The anatomic cause of electrocardiographic changes in virus myocarditis of rabbits

Electrocardiographic studies were made on 25 rabbits which had been inoculated intratesticularly with virus III. During the acute stage of the resulting disease, the majority of these animals developed a histologically demonstrable myocarditis, and, after recovery from the infection, small scars were found in the myocardiums of many. Definite abnormalities in cardiac function, including complete auriculoventricular heart block, were demonstrated in the electrocardiogram during the period in which the acute myocarditis existed. The electrocardiogram failed to show the presence of a noteworthy myocarditis in only 3 animals, and in only one instance was it impossible to demonstrate myocarditis when the tracing was significantly altered. The electrocardiographic diagnosis was thus accurate in 84 per cent of the cases. This association of the abnormal electrocardiogram with the structural lesion in the heart leads to the conclusion that, in this disease of the rabbit, disturbed function is caused by actual lesions, and not by the toxicity of the disease.Twenty-one rabbits which were inoculated intratesticularly with Andrewes' inflammatory strain of the Shope fibroma virus were studied similarly. Although in the hearts of a few of these animals interstitial myocardial fibrosis occurred, the muscle cells escaped for the most part, and in no animal was any abnormality in the electrocardiogram demonstrated.     

EXPERIMENTAL SYPHILIS OF ORIENTAL ORIGIN: CLINICAL REACTION IN THE RABBIT

Two oriental strains of T. pallidum of Chinese origin were compared with two well known occidental strains, the Nichols and the Zinsser-Hopkins, on the basis of the clinical reaction to infection in the rabbit. Four experiments were carried out, two each in Peiping and New York. Animals from American and Chinese sources were represented in each experiment. The results obtained showed that the reaction to both Chinese strains was generally comparable to that of the American strains. But with both Chinese strains, lesions of the eyes were more frequent, the time relations of certain phases of the reaction were shortened, and there was a higher incidence of complete recovery (latency) within the observation period. In view of the well known variability of the syphilitic reaction, however, it was not felt that these qualitative differences in clinical response could be ascribed to inherent or biologically fixed properties of the strains.     

THE HEMOCYTOLOGICAL CONSTITUTION OF ADULT MALE RABBITS FROM FIFTEEN STANDARD BREEDS

A study of the red blood cells, hemoglobin, blood platelets, and the total and individual white blood cells was made on 180 male rabbits of known age and representing fifteen standard breeds. An attempt was made to eliminate or bold constant such variables as age, sex, season, time of examination, technical errors, food, housing, and disease. The mean, variance of the mean, and standard deviation were calculated for each breed sample and for the group as a whole. An analysis of the variance showed that the variation between the breed samples was significantly greater than the variation within the breed samples for the red blood cells, hemoglobin, blood platelets, total white blood cells, basophiles, eosinophiles, and lymphocytes per cubic millimeter and in per cent and the neutrophiles in per cent. No significant variations were detected in the monocytes except when the breeds were divided into heavy and light breeds. No variation in the neutrophiles per cubic millimeter was detected; a large number of the breeds had exactly the same mean neutrophile level. Characteristic blood formulae were found for the various breed samples having an adequate numerical representation. It was concluded that the varying blood formulae could not be explained on any other, except an hereditary (genetic) basis.     

EFFECT OF A FILTERABLE VIRUS (VIRUS III) ON THE GROWTH AND MALIGNANCY OF A TRANSPLANTABLE NEOPLASM OF THE RABBIT

A study of a malignant disease in rabbits has been made with reference to the presence or absence of a filterable virus, Virus III, in the tumor. The results are analyzed from the standpoint of certain characteristic features of the tumor process in order to determine any differences in degrees of malignancy. It was found that a more severe disease developed in the series in which the virus-bearing tumor was used than in the series in which the tumor was free of the virus, although the differences were not very marked and were not entirely constant. The influence of Virus III as a factor affecting malignancy has been discussed from the standpoint of its possible effect upon (α) the tumor cells and (b) the host reaction. It has been suggested that the greater malignancy of the pathological process usually induced by the virus-bearing tumor is attributable to a change in the response of the host to the tumor, which change is of the nature of a decreased resistance associated with the reaction of the host to the virus infection.     

THE RELATION BETWEEN BODY AND ORGAN WEIGHTS IN THE RABBIT

Data from 645 normal rabbits were used as the basis of an investigation of the relation existing between body and organ weights. Actual and relative weights were correlated with both gross and net body weight. The results obtained varied with different classes of organs but it was found that, in general, there was an agreement between the form and degree of the correlation shown and the structural and functional properties of the organs concerned.     

STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : VI. VARIATIONS IN GROWTH AND MALIGNANCY OF TRANSPLANTED TUMORS. PART 1. RESUTLTS OF TRANSPLANTATION FOR THE FIRST TWENTY GENERATIONS.

A report is given of the results obtained by intratesticular inoculation of a malignant tumor of the rabbit based on a study of the first twenty generations. The subject is presented from the standpoint of variations in growth and malignancy as they occurred with continued transplantation. Essential features of the experimental conditions and of clinical and postmortem observations are condensed and recorded graphically. On analyzing the results of these experiments, it was found that many changes had occurred in the behavior of the tumor during transplantation, but that the changes were of a very irregular character and as a rule did not proceed constantly in any given direction. Moreover, the evidence as to the effect of transplantation on the growth and malignancy of the tumor was contradictory in that there was a great deal of evidence to show that there had been a decided increase in the activity and capacity for growth on the part of the tumor cells. But, with the exception of a few generations, there was an apparent reduction in the incidence and percentage distribution of secondary tumors, while the death rate was unaltered or actually diminished. It was believed that this paradoxical situation afforded a basis for an explanation of the results that had been obtained by transplantation.     

PENETRATION OF NORMAL MUCOUS MEMBRANES OF THE RABBIT BY TREPONEMA PALLIDUM AND THE INFLUENCE OF THIS MODE OF INFECTION UPON THE COURSE OF THE DISEASE

Experiments were carried out with three strains of Treponema pallidum to determine whether infection could be produced by applying an emulsion, rich in spirochetes, to normal mucous membranes of rabbits and whether an infection produced in this manner differed in any respect from one produced by other methods of inoculation. It was found that a simple instillation of a spirochete emulsion into the conjunctival sac or the sheath was all that was necessary to obtain an infection. Still, the infection produced in this manner differed from that produced by intracutaneous or testicular inoculations in that it tended to pursue a mild or asymptomatic course and frequently without the development of a characteristic chancre. It is pointed out that these experiments may have a bearing on problems pertaining to obscure and atypical cases of human syphilis as well as the more immediate question of the infectivity of Treponema pallidum.     

STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : I. THE SPONTANEOUS TUMOR AND ASSOCIATED ABNORMALITIES.

A malignant tumor which developed at the site of a primary syphilitic lesion in the scrotum of a rabbit, about 4 years after inoculation, and eventually led to the death of the animal, has formed the basis for an extensive series of investigations beginning with the study of the spontaneous tumor. The present report contains the clinical history of the animal from the time of inoculation to its death and the results of pathological examinations. The most important events recorded may be summarized as follows: 1. A mild but persistent syphilitic infection with an occasional relapse and the eventual development of chronic inflammatory lesions in the skin associated with atypical epithelial proliferations. 2. The occurrence, at about the same time, of extensive degenerative changes in the dermis accompanied by an atypical growth of hair follicles, with the production of diffuse and nodular areas of thickening and induration (scleroderma). 3. The development of a growth in the skin of the left scrotum which recurred after removal and spread diffusely over adjacent parts of the skin, and metastasized to the regional lymph nodes and to internal organs. 4. The transplantation of the growth to other rabbits by intratesticular inoculation and the successful propagation of the growth over a period of nearly 2 years (twenty generations). 5. The development of a cachexia and of pressure phenomena from metastases involving the cervical and lumbar regions of the spinal column which eventually led to the death of the animal. 6. The discovery, post mortem, of an extensive leucoplakia of the tongue and buccal mucosa, chronic inflammatory lesions in the esophagus with atypical epithelial proliferation, and a nodular growth in the left testicle differing in character from that in the scrotum. 7. The presence of extensive degenerative changes in the vascular system, degeneration of the parenchymatous organs, atrophy of the thymus and lymphoid system, with chronic lymphadenitis, atrophy, degeneration, and necrosis of the suprarenals, and atrophy and hyperplasia of the thyroid with chronic thyroiditis. The conclusion was reached that the growth in the scrotum represented a neoplasm of epithelial origin which was composed of cells allied to those found in the bulb and root sheath of the hair. No explanation was offered for the origin or unusual malignancy displayed by the tumor pending the introduction of experimental data. It was stated, however, that the evidence presented was sufficient to warrant the assumption that the factor of foremost importance in the development of the tumor was constitutional rather than local.     

EXPERIMENTAL SYPHILIS IN THE RABBIT : VI. AFFECTIONS OF BONE,CARTILAGE, TENDONS,AND SYNOVIAL MEMBRANES. PART 1. LESIONS OF THE SKELETAL SYSTEM.

From a study of a series of rabbits inoculated with two old strains of Treponema pallidum, it was found that localized infection of bones and tendons was of frequent occurrence and led to the formation of a variety of lesions. The bones usually involved were those of the face and the feet and legs. Most often the lesions arose from the periosteum but developed also within the bone or marrow cavities and at lines of epiphyseal union. Grossly, the periosteal lesions were of two types—one being a circumscribed, indurated, and nodular mass and the other a process of a more diffuse character. Histologically, the lesions presented the typical appearance of syphilitic granulomata composed of more or less distinct layers which corresponded roughly with structural divisions of the periosteum. The composition of lesions of membrane and of cartilage bones differed somewhat in this respect, especially in the development of an osteoclastic layer. Invasion of the bone with absorption and necrosis were constant features of periosteal affections and were most marked in the case of the facial bones and the small bones of the feet. Lesions in the bone and marrow cavities were detected chiefly by radiographs or by the occurrence of bone destruction in the absence of periosteal involvement. They were characterized by a loss of structural detail in the bone, rarefication, increased fragility, necrosis, pathological fracture, and epiphyseal separation associated with more or less granulomatous reaction. Histologically, the bone lesions presented essentially the same picture as those of the periosteum, while the lesions which arose from the marrow cavities were composed chiefly of polyblastic infiltrations. In this group of affections, the most important were those which developed at the epiphyses. The destructive effects produced by all classes of lesions varied from a slight surface erosion or rarefication to extensive necrosis resulting in the formation of bony defects or in disintegration or fracture of the bone. These conditions differed very decidedly with the particular bones involved. Of especial importance in this connection was the occurrence of a peculiar form of mass necrosis which at times resulted in the destruction of considerable areas of bone even in parts where the granulomatous type of lesion was comparatively slight. The most characteristic injuries were the saddle-nose deformities and the epiphyseal separation in the small bones of the tarsus and hind feet. The marks of permanent injury were, on the whole, comparatively slight, but they also differed both with the degree of the original injury and with the bone affected. Granulomatous lesions of tendons or tendon sheaths were occasionally seen, and in a few instances, lesions of synovial cavities were demonstrated microscopically.     

THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC JAUNDICE : V. CHANGES IN THE ENDOTHELIAL CELLS OF THE LYMPH NODES AND LIVER IN SPLENECTOMIZED ANIMALS RECEIVING HEMOLYTIC SERUM.

In a large proportion of dogs that have been splenectomized for periods of two weeks or more, one finds a great increase in the number of endothelial cells of the lymph nodes. In most splenectomized dogs that succumb to an injection of hemolytic immune serum within forty-eight hours, the sinuses of the lymph nodes contain large numbers of endothelial cells, phagocytic for red cells. This is not seen in normal dogs receiving hemolytic serum. Likewise a similar power of phagocytosis is seen frequently in the stellate cells of the capillaries of the liver. Both in the lymph nodes and the liver these cells appear to be formed in situ; we find no evidence that they have been transported to these organs. Such findings suggest the development of a compensatory function on the part of the lymph nodes and possibly of the liver. Normally the spleen contains cells which have the power to engulf and presumably to destroy the red blood corpuscles. In certain pathological conditions this function is frequently greatly augmented and may sometimes be shared by the lymph nodes, for example, in typhoid fever, as was first clearly shown by Mallory. Our observations suggest that in the absence of the spleen, this function of forming red blood corpuscle-phagocyting cells, normally a minor activity of the lymph nodes, becomes highly developed in the latter organs, and that these cells, and the stellate cells of the liver, thus assume, in part at least, the function of destroying red blood corpuscles by phagocytosis. In view of the somewhat limited material at our disposal, we offer this, not as definitely conclusive, but as evidence which, in connection with the work of others, is highly suggestive of the possibility of the lymph nodes assuming some of the function of the spleen. Whether this activity of the endothelial cells of the lymph nodes and the liver has any bearing on the anemia that follows splenectomy and on the occurrence of spontaneous jaundice in the late periods after splenectomy, is not yet clear.