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ANTITOXIN IN THE TREATMENT OF DIPHTHERIA.
BY ALBERT ANDERSON, M.D., Wilson, N. C.

In 1883 Klebs, in his investigations as to the cause of diphtheria, found a bacillus in false membrane from a diphtheritic throat. Loeffler, in the following year, isolated the bacillus, discovered its culture medium, reproduced the disease in animals with all the symptoms except paralysis. Four years later Roux and Yerson, of Paris, produced this symptom, and thus gave to the world all the necessary proofs of a specific pathogenic microbe, namely: (1) Its constant presence in all cases of the disease.

(2) It is never found in the body except during the course of the disease or incubation period.

(3) Reproduction of the disease when properly introduced into an animal susceptible to that particular disease.

Scarcely had these proofs been given to the world before the principles of a specific remedy were conceived in the minds cf a few distinguished bacteriologists in different parts of the world.

The pioneer in this great work was our countryman, Dr. George F. Muttall, of Johns Hopkins University, the first to discover the bacteriocidal properties of the blood. Among his colaborers, faithfully as well as scientifically working upon the basis of this discovery, may be named the Frenchman Roux and the German Behring as occupying the next places of honor in the galaxy of original investigators. The result of their labors and of others is antitoxin-the serum from the blood of an animal "rendered refractory to the disease of diphtheria." It is a pale, amber-colored liquid. What I know of the process of making this serum is from observation and study of Dr. J. J. Kinyoun's work on this line during my stay in his laboratory last January and February. Through the kindness of the State Board of Health I spent about six weeks pleasantly and profitably under the instruction of Dr. Kinyoun and his able assistant, Dr. Rosenau, mainly in the study of bacteriology.

At Washington the horse is used to obtain the serum. He is first examined as to his health. Mallein and tuberculin are injected at different times to diagnose respectively glanders and tuberculosis. If there is no reaction. and the horse is apparently healthy other ways, he is selected.

To immunize an animal it is not necessary to inject the bacilli of diphtheria, but their toxins answer the purpose better. Dr. Kinyoun's method in preparing toxin is as follows: A virulent culture of the bacillus diphtheria, capable of killing a 500 gram guinea pig in 24 or 36 hours, is put into a flask containing alkaline peptone bouillon. This flask remaining in the thermostat.

*Read before the North Carolina Medical Society, May 15, 1895.

twenty-four hours at 36° C., grows sufficiently rich in bacilli to be termed a stock culture. Forty c.c. of this inocculates a certain quantity of sterilized alkaline peptone bouillon, which is put into a flask, having a straight neck and a small opening at the side connected with a tubulature. Several of these are inoculated at one time. Placing them in the thermostat at 37° C. for 24 hours to start them, when each flask is connected with an aspirator for the purpose of passing a moist current of air slowly through the bacilli from mouth to tubulature. After about three week's growth these cultures are filtered through a Chamberland filter tube into sterilized flasks and kept for use: If c. c. of this toxin will kill a guinea pig of 500 gram weight in 24 hours it is considered of standard strength and toxins are graded according to this standard. This is now injected into the horse selected subcutaneously, starting with o. 5 c.c. and gradually increasing the dose as tolerance is established, till 300 c.c. or more may be injected at one time-this producing no general reaction, but only a local œdema, which disappears in a short time. This condition indicates immunization. It has been found necessary to give large and frequent doses of toxin late in the treatment to produce a good quality of antitoxin. To test the strength of the serum, only a small quantity is first drawn. A protective strength of 1 to 50,000 is good serum. For drawing a large quantity of blood, the necessary apparatus consists of a trocar and canula, a rubber tube 20 inches long, one end attached to canula and the other to a glass tube about 10 inches long; this outfit is sterilized and kept in a 5 p. c. solution of carbolic acid. Widemouthed bottles, holding about two quarts, are used for receiving the blood. In preparing the bottles, a piece of paper is tied over each mouth and another piece in the shape of a hood is placed over this and then sterilized. Preparation of the Horse.-A nip is thrown over the lip of the horse and a cloth over his eyes for a blind-fold. Hair over the place selected to enter the jugular vein is clipped and shaven and the skin scrubbed well with a 5 p. c. solution of carbolic acid. Incising the skin down to the vessel, the trocar is thrust into the vein with a steady hand. The assistant, removing the hood of paper, plunges the glass tube into the bottle through the paper and the operator or another assistant compresses the veins below and the blood begins to flow. After drawing about a quart into each bottle, the assistant withdraws the glass tube and immediately replaces the hood of paper. From three to six quarts are drawn at one time. The blood is allowed to coagulate and then removed to an ice-chest in the laboratory to stay 24 hours, in which time the serum separates sufficiently from clot. The serum is then drawn off with sterilized pipettes into a receptacle, after which it is passed through a Chamberland filter, one-half p. c. trichresol solution is added for preservation, and in this condition bottled for use.

A syringe named after Roux is used for injection. It holds about 20 c.c. It is composed of a barrel consisting of metal and glass, which are separated

by two India rubber washers, an India rubber piston, a rubber tube with adjustments and a needle little larger than an ordinary hypodermic. The adjustable rubber tube serves an evident purpose in case the child moves. This syringe is sterilized in boiling water for five minutes before using. When ready to administer the serum, thoroughly cleanse the site of insertion and charge your syringe with just the amount to be used. Gather a fold of this skin in the flank with the left hand, insert the needle with the thumb and index-finger of the right hand at the base of the fold, allowing the barrel of the syringe to rest between three fingers and the palm of the right hand. Now, taking the syringe into the left hand, the right is used in gently pressing the piston with a gentle rotary motion. Place absorbent cotton over the puncture and the serum that flows back through the orifice, meeting with the cotton, forms a good serum plug. No massage is necessary after the injection.

The age of the patient, duration of the disease and severity of the case must determine the dose. As a prophylactic it has a better record than as a remedy. There has been no failure to protect when genuine serum has been given in time and in sufficient quantity. Wherever children are necessarily segregated, as in the family, schools, asylums and other such places, an injection of 5 c.c. for children under 10 years, and over that age 10 c.c.. This is thought sufficient to protect for about two months.

In a suspected case of diphtheria administer a full dose of antitoxin. Make a culture at once, and in 24 hours you can tell whether you have the bacillus diphtheria. If not found, discontinue your serum. If found, the symptoms on the following day will indicate the size of the dose. Some give half dose if symptoms are mild, and others give none. If there is no improvement, give full dose during the day, preferably in two divisions, Io c.c. in the morning and 10 c.c. in the afternoon. If there be found a mixed infection, streptococci with the bacilli, and the pulse, respiration and temperature indicate an alarming condition, you have to give full doses on two or three consecutive days. An ideal remedy would in such cases be an antistreptococci with the antitoxin. The presence of streptococci or other cocci does not interfere with the action of the serum, but the serum does not act on them, or remove the septic influences of the pyogenic microbes. If these poison and degenerate the cells beyond the reach of stimulation from antitoxin, your patient will die of septicæmia and not of diphtheritic toxæmia.

From 89 to 94 tracheotomies gave 85 p. c. mortality, while the serum treatment has not only reduced this rightful mortality half, but greatly reduced the number of cases requiring the operation. Given in time, paralysis, pneumonia, albuminuria are rare complications.

D. Kinyoun saw 82 cases treated with serum in Paris, of which 3 died, making about 4 p. c. mortality. Thirty cases in Berlin during two week's

stay, and he observed equally as remarkable results. The serum was exhausted and there was none for six weeks in August and September. During this time the disease increased the mortality. Out of 37 tracheotomies all died but 5. The following six weeks, with the use of antitoxin, there were only 8 tracheotomies and of these died.

D. L. Emmett Holt has had 20 cases treated with antitoxin up to the middle of April, and all recovered except a baby suffering from marasmus.

My friend Dr. W. T. Pate and myself saw five guinea pigs inoculated with from to I c.c. of toxin, giving to three at the same time c.c. of antitoxin, leaving the two receiving the least quantity of toxin as contral. The contral pigs, in 24 hours, were nigh unto death; the other three did not even even get sick. Two rabbits were inoculated with pure culture on trachea and left for 24 hours, when the sickest was given 1 c.c. of antitoxin and the other left as control and soon death controled him, and the other, by the aid of antitoxin, was enabled to gain the victory over death, diphtheria and degeneration.

We did not see it sufficiently tried on patients to express an opinion, but doubting as we were, to us venit vidit vixit our doubts. The following is what I have read from a personal letter: "Were I to have diphtheria I would have the serum administered, because I believe it the best agent we now have, remembering it is not a cure-all." Two hospitals in Paris-one not using the serum had 60 p. c. mortality—the other using it in the same epidemic and at the same time had 24.5 mortality, showing a difference of 35 p. c. in favor of antitoxin. Many months ago unbiased observers admitted, and still admit, that the mortality rate has been divided by two since the use of antitoxin.

These are my deductions:

1. It acts as a specific against diphtheritic toxæmia.

2. The earlier administered the better to limit the disease and prevent complications.

3. It does not restore any degeneration produced by the previous work of toxæmia and septicæmia.

Ophthalmologists who use the ophthalmometer and who ofttimes find the corneal reflection dull ani obscure, with no apparent reason, will find that a drop of liquid albolene instilled into the eye will yield a brilliant result in making the images sharp and clear-cut and with no effect on the estimation of the astigmatism.-Ex.

CLEAN MIDWIFERY, WITH REPORT OF A CASE OF UNCLEAN

MIDWIFERY.

BY F. H. RUSSELL, M.D., Wilmington, N. C.

By clean midwifery is meant midwifery not encumbered with anything useless-perfect, complete. Its principles are simple, its practice easy, requiring the virtues, perseverence, patience, thoroughness. Its results are too well known to dwell upon, depriving child-birth of much of its former horror, robbing death of many of its fairest victims, women in the prime of life performing their office of mother and help-mate, the time of all times at which they could least be spared.

History. This dates from the time when the true pathology of diseases of the puerperium was first properly appreciated, which was the key-note to their prevention and successful treatment. In the time of Hippocrates and Galen the results of unclean midwifery were thought to be due to the suppression of the lochia, this doctrine holding sway for about twenty centuries. This was followed by the doctrine of milkmestassis. These in turn were followed by the doctrines of inflammation of the womb, peritoneum, veins and lymphatics. Many considered it a specific infectious disease, such as typhoid iever. In 1850 Sir J. Y. Simpson published a paper entitled "The Analogy between Puerperal and Surgical Fever," which was the beginning of the modern doctrine. Several years previous to this Semmelweis asserted that puerperal troubles were common in the practice of those who examined patients after performing post-mortems, or students attending patients while working in the dissecting room. He was considered a crank, and was rewarded by ridicule, but with the advance in other branches of medical science, this branch also advanced, and to-day it is an established fact that puerperal diseases are due to germs, either putrefactive or infective. The putrefactive germs are termed bacilli, and depend for nourishment upon some foreign proteid substance, such as blood-clots, pieces of membrane, etc.

Their excreta are called ptomaines, which are capable of absorption by the uterus and are the offending agents. Puerperal troubles due to this cause readily respond to treatment, because as soon as the uterus is cleaned out the supply of ptomaines cease and the organism, with its wonderful eliminating glands, soon dispose of the dose it has. The infective germs are termed streptococci; these possess the power of invading living tissue and are in themselves poisonous. This germ is the cause of the true infective puerperal fever, although the putrefactive germs are found with it. These

*Read before the North Carolina Medical Society, May 15, 1895.

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