Ralph A. Kinsella

Effect of Sodium Salicylate on Intradermal Reactions of Rabbits.

Conclusion 1. Sodium salicylate suppresses the allergic dermal reactions of rabbits to filtrates of hemolytic streptococcus. This effect is most definite when sodium salicylate is given before the focus of infection has developed. 2. There is no relation between the presence or absence of this dermal reactivity and the character of the vascular pathology.

Filtrates From Scarlet Fever and Surgical Hemolytic Streptococcus Infections.

In scarlet fever it is held that there is a special strain of hemolytic streptococcus responsible for scarlet fever. Nevertheless, by agglutination tests, all strains isolated from cases of scarlet fever are not identical. It has not been argued that a special phase of reactivity on the part of the host can lead to the clinical picture of scarlet fever after infection by any hemolytic streptococcus. The criteria for investigating the specific nature of a given strain of hemolytic streptococcus, whether from scarlet fever or from other clinical infections, have been the preparation of a filtrate from special culture medium and the testing of such filtrate for its resistance to heating, its capacity to produce a dermal reaction in a susceptible subject, and its neutralization by anti-scarlet fever serum in skin tests. The following would indicate either that these criteria are not sufficient to establish the specific qualities of a given strain, or that the phase of reactivity of a patient is important in determining whether infection by hemolytic streptococcus will result in scarlet fever or some other clinical picture. The filtrates were studied from the throat cultures of three cases of scarlet fever, two of which were caused by infection of wounds; and of three cases of bacteriemia following operations, in one of which the attending nurse developed scarlet fever. In the three cases of scarlet fever the cultures from the throat failed to yield hemolytic streptococcus. In two of these cases, one of which was surgical scarlet and the other the usual variety, the predominating organisms were non-hemolytic streptococcus which were immediately used to infect filtrate broth. Subcultures of this broth failed to show any colonies of hemolytic streptococcus on blood agar plates.

Experimental production of streptococcus endocarditis with glomerular nephritis

In human patients subacute streptococcus endocarditis is a fatal disease. No authentic report of a recovery has even been published. The mechanism of production of this disease in human beings displays two constant factors—injury to the valve and later infection. The injury is usually represented by either congenital valvular heart disease or rheumatic valvular heart disease. The later implantation of green streptococcus on this injury usually takes place through the medium of an infection of the middle ear or throat or some other locality where green streptococci normally breed. In experimental work Rosenbach recognized these two factors in 1878 and reproduced infection in the heart valve after puncture of the valve. Although a beginning was made so long ago, and more perfect instruments have been devised for injuring the valve, no attempt has been made to reproduce the disease completely and glomerular nephritis of the type which characterizes the disease in human beings has never heretofore been reproduced. All clinical efforts to obtain a cure of the disease have failed. It seems, therefore, that we must have the disease reproduced in animals and then thoroughly study its features if we are to expect a cure. This work consists in injuring the aortic valve by inserting an appropriate instrument into the left carotid and then, after recovery, the animal is infected by intravenous inoculation of green streptococcus. The inoculated bacteria become implanted at the site of the valve injury and there set up a bacterial vegetation identical with that of human patients. Dogs were used in these experiments. Dogs living 12, 13 and 14 days failed to show any kidney Iesion of the glornerular type although large infractions were common.

Maturity of The Pituitary-Adrenal Axis in The Newborn Dog

Summary The apparent changes in steroid hormone production and release by newborn canine adrenals following the administration of appropriate agents indicate that the pituitary-adrenal axis is functional at birth in this species, rendering it capable of responding to stress. The newborn dog may be employed as a useful experimental model in exploring the endocrinologic status of the newborn.

Studies of Experimental Arthritis. III. Behavior of Skin Tests.

The purpose of this study was to observe the behavior of skin tests under the conditions of experimental arthritis. One of the questions which a clinical study of chronic rheumatism presents is whether a joint once infected can in itself be a focus from which further exacerbations of the disease may arise. Accordingly, in arranging the experimental conditions under which the subject of bacterial allergy was to be studied, arthritis was produced not only by inoculating animals intravenously but also by inoculating small amounts of bacteria into the joints. The organism used was a laboratory strain of hemolytic streptococcus, preserved by freezing and desiccating the culture. Skin tests were made on the backs of the rabbits, after the hair had been clipped and removed with sodium sulfide. This depilatation was carried out 2 to 3 days before the skin tests were made. The toxic filtrate used was prepared by seeding a 24-hour broth culture of the organisms into about 100 cc. of Harleys toxin media. This was incubated for 5 days, centrifugalized and filtered through a Berkefeld candle. Normal rabbits were found to give no skin reaction following the intradermal injection of 1/10 cc. of these filtrates. Animals so tested were used in these experiments. In the series reported 24 animals were used, the same number being inoculated intravenously as by the intra-articular route. After intravenous injection, rabbits usually develop a positive blood culture. Daily blood cultures then show one of two things. The animal tends to recover and the daily blood culture shows fewer and fewer organisms, or the animal grows rapidly worse with more and more organisms per cc. of blood and soon dies. The rabbits surviving may or may not develop metastatic joint infections.

Metabolism of progesterone in the canine feto-placental unit.

Abstract Progesterone (P), a major hormone of pregnancy, was selected for study under the conditions of an intact utero-placental-fetal unit. A preparation of the canine gravid uterus, near term, is described and shown to permit observation of the metabolic relationships of the steroid hormone P between maternal and fetal organisms. [1,2-3H] P or [7α-3H]P was injected into pups, while [4-14C]P was injected into the uterine circulation. Perfusion was continued for 1 hr with excellent survival of the pups. Identified metabolites in the fetal and maternal tissues suggest a metabolic pool that is shared throughout the unit.

Adrenal response to hypophysectomy in the newborn dog.

Summary Hypophysectomy in the newborn dog results in a prompt fall in the secretory rate of cortisol during collection of adrenal effluent blood. Due to the rapid rate of clearance of ACTH, lowest secretory rates were expected at 2–5 hr after hypophysectomy but, at 16–20 hr, an even lower rate was found. This unexplained observation was significant. The procedure of hypophysectomy recommends itself as a valuable means of exploring the endocrinologic status of the newborn.

Further Study of the Bacteriemia of Experimental Streptococcus Endocarditis.

When the aortic or mitral valves of dogs are injured by passing a suitable steel rod down the left carotid artery, the resulting wound of the valve shows, at the end of 49 days, a hyalin-like mass at the point of injury. As late as 60 days after such injury the injection intravenously, of non-hemolytic streptococci results, constantly, in a bacterial vegetative growth on the injured area productive of petechiae, infarctions, thrombo-glomerular nephritis, and small areas in the heart muscle in which a round cell infiltration follows a punctate hemorrhage. In four dogs the healing of the injury was not altered by the injection either before or after injury, of egg albumin, followed in three weeks by a second injection, which was in turn made three days before autopsy. A strain of non-hemolytic streptococcus isolated from the blood of a patient with acute rheumatic fever, and having some virulence for white mice, and a strain from a normal throat having no virulence for mice, were equally successful in producing the infection of the injured valve. Subacute bacterial endocarditis in humans is characterized by the presence in the blood stream of avirulent non-hemolytic streptococci. These streptococci are said to be avirulent from the standpoint of the action on white mice. They may or may not have been virulent before infecting the human subject. Cultures of the strain from acute rheumatic fever, recovered from dogs with endocarditis produced as above, failed to infect fresh animals in two instances. A culture of the strain from a normal throat after such passage through a dog failed to infect a fresh animal which had had a valvular injury. Furthermore two different strains from clinical cases failed to infect animals whose valves had previously been injured.

Active immunization with sensitized and non-sensitized bacteria

In a previous communication 1 we reported that the serum of rabbits which had been injected with sensitized vaccine or living cultures of Streptococcus viridans, did not contain agglutinins, complement fixing antibodies or protective antibodies. Later similar results were obtained with sensitized vaccines of pneumococci, with the exception that the serum of animals inoculated with sensitized living pneumococci showed a rapid production of these antibodies. We then attempted to determine whether there was evidence of active immunity even though no antibodies could be demonstrated in the serum. It has been found impossible to immunize mice with green streptococci. Rats may be immunized with green streptococci, but the virulence of these organisms is so low that it is impossible to compare the results of immunity with the different forms of vaccines. For comparative study pneumococci are more satisfactory because of the high virulence of these organisms. Throughout the work type I pneumococcus has been used. Four types of vaccine have been studied, (A) plain stock vaccine, killed at 56°; (B) sensitized stock vaccine, killed at 56°; (C) freshly prepared sensitized vaccine, killed at 56°; and (D) an alcohol precipitate of sensitized vaccine similar to that used by Gay in the preparation of typhoid vaccine. Immunization was carried out by intraperitoneal injection of increasing quantities at three or four day intervals. Immunity has been studied in mice, guinea pigs and rats. Mice immunized with three injections and tested from seven to eleven days after the last immunizing dose, showed immunity from all types of vaccines. The mice immunized with vaccine D were uniformly less immune than those with the other vaccines. There were only slight differences in the animals immunized with plain and sensitized vaccine, and in different experiments the results varied so that neither vaccine can be said to be better.