PANMYELOPHTHISIS WITH HEMORRHAGIC MANIFESTATIONS IN RATS ON A NUTRITIONAL BASIS

Abstract

During the 12 months ending May, 1937, 72 rats were observed that manifested typical symptoms of panmyelophthisis. The disease may start as agranulocytosis, thrombocytopenia or pure red cell anemia, leading progressively, often rapidly, to aleukia hemorrhagica with its typical manifestations (epistaxis, melena, hematuria, purpura). Blood examinations revealed correspondingly low white cell, red cell and platelet counts with very pronounced granulocytopenia (0 to 4 per cent). Bone marrow smears and histological findings were consistent with the diagnosis of panmyelophthisis. Suprarenal hemorrhage was a frequent postmortem finding. The pathogenesis of this experimental panmyelophthisis and this hemorrhagic diathesis is confined to special nutritional conditions. These diseases have been observed by us in rats kept on a diet deficient in vitamin B₆, containing cane sugar and supplemented with vitamin B₁ and crystalline natural or synthetic lactoflavin. Lack of vitamin B₆, however, is not a necessary condition, since the disease was encountered in the majority of the animals after the specific deficiency disease which became apparent in rats kept on the B₆ free diet was successfully treated with purified B₆ preparations. Even in the untreated animals kept on the B₆ deficient diet acrodynia was, as a rule, in distinct remission before symptoms of panmyelophthisis and hemorrhagic diathesis became manifest. By means of the addition of Peters' eluate to the basal diet, panmyelophthisis could be prevented and, in animals where it was recognized in an early stage, cured. In view of these facts it is suggested that Peters' eluate contains a specific maturation factor for the primary blood-producing tissue, the reticulo-endothelium, a factor which, being different from lactoflavin, vitamin B₆ and probably also from the so called filtrate factor, constitutes another distinct component of the vitamin B₂ group. Bacteriological studies brought forward no conclusive positive evidence for the infectious etiology of the experimental panmyelophthisis in our rats. The possible relation of this new disease in rats to aleukia hemorrhagica and its partial manifestations in man, as well as to the so called Waterhouse-Friderichsen syndrome, is discussed. Administration of amidopyrine, at least under the conditions chosen, failed to provoke panmyelophthisis in rats kept on the same diet as that given to rats in which the disease spontaneously developed.

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