The result in these cases treated with antitoxine is not unusual under the old treatment, except as to the rapidity of recovery and the little trouble to both the doctor and the patients of the application of the treatment. It is unusual for me to see a patient die of diphtheria whose larynx is not involved. The death-rate in this section of the country is small compared to that in Europe or the older countries.

The following is an extract from an editorial of the Philadelphia Medical News:

Loeffler was probably the first to render an animal immune to the virus of diphtheria. A guinea-pig which he inoculated wih a small quantity of a pure culture of the bacillus recovered from the infection, and afterward proved to be resistant to repeated inoculations with virulent cultures. Behring, Fraenkel, Boer, Lübbert, and Wernicke have tested various methods for producing artificial immunity from diphtheria, among them vaccination with sterilized bouillon cultures, with bouillon cultures treated with iodin trichlorid, or with tissue or tissue-juices of animals sick or dead of diphtheria, and also by feeding with the toxines of the diphtheria bacilli. Brieger, Kitasato, and Wassermann in the beginning of 1892 grew diphtheria bacilli in thymus-bouillon, thinking, according to Behring, erroneously, that the thymus extract exercised an antitoxic influence on the specific diphtheria poison. They used the product thus obtained for purposes of vaccination. Results have taught, however, that immunity against diphtheria can be most successfully produced and can be carried to the highest grade by beginning with injections of much weakened and highly diluted virus.

A horse, after receiving injections at intervals of from one to four weeks, becomes only very gradually immune, and it is not until the end of from four to six months that the serum has gained any considerable antitoxic power. The amount and strength of the virus are gradually increased as the immunizing process proceeds, so that finally an animal is able to bear several liters of undiluted toxine solution. It is to be noted, however, that the antitoxic value of the blood-serum of the immunized horse bears no definite relation to the amount of toxine that has been introduced into his system. The antitoxic strength of the serum of the horse has to be tested from time to time by experiments on guinea-pigs, the serum being tried not too soon after an injection of the virus. When the desired antitoxic strength has been attained, from one to three liters of blood are drawn through a canula from the jugular vein into sterilized vessels, and cooled in the ice-box for from twelve to fourteen hours. The serum is then poured off, and after 0.5 per cent carbolic acid has been added its exact antitoxic strength is tested upon animals. After the blood has been extracted the animal is usually hungry and thirsty. If it bears the blood-letting well the process may be repeated two or three times in the course of eight days, after which there must be a renewal of the vaccinations for several weeks.

Having now acquired your serum from a reliable source, diagnosticate your case correctly. And as to the possibility of doing this correctly, short of inoculation of some of the lower animals, Park, Beebe, and Biggs, in a recent article published in the November number of the Journal of Laryngology, Rhinology, and Otology, say:

After a year's trial, the following conclusions have been arrived at: The examination by a competent bacteriologist of the bacterial growth in a blood-serum tube which has been properly inoculated and kept for fourteen hours at the body temperature can be thoroughly relied upon in cases where there is visible membrane in the

throat, if the culture is made during the period in which the membrane is forming, and no antiseptic, especially no mercurial solution, has lately been applied.

In cases in which the disease is confined to the larynx or bronchi, and where, therefore, there is no visible exudate against which the swab can be rubbed, surprisingly accurate results can be obtained from cultures, but in a certain proportion of cases no diphtheria bacilli will be found in the first culture, and yet will be abundantly present in the later ones. We believe, therefore, that absolute reliance for a diagnosis can not be placed upon a single culture from the pharynx in purely laryngeal cases. The apparent mistakes have, however, been few. In nasal diphtheria it is possible to obtain negative results from a culture made from the throat, and yet the bacilli be found in cultures from the nose. In making a diagnosis from a culture it is essential to know the duration of the disease in the case from which it was made, for, although bacilli may remain present and alive in some throats for a surprising length of time, nevertheless it is important to remember that they may vanish early and suddenly, and that, therefore, the cultures can not be certainly relied upon after the membrane begins to disappear.

Escherich, in conclusion, states his position as follows: "Since we have found constant cultural differences between true and the pseudo-diphtheria bacilli we can give the pseudo-diphtheria bacilli no diagnostic value. We do not find it to be a frequent inhabitant of the mouth. Chronic throat inflammations and measles seem to render the throat more liable to its invasion."

The results of these investigations, together with those recorded by others, seem to indicate that there are at least two varieties of bacteria, and perhaps more, to which the name pseudo-diphtheria bacillus has been given. It seems to us that these different bacilli should be separated in name as they are in fact.

First: There are bacilli which differ in no respect from characteristic diphtheria bacilli, except that they lack virulence. As Roux and Yersin, Fraenkel and others have pointed out, this loss of virulence occurs naturally at times (virulent and nonvirulent bacilli even existing at the same time in a throat), and can also be produced artificially.

It seems to us that these bacilli should be classed with the virulent diphtheria bacillus, in spite of the fact that their lack of virulence gives them an entirely different relation to the disease diphtheria. The twenty-four cases in which these bacilli were found never developed diphtheria while they remained under observation, nor was any case of diphtheria ever traced to them. This seems to accord with the experience of others.

With the diphtheria bacilli should be classed temporarily such exceptional bacilli as those found in the two special cases described above, for we know that even among virulent bacilli there are marked differences in the luxuriance of their growth.

Second: There are the bacilli especially described by Escherich and photographed by Koplik. These are so uniform in their peculiarities in staining, size, shape, and the production of an alkali instead of an acid, that there seems to us to be even more reason to separate them from the diphtheria bacillus than there is, for example, to separate the colon bacillus from that of typhoid.

We have never found bacilli possessing these peculiarities to be virulent, nor have they seemed to have any connection with diphtheria. It seems to us that to these bacilli alone the name pseudo-diphtheria bacillus should be given.

The few bacilli which do not seem to come under either of these divisions must await further study before being classified.

*Statistics on the antitoxine treatment of diphtheria are getting quite voluminous; they are by reliable and prominent men and are exceed

* For much of the statistics I am indebted to Dr. J. A. Flexner.

ingly encouraging. We all of course know the reliability of such, and consequently make due allowance.

The following are extracts from the Deutsche medicina Wochenschrift, May 31, 1894:

The use of diphtheria antitoxine serum for clinical purposes began in December, 1893, in a small way. A more extended trial was first inaugurated in April, 1894. The first clinical reports of any extent are of Dr. E. Schubert, in the service of Professor Dr. Rinne. Dr. Rinne in the Elizabeth Hospital, in Berlin, reports within the period from February 5th until May 4th, 34 cases, of which 20 were subjected to tracheotomy; of these 28 children recovered and 6 died, the latter of whom were tracheotomized, 14 of those tracheotomized recovering.

Eugene Boswinckel, at the Hospital Urban, Berlin, in the service of Körte, reports concerning the epidemic from December 20, 1893, to January 20, 1894: Since the use of the serum therapy there were 71 cases, of which 53.5 per cent were cured; of these 34 per cent were tracheotomized. These, in addition to those treated up to March 22d, including tracheotomies, give a total of cures of 54 per cent.

Körte says that the results which we have seen certainly warrant us in the further use of this remedy, and from none of the other numberless remedies used against this murderous disease have we had such favorable results as these.

Dr. Canon, assistant professor of Dr. Sonnenburg, at the Hospital Moabit, reports that from December 1, 1893, to March 22, 1894, there were 44 children injected; of these 75 per cent recovered; 13 were tracheotomized, with 62 per cent recoveries. After the June epidemic of the same year, were the figures added to those previously obtained, the results would be 76.3 per cent recoveries, and of the tracheotomies 76.9 per cent recoveries.

The following appeared in the Berliner klinische Wochenschrift of November 8, 1894:

Körte reports the results obtained in the treatment of 121 cases of diphtheria with the antitoxine. He divided the cases into three groups: (a) severe cases; (b) cases of moderate severity; (c) mild cases. Of the whole number recovery ensued in 81 (66.9 per cent), and death in 40 (33.1 per cent); while from June, 1890, to December 31, 1893, among 1,160 cases of diphtheria the proportion of recoveries was 54.9 per cent, and that of deaths 45.1 per cent. In the intervals between the periods of treatment with the antitoxine, at a time when none of the remedy was to be had, among 106 cases there occurred 49 recoveries (46.2 per cent), and 57 deaths (53.8 per cent). Considering 121 cases treated with antitoxine according to their severity, there occurred among (a) 43 severe cases, 41.8 per cent of recoveries and 58.2 per cent of deaths; among (b) 47 cases of moderate severity, 70.2 per cent of recoveries and 29.8 per cent of deaths; and among (c) 31 mild cases, 96.7 per cent of recoveries and 3.3 per cent of deaths. Fifteen of the cases occurred in children under 2 years of age, with 8 recoveries and 7 deaths. Tracheotomy became necessary in 42 cases on account of threatening dyspnea; of this number 20 (47.6 per cent) recovered, and 22 (52.4 per cent) died, as compared with 22.5 per cent of recoveries and 77.5 per cent of deaths in previous years. Of 108 children under 2 years of age, in whom tracheotomy became necessary between June, 1890, and March 31, 1893, 10 (9.2 per cent) recovered; while of 8 within the same age-limits treated with the antitoxine, 3 (57.5 per cent) recovered. Fourteen severe cases came under treatment within the first three days of the disease. Of these I recovered, while three died. In 29 others the treatment could not be instituted

earlier than on the fourth day. Of these but 7 recovered, while 22 died. Twentythree cases of moderate severity came under treatment within the first three days of the attack. Of these 18 recovered and 5 died. Twenty-two others did not come under observation until after the fourth day. Of these 14 recovered and 8 died. In the one mild case that terminated fatally diphtheria bacilli were not found in the exudate. It appeared that in some cases general intoxication took place so rapidly as to render useless the employment of the antitoxine when the cases came under observation. It also appeared as if the results were better when the initial small dose (200 immunityunits) was increased. In the fatal cases death was due to causes over which antitoxine was capable of exerting no influence. Nephritis was the most common complication. It was not observed that the treatment had any influence upon the temperature or upon the local condition, although the injections were soon followed by distinct improvement in the general condition.

The Children's Clinic at Munich, with a very few exceptions, have had to deal only with severe and severest forms of diphtheria. Within the last seven years, of 1,048 cases there died 49.2 per cent; out of these 575 were tracheotomized, of whom 65.2 per cent died, and of those not tracheotomized 26 per cent died. Especially within the last few months, before the use of the serum began, the results were exceedingly bad. Out of 32 cases intubated 30 died, and of 64 children 43 died. In direct connection with these very unfavorable results 9 were treated with Aronson's serum; of these cases, all of which were very severe, 7 were tubed; of the total, 3 died. Still more favorable are the results of ten children treated by Behring's serum, only one of whom died. And this case was a very severe septic diphtheria, and was received only on the fourth day. Three cases were tubed, and all recovered. In addition to this, it was possible to remove the tube much earlier than usual, in one case after thirty-six hours. In many cases a rapid decline in temperature was noticed.

November 22, 1894. Von Ranke, with many other authors, is of the opinion that where there is much sepsis with the diphtheria the serum does not indicate any particular influence, but on the contrary, where the Behring serum is used in the earlier stages of diphtheria, and before the general sepsis has taken place, the results are much better than by any other treatment. Dr. C. Seitz reports an instance of eight children, from one to seven years old, whom it was impossible to isolate from the infected family. In all of these cases two cubic centimeters of Behring No. 1 serum was injected, and though continuously exposed to the infection none of the children became ill.

Dr. John T. Malcolm, in the British Medical Journal, No. 1765, reports a case of diphtheria, in a thirteen-year-old boy, treated with Aronson's serum. He was first injected on the fifth day and received 2.4 grams, and owing to the intense local inflammation in the throat local treatment was impossible, and the case went on to full recovery.

Dr. Frith, in the British Medical Journal, No. 1766, reported a case of an elevenyear-old child which on the third day of illness (the Loeffler bacillus having demonstrated diphtheria) received 19.5 cubic centimeters of antitoxine, and was reported on the fifth day as fully healed.

Dr. Fowler, in the same British Medical Journal, reports a case of a thirteen-yearold girl, who, on the third day, received two cubic centimeters of Aronson's serum, after which the temperature fell to normal and the membrane came away, and after twelve days the child was entirely healed. In another case the same author, with the same treatment, observed a slight paralysis.

Dr. Wakeling reports a case of a six-and-one-half-year-old girl, who, on the sixth day of illness, with a general sepsis, evidenced by chills, otitis media, glandular swelling in the neck, enteritis, and albuminuria, received on the following day

respectively five and three cubic centimeters of Aronson's antitoxine. The local effects were very beneficial, and the general condition was much improved; it died on the fifth day afterward from the general sepsis. The doctor states that this case is in keeping with the hitherto demonstrated fact that the remedy is without influence in such cases where sepsis has become general.

Dr. McGregor, in the London Lancet, No. 3714, reports a case of very severe diphtheria in a ten-year-old boy. On the fifth day the tonsils, half the pharynx, the uvula, and the soft palate were covered with the diphtheritic membrane. There were no laryngeal symptoms, yet there was danger of collapse. An injection of one gram of Aronson's serum brought a very refreshing sleep, and after two further injections a decided improvement set in, which ended in full convalescence on the twelfth day. The writer states that after this experience he will no longer wait for the appearance of severe symptoms, but will use the injection immediately.

Dr. Borger, assistant at the Greifswalder Medical Clinic, reports that they have treated thirty cases, of whom there were two deaths and twenty-eight recoveries. Five tracheotomies and one death, or 93 per cent cures without tracheotomy and 80 per cent with it.

In No. 1768 of the British Medical Journal Dr. Newington reports a result of four cases treated by him in Sussex County Hospital; of these four, three were light and one severe. The last case was tracheotomized on the fifth day; all four recovered promptly and without complication.

Dr. Kuntzen, Marine Surgeon at the Hospital Oschersleven, reports twenty-five cases with twenty-two recoveries, of whom five were tracheotomized with two deaths. These cases varied from the first day to the eighth day of the disease.

Dr. Hager, in the Central. Blatt. f. Innere Medicine, No. 48, of 1894, reports 26 cases of diphtheria; of the 26 one is to be excluded. Of the other 25 the ages were from eight months to six years. The eight-months-old child, which came under treatment in a moribund condition, died. The other 24 recovered. The character of the disease was 8 light, 6 severe, and 10 very severe. The recovery followed so promptly and in so typical a method that there is no room for doubt as to the satisfactory effects of the remedy. Twenty-four hours after the injection most of them were feeling well, and after forty-eight hours the fever had disappeared. After another day the pulse fell to normal. In all his cases, after twenty-four hours, the membrane was sharply marked off from the sound tissue, and in four days entirely disappeared. He had two cases of paralysis and one of dysentery following the disease. Albuminuria was observed only seldom and transient, and this only in the severest cases of the disease. He had urticaria, light erythema in 5 cases in the neighborhood of injection and once on a remote part of the body. He further reports 35 cases who were inoculated for prophylactic purposes, and only 3 showed symptoms of the disease later. Of these one recovered after an injection of the No. 1 vial of Behring serum, and the other two without any further treatment.

A Vienna letter in the Journal of the American Medical Association was as follows:

One day, on entering the ward of Kossel, there were found three children breathing through tracheotomy tubes, aged respectively two, four, and seven years. The doctor explained that the two-year-old child was on the point of suffocating when he entered the barracks; the four-year-old child came to the hospital on the sixth day. His larynx was involved at the time, and before the serum had had an opportunity to retard the progress of the disease stenosis occurred, and tracheotomy became necessary. The seven-year-old child was brought in on the third day with a thick mem