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birth to a foal, which, as far as external appearances were concerned, was perfectly healthy, except that it was extremely weak. Being very young, however, no trouble was anticipated from this cause. In all these cases the fœtal membrane was always abnormal in appearance.
Appearance of Membranes when Found. -The membrane of this particular case, when found in the morning after the labor (upon a hill-top), and a close and minute examination made, revealed the following facts: That portion of the membranes accompanying the horns of the uterus, was found to be undergoing decomposition, having a deep red, congested appearance, this followed by a leaden greyish color later, and exhaling a very sanious odor. Small patches of the membranes were entirely destroyed, and small quantities of a muco-purulent matter were to be found. From these membranes, septic material was obtained for future use for experimental purposes. The method will be found hereafter in "History of Experiment and Result so far as Ascertained," the direct operating cause being a microscopical parasite, with its classification not yet definitely determined; the life, history of the parasite, and its habits, are yet also to be determined.
Symptoms. In this trouble — infectious abortion no symptoms save those premonitory signs, as a possible uneasiness noticed in simple abortion, are noticed, and most frequently nothing at all is to be seen. However, in the joint However, in the joint affection, due to the same organism which caused abortion, as shown by investigation hereafter noted, affecting the foal which lived, the following symptoms were noticed About a week or ten days after the birth of the foal there was a swollen condition of some of the joints of the limbs. These increased in size, and became very painful. They often ruptured and a muco-purulent discharge escaped. Usually, however, there was no rupture, but a continuous distention of the synovial sac. Upon manipulation, these swellings were found very tense and feverish, the little fellows, with a most dejected look, stood or reclined alternately, moving around very little, on account of the extreme pain caused by any motion whatever. A severe synovitis, at times partaking of a suppurative character, was
1. If the mare aborted in an open paddock or pasture, the foetus and foetal membranes should be burned, and the mare taken to a stable or small lot where she can be easily treated.
2. If the mare is removed to a stable, it must be apart from any other stable containing pregnant animals, and must not be on high ground, the urine of which will run into lots, paddock, or field occupied by pregnant animals; if removed to a small lot, the lot must be low or situated in such a place that no pregnant animals will by drainage be exposed to the germs causing the trouble.
3. (This third measure is only necessary in mares that have aborted and are not doing well.) The external parts should be thoroughly cleansed with a solution of hydrargyrum bichloride (corrosive sublimate), I part to 1000 parts of water. The tail itself should be thoroughly washed with the same, or if in fly time, a solution of carbolic acid may be supplemented to the corrosive sublimate, of the strength of one part of acid to 100 parts of water. This having been done, the vagina and uterus should be thoroughly cleansed with injections of pure tepid water. After this, use the solution above mentioned for injections per vagina. Continue these injections once a day for two or three days.
4. The attendant treating mares should thoroughly disinfect his hands, and if possible change his clothing before he goes into the presence of pregnant animals.
5. The mares, after two or three weeks of treatment, may be allowed to the stallion with safety.
6. The foals affected with joint-ail (it being the same disease differently main
fested and capable of producing abortion) should be destroyed, and their carcasses burned.
7. If, however, the foal is suffered to live, it should be separated from pregnant animals, before any of the swellings exhibit suppuration or sores.
8. A mare, the dam of a foal suffering from the joint-ail, should undergo the same antiseptic treatment as though she had aborted, providing she is not doing well.
9. Mares that have aborted and done • well should not be allowed to stallion sooner than two or three weeks after the accident.
History of Experiment and Result so far as Ascertained. A few days after arriving at the ranch, June 25, "Biddy Mac, a trotting brood mare, gave birth to a foal. This foal, previously mentioned, was very weak, and died from starvation in two days after its birth. A post-mortem examination was held, but nothing could be found sufficient to cause death. The udder of the dam was then examined, and no milk found. Cultures were made from the blood and several of the glands of the colt, to see if they might possibly contain any of the germs causing the trouble. It is not intended to give the results in detail, as many of the minute points were only tedious and of no practical value to the general public.
Cultures were made from the diseased foetal membranes from "Biddy Mac," and inoculation made therefrom. One bay mare in foal received the inoculation on June 6, and on the following night she foaled. On June 29, the foal showed signs of joint trouble in right knee, and on July 1, the hock joint was as large as a man's head. Thus, from this experiment, almost just begun, we might say, do we produce the disease in a colt that when born was apparently in health, and that, too, after the inoculation had only been introduced a few hours.
Another mare, a dunn, inoculated with a culture from the blood of Biddy Mac's colt on the 20th day of June, gave birth to a dead foal. This was an abortion, as evinced by the diseased placenta. Hence we see that from these two inoculations with culture, we have produced both the diseases, abortion and joint trouble. The germs causing these two diseases are the same, as shown under the microscope. That these two maladies are one and the
same disease differently manifested, there is no doubt.
Other and more varied experiments were tried, and are still in progress, concerning other matters with reference to the possible nature of the malady in regard to immunity and length of incubation after natural exposure. The investigation in these lines is not yet consummated, and much time and attentive work must be done ere the public receive any further statements.
From the foregoing it will be seen, that antiseptic measures in the way of washes, etc., in treating mares that have aborted, are not sufficient, and perhaps of doubtful benefit, the germ causing the malady being in the system and not a local parasite ; that strict sanitary measures are necessary; that medicinal treatment, of whatever nature, will be of no benefit so far as removing the cause or preventing the accidentis concerned; that joint-ail and abortion are the same malady differently manifested; that local application to umbilicus of a recently born foal whose dam has been infected previous to foaling, will not prevent the occurrence of joint-ail in colts.
The following facts may be determined by experimentation :
Whether one attack gives immunity to another the succeeding year; whether we will or will not be able to vaccinate against its appearance; what is the length of time required for incubation under natural or accidental exposure; whether or not the germ is capable of producing abortion save at certain stages in its life; and what is the length of time during which the germ remains in the animal economy.
TYPHOID FEVER IN THE LIGHT OF MODERN RESEARCH.
BY L. BREMER, M. D., St. Louis, Mo.
Introductory Remarks. When, under the stimulus of the cell-doctrine, the pathological anatomy of typhoid fever had been settled to the satisfaction of the inquiring medical mind, a great step, and in the opinion of some, a final one, had been taken toward the understanding of the nature of that disease. Of course there was still that intangible, mysterious something, the air and the soil in their varying conditions, which baffled the in
vestigators of those times, and hovered over the minds of the hygienists and practical physicians as the Kismet does over the Turk. The pathological anatomy was well understood; but what was the ultimate cause of the histological changes peculiar to the lesions found in the typhoid, and what gave rise to the variegated symptomatology of the disease? This was the question of questions which engrossed the minds of pathologists and epidemiologists of that period of medical history which preceded the bacteriological era.
The enthusiasm which arose, not only in the medical laboratories, but among the educated of the civilized world, in the beginning of the eighties, the springtime of bacteriological research, when, together with many other pathogenic microbes, the bacillus of typhoid fever was discovered, can be fully appreciated. by those who, though in a modest way, participated in the movement, and shared the hopes it awakened as to the reach and ken of the physician of the future.
Very naturally it was presumed that, once the causes being determined and located in these vastly preponderating diseases of afflicted humanity, the infectious, it would be a step of less difficulty to find the agents endowed with the faculty of destroying those causes.
At that time it was considered a great triumph of progressive science to discover a new coccus or bacillus in a given infections disease. The specific microbe having been determined, the next logical step was to seek out such chemical substances as were most incompatible with the lives of the several species of cocci and bacilli, and thus to lay the foundation of the "only rational" method of treating infectious disease. The watchword, "antibacterial therapy," was then heard for the first time.
But the hopes founded on this new departure gradually dwindled down; and how the pessimists had in this, as in other matters generally, once more the better of the enthusiasts, I need not particularly emphasize before a body of medical men, most of whom have watched with interest the developments in the history of our science during the last twelve years.
Practical tests showed that antibacterial therapy, with the sole exception of surgery and, though to a lesser extent, dermatology, did not materially affect the
results of treatment, and what was particularly discouraging to those who looked hopefully forward to a speedy achievement of cure and prevention in infectious diseases, was the fact that by the mere finding of a specific and pathogenic bacterium, only a very slight advance had been made toward arriving at a knowledge of the true nature of the disease, especially of the manner of its spread, the channels of infection, the local and temporal conditions favoring or hampering and preventing its development, etc.
It was found that a bacterium, which, by common consent, had been recognized as the exclusive visible etiological factor of a given disease, was far from presenting the same morphological and biological characteristics which the discoverers had established and described; and that the teaching of the oft-insisted-on constancy of form, life-habits, and pathogenic effect. had to be considerably restricted in the course of time, with the broadening of the light shed by experiments and counter-experiments on these questions. Much that had been proclaimed as incontrovertible fact, did not withstand the test in the crucible of clinical, and especially epidemiological observation.
The conviction had not in those times settled so firmly as to-day, on the minds of investigators, that what is true in vitro in the test-tube and the flask may not be true in nature.
The insufficiency of the results obtained so far in the laboratory, for the purpose of clearing up the heretofore mysterious features of infectious diseases, applies in a peculiarly forcible manner to the history of typhoid fever investigation during the past decade; but I hasten to add, that in spite of disappointments in some directions, there is perhaps no other disease where painstaking and untiring labor has. met with such brilliant scientific, and in some instances, surprising and eminently practical, results.
Effect of Eberth's Discovery on Formerly Prevailing Notions. After the bacillus, which is now recognized by the overwhelming majority of authorities as the exclusive morbific agent in the typhoid fever process, had been discovered by Eberth,' Pettenkofer's theory seemed to
1 It is very questionable whether the one described previously by Klebs is identical with the one now regarded as specific.
have been deprived of its mainstay; and the tide of clinical evidence tending to show the simply contagious nature of typhoid fever, seemed to have gathered sufficient force to sweep off the grounds of scientific medicine a structure which had been erected and finished by untiring energy and wonderful ingenuity.
For years previous to Eberth's discovery, clinicians, restive under the therapeutic, and, in a measure, prophylactic nihilism, which the prevailing epidemiological notions indirectly implied, had been at work to undermine Pettenkofer's edifice by the force of argument based upon the facts gathered at the bedside and in the surroundings of typhoid fever. patients. The demonstration of Eberth of a bacillus found invariably in the organs most affected by the morbid process in every case of typhoid fever, seemed to furnish the missing link in the chain of those arguments.
Inadequacy of Bacterial Demonstration. But the simple demonstration of a bacillus in all cases in which the clinical picture was that of unequivocal typhoid fever, though accounting satisfactorily for the pathogenesis of the disease as such, fell far short of explaining all the problems, which, in the course of the histories of epidemics, had presented themselves for solution, and which, since the discovery of the microbe, were constantly multiplying.
Pettenkofer's Theory. Above all, there was the remittent character of the epidemics which called for a factor back of the bacillus, and which seemed to be felicitously furnished in the form of the hypothetical, local, and temporal predisposition. After the germ, formerly only a logical postulate of Pettenkofer, had been found, it remained to be proven that under certain atmospheric conditions coupled with a low level of the ground water, the bacillus not only underwent a maturing process, necessary for a successful invasion of the human organism, but also that it was dispersed throughout the atmosphere in order to reach its victims. This proof has never been furnished. Besides, many of the phenomena which formerly were utilized by Pettenkofer in favor of his theory, have been interpreted by modern observers in an opposite sense. It seems, therefore, that, as in cholera, so in the typhoid question, one after another of Pettenkofer's arguments have to yield
to the doctrine of contagion as against that of the miasmatic origin of disease, in spite of the fact that bacteriology in its present state is still very far from explaining everything, and that we are still in absolute darkness as regards some of the most vital points touching the question under discussion.
Morphology and Biology of the Typhoid Bacillus. In order to have a proper appreciation of the difficulties barring the road to exact knowledge, but at the same. time, of the palpable and demonstrable results which have been obtained through the study of Eberth's microbe, a short account of what we know of its forms and life habits may be in order at this place.
Unfortunately, the most elementary of all criteria, its form, offers nothing characteristic. It looks like many other bacilli, and, what is worse, varies very much according to the media on which it grows. This polymorphism it shares with many water and ground bacteria, and with a number that are normal inhabitants of the intestinal tract. The one most frequently met with, and with which it is most apt to be confounded, is the bacillus coli communis. The ends are rounded off, so that a short specimen of the microbe may give the impression of an ovoid-shaped coccus. Under some conditions it develops seemingly into threads, which on close inspection, however, are found to consist of a continuous chain of bacilli.
Motility. Their motility is effected by vibratile cilia (flagella), of which the fully developed bacillus possesses from three to six, or more. The larger individuals have a snake-like motion.
Nutrient Media as Affecting the Growth of the Microbe. Like many other similarlooking bacilli, it grows in gelatine at ordinary temperatures, without liquefying it. Hitherto it has been held that its growth on potatoes is quite characteristic. But a close research has demonstrated that the thin, glistening, almost invisible film which covers the potato, is produced by other bacteria likewise; and that, when the surface of the potato is rendered alkaline, a yellowish brown covering results. If to this uncertainty of the potato culture, which up to a short time ago was held to be absolutely diagnostic, is added the fact that Koch found five bacilli which in all respects are similar to, or even
identical with (excepting their pathogenic properties), the typhoid germ; and that Kitasato, a Japanese physician, and one of the ablest and most reliable observers of Koch's school, has a list of sixteen different bacteria, all of which may be easily confounded with our microbe; it becomes evident how perplexing may be the task of demonstrating the presence of the typhoid bacillus under certain conditions; when, for instance, water or solid substances are to be examined for the typhoid germ. Of course, there is little difficulty in determining it when the material for examination is taken from the living body or from one of the organs in which it is known to form colonies by preference.
Organs Harboring the Bacillus.-These organs are, besides Peyer's patches, the spleen, liver, and mesenteric glands. Here the bacilli congregate and entrench themselves; only occasionally are they found in the blood. I myself have examined the blood of six patients without being able to demonstrate their presence either microscopically or by culture. By tapping the spleen with a hypodermic needle, they have been found by several investigators in the blood thus obtained; as a diagnostic means, however, the spleen puncture does not, as a matter of course, recommend itself. Sometimes they are found in the brain and spinal cord. One observer claims to have discovered them in the roseolar eruptions which, he says, are the result of bacterial capillary embolism. This observation has not been verified. In two cases which I examined, no bacilli could be demonstrated. More probably the roseolar spots are the result of the action of toxic materials circulating in the blood.
Difficulties in the Way of Investigation. But the chief difficulty barring a successful study of the typhoid bacillus, lies in the utter absence of animals sponany the disease. taneously susceptible to Rabbits, guinea-pigs, rats, and mice have been inoculated; and in isolated instances the characteristic lesions in Peyer's patches were the result of such inoculations with pure cultures. But generally there was no infection, merely a toxæmia,'
1 In a true infection the bacteria, when introduced into an animal organism, develop and multiply, and the number of germs is, theoretically at least, of no importance. A toxæmia will result secondarily from the poisonous products secreted by the pathogenic germs. In toxemia, pure and simple, it is the amount of bacteria together with their poisonous secre
which made the animals sick or killed. them. And it is not the typhoid bacillus alone which possesses the power of producing both intoxication and ulceration of Peyer's patches in animals. There are many ordinary water and ground bacteria. that are not known as having pathogenous power, and yet they yield the same result when introduced into the circulation of animals.
It seems, however, that of late, white mice have been successfully infected by some French experimenters. The introduction of typhoid bacilli direct into the duodenum analogously to Rietch's and Nicati's experiments with the cholera germ, seem to have been negative.
Variation in Virulency of the Bacillus.— Another great obstacle to obtaining uniform results is the changeableness of the virulence of the typhoid microbe. When bacteriology was still in its infancy, the notion prevailed that there was not only a constancy of form, but also a constancy of virulence, in the various species of pathogenic and other bacteria. In fact, this was one of the fundamental doctrines in the new science. Pasteur was the first to do away with the latter error, and today there is nothing so well established, but at the same time so confusing and leading to contradictory results in experimenting, as the variability of microbian. virulence.
The typhoid bacillus is no exception to the rule, but may, on the contrary, be looked upon as a paradigm. Just as the cholera vibrion may be changed from an exceedingly poisonous to a perfectly harmless state, and vice versa, so the typhoid germ is able to acquire and lose pathogenous properties, by varying surrounding conditions.2
tions, that determines the result; absence of any effect, or intoxication followed or not, by death. In toxæmia, then, the microbe may be found in the blood during life or after death; but it has been simply preserved, though perhaps in a viable
To make this unstableness of poisonous properties of the lowest forms of plants, the microbes, comprehensible, analogous examples in higher plants are generally adduced to the text-books on bacteriology. The bitter almond is in every respect like the sweet almond, and the bitter almond tree has been shown to be the parent of the sweet variety; but there are the well-known poisonous properties of the bitter, which is the only difference between it and the sweet almond. Another example is found in foxglove. When Linnæus visited Lapland, he was astonished to see the natives eat this plant made up as salad. He ate of it himself, and found that what is regarded as one of the most poisonous plants in the moderate zone, especially in mountainous regions, is perfectly harmless and used as a vegetable in the extreme North. Perhaps the variability of typhoid fever epidemics as to morbility and mortality, is to some extent attributable to the changeableness of virulence in the bacillus, although this is certainly not the only factor capable of explaining it.
(To be continued.)