THE INTRAVENOUS INJECTION OF ANTITOXIN IN DIPHTHERIA.

1774 and performed abdominal enterostomy. Kermisson reached success than the latter. In duodenal occlusion the intestine the distended small intestine by the perineal route and is better developed than is the distal segment in an obstruction of the ileum. opened and drained it. In a jejuno-ileum occlusion the anastomosis should be Entero-anastomosis has been performed at least six times. Mangoldt, quoted by Braun, operated upon an infant three effected as close as possible to the deformity, to leave as days old with five points of occlusion in the ileum. The much small intestine as possible in the circuit. Often the jejunum was anastomosed to the colon immediately obstruction is so near the colon that the ileum will have to beyond the csecum. Franke 2A anastomosed the ileum to be anastomosed to the latter. The extreme contraction of the ileum for an obstruction from 23 to 25 centimetres the distal segment being one of the causes of failure after above the caecum. Death occurred from general peri- this operation it has occurred to me that it might be possible tonitis, the result of leakage around the line of suture. to overcome this by water pressure. It seems certainly Simmonds ’0 anastomosed the ileum to the cascum and after worthy of a trial. This would have an additional advantage the operation symptoms of obstruction persisted and at the that it would test whether or not there were a second necropsy there was found in addition an atresia of the obstruction present lower down. Before suture the distended sigmoid flexure. Braun, suspecting a high rectal occlusion, bowel should be drained. If multiple points of atresia be present anastomosis would endeavoured to reach the proximal end from the perineum ; being unsuccessful he incised in the left iliac region and generally be impossible. Occasionally it may be possible as here found contracted small and large intestine. He then in Mangoldt’s case. Single obstruction in the large bowel, a If incised in the right iliac region and found the csecum and most rare condition, would necessitate colostomy. lower ileum contracted. A distended coil of small intestine anastomosis be impossible on account of the infant’s condition or from the conditions of the occlusion temporary was seen but it was impossible to draw this into the wound and so a median abdominal incision was made. Braun found relief should be given by enterostomy. the obstruction and anastomosed the ileum to the ileum. Although all attempts so far to save these infants have On pressing upon the proximal end intestinal contents could been so universally unsuccessful, it is not too much to hope not be made to pass into the distal end. He then anasto- that with an early diagnosis, an infant in good condition mosed again more distally, still nothing would pass. At the otherwise, and a suitable abnormality gastro-enterostomy necropsy it was found that nothing had passed into the or ileo-anastomosis may yet be successful here as it is in so distal contracted intestine. Wanitshek3l for an obstruction many acquired conditions of intestinal obstruction. between the ileum and the cascum joined the ileum with Harlev-street, W. what appeared to be the largest part of the large intestine. Oliver,3’ in a case where the two ends of the intestine were separated about one and’a quarter inches, performed THE INTRAVENOUS INJECTION OF ANTIan end-to-end anastomosis. Death occurred five hours TOXIN IN DIPHTHERIA. later and the necropsy showed that the intestine below the anastomosis was greatly contracted and apparently BY JOHN BIERNACKI, M.D. GLASG., nothing had passed into it from the proximal segment. In MEDICAL SUPERINTENDENT, PLAISTOW HOSPITAL; five of these cases the patients died within a few hours of AND the operation. Franke’s case lived three days and then succumbed from general peritonitis. I cannot find a J. C. MUIR, M.D. CANTAB., recorded case of an operation for a duodenal occlusion. The MEDICAL SUPERINTENDENT, ST. GEORGE’S INFIRMARY ; LATE ASSISTANT MEDICAL OFFICER, PLAISTOW HOSPITAL. majority of these operations were performed during the first three days of life-eight on the first or second day and 12 on the third day. The majority of cases treated by enteroTwo years ago Dr. D. L. Cairns published a report stomy succumbed within 24 hours. Three lived to the second on the above subject.l He claimed increased efficacy for day, one to the fourth, one to the fifth, and one infant lived antitoxin when given intravenously, stating in particular 15 days. Such are the statistics for the relief of congenital that there resulted a strikingly rapid decline in the toxaemia, intestinal occlusion and it may well be asked, Is surgical quick subsidence of glandular enlargement, and in pneuinterference justifiable ? The failure of enterostomy is not monic cases a marked diminution of the accompanying so much the shock of the operation as the short length of restlessness. In 50 cases of diphtheria, 20 of which were intestinal tube left for the absorption of nourishment. This will in itself always render enterostomy nothing more than a treated by this method, there were three deaths, a mortality palliative operation. It has been suggested that entero- of only 6 per cent. Of these 17 were tracheotomy cases stomy as a palliative measure should first be performed and with one death, a remarkably low mortality (5’88 per cent.). later under mere favourable conditions the anastomosis should On the publication of Dr. Cairns’s results we commenced the be proceeded with. The results of the cases submitted to administration of serum by the intravenous method in grave enterostomy at once show the uselessness of this suggestion. cases. In 1903 seven patients (Series A) out of a total of The anastomosis, the ideal operation, is attended with 334 were so treated ; the results were so equivocal that some considerable sliock which in itself is often sufficient to the latter half of the year the method was disconduring prove fatal, differing from enterostomy. In addition, the tinued. In the first nine months of the present year, howdistal segment of the bowel is often, nearly always, so ever, it has been given a further trial, 38 cases being selected extremely contracted that suture is very difficult, and if out of 246 (Series B). successful thus far in more than one case the obstruction SERIES A.—SEVEN CASES 1B’ITH FIYE DEATHS. has not been relieved, since the intestinal contents, thick, viscid, glairy meconium, cannot easily pass into this distal A brief report of these cases may be given. contracted bowel. Yet this has done so. In one case out of CASE I.-A female patient, aged 11 years, was admitted on six the infant lived to the third day and then suddenly Jan. 24th, at 12.15 P.lIi., on what was stated to be the second collapsed and died from peritonitis. The outlook in this day of illness. There was thick membrane over both sides case would have been hopeful otherwise. This case at least of the fauces and half of the soft palate. Both sides of the gives hope that the condition is not beyond the reach of neck were greatly swollen. There was profuse discharge surgery entirely. If only one infant can be saved something from the nose. The skin was pale. The temperature was is gained. The disease is most certainly fatal if left alone. 1010 F. ; the pulse was 128 and of low tension. At 4.15 P.lII. The exact abnormality cannot be foretold. Even with such 30,000 units of antitoxin (Serum A) were given intraslight hope the abdomen should be opened. The median inci- venously. At 5.30 P.M. the patient had a rigor and the sion should always be used. It is waste of time to expose fromtemperature rose to 105-2°. At 6.20 it was 106 2°, after the perineum or the iliac regions. If the obstruction be in the which it gradually fell to 101 - 2°. On the 25th 26,000 units duodenum and jaundice exists operation is useless. Other- (Serum A) were given intravenously. There was no rigor or wise gastro-enterostomy should be performed. I am not r.se of temperature. On the 26th the local lesion showed aware that this has been done but it is no more severe than signs of retrogression. On the 27th there was a decided intestinal anastomosis and, I think, affords a better hope of decrease in the membrane and the nasal discharge was much less. On the 31st severe vomiting commenced. The heart 29 der Deutschen Gesellschaft für Chirurgie, 1898, Verhandlungen was dilated and the pulse was soft and slow (60 per minute). 30 Münchener Medicinische Wochenschrift, 1900. 31 Medicinische 1898. Wochenschrift, Prager 1 THE 32 Journal of the American Medical Association, 1901. LANCET, Dec. 20.h, 1902, p. 1685.

1775 The urine was scanty and contained a large amount of less remarkable. Cases 2 and 4 ran an ordinary course toIn Case 3 albumin. The voice was very nasal in tone. From this a fatal issue and Case 7 to a favourable one. condition a slow recovery was made, the patient being the outlook from the time of admission was hopeless. Thechild in Case 6 lived only seven hours after admission, ultimately discharged in the fifteenth week of the attack. CASE 2.-A male patient, aged three years, was admitted but we have thought it advisable to include it in the series. at 9 P.M. on Jan. 24th. the sixth day of illness. On admission In Case 5 there was a large septic element, so that marked there was membrane all over both sides of the fauces and on benefit was hardly to be expected. On the whole there wasthe uvula. There were profuse nasal discharge and marked no evidence that the serum was more effective than when. swelling of the neck. The pulse was 120 and of low tension. given subcutaneously. 30,000 units of antitoxin (Serum A) were administered intraSERIES B.-38 CASES WITH THREE DEATHS. venously. On the 25th the membrane had almost separated, The absence of disturbance following the injection of the glandular swelling was much less, and the nasal discharge was reduced. The pulse had fallen to 84. On the Serum B led to its exclusive use during 1904 in a second 26th the pulse was 60 ; the heart-beats had a marked gallop series of cases. No useful purpose would be served by rhythm due to a reduplicated second sound. The urine presenting clinical reports of all these cases. They are contained a large amount of albumin. The patient was primarily grouped as naso-pharyngeal, pharyngeal, and On the 27th there was vomiting and the laryngeal. In the first group there are 14 cases with novery drowsy. drowsy state continued ; the urine was scanty. The patient deaths. In five cases intravenous injections only were used, in six cases relatively small supplementary doses were given died on the 28th. CASE 3.-A male patient, aged four years, was admitted by the subcutaneous method, in two cases both methods were on Jan. 26th at 12.45 P.M. He was in the fourth day of the equally employed, and in one case the greater part of the attack. There was extensive membrane on both sides of the antitoxin was injected subcutaneously. The following case fauces and on the uvula, with extreme swelling of the neck is taken from the group. CASE 10.-A male patient, aged three years, was admitted and profuse nasal discharge. There were pallor and some cyanosis. The temperature was 103’ 8° F. ; the pulse was on Feb. 9th, the fourth day of illness. There was membrane 144 and very feeble. At 2 P.M. 40,000 units of antitoxin on the whole of both sides of the fauces, overlapping forwards (Serum A) were injected intravenously. At 4.15 P.M. the on to the palate, and some also on the pharyngeal wall behind temperature had risen to 105’ 6° and there were increased the tonsils; there was profuse nasal discharge and the glands cyanosis and collapse. Death occurred at 7.25 P.M., the of the neck were considerably swollen. The pulse was 120’ and of low tension. The urine was normal. At 4 P.M. antitemperature then being 10361. CASE 4.-A female patient, aged four years, was admitted toxin was given intravenously, the dose being 20,000 units on July 29th at 2 P.M., the illness being then in the fourth (Serum B). On the following morning a further dose of day. There was extensive membrane all over both sides of 20,000 units was administered by the same method and at the fauces, on the uvula, and on one-half of the soft palate. night the membrane had commenced to separate, but there There was not much swelling of the neck. The general was still profuse discharge from the nose. On the 13th the condition was good; the pulse was 144. The urine con- fauces were noted to be quite clear. The further progress of A serum rash tained a trace of albumin. At 6.40 P.M. antitoxin was given the case was without special features. it at the end first was not accomoccurred of the units On the dose week ; intravenously, (Serum B). being 18,000 the 30th the membrane was still very extensive. A sub- panied by other symptoms. Paralysis developed in the sixth cutaneous dose of 12,000 units of antitoxin was given. On week but was not severe. The child left the hospital in the. the 31st the membrane was quite loose. On August lst the tenth week. Of pure pharyngeal cases there were 12 with one death.. membrane had separated, leaving the throat very dirty and sloughy. On the 3rd vomiting commenced and the child The administration of antitoxin was solely intravenous in, sank rapidly. Death occurred on the following day at two cases, mainly intravenous in five, about equally intravenous and subcutaneous in two, and chiefly subcutaneous6.15 A.M. CASE 5.-A male patient, aged four years, was admitted in three. A single case only need be quoted here. CASE 23.-A female patient, aged six years, was admitted on July 23rd at 2.30 P.M. on the third day of illness. There at 9.45 P.M. on what was stated to be the second day of the was membrane all over both tonsils with considerable oedema of the fauces and profuse nasal discharge. The pulse was attack. There was extensive membrane thickly covering128; the urine was normal. An intravenous injection of both tonsils and involving the greater part of the soft palate12,000 units of antitoxin (Serum B) was given. On the 24th on the right side. The neck on the right side was greatly there was slight epistaxis. A subcutaneous injection of swollen. There was no nasal discharge. The pulse was 144 ; 12,000 units of antitoxin was given. The further progress the urine was normal. At 11.30 P.M. a dose of 20,000 units of the case was very slow, the septic element being pro- of antitoxin (Serum B) was given intravenously. On the minent with profuse rhinorrhoea and ulceration of the fauces. following day (March 28th) the membrane had extended over On August 9th the patient had profuse haemorrhage from a considerable part of the left side of the palate and hadB the pharynx and died shortly afterwards. covered the uvula. There was great swelling of the neck.. CASE 6.-A female patient, aged four years, was admitted A second dose of 20,000 units of antitoxin was given intraat 3.20 P.M. on July 25th, which was stated to be the third venously at 2 P.M. There had been some vomiting and the day of illness. There were a great deal of membrane all general condition was serious with a tendency to failure of over both sides of the fauces and much swelling of the neck. the circulation. On the 29th the membrane was no longer Under ether 12,000 units of antitoxin (Serum B) were spreading but retrogression was not evident. Vomiting given intravenously and 22,000 units subcutaneously. Death continued and the patient was fed by the rectum. On the occurred at 10.30 P.M. 30th the neck was much less swollen. The general condition On April lst the general improvement was CASE 7.-A male patient, five years of age, was admitted was better. at 5.30 P.M. on July 17th, the third day of illness. Both marked and vomiting had ceased. The case then ran an tonsils were covered with membrane. There were laryngeal ordinary course. There was slight paralysis in the sixth cough, stridor, and aphonia, but no recession or definite week. The child was discharged in the tenth week. The laryngeal cases fall into three groups-those not dyspnoea. The pulse was 100. Under chloroform 12,000 units of antitoxin (Serum A) were injected intravenously at requiring operation, those intubated, and those in which 9.45 P.M. At 11 P.M. there was slight rigor and by 12.15 A.M. tracheotomy was performed. In the first group there are the temperature, previously normal, had risen to 103’ 6° F., two ordinary cases, both ending in recovery. One was after which it gradually fell. The urine was normal. On treated wholly and the other chiefly by the intravenous the 18th a subcutaneous dose of 16,000 units (Serum A) was method. In a third case the lesion was mainly pharyngeal given. The case followed a usual course. The patient was and nasal but there was slight laryngeal involvement; it discharged in the sixth week. proved fatal and is quoted later. Six cases required intubaIt will be observed that two brands of serum (A and B) tion only and all the patients recovered. In four cases the were employed. Serum A was previously in use for hypo- treatment was purely intravenous, in one mainly so; in the dermic injection and, when given intravenously, in three remaining case an equal subcutaneous dose was given. One cases out of four-viz., Cases 1, 3. and 7-it caused within a case may be detailed. short time a varying degree of chill, pyrexia, and circulatory CASE 38.-A female patient, aged four years, was depression. With neither serum was there any aggravation admitted at 12.50 P.M. on May 30th, the seventh day of of the rash or of other later effects. Though Case 1 was illness. There were stridor, recession, and cyanosis. Intu. extremely grave the age of the patient made her recovery bation was immediately performed and gave complete relief,

I

1776 There were patches of membrane on the tonsils. The pulse 112 after the child had settled down. The urine contained a trace of albumin. At 2.30 P.M. a dose of 20,000 units of antitoxin (Serum B) was given intravenously. At 10.30 P.M. the tube became blocked ; it was pulled out and replaced. At midnight 20,000 units were injected intravenously. On the 31st the tube was twice removed and replaced. On June 2nd the tube was dispensed with. The progress of the case was then uneventful. Early in the second week there was a serum rash with slight pyrexia. The patient was discharged in the sixth week. Tracheotomy was performed in three cases with one death. In one all the antitoxin and in a second half of it was given intravenously ; in the third the intravenous dose was subsidiary. The history of the first of these is as follows. CASE 43.--A female patient, aged four years, was admitted at 10.45 P.M. on June 17th, the fifth day of the disease. There was membrane in patches on both tonsils, which were very large. There was profuse nasal discharge. The neck The cough was laryngeal. The was moderately swollen. general condition was unfavourable, the child being illnourished. The pulse was quick and feeble. A trace of albumin was found in the urine. A dose of 18,000 units of antitoxin (Serum B) was given intravenously at 11.50 P.M. By 7.30 A.M. on the 18th the laryngeal obstruction had considerably increased ; at 9.30 A.M. intubation was performed and 20,000 units of antitoxin were injected intravenously. The child became pale and cyanosed towards the end of the injection but she quickly recovered when put to bed. At 11.30 P.M. tracheotomy was performed as the great enlargement of the tonsils and the nasal obstruction prevented the intubation from relieving completely. On the 20th the tube was removed. The further course of the case showed The patient was discharged at the end no special features. of the seventh week. The fatal cases in Series B are all of sufficient interest to be reported. CASE 25.-A male patient, aged seven years, was admitted at 2 P.M. on March 30th. The tonsils were very big and covered with rather thin membrane. The glands on both sides of the neck were enlarged. Somnoform was employed as a general anaesthetic when the intravenous injection was given. It was taken very badly, asphyxia threatened owing to pharyngeal obstruction, and tracheotomy had to be performed. The injection was thus interrupted, only about 4000 units having been given. The remainder (24,000 units) was injected subcutaneously. On the 31st the neck was very greatly swollen on both sides. The membrane was thick and much increased. The general condition of the patient was very bad. At 2 P.M., under chloroform, 30,000 units of antitoxin were given intravenously, followed by 20,000 units by the same method at 5 P.M. The patient continued to lose ground and died on the following day. CASE 34.-A female patient, aged three years, was admitted at 7.15 P.M. on Sept. 8th, the eighth day of illness. There was thick membrane over the whole of the fauces on both sides. There were some nasal discharge and enlargement of the glands on the left side of the neck. There were laryngeal cough and slight stridor but no marked obstruction. The general condition was bad, the pulse was 132 and of low tension, and the heart was slightly dilated. A dose of 20,000 units of antitoxin was given intravenously at 9.30 P.M. On the 9th the urine was scanty and contained much albumin ; it became almost solid on boiling. It had also the green tint associated with carboluria.2 At 9.30 A.M. 23,000 units were injected intravenously. By evening the membrane appeared to be separating. On the 10th it was coming away but the patient’s general condition was not improved and there was some vomiting. More urine, however, was being passed. During the next few days there was gradual loss of ground with increased vomiting. No urine was passed in the last 36 hours. Death occurred on the 15th. CASE 44.-A female patient, aged two years, was admitted The illness was stated to be of two on April lst at 8.10 P.M. days’ duration. There was very extensive membrane over the whole of the fauces on both sides, over the whole of the uvula, and over a part of the palate. The glands were moderately enlarged and there was some nasal discharge. There were slight laryngeal stridor and recession. The pulse was

2

The patient had not worn a carbolic cap since admission to hospital and there was no history of carbolic acid having been used in the treatment of the sore-throat; hence the question arose whether the condition of the urine was due to the antiseptic in the serum.

120 and feeble. On the night of admission 20,000 units of antitoxin were given intravenously. At 6 A.M. on the 2nd there was rapidly increasing obstruction with cyanosis. Tracheotomy was performed and gave complete relief. A dose of 20,000 units of antitoxin was injected subcutaneously. During the next two days the tube was frequently blocked with thick, dry mucus and pus and the child died from exhaustion and toxaemia at 7 A.M. on the 5th. CONCLUSIONS. In attempting to estimate the beneficial effect of antitoxin given intravenously those cases must be discounted in which a marked improvement follows intubation or tracheotomy, since this may be due mainly, or entirely, to relief of the obstruction. Nevertheless, it will be noted that of nine was

operated on only one died, and this must be regarded mortality. Even in cases other than laryngeal it seems to us very difficult, if not impossible, to say of any individual patient that a better result was obtained than might have followed subcutaneous injection. However, taking Series B (from which deaths occurring within 24 hours are not excluded) as a whole there was a fatality of 3 in 38 cases

as a

low

selected severe cases. This result seems to be in favour of the intravenous method. At the same time, although many of the cases treated were undoubtedly very severe, there has been a general fall in the fatality of diphtheria in the district and this leaves room for speculation as to whether the subcutaneous method might not have yielded better results than in the past. THE

PARASITES

(From

OF SMALL-POX. AND VARICELLA.1

VACCINIA,

BY W. E. DE KORTÉ, M.B. LOND. the Bacteriological Laboratory, King’s College,

London.) to ascertain the cause of amaas or Kaffir it was milk-pox hoped that if the morbific agent of that disease could be established light might be thrown on the But all cause of the analogous eruptive fever of small-pox. a for amaas to attempts proved separate specific organism as fruitless as have hitherto been all efforts to separate the agent of variola. That the specific cause or causes of variola, vaccinia, and amaas are in their respective lymphs is manifest. How, then, can the fact that so many capable observers have failed to detect the contagium in the vesicular contents of those diseases be accounted for ?’? Three possible explanations suggest themselves in this connexion. First, the organism may from the smallness of its dimensions escape detection. Chauveauin his original investigation on calf lymph clearly proves that the contagium of vaccinia is due to visible particles and that the elimination of these particles removes the effectiveness of vaccine lymph. The assumption that the cause of vaccinia is microscopically invisible is therefore not tenable. Secondly, the failure to recognise the germ may arise from the lack of a staining reaction which would serve to differentiate the pathogenic organism of variola or vaccinia from the debris present along with the organism in the pock. A third cause for the want of success in demonstrating the causal agent of variola or vaccinia by the methods usually adopted may be that, on account of its fragile nature, the ordinary methods of staining and fixing invariably lead to its destruction. Fortunately this third hypothesis is one which could easily be tested and its disregard is, as I hope to prove, the reason why the arduous labours of many investigators have failed to bring to light the contagium vivum of variola and vaccinia. With the object of testing this view of the case a hangingdrop preparation was made of amaas lymph which had been stored in a capil1ar.y tube for six months, no other manipulation beyond that of allowing the lymph to gravitate out of the tube on to the cover-slip being employed. On examination this specimen was seen to contain a large number of circular elements, a few of them showing a

IN

attempting

1 As demonstrated

before the

Pathological Society

of London

on

Nov. 15th, 1904. 2

3 Comptes

Vide THE LANCET, May 7th, 1904, p. 1273. Rendus de l’Académie des Sciences, 1868,

pp. 289-93 and 317-22.

vol. lxvi.,