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.

Hepatic Injury on a Nutritional Basis in Rats

“…This is an illustration of the phenomenon of "concurrence" or "competition" of vitamin deficiency diseases. In a previous paper (3) observations were reported to the effect that this rule might have its exception even under identical conditions. For example, in several instances of acrodynia which had developed in rats kept on the diet deficient in vitamin Be, spontaneous improvement of the skin lesion occurred but the rats became, at the same time, progressively anemic, exhibiting the typical picture of panmyelophthisis with all its manifestations--agranulocytosis and hemorrhagic diathesis in addition to the anemia.…”

“…The diet originally (1) and still commonly used for the production of "rat acrodynia," the specific vitamin Be deficiency disease in this animal, consists of casein, cane sugar (or rice starch), melted butter fat, cod liver oil and salt mixture and is supplemented with vitamin BI and riboflavin. During the last few years it has become evident that this ration lacks at least two (2) and probably more factors (3), one of which is vitamin Bs. Under the conditions chosen, vitamin Be deficiency is the primary disturbance and prevails over the other deficiencies.…”

SELECTIVE ADRENAL NECROSIS AND APOPLEXY INDUCED BY 7,12-DIMETHYLBENZ(a)ANTHRACENE

“…GySrgy et al (7) found that a nutritional deficiency leading to panmyelophthisis caused adrenal hemorrhage in rats. The dietary deficiency causing adrenal damage has been related to deficiency in some fraction of the vitamin B complex (8,9).…”

Choline as a Member of the Vitamin B2 Complex

“…The addition of 2 rag. of choline daily had no appreciable preventive effect either on suprarenal hemorrhage or on panmyelophthisis (10) in rats fed a diet deficient in vitamin B6.1 Furthermore, in only 2 rats was hemorrhagic necrosis of the suprarenal glands found associated with cortical necrosis of the kidneys, while patchy or diffuse necrosis of the liver (11) was not observed in any of the animals with cortical necrosis of the kidneys.…”