Aaron Miller

The Intracellular and Membrane Effects of Oxidant Agents on Normal Red Cells

Oxidant drugs produced different patterns of oxidative change in red cell GSH and haemoglobin. Naphthoquinones were associated with a marked increase in methaemoglobin, a marked decrease in GSH and the ready formation of Heinz bodies. Phenylhydrazine, at the lower concentrations, produced Heinz bodies while methaemoglobin levels were only minimally increased and GSH levels unchanged. p‐Aminophenol markedly increased the concentration of methaemoglobin while decreasing that of GSH but formed no Heinz bodies. With hydroquinone, GSH was virtually depleted before small amounts of methaemoglobin were produced.

Hematologic Effect of cis-Platinum-Bleomycin Therapy

A prospective study of the hematologic findings in 19 patients receiving cis-platinum (C-P) bleomycin (B) for squamous cell carcinoma of the head and neck was performed. CP 3 mg/kg was given on day 1, B 15 mg/m2 on day 3 and then by continuous infusison from day 3 to 10. Hematocrits declined in all patients from a mean of 41.6 +/- 3.9 to 36.6 +/- 4.9 (p less than 0.001) with the nadir seen by 10 days, reticulocyte count was unchanged. In 1 patient marked hemolysis occurred over 10-day period associated with the appearance of irregular spherocytes on smear, a situation similar to the index case which initiated this study. 5 other patients had spherocytes. A significant lymphopenia in the absence of neutropenia and thrombocytopenia was also observed.

The influence of glucose and exogenous glutathione on the red cell membrane effect of the antimalarial drugs 1,4-naphthoquinone and β-naphthol.

Glucose‐depleted red cells incubated with primaquine, primaquine degradation products, quinine and quinacrine demonstrated far less osmotic fragility than did glucose‐repleted cells. The increase in osmotic fragility in the presence of glucose could not be correlated with an effect of the drug on the levels of glutathione or methaemoglobin. The prelytic loss of cell K+ caused by these agents was unaffected by the presence or absence of glucose. In contrast to the antimalarial drugs, the osmotic fragility produced by 1,4‐naphthoquinone and β‐naphthol was not glucose‐dependent. Glutathione added to incubating cell suspensions in molar concentrations seven and one‐half times that of the drug, greatly decreased, but did not eliminate, the hypotonic haemolysis and the prelytic loss of cell K+ caused by 1,4‐naphthoquinone. It offered red cells no protection against the membrane action of antimalarial drugs and β‐naphthol. 1,4‐Naphthoquinone was the only drug capable of reacting stoichiometrically with glutathione.