Talk:The Johns Hopkins Medical Journal 6 (1895)
If we are able theu to free tliem from this terrible affliction for a louger time than this, even though recurrence does result in the end, are we not justified iu the jirocedure? The indication for operation is to obtain a cure, although ultimately there may be only temporary relief.
Our results clearly illustrate this fact, as sixteen of the twenty-one cases still living have passed the limit of two years and are enjoying good health — a period of exemption well worth the trial.
The following forty-seven cases of hysterectomy for carcinoma of the uterus include all those operated upon by Dr. Kelly and myself since the opening of the Gynecological wards in October, 1889, and in Dr. Kelly's private practice up to October, 189.5, thus giving a time limit of from one to five years.
Many of these cases we have seen personally within the past three months, and where they lived at a distance we have obtained our information by writing to the local consultant or to the patients themselves.
Vaginal hysterectomy has been employed iu forty cases, abdominal in four, and the combined operation in three cases.
Grouping them all under one head the results are as follows :
Death from primary effect of operation 5 = 10 per cent.
Patients still living 21 = -ll "
Patients died with recurrence IG = 34 "
Patients not heard from 4=8 "
Died from heart lesion. 1= 2 "
Three of the deaths immediately following the oi^eration were due to peritonitis and two to ligation of the ureters.
Kecurreuce and death took place in the sixteen cases within eighteen months, but the prognosis in eight of these at the time of operation was unfavorable.
One patient of the twenty-one still living was operated upon nearly five years ago for extensive disease springing from the cervix. She presented herself in perfect health about every six months for examination, but we were never able to find any return of the trouble locally. About sixteen months ago there appeared in the left side of the neck above the clavicle a nodule, to which she called our attention. Since then other glands in this region, on the ojiposite side of the neck and in the axillaa, have become similarly affected, some of which have broken down and discharged externally. She is at present in a critical condition. As her home is at a considerable distance, we are compelled to accept this as a metastatic manifestation.
Two cases died within four months after the uterus was removed. One had at time of operation such extensive infiltration on either side of the cervix that the case was considered hopeless. The uterus in the second case was found during the operation converted into a friable carcinomatous mass adherent in every direction to the bowels, so that complete enucleation was impossible.
Carcinoma of the breast developed and was removed in two cases several months after the uterus was extirpated. One of these died of a pre-existing heart lesion without any evidence of a local return, and the other is at present also free from
any pelvic trouble, but the carcinoma has again appeared in the breast.
The Fallopian tube prolapsed iu three cases in which it had not been removed, and during the healing of the vaginal incision was caught so that it protruded into the vagina, greatly reddened and swollen. These upon examination made us suspicious that there had been a return of the disease, but the microscope proved their true character. Two of these patients are still in good health ; the third died from a recurrence.
Another patient returned a year after operation with a note from her physician telling me that he had discovered a mass in the vaginal vault which he believed to be of a malignant character. There had been associated with it a profuse vaginal discharge, and occasionally some bleeding. This mass proved to be a large silk ligature which had been left on the broad ligament and had become imbedded in the granulation tissue. Since the removal of the ligature the patient has been absolutely well.
The most interesting of these cases is a patient who presented herself three mouths after vaginal hysterectomy for carcinoma of the cervix, with a fungus-like growth arising in the vaginal vault along the scar resulting from the operation. Dr. Kelly dissected the mass carefully out and thoroughly cauterized the surrounding area. This took place two and a half years ago, and the patient at present continues to be in excellent health.
Local return occurred in all the cases terminating fatallv, but in none could we elicit any history of metastatic growths in other parts of the body, the single exception being the one case above cited where the patient is still living.
Pneumonia was the cause of death in one instance thirteen mouths after the operation ; here there was an extensive malignant ulcerated area in the vaginal vault, which had appeared a few mouths after she left our care.
Adeno-carcinoma, body of the uterus 9 cases.
Carcinoma, cervix 38 "
KesuUs of hysterectomy for carcinoma of the body:
Patients still living 7 = 77 per cent,
•' died recurrence, operation incomplete 1 = 11
" died primary effect of operation 1 = 11
No. cases still living, 5 yrs. elapsed 1
'^ 3 " •• •• 2
" " 2 " " . . 2
" 1 " " 2
The uterus was removed by supravaginal amputation in three cases. An ordinary vaginal hysterectomy was performed in the remaining six. Kecurrcnce has taken place therefore only in the case where the operation was not completed.
In some of the cases the growth had penetrated the w.nlls of the uterus so that it could be seen just beneath the peritoneal covering, and yet no evidence of involvement of the lymphatics or the parametrium could l>e detected. The three cases in which the cervix was left have proved as satisfactory ivs those iu which the whole uterus was removed.
156
JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 56-57.
Kesults in hysterectomy for carcinoma of the cervix :
Patients died from primary effect of the
operation 4 = 10 per cent.
Patients still living 14 = 3G "
Patients died with recurrence 15 = 38 "
Patients not heard from 4 = 10 "
Operations over 4 years ago and patients still living 3
3 " " " 4
" 2 " " " 4
" 1 " " " 3
The uterus was removed in four cases by the combined method. One of these died a few days after the operation from ligation of the ureter, and another in which the disease was associated with pregnancy died several months after operation with a recurrence in the vagina. The remaining two are reported as free from any suspicious signs.
Vaginal hysterectomy was employed in thirty-four cases, three of which died from the operation, and fourteen afterwards from the original disease.
The four cases not accounted for up to the present time were considered at the time of operation favorable for cure. Two of them I have since seen, one two years after operation and the other one year, and both at that time showed no evidence of ulceration or induration by vaginal examination.
The fourteen women who are still living do not giv6 symptoms pointing to metastasis or local recurrence, except the one mentioned with the nodules in the neck and axilla. This single case proves that even after a lapse of four years we are not justified in claiming a cure. We cannot definitely at present fix a period of years through which a patient must live in order to pass the danger limit. Fritsch, Schauta, Hofmeier, Leopold and Boldt have followed their cases from
five to seven years after the removal of the uterus, and even as late as seven years there continues to be a fall in the percent, of cures.
Olshausen, Schauta and Fritsch report over 47 per cent, without recurrence after a lapse of two years. It is a striking fact that in our cases thus far, all recurrences but one have taken place within eighteen months.*
We have not attempted to show the relationship of the different forms of carcinoma to their tendency to recurrence, but the form of disease has undoubtedly a great infiuence upon the ultimate results. This point is clearly demonstrated by our experience, as in not a single one of the seven cases in which the uterus was completely removed for adeno-carcinoma of the body has a recurrence been noted; while in the thirty-eight cases where the cervix was diseased, fifteen have died with a return of the trouble.f
Metastases were found only once beyond the pelvic and retroperitoneal glands, in ten autopsies performed in the pathological laboratory upon patients in whom carcinoma of the uterus was present. This was an adeno-carcinoma of the body of the uterus, and a few nodules were found in the liver. In four others there were carcinomatous deposits in the pelvic and retroperitoneal glands.
This, in conjunction with the fact that by far the greater majority die subsequent to hysterectomy with a continuation of the growth in the vagina and parametrium, proves the possibility of complete eradication.
- Statistics obtained from Winter, Berliner klin. Wochenselirift,
1891, No. 33, and Ztsch. f. Geburtsh. u. Gyn., Vol. XXIV, p. 135 ; also Boldt, American Jour. Obstet., Vol. 26, p. 517.
fKinkenburg (.Ztsch. f. Geburtsh. u. Gyn., Vol. 23) and Hofmeier (same journal. Vol. 32) have made similar observations.
St.vtistics of Forty-seven Cases of Cakcinoma.
Name.
Seat of Disease. | Operation.
Date of
Operation.
Date of Death.
Remote Resllts.
Mrs. L.
Cervix. Fungating mass iiiin.- \ lu'iiial hystcreAomy.
upper portion of vagina.
11-31-89
8-30-91
Local return.
E. C.
Body.
\ affinal bystuiectomy. Uterus
ruptvired dui'ing removal.
1-2-^
Patient continues to be in excellent
health.
C.G.
Cervix. Previous operation, high
amputation.
Vaginal hjsteicctuiny. First use
of ureteral catheter.
6-18-90
Patient last examined 10-3-93. No sign
of return.
D. J. B.
Body.
Vaginal hysterectomy. Bladder
opened. '
8-38-90
Five days after operation.
Death, peritonitis.
Mrs. H.
Cervix. Extensive lateral in 111tratlon.
Vaginal hysterectomy.
3-38-91
Fire mouths after
operation.
Local return in vaginal vault.
M. W.
Cervix. Fungating mass in vagina.
Vaginal hysterectomy.
4-4-i)l
Last examination 10-3-95. No evidence
of return.
J. B.
Portlo vag. Disease extends I cm.
on vaginal walls.
Vaginal bysterectotny.
5-4-91
Discharging gland.s in neck and axilUe.
No local return, )<-15-y5.
E. C.
Cervix. Disease circumscribed.
Vaginal hysterectomy.
7-1-91
Last seen S-9-93. In perfect condition.
M. A. B.
Cervix. Fungating mass in vagina. F.xtenVivc lateral involvement
Vaginal hysterectomy.
11-9-91
9-5-93
Local return in few months.
Dr. Miller's
Patient.
Cervi
Vaginal hysterectomy.
4-23-91
Excellent health. No evidence of return, 9-11-95.
Mrs. W.
Cervi.x. I,:itiriu iinoivuuieut.
Myoma at fundus.
Vaginal hysterectomy.
13-23-91
1-1-93
Local return.
K. K.
Cervix. Exlcusivc lateral inllltratlon.
Vaginal and abdominal.
1-30-93
Died from operation. Ligation of
ureters.
Mrs. M.
Cervix.
Vaginal hysterectomy. Cauterization of left pedicle on account
of inBltrated area. Prognosis
bad.
,.8-18-92
Patient in excellent health. No local
return, 9-1.5-95.
November-December, 1895.] JOHNS HOPKINS HOSPITAL BULLETIN.
157
Name.
Seat of Disease.
Operation.
Date of
Operation.
Date of Death.
Remote Resclts.
Miss B.
Body.
Incomplete vaginal hysterectomy
on account of extensive disease
and inflltration of fundus.
'^-33-93
About three months
after operation.
Disease had brolien through uterine
wall and spread out on intestines.
Mrs. G.
Cervix.
Vaginal hysterectomy.
8-3-92
9-38-92. Portion of tube in incision
removed with cautery. 9-1-95, patient in L'ood li'-iilth.
F. C.
Cervix. Two nodules found in
uterus entirely separate from
cervix.
Vaginal hysterectomy. Bladder
perforated and afterwards closed
with good result. Bad prognosis.
11-37-93
10-18-93
13-12-(iri ised.
Loca;
C. T.
Cervix. Complicated by 4 months'
pregnancy.
Vaginal and abdominal.
11-10-9J
.5-1-94
Patient died in Hospital. Local return
with perforation of bladder and rectum.
R. A.
Body. Associated with myoma.
Supra-vaginal amputation. Cervical canal cauterized.
11-38-93
Patient In good health, 9-13-95.
Z M.S.
Cervix. Fungating mass in vagina.
Vaginal hysterectomy.
12-17-93
5-13-93. Ulcerated area in vaginal
vault dissected out and cauterized. —
9-31-9.1. No sign of local return.
A. E.
Cervix. Fungating mass iilliug
vagina. Invasion of vaginal
mucosa.
Vaginal hysterectomy.
6-25-93
Unable to find patient.
Mrs. D.
Cervix.
Vaginal hysterectomy.
3-6-93
Patient continues in good health,
10-1-95.
Mrs. C.
Cervix.
Vaginal hysterectomy.
4-13-93
Unable to obtain information regarding patient.
Mrs. G.
Cervix.
Vaginal hysterectomy. Impossible to remove all disease laterally.
4-18-93
7-1-93
Local return.
E. B.
Body.
Vaginal hysterectomy. Uterus
ruptured in removing.
5-10-93
Breast removed for cancer about one
year after hysterectomy. 10-1-95, no
return in vagina, but patient under
treatment for some recurrence in
breast.
Mrs. S.
Cervix.
Vaginal hysterectomy.
8-30-93
Died one year later.
Local return.
8. L.
Cervix. Vagina fllied with fungating mass, and inflltration for
a cm. about cervix.
Vaginal hysterectomy. Bladder
perforated. Transfusion of salt
solution in radial artery.
10-10-93
8-15-94
Local return.
P. H.
Cervix. Circumscribed nodule.
Vaginal hysterectomy.
11-8-93
Last heard from S-20-95. Donblful return in cicatrix.
L. W.
Body. Associated with myoma.
Supra- vaginal amputation.
2-1.5-93
Continues in excellent health, 10-5-95.
C.8.
Cervix.
Vaginal hysterectomy.
11-25-93
Died from operation. Peritonitis.
M. F. W.
Portio vaginalis. Disseminated
nodules in vaginal mucosa.
Vaginal hysterectomy. Whole
upper third of vaginal mucosa
removed.
11-25-93
2-1-95
Death from pneumonia. Local retam.
M. G.
Body.
Vaginal hysterectomy.
12-1-93
Continues to be in excellent health,
S.17-95.
M. D.
Cervix. Lateral intiltration so far
advanced that a bad prognosis
given.
Vaginal hysterectomy. Bougie
in ureter.
12-11-93
1 No evidence of local return. Patient in
' excellent health, 9-13-95.
A. R.
Cervix. Post, lip only involved.
Vaginal hysterectomy.
1-31-94
Sent by physician (or examination on
account of suspicions nodule in scar,
which proved to be silk liirature imbedded in granulation tissue. No
evidence of return of disease, 9-13-95.
L W.
Cervix. Fungating mass filling
upper portion of vagina. Mucosa of vagina not diseased.
Vaginal hysterectomy. Bougie
passed into ureter.
2-15-94
About nine months
after operation.
Local return.
N. C. J.
Cervix. Uterus torn olf above internal OS. Lateral infiltration.
Bad prognosis.
Vaginal hysterectomy.
3-17-94
6-8-94
Local return.
E. O.
Cervix. Lips entirely disappeared. Disease far advanced laterally.
Vaginal hysterectomy. Uterus
ruptured during removal.
3-3-94
11-5-94
Local return.
8. B. H.
Cervix. Nodules fell beneath vaginal mucosa. Prognosis bad.
Vaginal hysterectomy. Bougie in
ureter. Pus cavity beside uterus
in abdomen.
8-5-94
Five months after
operation.
Local return. Death sudden.
M. E.
Cervix. Vagina and parametrium involved. Bad prognosis.
Vaginal hysterectomy. Nodule in
broad lig. dissected out.
8-5-94
Eight months after j Local return,
operation. [
M. 11.
Cervix.
Vaginal hysterectomy.
8-7-94
Died from operation.
Death due to pcrltooitis.
M. Q.
Cervix.
Vaginal hysterectomy.
8-21-94
Died from oueratlon.
Death due to peritonitis.
B. Z.
Portio vaginalis. Disease had encroached upon vaginal walls 3
cm.
Vaginal hysterectomy. Ureter
cut.
8-23-94
Ureter dissected out and sutured into
incision in l>ladder. S-1.5-S6. no sign
of return. No urinary diflicalty.
M. P.
Body.
Abdominal hysterectomy.
7-35-94
Perfect health when last soon, 8-18-85.
A. R.
Cervix. I'.iniliiiu .1 oiuiation, vaginal and
- ib.l..iiiinal.
8-8-94
No local induration or ulceration.
Good hoallh, ^16-a5.
8. A.
Cervix. Converted into shell.
Cumbimil operation, vaginal and
abdominal.
0-5-94
Doctor write* that p,itient Is in good
condition, with no sign of recurrence
of disease, l(V-lC>-lVi.
K. A.
Body.
Supra-vaginal amputation. Cervix cMipiu'd out.
6-30-94
No evidence of recurrence, 9-13-»5.
B.C.
Cervix. Vaginal livstcrectomy. Tube
caught in vairinal incision.
3-17-94
Patient in good health and vitbont
symptoms pointing to return. 9-1 i-a5.
Carcinoma of breast removed about one Tear after the vaginal hysterectomy. I'aliont died of hc,»rt lesion.
Mrs. W.
Cervix.
Vaginal hysterectomy.
11-15-91 Died about eighteen
months affcr op1 eration.
158
JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 56-57.
NOTES ON SOME OASES OF ANGINA TREATED WITH BEIIRING'S ANTITOXINE.
By George Blumkk, :M. D., Assidant in Pathology, The Johns Ifnph'vs Hospital
The following cases of siugina, either due to the bacillus diphtheriae, or simulating true diphtheria and due to other organisms, have been observed iu the hospital since the intro•ductiou of the antitoxiue treatment.
Some of the cases are of interest as relating to the eilect of the autitoxine on diphtheria; others were not treated by antitoxiue, but present some special point of interest bearing more or less upon diphtheritic or diphtheroid inflammations.
In the cases treated by autitoxine, the preparation prepared under the direction of Behring was exclusively used, the various strengths being indicated according to the severity of the case and regardless of the age of the patient.
The autitoxine was usually injected into the cellular tissue of the back, though occasionally into the musculature of the thigh, the injection being done with a syringe previously sterilized by boiling, the skin of the part to be injected having been prepared by the methods usual before operative procedures.
The cases, which number eighteen, may be grouped under the following heads:
MEMBK.-VNOUS ANGINA DUE TO THE BACILLUS DiPHTHERIAE.
Case 1.— Female, aged 11, white. Admitted to the hospital December 31, 1894, complaining of sore throat.
JJi«/oij/.— The family histor.v is negative. The patient had measles, whooping cough and typhoid fever as a young child.
The present illness began four nights ago, the patient waking up in the middle of the night with an attack of nausea, followed by vomiting and headache. The throat did not feel sore until the following night, and she then noticed pain on swallowing. .-Vt first the soreness was confined to one side, but later both sides became involved.
On admission the general condition was good. There was great swelling of both tonsils, the glands almost meeting in the median lino. The inner surface of each tonsil was lined by a purulent membrane, whicli, on removal, loft a bleeding surface.
January 1. The membrane has extended to the uvula, and soft palate. There is slight glandular swelling on the left side.
.January 2. The child looks rather pale and is dull and apathetic. Bohring's Antitoxine No. 3 was injected into the snl)outaneous tissue of the back.
.Tanuary 3. The child is much brighter, states that s!ie feels better, and voluntarily asks for food. Tlio swelling of the tonsils has diminished, though the uvula is still covered by membrane. The tense oedema of the tonsils and adjacent parts observed yesterday has disappeared.
January 4. The membrane has almost disappeared.
The temperature on admission was 101.5° F., and ranged between this point and 103° F. up to the time of the Inoculation, when it wjis 103° F. Following the inoculation it sank gradually; the morning following It was 100.5° F., but after this never passed above 100° F., the convalescence being uninterrupted.
The pulse was noted to be a little feeble the day on which the inoculation was made; the following morning it was much improved. About six days after the inoculation the patient began to have attacks of urticaria, coming and going over a period of a week. The eruption was not confined to tlie region of the original Injection, but occurred in various parts of tlie body.
BacteriiiUnjical Examination.— Cn\cr-s\\\>a from the throat did not show definite diphtheria bacilli.
Cultures after 24 hours sliowed almost a inire ciilturo of the bacillus diphtheriae.
A guinea-pig inoculated with a 24-hour buuillon culture died 14 days later with characteristic lesions, diphtheria bacilli being obtained from the seat of inoculation.
Case 2.— Female, aged 35, white. Admitted to the hospital January 7, 1S95, complaining of sore throat.
Histonj.—Hev father died of some disease of the liver, her mother of heart disease. No other diseases in the family.
.\s a child she had the usual exanthems. Slie liad an attack of diphtheria at 9 and another at 29, the latter being a severe attack. She has had four attacks of tonsillitis in the last three years.
The present illness began with a feeling of malaise three days ago; the following day she had chilly feelings and pain in the limbs and back. The throat was not noted to be sore till yesterday.
On admission the general condition was good. There was a general reddening of the throat and a large patch of grayishwhite membrane over the left tonsil, which was detached with difficulty and left a bleeding surface.
Behring's Antitoxine No. 1 was injected into the muscles of the back.
January 8. The membrane on the left tonsil remains the same. There is a small patch on the right tonsil which was not noticed yesterday.
January 10. The membrane has completel.v disappeared.
The temperature on admission was 100.5° F. At the time of the inoculation, two hoiu's later, it was 101.5° F., and had risen two hours later to 102° F. The following morning it had fallen to 100° F., but rose again slightly, reaching 100.5° F. at 4 P. M.; from this time on it fell, reaching normal in four hours and never again rising above that point. The pulse was good at all times. No skin eruption was observed.
liactcrinlogical Eraminatinn. — Cover-slips from the throat showed typical diphtheria bacilli. Cultures on blood serum showed many colonies of the bacillus diphtheriae and a few of the streptococcus pyogenes.
An animal inoculated with a 24-hour bouillon culture failed to react either locally or constitutionally.
The organism isolated was certainly not the pseudo-diphtheria bacillus. It acidified litmus bouillon, and grown side by side with a culture of the pseudo-bacillus, could easily be distinguished. The patient was discharged seven days after the disappearance of the membrane, the bacilli still being present in the throat.
Februaiy 17. The patient again comes under observation after a five weeks' holiday. The throat is quite clear. She states tliat during her absence, and about three weeks after the cess;ition of the first attack, she had a second fairly severe attack of sore throat, which was diagnosed tonsillitis by the attending ph.vsician, but without a bacteriological examination.
Cultures were again from the throat, and diphtheria bacilli and streptococci found to be present.
The patient was kept under observation, and three d&ys later cultures were again taken. tl)o patient having used at frequent intervals for the preceding 24 hours a bicliloride spray and a solution of h.vdrogen peroxide as a gargle. Large numbers of diphtheria bacilli were still present.
Two days later a tliird set of i-ultures were made, the patient in the meanwhile liaviug had Lii(Uor"s toluol solution vigorously applied to botli tonsils five or six times. The diphtheria bacilli were still prtksent, though in smaller numbers.
These organisms, like those isolated in the first attack, were harnih'ss for animals, so the patient was allowed to return to her wiu-k. Three weeks later she was again admitted to the ward with a history of having been taken with sore throat. fever and malaise four days previously. She had been attended
November-December, 1895.] JOHNS HOPKINS HOSPITAL BULLETIN.
159
for a time by her own physician, and creosote had been applied locally. On admission there was a glossy white membrane over each tonsil, very tenacious in character. The patient was practically convalescent at this time. The membrane gradually disappeared and had entirely goue seven days froiA admission. There was no fever.
In the interval between the first and last attacks, and in the last attacli, the diphtheria bacillus could always be obtained from the throat. It was on several occasions inoculated into animals and never produced either local or general reaction.
The organisms finally disappeared from the throat three days after the disappearance of the membrane caused by the last attack, or three months and three days from the beginning of the first attack.
Case 3.— Female, aged 8, white. Admitted to the hospital February 1, 1895, complaining of sore throat.
History.— The family history is negative. She has had the usual exanthems and has been treated for some chronic throat disease since August last.
The present illness began five days ago with a shaking chill lasting about half an hour. She felt well the next day until evening, when she had some fever. She complained of sore throat from the first.
On admission the general condition was good. The right tonsil was swollen and covered by a large patch of yellowish-gray membrane; the left tonsil also swollen and shows a smaller patch of membrane; the uvula free.
Behring's Antitoxine No. 2 was injected into the subciitaneuus tissue of the back.
February 2. The membrane is still i)resent, but looks swollen and has a shining translucent appearance.
February 3. The edges of the membrane are curling up. There is a fine pink papular eruption over the face and back, not itchy.
February 5. All the membrane has gone but a small patch over the right tonsil. The eruption has disappeared.
February 8. The child complains of itching of the back. There are ten to twelve urticarial wheals about the seat of inoculation.
February 9. The urticaria has disappeared.
The temperature on admission was 101° F., but had fallen to 99° F. when the inoculation was made; it never again passed 99.3° F. The pulse was always satisfactory.
Back'rioloyical Examination. — Cover-slips from the membrane showed a fair number of typical diphtheria bacilli. Cultures showed the same organism in an almost pure state.
A guinea-pig inoculated with a 21-hour bouillon culture died 76 hours later, the autopsy showing the typical lesions of experimental diphtheria, and the organism being recovered from the seat of inoculation.
The organism disappeared from the throat five days after the disappearance of the membrane.
Case 4.— Female, aged 30, white. Admitted to the hospital February 5, 1895, complaining of sore throat.
Hi.story. — The family history is unimportant. The ijatient h;iil the usual exanthems as a child. She has had two attacks of appendicitis, the last one two years ago. She had right-sideil pleurisy 20 mouths ago. Since the age of 15 she has had nine or ten attacks of tonsillitis, none of them very severe.
The present illness began two days ago witli chilly feelings, which lasted for twenty-four hours. Last night she began to have frontal headache, which persisted up to a short time ago; all day yesterday she had pains through the limbs. The throat felt a little sore from the first.
On admission the general condition was good. The fauces and tonsils were slightly ccmgested, the tonsils quite swollen, especially the right, which was almost covered with a patch of yellowish-gray adherent membrane; a smaller patch was present on the left tonsil.
Behring's Antitoxine No. .T was injected into the subcutaneotis tissue of tlie back. In the afternoon some pain at the seat of Inoculation was complained of.
February (>. The patient fools much better. There is still some pain at the seat of inoculation. The throat Is less swollen,
though the patch on the left tonsil is somewhat increased in size.
February 7. The throat is almost clear; what membrane remains is swollen and pearly looking.
February 8. The membrane has entirely gone.
The temperature on admission at 2 I'. M. was 102° F.; at (! P. II., about two hours after the inoculation, it had risen to 1(12.5° F.; it then fell, reaching 99° F. at 8 the following morning. At 12 noon on the Oth the temperature was 100° F.; it then fell gradually, reaching normal at midnight and never ag.iin going higher than 99.6° F.
The pulse ranged from 76 to 106; it was always strong.
No skin eruption was noted.
liactcrioloyical Examlruition. — Cover-slips from the membrane showed typical diphtheria bacilli. Cultures showed the same organism associated with the staphylococcus aureus and a few St roptococei.
A guinea-pig inoculated with a 24-hour bouillon ciUture showed marked local tumefaction, but did not die.
The diphtheria bacillus disappeared from the throat 22 days after the disappearance of the membrane.
Case 5.— Male, aged 26, white. Admitted to the hospital March 6, 189.5, complaining of sore throat.
History.— Aside from a history of tuberculosis in two sLsters the family history was negative. The patient had the usual exanthems as a child, and malaria and typhoid as an adult. He has been subject to attacks of .sore throat ever since childhood. some of these attacks having been severe enough to confine him to bed.
The present illness began three days ago with dryness and. later on, soreness of the throat. No cliill or fever. He has beadache and pains through the limbs.
On admission the general condition was excellent Both the tonsils were swollen and reddened, and the middle part of each was covered by a thick yellowish membrane, which, on being detached, did not cause bleeding. The neck glands were a trifle enlarged and tender.
Behring's Antitoxine No. 2 was injected into the sulwutaneous tissue of the back.
The membrane gradually disappeared and was entirely gone three days after admission.
The temperature on admission was 99.5° F.. and never again pas.sed above 99° F. The pulse was always strong.
No skin eruiition was noted.
rtncteriological E .ramiMition.— Coyer-slips from the tliroat showed a few typical diplitheria bacilli. Cultures gave an almost pure growth of the same organism.
.\ guinea-pig inoculated with a 24-hour bouillon culture died 48 hours later, the autopsy showin,g typical lesions of exiierimontal diphtheria, and the bacillus being recovered from tie seat of iuocidation
Tlie organism dis.appeared from the throat three days after tlie disappearance of the membrane.
Case 6.— Male, aged 24. white. Admitted to the hospital March 10. 1S95. complaining of sore throat.
History. — The family history is negative. The patient had the ustial exanthems as a child, and la grippe and dengue as an adult. lie has always been subject to attacks of tonsillitis.
The present illness began two days ago with soreness in the region of the left tonsil and chilly sensations. The attack l>eg:in in tlie morning, and b.v evening a small patch of membrane was noticed on the left tonsil. On removing the membrane a bleeding surface was exposed.
C~>u admission the general condition was good. The tonsils were swollen, and over each was a blackish eschar caused by the use of I.ollior's toluol solution; beneath the eschar a gray membrane could be made out. The glands lu the neck were slightl.v enlarged.
Behring's Antitoxine No. 3 was injected into the sulK'Utaneous tissue of the back.
Two days after the inoculation the membrane bad entirely disappeared, though the tonsils still looked a little rod.
The temperature on admission was 104.S» F.: the next morn
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ing it had fallen to 99.5° F., and did not rise alx)ve 100.5° F. all that day. The following day it began to rise at 8 A. M., reaching 103.5° F. at noon, after which it fell gradually, being 99.5° F. at S the ne.xt morning and never again passing the normal. The pulse was always good.
No skin eruption was noted.
Baclcrioloijical Examination.— CoYcr-sUps from the throat showed a fair number of typical diphtheria bacilli. Cultures showed an almost pure growth of the same organism.
A guinea-pig Inoculated with a 24-hour bouillon culture showed a marked local reaction, but did not die.
The bacilli were still present thirteen days after the membrane disappeared, though not virulent
Case 7.— Male, aged 5, white. Admitted to the hospital .Tune 13. 1895.
Hts^rj/.— Could not be obtained.
On admission it was noted that the child was small and iUnourished. The skin was pale. Tlie mucous membranes not cyanotic. The respiration was loud but not stridulous. 'Ihere was a constant purulent discharge from the nostrils, and much muco-pus dribbled from the mouth. Membrane could be made out on the soft palate, but examination of the tonsils and pharynx was not satisfactory. The temperature was 105° F. on admission.
Behring's Antitoxine No. 2 was injected into the muscles of the right thigh. The child was practically moribund on admission and died suddenly eight hours later.
Bacteriological Examination.— CoviM-sUps showed the diphtheria bacillus and cocci in groups or chains. From the cultures the diphtheria bacillus and the streptococcus were isolated.
An autopsy was not permitted.
Case 8.— Female, aged 29 months, white. Admitted to the hospital with dyspnoea August 12, 1895.
His^o/v/.— Family history negative. The patient had measles five weeks ago. She has had a discharge from the right ear for seventeen months.
The present illness began three days ago with cough. The child, however, ran about and played as usual up to last night. This morning about 4 A. M. she woke up with a severe attack of dyspnoea, which has gradually increased.
On admission the child was dull and apathetic. The mucous membranes and finger-tips were slightly cyanotic. There was marked obstruction to inspiration. Both tonsils were swollen and covered with a grayish exudate. Tliere was no exudate on the posterior pharyngeal wall. Temperature 100.5° F.
Behring's Antitoxine No. 3 was injected into the subcutaneous tissue of the back.
The dyspnoea became rapidly worse about three hours after admission, and the patient died during an attempt at' tracheotomy.
liriclrriolof/ical Exami)wtion.—CoysT-s\\ps from the membrane showed many typical diphtheria bacilli. Cultures showed the same organism. An autopsy was not permitted.
Case 9.— Male, aged 2 years and 10 months, white. Admitted September 8, 1895, complaining of sore throat.
History.— The family history was negative. The child has had no previous illness.
The pres(!nt illness began tive days before admission with anorexia. Two days later the child complained of i)ain on swallowing. This morning a membrane was discovered in his throat by his physif'ian and he was brought to the hospital.
On admission the general condition was good. Both tonsils were swollen and covered with patches of grayish-yellow exudate extending on each side Into the uvula. The pharynx is clean. The glands of the neck are not enlarged.
Behring's Antitoxine No. 2 was injected into the subcutaneous tissue of the back.
Seittember !). The membrane seems to have spread slightly. The child Is bright.
September 10. The child Is better; the membrane has ceased spreading.
September 11. The membrane has largely disappeared.
September 13. The throat is entirely clear.
The temperature on admission at 8 P. M. was 100.4° F. At 2 A. M., four hours after the inoculation, it reached 101.8° F.; it then fell gradually, reaching normal 24 hours later and never again jmssing 90.2° F. The pulse was always strong.
Nil skin eruption was noted.
Baclii-Uihtijiciil Bd;omin«<w».— Cover-slips from the throat showed suggestive bacilli, but no typical ones. Streptococci were present in fair numbers. Cultures showed the diphtheria bacillus and the streptococcus.
A guinea-pig inoculated with a 24-hour bouillon culture of the bacillus died 48 hours later with the lesions of experimental diphtheria, the organism being recovered from the seat of inoculation.
Case 10.— Male, aged 2, white. Admitted to the hospital September 20, 1895, with dilBculty in breathing.
Hixtorii. — A satisfactoiy history cannot be obtained, as the mother speaks only Bohemian.
From the mother's account the child lias only been ill twentyfour hours, its only symptoms being irritability and loss of appetite.
On admission the child looked ill. The breathing was rai)id and slightly obstructed. The voice was, however, clear. Over the tonsils and the neighboring parts of the soft palate a thick white membrane was seen.
Behring's Antitoxine No. 2 was injected into the buttock.
The breathing was somewhat more obstructed in the evening and the voice a trifle brassy.
September 22. The membrane has entirely disappeared. The child looks perfectly well.
The temperature remained steadily up about 102° F. until the 23d. when it fell gradually, reaching 99.4° F. at 10 P. M. and not rising again.
Bactcrisloijical Examination. — Cover-slips from the membrane showed a fair number of diphtheria bacilli. The cultures showed an almost pure culture of liaeillus diphtheriae.
Case 11. — Male, aged 7, white. Admitted to the hositital November 4, 1895, complaining of sore throat.
Bifttory. — The family history is unimportant except that he lost one sister from croup. He has had measles but no othei' illness. The present illness began four days ago with pain in the throat, which was increased by swallowing. The pain was at its worst two days ago, and he felt weak at that time. The pain and the weakness are the only symptoms complained of.
On admission the general condition was good. Both tonsils were swollen and showed numerous areas of membrane formation with rather a iiatchy arrangement. There was also a patch of membrane on the soft palate to the right of the uvula. The breathing was somewhat harsh, but there was no great dyspnoea.
Behring's Antitoxine No. 2 was injected into the muscles of the- left thigh.
November 6. The patient is quite comfortable; he has no pain on swallowing.
November 7. Only a small patch of membrane remains.
November 8. The membrane has quite gone.
The temperature on admission was 100° F., and sank following the inoculation to 98.8° V. It was up to 100° F. at noon on the Gth, and then fell gradually, never again reaching above 99.5° F.
Bavtcrioloiiical Bir'«Hniio<iow.— Cover-slips showed a good many typical diphtheria bacilli. Cultures showed the same organism, almost a pure growth.
The cases recorded in this group arc of that class which from a clinical standpoint alone would be regarded as diphtheria, /. e. they are characterized by definite membrane formation. Aside from the question of the influence of the autito.\ine on the progress of the disease they present no special points of interest, with the exception of Case 2. This case is of interest from several points of view : 1. As showing the duration of antitoxine iinmunization and of natural immunization.
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2. As showing the possibility of auto-infection.
3. As demonstrating that the diphtheria bacillus can exist for long periods in the throat.
4. As demonstrating the resistance of the diphtheria bacillus to chemical agents.
That the immunity conferred by the antitoxine (passive immunity) does not protect over as long a period as natural immunity (active immunity) has long been known as far as animals are concerned. Cases showing the duration of this artificial immunity in man are not, however, common. Henach has reported a case in which a recurrence of the disease occurred from 35 to 30 days after the use of the antitoxine, and Wolff-Lewin reports a case where a child who had apj)arently recovered perfectly after the use of antitoxine develojjed symjjtoms of a fresh attack ten days from the beginning of the first one. In our case the patient was immunized on January 7th and contracted a second attack of what was presumably diphtheria about three weeks later; it is true that the patient was not under observation during this second attack, but cultures made only a week later showed the diphtheria bacillus to be present in the throat. During this second attack no antitoxine was used, and yet a third attack occurred thirty-seven days after the beginning of the second. In this case, theu, the period over which active immunity lasted would seem to be about thirty-seven days, whilst that over which passive (antitoxine) immunity lasted was only twenty-one days.
It seems highly probable that auto-infection occurs in most cases of croujjous pneumonia and in many of streptococcus throat; it is also known that virulent diphtheria bacilli are occasionally found in the throats of healthy people. This case would seem to prove definitely that auto-infection does occur in diphtheria, as it was shown that the diphtheria bacilli were constantly present in the throat between the second and third attacks, the throat all this time pi'esenting a perfectly normal appearance. It is only fair to conclude that when the immunity was worn out the individual became infected by the bacilli then present.
Although the patient was not under constant observation from January 7th, when the first attack began, until April 10th, when the diphtheria bacilli finally disappeared from the throat, yet cultures were made frequently enough to warrant the assumption that the bacilli were continuously present over the period between the dates specified. In an observation recorded in the British ^ledical Journal of which Sevestre speaks, the bacilli were obtained from the throat seven months after the disappearance of the membrane; but in this case the cultures were few and far between. The question of the survival of the diphtheria bacilli after the disappearance of the membrane is an important one from a prophylactic point of view, for we must admit the possibility if not the probability of individuals such as our patient transmitting the disease to others. Such a possibility once being estublislied, the isolation of diphtheria cases would not be subject to any fixed law, but would depend on the demonstration of the presence or absence of the bacillus in the throat.
The fact that the bacilli in this case were only in part destroyed by the repeated action of Loffler's toluol solution is
an interesting one, especially as the solution was acting on a throat devoid of membrane. The fact that the bacillus appears so resistant should not, however, deter us from the use of such chemical agents, as clinical experience has amply proved
their value.
Diphtheria Simulating Follicular Toxsillitis.
Case 12.— Female, aged 23, white. Admitted to the hospital .January 17, 1895, complaining of sore throat.
History.— The family history was uuimportaut. The ijatient had the usual exanthems as a child; slio has not been subject to sore throat. The present illness began four days ago with backache, headache, sore throat and pains in the limbs. There was slight pain ou swallowing.
On admission the general condition was good. Both the tonsils were swollen and on both sides covered with numerous yellowish i)atehes, apparently plugging the follicles. No definite areas of membrane were to be made out.
Behriug's Antitoxine No. 2 was injected into the subcutaneous tissue of the back.
.January 18. This morning a small patch of membr-iue about the size of a split pea was noticed on the soft palate; it was quite adherent.
January 19. The membrane is disappearing.
.January 21. The membrane has entirely gone.
The temperature on admission was 100.2° F., and about the same at the time tlie inoculation was made; the following morning it was 99° F., and never passed above this point subsequently. The pulse w^as always strong. There was some itching about the scat of inoculation three days after its performance, but no skin eruption was noticed.
Bacteriological Examination.— Coyer-sWps from the throat showed suspicious bacilli, but nothing definite. Cultures showed the diphtheria bacillus in practically pure culture.
A guinea-pig inoculated with a 24-hour bouillon culture showed marked local i-eaction, but did not die.
This case corresponds to those described by Koplik as acute lacunar diphtheria of the tonsils. It illustrates the necessity, not yet fully appreciated, of a bacteriological diagnosis ju all cases of throat inflammation. It is just such cases as this which would be clinically regarded as a non-infectious tonsillitis, which may give rise to serious epidemics of diphtheria.
Diphtheria Without Membkaxe.
Case 13.— Female, aged 35, white. The patient has been in the hospital for fifteen mouths with progressive muscular atrophy. Ou February 17, 1S95, she complaiued of sore throat. The throat was examined aud found to be a little swollen and reddened, but there were no signs of membnine. On the ISth the throat was again examined and showed the same appearances. Cultures were made at this time aud showed, the following day, many colonies of typical diphtheria Kicilli.
The patient was transferred to the isolation ward .January 19. Her throat then was a little swollen and reddened, but there Avere no signs of memJirane. There was no dyspnoea, no running at the nose. The general condition was excellent. The throat rom;uned reddened and swollen over a period of eight days, the swelling subsitliug duriug this period and the redness decreasing.
The treatment consisted of a bichloride spray locally, and whiskey as a stimulant.
The temperature, which was 100.2 F. on the night of January 17, rose to 101.5° F. l>y noon of the next day. and remained up fill G P. M.; it then gradually fell, reaching normal ou the lOtli and never passing 90.5° F. substMiuently.
BactiTiologinil A'.r(iminur bouillon culture showed a well-marked local reaction, but did not die.
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This case again illustrates the necessity of a bacteriological diagnosis in all suspected throat cases ; cliuically, no feature was present in tliis case to indicate diphtheria.
Multiple Infection with Bacillus Diphtheriae.
Case 14.— Male, aged 4. white. Aduiilted to the hospital March 29, 1S95, on account of fevei- nnd a disohaiiic from tho right ear.
Histori/.—'rhc family history is imitiipurtant. Tlio patient was in the hospital the June previous with malarial fevor. but recovered completely. The present illness began three days ago with pain in tho head. At this time the ehild was noticed to hold his hand constantly to the side of his head. The morning following the onset of the pain he seemed better, but it was noticed that there was a discharge from the right oar, which has eontinued since. His nose has been discharging for a month or two; he has never complained of sore throat.
March 31. On admission to the isolation ward the child looked rather pale and stupid. There was a thick, creamy, odorless discharge from the right ear which was very profuse. From both nostrils there was a thick muco-purulent discharge. There was no sign of memijrane in the nose. The tonsils and pharynx were reddened, but showed no signs of meml)raue. The neck glands were enlarged, hard and tender to the touch. There was a small area of dullness at the base of the left lung over which the breathing was feeble. On tho radial side of the right thumb there was an e.xcoriated area at the root of the nail. This area was covered by a whitish-yellow membrane, which, on being stripped off, left a raw, non-bleeding surface.
Behring's Antitoxine No. 2 was injected into the subcutaneous tissue of the back. >
.\pril 2. The child seems about the same. The ear is still discharging profusely; the nose less so than formerly. A slight nuMubi-ane has reformed over the wound in the right thumb. The throat is perfectly clear. In the afternoon the ehild did not look quite so well.
April 3. The child looks better this morning. About midday the left ear was noticed to be discharging; the patient had not complained of any pain in the ear region. There is still a slight menjbrane f)ver the right thumb.
April 4. The left thumb is excoriated at its base; there is no membrane over the excoriation.
The ehild was taken home against advice this afternoon.
The temperature on admission to the liospital was 104° 1'. It sank in the evening to 101° F., and from March 30 to the time of admis.sion to the isolating ward varied between normal and 101° F. .■Vt the time of the injection of the antitoxine tlje temperature was 100.8° F.; it sank gradually over the next fortyeight hours, the highest point reached after the inoculation being 101° P. at 8 V. .M. on the day following. The pulse was always fah'ly strong.
No reaction about the seat of inoculation and no skin eruption was noted.
Hactcrioloniail nxaminatimi.— Cover-slips from the discharge from the right ear showed the predominating organism to be a bacillus morphologically resembling the diphtheria bacillus; a good many cocci in chains were also present. Cultures showed many typical diphtheria bacilli and a fair number of streptococci.
A guinea-jiig inoculated with a 24-hour bouillon culture showed very marked local reaction and was very ill for two or three days, bnt eventnally recovered.
(Jultures from the nasal cavity, the tonsils and the pharynx all showed the bacillus diphtheriae associated with the streptoioccus pyogenes; in the tub(!s from the nasal cavity a few colonies of the staphylococcus aureus were also present.
Cultures from the right thumb showed the dlplitheri;i l)acillus with the streptococcus pyogenes and the staphylococcus aureus. Cultures from the left thumb showed the diphtheria bacillus and the streptococcus pyogenes.
The organisms were still present when the child was removed from the hospital.
The two main points of interest in this case are the double otitis media and the occurrence of wound diphtheria.
It is possible that many cases of otitis media in which the diphtheria bacillus is concerned are overlooked, the reported cases not being very numerous. Councilman has reported cases in this country, and Kossel and Kutscher in Germany. In Kossel's cases the diphtheria bacillus could not be isolated from the throat, though membrane was present, a fact which Kossel explains by the overgrowth of the diphtheria bacillus in this locality by other organisms. Most of these cases of otitis media have not been pure diphtheria infections, so that it is often impossible to say whether we are dealing with a primary mixed infection, or whether the diphtheria bacillus was the original causal factor and other organisms afterwards crept in.
Cases of wound diphtheria would also seem to be uncommon, that is if the term wound diphtheria be limited to the infection of woitnds with the Klebs-Loffler bacillus.
Abel has reported a case in which the diphtheria bacillus alone was present in the membrane, proving conclusively that this organism is capable of membrane formation per ,se, a fact which had been disputed by many writers.
It is interesting to note in our case, that while the diphthei'ia bacillus was obtained from the wound on each thumb, membrane was only present over the wound of the right thumb.
Angina Caused by the Pseudo-Diphtheria Bacillus.
Case 15.— Female, aged 22, white. The patient had been in tlie hospital for some weeks with chlorosis. On the evening of .January 31, 1895, she complained of slight sore throat, and examination showed a reddened and swollen condition of the tonsils, with a small patch of membrane (?) on the left side. The next morning the membrane could not be seen and the patient felt perfectly well.
The temperature had risen sharply on the evening of the 31st to 100.5° F., but was normal by 8 A. M. the next morning, and no further elevation occurred.
Bactcriolixjical Examination. — Cover-slips showed apparently characteristic diphtheria bacilli. The cultures were overlooked until the second morning after they wore taken, when the meditmi was seen to be thickly studded with white colonies resembling diphtheria colonies. On cover-slips the organism much resembled llie diphtheria bacillus; it was, however, shorter and thicker, and the individual organisms showed a strong tendency to lie in rows parallel to one another. Culturally, the organism also resembled the diphtheria bacillus, but was a much more profuse grower and alkalinized litmus milk.
.V guinea-pig inoculated with a 24-hour bouillon cultm-e showed neither local nor general reaction.
Tho organism could not be recovered from the throat eighteen days after the attack.
The organism isolated in this case corresponds in all its characteristics to that first described by Hofman and subsef|ueutly by Loffler aiul others. Koplik has described cases in which this organism was found, but not associated with membrane. The membrane in our case seems rather doubtful, as the examination at which the membrane was seen was made by candle light, and on the following morning no membrane was to l)e made out.
Mejibiianous Angina simulating Diphtheria hut due to Oro.vnisms other than the Klehs-Lopfler Bacillus. Case IG.— Male, aged 32, white. Admitted to the hospital
.lauuary 24, 1895, complaining of sore throat.
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History. — The family history was unimportant. Th(> putiont had tlie usual exanthems as a cl)ilfl and thiiilvs he liad diphtheria at three years of age.
The present illness began two days ago with severe headache and a violent shaking chill la.sting about twenty minutes and followed by fever. The following day he felt better, but woke, up on the morning of the third day with fever again. The throat has only been slightly sore.
On admission the general condition was good. Both tonsils were swollen and congested and covered with a thick grayyellow membrane, which was quite densely attached. The uvula and soft palate were not invaded.
Behring's Antitoxine No. ?, was injected into the subcutaneous tissue of the back.
.Tanuni-y 2.5. The patient feels nnu-li In-ttcr. 'I^lio membrane lias iiartly disappeared.
.Tanuary 26. The membrane has entirely disappeared.
The temperature on admission was 100° F.; it had risen to 102° F. two hours later, and then fell rapidly, reaching normal in twelve hours. The pulse was always strong.
Bactcriolor/ical £j"rt/«.in«/io;(.— Cover-slips were negative for diphtheria bacilli.
In cultures the predominating organism was a sliort, slim bacillus which grew well on all media, producing a bright green pigment. The organism corresponded in all its culture reactions with the bacillus pyoeyaneus.
Case 17.— Female, aged 41, white. The patient had been in the hospital for several months with acromegaly. She was admitted to the isolating ward January 2.5, 1895.
History. — The evening before admission the temperature rose and she complained of sore throat. The following morning, wlien the patient was seen, she was quite short of lireath and sitting up in bed. Examination of the throat showed both tonsils to be much swollen and reddened. Over the left tonsil was a large grayish-yellow patch the size of- a quarter, which had the appearance of false membrane. By 7..30 in the evening several spots of exudate were seen on both tonsils and the case presented more the appearance seen in follicular tonsillitis.
Behring's Antitoxine No. 3 was injected into the subcutaneous tissue of the back.
January 2G. The throat looks a little better. The patches still remain, but the swelling has subsided somewhat.
January 27. The patches are fewer in number.
January 28. The exudate has almost gone. The patient complains of a little pain and stiffness in the neck and back.
The temperature on admission was 102° F. By the following morning it had fallen to 100° F., but rose again in the evening to 102° F. A similar exacerbation occurred the following day, after which the temperature gradually fell to normal. The pulse was strong all through the course of the illness.
No skin eruption was noted.
Bacteriological Examination. — Cover-slips showed no diphtheria bacilli; a variety of organisms were present, no one apparently predominating.
Cultures showed an almost pure culture of the streptococcvis pyogenes.
Case 18.— Male, aged 31, white. Admitted to tlie hospital March 11, 1895, complaining of sore throat.
History. — The family history was uninijiortant. The patient had the usual exanthems as a cliild; he has not been subject to sore throats.
The present illness began three days ago with soreness of one, and later, of both sides of the throat. He had headache and general aching all over. No chill or chiil.y sensations.
On admission the general condition was good. Tlio throat was congested, and tlie .tonsils were much swollen, almost meeting in the middle line. On the inner side of each tonsil there was a sloughy-l(x>kiug yellow-gray membrane. The neck glands were enlarged and tender.
Behring's Antitoxine No. 2 was iiijccli'd into llic sulicutaiicous tissue of the back.
In the evening of tlie day of admission the throat was so swollen that the patient had ditticulty in swallowing even liquids.
March 12. The swelling Is decreasing; the patient feels better.
Mai'cli It. The swelling is much less.
Marcli 19. The membrane has entirely disappeared.
The temperature on adraissioil was lO.'J.o' F.; bj- 8 A. M. the next morning it was down to 101° F.. but by 8 P. M. was up to 104° F. : it fell in the night, but rose the next afternoon to 102.5° F., after which it gradually .sank to normal.
No skin eruption was noted.
Bacti rioliiiiiral Exiiminatiori.—CoYer-sVips from the membrane showed numerous cocci in chains, but no diphtheria bacilli.
Cultures gave a practically pure growth of streptococcus pyogenes.
These cases again show the necessity of bacteriological examination in all inflammatory throat affections.
Case 16 is interesting from a bacteriological point of view, for, so far as we have been able to make out, a membranous angina due to the bacillus pyoeyaneus has not been described hitherto. This organism, though usually comparatively harmless, has been described as a factor in various diseased conditions, usually in association with other organs; in our case it was apparently in pnre culture, but this may be due to the fact that it had overgrown the organisms with which it was associated. The comparatively frequent presence of the pyoeyaneus in chronic otitis media would lead one to suspect that it may not be an infrequent inhabitant of the nasal or buccal cavities.
The Effect of the Axtitoxixe Treatmext.
Of the eighteen cases above recorded, si.xteen received the antitoxine treatment, three of these cases being non-diphtheritic.
While this of course is too small a number of cases on which to base any statistical conclusions, several facts in connection with the treatment seem worthy of attention.
Two of the cases died, but both of these were moribund on admission, one dying three and the other eight hours after admission, so that the antitoxine was given no chance.
The other thirteen diphtheria cases were most of them mild, in fact none were very severe, but both on the general condition and on the temperature the antitoxine seemed to have a marked effect. It was almost invariably noticed that the day following the injection the patient was much brigiiter, and in the case of children the return of the appetite was the most marked indication of improvement.
Ill looking over the cases it will be noted that in those due to the bacillus diphtheriae the autitoxiue.as a rule, causeda reduction of the temperature to the normal inside of twenty-four hours ; in one or two of the cases there was a slight rise in the temperature eighteen to twenty hours after the inoculation, but in only one case was no effect on the temperature noted. The last two cases afford excellent examples of the effect of the antitoxine on non-diphtheritic cases : both were early cases, so that a spontaneous fall of temperature can be e.xcluded, and in both the temperature was not influenced in the slightest degree by the antitoxine.
Skin eruptions following the antitoxine injections were noted in several of our cases: they have been noted by varions observers since the inauguration of the treatment, but not enough stress has been laid on the fact that these eruptions are iu all probability due to the serum ;x'r sf, and not to the antitoxic agents contained therein. TUe deleterious effects of the serum of one species of animal when injected into a
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member of anotliui . , , i .: ue too well known to be repeated here, but it is interesting to know that Sevestre, by injecting horse-serum in twenty-centimetre doses into children with non-diphtheritic sore throats, was able to produce urticaria and other forms of skin eruption similar to those observed after the use of the autitosine.
The skin eruptions were the only bad effects, if one could so call them, which were observed after the use of the antitoxine. No other appreciable symptoms plainly due to the injection could be observed, nor did the examination of the urine give evidence of any such.
PROCEEDINGS OF SOCIETIES,
THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.
Meeting of October 1, 1895.
Pjartlirosis— Discussion onDr. Finney's paper. (See September-October Bulletin, page 144.)
Dr. Halsted. — In these cases of knee-joint irrigation we do not hope to do more than to greatly inhibit the activity of the micro-organisms — to assist the tissues to destroy the microorganisms. It is rarely necessary to do more than incise an acute abscess ; the tissues do the rest. And yet we know that the tissues about the abscess have been invaded by the pyogenic micro-organisms. In irrigation of the knee-joint we do not expect to reach the micro-organisms outside of the joint.
In the last case reported by Dr. Finney — the one with triple infection — I do not feel at all sure that we could not'have taken care of the joint itself. We amputated because in a few days we found the tissues in the thigh almost up to the hip-joint invaded by the organisms to a shocking extent, with lesions characteristic of the air-producing bacillus.
That solutions of bichloride of mercury are more efficacious than salt solutions in destroying and inhibiting pyogenic organisms outside of the body we have sufficient proof. There is also abundant clinical, if not wholly conclusive experimental evidence that the same is true in the tissue spaces, in joints, etc.
The irrigation of the urethra in the treatment of gonorrbcea furnishes a good clinical example of the benefits to be derived from solutions of corros. sub. Here, too, the specific micro-organisms have been demonstrated in the tissues outside of the urethra.
I speak from a great deal of experience, from daily observations for five years in the Roosevelt Hospital Dispensary, New York. In this work I was very ably assisted by Drs. Itichard Hall and Frank Hartley of New York. The salt -olutions are worse than ineffectual in the treatment of gonorihcta. With them we never succeeded in aborting a case of gonorrhoni, either in private or dispensary practice, but we constantly induced a cystitis and ejjididyniitis. With the bichloride irrigation, not a single case of cystitis or epididymitis occurred in these five years. I think that we have had tlie same exi)erience in the dispensary here. Doctor Brown told me less than a year ago that he had never produced cystitis or ejjididymitis with bichloride irrigation. In private jn-actice it is very common, indeed it is the rule, to abort a gonorrhcea within a week or ten days with bichloride irrigation. Previous to the use of this irrigation I used to dread to have a case of gonorrhcea come to my office; after its
introduction 1 was glad to see them. The treatment became so pojnilar that certain specialists in New York said that they would never use it because it was ruining their practice. Men after a few visits were cured. Nor would they return when a fresh urethritis was contracted. 'Furthermore, they taught their friends h'ow to treat themselves. It would be too much of a digression to give the details of this treatment at this time. But I must ask your permission to say that everything depends upon the intelligent use of the method. The strength of the solution is determined by the use of the microscope and by the tolerance of the particular urethra. The strength to be used varies from 1-200,000 to 1-25,000. A tolerance of the stronger solutions has, usually, to be acquired. ftleu with red hair have, as a rule, sensitive urethras.
The gonococci disappear jiromptly from the ui-ethral discharge after irrigation with solutions of corrosive sublimate, but are uninfluenced, apparently, by irrigation with the salt solution.
A t'ase of Congenital Ptosis.— Dr. Thomas.
The patient, B. L., dispensary No. B 587, whom I wish to show to you to-night, is a boy fourteen years old. He applied at the dispensary a few days ago complaining that he was unable to open his left eye. No similar case had ever occurred in the family so far as was known. The patient was the eighth child and the only son. His birth was natural but difficult. It was noticed soon after birth that he did not open his left eye, and this condition has remained unchanged ever since. In other resj^ects the boy has developed normally.
In looking at him you notice that while his right eye is widely opened, his left eye is nearly closed by the drooping upper lid. The skin of the forehead on the left side is drawn into deep furrows, as if he were trying to lift the eyelid by a strong action of the occipito-frontalis muscle. If the left eye be covered by the hand the forehead becomes smooth. When asked to look up, the patient opens his right eye wider, rolls the eyeball upward and contracts the occipito-frontalis on that side. On the left side the eyeball remains stationary, and the only noticeable change is a still greater contraction of the occipito-frontalis muscle ; if, however, the left eye bo passively opened, the eyeball is moved upward to some extent, but not so far as on the right side. In looking down, the eyes move normally, but the left upjier lid does not follow the movement as does the right.
The lateral movements of the eyes are normal in extent, but there is a curious disassociation ; they appear to move independently of each other. His pupils are equal, moderately
November-December, 1895.] JOHNS HOPKINS HOSPITAL BULLETIN.
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coatracted ; they react to light and during accommodation. Ophthalmoscopic examination shows the fundus to be normal. The facial muscles and those of mastication act normally.
In this case we have a congenital defect, consisting of a paralysis of the left levator palpebrse superioris, paresis of the superior rectus, and an associated over-action of the occipito frontalis on the same side, forming the common picture of congenital ptosis. The disassociation of the ocular movements is also of interest.
Congenital ptosis is, in our experience, not a common affection, this being the first case which I have had an opportunity of studying. The cause of the trouble is believed to be some abnormality in the nucleus of the third nerve, from which the muscles involved receive their motor nerve fibres. As far as I know, but a single careful anatomical examination of such a case has been made. I refer to the case of Prof. Siemerling, reported in the Archiv f. Psych, u. Nervenkrank.,Y6\. XXIII, p. 764, 189;'. The patient died from general paralysis, but during life he showed no ocular symptoms referable to that disease except the Argyle-Robertson pupils. The congenital ptosis was of the left eye. Siemerling discovered a lesion in the dorsal and ventral parts of the principal group of cells in the nucleus of the third nerve, and what seemed remarkable, the lesion was bilateral, although the left upper lid was alone affected. The nucleus of the third nerve is a complicated structure. It is, however, impossible to go into this question to-night, as I want to call your attention to some other interesting points in connection with congenital ptosis.
In 1883 Ml-. Marcus Gunn exhibited a case before the Ophthalmological Society of London, which showed remarkable associated movements of the paralysed eyelid. When the patient opened his mouth or moved his jaw towards the right, the paralysed left ujjper lid was raised. This case created a great deal of attention, and a committee including Dr. Gowers, Dr. Stephen McKenzie and others was appointed to examine the patient. They confirmed Mr. Gunn's observation and expressed the opinion that in that case the levator palpebrfe "is innervated both from the nucleus of the third nerve and from the external pterygoid portion of the nucleus of the fifth nerve."
Since the publication of this case, a number of cases have been reported, and in May, 1894, Bernhardt {Neurol. CentralblL, Vol. XIII, p. 325) was able to collect twenty-four cases, eighteen of which he used for comparison. In nearly all of those the associated movement of the paralyzed lid occurred, either when the mouth was opened or the jaw moved away from the side on which the ptosis was present, i. e. during the action of muscles supplied by the fifth nerve. In two remarkable cases the fallen lid was raised when the other eye was voluntarily closed, an associated movement between a muscle supplied by the facial nerve on one side and one supplied by the third nerve of the opposite side.
The extent of the associated movement apparently varies in the different cases. The most striking report that I have seen was published in the Arrliiivs of OpJt/kiilmologi/, Vol. XXII, p. 65, 1893, by Dr. A. A. llubbell, in which there are three excellent photographs, illustrating this associated movement. In this case the paralyzed upper lid was raised quite
as much if not more than the normal one when the mouth was opened.
As you see, when the patient whom I have here to-night "opens his mouth wide, or moves the lower jaw strongly towards the right, there is no very evident raising of the left upper lid. If, however, careful measurements are made, it is found that the visual aperture widens two or three mm. The widening is greater when the patient looks down during the movement of the jaws. Voluntary closure of the right eye produces no effect on the left. It is not at all certain that this slight widening of the aperture is due to a contracture of the levator palpebrae and not to other mechanical causes.
The explanation of these associated movements is not clear. Most observers agree with the English committee in the belief that it is due to the third nerve's receiving axis cylinder processes from cells situated in the fifth nucleus. We know that fibres running in motor nerves may arise from cells quite widely separated in the central nervous system. You will see from the diagrams of the nuclei of the motor cranial nerves, which I have placed on the blackboard, the relative positions of the third and fifth nuclei. The third nucleus is under the aqueduct of Sylvius; the principal motor nucleus of the fifth is about the middle of the upper half of the fourth ventricle. The descending root of the fifth extends quite to the level of the third nucleus. There is some doubt as to whether this root should be considered sensory or motor. It is not difficult to believe that nerve cells might send their axis cylinder processes from either the motor nucleus, or from the nucleus from which the descending root arises, to leave the brain by the third nerve. If such a condition underlies the associated movements which occur in congenital ptosis, the question suggests itself whether the condition is a normal one, or whether it only occurs in connection with the abnormality of the third nucleus upon which the ptosis depends. In two cases in which the ptosis was acquired as one of the symptoms of ophthalmoplegia externa due to nuclear disease. Dr. Ilughlings Jackson was unable to demonstrate any associated movements of the paralysed lids, and in the case before you I have not been able to convince either you or myself that there is any actual contraction of the paralysed levator muscle. These cases, so far as they go, would seem to indicate that this connection is not always present. I know of no anatomical investigations that bear on the subject.
Dr. Jackson, in the article referred to above {Lancet, Jan, 6, 1894), suggests another interesting question in connection with cases of congenital ptosis, /. c. whether Muller"s muscle is also paralysed. You may remember that the eyelid contains, besides the levator palpebral smooth muscular fibres, the so-called iliiller's muscle, which help to elevate the lid. This muscle receives its nervous supply from the cervical sympathetic. These nerve fibres leave the spinal cord by the upper four or five dorsal roots. The nerve cells from which they arise have not been localized, but it is believed that they are situated somewhere near the third nucleus. Since we believe that congenital ptosis is due to some central legion, it is important to know whether Midler's muscle is paralysed. Dr. Jackson suggests a method by which this may be determined. It was pointed out by Jessop i^Proctcd. of Royal Soc.,
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[J^os. 56-57.
Vol. XXXVIII, p. 432, 1885) that if a solution of cocaine be dropped into the eye the pupil dilutes and the visual aperture widens. He demonstrated by experiments that this was due to a stimulation of the endings of the sympathetic nerve, causing contraction of the dilator muscles of the iris and of Jliiller's muscle in the lid. Dr. Jackson urges the importance of applying this test in nervous diseases wherever the sympathetic may be involved, and points out the desirability of testing a ease of congenital ptosis in this manner.
We dropped into both eyes of this patient three or four drops of a four per cent, solution of cocaine. At the end of half an hour both pupils were dilated and the visual apertures of both eyes had widened about two mm. It would appear from this that the cocaine acted equally on the two sides and gave no evidence of paralysis of Miiller's muscle.
Note. — The patient has been examined on several occasions since he was shown to the Society. The observations differ but little from those recorded, but it may be of interest to give the last note of the examination under cocaine.
December 9, 1895. 10.50 a. m., visual aperture, R. eye opened normal, 12.5 mm.
L. eye opened normally, 5 mm. Eye wide open, 5 nun. Pupils equal, about 5 mm. in diameter. One minim of an 8-per cent, solution of cocaine was put into each eye.
11.40 a.m., visual aperture. E. eye opened normajly, 11 mm. Wide open, 15 mm.
L. eye opened normally, 7.5 nun. Eye wide open, 8 nun., and with mouth open, 9 nun. I'ujiils e(iua], diameters about 9 mm.— H. JI. T.
Dr. L. F. Barker. — The case which Dr. Thomas has shown is of more than ordinary interest. As to the connections of the nervus trigeminus and its motor and sensory nuclei with the nucleus nervi oculomotorii, there is little that can be said to have been definitely established. This much is certain, that fibres run from the gray matter connected with the sensory portion of the fifth nerve (t. e. the substantia gelatinosa near the spinal tract of the 5th and the so-called sensory nucleus of the 5th) into the fasciculus longitudinalis medialis, and the intimate relations of the latter bundle to the oculomotorius nuclei have been very definitely proven. Whether or not the motor nuclei of the trigeminus (nucleus princeps and nuclei minores [radicis descendeiitis]) are directly connected with the nuceus n. oculomotorii, does not as yet seem clear. A large amount of work has been done with regard to the various groups of ganglion cells of which the nucleus of the oculomotorius nerve is made up, but up to the present the cells which have to do with individual muscles have not been satisfactorily localized. Neurologists have recently been inspired with new hope as regards this point through the introduction of a new method of investigation. In June of last year Nissl of Frankfurt-am-llain, in an address in Baden-Haden {Ccntrnlblt. fur Nvrnmheilk. u. Psyihiatrie, 1894, Bd. XVII, pp. 337-344), described a procedure which, although of relatively narrow api)lication, has the advantage of establishing exactly the location and relations of many of the nerve cells in the gray masses. For example.
he states that the method will determine for each individual eye-muscle the localization of its corresponding nerve cells in the central nuclei, a result to which the most careful investigators with the use of other methods (c. g. v. Gudden's or llarchi's) have hitherto been iniable to attain.
In an adult or half-grown animal a solution of continuity of the fibre connecting a nerve cell with a peripheral part, be it muscle fibre or epithelial surface, leads to retrogressive changes in the body of the nerve cell. These alterations, though somewhat different in nerve cells of different types, are very characteristic and easily recognizable, Nissl claims, after some experience. Very soon, too, changes occur in the neuroglia cells which are in the neighborhood of the affected neurons. The changes in the cells are recognizable in alcohol tissues sectioned and stained according to the latest directions of Nissl, and his staining reaction has to be looked upon as one of the most delicate we possess for the study of degenerations of the body of the nerve cell. In order to apply the method to the eye muscles, one would either extirimte a given nuiscle or cut the nerve supplying it, and subsequently (the lesions in the rabbit are most characteristic between the 8th and the 15th day) kill the animal and study serial sections of the nucleus of the third nerve. As Nissl points out, the very delicacy of the reaction necessitates the greatest caution in its application. Operations must be done asepticalh', one must be absolute master of the technique and must be familiar with the appearances of the various cell-forms in the normal condition, otherwise the investigator will be led into serious error. Nissl suggests that his method be called "Die Methode der primiiren Reizung." Should this method prove to be as useful as it promises, and already confirmatory work has been done by other investigators, we can hope for a speedy settlement of the much vexed questions regarding the cells of the eye-muscle nuclei. Now that the importance of the gray matter in the anterior corpora quadrigemina as a governing centre for the various movements of the eye muscles is generally recognized, and the connections of the axons of the cells situated there by means of collaterals with the various eye-muscle nuclei have been definitely established, the possibility of an exact localization of the cells in the nuclei concerned directly with the individual muscles comes opjiortunely.
Another point in connection with the case Dr. Thomas has just reported seems to me worthy of remark.
In the formation of an associated movement there has been a marked dissociation of muscular contractions ordinarily assocuited. Dr. Thomas has spoken of the dissociation of movements of the muscles of the two eyes. Usually in contracting the frontalis muscle the fibres on both sides of the forehead are contracted at once. This -boy possesses in an extraordinary degree the power of unilateral contraction of the frontalis ; indeed, when his eyes are open the left frontalis is continually forcibly contracted, while the muscle on the right side is at rest. This is by no means surprising, for we know of many so-called associated movements which, tlirough training and education, can be dissociated, as for example the isolation of finger movements observable in an accomplished pianist.
NOTES ON NEW BOOKS.
BOOKS RECEIVED.
INDEX TO VOLUME VI OF THE JOHNS HOPKINS HOSPITAL BULLETIN.
