cure or relief. If this physician have a speeific he will be glad to employ it; if radical cure be impossible he will not neglect the palliative; if at last the exitus


lethalis cannot be prevented he will at least see that the end is euthanasic.


A COMPARATIVE STUDY OF SOME MEMBERS OF A PATHOGENIC GROUP OF BACILLI OF THE HOG CHOLERA OR BAC. ENTERITIDIS (GARTNER) TYPE, INTERMEDIATE BETWEEN THE TYPHOID AND COLON GROUPS.

WITH THE REPORT OF A CASE RESEMBLING TYPHOID FEVER, IN WHICH THERE OCCURRED A POST-FEBRILE OSTEOMYELITIS

DUE TO SUCH AN INTERMEDIATE BACILLUS.

By Harvey Cushing, M. D. {From the Laboratory for Surgical Pathology of The Johns Hopkins Hospital.)


The possibility that under varying conditions of environment different characteristics may be acquired by the members of the large typhoid-colon group of bacilli has inclined some investigators to regard them as closely related or even interchangeable organisms. Nevertheless, there are certain forms which possess, as. ordinarily encountered, such definite cultural and pathogenic peculiarities, and which have a tendency to retain the same with such a degree of permanency, that they may be recognized as distinct and constant variations. That this applies to B. typhosus and B. coli communis, the extremes of the group, is too well known to be dwelt , upon. There exists, however, intermediate to these forms, one especially recognizable subdivision, the clinical significance of which as a definite type has been much slighted.

The members of this particular intermediate group arc bacilli which possess the morphological and motile properties of p]berth's bacillus but differ from this organism chiefly in the fermentation reactions, since they produce gas in the presence of glucose and other more easily fermentable carbohydrates. Their chief distinguishing feature from the bacillus of Escherich, on the other hand, rests upon the fact that fermentation in various media made from milk does not produce sufficient acidity to precipitate the casein, but, on the contrary, the acid production is but a transient process and is followed, in the presence of air, by a prompt (2-3 days) and distinguishing alkalinization of the media which furnishes a ready means of differentiation from both the typhoid and colon type.

Herbert E. Durham. 1 in 1898, boldly divided this whole family into three groups as follows:

I. The Ebertb group including /;. typhosus and its near allies.

IT. The Gartner group including B. enteritidis ami its near allies.


III. The Escherich group including B. coli communis and its near allies.

He states in parentheses that the " allies " of the typhoid group are almost unknown,* while those of groups II and III have never been sufficiently worked out.

In this intermediate or Gartner group Durham has placed the following organisms: Bac. enteritidis of Gartner, 2 B. Breslaviensis (von Ermenghem)," B. morbificans bovis (Basenau),* the " Wurstvergiftung " bacillus described by Fischer," B. Friedebergensis (Gaffky und Paak).° the Cotta "Fleischver


1 Durham, Herbert E.: On the serum diagnosis of typhoid fever, with especial reference to the Bacillus of Gartner and its allies. The Lancet, Vol. I, p. 154, January 15, 1898.


  • Organisms culturally indistinguishable from B. typhosus have

been encountered in the surgical laboratory on several occasions during the past two years. These have been obtained from a perirenal abscess, from the urinary bladder and from peritoneal infections of intestinal origin unassociated with typhoid; on one occasion from the lumen of a chronically inflamed appendix. Similar organisms have been met with in the alimentary canal of healthy dogs. We have hesitated to regard these as B. typhosus from the absence of a definite reaction with typhoid serum though they are doubtless closely related forms. From what I have seen of Shiga's bacillus dysenteria?, a specimen of which, obtained in the Philippines, was kindly given to me by Dr. Flexner, I should regard it also as an allied form of B. typhosus.

2 Gartner: Ueber die Fleisehvergiftung in Frankenhausen am Kyffhiiuser und den Erreger derselben. Correspondenz-Bliitter des Allgemeinen iirztlichen Vereins von Thiiringen. No. 9, 1888.

3 Von Ermenghem: Recherches sur les empoisonnements produits par de la viande de veau a Morseele. Travaux du laboratoire d'Hygiene et de Bacteriologie de 1' Universite de Gand. Tome I, fassicule 3, 1892.

'Basenau, Fritz: Ueber eine im Fleisch gefundene infectiose Bacterie. (Bac. morbificans bovis.) Archiv fur Hygiene. Bd. XX, S. 242, 1S94, and XXXII, p. 219, 1898.

"Fischer, Bernhard: Ueber einige bemerkenswerthe Befunde bei der Untersuchung eholeraverdaehtiger Materials. Deutsche medicinische Wochensehrift, Jahrg. XIX, S. 575-598, 1893.

6 Gaffky und Paak: Ein Beitrag zur Frage der sogennannter YVurst-und Fleischvergiftungen. Arbeiten aus den kaiserlichen Gesundheitsamte. Band VI, S. 159, 1890. Also Deutsche med. Wochensehrift, Jahrg. XVIII, S. 297, 1892.


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giftung" bacillus. ' as well as the organisms described by Gunther/ Karlinsky,' Kaensehe'" and others.

These bacilli, it will be seen, come almost uniformly from meat-poisoning epidemics which occurred on the continent, and presumably they are the identical organism which Gartner first described in 1888.*

Durham further believes that the gas-producing " typhoid " bacilli of various observers almost certainly belong to this group as well, and not improbably also those cases of " septicaemia typhoid fever " of French authors, in which death occurred before typical lesions had appeared and which were supposed to be due to Eberth's bacillus. In other words, there are possibly intermediate gas-producing forms of the typhoid-colon family which may be the cause of infections giving clinical symptoms easily mistaken for typhoid fever. This is of importance in relation to the cases which are to be described later.

Theobald Smith," during his investigations concerning the bacteriology of infectious swine diseases in 1893, had noted the great similarity between B. cholerae suis and a variety of


r Die Fleischvergiftung in Cotta. 21 Jahresberieht iiber das Medicinahvesen im Konigreich Sachsen auf das .Tahr. 1SS9, S. 104. Ref. Hygienische Rundschau, 1891, S. 716.

'Gunther, Carl: Bacteriologische Untersuchungen in einem Falle von Fleischvergiftung. Archiv fiir Hygiene, Bd. XXVIII. p. 146, 1897.

■ Karlinsky. Justyn: Zur Kenntniss des Bacillus Enteritidis Gartner. Centralblatt fur Bacteriologie, Bd. VI, S. 289, 1889. .

10 Kaensche. C: Zur Kenntniss der Krankheitserreger bei Fleischvergiftungen. Zeitschrift fiir Hygiene, Bd. XXII, S. 53, 1896.

  • This was found under the following circumstances:

In Saxony a diseased cow had been slaughtered and the flesh sold for food. Fifty-seven people who had eaten of this meat became ill, the severity of symptoms being directly proportionate to the amount consumed and inversely to the thoroughness of cooking. One young working man ate 800 grams raw. and died in about 35 hours. Gartner isolated from the flesh of the diseased cow and the organs of this fatal ease his so-called />'. enteritidis. Durham himself 12 has encountered the same organism in the liver of a fatal case from an epidemic in England, and he alone among English writers has concerned himself with these infections. In his valuable address" given at Oldham in 1898 In- lays ('special stress upon the importance of /;. enteritidis as the cause of the various meat-poisoning epidemics and describes his observations on the Chatterton outbreak."

"Smith. Theobald, and V. A. Moore: Additional investigations concerning infectious swine diseases. Bureau of Animal Industry. I'. S. Department of Agriculture. Bulletin No. 6, p. L0, l > :

"Durham, Herbert E.: An epidemic of gastroenteritis asso

dated with the presence of a variety of tin- bacillus enteritidis

(Gartner). British Medical Journal, Vol. II, p. 600, Sept. :;. 1898.

Durham, Herbert E.: An address on the present knowledge

of outbreaks due to meat poisoning. British Medical Journal,

Vol. II. p. IT'.iT. Dee. 17, 1898.

"Bowes and Ashton: An outbreak of Food Poisoning; being

a report on 35 eases of veal-pie poisoning occurring in Chatterton. British Medical Journal, Vol. II, p. 1456, Xov. 5, 1898.


other pathogenic forms among which were Gartner's B. cnterifiilis. Looiiler's />'• hi phi murium, a bacillus found in a mare after abortion, etc. He in consequence has since referred to them as members of the " Hog Cholera Group " of bacilli in much the same significance as Durham uses the term " Uii liner group." Unfortunately, however, owing to what seemed at the time (1885) an advisable change in terminology, the name hog cholera bacillus was given to an organism previously called swine plague bacillus and some misinterpretation has arisen abroad concerning the variety B. cholerae suis as it is now recognized in this country, from' the confusion in nomenclature resultant to this change.*

Recent observations by Reed and Carroll " have further demonstrated that there is a close biological relationship between Sanarelli's Bacillus icteroides and B. cholerae suis and through their report has occasioned much discussion , le the former organism also doubtless belongs in the group under consideration. Some months previous to their published report, acting upon a suggestion of Dr. Welch, I had found that it was almost impossible to recognize any cultural differences between these organisms and bacilli of the B. enteritidis (Gartner) type which I was studying.!

We thus see that the close biological relationship of many of these organisms has been recognized, though no attempt


  • Kruse in 1896 (C. Fliigge, Die Microorganismen, Zweiter

Theil, S. 401) describes the present B. chol. suis of American writers under the name Bacillus snipestifer, which he places in the Hemorrhagic Septicaemia group.

15 Reed, Walter, and James Carroll: Bacillus Icteroides and Bacillus Cholerse Suis — a preliminary note. The Medical News. Vol. LXXIV, p. 513, April 29, 1899.

"1, Sanarelli, G.: Some Observations and Controversial Remarks on the Specific Cause of Yellow Fever. The Medical News. Vol. LXXV. p. 193. Aug. 12, 1S99.

2. Sternberg, Geo. M.: The Bacillus Icteroides as the Cause of Yellow Fever. A Reply to Professor Sanarelli. Ibid. Aug. 1!'. 1899.

3. Reed and Carroll: The Specific Cause of Yellow Fever. \ Reply to Dr. G. Sanarelli. Ibid. Sept, 9, 1899.

4. Novy, F. G.: The Bacillus Icteroides. A Reply to Dr. Sanarelli. Ibid. Sept. 23, 1899.

5. Sanarelli, G.: The Bacteriology of Yellow Fever once More. Ibid. Dec. 9, 1899.

t The culture of B. icteroides which was used had been originally obtained from Rome's laboratory and was but one removed from Sanarelli's original organism. Dr. Heed has since kindly furnished me with three varieties of /{. ictcrnidcs obtained from Santiago and Havana. These organisms belong to the Gartner group and possess no cultural characteristics sufficient to distinguish them from /(. enteritidis or B. eholerw suis. Difference in pathogenic activity in man and animals and in the serumreactions doubtless exist just as do variations in pathogenicity among members of the /•'. COU group, and consequently to state that the hog cholera bacillus is culturally indistinguishable from /(. icteroides does not sreni to me necessarily to indicate that the latter may not be the cause of a specific infection (yellow fever). As will be seen in I lie experiments on pathogenic action, the serum test alone is a means of distinguishing members of the group and cultural similarities are by no means an indication of equalities in pathogenic virulence.


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h made to classify them on other grounds thou variations of pathogenicity in which peculiarity the individual members of a species naturally differ within wide limits, which in no way affects phylogenetic relationship. The variability in nomenclature itself shows how little recognition has been paid to the similarity of cultural as well as of clinical and pathologic manifestations of the members of this intermediate group.

In 1897 Widal " described an organism which was isolated from an oesophageal abscess some years after an attack of typhoid fever, and adopting the nomenclature of Gilbert IS he designated it a " paracolon " bacillus. With this organism he grouped several others having similar characteristics, as the bacillus psittacosis of Nocard and the " microbe de la septicemic des veaux " of Thomassen.™ From Widal's brief description it would seem that this organism is a member of the intermediate group under discussion. It was an actively motile bacillus producing no indol and fermenting glucose but not lactose. Widal's claim for specificity of this particular type was based on the definite serum reaction which the patient's blood showed toward the organisih.

The terms paracolon and paratyphoid, however, Durham does not consider at all appropriate, as the members of the group are quite distinct from both B. typhosus and B. coli.

Gwyn " in 1898 reported a remarkable case which occurred in Dr. Osiers clinic and which presented all of the clinical symptoms of typhoid fever, but in which no serum reaction was at any time demonstrable toward the Bacillus typhosus. From the blood of this patient Gwyn isolated in pure culture an organism having cultural characteristics akin to the Gartner group, and which under the influence of Widal's terminology he designated as a " paracolon." Toward this organism the patient's serum had an agglutinative reaction in further evidence of the infection. The failure on repeated examinations to demonstrate any serum reaction toward B. typhosus was of course not conclusive evidence of the absence of typhoid fever, but the query was naturally raised whether the clinical symptoms could not have been due entirely to an infection with the isolated "paracolon" alone. Of the several hundred cases of typhoid fever which have occurred in Dr. Osier's service since the employment of the WidalGruber reaction has become a routine measure of confirming diagnosis, (inly a few individual cases have failed to show a definite agglutinative reaction toward B. typhosus. It is not impossible thai these eases may have represented infections with members of the intermediate group. Durham mentions in his paper a personal experience with an infection resem 17 )•'. Widal: Seroreaction dans une infection a paracolibacille. La Semaine Medicate, 4 aout, 1897.

"Gilbert: Be la Colibacillose. Semaine Medicale. 1895, p. 1-3.

" Thbmassen, M.: Une nonvelle septicemic des veaux. Annates de ri nst it ut Pasteur. Tome XJ, p. 523, 1897.

M Gwyn, Norman B.: On Infection with a Paracolon bacillus in a case with all the clinical features of typhoid fever. The Johns Hopkins Hospital Bulletin, Vol. IX, p. 54. March, 1898.


bling a mild typhoid, after which he found a persisting serum reaction toward B. enteritidis and which he naturally accredited to a presumable original infection with this bacillus.

A case recently entered the surgical wards (Dr. Halsted's) of The Johns Hopkins Hospital which furnishes the subject of this communication. An organism almost identical with that of Gwyn's and belonging to or closely allied to the Hog Cholera or Gartner group was isolated from an abscess of the rib which appeared during the convalescence from a prolonged fever of enteric type. That a general infection had occurred was clear from the specific action of the patient's serum toward the isolated organism; there was no agglutinative reaction whatever evidenced toward B. typhosus. Whether this infection was of intestinal origin and occurred through the atrium afforded by typhoidal lesions or whether it was in itself the cause of the fever, must remain undecided, though it seems from these two eases' not impossible that a prolonged fever with the clinical picture of typhoid may be induced by the members of this intermediate group. Had there been a mixed infection, one would have expected a double agglutinative reaction which was not present.

CLINICAL SUMMAHT.

Typhoid fever (?) with relapse. Costochondral osteomyelitis during convalescence. Abscess with rupture six months later. Persisting sinus for three months, showing pure culture of intermediate bacillus at operation.

Case. Surgical No. 8753. M. Burley, colored, aged 27. was admitted into Dr. Halsted's service, March 1st, 1899, with the following history: From early in June, 1898. nine months before admission, he had suffered with a prolonged course of fever extending over a period of ten weeks. A note from his physician, Dr. Hammond, of Jessups, Maryland, describes the case as one of typhoid with a severe but typical clinical course. The history is without particular note except that he had a distinct relapse of the fever which was ushered in by a profuse hemorrhage from the nose. During his convalescence, the patient says that he had noticed two tender nodules near his breast bone, one the size of a dollar, the other somewhat smaller. The latter subsequently disappeared but the larger one increased in size and six months later broke open, evacuating a large amount of pus. Since that time it has continued to discharge, the sinus persisting without tendency to heal permanently, though it has closed on several occasions for a short period.

Examination showed the opening of a sinus, lined by pale granulations and discharging a small amount of pus. situated on a level with the fifth rib at the edge of the sternum. There were slight oedema of the surrounding tissues and tenderness for a few centimetres along the course of the fifth rib. A probe could be inserted for five centimetres downward and to the left about to the junction of the rib and cartilage where a grating bony substance could be felt.

The patient's physical examination was otherwise negative.


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No clumping reaction could lie demonstrated toward B. typhosus with the patient's serum.

Operation March 6th, 1899. The sinus and surrounding tissues, with a button of chest wall including the cartilage of the adjoining ribs were excised and the wound closed over a blood clot by a plastic skin flap.

The tissues removed consisted of the cartilage and portion of bone of the diseased rib. A cavity measuring about one cm. in diameter lined with pale granulation tissue w : as situated in the cartilage near the end of the bone. A sinus led from this through the cartilage toward the sternum. No bone formation could be demonstrated in this cartilage. The cartilages of the adjoining ribs (6th and 7th), portions of which were excised as described, showed marked evidence of beginning ossification as a fine network of new bone-formation preventing easy section with the knife.*

Cultures were taken at the operating table from the bottom of the sinus immediately on making the first incision into it. These cultures showed a pure growth of a bacillus which fermented glucose and did not coagulate milk. Appreciating the rarity in such situations of bacillary forms other than B. typhosus, the organism was carefully examined with the results to be appended, namely, its identification as a member of the intermediate, the Hog Cholera or Gartner group. For convenience this bacillus will hereafter be called Bacillus 0.

Agglutination reactions with the isolated organism.

The following early observations upon the agglutinative reactions of the patient's serum toward the isolated organism and toward other members of the typhoid-colon family which were at hand, as w'ell as a comparison with the reactions of sera obtained from other sources toward these same organisms were kindly made for me by Dr. Gwyn. Unfortunately, at this time the relation of B. chol. suis and B. icteroides with the organism in question was not recognized, and not until later did I come into possession, through the courtesy of Dr.


  • It is noteworthy that postenteric and traumatic osteomyelitides in children almost invariably have their starting point

in the epiphyseal ends of the long bones of the extremities, while only in adults do we find similar processes originating at the costoehrondra! articulations. The natural explanation seems to be that the seat of most active bone-formation is especially susceptible to infectious processes. In adults the cartilages of the ribs represent practically the only situation where ossification in cartilage is taking place. The occasional seat of posttyphoidal infection in the thyroid cartilage of adults may be accounted for in similar fashion. In a post-typhoidal case operated upon two years ago at this hospital by Dr. Finney, I had an excellent opportunity of examining the tissues, since there had been no preformed sinus and the infected area with portions of the two neighboring ribs had been removed in toto. The abscess had apparently started in the cartilage of the sixth rib close to the rib itself, where ossification, as was seen by comparing sections of the cartilages of the adjoining ribs, had been in progress. A pure culture of B. typhosus in this case was obtained from the cavity in the cartilage.


Durham, of Gartner's bacillus, B. morbificans bovis (Basenau) and the variety " Hatton " which Durham has described. When these organisms were received, three months after the operation, 1 found that the patient's serum had so far lost its reaction toward the intermediate bacilli that the results were unsatisfactory for comparative purposes and none of the original serum had been saved. This, however, was compensated for by comparing results with the serum obtained from an immunized animal, as will be described later.

(A) Effect of a variety of sera upon Bacillus 0, the organism isolated from the abscess.

I. Reactions with patients' serum. Two observations with 10-hour cultures showing active motility. A marked immediate reaction * occurs in slight dilutions, with instant cessation of motion and the formation of large clumps, in | to 2 minutes. Reaction is slower but distinctly marked in a 1-800 dilution in two hours.

II. Reactions with other agglutinating sera. Typhoid sera, A., B. and C, agglutinating B. typhosus in dilutions of 1-400. All were quite negative in dilutions of 1-10 in two hours. The motility in all cases was but slightly if at all affected.

III. Reactions with sera of healthy individuals. Five normal sera were tried in dilution of 1-10. The reaction was absolutely negative in all cases.

(B) Effect of the patient's serum upon other agglutinable organisms of the typhoid-colon group.

I. Bacillus typhosus reacting w : ell to typhoid serum in dilutions of 1-200 and 1-300. Little or no effect upon motility in two hours in dilution of 1-10.

II. B. coli communis. Six varieties from stock cultures of the pathological laboratory.

i Well marked clump ^., ,. _ „„„ ing. Motility not abA. Motility active. Dilution 1-200 j f 3 , .

J solute] y stopped in two

l hours.


B. Motility slight. Dilution 1-50


C.

D. E. F.


very sluggish


1-10


j Fair reaction in two I hours.

I Fair reaction in one

' hour.


1-10 f 1-10 j 1-10


No appreciable effect in one hour.


III. B. Paracolon (Gwyn). Motility very active. Dilution 1-10. Slight evidence of reaction. Cessation of motility.


  • For a reaction to be positive we understand that there must

be a complete cessation of motility, «itli clearing of the field of individual organisms and the formation of large clumps. The figures may seem low, but " a reaction " is looked upon very critically.


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[Nos. 112-113.


(C) I omparison of the effect of the typhoid and normal sera used in (A), II and (A), III upon these same organisms of (B).



Typhoid serum


Normal serum (a)


Normal Berum (b)


B. tvph.


1-300 Positive.


1-10 Negative.


1-10 Negative.


I!, coli A.


1-100 Positive.


1-10 Positive.


1-10 Positive.


3. coli R.


1-50 Suggestive.


1-10 Suggestive.


1-10 Suggestive


B. coli C.


1-10 Negative.


1-10 Suggestive.


1-10 Negative.


B. coli D.


1-10 Suggestive.


1-10 Positive.


1-10 Positive.


Paracolon





(Gwyn)


1-10 Negative.


1-10 Negative.


1-10 Negative.


These results show the absence of any reaction on the part of the patient's serum toward B. typhosus or toward any other organism tried except an occasional variety of B. coli. It is, however, a not uncommon observation to find an agglutinative reaction toward colon, since sera from apparently healthy individuals, as the above results demonstrate, often read in some degree toward members of the colon group, doubtless from the more or less frequent slight colon infections which occur in the course of occasional mild enteritides. In the absence, therefore, of a double agglutinative reaction we may with propriety exclude the possibility that the infection with Bac. was superimposed upon a typhoidal infection and that the former organism and not B. typhosus was responsible fur the clinical symptoms.

Jfote on the Pathology and Bacteriology of the Lesion.

The isolation of this organism from an osteomyelitic process secondary to an enteritis and the positive agglutinatve reaction of the patient's serum toward it are conclusive evidence of a peripheral septicaemia, such as frequently occurs during the progress of enteritides occasioned by B. typhosus. It is, of course, possible that many of these intermediate organisms may have their habitat at one time or another in the intestine and, through the atrium afforded by lesions such as occur in typhoidal enteritides, they may enter the portal circulation, or, indeed, by way of the thoracic duct, the peripheral circulation, provided they are not checked by the mesenteric glands. Thus a peripheral septicemia, such as in typhoid fever frequently occurs from an invasion with the specific organism of the disease itself, may supposedly be occasioned by the entry of any intestinal bacterium. Such .i secondary invasion Dr. Welch,""' in 1890, demonstrated to be possible with B. rati, but it has been a common observation that in such superimposed colon infections the organisms only exceptionally pass beyond the confines of the abdominal cavity.* It is therefore exceedingly unusual to find in peripheral post-typhoidal lesions organisms of intestinal origin


11 Welch. Wm. H.: The Bacillus Coli Communis; the Conditions of its Invasion of the Human Body, and its Pathogenic Properties. Medical News, Vol. LIX, p. 669, Dec. 12, 1891.

  • This has been discussed in a recent paper. 22

22 Observations upon the Origin of Gall-Bladder Infections and upon the Experimental Formation of Gall Stones. The Johns Hopkins Bulletin, Vol. X, Nos. 101-102, p. 166, 1899.


other than the typhoid bacillus itself, though complicating pyogenic skin (coccal) organisms are common. The abdominal complications, occurring in the liver and gall-bladder, for example, by way of the portal circulation are. on the other hand, frequently due to such secondary invasion. For these reasons, as well as those given above, it seems unlikely that Bac. was such a secondary invader. In suppurative sequela?, in bone especially, it has been exceptional, if we may draw conclusions from such lesions as have occurred secondary to typhoidal enteritides. to find intestinal bacilli other than the specific organism of the disease. As has been stated, the latter is frequently present in the peripheral circulation and. as Quiiike M has demonstrated, it finds the bone-marrow a habitat of especial predilection. Of the fifty-one cases of post-typhoidal bone lesions which Keen :4 collected, and in which authentic bacteriological studies had been made, thirtyeight were associated with a pure or mixed infection with B. typhosus. In only one case was there a supposed mixed infection with />'. coli, which naturally would be the most common secondary invader. This was a case of Klemm's. :j Dehu : * (1893) in his elaborate statistics stated that B. coli had never been seen in bone abscesses and without excluding the possibility of its occurrence he regarded it as extremely improbable that the colon bacillus held any relation to the production of ostitides.

Recently Blumer " has reported a case in which B. coli was supposed to have been isolated from a post-typhoidal rib abscess. His organism, however, was an alkali-producer in milk and therefore probably did not ferment lactose and should hardly be regarded as a colon bacillus. No mention occurs of serum reactions in his report, and it is quite possible that the organism isolated was the specific cause of the fever preceding the osteomyelitis and was a member of the group in question.

Bacteriological Survey of the Bacillus. (Bar. 0.)

For purposes of comparison inoculations were made upon all media, with the following organisms:*


21 Quiiike, H., und A. Stiihlen: Zur Pathologic des Abdominal typhus. Typhusbaeillen im Knochenmark. Berliner klinische Wochenschrift, Bd. XXXI, No. 15, p. 351. April 9, 1894.

21 Keen, W. \Y.: Complications and Sequels of Typhoid Fever. Philadelphia, 1898, p. 113.

B Klemm: Quoted by Keen, op. cit.. p. 113.

2 " Dehu, Paul: Etude sur le rule du bacille d'Eberth dans les complications de la fievre typhoide. These de Paris, 189.'!, p. 91.

Blumer, George: A Case of Posttyphoid Bone Inflammation

due to the Colon Bacillus. The Pacific Record of Medicine and Surgery, Vol. XIII, p. 105, November 15, 1898.

  • 1-2-3-4-5-9-10-11 were obtained through the kindness of Dr.

Harris from the laboratory stock cultures. To Dr. Harris and his assistants, Mr. Winnie and Mr. Holden. I am indebted for confirmation in some of these observations. 6-7-S were obtained from Cambridge through the courtesy of Dr. Herbert E. Durham. Three additional varieties of B. icteroides from different sources were kindly sent to me by Dr. Reed from Washington.


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1. B. typhosus (a), an early alkali-producer (3 weeks);

2. B. typhosus (b), a late alkali-producer (months):

3. B. coli communis (a), var. not fermenting saccharose;

4. B. coli mm nui ii is (b), var. fermenting saccharose;

5. B. paracolon (Gwyn);

li. B. enteritidis ((iiirtner):

T. B. morbificans boris (Basenau);

8. B. car. " Halton " of Durham;

9. B. cholera suis;

10. B. icteroides (Sanarelli);

11. B. typhi murium (Loeffler);

thus giving a variety of intermediate forms, as well as the chief variations in the extreme groups of colon and typhoid.

Morphology, etc. — Bacillus could not be distinguished from the typhoid bacillus in form or staining qualities and its description is therefore unnecessary. It decolorized by Gram. Variations in size were observable upon different media and occasionally sedimenting organisms were found to take a bipolar stain. Flagella in number and distribution resembled those of B. typhosus. Twelve to fourteen were counted on some specimens and occasionally exceedingly long terminal flagella were observed. Of the above bacilli it is possible that Basenau's organism (No. ?) alone could have been distinguished from the rest with any degree of probability. The variety which Dr. Durham had presented tended to grow in filamentous forms quite recognizable upon most media.

Active motility was present with all varieties except those of B. coli which, under the same cultural conditions, showed very sluggish movements, or no motility whatever. The motility of Bar. was especially active, being darting in character, and remained present for many days.

Agab and Gelatin. — The appearance of colonies and of the surface growth upon these media presented no features by which they could with any certainty be distinguished. All were very typhoid-like, the luxuriance of surface growth depending somewhat upon the initial reaction. Basenau's organism again is perhaps an exception, as the surface colonies on gelatin presented a more irregular fringed edge than the others which ordinarily showed a pale brownish-yellow centre fading toward the periphery; this was usually slightly scalloped, well defined and almost colorless.

Growth in Bouillon. — Bacillus and Gwyn's "paracolon" in bouillon and similar media grew much less luxuriantly than did the various intermediate forms used for comparison. The hog cholera and Gartner type cloud the media very rapidly and more abundantly than B. coli, and usually a surface pellicle is formed which may or may not fall. The former organisms, en the contrary, produce but slight turbidity and thus resemble the typhoid rather than the colon end of the group. One series of bouillon inoculations, the medium having an initial reaction of + 1.2 (that is, 1.2 cc. of a normal tenth standard solution of sodium hydroxide


was required to neutralize 10 cc. of the medium), gave after five days of incubation the following reactions:*

/.'. coli (a).

/{ranch. Slightly cloudy; large bubble of gas. Initial reaction + 1.2; terminal reaction + 1.6; production of acidity .4 per cent.

Bulb. Very cloudy; abundant precipitate; slight pellicle. Initial reaction + 1.2; terminal reaction + 1.6; production of acidity .4 per cent.

B. typhosus.

Branch. Very slight cloud: no gas. Initial reaction + 1.2; terminal reaction + 1.4; production of acidity .2 per cent.

Hull). Slight cloud: slight precipitate. Initial reaction + 1.2; terminal reaction + 1.4; production of acidity .2 per cent.

Bacillus 0.

Branch. Very slight cloud; small bubble of gas. Initial reaction + 1.2; terminal reaction + 1.3 ; production of acidity .1 per cent.

Bulb. Slight cloud; abundant precipitate; no pellicle. Initial reaction + 1.2; terminal reaction + 1.0; production of alkalinity .3 per cent.

B. Gartner et al.

Brunch. Very slight, cloud; small bubble of gas. Initial reaction + 1.2; terminal reaction + 1.4; production of acidity .2 per cent.

Bulb. Very cloudy with abundant precipitate and pellicle. Initial reaction + 1.2; terminal reaction + 0.9; production of alkalinity .5 per cent.

It is thus seen by the cloudiness of the closed arm and by the acid produced that a carbohydrate present in ordinary bouillon permits all of these organisms to grow anaerobically. The intermediate (Gartner) and colon forms with their allies produce a small amount of gas. The aerobic growth in the open bulb remains acid in the case of colon and typhoid but produces with the rapidly growing Gartner type some degree of alkalinity, which in a short time is sufficient to overcome the preliminary acidity.

Growth in Dunham's solution and Dextrose-freeboiillon with Indol eeactions. — In dextrose-free-bouillon the vigor of growth of the Gartner-Hog Cholera type is especially well shown, the great cloudiness and rapid formation of surface pellicle, most marked with B. typhi murium and B. morbif. bovis, being very characteristic. Bac. and Gwyn's organism here again grow much more like the typhoid


  • The percentage of reactions given throughout this paper

represents the amount of normal sodium hydroxide or oxalic acid solution requisite to neutralize, by the phenolphthalein test, 10 cc. of the fluid in question. For the purpose of titration normal tenth solutions were used. In all cases an uninoculated control, having undergone corresponding incubation and exposure, was similarly tested to give the initial reaction. As recommended by the committee of American bacteriologists, 2 * the plus and minus signs are used to indicate respectively acidity and alkalinity.

28 Procedures Recommended for the Study of Bacteria: Submitted to the American Public Health Association in Phila., Pa., Sept., 1897. Rumford Press, Concord, N. H., 1898.


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[Nos. 112-113.


bacillus. The same may be said of their growth in Dunham's solution.

In the latter medium after seven days incubation no indol coidd be demonstrated for any of the intermediate forms, while B. coli gave its usual marked reaction. Theobald Smith, however, has shown 1 ' that the carbohydrate which Dunham's peptone solution (generally used for this test) contains, exercises a restraining action on the production of indol, while in dextrose-free-bouillon * there is no such retardation. A careful test, therefore, was made for B. typhosus, B. coli com., Bac. and B. paracolon (Gwyn) on the principles laid down by Dr. Smith, and by this means very slight traces of indol, not apparent in Dunham's solution, were appreciable for the two latter organisms after the 8th, 9th and 10th days. The method employed was as follows:

Daily, over a period of ten days, four tubes of dextrose-freebouillon (properly tested for muscle sugar) were inoculated respectively with a typhoid, colon, paracolon (Gwyn) and Bacillus and placed in the thermostat. At the end of this period all 40 tubes were tested at the same time for indol with freshly prepared standard solutions. The colon bacillus showed after 21 hours a faint trace of indol which increased in intensity up to the 10th day. With typhoid no trace was demonstrable. Gwyn's paracolon on the 8th, 9th and 10th days showed a faint trace and similarly Bacillus in the older tubes gave evidence of a slight production of indol, possibly a little more than the paracolon. These reactions were positive, though slight, and might readily have been overlooked on a single tube test. In Gwyn's original report a belief is expressed in the non-production of indol. On another occasion a similar series of inoculations for comparison with the other members of the intermediate group gave no reaction whatever for any of the organisms up to the 10th day. The culture of Bac. O used at this time was several generations removed from the original.

Apparently, from Peckham's elaborate observations/ the reaction for indol should not be given the prominence in questions of differentiation of bacillary types that has been attributed to it by Kitasato and other writers who have regarded this as a most important and distinguishing characteristic of B. coli communis. According to the source of the culture, however, aud possibly depending upon the proteid characteristics of the nourishing medium, there is great varia


29 Smith, Theobald: A Modification of the Method for Determining the Production of Indol by Bacteria. The Journal of Experimental Medicine, Vol. II, p. 543, 1897.

  • For method of preparation cf. Smith, Theobald, Ueber

Fehlerquellen bei Priifung der Gas-und Ssiure-bildung bei Bakterien und deren Vermeidung. Centralblatt fur Bakteriologie, u. s. w. Band XXII, 1897, No. 2/3, S. 49.

  • ° Peckham, Adelaide Ward: The Influence of Environment

upon the Biological Processes of the Various Members of the Colon Group of Bacilli. The Journal of Experimental Medicine Vol. II, p. 549, 1897.


bility in indol production, which, if the observations of de Klecki, Dreyfuss, Sanarelli and others are to be depended upon, is in some degiee a measure of pathogenicity. Peckham has shown that in vitro this property of indol production may be made to vary within wide limits by cultivation on various media. Indeed she has been able to obtain an indol producing typhoid and to cause B. coli to lose this property. As ordinarily encountered in the human body, however, B. coli produces indol, and the members of the intermediate group under discussion barely appreciable amounts, if any, through the forms Bac. and Gwyn's paracolon were obtained from sources and under conditions which, according to Peckham, would have been most favorable, if the colon observations are a standard, toward the acquisition of this characteristic.

Growth on Potato. — This is a very uncertain means of differentiation. B. coli doubtless grows more luxuriantly on this medium and shows more marked chromogenetic properties. All depends, however, upon the initial reaction of the potato. Occasionally the intermediate bacilli have been seen to grow almost like B. typhosus, at other times almost as profusely as colon, but on such occasions the typhoid bacillus itself after a longer incubation would present the same appearance. Bac. O and B. paracolon (Gwyn) behaved like typhoid, i. e., grew more slowly, darkened the potato less rapidly and assumed a yellow color later than the other intermediate varieties. On one occasion a series of inocidations was made on potato which had an initial reaction of -f- 8.O.* All of the intermediate forms of Gartner type gave an abundant, visible, slightly elevated, smooth, glistening, opaque growth of light-yellow color in 24 hours, which deepened in 48 hours, with an accompanying discoloration of the potato. In four days the potato had assumed a dirty-gray color for all these intermediate forms. B. typhosus, Bac. O and B. paracolon growing more slowly finally gave the same appearance in six days or more. At the end of four days in the presence of the Gartner type the potato had a reaction of — 4.0, thus 12 per cent of alkalinity had been produced by the growth of the organism in this time. The unreliability of the potato reaction is thus exemplified. These intermediate forms, as well as B. typhosus, are alkali-producers when grown in the presence of air, and this alone is responsible for the chauge in appearance of the medium. This may be demonstrated by adding a corresponding amount of alkali to the potato and incubating it for a few hours, when it assumes the same dirty-gray color. B. coli, however, produces its abundant growth without formation of alkaline products, the medium remaining free from the discoloration of the alkali-producers.


  • These reactions were roughly made by titrating 5 cc. of a

neutral solution, in which the potato had been shaken up for five minutes, both before inoculation and 5 days after the growth. Presumably this represents but a small measure of the true reaction.


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103


Milk. — The reactions in milk and the various media made from it, depending upon the variations in the rapidity and degree of acidulation or alkalinization of the medium, constitute one of the most important means of differentiation of members of the typhoid-colon family.

B. coli, as is well known, acting upon its carbohydrate constituents, acidulates milk up to the point of precipitation of the casein (6-8 per cent of acidity) in periods varying from two to seven days and at the same time there is a liberation of gas amounting to about l/6th of the closed arm of a fermentation tube. Here acidulation ceases, the organism dying out or being inhibited in its growth by the acid formed. That the organism is capable of producing a larger amount of acid from the contained carbohydrates is shown by the coagulation of milk which, having acquired a previous alkalinity of 4 per cent from the growth of an intermediate form, is subsequently inoculated with B. coli, which not only overgrows the original organism but overcomes its alkali-production and finally precipitates the casein which this had held in solution.

B. typhosus also is an acid-producer but, unlike colon, not to the degree of coagulation of the medium. If plain milk requires 6 per cent to completely precipitate the casein, milk in which B. by ph. has been grown for 48 hours requires but 4-5 per cent. There are varieties, however, which when grown in milk in the presence of air, lose their acid reaction and become neutral or alkaline. Occasionally this is a noticeable and early change, occurring in a few weeks, and has given rise to the name " blue typhoid " from the unusual color which follows its growth in litmus milk. It is a characteristic, however, which seems to belong remotely to all examples of B. typhosus.

The intermediate bacilli under discussion have a very diil'erent action in milk, namely, that of an early and distinctive alkalinization of the medium in the presence of air, which appears after a transient acidity of a few hours. This alkalinization progresses up to the point of solution of the casein (about 4 per cent of alkalinity) and thus with the liberation of the fat-globules gives to the medium the peculiar greenish opalescence and translueency which has been said to be characteristic alone (?) of the Hog-Cholera bacillus, but which occurs similarly from the growth of all members of the group and in fact without the bacteria can be occasioned by the addition of a coresponding amount of alkali to the milk. This reaction in the presence of the growing organisms begins to be apparent in about two weeks, that is, sufficient alkali has been produced to partly dissolve the casein and render the milk slightly translucent. After entire solution has taken place (4-6 weeks) the liberated fat-globules, freed of their enclosing casein envelopes, are found floating upon the surface, leaving the medium fairly clear, often with a gelatinous clot at the bottom of the tube, consisting chiefly of a mass of organisms which take a feeble and bipolar stain and are apparently dead. The opalescent medium above contains a comparatively small number of viable evenly staining bacilli.


The accompanying photographs (Plate VI11, Fig. I (a) and (b)) of a series of tubes show the appearance of this reaction in the case of the intermediate bacilli contrasted with that of B. typhosus, B. coli and a control tube, all of which have retained their original opacity. Boiling has no apparent effect on the milk which has undergone this change.

Iu litmus milk the transient acid reaction * and subsequent alkalinization are shown by the color changes. The opalizing reaction from solution of the casein, if present, is not apparent in the litmus medium. The bulb of the fermentation tube after a few days acquires a blue color which deepens in time to a dark navy blue corresponding to the color which follows the addition of 4 per cent or more of alkalinity to a control tube. At varying periods, during the activity of growth, at the bottom of the test-tube or in the closed arm of the fermentation tube the litmus becomes reduced and colorless. These reactions all take place more slowly with Bac. and Gwyn's paracolon, and in fact Gwyn did not recognize this terminal alkalinity of milk, which does not occur for 12 to 14 days. The neutralization period for Bac. does not appear till the 8th day. This relative slowness in alkalinization should hardly separate these two varieties from the Gartner or Hog Cholera type any more than that slow production of acidity sufficient to precipitate casein should separate one variety of colon from another which coagulates milk in half the time.

These results may be expressed as follows:

1. Colon acidulates milk up to the point of precipitation of the casein in from 2 to 7 days.

B. coli. Seven-day growth in fermentation tube of milk having an initial reaction of + 2.2. Total gas %. Coagulation of milk in 2 days.

Branch (terminal) + 8.8 less 2.2 = 6.60% acid produced. Bulb (terminal) + 8.8 less 2.2* = 6.60% acid produced.


Reaction


2. Typhoid produces in milk from 1-2 per cent of acidity, not enough to coagulate the medium. In other words, it requires 1-2 per cent less of acidity to precipitate the casein after the growth of B. typhosus than in control milk. Further, as Theobald Smith " has shown, the addition to milk in sufficient amounts of a carbohydrate, such as dextrose, which can be acted upon by B. typhosus, will lead to the coagulation of the medium.


  • This slight early acidification in milk, so rapidly overcome

by the production of an alkaline product, is presumably due to the presence in milk of traces of a fermentable substance which Theobald Smith believes to be a second carbohydrate, possibly dextrose. Neither B. typhosus nor any member of the intermediate group appears to have any reducing effect upon lactose in otherwise sugar-free media. For this reason the reactions in lactose sugar-free bouillon and in milk are not supplementary as ordinarily supposed.

81 Theobald Smith: The action of typhoid bacilli on milk, and its probable relation to a second carbohydrate in that fluid. The Journal of the Boston Society of Medical Sciences, Vol. TT, No. 12, p. 236, June, 1898.


164


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 112-113.


B. typhosus. Seven-day growth in fermentation tube of milk having- initial reaction of + 2.2. No gas. No coagulation.

I Branch (terminal) + 3.8 less 2.2 = 1.60% acid produced. Reaction j Bulb ( terni i na i) + 3 . 8 i ess 2.2 = 1.00% acid produced.

.'!. the intermediate type produces a transient acidity followed by a marked alkalinity in the presence of air which increases from per cent in 3 days to 4 per cent in two weeks with solution of the casein and the consequent production of partial translueence of the medium. This, however, only occurs in the presence of air. Such opalization does not occur in the closed arm of the fermentation tube. When such a reaction has occurred the addition of 4 per cent of acidity will again render the medium opaque and 10 per cent (6 per cent of acidity must be reached) must be added to precipitate the casein formerly held in solution by the alkali. Thus there is 10 per cent difference of reaction between the point of coagulation produced by the acid of B coli and the point of solution of the casein produced by the alkali of the intermediate group.

B. Gartner et al. Seven-day fermentation reactions with milk of + 2.2 initial reaction. Total gas = bubble. No coagulation.

( Branch (terminal) + 3.8 less 2.2 =1.60% acid produced . ) (ef. B. typhosus (2)).

Reaction < Bulb ( term i na i) + .2 less 2.2 + 1.6 = 3.60% alkali proI duced.

3a. The allied forms, Bac. and B. paracolon (<iwyn) show a corresponding but slower reaction.

Bac. O, etc. Fermentation reaction in plain milk (7 days) with initial acidity of + 2.2. Gas bubble +. No coagulation.

'Branch (terminal) + 3.9 less 2.2 = 1.70% acid produced (ef. B. Gartner (3)). ReaeHon{ Bulb (terminal) + 0.6 less 2.2 + 1.7 = 3.30% alkali produced (ef. 30% less than with Gartner type in same time).


Fermentation Keactions with Various Sugars.

A valuable means of distinguishing varieties of the colontyphoid group lies in their reactions in the presence of various carbohydrates. Theobald Smith regards this process of differentiation as most essential; " a relief from the uncertainty of the usual potato culture and the variable intensity of the indol reaction." The methods which he advocates were adopted and his precautions observed. Several series of inoculations were made with most of the organisms in the list which has been given, in fermentation tubes of sugar-free bouillon containing 1 per cent of glucose, lactose, mannite or saccharose sugars. The rapidity of gas-production was daily registered at the level of fluid in the closed arm; the proportion of C0 2 to explosive gas was finally noted and the reactions of the bulb and closed arm at varying periods were made an object of record and comparison. All of the observations


were made during incubation at a temperature of 37° C. The original bouillon * in all instances, to insure its freedom from muscle sugar, was tested by inoculation and incubatiou with a gas-producing organism before its sugar percentages were added.

Reactions in Lactose. Owing to the observations of Smith, which have been reviewed above, upon the presence in milk of a fermentable substance other than lactose, some reservations must be made to the common belief in the con-elation between the reactions in plain or litmus milk or in the litmus whey of Petruschky, 32 on the one hand, and the reactions occurring in media made by adding the carbohydrate to an otherwise sugar-free bouillon. In consequence of this fact a source of error may creep into the observations upon the fermentation of lactose, since the commercial product made from milk may be adulterated with this second carbohydrate. Similarly, mistakes may arise owing to the ease with which during the sterilization of lactose media some of the carbohydrate may be converted into a simple and more readily fermentable sugar. For this reason preparation in the autoclave should be avoided and the fractional method of sterilization be employed for this as well as for saccharose media. Furthermore, failure to insure complete freedom from muscle sugar in the original bouillon may lead to mistaken observations and it is doubtless due to these possibilities of error that so many conflicting statements are encountered regarding the fermentation of lactose by various bacteria. The accompanying photographs (Plate IX, Figs. 2 and 3), representing series of inoculations into lactose media, show how such erroneous observations may originate. In the series reproduced in Fig. 2 gas production was present in slight amount in all instances except with B. typhosus, and was presumably due to some dextrose adulteration. In the latter series, shown in Fig. 3, the original bouillon bad not been completely freed from muscle-sugar, fermentation of which gave a small amount of gas. Before the addition of the 1 per cent lactose to the medium used in this series a corresponding amount of gas was produced in it by the inoculation with B. coli communis. Fig. 4 represents the typical reaction, B. coli alone producing gas from the carbohydrate, the other organisms producing no fermentative change whatever.

In the following table are given the reactions occurring in bulb and branch of the fermentation tube resultant to the growth of these organisms in 1 per cent lactose media. The figures throughout these tables represent the amount of normal tenth sodium hydroxide or oxalic acid solution required to neutralize by the phenolphthalein test 10 cc. of the medium. An uninoculated control was in each instance similarly tested and these results represent the calculated production of alkali or acid. It will be seen that the figures for the intermediate group are practically the same in all cases.


  • For methods of preparation cf. Theobald Smith, p. 546.

'- Petruschky, Johannes: Bakterio-chemisehe Untersuehungen. Centralbl. f. Bakteriologie. Bd. VII, S. 1, 49, 1S90.


July- August, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


105


COMPUTED REACTION* AFTER 8 DAYS' INCUBATION WITH lg LACTOSE SUGAR-FREE BOUILLON HAVING INITIAL ACIDITY OF 1.40%\



B. typhosus (a).


Bacillus 0.


B.paracolon (Gwyn).


B. morbit. bovis.


B. var. " Hatton."


It. enter itidis.


B. chol. suis.


B. icteroides.


11. typhi mur.


It. eoli comm. (a).


B. coli comm. (b!.


Reaction of Bulb

Reaction of Branch .... Total Gas


Alkaline .40$

No change



Alkaline .95%

No change


%


Alkaline .90%

No change


%


Alkaline 1.60%

Alkaline .30%


%


Alkaline 1.00

Alkaline .10%


%


Alkaline 1.00%

Alkaline .10%


%


Alkaline

.80%

Alkaline .10%


%


Alkaline 1.60%

Alkaline .30%


%


Alkaline 1.60%

Alkaline .20%


%


Acid 3.60%

Acid 8.60%

1/2 +

2 4/1


Acid

4.2%

Acid 3.6%

8/4

2 + /1


Proportion of H/CO, . .


  • The reactions represent the amount of acidity or alkalinity produced, and are computed from the initial reaction.


B. coli ferments lactose, producing an equal amount of acidity in closed arm and bulb, and gas composed of C0„ and an explosive element (hydrogen) in the proportion of 1: 2. Xo acid is produced by B. typhosus from pure lactose, despite the fact that ordinary milk is acidulated by its growth. The amount of alkalinity in the bulb, which occurs with this organism as well as with Bac. is slightly less than that which follows the growth of the intermediate bacilli, possibly


owing to the fact that they grow with less luxuriance than the intermediate variety, which, in the presence of air, multiply rapidly in bouillon. Theobald Smith states that alkali production bears a distinct relation to vigor of growth. The slight alkalinity of from .1 to .2 per cent in the closed arm with the more rapidly growing intermediate forms may be due to some interchange of reaction with the very alkaline medium in the bulb.


COMPUTED REACTIONS IN DEXTROSE SUGAR-FREE BOUILLON HAVING INITIAL ACIDITY OF 1.50%".



B.

typhosus.


Bacillus


B.paracolon

(Gwyn).


B. morbif. bovis.


B. var. " Hatton."


B. enter itidis.


B. chol. suis.


B.

icteroides.


B. typhi mur.


B. coli comm. la).


B. coli comm. (b).



Acid


Acid


Acid


Acid


Acid


Acid


Acid


Acid


Acid


Acid


Acid


Reaction of Bulb


3.50%


3.50%


3.60%


3.70%


3.7056


3.70%


H.70%


3.70%


3.70%


3.90% 4.10%


3.80% 4.10%



Acid


Acid


Acid


Acid


Acid


Acid


Acid


Acid


Acid


Acid


Acid


Reaction of Branch ....


3.50%


3.70%


3.70%


3.90%


3.90%


4.10%


3.90%


4.15%


4.15%


4.15%

1 MK,


3.90% 4.50%


Total Gas



i i


i i


2 _ 1


?->


2 _ 3


2 1


1_3


2 _ 1


1 +


i


Proportion of H/CO a . ..


%


3 f /l


2/1


2 + /1


2 + /I


3+/1


2 + /1


2 + /1


3/1


2/1


2/1


Reactions with Dextrose. All of the members of the Hog Cholera or Gartner group produced gas, in correspondence with B. coli and its allies, when grown in the presence of dextrose. The total displacement in the closed arm of the fermentation tube was found to vary somewhat under different conditions of inoculation. Two series as represented in the photographs (Plate X, Figs. 5 and 6) are given in illustration of this irregularity. One feature, however, is broughl out in each series, namely, the relative slowness of gas-pro duct ion with the two allied forms, Bacillus and Gwyn's paracolon, which in the first twenty-four hours produce U than half as much gas as the other organisms.

Reactions with Mannite. Like dextrose, this carbohydrate is readily fermented by the organisms in question (cf. Plate

XI) with the production of even a greater amount of gas, which, under some circumstances (cf. Fig. 8), may displace


the larger part of the fluid in the closed arm. In this series Bac. was, as in the presence of dextrose, slow in its liberation of gas. One peculiarity of the reactions witli mannite lies in the terminal reaction of the bulb which remains neutral or slightly alkaline, as does the media containing nonfermentable sugars (lactose and saccharose). The proportion of C0 2 in the gas was less than witli dextrose, being 1/3 or le>s of the total amount. In several instances there was failure to demonstrate thai the remainder contained any II or other explosive element.

Reactions with Saccharose. In the preparation of saccharose bouillon, as well as with lactose, precautions must Intaken during sterilization to avoid any conversion of tin' carbohydrate into more readily fermentable sugars. No uas is produced and no acid formed by any of the intermediate group in this medium. Certain forms of />. coli also fail to


166


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 112-113.


ferment saccharose, as is shown in Plate XII, Fig. 9. This has been pointed out by Theobald Smith. Other varieties of colon produce an abundance of gas, as is shown in Fig. 10 (B. coli comm. (b)). In the series presented in this latter photograph there had been a slight conversion of the sugar as the medium had been autoclaved. In several instances, consequently, a slight production of gas has resulted, showing the source of error which may result from this method of sterilization. The slowness of the growth of Bacillus and Gwyn's paracolon heretofore commented on was shown in the closed branches of these tubes by the tardy reduction and decolorization of the litmus which had been added to the media. This ia apparent in the photograph. In the accom


panying table are given the reactions which occur after growth in saccharose media. It will be seen that the more rapidly growing organisms have produced a greater percentage of alkalinity in the presence of air and that a small percentage (.2 per cent) is present in the closed arm, possibly due as in the case of lactose reactions to some interchange in reaction with the bulb. The initial reaction of the medium in this series was -+- 1.0 and the reaction for the Gartner or Hog-Cholera type after 9 days when the tests were made was -+- -8 for the closed arm and — 1.4 for the bulb. On the occasions when there was slight gas-production due to faulty preparation of the medium, a sufficient amount of acidity was found to delay alkaliniza.tion in the bulb.



TABLE


OF COMPUTED REACTIONS IN 1$ SACCHAROSE


SUGAR-FREE BOUILLON.





B.

typhosus.


Bacillus 0.


B.paraeolon (Gwyn).


B. morbif. bovis.


B. var. " Hatton."


B. enter itidis.


B. cholera 1 suis.


B.

icteroides.


B. typhi mur.


B. coli comm. (a).


B. coii comm. (b).



Alkaline


Alkaline


Alkaline


Alkaline


Alkaline


Alkaline


Alkaline


Alkaline


Alkaline


Alkaline


Acid


Reaction of Bulb


3.056


2.0%


8.056


2.458


3.4« 


2.4%


2.4%


2.4%


2.4%


2.4%


5.0%



Neutral.


Neutral.


Neutral.


Alkaline


Alkaline


Alkaline


Alkaline


Alkaline


Alkaline


Alkaline


Acid


Reaction of Branch. . . .





0.2*


0.256


0.2®


0.2%


0.2%


0.2%


0.2%


5.0%


Total Gas















Occasional bubble.


%


(cf. Plate V).


Proportion of H/CO a . .



%


%


%


%


56


%


fo


%


•>


2 + /1


Pellicle formed on bulb with 4, 5, 8, 7, 8, 9. Reactions taken on 9th day. Five days of original incubation.


SCRAPED-TUBE REACTION.

For the differentiation of closely related bacilli, Achard and Renault 33 originated a method of inoculation of one organism upon a base which previously had served for the growth of another allied form. The development of the growth upon such a substratum was regarded as evidence of individuality and its failure as evidence of identity of the organisms. Many inoculations of this nature were made in the following way: After 72 hours of incubation at 37° C, the growth from the upper half of an inoculated agar slant was carefully removed and the tubes replaced in the thermostat to insure no further growth. Inoculations of these tubes were then made in a single streak along the centre of the area formerly occupied by the original growth and the results recorded after 72 hours of further incubation. How much reliance is to be placed upon this method of Achard is undetermined. Smith 34 does not regard it as an important


" Achard et Eenault: Sur les bacilles de l'infection urinaire. Semaine Medicare, 1892, p. 136. Sur les difrerents types de bacilles urinaires appartenant au groupe du bacterium coli. Ibid., 1892, p. 512.

34 Smith, Theobald: Notes on the Bacillus Coli Communis and Related Forms. American Journal of Medical Sciences. Vol. CX, p. 283, 1895.


criterion, since slightly increased sensitiveness to acids or alkalies which may characterize dosely related organisms may affect it.

It can be seen on consulting the table that none of the organisms could furnish a visible growth when reinoculated on their original substratum. In the case of Bacillus 0, both typhoid and colon grew on its original surface of growth, while none of the allied forms grew with any luxuriance. Gwyn's paracolon did not furnish any growth, but on the contrary Bac. O grew well upon the substratum of the paracolon. Similarly, although B. coli grew well upon the base of Bac. O, the latter gave no growth whatever on a colon substratum, though this was repeated with eight varieties of colon. It can, however, be said that the members of the intermediate group under most circumstances in which the reactions were tried failed to show on a substratum of one of its allies a growth of any vigor.

Thermal Death-Point. Tests made by Mr. Winnie to determine the thermal deathpoint showed that an exposure at 60° C. for five minutes would prevent further growth of Bacillus 0. A corresponding incubation at 55° C. failed to completely destroy the organisms, many colonies appearing on plate culture. Similarly, after a ten-minute exposure at the same temperature.


July- August, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


167


a number of colonies appeared, though many less than after the shorter period of incubation.

Pathogenicity.

The object of this study has been merely an attempt at classification, and a lack of correspondence in pathogenic action may be no indication of the absence of phylogenetic relationship. Nevertheless, the following experiments, undertaken with some of these bacillary forms under discussion, are not without their instructive features. Most of the organisms which are members of this intermediate group pos


sess pathogenic properties of considerable virulence toward animals and may be the occasion of epidemics in hogs, cattle and other live stock, mice, birds, etc., and toward man as well as animals, as is evidenced by the various epidemics of meatpoisoning, yellow fever, etc.

Pathogenic experiments have never been undertaken with Gwyn's paracolon, and the notes concerning Bat illus 0, found under somewhat similar circumstances in a case clinically one of typhoid fever, show that its virulence toward the Lower animals in the condition of its isolation was not an intense one, but resembled the action of B. typhosus rather than that of other members of the Gartner or hog-cholera group.


S 1

Z i.

<c

Pk

Z ■<

Substratum of— C


Bacillus 0.


B. coli.


B. paracolon.


B. typhosus.


B. enteritidis.


1!. var. " Hatton. 11


B. cholera* suis.


B. icter oides.


1!. raort.it.

lio\ IS.


I!, typhi, mur.


Bacillus O


No growth No growth Good growth No growth No growth No growth Faint

No growth No growth No growth


Good growth No growth Fair growth Good growth


No growth Faint

No growth Fair growth No growth


Good Growth

Faint

Faint

No growth


No growth No growth No growth Fair growth No growth


Faiut

No growth


Faint


No growth No growth


Faint

No growth No growth

No growth



B. coli





B. var. " Hatton"







No growth



A mouse was killed in 24 hours by a large subcutaneous inoculation of an 18-hour bouillon culture. The autopsy revealed lesions typical of an acute general septicaemia. A guinea-pig inoculated subcutaneously with a number of organisms sufficient in amount to invariably be fatal in the case of B. chol. suis, recovered after a small local area of induration which persisted for a week or two. Rabbits inoculated intravenously with large doses recovered after an acute illness and an occasional local lesion. No intraperitoneal inoculations were made.

Possibly the most interesting feature of the animal experiments lies in the fact that although the serum of an animal which had recovered from an inoculation did not possess any very marked agglutinative properties toward the other bacilli related to that which had been inoculated; nevertheless, a certain protective immunity seemed to have been acquired. For example, a rabbit which had recovered from several infections with Bac. and whose serum agglutinated this organism in 1-5000 dilution, recovered after an intravenous inoculation with a large dose of B. chol. suis. which was fatal to a control rabbit in a few hours. When killed 25 days later the former animal was found to have typical hog-cholera


lesions in the liver and elsewhere. Animals killed by infections with B. enteritidis had similar lesions in the liver, gallbladder, duodenum, etc., and in fact the liver necroses do not seem to be characteristic of any one of these varieties, but merely to represent focal destructions of liver substance by accumulations of organisms present in too great abundance for elimination. There can likewise be seen in all cases lesions of the gall-bladder, with clumped organisms in the bile, which shows the usual changes seen in enteric diseases, of the gall-ducts and of the duodenum which is usually deeply injected and from which the organisms of infection may usually be isolated.

One observation of especial interest was the occurrence in the liver of a rabbit which had rapidly succumbed to an overwhelming dose of B. cholera suis, of extensive fatty degeneration of the liver-cells resembling very closely the condition which is seen in the liver of human beings who have died from yellow fever. It is unusual to find this change in the livers of animals experimentally inoculated with />. icteroides, and this has been used as an argument against the possibility that Sanarelli's bacillus could be the cause of yellow fever and its characteristic hepatic degeneration.


168


JOHNS HOPKINS HOSPITAL BULLETIN.




[Xos


112-113


Dilution.



Reaction.


up to


1-5000

1-5000

1-100

1-200

1--50

1-10



Positive.


" "


1-10



Negative.


" "


1-10




•• "


1-10



"


" "


1-10



"


Results of Experimental Inoculations.

White Rabbit I. Weight 1600 gins. Serum does not react to any member of the intermediate group.

July 13th, 1899. Inoculation in posterior ear vein with one cc. of a 24-hour bouillon culture of Bac. >>.

July 15th. Ear greatly swollen. Animal quite ill. Refuses food. Temp. 106°.

July Kith. Temperature 104°. Much better.

July 17th. Apparently well. Lively. Eating.

July 20th. Blood taken for serum reaction. Thrombus in ear vein at seat of inoculation. Cultures from thrombus show subsequently several colonies of Bac. 0. Serum agglutinates Bac. in 1-700 dilution. Reaction complete in 30 nuns. No reaction in dilution of 1-50 with B. enteritidis, B. morbificans bovis or B. " Hatton."

July 22nd. Reinoculated in other posterior ear vein with two ee. of 24-hour culture of Bac. 0. Animal remained quite ill for several days. Recovered.

July 28th. Apparently well. Blood-culture negative. Serum reaction positive in 1-4800 dilution. Comparative serum reactions with other bacilli; B. chol. suis 1-200, fair reaction. B. enteritidis (Gartner et al.) 1-10, negative.

Tin- slight agglutinative reaction toward B. chol. suis suggested that the animal had acquired some resistance against hog cholera and a large fatal dose was given to this animal and to a control animal with the following results:


White Rabbit I.

August 8, 1899. Intravenous inoc. of 1 ce. of 24 hour bouillon culture of B. chol. suis.

Aug. 10. Rabbit well.

Aug. 20. Blood taken for serum reactions shows a reaction toward Bar. O and B. chol. Suis in 1-5000 dilution.


Control animal, of same weight with negative serum read ions.

Aug. 8. Corresponding inoculation.

Aug. 9. Found dead (1 s hours.)

Autopsy, (leneral septicaemia. No mac. changes except injection of duodenal mucosa and an acute cholecystitis with bile thin and pale. Stained preparations from all organs, urine and bile showed a multitude of bacilli.

Cultures. Heart-blood, liver, gall-bladder, peritoneal cavity, and kidneys. B. chol. suis pure; urine, B. Chol. suis and B. Colt communis.

Organs. Acute fatty degeneration of he liver.


August 28th. Comparative serum reactions of White Rabbit 1 * with uninoculated organisms of the intermediate group as well as with B. typhosus showed that a slight tendency to agglutination more marked than before the last inoculation had been acquired. The reactions were as follows:


  • Agglutinations were also positive with this serum, having

a high reaction toward H. chol. suis. toward three individual cultures of B. icteroides (Sanarelli). sent by Dr. Heed from tinWashington laboratory as follows:


Organism. Bacillus O. Bac. chol. suis. B. icteroides B. typhosus B. enteritidis (Gart.) B. var. " Hatton " B. morb. bovis B. typh. mur. B. paracolon (Gwyn) B. coli com.


1. Orig. culture from Roux's laboratory. Serum reaction positive up to 1-200, suggestive to 1-1000 in 2 hours.

2. B. icteroides from Santiago case, 1898. Serum reaction positive to 1-50; suggestive to 1-200 in 2 hours.

3. B. icteroides from Havana case, 1899. Serum reaction positive to 1-200; suggestive to 1-1000 in 2 hours.

Believing from these results that the animal had acquired in some degree a protective reaction toward other members of the intermediate group, although the clumping reaction was not marked in high dilutions, it was then inoculated with a fatal dose of B. enteritidis (Gartner), as was also a normal control animal and another rabbit which had been immunized to B. typhosus.

Inoculation with Bac. enteritidis (Gartxer).

White Babbit I. Serum reactions given above (Aug. 28).

Aug. 30. Inoc. in post, ear vein with 1 cc. of a 24-hour bouillon culture of B. enteritidis (Gartner).

Aug. 31. 111.

Sept. l. Animal killed. Immediate autopsy. Caseous tubercle of ear at site of original Bac. inoculation. (July 13.)

Abdomen. All organs apparently normal except liver and biliary apparatus. Section of former showed small focal necroses, (iall-bladder normal in appearance but containing bile which was thin and pale and which had a yellow precipitate showing through the thin bladder walls. This consisted of desquamated cells and amorphous precip. of bile pigments. Xo organisms identified. Duodenal mucosa showed several minute hemorrhages in upper ."> cm. Duodenal papilla was erect and injected.

Cult una. Tubercle of ear, heart-blood, kidney and liver, sterile. From the gall-bladder on " intermediate " bacillus was isolated which could not be identified culturally. Identified by serum reaction, however, and shown to be Hue. enteritidis {Gartner), as serum taken from rabbit with pure Gartner infection clumped the organism in t-500 dilution and had little effect on hog cholera and Bae. 0.

Duodenum. An unidentified intermediate bacillus was isolated, presumably B. Gartner, in pure culture.

Sections of the liver showed areas of focal necrosis involving whole lobules.

Black Rabbit — normal control.

Serum reactions negative in 1-10 dilutions to Bae. 0, B. chol. suis. B. enteritidis and B. typh.

Aug. 30. Corresponding inoculation. (Cf. White Rabbit I, Aug. 30.)

Aug. 31. Very ill.

Sept. 1. Found dead.

Autopsy. No decomposition.

Abdomen. Stomach full of food. Urinary bladder distended. Xo macroscopieal changes apparent except in the biliary apparatus and duodenum. The gall-bladder was distended and injected: full of hemorrhagic bile containing a flocculent precipitate.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY-AUGUST, 1900.


PLATE VIII.



1. B. typh. 3. B. paracolon (Gwyn). 5. B. var. " Hatton." 7. B. icteroidos. 9. B. ooli.

■-'. Bae. O. 1. B. enterit. (Gart.) 6, B.chol.suis. 8. B. morb. bov. (Bas.) LO. Control.

Fig. 1 (a) — Photograph of reactions in plain milk utter 4 weeks. The diminution in opacity of the intermediate forms is well shown. Paracolon (Gwyn), producing alkali more slowly than the others, has not yet reached 4.0 per eent necessary for complete solution of the casein. B. chol. suis and B. icteroides have been shaken up and show the temporary settling of the surface layer of liberated fat-globules.



Ft... l (b —Photograph taken with transmitl I li i f the same tubes as Fig. 1 (a), Bhowing the comparat translucency of the intermediate group.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY-AUGUST, 1900.



V V >



Control. B. paracolon. li.culic.iiMn. B. ent. (Gart.) B. chol. suis. B. typhi mur.

Bac. O. B. typhosus. I!, moil., i.ovis. B. var. " Hatton." li icteroides.

Fig. 2 — Reactions in sugar-free bouillon containing 1 per cent of commercial lactose. Gas-production slight in intermediate group due to dextrose (?) adulteration,



B. morbif. bovis. B. choLsuis. I!, icteroides.

B. enteril ides. It. paracolon Fig. 3. — Reactions in the 1 per cent lactose bouillon not completely freed during its preparation from muscle-sugar; Slight gas-production except with B. paracolon.



Fig i Typical reacti ins in 1 per millon.

FERMENTATION REACTIONS IN LACTOSE BOUILLON.


THE JOHNS HOPKINS HOSPITAL BULLETIN. JULY-AUGUST. 1900.



Bac. O. B. enterit. (G&rt. B. ohol. suis. B.typhimur

B. paracolon ((Jwyn). li. var. "Hatton." IS. icteroides.

Fig. 5. — Gas-production in sugar-free bouillon containing 1 per cent of dextrose.



Fig. 6.— Gas-production in sugar-free bouillon containing 1 per cent ol dextrose. For comparison with Fig 5. Snowing relative slowness of gas-production with Bac. and Gwyn's paracolon. The dailj production of gas is indicated bj label


FERMENTATION REACTIONS IN DEXTROSE BOUILLON.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY-AUGUST, 1900.



Fig. 7. — Reactions in sugar-free bouillon containing 1 per cent manuite



■ ili l per cenl mannite. Showing usual proportion of gas and rapidity of production with Bacillus The production of gas in the first twenty-four

'""i 1 - : rison with the others unlike Fig. 7.


FERMENTATION REACTIONS IN MANNITE BOUILLON.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY-AUGUST, 1900.



Fig. 9. — Reactions in sugar-free bouillon containing 1 per cent saccharose.



Fig. If) Reactions iu 1 per cent litmus saj liarosi which hail been partially converted during sterilization.

Slight prod net ion of gas in tubes 3, 3, 6, 7, 9, LI, after l v hours of incubation. At this time the litmus is completely reduced in the closed arm of the tubes containing the more rapidly growing organisms, 7, 8, 9, 10, 11, 18. Reductions of litmus in 2 and '■'>, slower in growth, arc not completi till five days. The photograph shows the darker color of these tubes which have varied luit little from the control.


FERMENTATION REACTIONS IN" SACCHAROSE BOUILLON.


July- August, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


169


The mucous membrane of the duodenum in its upper 8 cm. was deeply congested, showing punctate hemorrhages, and the whole bowel and serosa over it were oedematous. The duodenal papilla was swollen and, prominent and had two bright punctate points of hemorrhage on it.

Stained preparations of all the organs, bile and urine showed myriads of bacilli.

Cultures showed a pure septicemia as follows: Heart-blood, spleen, kidney, liver, and gall-bladder, B. ent. (Gartner), pure culture; duodenum and urine, B. ent. (Gartner), and B. cvli com. and an unidentified bacillus.

Sections of liver showed hepatic cells greatly swollen and having undergone a fatty change. No focal necroses.

Black and White Rabbit. Same weight.

Previously immunized to B. typhosus.

Preliminary serum reactions.

B. typh. 1-2000 positive.

B. rut. 1-10 posithe and suggestive to 1-100.

Aug. 30. Corresponding inoculation. (Cf. White Rabbit I, Aug. 30.)

Aug. 31. Lively.

Sept. 5. Died 3 P. M. Immediate autopsy. Blood taken just before death shows an agglutinative reac. toward B. ent. of 1-500.

Uucroseop. lesions. Liver pale, soft, showing small yellowish areas of apparent necrosis.

(iall-bladder greatly distended, thin-walled and transparent. Bile, thin and watery with an abundant mucoid yellow precip. showing through the walls. Stained preparations from this fluid show masses of bacteria, chiefly in clumps, and desquamated goblet cells. No motile bacilli seen on hanging drop.

Duodenum negative. A few slightly injected points. Other organs were mac. negative.

Cultures. Heart-blood, sterile; spleen, few colonies of 8. Gartner; kidney, sterile; liver, few colonies of B. Gartner; gall-bladder, multitude of colonies of B. typhosus, an unidentified Bac. and B. Qart. (?).

Duodenum. B. pyocyttneus, B. ooli com., unidentified bac. peptonizing milk.

Sections of liver show large areas of focal necrosis similar to those seen in White Rabbit I.

From these last experiments we see that the normal control rabbit died of an acute general infection from Bac. Enteritidis with the usual characteristic lesions, especially referable to the eliminative system, namely, of the liver, gallbladder and duodenum, from which organisms were obtained in greatest numbers. The rabbit (White Rabbit 1), which had apparently recovered from its infections with Bacillus and B. cholerce suis, was killed at the same time, and it was found that no bacteria remained or could be found in the general circulation or organs, but an organism persisted in the gall-bladder which could be identified by serum reactions alone and was shown to lie that of the most recent infection, namely, B. enteritidis.

The "typhoid" rabbit succumbed to his infection in sixdays with the characteristic lesions found after fatal inoculations with B. chol. suis. B. icteroides or other members of the group which are actively pathogenic. Necroses of the liver similar to those seen in this animal were found in WHITE Rabbit I when killed, and were probably due to tin 1 hog cholera rather than to the more recent Gartner infection else the control rabbit would have exhibited them.


These observations are too few in number to lead to any broad conclusions. They, nevertheless, are very suggestive of the possibility that immunization with one of these forms endows the animal with a certain degree of resistance toward infection with the others. Furthermore, an acquired serum reaction toward one form does not furnish agglutinative properties of equal degree toward other varieties even though they are so closely related as to be culturally indistinguishable. Thus agglutinative sera for individual forms may be obtained, by which means alone we can differentiate the organisms.

In Review.

A consideration of the cultural properties of the organism, Bacillus 0, which has been dwelt upon at such length, demonstrates its close relationship to the definite and hardly recognized group of bacilli of the hog cholera or B. enteritidis of Gartner type, which bacilli, having some characteristics peculiar to both the typhoid and colon groups, may be said to occupy a biological position intermediate to them. Whether the cultural characteristics of these organisms are but temporarily acquired, and whether they should merely be regarded as having a transient intermediary existence, may be a question of dispute; but, nevertheless, a certain distinct isolarity for these particular forms is demonstrable, and the definiteness of the serum reactions, pathogenicity, and perpetuation of cultural features justifies their installment in a separate group.*

The elaborate tables of Germano and Maurea," of Tavel and Lanz, of Gilbert, Booker, Smith and others show what a variety of closely related bacillary forms of this family may be isolated from one source or another. In a recent study of the intestinal flora of dogs. Dr. Livingood and the writer f isolated about fifteen varieties of bacilli, chiefly of the colon and paracolon type, though several more intermediate forms were found, and on not a few occasions organisms indistinguishable from B. typhosus. It can thus be readily understood, if typical or allied forms of these various groups occupy at one time or another the alimentary tract, that during the course of fevers associated with intestinal lesions they may easily find their way into the portal circulation and cause an infection superimposed on that of the original disea.se. It has been shown, however, that colon, which is a permanenl inhabitant of the lower intestine where these lesions are usually situated and consequently the most frequent secondary invader, is rarely found in infections beyond the confines of


  • Cf. Flexner, Simon. Microorganisms. Twentieth Century

Practice of Medicine, Vol. Will, p. 655, 1900.

"Germano and Maurea: Vergleichende CJntersuchungen iiber Typhusbacillen und ahnliche Bakterien. Ziegler's Beitrage, Bd. XII, S. 49r>. 1893.

f Experimental and Surgical Notes upon the Bacteriology of the Upper Portion of the Intestinal Canal, etc. Contributions to the Science of Medicine, dedicated by his pupils to William H. Welch, p. 571, 1900.


170


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 112-113.


the abdominal cavity. Gwyn's paracolon and Bacillus 0, on the contrary, were isolated, one from the peripheral circulation and the other from a surface lesion, and consequently it is unlikely that they were secondary invaders. Furthermore, the patient's blood reacted strongly to these organisms and not to B. typhosus, and it is not improbable that they were the specific cause of the disease, which resembled clinically typhoid fever. For similar reasons the recovery of B. icteroides from the peripheral circulation of patients suffering with yellow fever would favor Sanarelli's view that it is the cause of a specific fever and not a secondary invader, as many are inclined to believe.

The individuals of this group of organisms spoken of as an intermediate group present a wide range of pathogenic activity toward man and animals, and though they can be distinguished by their response toward various specific sera, they are practically identical in their cultural reactions. Their chief distinguishing features from B. colt and B. typhosus may be given as follows:

Chief distinguishing features of the Eherlh or typhoid, Gartner or intermediate and Escherich or colon groups.

B. typhosus. An actively motile bacillus possessing as many as 11 flagella at times and having marked pathogenicity toward man though slight toward the lower animals. Eeaction in milk is acid, with a very late (months) or no terminal alkalinity. The organism ferments glucose but not lactose and produces no gas from any carbohydrate medium. Under ordinary conditions of isolation there is no production of indol.

Fermentation reactions:


Dextrose. Total gas

Aerobic : Acid


Anaerobic :


Acid


Lactose. Saccharose.


Alkaline Alkaline

Neutral Neutral


Intermediate Group. B. Gartner and B. chol. suis type. Bacilli with the morphology of B. typhosus and possessing an equal or greater number of flagelke. Actively motile and in many cases having a distinct pathogenicity for both man and animals. Eeaction in milk presents an early and terminal strong alkalinity in the presence of air, appearing after a transient acidity. Milk is never coagulated. They ferment glucose, with the production of gas, never lactose or saccharose. Under ordinary cultural conditions no indol is produced.

Fermentation reactions:




Dextrose.


Lactose.


Saccharose.



Total gas


1/2



or bubble



H/CO,


2/1






Aerobic :


Acid


Alkaline


Alkaline


Reactions :







Anaerobic :


Acid


Neutral


Neutral


Bacillus and B. paracolon (Gwyn) may represent a subdivision of this group, being' slower in their action on milk and growing - less luxuriantly and more like B. typhosus in various fluid media and resembling it in their pathogenic action on animals.

B. coli and its many allied forms. A bacillus with sluggish motility possessing few flagella;. Pathogenicity ordinarily is slight for man and animals. Growth on potato is abundant and colored. No alkalinization in aerobic growth. Eeaction in milk is acid, invariably sufficient for coagulation. It ordinarily produces a large amount of indol. It ferments glucose and lactose. Saccharose may or may not be acted upon.

Fermentation reactions:


Dextrose.

Total gas 1/2 H/CO a 2/1

Aerobic : Acid

Anaerobic ; Acid


Lactose.


Saccharose,


var. (a) var. (t»

1/2 2/3 slow

2/1 3/2

Acid Alkaline Acid


Acid


Alkaline Acid


CHARLES FREDERICK WIESENTHAL, MEDICINE PRACT1CUS, THE FATHER OF THE MEDICAL

PROFESSION OF BALTIMORE.*

By Eugene F. Cokdell, M. D.


The first name of any importance in the medical history of Baltimore is that of Charles Frederick Wiesenthal, who was born in Prussia in 1720 and who settled in Baltimore in 1755. Family tradition asserts that he was " physician to Frederick the Great," but we possess no further details of his life in his native land. His familiarity with the organization of the medical department of the Prussian army, shown in his letters to the Maryland authorities during our Revolutionary War, lends some plausibility to the supposition that he may


  • Read before the Johns Hopkins Historical Club, Feb. 12, lion.


have been connected with that service during his early professional life. There is evidence to show that his family enjoyed a good social position, and his educational advantages must have been considerable.

It is uncertain whether he possessed a medical degree or not. Dr. Ezekiel John Dorsey, a pupil, in dedicating a thesis to him (Edinb., 1776) adds M. D. to his name, while another pupil, Dr. George Buchanan, in a similar dedication (Phila., 1789) gives the name only without title. He does not appear ever to have used the degree himself, and in the account of the establishment of the first Lutheran church in


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY-AUGUST, 1900.



CHARLES F. WIESENTHAL.

REPRODUCED FROM A PENCIL SKETCH BY HIS SON ANDREW.


July-August, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


171


Baltimore, drawn up it is believed by himself, lie is referred to as " Karl Fried. Wiesenthal, Medicines Practicus." He makes no allusion to the subject in any of his letters, not even in that urging upon Andrew the importance of a degree.

There were not many inducements for an aspiring young physician in " Baltimore Town," when Dr. Wiesenthal settled here at the age of 29. It was then but a small village of some hundreds of inhabitants, with unpaved streets, with but one church and without a newspaper. Its chief thoroughfare, " Long, now Baltimore, St., was in a wretched condition — indeed at times impassible. Within live years certainly it had been enclosed by a picket fence and gates to protect it from Indians. Annapolis, on the other hand (where Upton Scott had settled two years before) was the seat of government, the centre of the fashion, influence and culture of the Province. But Baltimore, under the guiding genius of her " Komulus," as he was called — Dr. John Stevenson, a north Irishman — was even then looming up as the commercial metropolis of the state and it may be that he foresaw the future greatness which awaited it. Or he may have emigrated with a party of his countrymen, who selected Baltimore for a home, and from w'hom he was unwilling to be separated. Furthermore the country around was well settled and many of the landed proprietors were men of means, and able to compensate a physician liberally for his services.*

The summer that he arrived was signalized by the defeat of Braddock's army, an event that favored the growth of the town by deterring settlers from going westward. Shortly after his coming he married a lady of York, Pa., who bore him one son and three daughters. In 1771, he became naturalized. During the Revolution, he warmly espoused the cause of the patriots and his services and advice were of the greatest value to the state and country. In January, 1775, he was made a member of the Committee of Observation of Baltimore County and in December of the same year he received the appointment of superintendent of the manufacture <>f saltpetre for the state. In one of his letters he describes a journey made to some caves on the south branch of the Potomac, where an abundant supply of saltpetre was found. He published his method of manufacture of this substance in the Maryland Gazette. January 2d, 1776. On March 2d, 1 i ', 6,f he was commissioned by the Council as Surgeon-Major of the 1st Maryland Battalion commanded by Col. Smallwood. In a letter to the Council of Safety, written at this time and still extant, he expresses his willingness to assist the cause to the extent of his power, strength and abilities and to go with the troops wherever they should be ordered. On the 12th of March, 1776, he published an appeal to the public


  • Gov. Sharpe reports, May 2, 1754, that the town has the appearance of the most prosperous one in the Province. Few, he

says, except Germans, who are commonly the possessors of small sums of money, have settled and built in it. Letter quoted in Trans. German Uistor. Soc. of Md., / t th Ann. Report.

t Quinan's Annals.


" for linen rags & old sheeting for bandages." In the same year he was Medical Purveyor for the Maryland troops and Examiner of candidates for medical positions in the Service. In 1777, according to Quinan he was Surgeon-General of the Maryland troops, in which position he received a salary of " 35 shillings a day & no rations." Dr. Wiesenthal does not appear to have served with the troops in the field, although he visited them in an official capacity in their camps. He seems to have had the general supervision of medical affairs in Baltimore, establishing and conducting a hospital, purchasing medical stores and instruments, examining candidates and rendering professional services to the soldiers and sailors in the service of the state at this point.

According to Mrs. M. E. Reigart, of Baltimore, his granddaughter (who is here present this evening), Dr. Wiesenthal resided first in the suburbs of the town in a stone house on the Clifton Road, which is still standing. At what time he moved to his Gay Street house does not appear, but there he lived for many years, occupying two adjoining 2£ story dwellings, the one to the north as a dwelling house, and the other as an office.* These houses were demolished about 2"> years ago and a large shoe store was built on their site. The lot extended through from Gay to Frederick Street, and on the rear of it Dr. Wiesenthal erected buildings for his medical school and dissecting room. In these, which are still standing, he taught many students, among whom were Drs. William Augustus Dashiel, George Buchanan, Ezekiel John Dorsey, Andrew Wiesenthal and Frederick Dalcho. t In one of


  • Southeast corner of Gay and Fayette Streets, now Hill's

Shoe Store. Fayette Street was not opened east of Gay until about 50 years ago, so that there was no corner there in Dr. Wiesenthal's day.

t Frederick Dalcho was born in London in 1770, his mother being Elizabeth Wiesenthal, a sister of Dr. C. F. Wiesenthal, and his father a distinguished officer \inder Frederick the Great, who having been severely wounded in battle had been permitted to retire to England for his health. Upon the death of his father, at the invitation of his uncle, young Dalcho came to Baltimore to prepare for the profession of medicine. He arrived in Baltimore in a sailing vessel on the 2?,d of May, 1787, " after a boisterous passage of 8 weeks." Here he obtained a good classical education, after which he devoted himself successfully to medical study including an extensive course of botany. He is said to have taken the degree of M. D. (his name is not included in the Catalogue of graduates of the University of Perina., but that catalogue is known to be very defective), and then to have obtained a commission in the medical department of the U. S. A. While stationed at Charleston, S. C, some difficulty arose between him and his fellow officers and he resigned (1799). He then entered on practice in Charleston and assisted in the establishment of a Botanic Garden. In 1807 he became coeditor of the Charleston Courier. He was also a very influential member of the Masonic body and later their Grand Chaplain. By request he published a work upon masonry which was adopted by the Order as an authority. In 1811 he became much interested in theology and a lay reader in the Episcopal Church. He was ordained Deacon in 1814 and Priest in 1818. In 1819 he was elected assistant minister of St. Michael's Church, Charleston, and continued with fidelity and acceptance to discharge the


172


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 112-113.


his letters (June 5, 1787) he speaks of the dissection of a little negro boy which young Dalcho was at that moment engaged in making. It must have been here, too, that the body of the murderer Cassidy was being dissected in 1788 when the mob collected and put a forcible end to the procedure.*

Dr. Wiescnthal was a zealous Christian and it was largely through his efforts and liberality that the first Lutheran church was built in Baltimore.! He " i,s ;, ' so President and Physician to the German Society (1784)4

|)i-. Wiescnthal was not only a public-spirited and useful citizen, but he was also a learned and skilful physician; devoted to his profession and ever seeking to promote its highest interests. His letters to his son Andrew, who studied first in Philadelphia (1781-2) and later in London (1786-9), designed for bis son's eve alone, display the purity of his character and the loftiness of bis motives. They contain also many interesting items, advice and allusions upon which 1 shall proceed to draw in further illustration of my subject. § In the first of the series dated Dec. 25, 1781. he says: "We receivd your Letters ... in which I see your beginning to dissect yourself which pleases me and I insist that you continue to do the same manually in propria persona, and not being content with merely demonstrations after the Subject is prepard, as


ilnties of that position until declining health compelled him to seek repose. His vestry declined his offer of resignation but pave him an indefinite leave of absence with continuance of his salary. He died Nov., 24, 1836, aped 76. His principal work was a history of the P. E. Church in S. ('. during the colonial period, which is considered an authority upon that subject. He wrote other religious works, sermons and essays, and edited a church paper. A monument was erected over his grave by the vestry of the church. He was about 5>/ 2 feet high and well proportioned. His manners were genial, his intellect vigorous and veil cultivated and he was a general favorite in the community. See Innate of American Episcopal Pnl/iit. p.y Wm. B. Sprague, N. Y. 1859.

  • Griffith's Annals.

t This church stood on the south side of " Fish" (Saratoga) St.. near " Bridge " (Gay) St., and near the site of the present Bethel African M. E. Church. The first building was erected mi 1762 and was an unpretentious wooden structure used also as a schoolhouse. It stood on a high and steep hill. About 1771 the excavations for streets in the vicinity, made the building insecure and shortly after it was pulled down, the material sold and the hill leveled. A brick building was erected on the same site (Quinan says in 1773). "After twelve years," to provide further accommodations for the growing congregation, an addition was made to it. The late Rev. Dr. H. Scheib recollected this ugly structure with its organ. Tt was entered by a high stairway at the side. In 1808 it was sold to the African church and a large church was built on ground further to the north, the present Zion Independent Lutheran Church. Dr. W. was a liberal contributor to the early church; he was an elder of the congregation and his name comes always at the head of the lists of members. See The Zwn Church of the City of Baltimore, by Rev. H. Scheib, Sd Ann. Rept. Germ. Hist. 800. Of Mil.

t Quinan, op. tit.

§ They are closely written in a fine, neat hand. They are closely copied in the extracts here given.


I want the practical part, it will lead you towards Operations and will make that part of Surgery more intelligible. I hope you will not be content with merely knowing the Situation of the Viscera, but will examine them minutely, their contents Vessels Ducts &c." . . . " I hear Doctor Shippen has a young Gentleman who prepares the Subjects for his Demonstration I would have you cultivate a strict friendship as far as his Morals will admit of (in which particular you know my firm Opinion) and frequently make Inquiries of the Doctor himself, who I hope is often with you himself & teaches."

In Dec, 1787, he expresses his satisfaction at Andrew's predilection for surgery, " in which the Quack must stand aside, whereas in Physic in this part of the World the most errant Quack if he has Assurance enough will often claim the preference & obtain it before the Man of real and true Abilities."

Here, from the first letter, is an allusion to Dr. Thomas Bond, of Philadelphia, the founder of the Pennsylvania Hospital and the first clinical lecturer in America: "I am glad you have introdue'd yourself to Doctor Bond though he may have some Oddities, you may nevertheless rely on this that his Acquaintance will be valuable to you both his Learning and Experience are unquestionable, and he moreover is very communicative and takes a Delight in instructing young Persons and that in proportion to their Diligence and Application you will therefore visit his Lectures frequently and freely • apply to him to resolve Such things as may be obscure to you, he is a good Surgeon besides and may give you Some good hints in the hospital."

There are but few allusions to cases and operations. "Mr. Yates . . . was formerly to become a Surgeon but has quitted it . . . but although he quitted Surgery that did not quit him, he having a fistula in Ano and undergoing an operation in London unsuccessful he came over to Maryland and recomended to me by Governor Smallwood. I laid it open very extensively, and found it proceeding near the root of the penis up to that region between the bladder and the Rectum as well as along the Anus and to the Ischium where I was even apprehensive of a Caries, he having once had a Caries on the Tibia and lost a large Exfoliation, it moreover enters the Rectum as he says he has found some Excrements pass through

the Wound and frequently flatus." "I hail last

Summer a Child 4 Months old of M r Will" 1 Buchanan's under my Care whose head bulgd out and distended every Suture it was taken with Convulsions, it was cured by applying blist™ to the Spots for Some Weeks." He sends the report of a case in which " the quantity of matter issuing from a tumor no bigger than a walnut was nearly 3 pints." In Sept., 1788, he writes: "M r Wolsenhome from St Mary 8 City was this Morning with me for my Advice he came but lately from London has formerly had my Opinion in writing concerning some nervous Symptoms deriv'd from the Gout, he has consulted several eminent Physicians in London especially D r Letsome & Heberden. he show'd this Letter I mean Heberden. my Opinion in writing concerning the Complaint &

Treatment which being approved of by the Doctor furnished some little Stoff for my Vanity." In an earlier letter to the Council of Safety (.!/</. Archives, Dec. 8, 1776) to which my attention has been called by Dr. Jackson Piper, he des ribes a curious case of " Eresypelas " in a soldier, due to taking cold, ami involving the entire body "from head to foot." " the Vesications common in that Disorder displaying a humour so sharp that in a few days he was all over deprivd of his skin." He had likewise lost his eyesight and his life had been saved with the utmost difficulty. The doctor regarded the blindness as incurable. He advises Andrew to study to become skilful in surgical operations especially lithotomy and "extraction" of cataract. He refers to the great success of Dr. Tyler, a young physician of Frederick who had made considerable reputation in "couching the cataract." He tells him to study closely the action of drugs and to make himself acquainted with all new discoveries.

He was very anxious for Andrew to take a degree and expresses regret that the latter had not gone to Edinburgh to study instead of to London. He longs to see something in print "over the name of A. Wiesenthal that may meet the approbation of the learned." He asks what is to lie the theme of his inaugural essay? in what language shall it appear? Is he sufficiently master of the Latin to hold a public disputation? In Leyden, at least, a public disputation is not demanded — perhaps at Rheims the same is the case. Would that he were with him to assist with advice and counsel! He sends A. from time to time copions notes of cases and opinions on various medical subjects, which he urges him to put into shape for a thesis or for publication in some journal. Oct. 11. 1787, he writes: "I have sent yon various Cases in Physic and will consider of some more, and I think I will likewise send you some of my Theoretical Opinions which you may be probably able to elaborate something farther and should it lie worth the Notice of some of your friend- it might be perhaps worth while to have it published, for this is Truth that a great many more silly things have been published than what we should." In Nov., 1788, he tells him that a diploma is indispensable and suggests that he might obtain one in some institution without residence, or an honorary one. " Doct. Brown the great opposcr to I > r ( lullen's Doctrine and who now resides in London and as common Report Bays even in the Fleet's prison where he lectures, has wrote many a young Students Thesis on which he obtaind In- Diploma blindfold."

The substantial- of life are not forgotten. The Christmas letter of 1781 already spoken of concludes: " We congratulate you to these Christmas holidays and wish you had one of our very good min'cd pyes." In Oct., ITS"., hi Andrew a box of " hommany Beans & Sweetmeats." In another letter: " Mr. Yates sails on the Willing Tom next Week and I hope he will be able to take the Geese with him but I am allmost afraid we are too late. Mama I apprehend by wanting to extend her bounties will be the Cause of your getting none." The next day — in a postscript — " My Sugges


tions arc but too true, the Willing Tom is sailing from l'atowmack ami the smoaking the Geese requiring a little more [time] lay till at last the S(c)hooner saild from Annapolis by which all remaining Stores were sent and M r Yates going by Land obligd us to postpone it to another Opportunity which we hope will soon happen."

Dr. W. was very anxious to have a law passed for the regulation* of medical practice in the stale and headed a movement with that object in view. The prevalence of quackery, the low standard of medical training and the reprehensible conduct of many physicians in good standing, made an organization of the profession and a regulation a necessity. (In Sept. 12, 1788, he writes thus: "To rescue the Dignity of Physic from that horrid State into which it is plungd within these few years and most especially since my Sickness will require a Herculean Labour, and it will fall in some Maisure to your Lot to undertake the laborious Task." After a full and public discussion of the matter in the town paper, a meeting was called for Nov. 27, 1788, the call being signed by himself. At this meeting which was most probably held at his house, he was chosen chairman. There is mention of it. in a letter dated Nov. 28, 1788: "We are just, about procuring a Medical Regulation in a little more earnest than heretofore, it nevertheless meets with some underhand jalousy and what amazes me it comes from Doct. B . . . we have had 3 meetings he has had allway" written Invitations and each Time evaded it. The reason we only guess at. Last Nights meeting it was proposed for the Sake of Order and to have jointly more Weight to organize ourselves into a Society under Rules. T was unanimously nominated President and M r Frederick for Clark, so that he has now an office." The plan which was then framed embraced the entire state in its operations and was similar in its features to the Charter of the Medical and Chirurgical Faculty adopted eleven years later. But for Dr. Wiesenthal's ill-health and death the following spring, there is little doubt that he and his associates would have succeeded in their object, and thus have anticipated by ten years the founding of the Medical and Chirurgical Faculty.

Dr. Wiesenthal almost idolized his son Andrew — his only son. His letters abound with the most endearing expres sions, as this: "so tender a father as I am who makes his Sons welfare his only happiness in this World." and he lavished his money freely in giving him the best opportunities then available for education. In Sept.. 1788, he estimates that he has supplied Andrew with nearly £450 sterling — "a pretty Modest Sum in these dreadful Times." he adds. Moreover we must remember that Andrew lived with his aunt during his stay in London, and that the above amount did not include his books, instruments, medicines and the passage money home, which were still to be provided. He chides him mildly on one or two occasions and refers to a letter of A.'s headed "sans six sown," which seems to have w-orried him a deal.

The following pathetic passage occurs in a letter of No

vember 28, 1788: " I for my part am allready discarded and laid up like an old Man of Warship, although the Shafts of Jalonsy are still continued to be let off against me as if they dreaded my returning to my usual Strengt again nay I vervlv believe, they will hate my very Memory ten Years after my having returned to Dust, and be afraid and Jalous of me (horrid indeed!) if I reflect that at all Times I have acted up to the Dignity of the Profession, have disdaind all mean Empyrical Methods, because I had no Occasion I think that I ought to be respecteil as a father and Supporter of the Profession and be treated friendly." In another letter about the same time he writes: " I find no remedy now in the late Evening of my Life as to prostrate myself before the Throne of the Allmighty and expect in the other World that which this has denied me."

Towards the last. Dr. Wiesenthal, who was of a highly nervous temperament, suffered greatly from hypochondria. Every circumstance became irksome to him and he sought and found relief from his despondency in the tinctura thebaica which he supplemented with the liquor anodyni Hoffmanni. The dose which he took of the former was not extreme, not exceeding, according to his statement, 40 to 45 drops.

His last letters show that he was failing. Sept. 12, 1788, he writes: "My health, my dear son, is very precarious and being in my grand Climacteric, the 63d year of my Age I find myself declining every day." Although he lingered on to the spring of 1789, his eager longing to see his son before he died was not gratified. There is something inexpressibly sad to see this good old father sinking into the grave, hoping day by day for the return of his son beyond the sea and with his life lit up by that one thought alone.

The following is the notice of Dr. Wiesenthal's death taken from the Maryland Journal and Baltimore Advertiser of June 2, 1789: "The shaft he so often warded from others has pierced him at last. Yesterday morning about half past seven o'clock departed this life Dr. Charles Erederick Wiesenthal, in the 63d year of his age after having practiced in this town for 34 years. If the strictest attention in his profession which humanity could excite & that success which might be expected from superior medical abilities improved in an uncommon measure by reason & observation deserve to be remembered, the tears of gratitude must flow in sorrowful profusion. He is gone! & the pain of reflection is the more heightened because it is at the time when he was in daily expectation of the return of an absent & only son whose virtues & abilities are beloved & admired by all who know him."

Dr. Wiesenthal's picture suggests a large, fine looking dignified man with a German type of countenance. He was generous and hospitable and particularly kind to the poor,


often remitting his charges against them when they seemed unable to meet them.* His dress is described as follows: " a scarlet cloak, three cornered hat, blue velvet coat with gold buttons & buff facings, buff vest, lace ruffled shirt, knee breeches, stockings, shoe buckles, plain white cravat surrounding neck, wig & cue tied with a black ribbon." He was the first physician in Baltimore to drive a four-wheeled carriage. On this was inscribed his crest & motto — " a horse's head bridled & bitted with two crossed arrows beneath & the words Premium Virtutis."

Dr. Wiesenthal's remains were interred in the burial ground attached to the church, but were afterwards removed to Loudon Park Cemetery. No tombstone was ever erected over them. Andrew died in 1798, at the early age of 36, leaving a son Thomas Van Dyke Wiesenthal, who became a surgeon in the IT. S. N. There is only one person now living bearing the name of Wiesenthal, an aged single lady residing in Boston, but whose present residence we have not been able to find.

One of Dr. Wiesenthal's pupils in dedicating his graduation thesis to him, speaks of his " great professional skill, his rare & singular virtues & his nobility of character";! another compares his position in Baltimore to that of Sydenham in London. J I venture to think that after what we have heard this evening we shall not consider him unworthy of the further title — one which he so much coveted — "Father of the Medical Profession of Baltimore."

[In connection with the above paper, there were shown a pencil portrait, drawn by his son Andrew, his crest and motto, and a photograph of his medical school, still standing.]

Authorities consulted:

Letters of Dr. C. F. Wiesenthal, MS.

Quinan's Annals.

Maryland Archives.

Newspapers of Baltimore and Annapolis.

Griffith's Annals.

Rev. Dr. II. Scheib's Article (Germ. Histor. Soc. Pubs.).

Family Tradition (Mrs. M. E. Reigart).


  • " When patients came to settle bills, if poor, he would look

in his books and say: 'I don't find anything against you.'" — Mrs. Reigart.

t Disaertatio Ivaugwralis dc Nutritione. Ezekiel John Dorsey, Edinb., 1776.

f Vir TcnerabiHs, CaroVus Fredericus Wiesenthal, rri mediate apud Baltimorimscs cultor felicissimus, qui oh magntim omnium quae medicinam spectant, notitiam, iwn minorls ibi qvam Sydenhamius olim apud Britannos fuit aestimatus, penditur. Inaugural Thesis of Dr. George Buchanan. Univ. Pa., 1789.


THE JOHNS HOPKINS HOSPITAL BULLETIN.

The Hospital Bulletin contains details of hospital and dispensary practice, abstracts of papers read, and other proceedings of the Medical 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 XI is now in progress. The 'subscription price is $1.00 per year. The set of ten volumes will be sold for $20.00.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY-AUGUST, 1900.



Dr. Wiesenthal's Medical School, the first established in Baltimore. We do not know when it was opened, but there are grounds for conjeetaring that it was between lTt',0 and 1770. In February, 1774, Dr. W. A. Dashiell defends the views of his preceptor (C. F. W.) in the newspaper, a < ersy having- arisen between the latter and Dr. Ephraim Howard, concerning the use of venesection iu a case of pneumonia, and in his inaugural thesis at t lie University of Edinburgh, 1776, Dr. E. .1. Dorsey speaks of Dr. W. as having taught him the elemeuts of medicine. The view was taken from a second-story window of house northeast corner of Frederick ami Fayette streets, and one is looking a little south of west. The street before

us is Fayette, between (Jay and Frederick. In the distance one sees over the tops of the houses, the cross of Church of the Messiah (P. E.. \

street). In the centre of the square is the long two-story schoolhouse containing the sign "Hill's Hand-made Shoes". The smaller two-story building, at the nearer end of the square, also stood in Dr. W.'s day, and is believed to have been his dissecting-room. At the further corner of the square is Hill's shoe-store, built about twenty-live years ago, on the site of Dr. W.'s residence. Fayette street, formerly "East Street," was not opened between Gay and Frederick until about fifty years ago, and tin- doors and windows of the school-house ou that side must have been made at that time. The stone steps at the side used to be at the front entrance. The old lady is Mrs. Reigart, granddaughter, and the young gentleman to her left, at the edge of the pavement, is Mr. John Milton Griffith, great-great-grandson of Dr. W. Mrs. Reigart lives at '-'Hi Girard avenue, and is

33 years of age. Behind them is the writer of this sketch. After his father's death in 1789, Andrew taught here until his death, in L798. Shortly after the latter event, the house, which was then 4" N. Gay Street, passed out of the possession of the family. It is now unoccupied. About fifty years ago it was used by Mr. McMulIan (who is still living) as a furniture storeroom. Mrs. Reigart is the daughter of Juliauna Susanna Beneowsky Wiesenthal, '-the mischievous little Julianna, the pretty little babbler," of the letters, born four years before Dr. W.'s death and named from her godmother, Countess Beneowsky. sister of Mr. Messonnier, the importing merchant of Baltimore, who married Dr. W.'s daughter Elizabeth. To be absolutely certain that there was no mistake, the writer took Mrs. R. (who is a very intelligent person, with senses and faculties all good) to see the premises, which we inspected thoroughly. Although she never lived there, she has perfect recollection of the place, which she has often visited before. She says that her mother's nurse— a white woman — lived to an advanced age, and often talki d to bei of her grandfather and his family, and pointed to the building as her grandfather's school. The therefore, no question about its identity.


July-August, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


175


kiihn's glands. The latter had for the most part undergone cancerous transformation and were probably the origin of the neoplasm. No other growth was found.

Carcinomata occurring in the vermiform appendix are of the two varieties commonly observed in growths affecting the alimentary canal, namely, colloid carcinoma and adenocarcinoma with glands resembling proliferating glands of Lieberkuhn. An unusually large proportion of the cases occurring in the appendix if we accept the diagnosis made from the gross specimen are of the colloid type.

The clinical notes on the present case are briefly as follows:


I. PRIMARY CARCINOMA OF THE APPENDIX VERMIFORMIS; II. CARCINOMA OF THE APPENDIX SECONDARY TO CARCINOMA OF THE OVARIES.

By Elizabeth Hurdon, M. D.,

Assistant in Gynecology, Johns Hopkins University.

New growths of the vermiform appendix are so unusual and hitherto have received so little attention that each case is worthy of being recorded. The following cases, one of primary origin, the other secondary to an ovarian tumor, have recently occurred in the service of Dr. Kelly, to whom I am indebted for the privilege of making this report. Apart from its rarity the first case is of interest on account of the early stage in which it was discovered owing to the routine examination of the abdominal viscera made in all cases of abdominal section. The second case was also detected by this general examination.

In the literature there are references to ten cases of carcinoma originating in this organ. Of these, however, only the three cases in which the diagnosis was confirmed by a microscopic examination can be accepted as well established. These were shown to be of the usual type of carcinoma of the intestines. In two cases the growth had penetrated the abdominal walls appearing externally as large crater-like ulcers with thick irregular margins.

In Thiersch's case, reported by Bejer, the extension had taken place along a sinus which had persisted for three and one-half years after the opening of a large pus-sac in the right iliac fossa. On partly removing the external mass a fingerthick cord was disclosed which extended down into the peritoneal cavity. This proved to be the vermiform appendix, and in the cecum a tumor the size of a walnut could be felt surrounding the orifice of the appendix.

The writer calls especial attention to the early formation of adhesions and infiltration of the abdominal wall and to the absence of intestinal symptoms. He is of the opinion that the growth began in the apex of the appendix and slowly extended along the mucosa to the cecum.

In the case described by Kolaczeck the right lumbar region presented a deep ulceration, at the base of which was the denuded os ilii. At autopsy the appendix was found to bo destroyed by a tumor which had invaded the walls of the cecum, and also the surrounding cellular tissue and the psoas

muscle.

Afi 'iso and Daumie report a case occurring in a woman 50 years old who had died of heart-disease. The vermiform appendix floated free in the peritoneal cavity, was 1 cm. long, 4.5 cm. in circum. and cylindrical in shape. On transverse section the muscular layers could be seen enclosing a hard mass within which was a narrow canal opening into the cecum. The tumor did not project at all into the cecum and was limited to the appendix. Histological examination showed the muscular coats for the most part normal, but in places separated by small islands of epithelial cells. The peritoneal coat was normal. In the central part of the tumor near the canal were seen remains of the mucosa and of Lieber


Gyn. No. 6646. Mrs. G. Age 24. Married 9 years. II para. The oldest child 8 years, the youngest 3 years old. 2 miscarriages, the first six years ago, the last in August, '98. Her family history is unimportant, with the exception that one brother died at the age of 18 after amputation of the leg for a " cancer."

The patient had always enjoyed excellent health until the birth of her first child. At varying intervals thereafter she suffered pain in the lower part of the abdomen and back. The pain was described as aching or dragging in character and was most severe the week preceding and following menstruation. Last spring the patient had a fall and afterwards the pain which previously had been limited to the pelvis became more marked higher up in the right iliac fossa and was associated with constant aching in the right lumbar region. This was ascribed by her physician to a -floating kidney which was found to be present. Her appetite failed and at times she suffered from nausea and vomiting.

On palpation the abdomen was non-resistant, and there was no tenderness in either iliac fossa. The right kidney was palpable and slightly movable; on bimanual examination the uterus was found in acute retroflexion and its mobility was restricted. Further examination was negative.

Operation by Dr. Kelly. Feb. 21st. 1800. Release of pelvic adhesions; suspension of the uterus: removal of the vermiform appendix.

The uterus was found retroflexed and bound down by a few light adhesions. The tubes also presented a few adhesions somewhat stronger on the right than on the left side. Apart from these adhesions the tubes were perfectly normal and no cause for the pelvic peritonitis could bo discovered until on looking for the appendix it was found hanging down into the pelvis over the right infundibulo-pelvic ligament and enveloped in dense vascular adhesions. A shortened mesentery caused the outer third to redouble on the inner portion, and at the point of flexion there appeared to be a foreign body in the canal.

The appendix was amputated close to the cecum, the uterus


176


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 112-113.


and tubes freed from adhesions and the uterus suspended. The abdomen was then closed in the usual way.

The patient made an uneventful recovery and was discharged March 16th. In a letter written Dec. '99, she stated that she had gained twenty-three pounds aud her general health was excellent. She suffered, however, from some discomfort in the right lumbar region, probably owing to the movable kidney.

Pathological report: Gyn. path. No. 2854. The appendix is 10 cm. long. At the junction of the middle with the « mter third it is slightly flexed and held in this position by broad velamentous adhesions. The proximal end is practically normal but the part beyond the flexion is distended, having a diameter of 12 mm. and contains a soft concretion of about the size and shape of a date-stone. The walls here are thinned, averaging not more than 1 mm. Their internal surface is smooth. Joining the distended extremity to the normal inner half of the appendix is an intermediary portion about 1.5 em. long, of firm consistency. Previous to removal this was supposed to contain a concretion but on transverse section it is seen that the lumen is practically obliterated by a small oval swelling which impinges upon the canal so that merely a small erescentic slit remains. This is displaced toward the inferior border of the appendix by the tumor which encroaches from above. To the naked eye this minute tumor appears to be about 1 cm. long, and 5 mm. in its greatest thickness. Its cut surface presents a whitish dense appearance and is partly homogeneous, partly finely striated. It is enclosed by the muscular coats into which its external margin imperceptibly merges.

Histological Examination. — In a transverse section through the portion of the appendix occupied by the new growth it is seen that all its coats to a greater or less extent are infiltrated with epithelial cells in the form of nests or cylinder-like processes. The muscular coats are not thickened and the epithelial processes which here are slender and cord-like invade the interstitial connective tissue while the muscle bundles remain unaffected. The epithelial proliferation is most evident in the mucous and submucous layers, which are markedly thicke I. forming a rounded prominence which encroaches upon the central canal. The cells in this portion are arranged in oval or irregular masses, or in parallel columns consisting of three, four or more rows of cells. The intervening stroma is scanty and indeed the epithelial masses are sometimes directly contiguous. In the i Hi' i' of the column of cells a narrow central canal is sometimes faintly visible, and in the larger masses the cells are now and then seen to be disposed in little circles which may present a minute central lumen. Extending downward from the surface of the mucosa there are a few normal glands of Lieberkiilin. Others which are found here and there between the cancer nests show beginning proliferation and alteration of the character of the epithelial cells and are undergoing early carcinomatous changes. The starting point of


the growth has probably been in the area included between points p. and c, Figure 2, as here all the glands have been replaced by masses of tumor cells.

The surface epithelium of the mucosa has not taken part in the tumor-formation and is intact, though where the growth impinges upon the canal the cells are flattened. The mucosa lining the opposite side is attenuated and its glands shallow and few in number but the epithelial cells exhibit no tendency to become proliferated and are unaltered in appearance. The lymph-nodes have disappeared. The submucosa is scanty. Both circular and longitudinal muscular coats are of normal thickness.

On higher magnification the tumor-cells are seen to be fairly uniform, the peripheral layer of the nests consisting of low columnar, the central mass of oval cells. Where the minute lumina are present in the cell masses they are also lined with low columnar cells. The cell nuclei are oval or spherical and are vesicular. Their chromatin is finely granular. There are, however, various large cells containing deeply stained hyperehromatic nuclei which are coarsely granular. Mitotic figures exhibiting the different stages of cell-division ' are moderately numerous.

The invasion of the muscular and peritoneal coats is associated with but little inflammatory reaction, but the mucous and submucous layers show a marked leucocytic infiltration and it is noteworthy that a considerable proportion of the infiltrating cells are eosinophiles.

In the superior segment of the appendix, that is, the portion farthest from the mesenteric attachment, the growth has penetrated all its coats extending to the peritoneum, which contains many large round or oval cell-nests, d. Fig. 2, but the inferior segment has apparently been invaded only in the circular muscular tunic where a few strands of epithelium extend almost entirely around, running parallel with the muscle fibers.

The various coats of the cystic extremity of the appendix though thinned out preserve their normal proportions. Its inner surface is smooth and even, and its epithelial lining intact. The glands are diminished in number and shallow but otherwise unaltered; the stroma scanty and the lymph follicles atrophic and widely separated from one another.

The cecal half of the diverticulum is normal in all respects.

The first cause of the formation of carcinoma affecting any organ remains to be discovered, but the presence in this case of the fecal matter suggests an important question as to the etiological significance of foreign bodies in the development of tumors. The occurrence of new growths of the bile-passages and kidneys with calculi intimately associated has frequently been observed and a few tumors of the appendix have been described which had developed around foreign bodies as their centers. An instance described by Lafforgue is a small lipoma situated in the wall of the appendix which contains a small concretion in its center.

Gilford reported a case of sarcoma surrounding a concretion in the appendix, the growth having apparently resulted from


THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY-AUGUST, 1900.



Fig. 1 Primary carcinoma of the appendix. Tin ti.iu and caliber of the canal are indicated by the dotted lines beginning at •' and extending to the apex, d shows the dilated extremity. Between b and c is an indurated portion gradually merging into the normal.

The flexion is not so acute as before cutting t lie mesentery.



Flu. ::. A higher magnification of a small area in Fig. :-', carcinoma of the appendix (350 diameters). Two glands of Lieberkiihn are seen at ". and masses of carcinoma cells at /*; <• indicates the stroma.


-I


)


a— ss


■<$,


&


^




M




m


'&'


'<--..%:









V ^'


iV^


.-V »«*T


Fig. 2. Transverse section of carcinoma of the appendix (IS diameters). The canal of the appendix is see mucosa and submucosa are practicallj oormal; a few strand .1 deeply stained tumor cells are present in the circular m coat; the longitudinal muscle and mesentery are normal. On the righl between 6 and t the -land- of Lieberkuhn have been replaced by the neoplasm, and islands of tumor cells, d, are scattered throughout the remaining coat


July-August, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


177


a previous appendicitis. The tumor was removed with a portion of ileum and colon to which it was adherent and the patient made a good recovery. On cutting open the tumor three or four small collections of pus were laid open and in one near the middle of the mass was a fecal concretion twice the size of a cherry-stone. A probe passed into this cavity passed down the appendix vermiformis into the cecum. The microscope showed principally large oval and spindle-shaped cells, and the growth was considered to be an undoubted sarcoma. A small nodule was also excised from the right psoas.

In the cases of carcinoma of the appendix reported in the literature one writer mentions that a fecal concretion was present in the dilated extremity, the growth in this case affecting the cecal end. In our case the foreign matter is of softish consistency and there is no evidence of irritation of the epithelium lining the canal at any point. It is conceivable, however, that the presence of the body with the impossibility of expulsion due to the kink has in some way incited the atypical glandular proliferation.

Several of the cases quoted gave histories of attacks of acute appendicitis occurring some years before the discovery of the cancer.

Diagnosis. — The difficulty of diagnosis in carcinoma of the appendix is indicated in the histories of the cases quoted above and is owing to the absence of distinctive symptoms in the early stages. Our attention is first directed to the iliac region by the onset of pain and the presence of tumefaction, and when these are manifest the growth is usually well advanced. As a rule there is no interference with the digestive function until the growth has invaded the cecum or the large or small intestine. This was observed in only two cases late in the course of the disease. The most constant symptom is the presence of a dull pain of a not severe type affecting the right iliac region and extending to the right groin and thigh. On making a physical examination a firm mass is found occupying the position of the appendix vermiformis. This is usually cylindrical and before adhesions have formed is freely movable within a limited radius. The appendix, however, may be small and nodulated as in the cases of scirrhous carcinoma and is then hardly to be distinguished from a calculous appendix. The diseases for which carcinomatous appendix is most apt to be mistaken are: cyst of the appendix, calculi, tuberculosis of the so-called neoplastic form, impacted feces in the cecum or small intestine. Floating kidney was diagnosed in the case of sarcoma of the appendix recorded by Gilford.

In many instances only an exploratory section will enable one to make a positive diagnosis.

Prognosis. — If we should consider the prognosis of carcinoma of the vermiform appendix from the standpoint of the outcome in the cases reported it would be rendered extremely grave. It must be remembered, however, that the majority of these cases were observed in an early time and before the period in which operative interference began to be so gener


ally employed. Moreover in one case death was due entirely to an intercurrent affection and in three other cases we do not know that the growth was in any way responsible for the fatal termination. On the other hand, however, the absence of functional symptoms and the little pain excited by the presence of the growth may cause it to be overlooked until the surrounding tissue has been invaded or until rupture occurs, and in the latter case the ensuing general peritonitis is itself attended with serious consequences. In the present time when the vague pains accompanying mild affections of the appendix are more carefully investigated and when operative interference is more generally employed for the relief of such cases the prognosis in carcinoma is rendered more favorable as it is for this class of cases that early carcinoma is liable to be mistaken.

Treatment. — There is little to be added regarding the treatment in cases of carcinoma, as when the symptoms or the results of the physical examination warrant the assumption that the appendix is diseased, the safest course is to perform an exploratory section, and if the suspicion is verified, to remove the appendix. If the appendix is found to be the seat of a new growth in order to insure its complete removal the head of the colon should be resected and should the growth have visibly extended beyond the appendix a more extensive resection may be indicated. In eases still further advanced and involving the abdominal fasciae a radical cure can scarcely be expected and the patient receives little benefit from an incomplete removal of the tumor.

Secondary Carcinoma of the Appendix. — Secondary carcinoma of the appendix is of interest chiefly from the scientific standpoint, since clinically, as it gives rise to no symptoms or to none that are characteristic, its presence is masked by the primary tumor. Moreover, if detected its removal does little to stay the progress of the disease. Metastatic carcinomatous growths in the appendix appear to be almost as rare as the primary cases, most of the secondary growths consisting of direct extensions from the cecum. The most frequent seat of the original tumor appears to be in the ovaries, the stomach or other portion of the digestive tract, or the uterus. The growth in the appendix corresponds in structure to the original tumor.

The case I have to report was discovered at operation for removal of a large ovarian tumor, and at the same time it was found that the pyloric end of the stomach was also the seat of a new growth.

Gyn. No. 52fi2. Mrs. S., age 57 years, was admitted to the gynecological service complaining of an abdominal tumor associated with some pain in the lower abdomen and a slight sanious discbarge of about six months' duration. She was a healthy-looking woman, her appetite was good but she suffered from slight indigestion and chronic constipation. Further than this her history is unimportant.

Operation by Dr. Kelh/. — Removal of both ovaries and tubes and the vermiform appendix.


178


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 112-113.


The left ovary was transformed into a large oval tumor of remarkably dense structure. On microscopic examination this was found to consist of small round or oval glands imbedded in a dense cellular connective-tissue stroma. The glands were lined with low columnar or flattened epithelial cells with protoplasm stained deeply with eosin and containing large nuclei of variable shape and intensity of color. The epithelium was mostly disposed in one layer but occasionally two or three layers were seen.

The remaining pelvic organs appeared normal with the exception that the mesosalpinx of each side was thickened and the peritoneal surfaces of the broad ligaments and uterus were studded with a few small flat white nodules. One of these was excised and examined under the microscope showing only fibrous tissue but doubtless further sections would have revealed their carcinomatous nature. Microscopic examination of the right ovary showed that though not enlarged it was also invaded by the new growth which was limited to two well-defined areas immediately beneath the albuginea, and a small area in the hilus.

The vermiform appendix was found to be thickened, nodular and very rigid in its outer half, the cecal half being normal. The mesenteriolum was indurated. On cutting open the appendix its outer third was found to be slightly distended, containing a small fecal concretion. Internally to this there is a nodular enlargement 1 cm. in diameter formed by the general thickening of all its coats. The lumen here is constricted. The proximal half is of normal caliber.

Histologically, excepting in the thickened median portion of the appendix, nothing of importance is noticed. At this point there is a marked hyperplasia of the lymphoid ele


ments of the mucosa and submucosa and on the side to which the mesentery is attached the peritoneal, muscular and submucous layers are infiltrated with a carcinomatous growth similar to that in the ovary, while here and there in the muscular coats generally are small islands of carcinoma cells sometimes contained in vessels, but whether lymph channels or veins is not determined. A few light adhesions are attached to the surface of the appendix, and in one of the6e there is a small nest of carcinoma cells. The mesenteriolum is also invaded by the growth chiefly in its outer half.

In this case it is probable that the carcinoma cells were carried through the peritoneal lymph spaces to the mesenteriolum and thereupon invaded the various coats of the appendix. This view is maintained by the occurrence of the few superficial nodules distributed over the peritoneum which are probably metastatic, as the main tumor is enveloped in a smooth fibrous capsule and not apt to give rise to implantation growths, and from the fact that the principal focus of invasion is at a point contiguous to the mesentery, which is also extensively involved in its corresponding portion.

Bibliography.

Rokitansky: Wien. med. Press., 1866.

Bejer: Berl. klin. Woch., 1882, S. 616.

Draper: Boston Med. and Surg. Journ. Vol. 110. 1884.

Croizet: These de Paris, 1865.

Lafforgue: These de Lyon. 1893.

Stimson: Ann. of Surg., 1896. Vol. 23. P. 186.

Bierhoff: Deutsche Arch. f. klin. Med., 1880. Bd. 27.

Gilford: Lancet, July. 1893. P. 241.


A CASE OF TRANSIENT SPASTIC CONVERGENT STRABISMUS.

By Samuel Theobald, M. D., al Professor of Ophthalmology and Otology, Johns Hopkins University; Ophthalmic and Aural Surgeon to The Johns

Hopkins Hospital, Baltimore.


Spastic convergent strabismus, or strabismus from tonic spasm of the internal recti muscles, a condition to be sharply differentiated from ordinary concomitant convergent squint and from squint due to paralysis of the abducens, is one of the well-recognized ocular manifestations of hysteria; but, apart from this, it would seem, deserves to be regarded as a rare anomaly, to which, as a rule, the text-books upon diseases of the eye devote but scant attention.

De Schweinitz, in the paragraph of less than five lines

which he devotes to "spastic strabismus," f says that it " oc aly under rare circumstances in hysteria and brain dis


  • A paper read before the American Ophthalmologics] Society,

Maj ::. 1900. t Diseases of the Eye, third edition, p. 554.


ease (meningitis). It is difficult of diagnosis, periodical concomitant squint in hypermetropia being sometimes inaccurately described as dtie to spasm of the internal rectus (Maufhner)." Jackson, in a paragraph of equal brevity, says "deviations of the eyes due to spasm of the ocular muscles attend hysterical seizures and some forms of brain-disease. They may assist in the general diagnosis, but have little localizing value, and require no treatment apart from that of their cause." *

Fuchs. though he states that "tonic spasms of the ocular muscles are extremely rare," adds that "many cases of intermittent strabismus belong under this head," and he mentions two cases of this character which he had observed in


' Diseases of the Eye, p. 234.


July-August, 1900.J


JOHNS HOPKINS HOSPITAL BULLETIN.


179


hysterical women.* Eoosa says children, in whom optic neuritis is found to be present, are often brought to ophthalmic clinics with strabismus in its early stages which is non-paralytic. *' Every careful observer," he adds, " will take great pains to determine in a given case of suddenly occurring strabismus, that there is not some cerebral lesion. During dentition, certain children are apt to squint." This, he thinks," '" may fairly be ascribed to cerebral irritation." j Duane, in his chapter upon " movements of the eyeballs and their anomalies," in De Sehweinitz and ltaxtdall's American Text-Book of Diseases of the Eye, Ear, Throat and Nose (p. 511), treating of paretic and spastic squint, says " spaam, which is much less frequent than paralysis, is due to irritative lesions (meningitis, etc.), chorea, epilepsy, and hysteria; rarely is idiopathic."' Noyes, .Morris and Oliver, hick, Nettleship and Swanzy, so far as revealed by a glance through their respective treatises upon diseases of the eye, make no mention of the subject of spastic strabismus.

In Norris and Oliver's System of Diseases of the Eye, Parinaud, treating of the ocular manifestations of hysteria, considers at some length the " anomalies of convergence " occurring in this condition. If we would understand the anomalies of the movements of the eyes in hysteria, we must, he says, "' consider that neither muscles nor nerves, but nerve centers, and, indeed, the higher centers, are affected — those whereby the movements themselves are brought into unison with psychic action "*; and, he adds, " another fact connected with a study of hysterical disorders of the ocular apparatus is that they are almost always of the nature of contractures, even when they present the objective characteristics of paralysis." \ In the same volume (pp. 708 and 710), Santos-Fernandez, writing of the " ocular manifestations in influenza," mentions cases of paralysis of the third and sixth nerves and of " convergent strabismus " as having been observed in this affection, while Culver, in the chapter upon " Anomalies of the motor apparatus of the Eye," says " Changes in the centers of innervation as primary causes of strabismus are admissible only in certain definite cases," and, again, " Convergent strabismus may be due also to a spasm of convergence, independently of accommodation and refraction. We have observed cases of this kind in hysteria. It is perfectly admissible that the same phenomenon is produced in consequence of other irritations of the center of convergence." §

Briefly described, the ease which I wish to report is as follows:

A little girl, seven years of age, convalescing from a pronounced attack of influenza, a marked feature of which had been persistent and severe headache, and during the course of which an otitis media had developed in the right ear, complained of diplopia, and on the following day exhibited an evident squint. At the request of the attending physician.


  • Text-Book of Ophthalmology, p. 576.

f Diseases of the Eye, p. 553. t Vol. IV, p. T54. § Op. cit., p. 100.


Dr. W. D. Booker, 1 saw the case on the second or third day after the squint manifested itself.

There was present at this time, m butli distant and near vision, a very decided convergent squint of the left eye. There were no signs of paresis of either rectus externus — each eye could be rotated outward farther than is commonly possible, and neither the extent of the squint nor the diplopia was influenced by the direction in which the head or the eyes were turned. The pupils were of normal size and there were no signs of either paralysis or spasm ol' I he ciliary muscles. The ophthalmoscope revealed a hypermetropia of rather more than 2 D., and, as 1 had previously performed a tenotomy upon the little patient's mother for a pronounced esophoria, 1 concluded that the influenza had been the straw which had broken the camel's back, and developed a concomitant squint in a child who had, probably, inherited insufficiency of the external recti muscles and who was decidedly hypermetropic. That the trouble would be overcome without glasses or an operation seemed to me highly improbable. Dr. Booker had already prescribed iron and quinine and a nourishing diet, and the general condition of the patient was improving from day to day.

At my second visit, four days later, although the mother reported that the eyes had been straight at times during this interval (?), I found the squint unchanged except that it showed, perhaps, a greater tendency to alternate. Thinking that suppression of the accommodation might favorably influence the squint, I directed a two-grain solution of atropia to be dropped into the eyes twice a day. Two days subsequently, the eyes being thoroughly under the influence of the atropia, the squint seemed somewhat less marked. My next visit was five days after this, and, to my gratification, I then found no trace of the squint remaining. Not only so, but even with the cover test it showed no disposition to recur, and an esophoria for distance of only four degrees was shown by the Maddox rod. A decided change for the better in the general condition of the patient was also evident.

After another interval of four days, the eyes meantime having remained quite straight, the atropia was discontinued, although, I confess, I still had serious misgivings as to what would occur when the ciliary muscles began to regain thru activity. However, my apprehension proved to be groundless, for a week elapsed without any recurrence of the squint, by which time she had recovered her power of accommodation sufficiently to be able to read ordinary print. The Maddux rod now showed an esophoria for distance of only 3°, while, more noteworthy still, the vertical diplopia test showed at 12" a so-called exophoria of 4° — a practically normal muscle balance. Since then the eyes have given no further trouble.

A few days since (April 26th), nearly two months having elapsed since the disappearance of the squint, the muscle balance was tested witli the following result:

Esophoria 20'= 1° ) ^ , , , •nt L , • „„, l Rod test.

No hyperphoria 20 I

Exophoria 12" = 1° (Vertical diplopia test).


180


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 112-113.


That the squint in this case was a purely spastic one, due, doubtless, to an irritation (of influenzal origin) of the innervation center which controls the associated action of the internal recti muscles, is. in my judgment, not open to question. Had it been a concomitant squint, precipitated by the attack of influenza, as I at first supposed, it might, indeed, have disappeared under the influence of the atropia and with the improvement in the patient's general condition; hut, under such circumstances, a normal muscle balance would certainly not have been reestablished in the space of a few days, as actually happened. On the contrary, a marked, and probably persistent, esophoria would certainly have been encountered.

As to abductor paresis, I have already said there were no signs whatever pointing in this direction; but, apart from this


fact, the rapid return of the lateral muscles to a condition of practical orthophoria, is as little consistent with this view of the case as it is with the view that the squint was a concomitant one.

An incomplete search through the literature of the subject has revealed only one case which bears a close resemblance to my own. In the Archives of Pediatrics, Vol. 1, p. 634, Dr. Samuel S. Adams, of Washington, reports an interesting case of convergent strabismus as a sequela of diphtheria, in which paresis of the external recti muscles was excluded, and which he attributed to " a spasm or over-action of the internal rectus " due to an irritation of the center of ocular adduction. The squint disappeared completely within a few days of its onset.


SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.


Arthur W. Eltixg. M. D. The Acute Pneumonic Form of

Tuberculosis. — The American Journal of the Medical Sciences, May, 1900.

Simon Flexner, M. D. Actinomycosis of the Human Lung. — Proceedings of the Pathological Society of Philadelphia, April, 1900.

Lewellys F. Barker, M. D. Protocols of Microscopic Examination of Several Gasserian Ganglia. — The Journal of the American Medical Association, May 5, 1900.

Harvey Gushing, M. D. A Method of Total Extirpation of the Gasserian Ganglion for Trigeminal Neuralgia — The Journal of the American Medical Association, April 28, 1900.

William Osler, M. D. and Thomas McCrae, M. D. A Study of the Blood in Cancer of the Stomach. — New York Medical Journal, May 19, 1900.

Howard A. Kelly, M. D. The Present Status of Operations for Cancerous Uteri. — Journal of the American Medical Association, May 19, 1900.

Thomas E. Brown, M. D. Cystitis Caused by the Bacillus Pyoeyaneus. — Maryland Medical Journal, May, 1900.

H. O. Eeik, M. D. Some Interesting Cases of Mastoiditis.— Maryland Medical Journal, May, 1900.

F. P. Mall, M. D. The Architecture and Blood-Vessels of the Dog's Spleen. — Zeitschrift fur Morphologie und Anthropologie. Bd. 2. Heft I, 1900.


Percy M. Dawson, M. D. Effects of Venous Haemorrhage and Intravenous Infusion in Dogs. — American Journal of Physiology, May, 1900.

Hunter Eobb, M. D. The Eesults of Modern Aseptic Surgical Technique. — American Journal of Obstetrics, May, 1900.

Ligatures and Sutures in Abdominal Surgery. —


Cleveland Medical Gazette, June, 1900.

Stewart Paton, M. D. The Hospitals for the Insane and the Study of Mental Diseases. — Philadelphia Medical Journal, May 26, 1900.

William H. Welch, M. D. Argument against Senate Bill 34, Fifty-sixth Congress, First Session, Generally Known as the " Antivivisection Bill." — Journal of the American Medical Association, May 19, and May 26, 1900.

E. L. Eandolph, M. D. Diseases of the Iris, Ciliary Body and Choroid; Sympathetic Inflammation and Irritation. — An American Text-Book of Diseases of the Eye, Ear, Nose and Throat, Philadelphia, 1899.

A Critical Eeview of German Ophthalmic Literature

for the Quarter ending March 31st, 1900. — Annals of Ophthalmology, April, 1900.


Otology: A Digest of the Advances, Discoveries

and Improvements in this Science during 1899. — Progressive Medicine, March, 1900.


July-August, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


181


BOOKS RECEIVED.

Archives of Neurology and Psychopathology. Vol. 2. Nos. 3-4. 1S99. Svo. ;;_l-5sj pages. State Hospitals Press, Utica, N. Y.

.1 Handbook for Nurses. By J. K. Watson, M. D. Edin. American Edition under the supervision of A. A. Stevens, A. M.. M. i). 1900. l2mo. 413 pages. \V. B. Saunders, Philadel phia.

American Laryngological Association. Transactions of the Twentyfirst Annual Meeting- held in the City of Chicago, 111.. Maj 22, 2::. and 24, 1899. 8vo. 833 pages. 1900. D. Appleton and Company, New York.

Proceedings of the American Vedico-Psyclwlogical Association at the Fifty-fifth Annual Meeting held in New York, May !3-26, 1899. -vi). 4;;T pages. Published by the American Medico-Psychological Association.

Transactions of the American Pediatric Society. Eleventh Session held at Deer Park, June 27, 2S and 29, 1899. With the Constitution. Edited by Floyd M. Crandall, M. D. Volume XI. 1899. Svo. 252 pages. Reprinted from the Archives of Pediatrics.


XOTES OX NEW BOOKS.

Surgical Pathology and Therapeutics. By Johtj Collins Warrex, M. D., LL. D., Professor of Surgery in Harvard University; Surgeon to the Massachusetts General Hospital. Second edition. (Philadelphia: IT. B. Saunders, 1900.)

The writings and reputation of the author of this muchneeded book are sufficient to warrant a scientific, practical and very useful work on surgical pathology. His physiological and pathological knowledge combined with his great experience in teaching are evident throughout the book. These make it not only a valuable test-book but also a reference-book because of the thoughtful combination of physiological and pathological knowledge with a fairly extensive use of historical and biographical references. There is a great present need of this book, which will be a guide to workers and a model on which future writers may build — adding here and there a few innovations in methods, if not in materials.

The new edition differs from the first one only in the addition of a more extensive appendix which is designed to act as a clinical guide in working up surgical cases. It also contains what is not commonly found in surgical works — an article which may bring it into the hands of the dental surgeon. This is a very useful section on the bacteriology of the mouth and howto prepare for filling teeth.

bacteriology may be considered completely treated when we add to the detailed work on bacteriological technique and surgical bacteria of the main body of the book, the appended bacteriology of the skin, pleura, joints, bladder, eye, ear and nose, and a paragraph on bacteriological examinations.

Omissions made in the original are supplied in the appendix.

It was a notable oversight in the first edition not to speak of one of the most important of the surgical bacteria, the Bacillus Aerogenes Capsulatus (Welch), and the omission of the Uonococcus as a cause of peritonitis. This has been rectified in the appendix and the Pneumococcus and Typhoid bacillus are given more scope as surgical bacteria.

A valuable introduction to the article on inflammation is given in Chap. Ill on Hyperemia in which the relationship between physiology and pathology is clearly brought out.

The chapter on inflammation is a type of the work, being eminently practical and scientific. The references t" works on the subject are full but not too extensive.

It is worthy of note that after reviewing- so usefully and


thoroughly the writings of those most worthy of quotation the author ends his chapters with his own healthy view of the subjecf .

Infective inflammation is dealt with in three chapters. This differs from the simple form in that it is due to bacteria and spreads, usually ending- in suppuration. The etiology is included with some practical points on invasion of tissues. Under the same head comes Acute Osteomyelitis with a very useful, complete description of the local action of the infective process. The various causative agents and their differences in action with the change in the part acted on are noteworthy. Repair is sharply separated from inflammation, as it should l>c The nervous theory of shock gits greatest credit after a historical review of the subject.

In five chapters the author gives a clear portrayal of the fevers of surgery, the physiological basis preceding the pathological condition being first described. Traumatic* Aseptic and Urethral Fevers, Septicaemia, Pyaemia and Erysipelas come under this head. Tetanus is thoroughly treated of in a special chapter; its bacteriology and treatment by antitoxins being described in other chapters.

Tuberculosis of bone is well handled — the manifold pathological appearances and clinical pictures being given in a concise, yet complete manner. The experimental work stands forth promiently — Cheyne and Krause getting credit for much good work.

Under tuberculosis of joints Warren very properly adheres to Cheyne's view that there are two forms, one beginning in the joint, another being primary in the bone. In the treatment of abscesses the healing power of iodoform is asserted.

Chapter XXVI deals with tuberculosis of the soft parts, ineluding the peritoneum, glands and genito-urinary tract. Diseases of bone have a special chapter and include all of the diseases not dealt with under the headings Osteomyelitis, Tuberculosis, and Tumors of Bone — there are many of them. Osteopsathyrosis, Senile Atrophy and Osteoporosis are said to denote closely allied conditions of bone, the absorption of the bone being due to " lacunar absorption." Neuroparalytic Atrophy, that due to the pressure of aneurisms and to malignant growths, is included under the heading Osteoporosis. Nearly all known diseases of bone are included in this chapter.

It is remarkable how the author has managed to include all the practical points of surgical pathology in some way, leaving out no important ones. If not found in their natural places they turn up somewhere else.

There is nothing of special note in the chapter on Tumors. The classification is the simplest possible. Endothelioma is classed with Carcinoma; yet, when writing about Sarcoma, it is shown how the endothelial tumors are closely related to them. The theories of tumor-formation are discussed, especially the parasitic theory, which still remains not proven.

In describing Sarcoma and Carcinoma each organ and locality of the body is taken up in order, with its peculiar tumor growths. The use of the Mixter punch in settling the question of malignancy of a new growth might be criticised.

Besides the surgical treatment of Carcinoma the author is not sure but that something may develop from the work on the injections of cancroin — extracted from cancer cells as recommended by Adamkiewicz.

\ Eew drawings of macro- and miero-scopic aspects of tumors are given but no special merit is noted in the illustrations.

The appendix has been written to fill in what did not tit well in the main body of the book and to give the special bacteriology of various localities and organs.

It is well that it was added, if for no other reason than the addition of a useful article on peritonitis. The old edition only alludes to peritonitis of tubercular origin.


182


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 112-113.


Here too are added certain good points on pathological technique and clinical microscopy and corrections are made of oversights in the main body of the book. Subjects not usually treated of in surgical text-books are here brought forward.

In the chapter on Scientific Aids to Surgical Diagnosis, which is a rather overcrowded article, after insisting that the surgeon should know enough of laboratory methods to be able to say which of them can give him positive results in case a specimen is sent for examination, he refers to some tilings to be learned from blood-examinations; gives some points in bacteriological technique, and speaks of the necessity for animal inoculation. In this chapter a great number of bacteriological data, urinary symptoms and findings are crowded together in marked contrast to l lie clearer writing of the original edition.

To the Rontgen rays is devoted a special article describing their value in detecting fractures, foreign bodies, calculi, etc. Their advantages and disadvantages are referred to, and several illustrations are added.

Chapter 11 deals with the surgical bacteriology of the skin, and treats of wound-infection and disinfectants in a brief and practical manner. Useful points in technique, such as the preparation of ligatures, of the patient, of instruments, of the surgeon, and the treatment of the wound, not included in the original are found here. Serum therapy is also dealt with in its relation* to tuberculosis, tetanus, syphilis and streptococcus infections.

The contents of the whole volume are of the greatest value, and the matter is presented in a very interesting manner by one who is a master and teacher.

The Medical Annual and Practitioner's Index, 1900. (J. Wright & Co., Bristol, and E. B. Treat & Co., New York.)

The present number, the eighteenth of its publication, is well up to the standard of previous years. In recently noting the Synoptical Index of this work for the years 1887-1898 we commented on its valuable features. The extracts and notes of articles are usually well made, some of them giving the important points more clearly than they are given in the original articles. Special attention may be drawn to the section on Malarial Fever, bj- Major Ronald Iioss. It gives an excellent short account of the recent work on that subject. Colonel Keith Hatch contributes an interesting article on Mycetoma which is well illustrated. To those who have used the Annual its good points are well known. It may be recommended to those who do not know it as being helpful in many ways.

Pye's Surgical Handicraft. Fourth edition, revised and enlarged, by Bertram Rogers, M. D. (John Wriyht & Co., Bristol, 1900.)

It is a pleasure to see another edition of this work, eight years having elapsed since the third edition. It was first published by the late Mr. Pye, in 1884, and some words of his original preface regarding the title of the work may be quoted: " Although surgery is doubtless becoming more scientific day by day, nevertheless it will never cease to be a skilled labor nor will surgeons ever cease to be handicraftsmen." His object in the book was to describe the details of surgical work from the point of view of house surgeons and " dressers " in the surgical wards. With this purpose the work is thoroughly practical and the descriptions are plain and accurate. At the time when one is first battling with the many difficulties and emergencies that come to the young house officer, this book is a great help. There are few surgical conditions that are not described and the advice given is usually sound. Every senior student and young graduate will find this work useful. We speak with grateful remembrance of its assistance in days gone by when one dwelt


with the fear of an improperly treated emergency' ever before his eyes.

Injuries to the Eye in their Medico-Legal Aspect, by S. Baudry, M. D., Professor in the Faculty of Medicine, University of Lille, France; translated from the original by Alfred James Ostheimer, Jr., M. D., of Philadelphia, Pa.; revised and edited by Charles A. Oliveb, A. M., M. 1)., Attending Surgeon to the Wills Eye Hospital, Ophthalmic Surgeon to the Philadelphia Hospital, Member of the American and French Ophthalmological Societies, etc., With an Adaptation of the Medico-Legal Chapter to the Courts of the United States of America, by Charles Slnkler, Esq., Member of the Philadelphia Bar. (Philadelphia, New York, Chicago: The F. A. Dm is Company, Publishers, 1900, pp. X-161. Price $1.) It is not long since that we had the pleasure of perusing another of Prof. Baudry's contributions, " Simulated Blindness " in The System of Diseases of the Eye, by Norris and Oliver (Vol. IV I, and perhaps the Lille professor is best known to many of his American readers as one of the contributors to that standard work on ophthalmology.

American ophthalmologists seem to be less familiar nowadays than formerly with what is going on in the domain of French ophthalmology, a condition of affairs which is to be attributed to the fact that in this branch of medicine more than ever before inspiration is being drawn from Germany. We should not forget, however, what de Wecker, Panas, Landolt and Meyer have done and that they are still working at the very front. The object of Professor Baudry's work is to equip the ophthalmologist with a medico-legal knowledge of injuries to the eye. It is surprising that ophthalmic literature is so poor in information of this character. The author has collected his personal observations and compiled the reports and published conclusions of others upon this subject. It is a short work consisting of scarcely one hundred and fifty pages and is full of practical information. The contents will not strike one as being something which is entirely new, for the clinical facts, at least, with which every page is full, are all old stories and form part of the mental equipment of every experienced ophthalmologist. The book will be useful, however, because it contains these clinical facts condensed and so arranged as to form what may be regarded as a distinct and important chapter in ophthalmology, " Eye Injuries." It is needless to say that such a presentation of the subject leaves a clear impression.

In its application to the legal status or value of an injury to the eye it is to be hoped that the work will be found useful, though we doubt whether it can be regarded as a preeminently valuable guide to the expert in estimating accurately the damage caused by the injury to the individual. Such a work we think ought to contain more clinical records with the legal points to which they give rise, and should be illustrated by pertinent cases with their legal conclusions or decisions.

It is divided into four parts: 1. " Traumatic Lesions of the Ocular Adnexa." 2. " Traumatic Lesions of the Eyeballs." 3. " Simulated or Exaggerated Affections of the Eye." 4. " MedicoLegal Expert Testimony."

We look upon Part Third, which treats of a theme on which Baudry is a recognized authority, as the best in the book; that is, from a medico-legal point of view. Professor Jacquey, of Lille, has contributed the legal portion of the last chapter, which is to the point and is an epitome of the principles which govern opinion-evidence and will be found to contain what every practitioner of medicine should know.

In conclusion we are happy to bear witness to the readableness of Doctor Ostheimer's translation and to this further token of the industry of Doctor Oliver, the editor.

E. L. R.


Vol. XI. -No. 114.


BALTIMORE. SEPTEMBER. 1900.


[Price. 30 Cents.


CONTEISTTS.

>'AGE PAGE

Morbid Conditions Caused by Bacillus Ai ; rogenes Capsulatus. A Contribution to the Study of Malignant Tumors Arising in By William H. Welch. M. D., 185 Congenital Moles. By R. H. Whitehead, M. D 221

On the Histology of the Islands of Langerhans of the Pan- Inorganic Ferments. By Harry C. Jones, Ph. D 224

creas. By Rugene L. Opie. M, D., 205

The Sterilization of Catgut. By G. Brown Mil i i i: M. D., . 225 The Distribution of Connective Tissue in New Growths. By

W. C. White. M. B 209 Summaries or Titles of Papers by Members of the Hospital

and Medical School Staff appearing Elsewhere than in On the Relation of the Electrical Conductivity of Blood-serum t ne Bulletin 220

to its Alleged Bactericidal Power. By Emma Lootz and Alice Weld Tallant 220 Books Received 229


MORBID CONDITIONS CAUSED BY BACILLUS AERiHiKNKS CAI'SULATTS.


THE SHATTUCK LECTURE.


By William II. Welch, M. D.. Professor of Pathology, Johns Hopkins Univer ity.


CONTENTS.


Introduction. — Historical. — Nomenclature. — Characters of Bacillus. — Distribution. — Gas-Bubbles in the Blood and Organs. — Emphysematous Gangrene. — Gaseous Abscesses. — Uterine Infections: Emphysema of the foetus; puerperal endometritis; physometra; emphysema of the uterine wall; puerperal gas-sepsis. — Infections of the Urinary Tract. — Infections derived from the Gastro-intestinal Canal: Local gastro-intestinal lesions; pneumo-peritonitis with and without perforation; hepatic and biliary infections. — Interstitial Emphysema of the Castro-intestinal. Genitourinary, and Biliary Tracts. — Pulmonary and Pleural Infections. — Bacillus Aerogenes Capsulatus in the Blood during Life. — Presence of Bacillus Aerogenes Capsulatus without Gas. — Meningitis and Pyogenic Capacity of Bacillus Aerogenes Capsulatus. — Cavities in the Brain.

Although the subject which I have chosen for this lecture relates for the most pari to infrequent affections, the scientific and practical interest attaching to them is consideral raried. Many instances of the presence of free gas in parts


Delivered before the Massachusetts Medical Society. June 12, 1900.


of the body where n does Dot normally occur and in a tion with various diseases were recorded by writers of past < 'in uries a ad were even then the subject of much speculation. The discussion turned generally around the question whether the gas was atmospheric air or the result of putrefaction — a question which in most eases could be solved only by bacteriological examinations. The most numerous and important of such examination; have been made during the last decade and. although these have left problems still unsolved, they

have corrected many current errors and have shed a tl 1 of

light upon conditions which were Eormerly among the most mysterious in pathology.

While it has been demonstrated that various bacteria may

be terned in producing gas is affections, it is now evidenl

thai the bacillus which I discovered in 1891, and to which I gave the name Bai illn a psulat us. is the one whose

causative agencj is best established and mosl Frequent!} in action. What I shall say will relate mainly to this microorganism and it- pal biogenic effects.

Historical. - As a certain amount < m oin


186


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 114.


the dates of the first publications' on this bacillus exists in foreign literature on this Bubject, it may be well to state thai I reported my observations in November, 1891, to the Johns Hopkins Hospital Medical Society and that the full report of these observations and of the characters of the bacillus was published in July-August, 1892, by Dr. Nuttall and myself. 3 E. Fraenkel's first publication ' was a short preliminary one which appeared in January. 1893, and was followed in the same year by his valuable monograph on gaseous phlegmons." In August, 1893, one year after the publication of the paper by Nuttall and myself, appeared simultaneously the interesting article- of P. Ernst ' and of Graham, Steward and Baldwin' on foamy organs. Early in 1894 Mann published from my laboratory an observation of emphysematous gangrene caused by Bacillus aerogenes capsulatus, 8 and in January, 1896, Dr. Flexner and i published an extensive paper reporting twenty-three human eases, including not only six personal observations of emphysematous gangrene but also examples of submucous gas-cysts, pneumoserositis, and various other pathogenic manifestations of this bacillus.' In July, 1895, appeared GoebeFs preliminary communication," and in the following year his full paper on the bacillus of foamy organs." Of the subsequent records the most numerous and valuable have appeared in this country, although they appear to be little known to most European writers.'" I shall have occasion


- Levy's description in 1891 (Deutsche Ztschr. f. Chirurg., XXXII) of " kleine, feine " bacilli, cultivated from a gaseous abscess and growing in long threads and chains only at body temperature and cultivable only in the first generation, without animal experiments, cannot be accepted as an identification of B. aerog. capsulatus, or indeed be readily reconciled with its characters.

  • Bulletin of the Johns Hopkins Hospital, 1892, III, p. 81.

' Centralbl. f. Bakter., XIII, p. 13.

s Ueber Gasphlegmonen. Hamburg u. Leipzig, 1893.

" Virchow's Archiv, CXXXIII, p. 308.

T Columbus Med. Journ., XII, p. 55.

8 Annals of Surgery, XIX, p. 187.

" Journal of Experimental Medicine, 1896, I, p. 5.

10 Centralbl. f. allg. Path. u. path. Anat., VI, p. 465.

11 Jahrb. d. Hamburgischen Staatskrankenanstalten, IV.

12 Thus v. Hibler in 1899 (Centralbl. f. Bakt., XXV, p. 513 et seq.), in an elaborate study of pathogenic anaerobes, is entirely ignorant of our work and that of other American investigators on B. aerog. capsulatus. The information of Hitschmann and Lindenthal (Sitzungsb. d. k. Akad. d. Wiss., Math.-Naturw. CI., Wien, 1899, CVIII, Heft 3, Abth. Ill, p. 67) on the American work is secondhand and both incomplete and inaccurate, in these respects being in unfavorable contrast to that of Muscatello, assisted by Gangitano (Riforma Med., 1900, II, p. 508 et seq.), who write also on the subject of emphysematous gangrene. Knowledge of Bacillus aerogenes capsulatus, under the name " Bacillus perfringens " (Veillon and Zuber), has begun to appear in Prance in the last two years, but without evidence of acquaintance with the American publications. Even allowing for the great difficulties in keeping pace with the literature of any subject in medicine, a decade would certainly seem sufficient for the light to penetrate even into dark places.


to refer later to many of these publications, among which those of Dunham, Dobbin, Norris, Bloodgood. Howard, Xicholls, and Pratt and Fulton, may here be mentioned as especially valuable.

Nomenclature. — Dr. Fraenkel has kindly favored me with cultures of the bacillus which he isolated from gaseous phlegmons and to which he gave the name " Bacillus phlegmones emphysematosa 5 ." There can be no question whatever but that his bacillus is identical with our Bacillus aerogenes capsulatus, a point upon which we are both agreed, and which is also made certain by Goebel's studies under Fraenkel's supervision. According to the generally accepted principles of the nomenclature of zoological and botanical species, the name '• Bacillus aerogenes capsulatus," as being the first one applied, should be preferred to that of Bacillus phlegmones emphysematosa 3 . It is, moreover, as pointed out by Muscatello, not open to the objection of implying exclusive relationship to a single disease, as is the case with Fraenkel's designation of the bacillus. As a matter of fact, as we shall see, the capacity to produce gaseous phlegmons is only one of many pathogenic manifestations of Bacillus aerogenes capsulatus. Unfortunately I think that we both erred against the canons of botanical nomenclature in using a trinomial rather than a binomial name for a species. 13

( 'ha meters of Bacillus. — Since our first publication only one material addition has been made to the extended description given by Welch and Nuttall of the morphological and cultural characters of Bacillus aerogenes capsulatus or the gas-bacillus as I shall briefly call it." Fraenkel noted the presence of spores in a few of the bacilli growing in one lot of agar containing sodium formate, and in 189? Dunham '" observed spores, with all of the specimens studied, in blood-serum cultures, but not in other media.

Our further studies of the gas-bacillus obtained from different sources have shown a moderate range of variation iu some of its properties. This is true especially of spore-formation, rapidity of liquefaction of gelatine, presence of capsules and virulence.


13 Migula, who, with considerable success, has attempted to reform bacteriological nomenclature, has given the binomial names " Bacterium Welchii " to Bacillus aerogenes capsulatus and " Bacterium emphysematosum " to Bacillus phlegmones emphysematosa? (System der Bakterien, II, pp. 392 and 383, Jena, 1900). He is, however, in error in describing this organism under two different names, as his Bacterium Welchii and Bacterium emphysematosum are identical.

14 As regards these characters it will suffice here to say that the microorganism is a rather coarse, non-motile, anaerobic bacillus; stains by Gram; grows on all of the ordinary culture-media under anaerobic conditions, best at body temperature, but also at room temperature; liquefies gelatine slowly; forms spores constantly according to the race and the culture-medium, and is capable of generating gas not only by fermentation of sugars but also from proteids. The full description of the characters may be found in Welch and Nuttall's paper.

15 Bulletin of the Johns Hopkins Hospital. 1897. VIII. p. 68.


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While some specimens of the bacillus seem never to form spores on any culture-medium, others, and these appeaT to be

the more common, do so occasionally, especially upon bloodserum, in mannite bouillon, and on plain agar. In animals

inoculated with pure cultures we have not observed sporebearing bacilli.

As a rule the bacillus liquefies gelatine slowly bul so

specimens do so scarcely at all. and others with fair rapidity. In our first communication we noted peptonization and softening of the gelatine, but this was so slow and slight with the particular specimen studied that we then preferred to class the bacillus among the non-liquefiers. further experience has shown that the bacillus is a liquefier, but generally a slowone.

As stated in our original article, capsules are not constantly present, but I have generally found no difficulty in demon strafing them in the situations and by the method described by us. and, with the exception of Hitschmann and Lindenthal, most other investigators have been able to demonstrate capsules, when these are searched for by suitable methods.

While the bacillus is to be ranked among those which stain by Oram, it is sometimes rather noticeable in coverslips from cultures that among w 7 ell stained bacilli, others are partly or wholly decolorized, and this may be observed in members of a single chain. In the tissues the bacilli stain well by Gram. Differences in the viability of cultures were pointed out in our first paper.

It sometimes happens that original cultures from human beings show only a feeble growth, with relatively weak power of gas-production, while subsequent cultures, especially those obtained after passage through the animal body, present the usual vigorous growth and other typical characters. Pratt and Fulton. 1 " from a typical case of foamy organs with gas throughout the body, wen' unable to cultivate the bacillus at all. although twelve anaerobic culture tubes containing various media were inoculated from different parts of the body. This negative result they attribute to the fad that the body had lain in a cold storage vault for sixteen hours after death, an explanation which has some support in an observation previously reported by Welch and Flexner, but -till seems hardly satisfactory, as under like conditions the bacillus has been often cultivated.

Lactose, glucose and saccharose are all fermented by the f$as-bacilliiB, the first with the largest production of gas and the last with the smallest. The gas. according I" Dunham's analyses, is composed approximately of C,\ per cent hydrogen. 88 per cent carbon dioxide, and 8 per cent of a residual gas believed to lie mainly nitrogen. It has no foul odor. The amount of hydrogen always greatly predominates over thai of carbon dioxide. There is apparently no fermentation of mannite, at least the gas is not appreciably more than in sugar-free media.

E. Fraenkel in 1893 was the first to demonstrate the etiological relation of thfi gas-bacillus to gaseous phlegmons, our


1 Boston Med. and Surg. Journ.. June 7, ltton. p. Finn.


previous investigations being concerned mainly with the socalled foamy organs (Schaumorgane) and the presence of gas in (he blood, our results being confirmed a year later by 1'. Ernst. Soon after Fraenkel's publication we were able to confirm his discovery of the causation of gaseous phlegmons by Bacillus aerogenes capsulatus, and to repeat with like results his animal experiments.

Material or cultures fresh from the infected body are usually highly virulent Eor guinea-pigs, pigeons and sparrows (E. Fraenkel). which succumb to arpidly spreading local necrosis of the tissues with abundant development of gas. the bacilli invading the blood during life only in small numbers or not at all. There is more or less bloody oedema, bul otherwise little inflammatory reaction, leukocytes being present usually only in small numbers in the exudate. Rabbits and mice, while not wholly immune, are far less susceptible than guinea-pigs and pigeons. Dr. Lanier in my laboratory in 1896 succeeded in producing typical gaseous phlegmons around the fractured bones of rabbits inoculated intravenously with pure cultures, and Muscatello has obtained the same results. There are considerable differences in the degree of virulence of the bacillus even in fresh cultures, and old ones may be of very slight virulence.

One of the most interesting and valuable tests of the gasbacillus is its power of producing gas abundantly in the blood, organs and tissues of rabbits killed a few minutes after intravenous injection, a power not possessed by colon bacilli. The differential value of this (est is as great as that of cultures in fermentation lubes. The blood and tissues of the dead rabbit make the culture-medium, the body of the animal takes the place of the test tube, the inoculation is an aseptic one, the bacteria are spread by the blood-current and the conditions are anaerobic. This procedure, which was introduced by Nuttall and myself and has been fully described by us. we have found useful under proper precautions in isolating the gas-bacillus, in separating it from other bacteria which may resemble it, and in the demonstration of one of its most fundamental characteristics, namely, the power to produce gas from proteid material.

Among the points distinguishing the bacillus of malignant oedema from Bacillus aerogenes capsulatus may be mentioned the following: The malignant oedema bacillus is somewhat thinner: has greater tendency to grow into filaments; is less readily stained by Gram; produces spores regularly in culturemedia; is motile: liquefies gelatine much more rapidly; produces a foul odor; generates less gas in lactose bouillon: clots and then peptonizes casein; generates little or no gas in rabbits inoculated intravenously and then killed; and by subcutaneous inoculation in susceptible animals causes spreading bloody oedema with little or no development of gas-bubbles, and appears after death in filaments on serous surfaces.

The bacillus to which Lindenthal" has quite unnecessarily given the name Bacillui emph^ emati vaginae is doubtless identical with Bacillus ae ni capsulatu The same is

"Wiener klin. Wochensch., 1897, p. ::. el aeq


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true of Veillon and ZuberV 8 Bacillus perfringens found by them in appendicitis, by Guillemot 1 ' in gaseous gangrene and by Soupauli and Guillemot" in gaseous abscesses, and of IUidavV Bacillus cadaveris butyricus, and Cesaris-Demel's "" bacillus, both found in foamy organs. I am strongly inclined to the opinion that the anaerobic bacillus isolated by Achalme and others from the blood and tissues of several cases of acute articular rheumatism and found by Savtchenko and Mielkich in the soil is likewise identical with our gas-bacillus. 2 " As will be considered later, Gwyn lias cultivated Bacillus aerogenes capsulatus also from the blood of a choreic patient during life.

Distribution. — The surmise expressed by Welch and Nnttall that the gas-bacillus is widely distributed in nature has since been confirmed. The natural habitat of the organism is the intestinal canal ami the soil, the homes of so many other anaerobic bacteria. Welch and Flexner in 1896 brought evidence of the presence of the bacillus in both of the situations mentioned. Clopton of the Johns Hopkins Hospital has found the bacillus twice in the normal appendix vermiformis. Howard 13 has recently reported the presence of morphologically identical bacilli in the intestines of twenty-five consecutive human cases examined post mortem, and in ten of these lie demonstrated the bacillus by cultures and inoculation of animals. The same conclusion concerning the regular presence of the bacillus in the intestine has been reached by Hitschmann and Lindenthal. The gas-bacillus has been repeatedly cultivated from the intestine in my laboratory, but we have made no systematic study of the frequency of its presence. 2 ' 11 I have found the bacillus also in the intestines of rabbits, dogs and swine, and here it is interesting to note the frequency with which submucous gaseous blebs arc found in the pig's intestine at autopsy.

. In 1896 Dr. Walker, at the Johns Hopkins Hospital, succeeded in finding Bacillus aerogenes capsulatus in dust collected by sweeping floors, proving its presence both by cultures and animal experiments. My assistant, Dr. Harris, has cultivated the bacillus from the contents of an old cesspool. I had


"Arch, de med. exp., 1898, X, p. 539.

,9 Compt. rend. Soc. de biol., 1898, 10. s., V, p. 1017.

" Bull, et mem. Soc. med. d. hop. de Paris, 1900, 3. S., XVII, p. 216.

-' Centralbl. f. Bakt., 1898, XXIV, p. 369.

21 a Giornale d. R. Accad. di med. di Torino, 1898, LXI, p. 256 and LXII, p. 190.

- Achalme, Ann. de l'Inst. Pasteur, 1897, XI, p. 845; Pic and Lesieur, Journ. de phys. et de path, gen., 1899, I, p. 1007, and Savtchenko and Mielkich. Arch, russes de path., 1899, VIII, p. 145.

23 Contributions to the Science of Medicine dedicated by his pupils to William Henry Welch on the 25th Anniversary of his Doctorate, p. 461, Baltimore, 1900.

■'"■ Mr. Hirshberg is now engaged in my laboratory in a study of the distribution of the gas-bacillus in human and animal intestines and in the outer world and will report his observations later.


previously reported in 1896 the isolation of the bacillus from a bullet removed from the head of the tibia in a case of gaseous phlegmon, and E. Fraenkel M has cultivated the gas-bacillus from a splinter of wood extracted from a wound in a case of tetanus. These observations confirm the natural inference to be drawn from the study of cases of traumatic emphysematous gangrene, in most of which the source of infection is manifestly foreign material, especially dirt, in wounds. In the light of these demonstrations of the wide distribution of the gas-bacillus in the outer world and in faeces, the conclusion is warranted that it must occasionally be present upon the human skin.

We are not informed whether there are differences in the regional distribution of the gas-bacillus. The fact that during the last decade a larger number of cases of emphysematous gangrene have been reported from Baltimore than from any other single locality is due probably to our interest in the subject and consequent search for cases. The bacillus has been found not only in America and Europe, but Dr. Flexner has brought reports of three infections with the gas-bacillus in Manila observed during a stay of three months.

<i \S-BUBBLES IN THE BLOOD AND OkGAXS.

We turn now to the consideration of the various conditions in which Bacillus aerogenes capsulatus has been found in human beings. We need not pause to consider the occasional presence of this bacillus in ordinary cadaveric decomposition, a circumstance sufficiently explicable by the occurrence of this organism in the healthy intestinal canal.

Of an entirely different nature are the cases in which gasbubbles are found in the blood and organs within a few hours after death and without any trace of ordinary putrefaction. Such a condition has been recognized at autopsies as soon as one, two, three, five, eight hours after death. It may occur not only after death from gaseous phlegmon, when, however, it is by no means constant, but also after death from the most varied causes. It has been observed repeatedly in autopsies on pregnant and puerperal women, especially after death from abortion and acute sepsis. Cases reported by Cless. 25 Jurgensen.™ Vachetta, 2 ' Dunin, 28 Vogel " and others as examples of entrance of air or gas into the circulation from gastric ulcers, typhoid or dysenteric ulcers, pulmonary tuberculosis, in septicaemia and various other diseases, find now their natural explanation in the invasion of gas-bacilli, instead of in the curious hypotheses propounded by the authors cited. In all probability, although I have had no opportunity to observe such a case, the free gas which has been repeatedly found in


-' Miinch. med. Woch., 1899, Nos. 42 and 43.

- 5 Luft im Blute, Stuttgart, 1854.

= a Deutsches Arch. f. klin. Med., 1882, XXXI, p. 441, and 1887, XLI, p. 569.

" Siill' embolismo gazoso per penetrazione d'aria nel sistema circolatorio, Pisa, 1880.

"Berliner klin. Woch., 1882, p. 11.

29 Ibid., 1882, p. 187.


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the blood-vessels and heart after deaths from chloroform is due likewise to the invasion of the gas-bacillus, and is not, as supposed by Hankel, 30 nitrogen derived from air pressed through the lungs into the pulmonary blood-vessels in violenl expiratory movements with closed glottis.

There is every gradation from cases with a few bubbles of gas in the blood or tissues to those with extensive emphysema of the organs and tissues. The term "foamy organs" ( Schaumorgane of the Germans) may he applied to the latter condition. The liver is the organ most frequently the seat of early and abundant development of gas. hut there is no definite rule as to the distribution and amount of gas in different i ases. The gas may he limited to the abdominal veins or to the pulmonary vessels or to one of the cardiac cavities, or he found only in the tissues at one place, especially near the stomach or intestine. It is more abund.int in the veins than the arteries, and may he only in the former. As will he explained later the invasion in the majority of cases is from the intestine. That the gas-bubbles may lie dislocated from their original position in liquid and soft material in the body is self-evident. but I have not found them unassociated with gas-bacilli

Formerly this early presence of free gas in the heart and vessels, without evident post-mortem decomposition, was very generally explained by the assumption of entrance of air into the circulation, even when no portal of entry could he found/' The most extensive application of this explanation was made in the pregnant and puerperal cases. It is remarkable that the first case of this nature to be examined bacteriologically was that reported by me in 1891. In this and in nearly all subsequent similar cases with satisfactory bacteriological examination Bacillus aerogenes capsulatus was found.

The main questions which arise concerning the interpretation of these cases are whether the invasion of the bacilli and whether the development of the gas are ante-mortem or postmortem phenomena.

Babbits survive the introduction of large numbers of gasbacilli directly into the circulation, unless there exists nun

wherein the body necrotic or damaged tis-ue offering littl

no vital resistance. If the animal he killed within a few minutes after the intravenous injection of the bacilli and kept in a warm place, there are abundant multiplication of the bacilli and large development of gas throughout the body within the space of six or eight hours] whereas if the bacilli be introduced at one point, as for example thi h^rt. of a rabbit just killed, it take- a much longer time. often twenty-four to forty-eight hour-, for gas and bacilli to make their appearance at points far distant from the -e.it oi inoculation. It seems justifiable to draw from these three groups of experiments, which have been fully reported by 'Veleh and Nuttall, the conclusion that when bacilli and gas are found within a few hours after death widely distributed


" Cless. Luft im Blute. Stuttgart. 1854, and Couty. Paris, 1875.


in the body, the gas-bacilli have entered the circulation during life, hut probably in most ease- only shortly before death.

There is one factor, however, to lie considered which is absent in the experimental cases and may he present in human beings, to wit. the quick disappearance of the bactericidal power of the blood. This factor is an important determinant of the rapidity of onset of post-mortem decomposition. Very soon after deatli from certain diseases, and particularly from snake-venom, bacteria may make their appearance in the blood and organs. An explanation of these cases is furnished by the experiments of Ewing and myself;'" which demonstrated that the blood of rabbits killed by rattlesnake venom is practically devoid of bactericidal power, so that immediately after or even shortly before death bacteria can start growing in the body as they would in a tube of beefbroth. But after all due allowance has been made for the possible reduction or loss oJ bactericidal power of the blood. I still consider that it i- not possible to explain some of the cases in which bacilli and gas have been found in the heart. I ilood- vessels anil organs ven -non after death, especially when the corpse has been kept in a cold place, otherwise than upon the assumption of the distribution of the bacilli by the circulating blood.

It is another question whether gas as well as bacilli may he present in the circulating blood and internal organs during life in the class of cases now under considerat ion. and 1 regret to be unable to furnish a positive answer to this question. I do not see how an affirmative answer can he obtained other wise than by the actual demonstration of gas in these situs tions either during life or immediately after death, Gasbubhles and bacilli have been found in the heart and vessels

within an hour after death, hut that is ti enough I'm- bacilli

which have already been introduced to multiply and begin to form gas. I at first thought that absence of nuclear slainin<. r around the gas-bubbles and masses of bacilli might serve as an indication of their presence during life, and this view- is advocated by P. Ernst, hut 1 have since learned from experi ments on rabbits that thi- is not a decisive criterion, although often both in rabbits and in human beings then i- no defect in nuclear staining around bacilli and gas-bubbles.

I know of no other pathogenic microorganism which offers such difficulties in determining whether it- effects in the interior of the body have been produced before or after death The difficulty arises from the circumstances that the e effei I m mo-t cases and most situations consist almost entirely in local necrosis and formation of ga . whether the invasion and jn, will of the bacilli I"' before or aftei death, and that unlike ,,,1-t pathogenic bacteria the gas bacillus grows better in tic dead than the living body. Possibly some importance in thi solution of the problem may attach to the demonstration of emboli of liver cells and of hone-marrow cells which were in enormous numbers in the pulmonary vessels in a c'asi aseous phlegmon of the sub-mammary tissues following infusion of -alt-olntjon. Al the autopsy made by Dr. Carroll


B Lancet, 1894, I. p. 1236.


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the liver and other organs were emphysematous. Further observations with reference to these emboli in this class oi eases are needed.

I do not consider that there is any inherent improbability in the supposition that gas-bubbles may be in the circulating blood during life without causing speedy death from gaseous embolism. It is only when a large volume of air is introduced quickly into the blood-current that sudden death results from air-embolism. Very exaggerated ideas have prevailed among physicians as to the dangers from the entrance into the circulation of small quantities of air. Laborde and Muron" injected into the external jugular vein of a dog 1120 ec. of air in the space of one hour and a half without causing death, and Jurgensen, 3 ' into the left femoral artery of a narcotized .log weighing foi kilo, 3050 cc. in the space of two hours ami twenty-five minutes with only slight disturbance of the respiration and of the action of the heart. Hare, 35 on the basis of experiments, likewise controverts current beliefs concerning the dangers from entrance of a moderate quantity of air into the veins.

I have come across in the older literature from tin' days when venesection was a common practice, reports of cases in which blood containing bubbles of gas escaped during venesection from veins of the arm. 38 In none of these was there evidence that air had gained entrance to the circulation. Maisonneuvo. 37 in incising two gaseous phlegmons of the thigh following compound fracture, observed the escape of blood containing gas-bubbles from the cut veins and was able to trace the gas within the veins for a long distance.

It seems to me very improbable that an anaerobic bacillus, such as the gas-bacillus, can multiply in the circulating blood, still this bacillus is less sensitive to the presence of oxygen than many anaerobes, and we do not know whether the loose combination in which oxygen is present in the blood would necessarily prevent its growth under all circumstances.

I see no reason why this bacillus might not multiply and form gas in the liver, spleen and most other internal organs, as we know it can do in parts open to inspection during life. We have positive evidence in the cases reported by Graham. Steward and Baldwin and by Dunham that gas-bacilli may In 1 conveyed by the circulation from an infected portal of entry — in the one case the puerperal uterus and in the other a urethral wound — to distant parts of the body and there produce subcutaneous emphysema and necrosis. There is no part of the body which offers such favorable conditions for the postmortem growth of the bacillus as the liver, probalily on account of its content of carbohydrate, and. if the liver like


" Comptes rend. Soc. de la biol., 1873. V.

M Deutsches Arch. f. kl. Med.. 1882, XXXI, p. 458.

M Therap. Gazette. 1889, 3. S., V, p. 606.

M Marshall's case reported by May, Trans. Path. Soc, London, 1858, IX, p. 157; Durand-Fardel's case also cited by May. and Pirogoff's case in his Grundziige d. allgem. Kriegschirurgie, p. 1063, Leipzig, 1864.

,T Cited from Hitschmann and Lindenthal. Sltungsb. d. k. Akad. d. Wiss., Math.-Naturw, CI., Wien, 1899. CVIII, iii. 3. p. 67.


the integuments were open to inspection during life, I believe that we should find evidence that in certain cases the emphysema of this organ, which is such a conspicuous post-mortem phenomenon in instances of invasion by the gas-bacillus, had begun during the life of the patient. As will be considered subsequently emphysema of mucous membranes open to inspection, we know can exist during life.

In the great majority of the instances, however, in which gas-bubbles are found in the blood and internal organs at autopsy the evidence is in support of the view that the development of the gas is a purely post-mortem phenomenon. Certainly the greatest caution should be exercised in the interpretation of any such cases as vital processes, even in early autopsies without ordinary putrefaction. One thing which our investigations have established is that the finding of gas-bubbles in the blood-vessels and heart within so short a time as one hour after death furnishes in itself no proof of the entrance of air into the circulation. Especially is it to be emphasized that the limitation of gas to the right heart and adjacent vessels may occur in cases of invasion by the gasbacillus and is not, as is often represented, peculiar to airembolism. I shall refer later to the question of gaseous embolism in cases of emphysematous gangrene and of physometra.

Emphysematous Gangkexe.

In a few instances we have found in wounds, usually compound fractures or gunshot injuries, in which dirt had gotten in. Bacillus aerogenes capsulatus without the presence of gas or other evidence that the bacillus was producing any characteristic effects. 38 Such cases have always been watched by the surgeons with anxiety, and it is probable that at least in some the early recognition of the bacillus followed by free incisions and thorough cleansing and disinfection has warded off a subsequent grave infection. In view of the wide distribution of the gas-bacillus in the outer world and in the intestinal contents it is probable that it must not so very infrequently gain access to wounds without securing a foothold. While this innocent behavior, with which we are also familiar in the case of the tetanus bacillus, may sometimes be due to attenuated virulence of the bacillus, it is probably oftener attributable to accessory circumstances, such as the resistance of the patient, the condition of the wound and surrounding tissues, and lack of association with suitable microorganisms and foreign substances.

Tt is as a cause of that most dreaded of wound complications, emphysematous gangrene, that Bacillus aerogenes capsulatus especially claims the interest of surgeons. The classical clinical descriptions of this disease we owe to MaisonJ neuve™ and to rirogoff," the former giving to it the name

38 Such cases have been reported by Bloodgood from the Johns Hopkins Hospital in Progressive Medicine, 1899, IV, December, p. 158.

»"Gaz. med. de Paris. 1853, p. 592.

40 Grundziige d. allgem. Kriegschirurgie. pp. 867 and 1006. Leipzig. 1864.


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■'•' gangrene foudroyante," and the latter designating it "primary mephitic gangrene" or "acute gangrenous oedema.' 3 Among other more or less common designations are "emphysematous or gaseous gangrene," " gaseous phlegmon," " septic emphysema," "erysipele bronze" (Velpeau), "progressive gangrenous oedema," " gangrenous septicaemia," ami " emphysematous cellulitis."

This wound complication was more common in preantiseptic times, especially in military surgery, than it is to-day, but at - have been reported during the last quarter of a century. In prebacterial days the affection was attributed by some writers to the penet ration of air into the tissues, but by most to the decomposition of the tissues, particularly of adipose tissue and bone-marrow, brought by an injury into contact with the atmosphere.

Bottim" in 1871 was the first to demonstrate the infective nature and transmissibility of emphysematous gangrene.

Later Gussenbauer" also recognized the disease as a definite infection and attributed it to the bacteria of putrefaction. After Pasteur's discovery in 1ST? of his "vibrion septique," more commonly, since Koch and Gatfky's investigations, designated Bacillus oedematis maligni, and especially after Chauveau and Arloing's* 3 paper in 1884, cases of emphysematous gangrene have been usually reported, especially in France, as instances of Pasteur's gangrenous septicaemia or Koch's malignant oedema. YV. Koch's" attempt to identify the disease with symptomatic- anthrax (Eauschbrand) was based on faulty bacteriological studies and has met with no confirmation. In 188-1 F. J. Rosenbach * reported finding in coverslip specimens from two cases of traumatic emphysematous gangrene coarse bacilli, some of which had terminal spores. These he was unable to cultivate, only aerobic methods being employed. It is probable that Rosenbach saw Bacillus aerogenes capsulatus in these cases, but without distinguishing it from associated spore-bearing bacilli.

A critical examination of the records of alleged malignant oedema in human beings shows that in very few was the organism concerned satisfactorily identified as the genuine malignant cedema bacillus. Very often it has been simply assumed without more than a microscopical examination that bacilli found in spreading cedematous conditions with or without gas have been those of malignant oedema, and even where cultures and animal experiments have been employed the descriptions are frequently so meagre as to leave the identity of the organism wholly in doubt. In France it is usually assumed without any discussion and even without any bacteriological examination that gangrene foudroyante is malignant cedema (Pasteur's septicaemia),*" and the same ignorance

" Gior. d. r. Accad. di med. di Torino, 1871, 3. S., X, pp. 1121 and 1138.

" Deutsche Chirurgie, Lief. 4, Stuttgart, 1882.

" Bull. Acad, de Med., 1884, 2. S., XIII, p. 604.

" Deutsche Chirurgie, Lief. 9, Stuttgart, 1886.

" Die Mikroorganismen bei den Wund-Infections-Krankheiten des Menschen, Wiesbaden, 1884.

'An exception is Guillemot (Compt. rend. Soc. de biol., 1898,


of the present status of this subject is still sometimes encountered in England, Germany ami elsewhere. Nevertheless the investigations of the last seven years, beginning with those of E. Fraenkel ami soon followed by observations of myself and collaborators, have demonstrated that by far the most common ami important specific cause of gaseous phlegmons or emphysematous gangrene is Bacillus aerogenes capsulatus.

Whether the bacillus of malignant cedema can produce an identical or similar anatomical and clinical affection in human beings 1 regard as an unsettled question. It is certainly remarkable in view of current doctrines in text-books that neither E. Fraenkel nor I, with our relatively large experience, nor indeed, so far as I am aware, any one who has made himself thoroughly acquainted with Bacillus aerogenes capsulatus, has encountered an instance of emphysematous gangrene in man caused by the bacillus malignant cedema. The whole subject of human malignant oedema is one which needs thorough revision and investigation by more exact bacteriological methods than have yet been applied to it.* ; I have already mentioned the chief points of difference between the bacillus of malignant oedema and Bacillus aerogenes capsulatus.

There is a relatively small group of cases of gaseous phlegmon attributed by those reporting them ** either to the colon bacillus or the proteus bacillus. In most of these cases anaerobic culture methods were not employed. No one has succeeded in producing experimentally gaseous phlegmon with either of these bacilli, and 1 think there is good reason to be skeptical concerning their capacity to produce this disease, unless perhaps Bacillus coli may do so in diabetics.

It is possible that some of those reporting the colon bacillus as the cause of emphysematous gangrene may have eonfounded with it a facultative anaerobic bacillus which we have isolated from two cases of this disease, and which has been studied in my laboratory by Dr. Lanier. It resembles in anaerobic cultures very closely Bacillus aerogenes capsulatus. but it is capable of aerobic growth also, and then the rods are thinner and more like colon bacilli. It has the power of producing gas abundantly in the blood and tissues of rabbits killed a few minutes after intravenous injection, a power not possessed by genuine colon bacilli. I have already spoken of


10. S., V, p. 1017) who has found B. aerog. caps. (B. perfringens) in a case of gaseous gangrene and who controverts the prevalent view of French authors who attribute this disease exclusively to Pasteur's vibrio.

' r In the case reported recently by Brabec (Wiener klin. Rundschau, 1900, XIV, pp. 145 and 167) the identification of the malignant redema bacillus seems satisfactory. Here there was extensive bloody cedema without gas, so that the case was not one of emphysematous gangrene. On the other hand, Hiimig and Silberschmidt (Correspondenzbl. f. Schweizer Aerzte, 1900, XXX, p. 361) bring no proof of any consequence that they were dealing, as they supposed, with the malignant cedema bacillus in two cases of gangrene foudroyante.

"Chiari, v. Dungern, Bunge, Klemm. Hlava, Evans, Grasberger, Hauser, Margarucci, Muscatello, Hitschmann and Lindenthal.


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the importance of this test, which has been employed by none of the writers who have claimed to find colon bacilli as the cause of gaseous phlegmons. This bacillus, when virulent, is capable of causing the same spreading and fatal emphysematous necrosis in guinea-pigs and pigeons as is Bacillus aeroi apsulatus.

I have been accustomed to speak of this bacillus, to which 1 have called attention in previous publications, as the aerobic variety of our gas-bacillus. I believe, however, that it is identical with Sanfelice's Bacillus pseudo-cedematis maligni," with which he is inclined to identify Klein's ""new bacillus of malignant oedema." 80 Chavigny™ has isolated apparently the same bacillus, which he likewise identifies with Sanfelice's Bacillus pseudo-cedematis maligni (not to be confounded with eudo-oedema bacillus of Liborius), from a case of gaseous gangrene, and he also calls attention to the probability that others may have mistaken it for the colon bacillus. While, therefore, unwilling upon existing evidence to accept the colon bacillus as a demonstrated cause of gaseous gangrene (except perhaps in diabetics), 1 am of the opinion that an aerobic bacillus, probably identical with Sanfelice's Bacillus pseudo-cedematis maligni, is capable of producing this affection, but it is much less frequently concerned than Bacillus aerogenes capsulatus.

I have collected 4G caes of emphysematous gangrene, in all of which Bacillus aerogenes capsulatus was demonstrated, and, therefore, all reported or observed during the last seven years. 55 This is a far larger number of cases than has ever been brought together before.


"Ann. d. Istit. d'Igiene sper. d. Univ. di Roma, 1891, N. S., I, p. 365, and Ztschr. f. Hyg., 1S93, XIV, p. 352.

M Centralbl. f. Bakter., 1891, X, p. 180.

SI Ann. de 1'Inst. Pasteur, 1897, XI, p. 860. Perhaps the bacillus found by Foi and Bonorue (Ztschr. f. Hyg., 1889, V, p. 403) in a case of anthrax-like septicaemia with gas in the tissues was Sanfelice's bacillus. Roneali in the Italian translation of Senn's Surgical Bacteriology (Bacteriologia Chirurgica, p. 109) also claims Sanfelice's bacillus as a cause of gaseous gangrene.

'•- This list includes 16 cases observed in Baltimore, mostly at the Johns Hopkins Hospital, of which 2 are unpublished, and the remaining 14 have been published by Mann (1), Ann. Surg., 1894, XIX, p. 187; Welch and Plexner (6), Journ. Exp. Med., 1896, I, p. 5; Martin (1), University Bulletin, 1896, I, No. 3, and Bloodgood (6), Progressive Medicine, 1899, IV, December, p. 158. The notes of an additional unpublished case observed in Manila have been given me by Dr. Flexner. There are also 3 unpublished eases for the records of which I am indebted to Dr. Carroll of Washington.

The references to the remaining 26 cases are as follows: E. Fraenkel (4), Ueber Gasphlegmonen, Hamburg u. Leipzig, 1893; Passow (1), Charite-Annalen, 1895, XX, p. 275; Dunham (5), Bulletin of the Johns Hopkins Hospital, 1897, VIII, p. 68; Ferguson (1), Trans. Indiana Med. Soc, 1897, p. 339; Erdmann (1), Med. Record, Feb. 5, 1898, p. 205; Le Boutillier (1), Med. Record, March 5, 1898, p. 353; Love and Cary (1), Med. Record, April 8, 1899; Norris (1), Amer. Journ. Med. Sc., 1899, CXVII, p. 195; Hitschmann and Lindenthal (5), Sitzungsb. d. k. Akad. d. Wiss., Math.-Naturw. CI., Wien, 1899, CVIII, Hft. iii, Abth. iii, p. 67;' Thorndike (2), Boston Med. and Surg. Journ., June 7, 1900, p. 592; Muecatello with Gangitano (3), Riforma med., 1900, II, pp. 508,


Thirty-two are reported by American observers and only 14 by foreign investigators. Of the former group of cases 16 were observed iu Baltimore, most of the cultures having been studied in my laboratory; of the foreign group of cases all are reported from Germany, Austria, Italy and France, 4 by E. Fraenkel, 1 (not absolutely certain) by Passow, 5 by Hitschmanu and Lindenthal, 3 by Muscatello assisted by Gangitano and 1 by Guillemot. 5 ' 1

Cases of gaseous phlegmon in which Bacillus aerogenes capsulatus was not demonstrated are not included, although many of these presented the same clinical characters and doubtless in some at least the gas-bacillus was the active agent. This is true especially of the cases of gangrene foudroyante, usually without satisfactory bacteriological examination, attributed by French writers to Pasteur's vibrion septique. Gertler's M eight cases of gaseous phlegmon cannot be utilized for our purposes at all, as they are without any satisfactory bacteriological reports.

A complete analysis of these 46 cases would afford material more than sufficient to occupy this entire address, so that I shall be able to present here only some of the more important points.

Thirty-five of the patients were males, 10 females and of one the sex is not stated. The preponderance of males is to be explained by the fact that most of the cases were due to severe injuries. Robust workmen in the prime of life furnished the largest contingent of eases.

In 80 per cent of the cases one of the extremities was the seat of the emphysematous gangrene, the lower being affected a little over twice as often as the upper extremities. In several instances the emphysema extended from the thigh to the abdominal wall or from the arm to the subcutaneous tissues of the shoulder and chest. There were three examples of primary emphysematous phlegmon of the abdominal wall: of these one following removal of the appendix (Bloodgood), one from an unrecognized strangulated Littre hernia (Martin), and one affecting the deep tissues of a nephrectomy wound (Muscatello). In all of these the infection is believed to have started from the intestine. In one of Dunham's cases there was emphysematous gangrene (originating in a prostatic abscess opening in the buttock) of the scrotum, penis, and anterior abdominal and thoracic subcutaneous tissues. In three instances (Carroll (2); Dobbin (1) reported by Bloodgood) the breast and submammary tissues were the primary


519 and 530; Guillemot (1), Compt. rend. Soc. de biol., 1898, 10. S., V, p. 1017. A few other cases in which the gas-bacillus was found are not reported with sufficient detail to be available for analysis. It is safe to say that B. aerog. caps, has now been found in over 50 cases of gaseous gangrene.

" Soupault and Guillemot (Bull, et mem. Soc. med. d. hop. de Paris, 1900, 3. S., XVII, p. 216) have reported two gaseous abscesses following hypodermic injections, and a third which they regard as metastatic, in which they found the gas-bacillus (B. perifringens), once in pure culture. These cases will be considered subsequently under the heading " Gaseous Abscesses."

H Ueber Gasphlegmonen. Inaug.-Diss. Halle, 1898.


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seat of the disease, all of these resulting- from the infusion of salt solution. In one ease (Dunham) the gaseous phlegmon appeared at the angle of the lower jaw after incision of a Eoul submaxillary abscess. In one instance (Welch and Flexner) it started within the pelvis from traumatic rupture of the rectum and extended through the sciatic notch down the thigh.

of especial interest are three examples of multiple or metastatic emphysematous gangrene, one of the forearm and opposite shoulder, another of the thigh and both shoulders, and still another of one shoulder and the buttocks. In the older literature are similar eases; thus Nelaton observed emphysema not only in the injured leg but also in the opposite, uninjured extremity. In 189? Leech' reported without adequate bacteriological examination a case id' emphysematous gangrene of the right leg following about three weeks after injury of the right thumb, which became inflamed, there b.ing no evident local cause of the affection of the leg. These cases aic to be explained by transportation of the bacilli through the lymphatic or blood-current from the primary focus of entrance.

In all but •"> of the 4b' cases the emphysematous gangrene followed traumatism or a surgical operation. The injuries were as follows: compound fractures, 18; bullet and gunshot wounds. ?; infusion of salt solution, 3; hypodermic injections, 2; ligation of the femoral artery for aneurysm, 3; external urethrotomy, 2; traumatic rupture of the rectum, removal of the appendix, prostatic abscess following self-cat heterization, operation for strangulated, Littre hernia, incision of a foul submaxillary abscess, and nephrectomy, each 1. Of the •"> non-traumatic cases the gaseous gangrene followed erysipelas in one, was consecutive to apparently spontaneous gangrene in 2, whether diabetic or not is not stated, and was without apparent explanation in two (Praenkel's Case 2 and Passow).

Compound fractures and next bullet and gunshot wounds occupy by far the most prominent place in this list, each of the other various causes being represented only l>\ scattered eases. Those injuries in which there are much laceration and crushing of tissue, comminution of bone and grinding of dirt, bit- of clothing or other foreign bodies into the wound are the ones most likely to be followed by emphysematous gangrene. That, however, severe traumatism is not an es factor is shown by the 5 cases (10.9 per cent of the entire number) following hypodermic injections and infusion of normal salt solution (see eases also under "Gaseous Abscesses.") These latter, however, were all of patients whose vital forces were greatly depressed, namely, by Asiatic cholera. typhoid fever, surgical shock, or post-partum haemorrhage. There is good reason to believe that the intact tissues of human beings in health possess marked resistance I" lb- gas bacillus.

In the great majority of cases it was evident that tl bacillus was introduced through the wounded skin from without. In three instances (removal of appendix, strangulated


Quart. Med. Journ. (Sheffield). 1896-97, V. p. 237.


hernia, and traumatic rupture of the rectum) the infection undoubtedly came from the intestine. This was also the probable source of infection in one of Muscatello's cases (gaseous phlegmon in the site of an extirpated kidne\ ). With our present knowledge of the frequent, if not regular, presence of Bacillus aerogenes capsulatus in the intestine, there is nothing surprising in this mode of infection. In three of Dunham's case- the infection followed injury of the urethra, and here also the bacilli may have come primarily from the intestine. In one of his cases (gaseous phlegmon at angle of the jaw) it was suggested that the bacilli gained entrance through decayed teeth.

Bloodgood thinks it probable that in one of his cases the gas-bacilli were brought by the circulation to the seat of infection. In this case the femoral artery was ligated for traumatic arterio-venous aneurysm in the popliteal space. There was no primary infection of the wound, but gangrene of the foot and leg ensued and on incision gas-bubbles were found in the blood of the aneurysmal sac and the tissues. With what we know about the entrance of intestinal bacteria into the circulation, there is nothing improbable in Bloodgood's opinion, which is also supported by Lanier's and Muscatello's experiments already mentioned. The clot in an aneurysm and tissues robbed of their nutrient supply would offer little or no resistance to the growth of bacilli which might reach them or their immediate neighborhood through the circulation and the conditions would be anaerobic. It was indeed a case of aneurysm in which I first found the gasbacillus, and here the clot was swarming with bacilli. It is interesting to note that three of the cases of emphysematous gangrene in my list followed ligation of the femoral or popliteal artery for aneurysm.

Pirogoft'"" distinguished clinically two groups of cases of traumatic emphysematous gangrene. He described under the name "primary mephitic gangrene" cases in which the emphysema appears within two days after the injury, the " local stupor" passing without inflammatory reaction into crepitating gangrene. Here the emphysematous necrosis spreads rapidly, the patient sinks into collapse with an icteroid hue of the skin, small, thready pulse and cold sweats, and death occurs usually within a few days after the onset. This type of the disease corresponds to Maisonneuve's gangrene foudroyante. In the second group, designated by Pirogoft' also as '"acute gangrenous oedema," there is reaction from the primary "local stupor" of the tissues, the emphysema is preceded ami accompanied by local, (edematous or purulent inflammation, is associated with febrile reaction, often appears later after the injury and spreads less rapidly, and presents in general a more varied anatomical and clinical picture than i be first class of cases.

Hitsehmann and 1, indent hal consider that Pirogoff's first. group corresponds especially to cases of pure or predominant infection with the gas-bacillus, and his second group to mixed infections. Efdmann is also of the opinion that in the un


' Grundziige d. allg. Kriegsrhlnirgie, p. 1006, Leipzig. 1864.


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mixed infections the emphysematous necrosis spreads more rapidly and is more likely to terminate fatally. On the other hand, Muscatello and Gangitano, who also divide the cases into two groups — pure infections and mixed infections — hold that the mixed infections are characterized by the rapidly progressive form of emphysematous gangrene, while the pure infections, at least in their early stage, show little tendency to spread beyond the injured tissues. According to the last named authors the gas-bacillus is incapable of exerting any pathogenic action itpon healthy tissues,, but attacks only tissues already altered in their vitality by injury, other pathogenic microorganisms, toxins, or other depressing factors.

The study of our cases has not enabled me to adopt in their exclusive form either of the two conflicting opinions just .-land. Of the collected 46 cases, 30 were mixed infections, f 1 were pure and of 2 there is no clear statement on this point. The most common associated bacteria were the pyogenic streptococci and staphylococci. Among other forms found occasionally were Bacillus coli, proteus, pyocyaneus, tetanus, Sanfelice's Bacillus pseudo-cedematis maligni, and , uncultivable, often spore-bearing, bacilli. It seems probable that the bacillus of malignant oedema, being a common inhabitant of the soil, must occasionally, like the tetanus bacillus, be present, but it was not isolated from any of these cases. My experience is that if reliance be not placed exclusively upon cultures, but careful microscopical examinations be also made, instances of unmixed infection with Bacillus aerogenes capsulatus are rare. It is by no means always easy to determine whether associated bacteria are exerting pathogenic action or not. Pyogenic cocci may be present without producing pus or marked inflammatory reaction.

We have found rapidly progressive forms of emphysematous gangrene botli with pure infection with the gas-bacillus and with mixed infections, and on the other hand we have observed with both types of infection cases in which the tendency to spread is much less marked. In all of the cases with much purulent inflammation mixed infection was present, but aside from this feature the division of the cases into pure and mixed infections does not, according to our experience, correspond to different, sharply marked, clinical features. Pirogoff's classification is doubtless of clinical value, but there is every gradation between the two groups.

I cannot agree with Muscatello and Gangitano, whose investigations of emphysematous gangrene are of great value, that tin- gas-bacillus is incapable of attacking healthy tissues. Virulent cultures, even in moderate doses, can produce rapidly spreading gaseous phlegmons when inoculated into the subcutaneous tissues of susceptible animals such as guinea-pigs and pigeons. In human beings the emphysema may extend very rapidly into the healthy tissues, frequently outstripping in its advance the inflammatory cedema. This may occur in pure, as well as in mixed, infections with the gas-bacillus. After amputation through apparently healthy tissues there may be rapidly spreading emphysema from (he stump (Welch and Flexner's Case II). The two instances of men


ingitis observed by Hitschmann and Lindenthal and by Howard speak also for the power of the gas-bacillus to attack healthy tissues. It is true, as urged by Muscatello and Gangitano, that toxins derived from the bacilli may prepare the tissues for the invasion and action of the advancing bacilli, but the same explanation has been put forward for the spread of other pathogenic bacteria in healthy tissues. In asserting that the gas-bacillus may attack healthy tissues, I would not be understood as minimizing the great importance of the various accessory causes of emphysematous gangrene which act by lowering the vitality of the tissues or the general resistance of the patient, or as failing to recognize the marked resistance to infection by the gas-bacillus offered by the healthy tissues, a resistance to which I have previously called attention and which I shall have occasion further to emphasize.

Gas may appear in the tissues as early as eight hours after the injury. In a case of gaseous phlegmon following a bullet wound of the knee joint, reported by Welch and Flexner, Dr. Bloodgood recognized gas in the joint " and surrounding tissues just twenty hours after the injury. In a case of Dr. Tiffany's, which we have reported, death from emphysematous gangrene, due to pure infection with the gas-bacillus, occurred forty-eight hours after a fall causing a compound, comminuted fracture of the patella with grinding of the underclothing into the wound. There was no other injury of the body. Any one who has seen one of these rapidly fatal cases of spreading, traumatic, emphysematous gangrene will receive an impression which he will never forget.

The anatomical and clinical study of uncomplicated emphysematous gangrene demonstrates that the disease is not, as many formerly supposed, simply an intense variety of ordinary phlegmonous inflammation or cellulitis, but is a disease sui generis. It may be combined with phlegmonous inflammation, but then some other microorganism, usually the streptococcus, is associated with the gas-bacillus.

In typical uncomplicated cases the lesions consist in necrosis of all the tissues, the presence of gas in the interstices, infiltration with blood, evidences of the mechanical action of the iias. and exudation of a variable amount of bloody serum. The amount of gas varies much in different cases. There may be only a few bubbles or the tissues may be everywhere blown up with gas. The nuclei disappear by karyolysis. The notable thing in most cases is a nearly complete absence of leukocytes and of cellular reaction, although in a few instances, even of pure infection, 1 have found leukocytes in considerable number, and even purulent foci, but generally at a distance from the primary necrosis. As will be shown later Bacillus aerogenes capsulatus in certain situations is capable of setting up purulent inflammation. In one of our cases, reported by Bloodgood, Dr. Gushing found gas-bacilli without gas in a small subcutaneous abscess of a stump two


" It is to be regretted that in the cases reported by Prutz (Deutsche Zeitschr. f. Chirurg., 1898, XLVII, p. 591), as traumatic entrance of air into the knee joint, no bacteriological examination was made.


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months after amputation of the thigh for emphysematous gangrene of the leg, the amputation having been followed by uninterrupted convalescence.

After death there may be rapid extension of the subcutaneous emphysema, and at autopsies made a few hours after death gas-huhbles may he found in the heart, vessels, liver and other organs, hut as to this occurrence there is no rule. As 1 have already explained wide-spread distribution id' gas in the blood and organs in early autopsies indicates entrance of the bacilli into the circulation during life.

As is to he expected from the etiology of many of the cases of emphysematous gangrene, emboli of fat and of bone-marrow cells are common in the pulmonary capillaries, but 1 do not know that in any case they contributed to the fatal result.

The prognosis of emphysematous gangrene is more favorable to-day than before the antiseptic period. The disease terminated fatally in 59 per cent of the eases in my list. In the cases observed and treated at the Johns Hopkins Hospital — 1(1 in number — the fatality was •"><) per cent, hut of these one was a gaseous phlegmon of the pelvis extending to the thigh, resulting from traumatic rupture of the rectum, a second was a gaseous phlegmon of the abdominal wall following removal of the appendix and complicated with diffuse gangrenous peritonitis, and a third case terminated twentyfive days after disappearance of a gaseous phlegmon of the thigh (treated by incisions) from a late streptococcus infection, gas and the gas-bacillus having disappeared. Of thu two remaining fatal cases in one — emphysematous gangrene following compound fracture of the thigh — amputation was refused by the patient until the fourth day when he was in a state of collapse and died fifteen hours later, and in the other — compound fracture of' the skull and both lower extremities — the patient died thirty hours after the accident, having never regained consciousness.

When the disease is accessible to surgical treatment, is not complicated by other grave conditions, and is promptly recognized and treated, the prognosis, according to the experience of my surgical colleagues. Professor Halsted and Dr. Bloodgood, is not very unfavorable.

The clinical evidence favors the view that, at least in mosl uncomplicated fatal cases, death is due to toxaemia. Nbrris was unable to demonstrate the presence of strong toxins in artificial cultures of Bacillus aerogenes capsulatus, but, as is well known, the same difficulty is encountered with many other pathogenic bacteria which arc believed to produce poisons in the human body. Muscatello is also of the opinion that the constitutional symptoms are attributable to to

I'!,,, suggestion that death may he due to gaseous embolism is not new. Pirogoff and other of tie- older observers knew that gas-bubbles may he found within the heart and very soon after the death of patients from emphysematous gangrene. In the discussion on Langenbeck's paper on trau matic infiltration before the Society of German Military Sur geons in 1870, Senator " advocated the supposition thai death


"Deutsche militararztl. Zeitschr., 1872, I, p. 2P>0.


is caused by gas-embolism. While the possibility of this occurrence as the cause of death may be admitted, there is at present no proof of this opinion. Gas-bubbles are by no means always found in the blood and organs alter death from emphysematous gangrene, and the clinical histories of those in whom they are found post mortem do not appear to ditfer from those where they are absent. In experimental gaseous phlegmons in guinea-pigs there is no evidence of the presence <d' gas-bubbles in the circulation during life.

In one id' our cases ( Mann) death resulted from tetanus and Verneuil" has reported three cases which withoul bacteriological examination he. in conformity with current French opinion, calls malignant (edema, where also tetanus intervened. There is nothing surprising in this association when one considers that the home of the tetanus bacillus, like that of the gas-bacillus, is the soil. The period of incubation for tetanus is longer than for infection with the gasbacillus, the former appearing rarely before the seventh day. and the latter usually within two or three days after the injury.

Prophylactic measures against emphysematous gangrene are sufficiently obvious from the etiological factors which have already been considered. It is important in wounds of the character most frequently followed by this complication to search microscopically and by cultures for Bacillus aerogenes capsulatus. The examination of coverslips, stained by Gram, w ill usually suffice for a probable diagnosis. I have already cited instances in which this bacillus has been detected before the onset of emphysema and in which there is good reason to think prompt surgical treatment warded off Severe infection. The possibility of infection from the intestinal canal, as well as from external sources, is to be borne in mind.

The cases were treated either by tree incisions or by amputation or both. The results were better after amputation than after simple incisions, of the cases of emphysematous gangrene affecting primarily the extremities, the recoveries numbered UN per cent after amputation, and :!.'{'., per cent after incision without amputation. Careful study of individual cases shows that amputation is by no means always necessary. Everything depends upon early recognition of the nature of the infection. Dr. Bloodgood," from a relatively large experience, says: " It the infection is recognized early, and t he destruction of the sofl parts and hone is not extensive, free incisions with immediate continuous hath treatment, should he tried. If the general symptoms id' infection are not immediately relieved, amputation should he done. It', however, the infection is recognized late one should take no risk

hid amputate at ome \n earlj diagnosis will probably

save life, and from many observations an amputation may not always he uecessary. '

A similar position as to prognosis and treatment is taken by Muscatello and Gargitano in their valuable paper on ga


s *Semaine med., 1890. p. 403.

'"Progressive Medicine. 1899. IV. December, p. 174.


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gangrene, in which they also emphasize the value of abundant miis with disinfectant and oxidizing solutions. In the service of Dr. Halsted at the Johns Hopkins Hospital the continuous bath treatment has been found useful. Hitschmaim and Lindenthal are certainly mistaken in their assertion that incisions are usually without favorable effect and that earlj amputations offer the only chance of recovery. As pointed out by Thorndike and others recovery may follow amputation even when it is impossible to remove the whole of the diseased tissues.

Gaseous Abscess i s.

The presence of gas in closed abscesses may be due to Bacillus aerogenes capsnlatus.

It seems t ptestionable whether Fraenkel's"' second

i ase should be classified under emphysematous gangrene. In the region of the right elbow joint there was a painful fluctuating swelling from which on incision fetid pus mixed with gas-bubbles escaped. The subcutaneous tissue was partly necrotic. A similar swelling over the left shoulder joint was also incised. Resides the gas-bacillus, streptococci and long delicate bacilli appeared in the cultures. There is no state ni concerning the causation of these abscesses. Passow's

, ase was also a peculiar one. Following a superficial, suppurating wound of the right hand there appeared panophthalmitis with septicaemia, during which a crepitating swelling of the righi shoulder and upper arm developed, from which on incision were evacuated pas ; nd a brownish, fetid secretion, but no actual pus Besides staphylococci a bacillus, believed by Passow to be identical with the gas-bacillus, was cultivated. I have included these two cases under the gaseous phlegmons or emphysematous panprene. although at least the former seems to have been one of definite abscesses.

Soupault and Guillemot" have recorded two cases of gaseous abscess, following hypodermic injections, due to the pas-bacillus. They call the organism "Bacillus perf ringens " (Veillon and Zuber), but identify it with Fraenkel's Bacillus phlegmones emphysematosa}. Of the American work on Bacillus aerogenes capsnlatus they have apparently never heard. In Soupault and Guillemot's first case a larpe abscess containing fetid pus and gas with the odor of sulphuretted hydrogen followed the iniection of 40 cc. of 5 per cent common salt solution into the thigh of a patient with advanced and rapidly extending pulmonary tuberculosis. The injection, made September *. was at once followed by a painful swelling of the thigh, over which the skin was reddened; on September 15, gas «as detected: on September 25. 300 cc. of ohocolatecolored, thick, viscid pus mixed with pas were aspirated, and 8 days later an incision, from which 200 cc. of reddish pus escaped, was made, after which the abscess slowly healed. Aerobic cultures were negative; in anaerobic cultures Bacillus aerogenes capsnlatus (Veillon and Zuher's Bacillus perfrin


n Ueber Gasphlegmonen, p. 15, Hamburg and Leipzig, 1893. " 2 Bull, et mem. Soc. med. d. hop. de Paris, 1900, 3. S., XVII, p. 216.


gens) was obtained in pure culture. From the foul odor of the pus and gas, which is said to have been distinctly that of sulphuretted hydrogen, it is probable that, at least at some stage of the process, other microorganisms were associated with the gas-bacillus, which survived for nearly a month in the abscess.

The same authors report a second case of gaseous abscess, which in this instance followed the injection of artificial serum into the abdominal walls of a child with grave typhoid fever. The abscess, which was opened by thermo-eautery, contained yellowish, viscid, inodorous pus. Three aerobic organisms, of which Staphylococcus aureus predominated, were found associated with Bacillus aeropenes capsulatus.

Soupault and Guillemot describe a third case of a young man. 19 years old. in whom a gangrenous phlegmon with extensive sloughing followed an injury of the left lep received in playing foot-ball. After the critical condition seemed to have passed, an emphysematous subcutaneous swelling appeared in the opposite, healthy lep near the inside of the knee. A hypodermic injection of salt solution had been made in the external part of the right thigh, but the authors do not consider that this had anythinp to do with the gaseous swelling, as the latter was too remote from the site of injection. Thev. therefore, attribute the gaseous phlepmon to transportation of bacilli by the circulation from the opposite extremity. Bacillus aeropones capsulatus was found in pure culture. Recovery was uninterrupted.

Soupault and Guillemot emphasize the benign course of the affection in their three cases, as well as in other instances of paseous abscess following hypodermic injections which they cite from published records. Conditions favoring the occurrence of such abscesses after these injections are the irritating quality of the fluids injected (ether, tincture of musk, camphor, acid solutions of morphine, concentrated saline solutions, etc.") and lowered general resistance of the patient produced by typhoid fever, tuberculosis, cancer, cholera, haemorrhages, and other grave diseases. When death occurs, they think that it is usually attributable to the primary disease, not to the infection with the pas-bacillus.

I have included in my statistics of emphysematous gangrene 5 cases of paseous phlepmon following hypodermic injections, 3 of these (Carroll 2, Dobbin 1) beinp of normal salt solution in puerperal women, and 2 (E. Fraenkel) beinp respectively of oil of camphor followed at once by ether in a patient after extirpation of a pvloric cancer, and of a solution in water of sulphuric acid and muriate of morphia in choleTa. That the most unirritatinp of solutions may be followed by paseous phlepmon is demonstrated by the three cases in which phvsiological salt solution was injected. Of these latter two died, and one recovered after incision of the phlepmon. Both of Fraenkel's cases terminated fatally.

Includinp Soupault and Guillemot's 3 instances of paseous abscess we have altogether S cases of paseous abscess or phlegmon following hypodermic injections of various substances, and caused by Bacillus aerogenes capsulatus. usually in association with other bacteria.


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Brieger and Ehrlich's" two observations of fatal gaseous phlegmon following the hypodermic injection of tincture of musk in typhoid fever are usually cited as the firsl instances of authenticated malignant oedema in man. luit ii cannol be said that the bacillus concerned was proven beyond doub! to be thai of malignant oedema, and with our present knowledge of the etiology of this class of affections it is permissible to question the accuracy of the identification of the bacillus in these two cases, notwithstanding the high authority of the observers. In the case of gaseous abscess following the intramuscular injection of ether reported by Bucquet," and in the two similar cases reported by Lauteret.'" all three ending in recovery, no bacteriological examination was made.

II is evident from the foregoing cases that Bacillus aerogenes capsulatus, in combination usually with pyogenic bacteria, is the chief, if not sole, cause of the gaseous abscesses or emphysematous gangrene which occasionally follow hypodermic injections. Although in mine of the cases reported has this bacillus been looked for in the fluids injected, the presumption is that it was present either in them or in the Byringe, although there is a possibility of the introduction of this organism from the skin of the patients, and even of its conveyance by the circulation from the intestine to (lie site of tissues damaged by the injection of irritating substances.

I shall refer subsequently to the occurrence of the gasbacillus in abscesses withoul nas and to other manifestations of its pyogenic capacity.

Uterine Infections.

Knowledge of Bacillus aerogenes capsulatus is of not less interest and importance to the obstetrician than to the surgeon. Infection of the puerperal uterus by this microorganism leads to a variety of morbid conditions, some comparatively mild, others of the utmost gravity.

The wide distribution of the gas-bacillus in the intestinal canal and the outer world renders as explicable the occasional e of this bacillus in the female genital tract as that of the colon bacillus in the same situation. Lindenthal " found flic gas-bacillus in the vagina without the presence of gas or other pathogenic effects twice out of six puerperal cases examined. According to the observations of others, Lindenthal's experience would si em to lie exceptional. As with so many other pathogenic bacteria the mere presence of the organism upon exposed surfaces does not necessarily signify infection.

I shall consider the uterine infections by the gas-bacillus under the headings of emphysema of the foetus, puerperal endometritis, physometra, emphysema of the uterine wall, and puerperal gas-sepsis, although these conditions may be associated with each other.

Emphysema of the Faius. — The occurrence of emphysema


" Berliner klin. Woch., 1882, XIX. p. 661.

"These, Paris, 1883.

"These, Paris, 1898.

"Wiener klin. Wochenschr., 1897, pp. 3 and 35.


in the dead fcetus in utero has been known for centuries,"' but it was not until 1897, when Dobbin published his paper on -Puerperal Sepsis due to Infection with the Bacillus aerogenes capsulatus'"" that the cause of this condition was determined t<> be invasion by Bacillus aerogenes capsulatus. In this ease gas ami the gas-bacillus were both recognized .luring the life of the patient in the foetus, the placenta and the cavity of the uterus, and after death there was general gasformation throughout the body.

Dr. Dobbin has kindly given me the notes of a second, unpublished case observed by him. He was called to see a woman in difficult labor, upon whom repeated attempts at delivery of a dead foetus had been made. Upon examination he recognized crepitation of the caput succedaneum while the fcetus was still in utero. Upon delivery the foetus was em physematous with foamy organs. The gas bacillus was found in pure culture in the fcetus and mixed with other bacteria in the amniotic fluid. No gas was recognized in the uterus after delivery. The patient made a good recovery without evidence of sepsis.

Menge and Kronig" have observed three instances of foetal infection by the gas-bacillus and have brought strong evidence that usually the invasion is through the mouth of the fn>tus, the bacilli being taken into the lungs or stomach by inspiring or swallowing amniotic fluid. Tn their cases the bacilli were not found in the part of the umbilical cord attached to the placenta, but in Dobbin's first case this as well as the placenta itself was infected with the gas-bacillus. The amniotic fluid within the intact membranes, as is well known, is usually sterile, and only exceptionally becomes infected before rupture of the membranes, so that the infection of the foetus from this source is generally after this rupture. As shown by Menge and Kronig, all grades of invasion of the fief us by the gas-bacillus occur, so that there may be only a small amount of gas. and this limited to (he lungs or the alimentary canal or both. The medico-legal importance of not mistaking for air this gas in the foetal lungs produced by gas-bacilli should be emphasized.

As is well known, foetal emphysema is usually unattended with danger to I he mother. In two of the five eases due to Bacillus aerogenes capsulatus in my list the puerperium was even without rise of temperature, in two there was mild fever, but in Dobbin's first ease there was rapidly fatal gassepsis. will be considered cases of acute uterine infection with the

Puerperal Endometritis. — Under the heading " gas


'■'■ It is usually stated that this condition was known to Celsus, but he does not expressly mention the presence of gas. although this is to be inferred. In the chapter on extraction of the dead foetus, he says: " Solet etiam evenire, ut is infans humore distendatur, exque eo profluat foedi odoris sanies." Milligan's " Celsus," p. 394, Edinburg, 1831.

68 Bulletin of the Johns Hopkins Hospital, 1897, VIII, p. 24.

" Bakteriologie des weibl. Genitalkanales, Teil II, p. 167, Leipzig, 1897.


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gas-bacillus followed by invasion of the Mood and organs by Lnnism. Here it may be mentioned that Bacillus aerocapsulatus may be present in the uterus, usually in association with other bacteria, in both mild and severe cases of puerperal endometritis without the recognition of gas in the fcetus, or the uterine cavity, or wall. An example of such a an unpublished one in the service of Dr. J. Whitridge Williams, of which the notes have been furnished me by Dr. Dobbin. A woman with rhachitic pelvis, upon whom delivery by forceps had been attempted before admission to the Johns Hopkins Hospital, was there delivered by craniotomy. There was no gas in the foetus. Forty-eight hours later Bacillus aerogenes eapsulatus, together with streptococci, was found in the uterine lochia. Xo pis was detected. The patient developed fever, but recovered.

In two cases, one reported by Dobbin'" and the other by Blumer, 71 the gas-bacillus, although not identified with absolute certainty, was probably present in the puerperal uterus in association with the typhoid bacillus.

Physometra. — Distension of the uterine cavity with gas (physometra or tympany of the uterus) was present in Dobbin's firs! case, already cited, and is often associated with emphysema of the dead fcetus, hid may occur without the latter and even in the uon-pregnant uterus. This curious condition was formerly ascribed to entrance of air or to ordinary putrefaction.' but it is now known to be the result of the activity of gas-producing bacilli.

Since the observations id' Lindenthal,™ reported in 1898, it cannot he doubted that Bacillus aerogenes eapsulatus is the chief cause of physometra. He found this bacillus in five

cases during life and reproduced the condition experi ntally

in guinea-pigs. He is justly skeptical id' the correctness of the previous reports of Gebhard" concerning the agency of the coli, ii bacillus in generating pis within the uterus. We know from Theobald Smith's investigations that the colon bacillus can produce gas only from carbohydrates, whereas it i- the most distinctive biological attribute of our gas-bacillus that it can produce Lias from proteids. Until it has been shown that the amniotic fluid and uterine contents may under any conditions contain enough carbohydrate to explain the devi lopnient of gas by the colon bacillus there is everj reason Hon the claims for this bacillus as a cause of tympany of the uterus."

My lis! of cases contains 1 ' * instances id' physometra in


Am. Journ. Obstetrics, 1898, XXXVIII, p. 185. 1 [bid., L899, XXXIX. p. 42.

" The older hypotheses and records on physometra and emphysema of the fcetus are fully presented by Staude. Zeitschr. f. Geb. u Gyniik., L878, III, p. 191.

Monatsschr. f. Geb. u. Gyniik., 1S98, VII, p. 269. 71 Zeitschr. f. Geb. u. Gyniik, 1893, XXVI, p. 480, and 1897, XXXVII, p. 132.

'■'■ Halban (Monatsschr. f. Geb. u. Gyniik., 1900, XI, p. 102) states that he has found lactose once in the amniotic fluid of a normal puerpera. Further studies of this subject are needed.


which Bacillus aerogenes eapsulatus was demonstrated. .Although as some of our cases show, this condition may lie associated with invasion of the bacilli into the wall of the uterus and by acute gas-sepsis, these occurrences are exceptional and the prognosis is in general a favorable one. Most of the cases furnish a good illustration of the resistance of living human tissues to the action of the gas-bacillus. Doubtless in these cases the bacilli grow simply in the amniotic fluid after rupture of the membranes, and in the dead fcetus, these offering no vital resistance, whereas we must suppose that the intact uterine wall offers ordinarily an effective resistance to the invasion and multiplication of the gas-bacillus. That occasionally the bacilli may find other dead material in the uterus, as in sloughing myomata and cancers, is evident from the histories of some cases of physometra.

Emphysema of the Uterine Wall. — Far graver in significance i> septic emphysema of the uterine wall, of which Halban " has recently reported an interesting case due to Bacillus aerogenes eapsulatus. Graham, Steward and Baldwin and P. Ernst were the first to demonstrate this bacillus in this condition, their papers, to which reference has already been made, appearing simultaneously in August, 1893. Eleven instances of emphysema of the wall of the uterus, all puerperal, have been reported, of which •") were recognized during life. In all but llalban's case there was also physometra. and this would seem to be a necessary accompaniment unless the cervical canal is open so as to permit the escape of the gas from the uterine ca\ it v. All of the cases were fatal, and in most gas was found at autopsy in the blood and internal organs.

Subperitoneal emphysema is a condition which has been observed after rupture of the uterus, Dischler " having collected reports of 1 1 cases. In most instances this has been attributed to entrance of air. but I think that it is safe to predict that the pis-bacillus will be found in similar cases in the future, if proper methods for its detection are employed. 1 know, however, of no instance of this condition in which it has been looked for.

Puerperal Gas-Sepsis. — 1 have adopted from Halban the term •"pis-sepsis" as a convenient one — although, perhaps, open to criticism — to designate the important group of fatal pin rperal cases in which gas-bubbles are found at early autopsies in the heart and vessels and often also in the organs and tissues under conditions where we must suppose that gasbacilli and possibly gas have passed from the uterus into the circulation during life. 78 Here in my opinion belong most of the cases which have been reported as deaths due to the entrance of air into the uterine veins.- This opinion which I expressed in my first communications on the gas-bacillus in 1891 and 1892, received prompt confirmation in the papers


7,1 Monatsschr. f. Geb. u. Gyniik.. 1900. XI, p. 88.

77 Arch. f. Gynak., 1898, LVI, p. 199.

78 Gas-sepsis in this sense occurs also in other than uterine infections with the gas-bacillus.


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!!><>


of Graham, Steward and Baldwin and of 1*. Ernst in August, L893, and has since been strengthened by other similar observations. Cases described by Wendeler™ as sepsis acutissnua belong also in the same category.

My list includes 13 puerperal eases in which gas-bubbles and the gas-bacillus were found at autopsy in the blood or organs; but in only T of these does it seem to me conclusive ot extremely probable that the infection occurred during life. 1 '

The most remarkable of these cases is that reported by Graham, Steward and Baldwin of a woman, upon whom abortion had been recently produced, who during- the four hours immediately preceding death became emphysematous over nearly the whole body. At the autopsy gas and gas-bacilli were found everywhere throughout the body. In Dalton and Bremer's"' case, also one of criminal abortion, an emphysematous swelling of the arm and pectoral region was likewise recognized during life. These cases are of importance as demonstrating the invasion id' the body by the gas-bacillus fnnn the uterus while the blood is still circulating. In Hah ban's and Dobbin's cases gas was also recognized during life within the wall or cavity of the uterus.

In the majority of cases of puerperal gas-sepsis there has been some operative interference preceding infection, such as criminal abortion, forced delivery lor placenta praevia or other causes, or the manipulations of an unskilled midwife. The fulminating character of the infection, death being sometune,-, very sudden, is a notable feature of many of the cases.

In a case of attempted criminal abortion reported by Perkins"' the patient, according to the statement of the practitioner in whose office death occurred, died suddenly, and at the autopsy twelve hours later in cold weather, gas was found in the vena cava, heart, and other vessels, with evidences of injury to the pregnant uterus. The case was reported by Perkins as one id' death from air-embolism, and certainly with as much and even more plausibility than most eases thus reported. After the publication, Dr. Perkins, upon the request of Dr. Dob!, in. was so good as to send the uterus, well preserved in alcohol, to my laboratory where Dr. Dobbin demonstrated in the uterine vessels and tissue bacilli morphologically and in staining reaction identical with Bacillus aerogene- capsulatus." 3

I would not be understood to deny the possibility of the occurrence of fatal air-embolism from the uterus. A very few of the reported cases are difficult to interpret upon anj


■' Monatsschr. f. Geb. u. Gyniik., 1896, IV. p. 581.

"' These are the cases reported by Graham. Steward and Baldwin, P. Ernst, Menge and Kronig, Dobbin, F. C. Wood (Med. Record, Apr. 15, 1899), Cesaris-Demel, and Halban, to whose papers references have already been given.

81 Am. Journ. Med. Sc, 1888, XCV, p. 594. This infection, although attributed to the bacillus of malignant oedema, was probably due to the gas-bacillus.

M Boston Med. and Surg. Journ., 1897, CXXXVI, p. 154.

"Dobbin has reported the results of his examination with tur ther notes of this case in the Monatsschr. f. Geb. u. Gyniik 1897, VI, p. 375.


other supposition, but I do (hum llial the foundations ol this doctrine have been seriously shaken by our discovery and investigations of the gas-bacillus, and that no case, however plausible, can be considered as positively proven without a satisfactory bacteriological examination. The limitation of gas to the right heart and adjacent vessels may occur from invasion by the gas-bacillus, and is not, as often represented, peculiar to air-embolism. Did we not know how long it takes new knowledge, especially that originating in this country, to penetrate throughout the medical world, it would be amazing that cases should still continue to be reported, as they are," of deaths ascribed to air-embolism without any bacteriological examination or even any reference to the possibility of any other explanation. 1 am not aware that in any instance of alleged air-embolism, a bacteriological examination has been made, which would exclude the presence of gasforming bacteria.

Whether, as suggested by Staude, in any of the cases with gas within the uterine cavity, death is attributable to gaseous embolism, is. I think, an open question. It is possible, although 1 know of no proof of it. that in some id' the eases of sudden death during or immediately after some manipulation or operation on the pregnant uterus and attributed to airembolism, gas. generated by bacteria, may have existed under pressure within the uterine cavity and have entered wounded veins in sufficient amount and so suddenly as to have caused death.

To what extent the free gas found in the blood-vessels, heart and internal organs, even very soon after death from what has been described as puerperal gas-sepsis, is there during life is a question difficult to answer. I have already considered this subject, and in this connection shall again emphasize the importance of caution in interpreting the presence of gas in these situations as a vital phenomenon, although there is evidence that it may lie such.

Infections of the I'hixahy Tract.

There is evidence that the urinary tract may not only he a portal of entrance for the gas-bacillus into the circulation or adjacent tissues but also be itself the seat of infection by this organism. Unfortunately for the decisive interpretation of many of these cases. Bacillus aerogenes capsulatus has. so far

as I am aware, hitherto I n found in the urinary tract only

after death, although in some instances so soon thereafter and under such conditions that its presence during life cannot be doubted.

I have already called attention to instances of emphysematous gangrene following external urethrotomy and other operations on the urinary passages.


"Zorn (Miinch. med. Woch., 1898, p. 567) may be cited as an example. Hiibl (Wiener klin. Woch., 1900, XII, p. Ill) has also recently reported two instances of alleged air-embolism— placenta praevia— without any bacteriological examination. Ho assumes incorrectly that the distribution of the gas at autopsy is a decisive point as between air-embolism and gas-sepsis.


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Among the eases of general invasion of the blood and organs (foamy organs) by the gas-bacillus observed 1>\ myself and others are several in which the portal of entry was the urethra, bladder or other part of the urinary tract. 85 h\ a ease of urethral stricture with cystitis, for which perineal section had been done, reported by Welch and Flexner, gasbacilli were found three-quarters of an hour after death in large numbers in the bladder, ureters and renal pelvis, and a few gas-bubbles and gas-bacilli were already present in the blood of the right ventricle. In Howard's case of meningitis caused h\ the gas-bacillus, to be cited subsequently, he considers that the portal of entry was the urinary tract.

(ias. generated by Bacillus aerogenes capsulatus, has been found in the urinary passages in r> cases which have come to my notice."' The gas may be either free in the cavity of the bladder, ureters or renal pelvis, or contained within submucous blebs, or in both situations.

Welch and Flexner 1 " have reported an instance of pneumaturia in a diabetic man in whom, six hours after death, without trace of cadaveric decomposition, the urinary bladder was found filled with frothy urine containing Bacillus aerogenes capsulatus in pure culture. This case indicates that the colon bacillus and Bacillus laetis aerogenes are not the sole causes of pneumaturia in diabetics. Dr. i'lexner has given me the notes of a second case of pneumaturia upon which he made the autopsy at the University Hospital, Philadelphia. This was of a patient with chronic cardiac disease who had been catheterized twenty-eight hours before admission and who died thirty hours after admission. At the autopsy, made one hour and a half after death, about G'U ec. of frothy urine were found in the bladder from which Bacillus aerogenes capsulatus, together with Staphylococcus aureus and Streptococcus pyogenes (no colon bacilli), was cultivated. Neither gas nor gas-bacilli were found elsewhere in the body. The mucous membrane of the bladder was cedematous. There can be little doubt that in this case the gas-bacillus was introduced by the catheter into the bladder.

In one of Welch and Flexner's cases (Case XVI11) of hypertroplned prostate with pyoureter and pyonephrosis, the renal pelves and ureters were found at autopsy distended with gas and containing pus mixed with bubbles of gas. Small gascysts were present in the mucous membrane of the renal pelves. .Neither gas nor gas-bacilli were present outside of the urinary organs. In this ease cocci and colon bacilli were associated with the gas-bacillus.


In a case of Hr. Kelly's, of winch the full records have been given me by Dr. Miller,' 8 there was pneumaturia deruon


K Such cases are reported by Welch and Flexner, Goebel, Dunham and Howard in papers already cited.

M These do not include some instances of very extensive postmortem emphysema of the organs with gas everywhere throughout the body.

Case XIII of our list in Journal of Experimental Medicine, 1896.

88 This case is briefly reported by Kelly and MacCallum, Journ.


strated by cystoscopic examination and ureteral catheterization to come exclusively from the inflamed left renal pelvis and ureter. Among cocci and other bacteria were found on coverslips bacilli morphologically resembling Bacillus aerogenes capsulatus, but unfortunately no anaerobic cultures were made. None of the bacteria which grew aerobieally piod need gas in lactose-agar, This case is interesting as demonstrating that the gas may come exclusively from one renal pelvis and ureter, but the microorganism producing the gas was not satisfactorily demonstrated. It seems certain that it was an anaerobic organism, and from the microscopical appearances may have been the gas-bacillus.

The subject of submucous gas-cysts will be considered subsequently; but here it may be mentioned that besides the gascysts in the renal pelves noted by Welch and Flexner in the case already cited, Coebel found gas-blebs, containing in pure culture Bacillus aerogenes capsulatus, beneath the mucous membrane of the urinary bladder, without gas elsewhere in the body, and Dunham has reported a like condition of the bladder in a ease of emphysematous gangrene with general invasion of the blood and organs by the gas-bacillus.

Bacteria have been found in emphysema of the bladder (cystitis emphysematosa) also by Eisenlohr, w Camargo/" and Kedrowsky," but it is impossible from the authors' descriptions to identify their bacteria. Kedrowsky considers that the bacillus isolated by him is allied to Bacillus aerogenes capsulatus, but less sensitive to oxygen. Perhaps it was Sanfelice's Bacillus pseudo-cedematis maligni, to which I have already referred, but Kedrowsky "s description of his cultures hardly inspires confidence in their purity.

Welch and Flexner and Howard have reported rinding the gas-bacillus, in association with other bacteria, in inflammatory lesions of the bladder, renal pelvis and kidneys, without the detection of gas. Howard considers that in one of his cases the bacillus was concerned in the etiology of suppurative lesions of the kidneys but in this case the colon bacillus and Streptococcus pyogenes were also present.

Infections Derived feom the Gastko-Intestinal Canal.

Mention has already been made of the frequent, if not constant, presence of Bacillus aerogenes capsulatus in the. intestinal canal, of gaseous phlegmons originating from this source, and of the readiness with which intestinal bacteria may gam access to the genito-urinary tract.

The intestine is by far the commonest source of the gasbacilli found together with gas-bubbles in the blood aud organs at autopsies. This invasion may occur either with or without definite intestinal lesions, and is probably in the majority of cases an agonal or post-mortem event. The mode of distribution and spread of the bacilli in these cases has


Amer. Med. Assoc, 1898, XXXI, p. 376, whose paper may be consulted for the full literature of pneumaturia.

8 " Ziegler's Beitr., 1888, III. p. 101.

"" These de Geneve, 1891.

" Centralbl. f. allg. Path. u. path. Anat., 189S, IX, p. 817.


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been well described by Howard.*" whose experience has been exceptionally large with this class of affections. Especially demonstrative of invasion of gas-bacilli from the intestine, usually post mortem, is the occurrence of gas-bubbles limited to the neighborhood of the intestine, as in the intestinal wall. within the portal or mesenteric wins, or lymphatics, in the Subperitoneal tissues, mesentery ami omenta, around the pancreas, in the mesenteric gland, and especially in the louse tissue near the gall-bladder and in the porta of the liver, without gas in more remote situations. 1 bave seen examples of each of these occurrences in very early autopsies without ordinary cadaveric decomposition.

Local Gastro-intestinal Lesions. — Interstitial emphysema of the gastro-intestinal wall will be considered subsequently.

Howard has described several cases with larger or smaller areas of superficial necrosis of the mucous membrane of the stomach and intestine, in which gas-bacilli were present in large numbers. These areas, which may occur either with or without gas-cysts, are found most frequently beneath the folds of the valvular conniventes and are characterized by absence of nuclear staining and disintegration of the cells and tissue, usually without marked inflammatory reaction.

Bacillus aerogenes capsulatus may undoubtedly be a cause, of meteorism. Instances of this are reported by Welch and Flexner and by Howard.

Pneumo-peritonitis with and without Perforation. — My records include 13 cases of diffuse peritonitis in the exudate of which Bacillus aerogenes capsulatus was found. Eleven of these were in autopsies made either by Dr. Flexner or myself, 1 having already been published by us in 1S9C. The remaining 2 cases (both being perforations of gastric ulcers) have been reported by Page, 8 ' and by Pratt and Fulton.'" It was the observation of these cases which first called my attention to the frequent presence of the gas-bacillus in the intestine.

Ten of the cases were perforative and 3 were non-perforative. Of the former 4 were the result of perforation of typhoid ulcers, 4 of gastric ulcers. 9 one of strangulated, gangrenous intestine and one of a cancerous ulcer of the duodenum. In the last ease (autopsy fourteen hours after Jr.:] in the exudate was sero-fibrinous and the gas-bacillus was Eound in pure culture" and abundantly in the peritonea] cavity and


K Op. cit., p. 491.

" Canada Lancet, May, 1900.

" Boston Med. and Surg. Journ., June 7, 1900, p. 599.

  • =■ Welch and Flexner have reported an instance of peritonitis

from perforated gastric ulcer in a rabbit, in which the gas bacillus was found.

"The purity of the culture in this case is explicable by the results of dishing and Livingood's interesting bacteriological and experimental studies of the duodenal flora published in Contributions to the Science of Medicine, Dedicated by his pupils to William Henry Welch on the 25th Anniversary of his Doctorate, p. 543, Baltimore, 1900.


was absent from other organs and the blood. In the other perforative eases the gas-bacillus was mixed with other bacteria, although in some instances it predominated. In all of

the eases the abdomen w a.- greatly distended with gas and

usually there was great tympanites.

I attach especial importance to the ease fully reported by Welch and Flexner,"' in which we brought conclusive evidenci of the occurrence of pneumoperitonitis without perforation, the first of the kind on record in which similar proof was obtained. The presence of gas ill the peritoneal cavity was recognized during life. Since our publication a similar ease has been observed by Dr. Flexner in Manila, who has kindly furnished me the notes. At the autopsy, twelve hours alter death, there was found hsemorrhagic infarction of the lower part of the ileum and adjacent part of the huge intestine, caused by the passage of this part of the intestine through a hole in the mesentery. The peritoneal cavity was greatly distended with gas which burnt with a pale, blue flame. There was a large amount of frothy, bloody serum in the peritoneal cavity together with a fibrinous exudate. The most careful examination showed no perforation. Bacillus aerogenes capsulatus was obtained in pure culture and abundantly from the peritonea] fluid. Gas was absent from the blood and other organs.

We have found the gas-bacillus, mixed with other bacteria, twice in circumscribed, gas-containing, intraperitoneal abscesses resulting from perforation of the appendix vermiformis.

Hepatic and Biliary Infections. — The development of gas in the liver is so sinking a phenomenon in most autopsies where the gas-bacillus and free gas are found in the blood and organs that I'. Ernst used the. term " Schaumleber " for

the title of his art ii b the gas-bacillus, published a year

after the paper by Welch and Nuttall, in which we first directed attention to the subject of foamy organs and the gas-bacillus.™ I have already considered the general subject of gas-bubbles in the blood and organs, and wish here to call attention especially to infections of the gall-bladder and biliary passages by Bacillus aerogenes capsulatus.

In cases of foamy liver gas may be found in the bile-duets and gall-bladder, but my experience is that, when the gasbacilli reach tin' liver through the blood-vessels, the appearance of gas in these situations is a rather late occurrence and met chiefly in advanced cases. In contrast to these cases are the observations of gas in the biliary passages, associated sometimes with definite lesions of the bile-ducts and liver. where the evidence is that the gas-bacilli entered from the


" Op. cit., p. 35.

" Heydenreich's paper on " Emphysem der Leber " (Centralbl. f. Bakter., 1897, XXI, p. 305) may be mentioned as a curiosity. He had never heard of the gas-bacillus or of any other investigation of the subject later than 1872. In contrast to this is the interesting article of P. Bernhardt on pneumathsemia and foamy organs with full consideration of the recent literature. Deutsche med. Woch., 1900, p. 83.


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intestine directly into these passages. Two such cases have been reported by Howard." 5 and I have observed two cases.

Pratt and Fulton 100 report a remarkable ease of cancer of the common bile-duci and pancreas in which cholecystotomy was performed, the edges of opening in the gall-bladder being stitched to the abdominal walls. At the autopsy the Liver ml studded with minute abscesses with greenish translucent walls. In coverslips, sections and cultures Bacillus - capsulatus was found in pure culture in these small biliary abscesses, but there was no gas in the abscesses, the liver, blood, or other organs. A somewhat similar case, in which cholecystenterostomy for gall-stones bad been performed, was previously reported by Nicholls ™ from Adami's laboratory. Here also multiple miliary abscesses containing the gas-bacillus were found in the liver, but in this ease gas was present in the liver, as well as in the blood and other organs, the autopsy being six hours after death. Larkin 10 " has likewise reported a case of hemorrhagic pancreatitis with fat necroses and small, multiple hepatic abscesses with gas-holes in the liver, from which Bacillus aerogenes capsulatus was isolated. The autopsy was eight hours after death.

Ilint/c' ha.- recorded a post-mortem observation of gas in the inflamed bile-ducts with cholelithiasis. He cultivated only the colon bacillus, but it does not appear that he made anaerobic cultures.

From the foregoing cases it is to lie inferred that the gasbacillus may invade the bile-duets and gall-bladder from the intestine, and sometimes during life, and that it may not only produce gas hut also necroses and purulent inflammation. The presence of gall-stones, cancer of the bile-ducts and operations on the gall-bladder favor this mode of infection.

Etisi "" found the gas-bacillus (Bacillus perfringens), without gas or other lesion attributed to it, in an extirpated gallbladder containing a calculus and clear viscid fluid.

[nteestitial Emphysema of the Gasteo-Intestinal, Genito-TJbinaey and Biliary Tracts.

One of the si interesting lesions produced by Bacillus

aerogenes capsulatus is the formation of submucous or subserous gas-cysts or blebs, of which the earliest examples attributed to this organism were reported by P. Ernst, Goebel, and Welch and Flexner. They are sufficiently common to have been observed by nearly all investigators who have had much experience with the gas-bacillus in human beings. My list of cases includes '.'•"> instances of this condition, of which .") were of the stomach, 11 of the intestine far oftener id' the small than the large intestine), 5 of the gall-bladder ami bile


™ Contributions to the Science of Medicine, Dedicated by his pupils to William Henry Welch on the 25th Anniversary of his Doctorate, pp. 475 and 476, Baltimore, 1900.

'" Boston Med. and Surg. Journ., June 7, 1900, p. 599.

"" Brit. Med. Journ., 1897, II, p. 1844.

m Med. Record, 1898, LIII, p. 354.

"" Miinch. med. Woch., 1895, XLIII, p. 209.

m These, Paris, 1898.


ducts, 3 id' the urinary bladder, 1 of the renal pelvis, and I of the vagina. The majority of the cases were observed by Flexner, Howard, and myself, and in all the gas-bacillus was demonstrated. The ease of emphysema of the vagina was reported by Lindenthal.'" 5

These gas-cysts vary in size from microscopic dimensions to large blebs. They are most common in the submucous coat, but may be present in the mucous membrane, the muscular coat or beneath the serous covering, in fact, in any part of the membranous wall. They may be few or in enormous numbers, in groups or scattered. In one of our cases the whole small intestine from the duodenum to the ileoccecal valve was studded with small gas-cysts. Gas-cysts of the same general character may be found in the mesentery and omenta.

These gas-cysts are in their inception simply such gas-holes as we are already familiar with in the liver and other organs in eases of local or general invasion with the gas-bacillus. They indicate a foamy or emphysematous condition of the walls of the stomach, intestine, gall-bladder, bile-ducts, urinary bladder and vagina, due to the invasion into these parts of the gas-bacillus.

The condition of the walls of the blebs and of the surrounding tissues varies. Some of the cavities are round and their walls smooth, others are irregular in shape and have ragged walls. They may correspond to dilated lymphatics, but more frequently they do not represent dilatation of any performed channels. There may be communication between adjacent cavities, but oftener the cysts are distinct from each other. The tissue in the immediate neighborhood of the cavities may present no alteration not explicable by the mechanical pressure of the gas, or it may show necrosis in varying degree and extent. Inflammatory changes or cellular reaction which could be reasonably referred to the presence of the cysts or of the gas-bacilli causing them were not noted. Sometimes a little coagulated, homogeneous or granular material is present in sections of the cysts in hardened tissues, as indeed may often be found in gas-holes in the organs.

In sections stained by (Irani there is usually no difficulty in demonstrating the relation of the gas-bacilli to the cysts. The bacilli may be in masses in the walls of the cysts, but sometimes they are not more numerous there than in the tissue at a distance from the gas-blebs, and occasionally it requires some searching to find them. By anaerobic methods the gas-bacillus can be cultivated from the cysts or the adjacent tissue.

All of the instances of submucous and subserous gas-cysts in my list were observed post mortem. In the larger number of cases gas-bacilli and gas-bubbles were more or less widely distributed in the blood and organs, but without evidences of ordinary post-mortem decomposition. There are, however, several cases in which these gas-cysts in various situations were the sole manifestation of the presence of the gas-bacillus in the body. Howard has shown that if careful, systematic


'Wiener klin. Woch., 1897, pp. 3 and 35.


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search is made for areas of necrosis and minute gas-cysts due to Bacillus aerogenes capsulatus in the stomach and intestine, these lesion? can lie found much more frequently than lias been supposed.

It is. with our present information, a difficuli matter to say in how many of these eases the emphysematous state existed before death. It is certain that, at leas! in the great majority of cases in my list, the emphysema was not the result of ordinary post-mortem decomposition. In a large numher of the cases the autopsy was made within a few hours after death. Howard, in one of his eases of gas-cysts, limited to the intestine, made the autopsy one hour after death. I have alreadj emphasized the importance of great caution in interpreting a- \ital processes the various gaseous conditions of parts and organs not open to inspection during life, even when autopsies are made soon after death and there is entire absence of putrefaction, and I can only repeat this caution here. Mere absence of nuclear staining around gas-holes 1 do not regard as proof of their origin (hiring life.

, It would lead altogether too far to enter here into a discussion of the general subject of submucous gas-cysts concerning which there is a large literature, the principal references to which will lie found in the articles of F.isenlohr."" Camargo."" Winands,'" Orlandi, 1 " 8 Dupraz 10 " and Lindenthal. 1 " 1 It would appear from a study of the records of the subjeci that anatomically different conditions have been described under the designation " gas-cysts " (cystides aeriferae). Some have Keen apparently of long standing and show chronic inflammatory changes in the walls of the cysts and the surrounding tissues. The most voluminous records relate to the gascysts of the vagina (kolpohyperplasia cystica of Wmckel, emphysema vagiine of Eppinger).

At present we have no warrant to identify the more chronic sts with thickened walls with the more acute emphysematous condition which I have described as referable to Bacillus aerogenes capsulatus. Nevertheless the former are probably of bacterial origin also, although I am unable to accept the bacteriological findings of Eisenlohr, Camargo, Orlandi and Dupraz as at all convincing, for they made no use of at lerobic methods of cultivation. It is quite possible I hat Bacillus aerogenes capsulatus is concerned also in the etiology of the gas-cysts of long standing; certainly it is important to apply hereafter anaerobic cultural methods to their study. Lindenthal lias no hesitation in identifying the emphysema of the vagina observed by him post mortem and from which in a single ease he cultivated what he chooses to call Bacillus emphysematis vaginae (in reality our Bacillus aerogenes cap sulatns) with Winckel's kolpohyperplasia cystica, hut. while


'"Zieglers Beitriige, 1888, III, p. 101.

' : These de Geneve, 1891.

"* Ziegler's Beitrage, 1895, XVII,, p. 38.

,M *Gazz. med. di Torino, 1896, XLVII, ]

"* Arch, de med. exper., 1897, IX, p. 282.

""Wiener klin. Wochenschr., 1897, pp. 3 and 35.


781.


Ic may he correct, further observations are needed before their anatomical and etiological identification can he accepted.

The only instance in which gas-cysts of the human intestine have been recognized during the life of the patienl is reported by Balm, 1 " who found them in large numher upon opening the abdomen. It is to ho regretted that no thorough bacteriological examination of this ease was made.

In my original communication on the gas-bacillus I ventured the surmise that the haeillus found by E. I'raenkel '" in hardened sections from a ease- of gastritis emphysematosa might he identical with Haeillus aerogenes capsulatus, and this suspicion has gained in probability by Goebel's statements based upon a re-examination of the sections, his work having been done under Fraenkel's supervision.

Notwithstanding an effort at compression, so much space has been occupied in the presentation of the foregoing subdivisions of our subject, which in less than a decade has grown to considerable magnitude, that I shall only summarize very briefly a few remaining topics, although all deserve fuller treatment.

Pulmonary ami Pleural Injections. — To the two instances of invasion of the lungs by the gas-bacillus reported by Welch and Flexner, I can add the cultivation of this organism front a gangrenous lung by Dr. flexner in my laboratory. It has been found also by Guillemot"' and Hist"' in pulmonary gangrene.

Of much importance is Levy's'" demonstration of Bacillus aerogenes capsulatus as a cause of pneumothorax without perforation. This case and those of pneumoperitonitis without perforation to which I have already referred have settled affirmatively the long standing controversy concerning the possibility of the generation of gas within closed serous sacs during life. Nicholls "' has reported an instance of pneumothorax and pneumopericardium without perforation in which the gas-bacillus was probably present. Rendu and Rist "' also isolated the gas-bacillus (Bacillus perfringens) in a case of putrid pleurisy with gas. May and Gebhart 1 " and Finley"" attribute their two cases of pneumothorax without perforation to the colon haeillus. hut in neither were anaerobic cultures made. It is important that in all gaseous affections anaerobeshould he searched for.

Bacillus Aerogenes Capsulatus in the BUmd during Life. —


1,1 Deutsche med. Woch.. 1899, p. 657. '" Virchow's Archiv, 1889, CXVIII, p. 526. 1,3 These. Paris, 1899. '" These, Paris, 1898.

1,1 Arch. f. exp. Path. u. Pharm., 1895, XXXV, p. 335. "° Loc. cit.

1,7 Bull, et mem. Soc. med. d. hop. de Paris, 1899, 3. S., XVI, p. 133. °" Deutsches Arch. f. klin. Med., 1898, LXI, p. 323. "* Philadelphia Monthly Med. Journ., 1899, I, p. 569.


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Extremely interesting is the demonstration by Gwyn,' "" both by eoverslip specimens and by cultures, on repeated examinations, of Bacillus aerogenes capsulatus during life in the blood of a patient, in the Johns Hopkins Hospital, with chorea insaniens and acute endocarditis. 1 had the opportunity of examining his cultures, which were entirely typical. The patieni died but unfortunately no autopsy could be obtained. There was no evidence during life of free gas in the blood or tissues. The case is of importance as demonstrating that gasbacilli may be in the circulating blood for days in sufficient number to be demonstrable both microscopically and culturally without evidence of free gas. 1 have already expressed my suspicion that Achalme's anaerobic bacillus, which has likewise been cultivated from the blond, as well as from the i 3sui -. of several cases of acute articular rheumatism, is identical with Bacillus aerogenes capsulatus.

Presence of Bacillus Aerogenes Capsulatus without Gas. — In this connection I may say that the gas-bacillus may be presenl and even multiplying within the human body without the production of gas. Certain organs, above all the liver, oiler much more favorable pabulum for the generation of gas than do others, but even in the liver the bacilli may be present without gas. 1 have found gas-bacilli in clumps within the spleen and kidney, surrounded by areas id' necrosis, without recognizable gas. 120 " I have already cited the demonstrations by Cushing and by Pratt and Fulton of the gas-bacillus in -mall abscesses without gas. the observation of the latter being particularly complete and satisfactory, liist '" has cultivated the gas-bacillus (Bacillus perfringens) from cases of fetid otorrhoea and of mastoid abscess. He does not mention the presence of gas in these cases. I have already cited his isolation of this bacillus from the gall-bladder which contained no gas.

Dr. Harris in my laboratory isolated the gas-bacillus in pure culture from an abscess containing blood and pus in the neck of a dog. following an operation on the jugular vein. There was no gas in the abscess. Aerobic cultures were entirely negative. These observations, however, are not the only ones demonstrating that the gas-baeillus may under certain circumstances and in certain situations manifest pyogenic capacity.


'■' Bulletin of the Johns Hopkins Hospital, 1899, X, p. 134.

'-"a Cesaris-Demel's (loc. cit.) opinion that generation of gas in the tissues is merely a putrefactive process pertaining not to any particular kind of microorganism but to irreparable necrosis or damage of the tissues, whereby they become the prey of indifferent gas-producing bacteria, is not proven by his own observations and is opposed by many facts described in this paper.

'-' These, Paris, 1898.


Meningitis. Pyogenic Capacity of Bacillus Aerogenes Capsulatus. — Howard,'""' in April, lsiil). reported a ease of acute fibrino-purulent meningitis, following operation for urethroperineal fistula. Bacillus aerogenes capsulatus was found in pure culture in the meningeal exudate. Likewise Hitschmann and Lindenthal " : ' have recorded another convincing example of acute cerebral meningitis, following fracture of the occipital bone, in which the gas-bacillus was found unmixed with other bacteria. These authors call attention to the pyogenic power of the gas-bacillus when it attacks the meninges, but. as already shown, the same power may be manifested elsewhere.

Cavities in the Brain. — Finally I would call attention to Reuling and Herring's'" and Howard's studies of cavities in the brain produced by Bacillus aerogenes capsulatus and to the light which their observations shed upon certain obscure examples of cerebral cavities previously reported.

In this excursion into pneumato-pathology I have invited you to the survey of fields comparatively new and little trodden. I can only hope that our journey has been not without some interest and some profit to you. To me the opportunity to present before such a body as the Massachusetts Medical Society the results of these investigations is one which I highly appreciate.

I desire in closing to pay my tribute of respect and to call to your grateful remembrance the founder of this lectureship. Dr. George Cheyne Shattuek. That the subject of this address would not have been without interest to him may be inferred from the title of his first Boylston Prize dissertation on the theme propounded in 1806 and entitled: " The difference between mortification produced by an external cause and that which is produced by a constitutional defect, the diagnostieks and proper mode of treatment of each." '"' By his noble character, professional services and liberality Dr. Shattuck deserved well of the medical profession of his city and state, and, indeed, of the whole country, and his memory is worthily perpetuated not only by the foundation of this lectureship but also by the endowment of the chair of morbid anatomy in the Harvard Medical School.


'- Bulletin of the Johns Hopkins Hospital, 1899, X, p. 66. ,M Op. cit.

'-* Bulletin of the Johns Hopkins Hospital, 1899, X, p. 62. ,!S Published in Boston in 1808.


THE JOHNS HOPKINS HOSPITAL BULLETIN.

The Hospital Bulletin contains details of hospital and dispensary practice, abstracts of papers read, and other proceedings of the Medical 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.

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JOHNS HOPKINS HOSPITAL BULLETIN.


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ON THE HISTOLOGY OF THE ISLANDS OF LANGERHANS OF THE PANCREAS.

By Eugene L. Opie, M. J).. Instructor in Pathology, Johns Hopkins University.


The pancreas is much more complex in structure than the other glandular organs which it closely resembles. Langer

buns, 1 in an inaugural dissertation published in 1869, gave the first careful description of its histology and showed that the organ has not the relatively simple structure oi' the salivary glands.

Langerhans studied the pancreas of rabbits which in its essential features does not dili'er from that of other mammals. The larger duets are lined by epithelium composed of a single layer of high columnar cells. As the branches of the duct become smaller, the epithelial cells become lower, cubical, and finally flat or, as seen in section, spindle shaped, the nucleus occupying the thicker central portion. The smallest duets end in the acini composed of high columnar characteristically glandular cells containing next the lumen numerous zymogen granules. Within almost every acinus in contact with the secreting cells Langerhans found one, two, or more cells of a different nature, and to these he gave the name centre acinar cells. They closely resemble the flat spindle-shaped cells lining the very small ducts and he thinks that the epithelium of the duct is continued over the secreting cells into the lumen of the acinus, but he admits that he is unable to determine with exactness the method by which the duet ends.

Distributed at intervals in the parenchyma are groups of cells differing markedly from those of the ordinary glandular type. Such groups are usually round and in tissue, treated two or three days with Midler's fluid, appear with low magnification, as intensely yellow- specks. With high magnification they are found to be composed of small, irregularly polygonal cells with a round nucleus and a refractive homogeneous cell body. Of the nature of these cell groups Langerhans declares himself entirely ignorant.

Numerous observers have described these structures which are usually designated islands of Langerhans. Reliant." regarding them as analogous to lymph follicles, speaks of them as -points folliculaires." Podwyssotski "' calls them pseudofollicles. They have been designated secondary cell groups, inter-alveolar cell islets, etc.

In injected specimens Kuline and Lea' found scattered through the organ glomerular structures composed "I' dilated


1 Langerhans. Beitriige zur mikroskopischen Anatomie der Bauchspeicheldriise. Inaug.-Diss., Berlin, 1869.

■ Renaut. Sur les organes lymphoglandulaires et la pancreas des vertebres. Compt. rend. d. l'Acad. d. Sciences, LXXXIX, 247, 1879.

  • Podwyssotski. Beitriige zur Kenntniss des teineren Baues

der Bauchspeicheldriise. Arch. f. mikrosk. Anat, XXI. 765, 1882.

'Kiihne and Lea. Beobachtungen iiber die Absonderung des Pancreas. Untersuch. a. d. Physiolog. Instit d. Univ. Heidelberg II, 488, 1882.


and tortuous capillaries and showed that these glomeruli correspond to the cell groups which Langerhans described. The islands are penetrated by numerous wide tortuous capillaries which lie between cells forming irregular anastomosing columns. Material injected into the duct of the gland does not penetrate the islands.

Interacinar cell islets have been studied by Harris and (low/' and recently by Diamare," in a great variety of annual species, including n niials, birds, amphibia ami reptiles.

Laguesse' has studied the development of these bodies in

sheep embryos and has reached conclusions which have not. I believe, been confirmed, lie finds that at an early period of growth the pancreas is composed of tortuous tubules formed by a single layer id' epithelial cells. Here and there occur cells which stain more deeply than those about them and. like the border cells of the stomach, arc situated near the outer surface of the tubule. These cells proliferate and form what he calls primary islands of Langerhans. Accepting the observations of Lcwaschcw. to be mentioned later, he thinks that after development of the organ is completed similar Structures, secondary islands of Langerhans, are formed from groups of secreting acini.

Various opinions are held concerning the nature of flic interacinar cell groups. The suggestions which have been advanced may be classified as follows: (1) The islands id' Langerhans. having the same origin as the secreting elements of tin- gland, aiv formed during embryological life and persisting thereafter probably subserve some special function. (2) They represent a stage in the embryological development of the gland acini and those found in the adult organ are persistent rudimentary structures. (3) They are follicles of lymphatic tissue scattered through the organ. (I) They are modified acini, transformed as the result of functional activity of a peculiar nature.

When throughout the gland structures are found composed of cells differing from those of the acini, having a different arrangement and bearing a peculiar relation to the bloodvessels, it seems probable that, formed in embryological life they possess an anatomical identity as definite as that of the glomeruli of the kidneys or the Malpighian bodies of the


  • Harris and Gow. Note upon One or Two Points in the Comparative Histology of the Pancreas. Jour, of Phys., XV, 349,

1894.

"Diamare. Studii comparativi sulle isole di Langerhans del pancreas. Internat. Monatsschr. f. Anat. u. Phys.. XVI. 155, 177. 1899.

' Laguesse. Sur les principaux stades du developpment histogenicnie du pancreas. Verhandlungen der anat. Gesellsch., 1897, 43.


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[No. 114.


spleen. Schafer* thinks that they are similar to the small ductless structures, the carotid and coccygeal glands and the parathyroid bodies which are like them composed of anastomosing columns of epithelial-like cells, between which is a network of delicate tortuous capillaries.

Laguesse" has suggested that these structures represenl a stage in the development of the glandular acini but has subsequently abandoned this view, in support of which there is uo evidence. A number of observers have emphasized the supposed resemblance of the interaeinar islets to lymphoid tissue. Kenaut '" has described the pancreas as a lymphoglandular organ composed, he conceives, of glandular structures and lymphoid tissue in intimate relation. He describes the cell groups as " points folliculaires," in which cells of a glandular type are situated in the meshes a reticular tissue. Mouret " lias supported Kenaut 's somewhat ill-defined conception of a lympho-glandulax organ, but lias regarded the cell group a.s small masses of lymphoid tissue. Kiihne and Lea and Dieckhoff" think it probable that they are small lymph follicles. Schlesinger 13 regards them as a variety of lymph follicle whose cells differ from those of ordinary lymphoid tissue. Podwyssotski calls them pseudo-follicles and states that though they resemble lymph follicles their cells have nothing in common with lymphoid cells.

The only attempt to investigate experimentally the nature of the islands of Langerhans has been made by Lewaschew," working in Heidenhain's laboratory, lie studied the pancreas of dogs ami eats, killed after having been subjected to conditions which cause the gland to secrete actively. After prolonged overfeeding or after the administration of pilocarpin, which stimulates the pancreas as it does the salivary glands, he claims to have found structures representing transitions between the gland acini and the interaeinar cell group. He observes acini containing one or more cells whose protoplasm is non-granular and stains lightly. A whole acinus or a number of acini may be composed of such cells. In such areas some of the cells may assume a polygonal shape and are no longer grouped to form a central lumen. Other cell groups consist entirely of polygonal cells without acinar arrangement, and these represent, he thinks, the fully formed islands of Langerhans.

In order to obtain a large increase in the number of altered acini one even maximal stimulation of the gland is not sufli


8 Schafer. Quain's Anatomy, Vol. Ill, Pt. IV p. 318.

  • Laguesse Sur la formation des ilots de Langerhans dans

le pancreas. Compt. rend. Soc. de biol., 9. S., V. 819, 1893.

"' Renaut. Loc. cit.

11 Mouret. Tissue lymphoide du pancreas et cellule centroacineuse. Compt. rend. Soc. de biol., 10. S. I., 731, 1894.

'- Dieckhoff. Beitriige zur pathologischen Anatomie des Pancreas. Festschrift f. Thierfelder, Leipzig, 1895.

" Schlesinger. Die Erkrankung des Pancreas bei hereditarer Lues. Virch. Arch., CLIV, 501, 1898.

" Lewaschew. Ueber eine eigenthiimliche Veriinderung der Pankreaszellen warmbliitiger Thiere bei starker Absonderungsthatigkeit der Driise. Arch. f. mikros. Anat., XXIV, 452, 1886.


eient, but by the repeated administration of pilocarpin this result is accomplished and the longer and more intense the action of the drug the greater their number. To cause their increase by overfeeding a very large quantity of food is necessary. Lewaschew believes that the cells composing the interaeinar groups may reassume the characters of secreting cells and again form acini. He mentions that he has found an unusual number of islands under conditions other than those of increased functional activity. They were very numerous in a dog which several days before its death had suffered with fever.

The observations of Lewaschew have not been confirmed. In the human pancreas one occasionally finds altered glandular cells. Xon-granular refractive cells may occur in otherwise normal acini and entire acini or groups of acini may lie composed of such cells. Laguesse,'" regarding them as transitions between acini and interaeinar groups, has adopted the view of Lewaschew.

It is by no means surprising that little is known concerning the function of structures whose nature is so little understood. Laguesse'" thinks that they represent secreting acini temporarily modified to adapt themselves to a new function, the elaboration of an internal secretion. Schafer 1 ' and Diamare think that the vascular islets probably furnish an internal secretion. The only evidence in support of this suggestion is contained in the short preliminary notice of Ssobolew." He states that after feeding animals on carbohydrates the cells of the islands become more granular. After ligating the duct of Wirsung in dogs the islands of Langerhans. he finds, are not involved in the sclerotic process which follows. He thinks that this fact explains the absence of glycosuria after ligation of the pancreatic ducts. In hitman eases I had observed after duct obstruction " similar resistance of the islands to the consequent inflammation. In pancreas of two diabetics Ssobolew was unable to discover islands of Langerhans.

I have attempted to determine the relation of the islands of Langerhans to the other elements of the pancreas. They have been observed in human cases under a great variety of conditions, in cats and in dogs. Their relation to the bloodvessels has been studied in injected specimens. Finally, I have attempted to repeat the experiments of Lewaschew in order to test the possibility of transforming acini into interaeinar cell islets.

In the human pancreas the islands were found to be more numerous in the splenic end or tail than elsewhere. To obtain a numerical statement of their relative abundance, their num


15 Laguesse. Sur quelques details de structure du pancreas humain. Compt. rend. Soc. de biol. S. 10., I, 667, 1894.

18 Laguesse. Compt. rend. Soc. de biol.. 9. S., V, 819, 1893. 17 Schafer. Internal Secretions. Lancet, 1895, II, 321.

" Ssobolew. Ueber die Structure der Bauchspeicheldriise unter gewissen pathologischen Bedingungen. Centralbl. f. allg. Path. u. path. Anat., XI. 202, 1900.

19 Opie. Pathological Changes Affecting the Islands of Langerhans of the Pancreas. Jour. Boston Soc. Med. Sciences, IV. 251, 1900.


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ber .was determined in a sectional area of 0.5 square centimetre. Sections about 10 ft thick were made from the enlarged duodenal portion of the pancreas or the head, from the mid-portion or body and from the splenic end or tail. The following table gives their number in an area of 0.5 square centimetre in sections taken from the head, body and tail of ten normal organs:


Body. 13


I

II

Ill

IV

V

VI

VII ....

VIII . . .

IX

X

Average .


The table shows that the islands are more abundant in the tail or splenic end than in the bead and in the body, where they are present in approximately equal number. They are almost twice as numerous in sections from the tail as in those from other parts. Since the number in only one plane is recorded, in order to obtain their actual relative abundance it is necessary to square these figures. They are then found to be slightly less than three and a half times as numerous in the tail as elsewhere.

The islands of Langerhans arc more numerous, as pointed out by Kasahara/' in the pancreatic tissue of the foetus and of very young children than in that of the adult, Should we assume that they are formed during embryological development and persist thereafter, this fact is readily explicable. The organ being much smaller in the foetus and in the young child, the same number of islands, though themBelves -mailer, are closer together and therefore appear to be more numerous in sections.

The cells composing (lie island- resemble those of the acini. They have a large round, occasionally oval, vesicular nucleus and a conspicuous cell body. The basal zone of the secreting (ell. as is well known, stains deeply with nuclear dyes, for example, hematoxylin or methylene-blue, while the central portion which contains zymogen granules remains unstained. The cells of the island, however, do not stain with nuclear dyes, while with eosin their protoplasm takes ;> homogeneous bright pink color. The nuclei differ but little from those of in ighboring acini. They vary considerably in size and not infrequently one finds very large round vesicular nuclei whose diameter is two or more times that of those about. < )< ally the cells, forming columns between which are the anastomosing capillaries, are very closely packed together and


M Kasahara. Ueber das Bindegewebe des Pankreas bei versehiedenen Krankheiten. Virch. Arch., CXLIII, 111, 1896.


nuclei are situated almost side by side; more frequently the cells of the island are less numerous and the nuclei are less closely crowded together.

The outline of the island is usually round or oval and is not infrequently accentuated by a delicate circle of fibrous tissue. In other instances the outline is less sharp and the body accommodates its shape to that of the neighboring acini. Occasionally one sees, apparently within the island, cells arranged, as in the acini, about a central lumen and, indeed, in many instances it is difficult to convince one's self that they do not form part of it. The impression is produced that the columns of the island are in continuity with cells having an acinar arrangement. Since the islands and the secreting acini have a common origin it is not inconceivable that they may occasionally remain continuous in the adult organ. When the foetal pancreas is affected by congenital syphilis, the islands, I have found," retain their continuity with the secreting structures.

In the human pancreas the groups of acini about terminal ducts are not sharply defined by connective tissue, so that individual lobules, as in the human liver, are indistinctly marked off and in places apparently fuse with one another. In the pancreas of the eat the lobules, like those in the liver of the pig, are much more sharply outlined by interstitial tissue. Details of structure have been studied in the pancreas id' the cat.

The parenchyma is divided by septa of fibrous tissue into small polygonal areas varying in size and shape. When injected with Berlin-blue a small ramification of the ducts is found to penetrate the isolated group of acini. These subdivisions or lobules often appear completely isolated by fibrous tissue from those nearby, but when one id' them is traced through :i series of sections its separation may not be uniform and in places one finds the parenchyma of adjacent lobules in contact, the dividing septa being incomplete. That these polygonal structures are actually independent id' one another and represenl units of structure is readily demonstrated by causing an inflammatory increase of the interstitial tissue. If the pancreatic <]\\i\^ of a cat are ligated and the animal killed at the end of two or three weeks, the gland is found to he the -eat of a chronic interstitial inflammation, characterized by an increase of the interlobular tissue. The Lobules are completely separated from one another by narrow bands of firm fibrous tissue and occur in sections as rounded triangular or polygonal areas id' parenchyma.

The islands of Langerhans occupy a position near the centre of the lobule and in the splenic cud id' the gland each lobule contains an island. In a given section many lobules whose limits are more or less distinctly outlined are seen to contain islands situated near their centre, while in neighboring lobules such structures may not be discoverable. If. however, serial sections are studied every lobule is found to contain an island. Its presence within the lobule is not constant in other parts of the organ, and in the extremity


Opie. Loc. cit.


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of the descending arm of the gland they arc very few in number.

The lobules are grouped about the medium sized duets. The mam dints give off branches approximately at right angles to their course. Brandling one or more times a dud forms the centre of a group of lobules, which is usually elongated in form and taper.- to a point at or near the surface of the gland. Such lobule groups arc separated from one another by relatively wide bands of areolar tissue much looser in texture than that separating the individual lobules. The lobule groups in the fresh state or in tissue macerated a few



Fiqi be 1. — Camera lueida tracing of the lobule boundaries in one of a series of sections from the splenic end of a cat's pancreas. The majority of the lobules are well defined. Those marked </, c, f, <j and h are poorly outlined but are found to be more readily distinguishable when traced through the series of sections. The lobules, which are lettered (a to o), were traced through the series and each was found to contain an island of Langerhans situated near its centre. The section passes through the island in lobules n, e, i, / and n.

days in Midler's fluid may be separated from one another by careful teasing. In the loose tissue lie (he larger duels. arteries, veins, and nerves. An artery and vein penetrate each lobule group in company with the duel and ramify between its lobules. The smallest arteries occasionally penetrate the lobules, but usually branches, diminishing in size, give off capillaries which enter the lobule and form a close network between the gland acini.

The capillaries id' the island of Langerhans form a glomerulus of tortuous freely anastomosing vessels, much thicker than those between the acini. A single afferent vessel like that of the glomerulus of the kidney does not enter this group


of dilated capillaries but numerous anastomoses make it continuous with the interacinar capillaries. When Berlin-blue is injected through the aorta into the arteries of the pancreas, it not infrequently happens that in portions of the gland which are poorly injected the vessels of the island are tilled with the injected mass, while the surrounding capillaries are for the most part empty. If instead of soluble Berlin-blue a granular injection mass, for example, cinnabar or ultramarine blue is used, the islands may be injected while the interacinar capillaries contain little of the injected material. The glomerular network is in very free communication with the smallest arteries and apparently has a richer blood supply than other parts of the lobule.

In the human pancreas lobules and lobule groups are not so regularly arranged as in the cat. But both structures arc more or less clearly definable. The lobules vary much in size and are usually not clearly separated from one another. Though an island of Langerhans is often situated in the centre of a more or less clearly defined lobule, no constancy id' position is discoverable. The lobule groups are separated by relatively wide bands of loose areolar tissue in which are contained the medium sized ducts, the blood-vessels and the nerves. Within the lobule group the arteries and veins which are side by side do not, as in the cat, accompany the ducts.

In the normal human pancreas one occasionally finds small groups of acini composed of cells differing from the typical glandular type and suggesting a transition from the secreting cell to that of the island of Langerhans. The cell-protoplasm does not take the nuclear dye as does the basal portion of the ordinary glandular cell, and when stained with eosin has a bright pink color and homogeneous refractive appearance. The nucleus, which shows no evidence of degenerative change. is situated near the centre of the cell. Occasionally one or more cells of the character described form part of an acinus which otherwise resembles those about it. Usually, however, a group of acini are changed, and such an area often corresponds in size to an island of Langerhans.

The presence of altered acini whose cells resemble those of the island confirms at first sight the view of Lewaschew that groups of acini may assume the characters of the interacinar structures. It is probable that such foci in part at least represent what Laguesse" and Pischinger "' have described as stages of transition. The arrangement of more or less columnar cells about a central lumen is. however, still preserved and one does not find similar areas in which this arrangement is lost. The lumen, indeed, is usually very conspicuous and is often considerably dilated, filled with products of secretion which stain deeply with eosin. It seems probable that these groups of acini are altered as the result of peculiar functional activity, it may he. of hyperstimulation of the gland. There is at least no evidence that they represent


22 Laguesse. Compt. rend., S. 10, I, 667, 1894. 2! Pischinger. Beitriige zur Kenntniss des Pankreas. Diss., Miinchen, 1895.


Inaug.


September. 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


■_•<)'. i


transitional stages between gland acini and islands of Langerhans.

Such altered acini are observed in a small proportion of normal glands. They were found in three of twenty-seven glands examined carefully for their presence. They were present in three of seven relatively normal organs from diabetic patients. The occurrence of voracious appetite ami increased food ingestion in individuals so affected may explain the occurrence of these areas which represent possibly loci of peculiar secretory activity. They were particularly abundant in one instance of chronic interstitial pancreatitis not associated with diabetes.

Lewaschew has claimed that he was aide to transform groups of secreting acini into islands of Langerhans by stimulating the pancreas with pilocarpin. A single administration of the drug does not suffice, hut by its repeated administration an undouhted increase in the number of islands may. he says. he obtained. Under such conditions these bodies appeared to be more numerous than usual, but he has made no attempt to determine their actual number. He does not record the amount of pilocarpin used nor the frequency of its administration. T I is experiments have not been repeated.

I have attempted to confirm the observations of Lewaschew by injecting subcutaneously pilocarpin muriate into dogs. Since the number of islands was found to vary in different parts of the gland, it was considered desirable to study sections from corresponding parts of the organ. Specimens were prepared from (a) the splenic extremity, from (b) the portion which is in contact with the duodenum, and from (V) the d( scending portion which lies in the mesentery of the duodenum. In order to determine with accuracy the relative abundance of the islands their number was counted in a measured sectional area and compared with that found in the pancreas of an animal to which pilocarpin had not been given.

Following is a summary of the experiments performed:

Dog No. 1. — The animal was given daily for nine successive days 0.02 to 0.03 grm. of pilocarpin muriate. Profuse salivation was produced often with vomiting and diarrhoea.

Dog No. .'. — During twenty-eight hours pilocarpin muriate


0.005 to 0.0] grm. was injected subcutaneously six times. The drug produced profuse flow of saliva.

Dog No. -:>'. — During twenty-four hours pilocarpin muriate 0.01 grm. was injected subcutaneously seven times. Profuse salivation followed each injection.

In the table the figures represent the number of islandin 0.5 square ceni tre of sectional area. The letters refer

to the parts of the gland indicated above.

TABLE II.


Dog No. l


Average .... 56.6 37.6 6.6


Dog No. I

No. II. . No. III.

Average


The figures show that no increase of the number of islands was obtained in the three experiments. Transitional stages between glandular acini and interacinar islets were not observed. The number of islands in that part of the descending portion of the pancreas which lies in the mesentery of the duodenum (c) is constantly much less than elsewhere. The number in different glands and in different parts of the same gland varies considerably. In the experiments of Lewaschew these sources of error have apparently not been given sufficient weight.

CONCLUSIONS.

(1 ) The islands of Langerhans are composed of cells ha\ ing the same origin as those of the glandular acini but forming structures which are independent of the secreting apparatus and in intimate relation with the vascular system.

(2) In the splenic end of the cafs pancreas they have a definite position within the lobule, each of which contains one of these structures.

(3) In the human pancreas they are more numerous in the splenic extremity or tail than elsewhere. Similar variation in their number is observed in cats and dogs.

(4) Prolonged stimulation of the gland does not. as claimed by Lewaschew. transform groups of acini info islands of Langerhans.


THE DISTRIBUTION OF CONNECTIVE TISSUE IN NEW GROWTHS.

liv W. C White, M.B. (From the Pathological Laboratory of U" Johns Hopkins University and Hospital.)


I here report the result of the study of the distribution of connective tissues (viz.. yellow elastic tissue, white fibrous tissue and reticulum) in seventeen new growths, obtained in the fresh state from the Surgical and Gynaecological Depart ment of the Johns Hopkins Hospital through the kindness of Dr. Cushing and Dr. Kelly.

The work was done in the Pathological Laboratory of tin Hospital at the suggestion of Dr. L. F. Barker, and I am


much indebted to him for In- willing and valued assistance

throughout. To Dr. F. I'. Mall I am also under obligations for many kind suggest ions. The following methods were employed:

]. for the study of elastic tissue.

(,i) Demidessication and artificial oedema; Eresh tissue stained w ith magenta.


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[No. 114.


(6) Weigert's ' elastic fibre staining of the hardened tissue. (c) Unna's orcein stain (hardened tissue). 2. Fur the study of white fibrous tissue and reticulum. ("I Mall's method/ Digesting the fresh frozen section in pancreatin solution.

(b) Spalteholtz' method.' Digesting sections of hardened tissues in pancreatin solution, alternate sections being stained with hematoxylin and eosin for comparison.

(c) Van Gieson's picric acid fuchsin stain.

|r/i Mallory's new connective tissue stain, the use of which was very kindly permitted by Dr. Mallory, although the formula is still unpublished.

In studying the distribution of these tissues it has been taken for granted (1) that the tissue staining purplish with magenta in the fresh preparations and deep blue with Weigert's stain in the hardened preparation is elastic tissue, and (2) that the tissue left after digestion in pancreatin solution and staining red with Van Gieson's stain and blue with Mallory's stain is either white fibrous tissue or reticulum, and I have called them such in writing this paper.

The object has been, not to study the distribution of one kind of connective tissue, but to study the character and distribution of the several kinds by many methods.

It has been a great drawback that there is as yet no certain method of distinguishing white fibrous tissue and reticulum. Siegfried* has found in reticulum a substance which he calls reticulin, thus distinguishing it from white fibrous tissue which yields gelatine, but this method was not practically applicable in the present study. Then certain structural differences, it is asserted, exist between the two substances; viz., the wavy more or less parallel fibrils of white fibrous tissue running in bundles as against the very fine anastomosing and branching fibrils of reticulum; but the two substances are s,, intimately associated in any structure that the question arises id' the possibility of the one being the final breaking up and di\ ision of the other.

In the sarcomata and myomata reticular networks were found which in structure coincided with reticulum, the fibrils definitely branching and anastomosing, but they were here intimately associated with bundles of wavy parallel fibres which were just as typical of white fibrous tissue. In some places this reticular network appeared to have Ms origin from these bundles, while in other cases it seemed only to gain an anchorage there, the fibrils extending only for a short distance among the fibres of the bundles. In other places, and this wa- very frequent in the sarcoma sections studied by Mall's method, the filirils of the reticular network appeared to arise from certain focal points suggesting the possibility of their being the processes of cells which had been digested away-, hut the most probable explanation of this appearance was to


1 Centralbl. f. alg. Path. u. path. Anat. IX, 1899.

2 Johns Hopkins Hospital Reports, Vol. I, 1896.

" Archiv f. Anat. u. Phys., Anat. Abth., 1897, Supp. Bd. ' Habilitationsschrift, Leipzig, 1892.


be found in the thickness of the sections, several fibrils overlying one another at certain points. Again, the fibrils which presented the structural characters of white fibrous tissue were frequently seen in the Mall preparations to break up into much finer fibrils, suggesting the possibility of the two substances, white fibrous tissue and reticulum, being the same substance, the latter being the final division of the former.

So that without some method of determining the distinction or relation between the two substances the description of what was found in the present study has necessarily been purely objective, the two substances being included under the one head. Still some endeavor was made to discover the relation after pancreatin digestion id' what was found in myomata to tendon and also to reticulum by the following methods suggested by Dr. Mall.

Tendon was obtained from the human tendo-achillis; Reticulum was obtained from the gut of a dog by drawing the small intestine between the handles of a pair of scissors and thus removing the muscular coats and mucous membrane, leaving only the submucosa. A myoma was secured after removal from the human uterus. Small sections of all three were cut and digested in pancreatin solution. 5

They were then thoroughly washed in water and later placed in test tubes containing (1) \ per cent hydrochloric acid; (•,') 1 per cent hydrochloric acid; (■'!) 1 per cent solution of caustic potash and immersed in a beaker of boiling water and the results tabulated.

I have given also by permission the tables of Dr. Mall ' and of Dr. Find. 7

TABLES. Dr. Mall's Table.


Boiling KOH 1$ 30 seconds. 1.5 minutes.

Boiling HC1 }£$ 1 minute. 18 minutes.

Tissues remaining in the solution one hour before boiling.


Dr. Flint's Table.


Solution.


Time required to dissolve.


Tendon.


HC1 0.5$ 3,'{ mins. 10 mins. 11 V mins.

KOH 0.13$ 3 mins. 14% mins. 22 mins.

In Dr. Flint's work the sections remained in the solutions two hours before boiling, and at the end of the time given the tendon was completely dissolved and the solutions clear, while the reticulum in each case remained as a granular detritus even after boiling for thirty-five

minutes.

Time required to dissolve


Solution. Tendon. Reticulum. Myoma.

Boiling HC'l .5$ 27 mins. 43 mins. 55 mins.

" HC1 1$ 12 mins. 22 mins. 27 mins.

KOH 1%. ... 27 mins. 29 mins. 30 mins.

At the end of the different times given the tendon in each


" Pancreatin (P. D. & Co.), 5 grm.; sodium bicarbonate, 10 grm.; water, 100 cc.

Loc. cit.

7 The Blood Vessels of the Adrenal. Contributions to the Science of Medicine. Dedicated to Wm. H. Welch, Baltimore, 1900.


Si II 1MBER. 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


211


i asi was completely dissolved ami the fluid remain 6 clear, but in the case of both the reticulum and tin there remained a minute granular detritus m a verj cloudj or turbid fluid. The appearance of tendon was also quite differenl both from the myoma and the reticulum, which two latter substances behaved very similarly. The edges of the tendon section within a Eew minutes became ver\ much swollen and assumed a gelatinous or translucent appearance, and this gelatinous area increased ai the expense oi an opaque centre, but at the same time dissolved awaj until all had passed into solution. The myoma and reticulum, on the other hand, became shreddy and granular in appearance and gradually broke up into very minute granules which remained suspended in the fluid. In the myoma in the I per cent hydrochloric acid solution it was noticed a1 the end ot Eoui minutes that there appeared some >\\ dl iti-; and translucencj ai spots nn the surface, hut this had all disappeared a1 i he end of ten minutes and after this n behaved \er\ similarly i" reticulum. A longer time was taken to accomplish lie solution than in the other two tables, hut this was probably due te the larger sections used. In the latter eases frozen sections were used, while in this work the pieces measured probably ."> em. square. In the caustic potash experiment the section of tendon was somewhat larger than the other two sections.

Also based upon Mall's 8 finding that tendon is much more quickly dissolved in pepsin solution than either reticulum or

yellow elastic ti-siie. several frozen sections of my a were

digested for twenty-four hours in pancreatin solution, then washed in water and subsequently put in pepsin solution in the thermostat ami removed at different times, •">. In. Lo ami 30 minutes. .Mall found that tendon was completely dissolved in a strong solution of 1'. 1). & Co.'s pepsin in from 5 to 30 minutes, while elastic tissue and reticulum onlj begin to hi' dissolved at the end of this time. In these sections all evidence of structure was lost, even at the end of five minutes, hut at the end of thirty minutes a considerable portion, pos sibly amounting to -third of the original section was removed upon the slide. This experiment, however, loses much in value from the fact that no control specimens of p tendon or reticulum were made.

Regarding the two methods of studying white fibrous tissue and reticulum by digestion, \iz.. that of Mall ami that of Spalteholtz, each one gives evidence of value that is not obtained from the other, and as Mint says, both should he \\>ri\ together since in Mall's method owing to the thickness of the section a suggestion of a thud dimension is obtained

and the fibrils may he traced in most cases througl t their

entire course. On the other hand, of the relation of the con nective tissue to the cells of the growth very little can In studied owing both to the spreading of the mount ing and to the difficulty in obtaining a near control section.

In Spalteholtz' method, however, since alien are easily obtained, one being digested and the otlu r stained


■Johns Hopkins Hospital Reports. Vol. I. 1896. Reticulated Tissue.


intact, the relation of cells and connective tissue is readily studied, but owing to the thinness of the section the fibrils aie cut short and in in.iiu cases appear onlj as minute spirillar

forms, H nol hem:; possible to follow their course for any

distance.

The subject of elastic tissue in new growths has received a

n her of contribut - since the publication of Weigert's

elasl ic fibre stain.

MelniUw 1,'a-WMlenkow m Ziegler's Beitrage, Bd. 26, 1899, has described the distribution of elastic tissue in various organs in normal and pathological conditions, and states that , lastic fibres in health^ and diseased tissues are derived mainly

from the vascular walls, and further that in tumors rj h

formation of elastic tissue occurs. In the discussion on the paper, however, in the German Pathological Society in Munich,' a number of observers reported cases where an increase in amount was present. Bansemann reported a large increase of elastin in a ease of metastatic tumor in the spleen but had not found any, as a rule, in malignant growths. Kchmorl reported a case where aumerous elastic fibres were found in a carcinoma of the stomach. Orth and Nauberck found in carcinomata cases very many elastic fibres present.

Alice Hamilton 10 has reported a case of fibro-sarcoma of the brain in which then' was a very large amount of elastic tissue present; the tumor presented a very peculiar rosette arrangement and in places masses of considerable size surrounding blood-vessels, all of which masses were of a fibrillar nature, but clastic tissue was also present as wavy fibrils running among the cells without any apparent relation to a vessel wall or to the cells of the growth. She agrees with Melnikow Raswedenko^ as to the origin of elastic fibres from vessel walls but contradicts his statement that in tumors no new

formati E elastic tisst ccurs. In this case the amount

was much more than normal, but the relation was frequently to the periphery of the vessel wall, and where this relation was not found, the presence of elastic tissue was ascribed to

the obliteratii E the vessel or to the severance of the original

connection of the fibres.

II. W. Williams." in a paper on the new formation of elastic- fibres, gives a report of his study of 31 case- of carcinoma: 12 in the liver, l in lymph mule-. 2 in the thoracii duct. ? in large veins, 2 in the cerebrum, 1 in the lung, 8 in

the mammae, 1 in the skin, I in the st ach and 1 in the

rectum. The following are his conclusions:

I. \\ hen the stroma of a carcinoma is itself of new formation n i- usually free from elastic fibres.

■.'. Newly formed elastic fibres may occur in the stroma through rarely, and they are likely to be fine in quality and small in number.

. Tin. tumors in which newly-formed elastii fibn

curred either contained a large an m of coi tive-tissue

"Centralbl. f. alg. Path. U. path. Anal., X. S32. "•Jour, of Exp. Wed Vol IV. Noi - 5 and 6, 1899. "Contributions to the Science of Medicine. Dedicated to Wm

II, Welch. Haiti nore. 1900.


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CSTo. 11 l.


1 1, una or the new I y-fornied fibres were in connection with pre-existing elastic elements of the original parts.

lie found evidence of now formation in three rases of cari of the liver. In carcinomata of lymph nodes the stroma was usually free from elastic tissue and when present it was ih>! possible to demonstrate its new formation. In one carcinoma of the thoracic dud there was new formation and in two of the venous growths, in two of the cerebral cases, one secondary from an adeno-carcinoma of the lung and one secondary from the stomach, there were fine elastic

fibres present possibly connected with some prolongat "I

the pia mater. In the carcinomata of the mamma nothing was seen in |>rn\ e new formation.

Kromaver ,J found in rapidly-growing condyl ata. warts

and carcinomata of the skin no newly-formed elastic fibres. These were present, however, in older papill ata and fibromata.

There are also a considerable number of papers on the new formation of elastic tissue in other pathological conditions, to which reference will be found in Dr. Williams' paper."

In seven of the seventeen case- in the series here reported.

elastic fibres were f id, the description of which will be

found under the individual cases. In all cases they apparently had their origin fn m the vessel walls. In mil\ one case, No. 6,

a carcin a of the breast does there seem to be sufficient

ground for claiming an increase in amount or a new formation. The sections from this ease were compared with those from three normal breasts and three other carcinomata and contained a much greater amount of elastic tissue than any of i he "i he: s.

The safest method of judging the amount of new formation if such exists in any case would seem to be that of comparison of sections of the growth with sections of the normal tissue in which the growth was situated. This, unfortunately was only done in one case (case 18). In this case a portion of the normal breast in which the carcinoma had grown was prepared in the same way as the growth itself. A description of the comparison will be found under this case.

Regarding the origin and normal development of elastic fibres whether from the transformation of cells, by fusion. into fibres or from the transformation of the intercellular mat n\ there is still no sat isfactory answer.

< »n the subject of the study of tumors by digestion methods u" literal ure was to be found.

Desi i;i p'i in\ of I \iii \ i iii vi Cases. Specimen- \'o-. 1. I and 8. film. my ata of the uterus

Elastic Tissue. -In these case- there were no elastic fibres found either in the fresh preparations or in the hardened stained with Weigert's elastic fibre slain.


VonatFSchrift t. prakt. Dermatologie. Bd. XIX.


White Fibrous Tissue and Reticulum. — To the naked eye these sections gave the appearance of a fibrillary structure and under the dissect ing microscope the fibrillary nature was mure clearly seen. The tissue remaining after digestion was collected in places in thick nias.-e- ami strands, from both of which branches were given off and these again branched in turn. The thicker strands presented in plate- a distinct whorled appearance, and between the masses and strands minute wa\y fibrils were seen running in a more or less parallel direction and passing into and becoming continuous at mt her end with the thicker portions of the section.

Under the low power of the microscope the masses formed nodal points from which prolongations were given off, an infinite number of very line fibrils appearing in places.

The larger strands were composed of minute fibres in very close apposition to one another. These strands divided and united again and gave off branches, and from these branches


lJMt



Fig. 1. — Section of a flbromyoma digested by Spalteholz' method, showing the bundles of white fibrous tissue and the reticular network in the meshes of which the muscle cells lay.


and Erom the sides of the strands themselves there arose ' '■ eeedingly minute, very wavy, interlacing fibrils running in a course more or less parallel to one another, and in some places

arising from one strand and passing into and bee ing losl

in another si rand.

In other parts of the section between the strands was seen a very fine network similar to that obtained by Spalteholtz' thod to be described later.

"With the high power the fibrillary nature was mure clearly seen in smne parts, the fibrils being very wavy, in others quite straight throughout their course. The strands themselves were composed of the wavy interlacing fibres of white fibrous tissue while the minute network presented very much the ap


September, 1900. |


pearance of reticulum excepl thai in the anastomosis was observed.

In the preparations by Spalteholtz' meUiod very Little could be made < mt either with the paked eye or with the dissecting microscope, but with the Latter very minute apertures throughout tlif section were plainly seen.

Under the Low power, however, the condition described under the Van Gieson and Mallory preparal ions is verj i Learlj seen; viz., a connective-tissue envelope for each muscle-cell.

The connective tissue was verj abundant and formed 1>\

far the major porti E the section. It was arranged in

two ways.

1. Running in every direction and forming a large irregular network, Leaving meshes of varying size, were large strands composed of wavy interlacing fibres which followed a more or Less parallel course. In places these strands divide and unite again, leaving spaces which are occupied by the network in In described Later. In the midst of these strands are seen also the apertures of blood-vessels surrounded by denser tissue, the size of tin' vessel varying with the size of the strand.

■.'. In the meshes formed by this stroma was found a minute network apparently formed by the division, subdh i-ion and anastomosis "1 the branches of this stroma proceeding from all sides of it as it surrounded the individual spaces. The minute meshes of this second network are filled in the control specimen with single muscle cells.

I an Gieson Preparation. — To the naked eye the general impression of this section was red. but on holding it tip to the light areas having a yellowish tint were seen. These varied in size and were surrounded by a capsule id' deep red. Besides these areas there were certain parts of the section of a lighter and apparently Uniform red color, intimately connected with the capsules of the yellowish areas. The capsules surrounding the yellowish areas formed an irregular network throughout the remainder of t he seel ion.

With the dissecting microscope the darker capsules mentioned above were seen to run through the section looking like an injected vascular network. Tin- branches from this network ran into and divided the yellowish area- which they surrounded into -till smaller area-.

The lighter reddish masses -ecu with the naked eye were here not so uniform in color, but appeared a- a very close network of red -tamed tissue, and held in the meshes of this network were yellowish cell bodies similar to those found in

the other area-, hut here the rod -tamed material was :li

more abundant, the strands being thicker and the meshe? smaller.

Tin- general network of red stained connective tissue was irregular, the meshes varying in size, the larger bundles of led surrounding the larger yellow ish ana- and branches from these forming tin- walls of smaller areas, but even in thi strands of red, -mall groups of yellowish cells were frequently

-cell.

With the low poue, the uniform reddish masses were een to be composed of a dense network of comparatively thick strands of red with small meshes containing the yellowish


JOHJ 3 HOPKINS HOSPITAL BULLETIN

id inn- no definite


213


i ed bodies. These yellowish cells were evidently the muscle cells and will he so called in the further dtscripl

The genera] network of red could he traced with this power io much smaller divisions, in some cases the branching and anastomosing forming so small a network that the meshes of the same contained only a single muscle cell.

The larger strands of red-stained connective tissue had in places a definite whorled appearance and throughoul their substance were seen scattered the connective-tissue corpuscles. In these strands were also seen numerous blood-vessels the larger ones occurring in the larger strands and so on. The muscle cells of the walls of these vessels were stained yellow, similarly to those contained in the gem ral network.

I'nder the high power the network of connective tissue could he traced to still liner divisions, so (hat each muscle cell was here seen to have an enveloping capsule of its own. very line in most instances hut comparatively thick in others. In the midsi of the larger strand- occasional muscle cells were also present

.Mallory'.- stain gave a very similar picture to that obtained by Van < fieson's stain.

Specimen No. 2 was from a sarcoma of the litems, but contained so small a portion of sarcomatous tissue thai it was of very little service for study: still in the Spalteholtz preparation a reticular network similar to that found in other sarcomata was demonstrated in one portion of the section.

Specimen No. 3 was a portion of the wall of a multiloeidai' ovarian cyst and showed only a dense while fibrous tissue structure in which no elastic fibres were found.

Specimen Xn. •"> was an epithelioma of the inferior maxilla. This growth was of live and one-half years' duration, hut for niie year previous to its removal had grown very rapidly. Il involvi d the whole depth of the left half of the inferior maxilla from the ramus behind to a point 2 to ;; cm. hey I the

middle line in front. Il presented a lobulated appearance

with a reddish surface looking like granulation tissue I had

an act ively grow ing appearance.

No elastic lissue was found by either method excepl around the vessels.

Mall'- preparation was very unsatisfactory for study; the connective ti>siio remains forming a more or les> solid ma--. from which nothing but a fibrillary construction could hi' made out.

Spalteholtz' method showed a distribution of connective (issue similar to that described below under Mallory's stain

the parts of il nirol seeti ccupied by the large irn gular

masses of cell- being in the digested specimen quite devoid if ' -ounce five i issue.

The section stained by Mallory's stain gave in this ease the best idea of the distribution of the while fibrous tissue, its absence in the cellular areas ami its distribution* being controlled by the Spalteholtz' preparal ion

The < d win I, of lie- Section w;i- made up of evi


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| No. 11 l.


strands and bay-like processes of epithelial cells joined together ly their minute protoplasmic processes winch were very plainly visible and appealed in places as a reticular network; of this, however, nothing remained after di These strands of cells formed a connected network bul in certain place.- became condensed, lying much closer together in rows surrounding larger and smaller irregular -pace- which contained a fine loose aetwork of connective tissue, liolding

m ii- meshes numbers ol connective-tissue corpuscles and polymorphonuclear cells.

The connective tissue in these -paces was collected in the centre into bundles and masses of wavy fibres, and from ll e minute fibrils radiated outward in all direction- as an exceedingly minute fibrillary network, becoming gradually looser in texture until at the edge just inside of the rows of cells they curved and formed an interlacing ring of tissue which, however, -cut no processes among the cells of the growth. This latter condition was only demonstrated by (be Spalteholtz' preparation.

In several of these spaces there were also seen small bloodvessels su mm m the network.

Besides the connective tissue in these .-pace- there were several strands id' white fibrous tissue fibrils which divided

the section into smaller portions, but had no1 I n invaded

by epithelial cells. These strand- were evidently the origin of the connective tissue in the spaces, as many of the latter were found continuous with the former. The connective tissue in the isolated spaces had apparently been shut oil' by the invasion of the epithelial cells and had then commenced to throw out new fibrils, for in these spaces the connective

i puseles were in a very actively multiplying condition, the nuclei dividing and undergoing mitotic changes. The larger strands carried in their substance several large

blood-vessels. In r two places in the sections areas of

degeneration were present Idled with granular debris and polymorphonuclear cells, and around these areas, extending lor some distance among the surrounding cells, many polyi phonuclear cells were to be found.

Spei n No. 6 was part of a carcinoma of the lefi breasl

in a woman ."a; years oi age. The growth was of one year's duration and al the time of removal measured 5.5x5 cm.

Besides this larger nodule there was a sec I smaller growth

box L.7 em. in size. The nipple was slightly retracted ami there were metastases in the cervical and axillary glands.

Elastii /' ' " The fresh tissue teased out upon a slide and lamed with magenta -bowed a considerable number of purple stained elastic fibres varying in thickness, quite wavy and ( tilled at their free i nds

The frozen section stained with magenta also showed

elastic Idee- a] al croup- of cell... around the 1,1

ami b nijilial ic dm t- and .,. I be connect i v e-tissile

stroma.

In the preparation hardened i i solution and

stained with \\ eigerfs i lastii Bl i In sections presented, even to the naked eye, many bltie-sta d areas, repre


senting the elastic tissue. This was distributed throughoul the section in two ways: (1) Surrounding certain definite areas and marking these off distinctly from the iv-i of the section. (2) As minute lines running for short distances through the balance of the section.

Under the low power the areas mentioned above were composed of the cells of the growth grouped together in varying numbers from 5 or 6 up to many hundreds, and immediately outside of these croups was an irregular or serrated encasement of elastic tissue iii single and double layers, and outside of this again a layer of connective tissue in which were scattered many minute fibrils of elastic tissue. These were evidently the lactiferous tubules which had been invaded by the growth. Many elastic fibres were also preseni in the walls of the blood-vessels. There were also a number of very small area- containing only three or four cells which were com






4


.



Fig. 2. — Section of carcinoma of breast No. 6. staineil by Weigert's elastic fibre stain, showing the distribution of elastic tissue around a large nest of cells and in the surrounding stroma.

pletely surrounded with elastic tissue and in some places these areas themselves appeared in groups of three and four. Besides the above distribution there were also numbers of fibres of elastic tissue running in the connective tissue strands in double lines as if the remains of a vessel no longer patent. It was with the high power, however, that the very large anioimi of very fine elastic fibrils running through the -eci - could be made oui following mainly the white fibroustissue framework but often seen among the cells of the growth with apparently no other connective tissue accompanying them.

Many of the groups of cells were quite devoid of elastic fibrils around I hem

There was, apparently, an increase in the amount of clastic tissue in this growth, for in comparison with three normal


September, L900.]


JOl INS HOPKINS HOSPITAL BULLETIN.


211


breasts two from cases younger than the patienl from the presenl growth was removed," and three other carcinomata of the mamma, this growth contained a very much larger amount than any of the others. There were also so many minute fibrils differing from thai around the vessels an ducts found through the growth away from their apparenl

origin, thai the increase in amount seei I more probable.

White Fibrous Tissve and Reticulum.— Mall's preparation showed a network of strands varying in width from the thickness of writing paper to six or seven times this width, with meshes varying in size from a pinpoint to a pinhead: These meshes were quite clear and appeared as open spaces throughout the section.




Fig. 3. — Section of a carcinoma of the breast No. 6, digested by Spalteholz' method, showing a group of cell spaces outlined by bundles of wavy fibrils and the entire absence of tissue of any kind in these spaces.

In plaee- the c ctive tissue forming the network was

collet-ted into masses of considerable size up to an eighth o] a sixteenth of an inch in size. In other plates the larger strands surrounded an open space which was subdivided into two or more -mailer meshes by threads oi the smallesl width. The meshes were for tin mosl pari more or less circular in outline.

Sections were examined with low power magnifical

The meshes were nearly all quite clear: some, however, had projecting into them from the strands which surrounded them the fn e ends of tin fibrils of which these were con

The strands forming the network were composed of minute fibres running in a more or less parallel direction interming ling wit] another and for the most part quite wavy. -"


1 The. elastic tis iue apparently decreases in amount mamma atrophies after the menopause.


much so that in places, instead of running a continuous course, certain fibrils appeared as a succession of minute spirillse. The majority of the fibres could be traced through out t heir course.

In many places there was a cross fibrillation, with longitudinal fibrils underlying it. both free ends of the former being

seen, evidently the fibrils of the third di nsion of the cell

-pace.

In the thinner portions of the section a bundle of fibrils could often be traced down one side of a mesh ami curving around a second side, then at the third side dividing some of the fibrils, continuing around the same mesh, while otherpassed in another direction in the strand between two adjoining meshes ami so on. intimately interlacing with one another.

With the high pover the finer fibrillary nature of the str a

was much clearer hut there was no branching or anastomosis of the fibrils, each being traceable alone its course without interruption.

Spalteholtz' preparation showed a number of absolutely i [ear spaces outlined by wavy fibrils in bundles which in some

places Completely surrounded them, while in others they were

continued onward between two adjoining spaces after passing around one or two sides of a mesh. These clear spaces in the control specimen were Idled with the cells of the growth and evidently these had no intercellular substance between them.

The rest of the section was occupied by bundles of wavv

white fibrous tissue fibrils which frequently separated, leaving

clear spaces which were in th ntrol specimen tilled with

small groups of cells.

Mallory's and Van Gieson's stains threw no additional buhl upon the distribution of the connective tissue in this growth

Specimen No. 1 was from a small round and spindle-celled sarcoma removed from the thigh of a woman 59 years of age. The tumor commenced in the adductor muscles of the thigh and extended downward in the muscles to the popliteal space. It diil no] involve the muscles about the knee joint, but passed I iet ween the hones of the leg and involved the muscles on the anterior aspect of this. There were also large glands on the

front of the thigh of similar structure. In the thigh it c

pletely surrounded the femoral vessels and extended outward between the muscles four or five centimetres. In the popliteal space ii surrounded the popliteal vessels. Portions were obtained from the growth in the thigh through the femoral vessels and from tin tside of the growth.

Elastic Tissue. — The fresh specimens, both the teased and the frozen section, stained with magenta showed considerable n u in hers of elastic fibres varying in size and character from the fine branching fibres similar to those in areolar tissue to the coarser curly fibres resembling those in the ligamentum

nucha'. These fibres ran i rag the cells of the growth and

were found both in the section taken through the femoral vessels and in that from the outside of the growth.

In the Zenker preparation, stained by Weigert's method the blue-stajned elastic fibres were plainly visible to the nal ed eye. I ' nder t he low power the se een to b


216


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 114.


divided into lobules of different size by strands of white fibrous tissue ; the lobules being closely packed with the cells of the growth with very little evidence of intercellular tissue. The elastic fibres oei urred in the midst of the strands of white fibrous tissue and were most abundant in the largest strands but also in places running among the cells.

In the strands they existed as very fine straight branching fibres with free curling ends and also as short curly fibres, due possibly to both ends being free. They occurred also here and there in the section as mentioned above a- curly fibrils running among the cells.

In the section near the femoral vessels the elastic tissue was much more abundant. With the high power the branching of the elastic fibrils was more apparent. Some of the white fibrous tissue strands Mere quite free from the blue fibres, and as one proceeded from the femoral vessels outward the amount of clastic tissue grew less, although it was still


From the very large amount of elastic tissue found in this growth and from its varying character it would seem fair to conclude that there was considerable new formation of the tissue.

White Fibrous Tissue and Reticulum. Mall's Preparation. — For purposes of description the fibres forming this section after digestion may be divided into two groups:

1. Long wavy, more or less parallel fibres running in bundles through the sections, the fibres interlacing with one another. These were evidently white fibrous tissue, and in the control specimen this tissue divided the section into lobules. and in the Weigerf preparation it carried the elastic fibres.

2. Exceedingly fine fibrils which formed the ground work ami main portion of the section and lay between the bundles of the first group. They formed a very minute meshwork running in every direction, definitely branching and anastomosing and presenting very much the appearance of reticulum



PIG. 1. — Section of sarcoma No. 7. stained by Weigert's method for elastic fibres, showing in dark curling lines the distribution of the elastic fibres. At one side of the section the femoral vessel is seen outlined by elastic tissue and surrounding this are seen layers of elastic fibres lying among the cells of the growth alternating with layers of white fibrous tissue.

present in considerable quantity in the sections from the

outside of the .".l"W I li.

A very peculiar arrangement was present around the femoral vessels. The small round cells had encroached upon the walls of the vessel to the endothelial lining, and from this outward were ranged in definite order layers of small

round cells with elastic fibre ig them, succeeded bj la i rs

of white fibrous tissue with very few elastic fibres one above the other for many layers. The fibres near the vessels were,

as a rule, much thicker than those found in th ttskirts of

the growth.

I Inna's orcein stain gave a verj imil tun to t he above

with the elastic tissue stained a silk\ brown


Pig. 5. — Section of sarcoma No. 7, digested by Mall's method, showing the strands of wavy parallel fibrils and the groundwork of minute reticular fibrils occupying the remaining portion of the section. The appearance of a focal origin of these fibrils is quite evident in certain spots.

of normal glands. In some places the fibrils appealed to arise from focal point- spreading out in all directions and uniting with fibrils from other points.

Under the high power the fibres of the first groups appeared as above but in the reticular network the branching and anastomosing of the fibrils was much more evident. This network seemed to have no direct connection with the first group but extended a short distance among its fibres as if t<> gam anchorage there, for in the centre of these bundles they were not nearly so evident.

Throughout the section the apparent focal origin of these fibrils may be due to four or five of these overlying each other at a certain spot.

Spalteholz' Preparation. — These sections were much thinner


September, 1900. J


JOHNS HOPKINS HOSPITAL BULLETIN.


than those by Mall's method, but showed the sari interest: the strands of white fibrous tissue dividing tl t ton into lobules, and between these strands, and forming tin balance of the section, an exceedingly minute network of deli cate fibrils which branch and anastomose, the meshes of which

were in the control specimen occupied bj the r id and

spindle cells of the growth, bj single cells in mosl cases, bul in

some cases apparently by groups of two or thn ■ possibly

iv Eowever, in those spaces which were occupied bj

groups of cells there was often seen in this specimen a jutting branch a- if it had been divided in cutting the section, The apparent focal origin of these fibrils was also uoticed in i bese sect ions.

Specimen No. 9 was from a carcinoma of the uterus.



Fig. 6. — Section of sarcoma Xo. 7 digested by Spalteholtz' method, showing the reticular network with the branching and anastomosis of the fibrils.

It showed no elastic fibres in the fresh preparations bul in ■ I ion stained l>y Weigert's stain then -■■en in the connective-tissue stroma minute curly fibrils

extending for some distance fr the vessel's wall, from which

they had probablj arisen.

White Fibrous Tissue.— The sections studied by Mall's method were too thick for accurate observation but the clear spaces of the carcinomatous growth were elearlj -ecu outlined by bundles of wavy parallel fibres of white fibrous tissue.

In Spalteholtz' preparation the cell nests and groups of cell

nests lay embedded in the connective tissi f the muscle

wall but were separated from the same by bundles d! parallel fibres. These bundles formed a delicate framework, enclosing large meshes which were quite clear in section and filled with cells in the i ontrol pei i


quently the bundles after passing around i side of a mesh

would divide into two -mailer bundles which would then take pari in the Eormation of the walls of adjoining meshes. Or again, complete rings of lour or five »;m fibres were found in apposition at certain points, leaving between them a clear space, which space was also Idled with cells in l he control section.

Tin' Van Gieson and Mallory preparations showed the closely packed cell nests lying in the muscle wall of the uterus surrounded by connective tissue, hut without the slightest i \ idence of intercellular i issue.

Specimen Xo. in was from a small round-celled alveolar sarcoma arising from the periosteum of the tibia and invading the tibialis anticus muscle in a girl thirteen years of age. It involved the popliteal glands and also a chain of glands extending along t he scial ic nerve.

The growth was exceedingly sofl and on cutting u a creamy fluid was expressed.

Xo elastic tissue was found except around the blood-vessels.

In the preparation by .Mall's method the connective tissue «;i» very abundant and disposed in a rather coarse network with comparatively thick strands enclosing varying sized meshes, which to the naked eye appeared quite clear.

Under the low power the section was seen to he composed of a network id' thick strands leaving meshes of varying size and shape. The strands were composed of bundles of minute fibres which ran a comparatively straight course. The fibres could often he traced curving around certain meshes, interlacing w ith li I ires going in an opposite direction and continuing on their course around and between neighboring meshes. 'fin- meshes were for the mosl pari quite (dear. Iii some, however, there was seen a minute reticular network, the fibrils of which branched and anastomosed.

The meshes in the control specimens were partially filled with small round cells. In many place- the meshes were divided by single fibres into smaller meshes, and in some

portions of the section when' the fibrous tissue was -i

abundant there was found a definite reticular network outlined \i\ bundles of wavy fibrils. This network was composed of anastomosing ami branching fibrils similar to that desi ribed ii ease No. '.- The -mall meshes of this network were filled

with the cells of t he grow th.

The larger meshes were so loosel} filled with cell-: in the stained specimens thai it would seem probable that they had contained also the creamy lliiid which was expressed on cuti nig the fresh i issue.

In Spalteholtz' preparation there was no connected network on account of the thinness of tie- section. It was composed of minute wavj fibrils running in various directions ami oul

lining irregular 3] - w Inch in the control specimen were

loose!} Idled with cells. The white fibrous tissue framework was here of a \>'v\ loose texture and the interstices lefl by this separation of its fibre ivere idled with -mall round cells in

I he eont lol -eel io||.

Iii the midsl of the clear spi frequently seen cir


218


JOHNS HOPKINS HOSPITAL BULLETIN.


| No. 11 1.


cular wavy fibrils completely enclosing small spaces which were also filled with cells in the undigested specimen.

Numerous vessels in the undigested section were repre sented in the digested section by small rings of connective \ ing in the framework.

The stained specimens showed numbers of groups of muscle fibres lying among the cells of the gro\i th.

Specimen No. 11 was taken from a carcinoma of the uterus

and contained only a very small amouni of carci latous

tissue.

\o elastin was present except around the blood-vessels. The other preparations resembled carcinoma No. 9 in every way.



  • - 3£nz



Fn ;. 7. — Section of scirrhous carcinoma of the breast No. 12, by Mall's method, showing the distribution of white fibrous tissue around the small irregular clear cell spaces.

Specimen No. L2 was a scirrhous carcinoma of the breast from a woman l!i years of age. The growth was of six months' duration and involved also the axillary glands on the same side. The nipple was retracted and the skin adherent to t he growth.

This growth showed both in fresh and hardened preparations considerable numbers of elastic fibres around the vessels ami lactiferous ducts; also around certain groups of cells, and scattered as short wavy fibrils through the abundant connec1 1\ e-1 issue -i roma.

hi the fresh digested specimen the white fibrous tissue was very abundant in bundles of line wavy parallel fibres running in every direction and i nclosing spaces of varying size. The bundles were in many places very thick ami the fibres composing them very close together es< however, gradually spread out leaving in their i [ear spaces. Or

again, branches from those larger bundles would gradually


thin out and divide to enclose clear spaces and frequently these spaces were separated from one another by a single fibril. There was no anastomosis of fibrils and no reticular network. The clear spaces were filled in the control specimen by small groups of cells, the largest containing probably fifteen or twenty cells, the smallest only two or three.

Spalteholtz' preparation gave in a thinner secti nuch

the same picture. Here the wavy fibres were present in bundles which gradually spread out and divided to enclose clear spaei's of varying size which were occupied by the cells of the growth in the control section.

This specimen differed from Nos. 6 and 18 (a) in the very much larger amount of connective tissue: {!>) in the smaller and irregular grouping of the cells, and (c) in the smaller amount of elast ic t issue.



Fio. 8. — Section of fibro-sarconia of the liver No. 13, by Spalteholtz' method, showing the large amount of fibrous tissue surrounding the clear cell spaces.

Specimens Nos. 13 and 1-t were from carcinomata of the liver and rectum in tin 1 same individual. The growth was primary in the rectum, where it formed a mass ', x ti cm. in size and Idled the whole pelvis. There were numerous secondary nodules in the liver from '.' nun. to ."> cm. in diameter. They were firm, opaque ami yellowish ami surrounded by a zone of greenish-yellow liver substance. The rectal growth had eroded the sacrum and was adherent to it.

These two specimens were of so similar a nature that only one description will lie given for both, noting any differences thai existed.

The specimens when obtained had already been kept about four days in the ice chest, so that the fresh preparations for elastic tissue were not satisfactory. In the rectal growth, however, by Weigert's slain a few scattered elastic fibres were found running in the mid-t of the general white fibrous stroma.


JOHNS HOPKINS HOSPITAL KULLBTIN.


219


White Fibrous Tissue — Both growths contained ;i greal deal of connective tissue, the liver growth more than th growth. The type was the same in both, bundles of waw more or less parallel fibres running in every direction and outlining clear spaces of varying size which were filled with epithelial cells in the control section. These sections resembled very much the scirrhous growths from the breast, bu1 the fibrous t i~>m- was here even more abundant.

In Spalteholtz' preparation the section was thin, the thickness of two or three fibres. The fibres ran in many din their further course in any one direction ceasing when iln \ ■encountered bundles running in an opposite direction. In the midst n!' the bundles minute openings were seen where the constituent fibrils separated slightly from one another, and in these spaces the connective tissue corpuscles were seen to lie in the control specimen. Eere also the curving ol the fibres around two or more sides of a clear space and onward between two adjacent spaces was clearly seen.

Specimen No. L6 was from a scirrhous carcinoma of the breasl of eighl years' growth in a woman forty-four years

This growth resembled very much thai described in No. 12. It contained, however, many more elastic fibres running through the white fibrous stroma, bul these were confined to the stroma and to the ducts and blood-vessels, and did no! in any rase surround groups of cells, nor were they oearly so abundant as in case No. 6.

Specimen No. 1' was from a small round and spindle-cell sarcoma taken from the axillary region. It had a thin translucent capsule and could so be separated from the surrounding tissues, the connection consisting only of fine branching

> 0] stive-tissue fibres and numerous small blood-vessels. Its

origin was evidently from the intermuscular connective tissue and the growth itself was soft, elastic and lobulated, measuring I3£xl0xl8 cm. Its duration was 20 months, and H involved also a number of glands in the supra-clavicular fossa.

No elastic fibres were funnel in either the fresh or hardened preparations.

The digested specimens, both by Mall's and Spalteholtz' method, showed tie same reticular network as that described in section No. ', . and also the same white fibrous bundles enclosing this network. Neither the Van Gieson nor Mallory preparations showed the large amount present nor its distribution.

Specimen No. 18 was from a car< inoma of the breasl of four months' growth in a woman thirty-seven years of age. V

i was present as a hard regular mass freely movable

and measuring I \ 2 cm. in size.

This was an exceedingly cellular growth, thus differing from eases No. 12 and 16, but it resembled very ram No. 6 both in the distribution of elastic and whiti tissue and in the type of cell of n hich it was compi


thai in the latter instance No. 18 was of a much more malignant type filled \utli young cells ami almosl resembling a small round-celled sarc a.

Elastu Tissue. The elastic tissue here was disposed in a very similar ua\ to No. r,. inn was not so abundant.

In tin- growth a comparison was made with a portion of normal breast Erom the same ease with reference to the amount and distribution of the elastic tissue with the following result: thai the elastic tissue in the growth was found to be not so abundant a- in the norma] breast, hut differed somewhal in distribution. In the normal structure the elastic tissue was confined to the coats of the vessels and lactiferous ducts occasionally occurring in bundles in the stroma of the gland, while in the growth, besides being around the vessels. it was present surrounding large groups of cells, evidently invaded duels, and as minute wavy fibrils was most abundanl

in the str a. hut frequently was found in among the cells

with apparently no white fibrous tissue accompanying it: also as bundles of fibres which were infiltrated w ith epithelial cells.



t'e a. — Reticular network from sarcoma of axilla No. IS. prepared by Mall's method.

In spite of the very cellular condition of the growth il presented on digestion the distribution of fibrous tissue desi ribed under case No. 6 of huge (ell spaces with no intercellular network.

( lONCLl -ion-.

1. Elastic fibres are frequently presenl in new growths: I'M in tic stroma; (b) among the cell-; (c) around the bloodvessels, and (d) iii breasl tumors around the lactiferous ducts which have been included and invaded bj the growth.

'!. When presenl thej are usually in connection with preexisting elastic-tissue elements in the original tissue in which t he I umor has grown.


220


JOHNS HOPKINS HOSPITAL BULLETIN.


| tSTo. 11 1.


3. N b formation probably occurs but can onlj bi deterbj a comparison of thai presenl in the growth with that present in the norma] tissue in which the growth has arisen.

I. Sarcomata present a large increase in connective tissue and possess an exceedingly fine intercellular retii alar network \.i\ similar in structure I" the reticulum present in normal glandular tissue.


5. ( larcinomata possess a stroma of w bite fibrous tissue, outlining the cell spaces, but have no intercellular network.

6. The digest inn methods present a possible means of diagnosis between carcinomata and sarcomata in doubtful eases.

7. Uterine myomata bavea very large amount of connective tissue both of a white fibrous and reticular nature, possessing a connective-tissue capsule for each muscle cell; ami it would he more correctly termed fibromyomata.


ON THE RELATION OF THE ELECTRICAL CONDUCTIVITY OF BLOOD-SERUM TO ITS

ALLEGED BACTERICIDAL POWER.

By Km ma Lootz \m> Alice Weld Tallant. (From tin Pathological Laboratory of the Johns Hopkins I niversity and Hospital.)


A- i- well known, it i- asserted thai bl l-serum possesses

iirt. mi bactericidal properties, and many experiments tend

tn show that these properties are lost when the ser heated t<> from 55-60° C. In a recent article Baumgarten 1 advances the theory that the bactericidal power of the serum is due. nut tn the actual existence of bactericidal substances in it. Imt to the fad that bacteria, in being transferred from their natural surroundings to another medium, undergo sudden changes in assimilation ami plasmolysis.

Following the hue of thought of this article. Dr. I.. F. Marker suggested that the writers undertake experiments to discover whether any physico-chemical change could he demonstrated in serum heated to the specified temperature. Electro-chemical examination of the conductivity of the serum was the method chosen, ami the Eollowing experiments were carried out:

The serum was carefully obtained from dog's blood in the

pathological laboratory; the work on conductivity ua- d ■

in the Chemical Laboratory of the Johns Hopkins University. through the courtesy of Dr. Harry ('. Jones. The apparatus used is described bj Dr. Jones 1 ' as follows:

"J is a small induction coil, with only one or two layers of wire. A larger coil must not he used, sine.' it does not sharp tone minimum in the telephone. The coil tuned to a very high pitch, should he enclosed in a bos -inrounded by a poor conductor of sound, and placed at some distance from the bridge where the reading is to he made. I'i" '"'I i- driven by a storage cell of medium size. A platinum wire, or better, one of manganese alloy, which has a -mall temperature coefficient of resistance, is tightly stretched over the meier -ink AB, which i- carefully divided into millimeters. A rheostat W. whose total resistance amounts to 1 1.1 10 ohms, is convenient. The resistance vessel R, containing the solution and electrodes — the electrodes are out from

1 P. Baumgarten. Beitrage zur Lehre von der natiirlichen Immunitat. Bert. klin. Wchnschr., No. 41. Oct. 9, 1899.

-Harry C. Jones. The Freezing-Point, Boiling-Point ami Conductivity Methods.


thick sheet platinum, ami into each plate a stout platinum wire, about an imh in length, is welded. Mass tubes are sealed on to the platinum wires and electrode plate-, by means of sealing glass. . . . These tubes pass tightly through a rubber cap, w Inch lits over the glass vessel. They are filled to a convenient height with mercury, ami electrical connection, established by means of copper wires, which dip into the mercury. One arm of (he telephone, T, is thrown into the circuit between the rheostal ami the resistance, ami the other arm i> connected with the bridge wire h\ means of a slider. This is moved along the wire until that point is found at



which the hum of the induction coil ceases to he heard in the telephone. Let this he some point ( '. and let us represent AC by a. and BC by h. the resistance of the solution in the vessel K by r. and the resistance in ohms m the rheostal by w: then, from the principle of the bridge, we bave


wh wb


But the conductivity of a solution, e. is the reciprocal of the resistance, r: therefore.


September, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


221


wb

... A cell-constant, C, must be introduced and determined for each cell before it can be employed for conductivity measurements."

In calculating the molecular conductivity of a substance, its molecular concentration must be taken into account, but in these experiments this was not considered necessary. The results given in the tallies express the conductivity simply as the reciprocal of the resistance, r. according to the formula

r , va c = C

wb

The material used in the experiments was dog-serum, obtained under proper aseptic precautions. In the first experiment the serum was heated from 34 to 70 I !., and its conductivity tested at the following temperatures: 3 1 . 30 , 38 . 50°, 51°, 52°, 53°, 54°, 55°, 56°, 57°, 58°, 59°, G0°, 70°. It was then cooled to 38°, and its conductivity again tested. The material was kept at each of these temperatures long enough to ensure a constant reading, and the temperature was not raised above 70°, on account of the changes in concentration which would have occurred from evaporation.

Five more experiments were performed with serum taken from different dogs. The conductivity was tested at 34°. the material was then heated to 57° and kept at this temperature for one hour, after which it was slowly cooled to 24°. and


the conductivity again tested, to discover if any change had taken place. The results of these experiments are incorporated in the following tables. The figures in each case repre-ciit the mean of three readings.



EXPERIMENT I.



24°


11.833


55°


. .. 19.388




5<;°


19.643



14.696


57°


19.881


50°


17.S73


58°


30.183


51°


IS. Hi


60°




18.536


.... 30.78




70°


23.253


54°


19.053


After eooling




3S°


14.743


The gradual increase in conductivity is. of course, due to the rise in temperature.


Experiment II. Experiment III. Experiment IV. Experiment V. Experiment VI.


24° 24° 24°


Before In iiTiiil'

to 51 e

for 1 hour.

11.436

11.786

11.48

11.446

10.546


After heating to

57° C. for 1 ur. and

again cooling

to 24° C.

11.466

11.763

11 186

11.446

10.56


The results of the above experiments go to prove that the alleged loss of bactericidal power in blood-serum heated to 57° is not due to any chemico-physical change which can be demonstrated by the conductivity method.


A CONTRIBUTION TO THE STUDY OF MALIGNANT TUMORS ARISING IN

CONGENITAL MOLES.

By R. H. Whitehead. M. D.. Chapel Hill, N. C. (From the Pathological Laboratory uf the Johns Hopkins I niversity and Hospital.)


In 1893 TJnna' announced his belief that melanotic malignant tumors which originate in pigmented moles should he classed as carcinomata. He based his opinion upon an examination of some tumors of this sort, and especially upon a study of moles obtained from newborn and very young children. According to him, the groups of pigmented cells commonly found in moles are derived from the epidermis during embryonic life or early childhood by being cut oil' from the interpapillary processes of the rete Malpighii, and afterwards losing their prickles and undergoing other metaplastic changes. He concluded, therefore, that melanotic tumors arising in moles are not sarcomata, but carcinomata.

Since, at that time, it was generally held thai tie so-called mevus cells were of endothelial origin, TTnna's statement aroused considerable opposition. Green 2 denied the epider


1 I'nna, P. G. Naevi und Naevocarcinome. Bert. kiln. Wchnschr., 1S93. XXX, 14.

2 Green, L. Ueber Naevi pigmentosi. Virchow's Archiv, 1893, CXXXIV, 331.


mal genesis of the nasvus cells, and pointed out that there is no relation between the amount of pigment in them and that in the epidermis — that it may lie present in either situation while absent from the other.

Then Bauer,* a pupil of Eihhert, investigated the subject, and reached conclusions quite the opposite of those of Unna, even after examining Unna preparations, lie convinced himself that the mevus cells were of endothelial origin, and staled, furthermore, that the individual cells in the groups were

separated froi le another by a line fibrous network, and

that, they were frequently branched so as to resemble stellate connective-tissue cells.

Luliarsch* stated that he had examined a considerable number of moles in newborn and young children, and had


■ Bauer, C. Ueber endothellale Hautwarzen und ihre Beziehungen zum Sarcom. Virchow's Archiv, 1895, CXLII, 407.

' Lubarsch-Ostertag. Ergeb. d. allg. Pathol., etc., Wiesbaden, 1896, Bd. II, S. 379.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 114.


not been able to detect any correspondence between the najvus cells and those of the epidermis.

Unna, however, did not tail to find supporters. Delbanco,* as the result of his study of two moles, stated that the interpapillary processes of the epidermis are frequently in direct connection with the groups of najvus cells, and that, owing to proliferation of the stroma of the mole, numerous epidermal cells are separated off into groups and afterwards displaced into the lymph vessels.

Kromayer" rejected Delbaneo's conclusion that the nanus cells are contained in lymph vessels, but agreed with him and with Lima in deriving them from the epidermis. This investigator describes in the moles of infants cyst-like spaces filled with cells containing vesicular nuclei. They are situated in the epidermis, between the epidermis and the subjacent connective tissue, or entirely within the latter. He thinks that all of these groups of cells become enclosed by connective tissue later on, and that then the cells throw off fibres, until finally little is left of the individual cells save nuclei closely applied to fibres — that, in fine, the epithelial are metamorphosed into connective-tissue cells.

Lubarsch, 1 in a critical review of the work done up to that time, expressed the opinion that the researches of LTnna, Delbanco, and Kromayer were individual interpretations of microscopic pictures rather than objective descriptions of appearances actually observed, and that their illustrations were susceptible of more than one interpretation. Thus, he claimed that Kromayer's picture representing nests of naevus cells in the epidermis could be reproduced by oblique sections of the skin in conditions characterized by elevations of the epidermis, as the result of growing or proliferating papilla?. Xor was he willing to accept Kromayer's metaplasia of epithelial into connective-tissue cells, holding that the law of the legitimate succession of differentiated cells was too well established to be surrendered on such proof as Kromayer presented. He criticized also the method with which Kromayer worked, and was not convinced by his original preparations. Still, he was unwilling to deny the possible existence of epithelial naevi.

A little later Scheuber* made serial sections of several pigmented moles, and convinced himself that Unna's view as to the origin of mevus cells was correct.

Recently Gilchrist' 1 1 as made an investigation of the subject, and. from the study of a pigmented mole in an infant, arrived at the conclusion that the naevus cells are developed in the waj described by Unna.


s Delbanco, E. Epithelialer Naevus. Monatsh. f. prakt. Dermat., 1896, XXII, 105.

• Kromayer, E. Zur Histogenese der weichen Hautnaevi. Dermat. Ztschr., 1896, III, 263.

'■ Op. cit., S. 591.

8 Scheuber, A. Ueber den Ursprung der weichen Naevi. Arch, f. Dermat. u. Syph., 1898, XLIV, 175.

» Gilchrist, T. C. On Malignant Growths Arising from Pigmented Moles. Jonrn. Cut. and Genito-Urin. Dis., 1899, XVII, 117.


Finally, Schalek "' has studied some pigmented moles and melanotic tumors of the skin, and has satisfied himself of the correctness of Unna's views.

In the midst of such difference of opinion one finds it difficult to reach a definite conclusion as to the nature of the naevus cells; but the pictures of Scheuber and of Gilchrist are, to say the least, exceedingly suggestive, and one may fairly be permitted to hold the view that in some moles, at Least, the groups of cells are modified epithelial cells of epidermal origin. Should a tumor spring from such cells, we should, naturally, expect it to follow the type of carcinoma. This expectation, however, is not always realized. Tuna." indeed, states that all id' these tumors which he has studied presented the structure of alveolar carcinoma (carcinoma simplex). On the other hand, the nine tumors of this class which I have been able to examine, had that histological structure which most pathologists have agreed to call alveolar sarcoma, and were so pronounced by competent observers. While we may well hesitate to be dogmatic in such matters. yet one is reluctant to regard as a carcinoma a tumor which presents so many characteristics of the sarcomata.

The following rases are reported not so much with the hope of throwing new light upon this vexed question as rather to call attention to the fact that tumors may spring from congenital moles which represent the same processes as those going on in the melanotic tumors, with the exception that they totally lack true melanotic pigment.

( lse 1. — The subject of this tumor was a white man aged 47 years. He had noticed, as long as he could remember, a " black mole " on the front of his right forearm a little above the wrist. For the last few weeks this had been enlarging rapidly, so that when I saw him there was in the situation mentioned a perfectly black tumor, conical in shape, and about 2 cm. high. The color was (\w largely to clotted blood, with which the tumor was encrusted, owing to frequent hemorrhages. The growth was removed by incisions carried widely into apparently healthy tissues. Eight months afterward- 1 learned that he had died "with tumors all over him." They were estimated as at least 200 in number, were situated in and beneath the skin, and varied in size from that of a pea to that of a hen's egg. Towards the end of his life he suffered much from frequent painful micturition, and on several occasions passed in his urine fleshy masses believed by his medical attendant to be pieces of tumor.

On section the tumor was deeply pigmented in places, and was spongy and friable, tending to crumble to bits when handled at all roughly. It arose by a broad, short pedicle a little more than one cm. thick.

In longitudinal sections through the pedicle the latter is seen to be formed by dense fibrous tissue containing sweat


10 Schalek, A. Contribution to the Histogenesis of Melanocarcinoma of the Skin. Journ. Cut. and Genito-Urin. Dis., 1900, XVIII, 145.

11 Unna, P. G., op cit.


THE JOHNS HOPKINS HOSPITAL BULLETIN. SEPTEMBER, 1900.


PLATE XVI.







Pig. L- Shows structure of the tumor in Case I






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September, 1900.]


JOHNS HOPKINS HOSPITAL BULLETIN.


223


and sebaceous glands and a few hair roots. Proceeding towards the tumor proper, many .young capillaries are encountered containing numerous polymorphonuclear Leucocytes and

surrounded, here and there, by groups of small round cells. In this region pigment begins to appear as small masse- of a yellow-brown color. In some cases these masses are contained in branched cells: in others I am unable to decide whether they are intra- or extracellular in situation. Near the pedicle the arrangement of the tumor is alveolar in character, though the stroma soon becomes very scanty, the walls ..I the alveoli being quite delicate and furnished by a lew spindle-shaped cells. The cells within the alveoli are, in the main, large and polygonal; their nuclei arc fairly constant in size and appearance, being vesicular with nucleoli and grains ■ if chromatin, (.'ells with several or budding nuclei arc frequently seen. In certain alveoli fnun which some of the tells have been removed by shaking, it can he seen that the cells are separated from one another by a very line reticulum, which appears t>> consist in large part of processes from the cells themselves. Many of the cells contain pigment in the form of yellow-brown grains. Farther towards the periphery -I the tumor the alveolar is succeeded by what may he termed a diffuse arrangement of the cells. Here the stroma, reduced to a minimum, is represented only by a few parallel rows of endothelial cells running here and there through the large masses of cells. It is difficult in this region to detect any intercellular substance; occasionally one sees cells with fibrillar processes. Very common are exceedingly large cells, spherical and multinucleated, containing many granules of pigment. The superficial portions of the tumor are inflamed or necrotic, and infiltrated with blood. The areas still living consisl of large vascular spaces lined by endothelium and surrounded by masses of tumor cells. The epidermis near the pedicle is thickened, but no connection can be made oui he t and the tumor proper. In other situations the epidermis has broken down before the invading masses of tumor cells, which grow through and project beyond it. II has entirely disappeared from over the greater portion of the surface of the tumor. In the thickened epidermis a few epithelial [i arls were noticed, some of which contained pigment. The tests i >r iron-containing pigment resulted negatively.

Here we have a typical example, in an advanced sta ih malignant melanotic growths which spring from the naevus cells of congenital moles — the najvocareinomata of Tuna, or the alveolar melanotic sarcomata of most author-.

Case '.'. — This tumor was obtained, through the kindness of Dr. ('. S. Mangum, from a white woman -">0 years old. She consulted Dr. Mangum concerning a large mole situated over the inferior angle of the left scapula, ft had been present "all her life," but only recently had been enlarging. Dr. Mangum thought best to remove the mole, especially as there were evidences of beginning ulceration. The mbse Mm ht history, unfortunately, could not be fully obtained. It was learned, however, that the wound made by the opera tion never healed, and that the lymph nodes in the left axilla


soon became enlarged. About eighteen months after the operation she was considered by her family physician to be dying of a malignant tumor of the uterus.

The tumor is about 2 cm. long, and 1 cm. thick. It presents the macroscopical appearances of soft papilloma, its surface being corrugated. It possesses a short, narrow pedicle. On section it is seen to be pigmented in streaks of a dark slate color.

In sections made through the center of the mole including the pedicle, the latter is found composed of fibrous tissue; its arteries are thickened, and there are some patches of small round cells. In these sections the structure is quite suggestive of carcinoma simplex. There are variously shaped alveoli, for the most part long and narrow, whose walls are thick and formed by dense fibrous tissue with scanty spindle cells. The cells within the alveoli are packed closely without visible intercellular substance. They are regular in size and appearance, being rather small polyhedral cells with pale vesicular nuclei. This area, doubtless, consists of normal mole tissue.

Sections made through the other portions of the tumor, however, present a different picture. The most prominent feature is furnished by large, more or less round collections of cells surrounded by capsules of dense fibrous tissue. They are not all alike, but may be divided into two varieties. The more numerous ones are composed, in the main, of small polygonal cells with deeply staining nuclei, though occasionally one sees a very large cell with more than one nucleus. The primary mass of cells is subdivided into much smaller masses by a spindle-celled connective tissue, which runs in from the surrounding connective tissue, and conveys vessels. In most cases this tissue is quite scanty, and often the subdivisions seem to be separated only by narrow cracks, the boundaries of which are the tumor cells, though sometimes a tew spindle cells can be seen bordering them. Xo intercellular substance can be made out between the cells in the subdivisions. In

si ■ ol' tin' masses the thickness of the connective tissue

septa is much greater than in those just described, and then .in appearance is produced somewhat like that described in sections through the center of the tumor.

The cell masses of the second variety are not so numerous as those of the first, and arc not so sharply circumscribed. The cells composing them are, for the most part, very large and round, and many of them contain more than one nucleus. They are separated from one another by a delicate reticulum, which frequently holds deeply staining nuclei; or several cells may be shut oil' into small groups by portions of the reticulum. As a rule, the cells towards the periphery of these masses tend to assume the spindle shape, and gradually fade away into the surrounding connective tissue. Areas are observed where a mass of the first variety is passing by gradual transition into one of the second variety. Moreover, in the case of both varieties, columns ol' cells advance into the surrounding stroma, where they usually lend to the spindle shape.

The stroma of the tumor is furnished by a central trunk of fibrous tissue, which gives off branches here and there to sur round the cell masses alluded to. It conveys many blood


224


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 114.


. around which are some patches of small round cells

and many plasma cells, and contains scattered, long, narrow

spindle nuclei. In several places this tissue is losl in diffuse

of large spindle-shaped cells, for which it seems to

form an intercellular substance.

The surface of the tumor is covered everywhere by epidermis, which is necrotic over a considerable extent of the tumor. Where the epidermis is intact, il is seen to be very thin — it is reduced to two or three layers of cells — and is separated from the subjacent tissue by distinct lines of connective tissue. Some epithelial pegs project from the epidermis, but they, too, are very thin, and show no connection with the tumor cells. The pigment was found chiefly along the course of the blood-vessels and in the most superficial parts of the growth, where hemorrhages had occurred. Much of it responded positively to the ferrocyanide of potassium


test, and the remainder was amorphous hsematoidin contained largely in polymorphonuclear leucocytes.

In this case, it, would seem, the processes which occur in the malignant melanotic tumors are undoubtedly going on — the development of a malignant tumor from the nests of mevus cells in a congenital mole, but with the exception that true melanotic pigment is not present. A priori, we should expect to find such tumors, for Green 1 " has shown that the naavus cells are not always pigmented, nor are tumors which arise in melanotic tissues invariably melanotic, but I have not been able to find the records of a similar case. Unna" hints at the possible existence of such growths, but makes distinct mention only of melanotic tumors.


12 Green, L. op. cit.

13 Unna, P. G. Die Histopathologic der Hautkrankheiten. Berl., 1894, pp. 746-752.


INORGANIC FERMENTS. 1

By Harry C. Jones, Ph. D.,


Associate Professor of Physical Chemistry Johns Hopkins University.


A paper bearing this title has recently appeared by Bredig and Miiller von Berneck. 3 The authors first point out certain analogies between the action of ferments and the contact action of metals. Alcohol is oxidized to acetic acid by the oxygen of the air as well by finely divided platinum as by the organic ferment mycoderma aceti. Calcium formate is decomposed into calcium carbonate, carbon dioxide and hydrogen, not only by certain bacteria, but by finely divided iridium, rhodium, or ruthenium, finely divided platinum, palladium, iridium, osmium, etc.. have the power of inverting cane sugar, like invertose.

The above relations are, however, only analogies. To determine whether there is any close relation between the action of organic ferments and finely divided metals, some reaction effected by both classes of substances must be carefully studied.

The reaction chosen by the authors of this paper is the decomposition of hydrogen dioxide. This reaction is effected by all organic ferments and, also, by finely divided metals, in the sense of the following equation:

ll ; o, = ILO +

The metal chosen was platinum, and a colloidal solution of this substance was prepared as follows: Two platinum wires about 1 mm. in diameter were immersed in a vessel containing very pure water. These were placed at a convenient distance apart, and a current of from 8 to 12 amperes and 30 to 40 volts passed between them. There was thus formed an arc between the platinum poles beneath the surface of the water. Platinum was torn off from the cathode in a


1 Presented to the Johns Hopkins Hospital Medical Society. "Ztschr. phys. Chem. (Jubelband zu van't Hoff), 31, 258.


very finely divided condition, and quickly gave a blackishbrown color to the surrounding water. The liquid was then rapidly filtered through a folded filter to remove any larger particles of platinum which may have been torn off. The colloidal solution of platinum is a clear, dark brown liquid, which, when examined