The Effects of Pyridoxine and Folic Acid on Thiouracil-induced Granulopenia in Monkeys *

In the repore in which Astwood described the use of thiouracil for the treatment of human thyrotoxicosis he was fortunately able to indicate the most serious hazard which the administration of this drug entails, that of agranulocytosis. A great volume of work has confirmed both the effect of thiouracil on thyroid hyperfunction and its occasionally toxic effect on the bone marrow. Since this idiosyncratic reaction has constituted the main obstacle to the universal use of the drug, search has been made for agents which would prevent the occurrence of granulocytopenia, or rapidly abolish it when it occurred. Prolonged administration of thiourea to rats was shown by Goldsmith et al.7 to produce a neutropenia which could be prevented by the simultaneous use of solubilized liver; the active agent in this liver fraction was thought to be folic acid.7 Vilter, Schiro, and Spies1' observed that intravenous injections of pyridoxine were followed by an increase in elements of the granulocytic series in the blood. Pyridoxine was reported by Cantor and Scott3' 4 to have a beneficial effect in human agranulocytosis. This view has been supported by the more recent work of Fishberg and Vorzimer.6 Menten and Graff8 have described a favorable response in the granulocyte count in sulfonamide-induced granulocytopenia in children following treatment with L. casei factor in conjunction with pyridoxine hydrochloride. On the other hand, Van Winkle et al."0 on the basis of an analysis of several series totaling more than 5000 clinical cases, stated that "there is no satisfactory evidence that pantothenic acid, pyridoxine, folic acid, vitamins or pentnucleotide influence the outcome of this disease or aid in preventing such reactions. The most important factor in the control of granulocytopenia resulting from thiouracil therapy