A study of the efficacy of 5 alpha- and 5 beta-androstanes in chronic experimental aplastic anemia in mice.

The efficacy of in vivo administration of a 5 alpha-androstane and two 5 beta-androstanes (3 alpha and 3 beta) on CFU/GM and CFU/E mouse bone marrow stem cells was compared. The subjects were two groups of Swiss Webster mice: one normal group and one group in whom chronic aplastic anemia was induced by irradiation followed by mesenteric node lymphocyte grafting from C57/Bl donor mice. In normal animals, the two types of androgens (5 alpha and 5 beta) had the same efficacy, and the injection of 5 beta-androstane, before that of 5 alpha, significantly increased its efficacy. In aplastic mice, 5 alpha and 5 beta-androstanes had the same efficacy on CFU/E but 5 beta-androstanes were more efficient on the granulopoietic committed stem cells. The efficacy of the association of the two compounds in aplastic mice was not superior to that of each drug alone, which can be explained by the depletion of the stem cell compartment induced by the stimulating effect of the first androgen.

[Anemia in renal insufficiency. I--Mechanisms of anemia in patients treated with periodic hemodialysis]. / L'anémie de l'insuffisance rénale. I--Mécanismes de l'anémie des sujets traités par hémodialyse périodique.

Fifty-two patients with anaemia due to chronic renal insufficiency treated by haemodialysis were divided into three severity groups. Except for bi-nephrectomized patients, none of the usual criteria such as age, sex, cause of the renal disease and duration of dialysis correlated with clinical severity. Kinetic studies showed that the severity of anaemia was unrelated to the degree of haemolysis, haemoglobin function or haemodilution. Stem cells were increased in all cases, irrespective of clinical severity. However, the degree of anaemia closely correlated with the degree of erythropoietic deficiency, as measured by radio-iron kinetics. A qualitative defect (slow release of labelled cells from the bone marrow) was associated with severe quantitative erythroid defect. These data indicate that kinetic studies of erythropoiesis constitute objective methods for measuring clinical severity. They favour the theory which makes a hypothetical inhibitor of differentiation and/or proliferation of erythropoietic precursors the main cause of anaemia.

[Anemia of chronic renal insufficiency. II. Effect of androgen therapy in 17 subjects treated with periodic hemodialysis]. / L'anémie de l'insuffisance rénale. II. Effet de l'androgénothérapie chez 17 sujets traités par hémodialyse périodique.

Seventeen patients with severe anaemia due to renal insufficiency treated by periodical haemodialysis received high parenteral doses (7 mg/kg/week) of androgens for a period of 10 months. Kinetic studies of erythroid stemcells (plasma clot method), erythropoiesis (radio-iron kinetics, bone marrow scintigraphy) and haemolysis (autologous and homologous red cell life span) were performed before and after treatment. Complete failure was observed in 6 patients, slight improvement in 4 and distinctly satisfactory results in 7. In three cases relapse was noted after treatment was discontinued. Clinical effectiveness was due to correction of the erythropoietic defect, without changes in the degree of haemolysis. Virilization was the only side-effect recorded. All subjects whose anaemia improved, even to a slight degree, felt much better. The following parameters were found to be predictive of androgen effectiveness: absence of bilateral nephrectomy, young age, and relatively slight erythropoietic deficiency. The clinical results were unrelated to the initial number of erythroid stem cells and to their increase under androgen therapy.

Two different in vitro growth patterns for erythroid precursors in 18 patients with pure erythrocytosis.

Growth patterns of marrow and blood erythroid progenitors were studied in 18 cases of pure erythrocytosis using different doses of erythropoietin. 8 cases demonstrated 'spontaneous' growth of CFU-E and blood BFU-E as observed in myeloproliferative disorders, but without an excess of circulating CFU-GM. 3 of these patients also had other symptoms of a pan-myelopathy. All these cases showed good sensitivity to 32P myelo-suppression. 10 cases demonstrated growth patterns of erythroid progenitors similar to those observed in normal subjects, except for an excess of blood BFU-E, which suggests an abnormality of homeostatic regulation. In 5 of these cases, myelo-suppression was not effective. It is suggested that a stem cell study could differentiate patients with pure erythrocytosis due to 'autonomous' abnormal stem cell growth from cases due to abnormal regulation factors, and that such a discrimination might be useful for the choice of therapy.