Lactic acidosis.

Abstract

47I submit, Sir, that an antenatal screening programme of a general population has nothing to recommend it at this time, and that to advocate such a programme in the absence of a full discussion of the relevant issues, some of which I have touched upon here, is little short of irresponsible. (14 November, p. 392) and to compare it with our work on clonidine. Since our preliminary communication' a detailed report has been published.2 Our work on methyldopa and clonidIne extended over a period of six months each, and we were able to study in 30 patients the side-effects, effectiveness, and tolerance of the two drugs. Unlike the experience with clonidine of Dr. Macdougall and colleagues who found that "side-effects from the drug were not disabling and were often transient" two of our patients developed such marked drowsiness that they refused to continue with clonidine. We feel that the greater number of side-effe-ts from dlonidine compared with methyldopa which has been observed by Dr. Amery and colleagues and by us, should make the clinician prefer methyldopa to clonidine, as one of the main factors dissuading a hypertensive patient from continuing with his therapy is unwanted side-effects. Tolerance occurred in six of our patients on methyldopa and in seven patients on clonidine. Our average dosage was 916 mg daily of methyldopa and 0-86 mg daily of clonidine.It seems a pity that Dr. Amery and colleagues used chlorthalidone in combination with both clonidine and methyldopa, as thiazides themselves may be effective hypotensive agents.-We are, etc.,

Lactic acidosis in biguanide-treated diabetics

“…Only the measurement of lactate in whole blood can finally elucidate the origin of the acidosis. The decision is important because the therapeutic regimens and the prognosis are quite different [160,161].…”

Buformin concentrations in a case of fatal lactic acidosis

“…It is possible that some time before the: occurrence of lactic acidosis a developing diabetic nephropathy and the existing hypertension had led to a decrease of renal function. This could have caused accumulation of buformin and subsequently lactic acidosis [6]. The acidosis may have caused cardiac failure [7,8], a further decrease of renal function [9] and a further increase of the severity of the lactic acidosis.…”

“…The effects of biguanides on lactic acid production have been reviewed [4,6]. Briefly, biguanides are probably bound to the mitochondrial membrane, changing its electrochemical properties, and thereby interfering with the entrance of NADH into the mitochondrion, shifting the reaction pyruvate + NADH ~ lactate + NAD + to the right.…”

“…The ability of biguanides to lower blood glucose concentration is explained by several mechanisms [2,6,10,11]. The effects of biguanides on lactic acid production have been reviewed [4,6].…”

Effect of metformin on insulin binding to receptors in cultured human lymphocytes and cancer cells

“…In order to evaluate if other biguanides have a similar effect in increasing insulin binding to its receptors, we have studied the effect of metformin [3][4][5] on insulin binding in vitro to IM-9 human lymphocytes and MCF-7 human breast cancer cells and have compared these findings with those obtained under the same conditions with phenformin.…”