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Anti-Charbon Vaccination And Immunity

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ABSTRACTS AND REPORTS. 79 animal made a perfect recovery. The point at which the ulceration took place filled up entirely, leaving only a barely appreciable cloudiness there, but enabling the animal to see with the left eye. The enlarged thyroid gland returned almost to its normal size, leaving only a thickening of the skin at that place. The abnormality of the heart's action and of the pulse disappeared entirely. SECOND CASE OF EXOPHTHALMIC GOITRE, ending fatally.-A valuable bay trotting mare four years old developed sickness the day following a hard race. She, lost her appetite, became very thirsty, languid, and sluggish. After all the domestic (home) medicines had been tried by the trainer, a veterinarian was called in. An examination showed the presence of fever, temperature 39'So c., increased and deepened respiration, accelerated heart's action, accompanied with quickened pulse. The right lobe of the thyroid gland increased in size. The surrounding tissues were also swollen. Some puffiness of both eyes and conjunctiva were present. Cerebral derange- ment was supposed, cold water was applied to the head, and calomel cathartics and enemata were ordered. As time passed on, and the disease, instead of responding to treatment, became more aggravated, a consultation was decided on, and four veterin- arians met, among whom the author was present. During two weeks' standing the disease advanced considerably in gravity. Both eye-balls protruded to the highest degree, preventing entirely the closing of the eye. The conjunctiva was deeply congested and partly protruding. The protruding eye-balls had an unusual lustre and rigid expression. The uniform enlargement of the thyroid gland was evidently due to a certain extent to the dilatation of the thyroid arteries. This was proved by the pulsation of these vessels, which were distinct enough, not only to be felt, but also to be seen. The contractions of the heart were increased in frequency, but did not convey any organic lesions even through the stethoscope, beyond an increased systolic sound; temperature 40'1° C. The animal refused to take food or water. It was agreed to administer internally potassic iodide; to wash the eye with bi-chloride of mercury (1'1000); then to apply compress dressing; to use cold-water baths and inject iodine into the thyroid gland, etc. This treatment was continued for about two weeks, but the animal perished, probably from the superadded grave attack of pernicious an<emia. Unfortunately, no post-mortem was made, as the practitioner in whose care the case had been was too busy at that time. ANTI-CHARBON VACCINATION AND IMMUNITY. M. N. GAMALEIA has contributed to the Annales de l'Institute Pasteurl a paper embodying the outcome of his researches at Odessa with regard to anti- charbon vaccination. Many of the points brought to light by M. experiments are of great interest, not only with reference to anthrax, but also from their wide range of applicability to other bacterial diseases. The vaccin used by M. Gamaleia was prepared after the antiseptic method of MM. Chamberland and Roux. Sterilised bichromate of potash was added to the bouillon used for the cultures in the proportion of 2 to 4 parts per thousand. This does not prevent the growth of the bacilli, but it insures that they shall not proceed to spore formation. Paripassu with the physio- logical impression (attenuation) effected during the process of incubation, the morphological characters of the organism were also affected. Microscopic examination showed that, besides the well-known im1olution forms to be met with in every anthrax culture, there were constantly present numerous 1 October 1888, Elude sur la 'l"accination chcr-rbonncuse.
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Page 1: Anti-Charbon Vaccination And Immunity

ABSTRACTS AND REPORTS. 79

animal made a perfect recovery. The point at which the ulceration took place filled up entirely, leaving only a barely appreciable cloudiness there, but enabling the animal to see with the left eye. The enlarged thyroid gland returned almost to its normal size, leaving only a thickening of the skin at that place. The abnormality of the heart's action and of the pulse disappeared entirely.

SECOND CASE OF EXOPHTHALMIC GOITRE, ending fatally.-A valuable bay trotting mare four years old developed sickness the day following a hard race. She, lost her appetite, became very thirsty, languid, and sluggish. After all the domestic (home) medicines had been tried by the trainer, a veterinarian was called in. An examination showed the presence of fever, temperature 39'So c., increased and deepened respiration, accelerated heart's action, accompanied with quickened pulse. The right lobe of the thyroid gland increased in size. The surrounding tissues were also swollen. Some puffiness of both eyes and conjunctiva were present. Cerebral derange­ment was supposed, cold water was applied to the head, and calomel cathartics and enemata were ordered.

As time passed on, and the disease, instead of responding to treatment, became more aggravated, a consultation was decided on, and four veterin­arians met, among whom the author was present. During two weeks' standing the disease advanced considerably in gravity. Both eye-balls protruded to the highest degree, preventing entirely the closing of the eye. The conjunctiva was deeply congested and partly protruding. The protruding eye-balls had an unusual lustre and rigid expression. The uniform enlargement of the thyroid gland was evidently due to a certain extent to the dilatation of the thyroid arteries. This was proved by the pulsation of these vessels, which were distinct enough, not only to be felt, but also to be seen. The contractions of the heart were increased in frequency, but did not convey any organic lesions even through the stethoscope, beyond an increased systolic sound; temperature 40'1° C. The animal refused to take food or water. It was agreed to administer internally potassic iodide; to wash the eye with bi-chloride of mercury (1'1000); then to apply compress dressing; to use cold-water baths and inject iodine into the thyroid gland, etc. This treatment was continued for about two weeks, but the animal perished, probably from the superadded grave attack of pernicious an<emia. Unfortunately, no post-mortem was made, as the practitioner in whose care the case had been was too busy at that time.

ANTI-CHARBON VACCINATION AND IMMUNITY.

M. N. GAMALEIA has contributed to the Annales de l'Institute Pasteurl a paper embodying the outcome of his researches at Odessa with regard to anti­charbon vaccination. Many of the points brought to light by M. Gamah~ia's experiments are of great interest, not only with reference to anthrax, but also from their wide range of applicability to other bacterial diseases.

The vaccin used by M. Gamaleia was prepared after the antiseptic method of MM. Chamberland and Roux. Sterilised bichromate of potash was added to the bouillon used for the cultures in the proportion of 2 to 4 parts per thousand. This does not prevent the growth of the bacilli, but it insures that they shall not proceed to spore formation. Paripassu with the physio­logical impression (attenuation) effected during the process of incubation, the morphological characters of the organism were also affected. Microscopic examination showed that, besides the well-known im1olution forms to be met with in every anthrax culture, there were constantly present numerous

1 October 1888, Elude sur la 'l"accination chcr-rbonncuse.

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80 ABSTRACTS AND REPORTS.

diminutive forms. The separate elements of the filaments were frequently not more than one-half or one-third of the length of the elements in a virulent culture, and their breadth was diminished in an equal or greater degree. Moreover, in some of the bacilli the normal square-cut end was pointed or dentated. Another variety of rod observed in the bichromate cultures is that which M. Gamaleia terms "digested" (digeree). The bacilli divide trans­versely into small fragments which swell, acquire the appearance of a large coccus, then become pale, and finally are reduced to the condition of a pale envelope deprived of contents. The same phenomenon is brought about in a few minutes when the bacilli are acted upon by the gastric juice. Still another variety of form exhibited by the attenuated cultures was one in which each rod was enclosed in a sheath two or three times the breadth of a normal bacillus.

It was found further that the process of attenuation had entailed some notable changes in the reactions of the organism when sown in milk, for whereas the ordinary virulent bacilli coagulate milk in three days at 35° C., the vaccin or attenuated virus had lost this power.

FeZler 0./ Vaccination.-M. Gamaleia took the temperature of all the sheep vaccinated by him at least twice daily, and he found that an the animals that exhibited as a result of the vaccination a considerable elevation of tempera­ture had acquired a complete immunity with regard to virulent subcutaneous infection, which did not then produce any febrile symptom. On the other hand, all the animals that did not exhibit the vaccinal fever failed to acquire the refractory state, not merely with regard to the virus, but even with regard to the vaccin, which could be reinoculated and give rise to the fever. It is therefore concluded that it is not the vaccin but the resulting fever that con­fers the immunity, for when vaccination passes without any febrile reaction immunity is not acquired. Further, it is indicated that in protective inocula­tions one ought to select a first vaccin of a strength that will produce a pro­nounced vaccinal fever, and the second vaccin of a strength sufficient to excite a second fever after the first vaccin.

Mechanism 0./ the Acquisition of Immunity.-With a view to tracing what actually proceeds in the system during the production of the vaccinal fever, sheep were killed at various periods after vaccination, and the investigation was pursued by (I) microscopic examination, (2) cultures on solid media, and (3) infection of animals. This method of study showed that during the vaccinal fever the vaccin inoculated (anthrax organisms) always penetrates into the internal organs of the animal vaccinated. Rarely, and only at the outset of the fever, the organisms are found in the blood and organs in a living and normal state. Ordinarily at the acme of the fever these are found only deformed and broken up (dissoutes) bacilli. Towards the end of the fever, and up to five days after the crisis, one finds only debris of the bacilli, principally in the liver and kidneys. In the spleen the bacilli were found free, and in the cells termed macrophagi by Metchnikoff, that is to say, the pulp cells provided with a large rounded nucleus. In the kidneys the destroyed bacilli were found in the medulla in the capillaries, ordinarily free, but often in cells with oblong and irregular nucleus and angular body-evidently apper­taining to the endothelium of the capillaries. Microscopic examination showed that the urine always contained bacilli, but attempts to obtain cultures or to infect animals with the urine failed, showing that the bacilli were dead. The vaccinal fever is always accompanied by this penetration of the bacilli into the internal organs, followed by their destruction. The vaccinal fever is related to the presence of the inoculated organisms in the internal organs. The bacilli are found both in the normal state and in deformed conditions. The living forms are found in the blood of the heart and of the capillaries; the bacilli of normal appearance, and in the first stages of disintegration, may

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ABSTRACTS AND REPORTS. 81

be found in the macrophagi of the spleen, of the marrow of bones, and of other organs; the destroyed forms are thrown into the capillaries with prin­cipallocalisation in the medulla of the kidney, where the endothelial cells lay hold of them, probably to reject them with the urine.

M. Gamaleia concludes that the sole difference between a benign vaccinal fever and one rapidly mortal is purely quantitative, depending upon the number of living bacilli; .while in the vaccinal fever the majority of the cultures inseminated from the internal organs remain sterile, in the fatal fever every culture gives rise to a virulent growth. In short, the vaccin produces a general attenuated affection.

The local phenomena observed during the vaccination at the place of injection were always insignificant. The bacilli first multiply before infecting the blood and internal organs, and then this local growth is arrested. The infection leads to the immigration of leucocytes followed by macrophagi, and at the same time the bacilli undergo retrogressive changes. Unfortunately, M. Gamaleia's researches did not enable him to reply with certainty to the important question whether these retrogressive changes are accomplished in or external to the cells, but he inclines to the latter opinion.

The Theory 0/ the Vaccinal Fever.--The essential phenomena of vaccina­tion are (I) a temporary multiplication of the bacilli at the place of inocu­lation, followed by a cellular immigration; (2) a passage of bacilli from this local centre into the blood and internal organs; (3) a retrogressive metamor­phosis and eventual destruction of the bacilli; (4) an elimination of the destroyed bacilli by the kidneys. The arrest of the multiplication of the bacilli at the seat of inoculation is apparently due to the influence of the migrated leucocytes. When inoculation is practised into the anterior chamber of the eye, where leucocytosis is effected slowly, the vaccinal fever is more intense than after subcutaneous inoculation. Going a step further, M. Gamaleia infers from his experiments that this inhibitory and destructive effect of the immigration of the leucocytes is not due to a simple phagocytary action (ingestion and digestion) of the cells on the bacilli, but rather that the leucocytes effect in the nutrient liquids a qualitative change that is hurtful to the bacilli. Thus he found that aqueous humour withdrawn from a sheep previously inoculated in the anterior chamber of the eye when used as a nutrient material produced diminutive regressive forms of bacilli. This was the case also with the humour taken from the eye opposite to the one inoculated. These regressive forms were never found in parallel cultures made in ordinary aqueous humour. Further, it was found that the aqueous humour of an animal upon which immunity had been conferred by inocu­lation under the skin or at any other part of the body remains for a certain time unsuitable as a culture medium for the bacilli, and this prejudicial effect on the humour as a culture medium is proportional to the intensity of the vaccinal fever. It is surmised that the chemical substance secreted by the cells is both antiseptic and pyrogenic, that is to say, it is accountable for the destruction of the bacilli and for the febrile reaction.

The Tlzeoryoj Acquired Illllllltllity.-M. Gamaleia's researches appear to prove that the hope of being able to protect by inoculation with dead cultures is delusive. Of the two phenomena of vaccination- multiplication of the bacilli and their destruction in the organs-it is the first that is important for the acquisition of immunity; and since it is the living bacilli that act it can only be by the specific products which do not exist in sterilised cultures, since these are tolerated without any morbid symptom. The charbon vaccination is an effect of the life and multiplication of the vaccins in the bodies of the animals. Necessarily connected with this reproduction is the formation of toxic products, perhaps specific alkaloids, and the outward sign of it is the vaccinal fever. This transitory culture of the vaccin in the body accustoms

F

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ABSTRACTS AND REPORTS.

the whole economy to the noxious action of the anthrax organism. Accustomed to the poison, the various cells-nervous, leucocytary, endothelial-are not paralysed by its action, and can comport themselves in its presence as in the case of a common bacterium or any foreign body.

ROYAL MEDICAL AND CHIRURGICAL SOCIETY.

ACTINOMYCOSIS HOMINIS.

AN ordinary meeting of this Society was held in Lrmdon on Feb. 12th, Sir Edward Sieveking, President, in the chair.

A paper on a case of Actinomycosis Hominis was produced by Dr R. DOUGLAS POWELL, Mr R. J. GODLEE, and Mr H. H. TAYLOR. A morpho­logical report of the actinomyces fungus obtained from the ca'e was submitted by Professor Edgar Crookshank. A boy aged nine was admitted into the Brompton Hospital for an insidious illness of four months' duration, attended with hectic symptoms, slight cough, and painful swellings on the right side of the chest. He was of somewhat tubercular family history, and the son of a dairyman. The symptoms present were irregular fever, emaciation, slight cough, attended with pain in the right chest. Physical signs: Enlargement of right side, with local swellings, elastic and painful in the infra-mammary and lower postero-axillary regions, displacement of heart, complete dulness over lower two-thirds of the right chest, with annulled respiration and vocal fremitus and weakened voice sounds; a short bruit over the base of the heart; liver and spleen normal; slight enlargement of the glands in the right axilla and neck. Exploration for empyema proved fruitless, and subsequent incision into the lower swelling, which had become fluctuating, with further exploration of the pleural sac, resulted in the removal of some semi-solid yellow matter mingled with blood, which on examination proved to be a degenerated tissue teeming with the ray fungus. The course of the disease was described. The naked-eye and microscopical appearances were fully illustrated, both in stained and unstained specimens. The supposed two varieties of the fungus met with in man were demonstrated to be one and the same, and the appearances of the fungus in man and cattle were compared. Pure cultivations of the fungus taken from the wounds were shown, and the results of inoculation experiments were given. Comments were made upon the clinical and pathological relations of the disease in the human subject, and, upon the position which the actinomyces fungus must be regarded as holding amongst the parasitic micro­organisms.

Dr JOHN HARLEY expressed his delight at seeing the elaborate and beautiful demonstration of the organism. The unprepared specimen was of interest to him, as it showed almost as well as the stained sections, and that the gruwth could be thus recognised was of great clinical value; for if looked for under the microscope, it could scarcely be missed. The case he brought before the Society some time ago agreed in all particulars with that of Dr Powell, only that he could not convince himself that the fungus was present. Might not this sinuous opaque growth in the liver be regarded as independent of the fungus? Was not the fungus itself an accretion upon the caseous material? In other words, was not the fungus the effect and not the cause? In autumn, leaves of coltsfoot would be found dotted over with crimson fungus; another adjacent leaf would have a black fungus, and this would only happen when the vitality of the leaf fell below a certain standard. Perhaps it was because the juice of the leaf was altered, and that this alteration allowed the fungus to grow. He thought the same thing might occur in the tissues, and the advent of the germ might be secondary to tissue disease.


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