Klebs-Loeffler bacilli, and even seventeen days after I discharged the child as cured there still could be found Klebs-Loeffler bacilli by a bacteriological examination. In all five cultures were made, which proved the presence of Klebs-Loeffler bacilli. This, therefore, is a very important point, proving the necessity of the extremest care in the sick and the isolation of the healthy children, and especially the useless disinfection as practised to-day too early. It has been proved by a great many observers that a child should not be discharged as cured until really two distinct cultures were made on two different days, and both proved negative. The one should be made, if possible, by an officer of the Health Department, and the second should be made by the attending physician.

The

Dr. Ladinski was called, on November 9th, to a child about two years of age, and diagnosed tonsillar diphtheria. He sent a culture to the Health Department, which reported the presence of Klebs-Loeffler bacilli and diagnosed diphtheria. Dr. Ladinski gave the usual antipyretic and antiseptic treatment, using corrosive sublimate internally, until the child appeared to get worse. He next resorted to calomel fumigation, as recommemded by Dr. Dillon Brown in this city. temperature rose in four hours from 102.2° to 103.6° F., and the child appeared very weakened. So I was sent for, in consultation, to use antitoxin. I injected 10 c.c. of antitoxin in the interscapular region on the midnight of November 21st. The temperature fell to 100.6° F. at 2.30 A.M., and was 101.5° F. at 4.30 A.M., and then fell slowly until eight o'clock the following evening, when the temperature registered 102.2° F. At eleven o'clock on the night of November 22d, the temperature was 99.6° F; therefore the temperature fell in this case in twenty-three hours from 103.6° to 99.6° F., without using any medication internally besides the injection of antitoxin. On Friday, the 23d, at four o'clock, in the afternoon, the temperature was normal and remained normal. The membranes which were visible previous to the injection had disappeared with the sinking of the temperature, and in the same way the glands at the angle of the jaw reduced in their size and slowly disappeared. The local treat

ment in this case was carefully followed out by Dr. Ladinski's orders, using a 1,000 to 2,000 sublimated solution on cotton swabs or by spray.

In this case, as in all other cases, we were indebted to the careful comments of the trained nurses in charge. The child remained well and had neither a complication of nephritis nor paralysis. The cases just cited have all of them been under five years of age. They were all cases in which we had recognized a severe diphtheria, and in which the prognosis was not only extremely grave, but in most of them the prognosis was fatal. The fact that the children were extremely weak, and had had different forms of treatment previously, did not seem to affect the action of the antitoxin, nor did it influence it in any way; it did not seem to exert any influence in the complications following the injection of the antitoxin whether treatment was or was not used before the injection of the serum.

Besides the cases above cited, I have seen other severe and complicated cases in consultation with Dr. Romm, Dr. Waechter, Dr. Samuel M. Landsman, Dr. David Goldstein, Dr. Lazear, Dr. A. C. Carpenter, Dr. Stieglitz, Dr. Landes and so on, in all 225 cases. In 45 of these cases it was necessary to intubate; in 3 of these cases tracheotomy was performed. One case, in consultation with Dr. Goldstein, died through the carelessness of the nurse, and it is hoped that Dr. Goldstein will publish his own report of the In none of these cases was intubation or tracheotomy performed unless it was found absolutely necessary. In some cases an emetic was first tried to dislodge membranes and possibly relieve stenosis. others ice-poultices, in the form of ice-bags on the neck, were used, and other palliative remedies. It is hardly

same.

necessary for me to cite other cases, having gone into detail with the last few, but I would rather speak of the indications necessary for the treatment of diphtheria with this new remedy.

If we consider that antitoxin is a product of the toxins of diphtheria injected into the horse, and that we use the blood-serum after an immunity has been produced in the horse, then we see that these toxins produce antitoxin and are only capable of healing diphtheria and really nothing but diphtheria. In one of his last reports Behring mentions the fact that he was prompted to produce antitoxin by watching the course. of pneumonia. He noticed that nature will in a good, healthy individual, suffering with pneumonia, permit the same to have a temperature as high as 105° F. on one day, say at the crisis, and without any medication. Without any reason the temperature will suddenly drop to normal, proving what? Proving that nature has generated in the body certain antitoxins, which have certainly neutralized all the septic poisons generated by the toxins in the course of a pneumonia, and hence, the septic material being neutralized, the temperature returns to normal and the febrile process is at an end. It is easier, however, to write this on paper than to prove it on the living, and I will caution you, therefore, not to believe that antitoxin is a cure-all, but rather, that it is a remedy which has served me well and which has served the most prominent clinicians in Europe, and besides, has reduced the mortality in a great many instances from forty per cent. and fifty per cent. to fifteen per cent., and even lower. Considering also the fact that epidemics of diphtheria vary in different seasons, it is a very welcome remark to read Professor Baginsky's paper in the MEDICAL RECORD, October 6, 1894, and note that he expresses himself in the following terms: That given our worst form of epidemic and our mildest form of epidemic, and the ordinary form of treatment as practised heretofore, the mortality was about thirty per cent., whereas since the introduction of the antitoxin the mortality sank as low as eleven per cent." This latter speaks volumes.

66

Loeffler bacilli the child is isolated and the treatment continued symptomatically and cultures again made; for how often has it happened, especially in the examination of newly formed pseudo-membranes, that no bacilli could be found, and how often can bacilli be found in older portions of the pseudo-membranes in almost a pure culture, so that we must also not forget that a technical error might be made in making cultures, and not be satisfied with one or two negative examinations. I saw a child with a severe form of septic diphtheria in which seven cultures on seven different days showed the absence of Klebs-Loeffler bacilli. This child died, and the post-mortem culture, two hours after death, was negative, and still no membranes involving larynx and trachea were present, as still no bacilli could be found. This shows that isolated cases may give us some trouble in verifying our clinical diagnosis. It is, therefore, perfectly proper to rely on the clinical diagnosis, as in the last case cited by me.

I was called to a child, about seven years of age, which had a severe pharyngeal, nasal, and tonsillar diphtheria, enormous infiltration on the throat and glands, not a very high temperature, extreme somnolence, fetor of the breath. The case was attended by Dr. Gengenbacher. In consultation, on November In consultation, on November 29th, and after a careful examination, we decided that we were dealing with rather a severe form of septicamia, and believing that antitoxin would do good in this case, I injected 10 c.c., exitus lethalis, after twenty hours. Had I known then what I know to-day of the value of antitoxin, I should not have injected that case, but would have warned the physician rather to use other remedies and not depend on antitoxin. To prove that, I was called in consultation, on December 3d, by Dr. N. S. Roberts to a severe form of septic diphtheria. I found the case to be the same as the clinical picture which I have given in the case of Dr. Gengenbacher. I decided not to inject this case, after consultation with Dr. Roberts, as it was really moribund and in the last stages of septic poisoning. The child was suffering from a mixture of scarlet fever and diphtheria. Another child, however, in the same family, which was two years of age, and which Dr. Roberts told me had been exposed to this infection, was injected by me in presence of the attending physician, with 2 c.c. of antitoxin for immunity purposes. Dr. Roberts wrote me that this child remained well and did not suffer any infection, proving the value of the immunity injection.

Contra-indications for the usage of antitoxin are: 1. Cases of mixed infection; cases of scarlet fever complicating diphtheria; cases of measles complicating diphtheria; cases of chicken-pox complicating diphtheria, and so on. 2. Cases that are moribund. 3. Cases that appear to be true septicemia, where we have rather a result of the diphtheria than a real diphtheria to contend with. 4. I found that it was very important to make a careful urinary examination microscopically, and cases that showed a distinct evidence of casts and large quantities of albumin should not be injected with antitoxin.

I find, furthermore, that in a great many cases where casts appear in the urine, and large quantities of albumin, before injecting the antitoxin, that we frequently had quite some hæmaturia, bloody urine, as also severer symptoms, like swollen joints, swollen extremities, etc.

The eruptions which most commonly appear to follow the antitoxin have been varied. Some look like scarlet fever, some appear like measles, most of them look like erythema; seven cases looked like urticaria ; nine cases showed purpura hæmorrhagica; where, however, these last purpura spots appeared it was found that coincident with these there was blood in the urine. I found these purpura spots chiefly surrounding the joints, on the face, and never did I find one in a case that received less than 10 c.c. of antitoxin, so that I was ready to believe that the greater the quantity of anti

toxin injected, the more liable are we to have eruptions, especially of purpura. In one typical case in which we had purpura hæmorrhagica spots, there also appeared spots in the throat, and the gums looked like a typical case of scorbutus. Whether these eruptions are due to impurities of the antitoxin, or whether they are due to a previous disease of the horse and some impurity of its circulation, I do not know. It is, however, a positive fact that I have seen twenty-five cases of diphtheria injected with one kind of antitoxin, in which I did not have any exanthema whatsoever, and again, in another twenty-five vials of antitoxin injected, I seemed to have an eruption in almost every case, one eruption milder and others severer. These eruptions would appear and disappear and reappear when the first, second, and third injection of antitoxin were given, so that there could be no question that the coincidence of the eruption and the antitoxin injection was positive and that one was due to the other.

Finally, permit me to state that the choice of the seat of injection is entirely secondary to me, because I had injected the arm, I had injected the leg, I had injected the abdomen, but chose the interscapular region, because children do not see the needle, and I always could eventually lay a child on the knees of the nurse, face down. It appears to me to be the same as the choice of vaccination of the arm or leg, as practised to-day with cow virus.

I had brought over a small syringe containing 201 c.c., which was recommended to me by the kindness of Dr. Aronson in Berlin, and which was used by Professor Baginsky in the Children's Hospital in Berlin. I have had this syringe constructed through the courtesy of Mr. George Ermold, instrument-maker of this city. I am informed, however, that the firm of Schering & Glatz has imported the original syringe from its maker in Berlin. I should like to emphasize what has already been reported and published by me last October and November, that 5 c.c. of Aronson's healing serum will serve me, and has served me, as well as 10 c.c. of Behring's No. 2, and sometimes as well as Behring's No. 3. No. 1 solution of Behring is so weak for healing purposes that it should only be used, if at all, for immunity purposes. When we think of the small quantity that can be injected by using a concentrated solution, as sold in this city, of Aronson's serum, it is wise in my opinion to use rather 5 c.c. than to be forced to inject 20 c.c., as the pressure of a larger quantity of fluid has in most of my cases made the children cry with pain for several days. Older children and adults described the pain as of a neuralgic character.

I have seen in all 225 cases in New York, in Brooklyn, and in Jersey City in consultation and private practice. I have reported in the American Journal of the Medical Sciences, January, 1895, 34 cases. In a great many of my cases I have injected two and three in one family; seven children for prophylaxis, besides injecting at times one, two, and three sick children for the curing of diphtheria. Several of my cases had been injected in the Children's Department of the German Poliklinik. One hundred and sixty-five cases were children under five years of age. I have also injected six adults. The other children were all over six years of age. Of these I have discharged as cured 191 cases in my own practice, and through the reports of the attending physi cians in the various other cases, my mortality has been 34 cases, besides one accidental death, due to the carelessness of a trained nurse in a case in which tracheotomy was performed. Of these cases 68 showed distinct symptoms of nephritis, which could be proven microscopically. The importance, therefore, of a careful microscopic examination of the urine cannot be overdrawn. Besides the cases just cited of nephritis, 141 cases showed albumin in the urine; in these cases, however, we could not find any casts. In 64 cases hæmaturia appeared about thirty-six hours, in some forty-eight hours, following the injection of antitoxin,

and in which, I believe, we can ascribe the existence of the same to the injection of the antitoxin. It is, however, of the extremest importance to wait some time, until we can definitely prove whether this is a fact or not. In a given case, a strong boy, three years of age, with albumin in the urine 5 pro mille, according to Eschbach, the quantity of albumin increased to 9 pro mille twenty hours after the injection of 5 c.c. Áronson's antitoxin. In this case there were distinct symptoms of hæmaturia present. The symptoms, however, disappeared in two days after the injection, as also every symptom of blood. This was verified by a microscopical examination. Three days later I gave another injection of antitoxin, and again the albuminuria was increased and also the hematuria. Then a distinct eruption of purpura hæmorrhagica was visible. The eruption disappeared in five days. A strange observation was the fact that the eruption appeared much heavier and much thicker in the evening until midnight and disappeared toward morning. These symptoms were found in one distinct consignment of antitoxin, consisting of twenty-five bottles. Strange to say, the next consignment of twenty-five bottles, which arrived from Berlin three weeks later, did not give me any exanthemæ, resembling measles, urticaria, or scarlet fever, so much so that I was greatly impressed with the idea that possibly the eruptions in my previous case were due to some specific impurity traceable to the horse's blood or his system, and possibly the other consignment of antitoxin, which did not yield eruptions, may have been drawn of a healthier horse.

The quan

tity to be injected is of very great importance. So I find that 5 c.c. of Aronson's antitoxin yielded just the same results as 10 and 12 c.c. of Behring's No. 2. This concentration of Aronson's antitoxin I regard as of very great value. This has been repeatedly pointed out by me in the MEDICAL RECORD-October 6, 1894, and later on, November 17, 1894, same journal.

Post-diphtheritic paralysis has been frequently ob served by me during the course of antitoxin treatment. I have in all had twenty-one cases of facialis paralysis, and also paralysis of motion; paresis of the upper and lower extremities has also been observed by me. In all these forms of paralysis, however, there appeared some symptoms, and some are still to-day under treatment, although it is three months since the injection of antitoxin was given. I do not, therefore, believe that we can modify the course or the form of the paralysis occurring during diphtheria by injections of antitoxin. I do think, however, and I have seen cases that were injected early, that did have very mild forms of paralysis, so much so that it is possible that the antitoxin neutralizing the poison of the diphtheria absorbed in the system prevents, and probably modifies, the amount of septic matter absorbed, so that the toxins in the system do not affect the muscles and nerves as if they were not neutralized so early. The technique of the injection consists of 1. A careful sterilization of the skin of the patient to be injected at the seat of injection, the interscapular space, or the pectoralis region. Sterilization consists of washing of the skin with soap and warm water, then sponging the skin with a 1,000 to 2,000 sublimate solution. 2. The hands of the physician must be carefully and properly cleaned and rendered aseptic. 3. The syringe should be completely sterilized by boiling fifteen minutes in a soda solution. The needle should be dipped in alcohol, followed by a two per cent. solution of carbolic acid. 4. It is necessary to inject slowly; at the same time to have the proper quantity of serum drawn into the barrel of the syringe, so that no time is lost. The needle should be pushed into the deep cellular tissue, at least two inches in a semi-horizontal position. 5. Massage of the fluid injected with the skin should not be practised; finally, I should apply a very small pledget of absorbent cotton over the injected space, and the oozing of a small quantity of serum makes a film

which completely prevents the entrance of septic material. The injected spot can also be sealed by dropping collodion over it.

The absorption of the antitoxin takes usually from one-half to one hour. At times I have seen a swelling produced by the injection of 5 or sometimes 10 c.c. of antitoxin remain for fifteen and even eighteen hours in one case. This is, however, rare. In other cases I can remember that the swelling disappeared within twenty minutes.

I have previously mentioned the fact that I refused to inject a case after consultation with Dr. Roberts. The same was true, later on, in consultation with Dr. Shulman, in which case the child was so moribund that we believed it useless. Both children died very soon afterward, and I have therefore reduced my mortality somewhat by not injecting these hopeless cases of septicamia. Finally, I desire to state that my mortality has been 35 in 225 cases treated; 22 cases were under five years of age; 16 of the latter were under three years. My mortality has, therefore, been equivalent to 151 per cent., although my percentage of cures in the first 34 cases reported was 5 per cent. The high death-rate given by me is far above what has been given in Berlin, the Children's Hospital, and in several other hospitals abroad. This can easily be explained by the fact that in the majority of cases in which I was called in consultation to use antitoxin, it was used as a last resort only, and therefore the majority of cases were looked upon as hopeless. I took chances of injecting a great many cases in which we considered a grave prognosis, and therefore have attained the results specified above.

In conclusion, I desire to state that antitoxin should be used early, and believe that if the rules given above be carefully carried out, it is a safe remedy and can cure every case of diphtheria seen early; and even the most malignant cases should be injected, because I have seen moribund cases that were considered absolutely beyond medical control get well. I again. state, however, that I do not believe it a cure-all, but believe it to be the best known remedy for the treatment of diphtheria in use to-day.

187 SECOND AVENUE.

perience with the disease I have never seen a more profuse exudation nor one of more malignant aspect. This view, as taken by me, was not due to the natural anxiety of a father, for Dr. H. M. Biggs, to whom the medical direction of the case was entrusted, concurred with me in the opinion.

On Tuesday morning the result of a culture showed Loeffler bacilli; temperature at 8 A.M., 1033° F.; cervical glands much enlarged and inflamed. The circumference of the neck was very much increased, and over the enlarged glands the skin was red. Eleven cubic centimetres of the same serum was injected at 9 A.M. On Tuesday night, 8 P.M., temperature, 102° F.; the membrane was detached along its free margin and a considerable portion of it was cast off. On WednesOn Wednesday, 8 A.M., temperature, 100° F.; the membrane was partly cast off, though a large, loose mass was still to be seen in the pharynx; the respiration was not much impeded, nor was it so rapid. The throat was sprayed for the first time with Dobell's solution, and this was continued during the waking hours at intervals of every two hours. This, with the exception of four grains of gray powder, given on Wednesday and Friday nights, was the only treatment in addition to the serum. On Thursday, 8 A.M., temperature, 98° F.; the membrane was nearly all gone, small granular spots of it only appearing over the tonsils (which were congenitally large) and over the posterior walls of the pharynx; the appetite on Thursday returned, for prior to this time during the course of the disease it had been difficult to induce the child to take milk, which was the only nourishment. On Friday, temperature, 8 A.M., 99° F. ; 8 P.M., 100 F.; appetite good, membrane entirely disappeared. On Saturday, 8 A.M., temperature, 991° F.; 8 P.M., 100° F.; throat normal, glands almost so; no redness of skin. On Sunday, temperature, 8 A.M., 98° F.; the afternoon temperature was not taken, but it appeared to be normal; the appetite was ravenous and the child could with difficulty be kept in bed, as he asserted he was well and had been for some time. He did not seem to have lost flesh, nor to have been much weakened by his illness. He is an unusually robust child.

CASE II-A girl, aged nine, also remarkably robust, but with extremely large tonsils and a very nervous temperament, was taken sick with sore throat on Tuesday morning, before the report from the culture taken from the boy's throat showed positively his disease was diphtheria. Within three hours, however, subsequent to the visible commencement of the attack she received 6 c.c. of the same serum that had been administered to the boy. Temperature, Tuesday night, 104° F.; throat much congested but no membrane, and the culture taken showed the presence of suspicious bacilli, the report from this culture being received Wednesday morning. On Wednesday, 8 A.M., temperature, 1021⁄2° F.; patches of grayish exudate appeared over both tonsils, but this was not sufficient to entirely cover them; pharynx and uvula much inflamed. Six cubic centimetres of the serum were again administered at 9 A.M. The child was much terrified by the method of administration and had to be forcibly held. Temperature, 6 P.M., 104° F. This high temperature was accompanied by a slight delirium, and was attributed to the effect on the nervous system of the struggle and fright incident to giving the antitoxin. By the advice of Dr. Biggs a single dose of ten grains of sodium bromide was given, and two drachms of whiskey administered every three hours. Within two hours and a half after the administration of the sodium bromide the temperature dropped to 100° F. On Friday, temperature, 8 A.M., 99 F.; 8 P.M., 994° F. Saturday, temperature, 8 A.M., 99° F.; 8 P.M., 991° F. The child appeared well and extremely anxious to get up. During the course of the disease this child's throat was frequently sprayed with Dobell's solution. The injections of the serum in both cases were made in the abdominal region. Beyond the

slight point where the needle entered the skin nothing is visible to show the site of any of the injections.

To a girl of twelve years, a sister of the children treated, 21⁄2 c.c. of the same serum was administered for preventive purposes. Notwithstanding the fact that she was closely exposed, has a sensitive throat, with hypertrophy of the tonsils, and is extremely subject to tonsillitis, she escaped infection, but on the seventh day developed urticaria, which at first was localized over the site of the injection. The eruption covered an oval spot three by four inches, but did not extend or appear elsewhere until the ninth day, when a number of shotty papules, very closely resembling chicken-pox, but not proceeding to vesiculation, covered the dorsal aspect of the arms and hands, the chest, abdomen, and lower extremities.

The rash was most profuse over the arms and legs, and the itching caused by it was a very distressing symptom. The papules lost their shotty feel after twenty-four hours and spread by increasing their diameter until they coalesced and covered the extremities almost uniformly, leaving little streaks of white skin visible in places. On the third day after the appearance of the rash it began to fade, and by the evening of the fourth day it had totally disappeared. The temperature just preceding the appearance of the rash was considerably elevated.

During the outbreak the temperatures were as follows:

On the eighth day after the injection the younger girl suffered from a profuse general urticaria. The eruption was intense and confluent, closely resembling the eruption of measles and involving the conjunctiva and mucous membrane of the mouth and palate. The itching and discomfort were so great that bromide and camphorated tincture of opium had to be given. The rash was preceded by a rise in temperature and persisted for five days. After the second day the eruption was much better at night, disappearing except in a few isolated spots, but reappearing after eating breakfast the following morning. During the middle of the day it appeared to be at its height. The temperatures taken night and morning were as follows:

Vaseline containing four per cent. carbolic acid appeared, in the case of the younger girl, to best allay the itching. In the case of the older girl, however, a solution of one ounce sodium benzoate in a pint of glycerine was made, and this being mixed with hot water in equal parts and used as a wash, seemed to give the most relief. The boy, who received the largest dose of the serum, and had the most profuse diphtheria exudate, did not, however, develop any urticaria until the seventeenth day after receiving the serum. Just preceding the appearance of the rash he seemed languid and complained of feeling tired. His temperature taken showed a rise to 102 F. During the course of the day a number of wheals appeared on his arms, legs, and face. The diameter of these blotches was from one inch to two inches. The patches were isolated and gave rise to intense itching, which was relieved by a four per cent. carbolated vaseline. The temperature at night had fallen to 101° F., and the following morning was normal. The rash disappeared within six hours of its appearance, and did not again appear.

The two girls did not have at any time during the course of the disease, or afterward, any albuminuria, though the urine was frequently examined. The urine of the boy, however, on the third day after the attack was found to contain a trace of albumin, which disappeared about the sixth day.

A study of this eruption is very interesting. The cases treated by antitoxin at Willard Parker Hospital have developed it in comparatively few instances. Dr. Somerset, the resident physician, has reported the following facts concerning it :

Of 117 cases treated with antitoxin in the Willard Parker Hospital, 12 had an eruption which appeared between the eighth and twelfth days. Of these 12, the character of 4 was erythematous, somewhat resembling measles in appearance, distributed principally on the extremities, and exclusively so in 2 cases. These 4

cases were differentiated from measles by the irregular distribution of the eruption, the absence of coryza, conjunctivitis, and the characteristic measles temperature. Of the remaining 8, 5 were urticarial. The distribution of the eruption was irregular, the wheals varying in size, but seeming to be larger in the vicinity of the site of the injection, where they first appeared in 3 of the 5 cases. Most of the wheals had extensive peripheral erythema. The other 3 cases presented a distinct blush, irregularly distributed in areas of varying size. These areas were scarlatinal in appearance, but the distribution, tongue, and temperature were in nowise characteristic of scarlet fever. None of these rashes lasted longer than thirty-six hours, but in the urticarial forms they would disappear and again reappear, the alternations occurring perhaps three or four times in a single case. The eruptions seemed to occasion no inconvenience nor discomfort, and received no treatment other than occasional washing with some simple lotion. The temperatures were very irregular, and were usually highest before the rash appeared, but were in some cases highest during the eruption or immediately after its disappearance. Four of the five urticarial rashes occurred in cases receiving antitoxin from one particular horse, whose serum would thus seem to be more likely to cause an eruption than that from the other

animals.

It will be seen there is a very distinct period of incubation after the administration of the serum and before the appearance of the urticaria. This period may be put at from five to seventeen days, and it shows, in my opinion, the eruption is not due primarily and directly to anything contained in the serum, but rather to the action of the serum on the system of the patient; or perhaps to the development in the blood of the patient of some pathogenic substance through this action. To effect this action, or, rather, to effect this change in the system of the patient, requires the time which elapses during the period of incubation. It is evident that not every person is susceptible to this effect of diphtheria antitoxin, or that the toxin of diphtheria is an antidote to the urticarial effect of the antitoxin. Time and a careful study of a great number of cases will alone demonstrate which, if either, of these two hypotheses is correct. The normal horse serum may have the property of causing the eruption in susceptible persons. Experiments are at present being conducted in the Health Department Laboratory, with a view of ascertaining the truth or falsity of this theory. It may be, however, I think, safely assumed that the eruption is a local lesion of a general disease, of which the serum is the cause. This seems to be proved by the distinct period of incubation and the rise in temperature, which, I think, will be found more or less characteristic in the majority of cases where the temperatures are carefully recorded.

Concerning the therapeutic action of antitoxin there is much conjecture. The agent does not act at once like drugs administered hypodermically, but requires a very distinct and somewhat prolonged period

of time to do its work. This period varies from ten to twenty-four hours, and makes it essential that the remedy should be given early in the attack to effect its object.

The theories advanced, when antitoxin was first used, and which seemed to be the most tenable from a bacteriological stand-point, were: the immune serum sufficiently reinforced the natural resistance to the disease to turn the balance in favor of a cure, and that the blood of the immunized horse contained a sufficiency of something that neutralized the poison of diphtheria as an alkali neutralizes an acid. These theories do not appear to be correct, for if they were, the action would follow the administration more promptly. It seems to me more probable that serum acts through the changes it effects in the blood itself, and that it requires time to bring about these changes. Whether it is that these changes are chemical and are due directly to the effect of the serum on the blood itself, or that they are brought about through cell stimulation, or that they are due to the development in the blood of some new substance, is not in the least apparent.

It is interesting to study the mortality among cases of diphtheria treated with antitoxin at Willard Parker Hospital, since January 1 to March 10, 1895. The total number of cases treated was 117; the total number of deaths 27; the per cent. of mortality, twentythree; per cent. of mortality for corresponding period of 1894, thirty-three. During January the antitoxin used was very weak, requiring about c.c. to protect a guinea pig weighing 250 gm. against an amount of toxin equivalent to ten fatal doses. This is about the strength of the solutions used for immunizing purposes. Of the 117 cases above named, 46 occurred during the month of January and the number. of deaths was 13. The per cent. of mortality, therefore, for January was twenty-eight plus. January 31st to March 10th the number of cases treated was 71, the number of deaths 14, and the per cent. of mortality nineteen. The serum used during this period was considerably stronger, the immunizing dose for guineapigs being from to go C.C.

The number of cases of croup since February 1st at Willard Parker Hospital was 30, the number of deaths since February 1st 10; per cent. of mortality 33; and the croup mortality for 1894 was fifty per cent.

The number of operative cases of croup since January 1st was 22; the per cent. of mortality among these cases forty-five; per cent. of mortality for 1894, eighty. The average number of days that the diphtheria cases were sick before admision and administration of antitoxin was, in the fatal cases, 51% days.