Effect of frusemide on carbohydrate metabolism, blood-pressure, and other modalities. A comparison with chlorothiazide.

Abstract

Ataxia-telangiectasis-Oppenheim et al.BEncsm 333 studies of Oppenheim et al. (1965a) and Moynihan et al. (1965) suggest that the proportions of immunocompetent lymphocytes may be temporarily increased in the peripheral circulation of normal humans and monkeys at such a time. The five ataxia-telangiectasis patients studied here manifested both a selective IgA immunoglobulin deficiency and a failure to react to a number of fungal, viral, parasitic, and mycobacterial antigens. However, they rejected skin homografts and could be sensitized to 2,4-dinitrochlorobenzene in a normal fashion. Therefore they were only partially defective immunologically, and, similarly, their in vitro lymphocyte transformation was only variably and partially impaired.The aetiology of the impaired leucocyte growth in ataxiatelangiectasis patients was investigated by varying the in vitro environment. Only when the patients' cells were cultured in medium with homologous instead of autologous plasma did survival of lymphocytes improve. Both the size and proportions of transforming lymphocytes stimulated with phytohaemagglutinin significantly improved and often approached normal in those cultures employing homologous plasma. However, the response to streptolysin-O and other antigens was not significantly influenced by homologous plasma. Conversely, normal cells were not adversely affected when cultured in the patients' fresh plasma. These findings argue against the presence of a toxic factor in the patients' plasma, but suggest that there may be a partial deficiency of factor(s) necessary for cell growth. The data also suggest that the decreased survival and impaired proliferation of the viable lymphocytes in ataxia-telangiectasis leucocyte cultures may not be due to an intrinsic abnormality of their lymphocytes, but be secondary to some non-lethal genetic deficiency, which can be rectified to some extent by factors present in normal plasma. The identification of these plasma factors, their relationship to clinically expressed immune-incompetence, and the impaired lymphocyte transformation noted in other disorders require further study. SummarThe leucocytes of five patients with typical ataxiatelangiectasis, IgA immunoglobulin deficiency, and partial anergy were repeatedly cultured with phytohaemagglutinin-M and antigens such as streptolysin-O, vaccinia vaccine, and homologous leucocytes. The cultures manifested more damaged lymphocytes and higher macrophage survival than did 18 normal controls. Lymphocyte proliferation, as measured by transformation, mitotic indices, and tritiated thymidine uptake in response to both phytohaemagglutinin and antigens, was significantly impaired. The Brit. med. J., 1966, 2, 333-336 The benzothiadiazine drugs have recently been incriminated as diabetogenic (Wilkins, 1959;Goldner et al., 1960;Sugar, 1961;Zatuchni and Kordasz, 1961;Wilson, 1963;Samaan et al., 1963;Rapoport and Hurd, 1964;Wolff and Parmley, 1964), and the onset of asymptomatic chemical diabetes has often been reported during their use. The...

Effect of furosemide on insulin and glucagon responses to arginine in normal subjects

“…There are no reported investigations concerning the effects of furosemide upon insulin and glucagon secretion in humans. Furosemide, given for three months (80 mg daily), to normal and diabetic subjects with moderate hypertension, did not cause deterioration of oral glucose tolerance or a change in glucose response to intravenous tolbutamide [10]. Two of the normal subjects, however, became diabetic after three months of therapy.…”

Effect of diuretics on mouse blood sugar following single dose administration

“…The ability of the benzothiadiazine diuretics to impair glucose tolerance in some individuals is well documented (Wilkins, 1959;Goldner, Zarowitz & Akgun, 1960;Shapiro, Benedek & Small, 1961 ;Wolff, Parmley, White & Okun, 1963;Weller & Borondy, 1965;Zamrazil, Dvorak, Oskera & Zamarazilova, 1967;Breckenridge, Dollery, Welborn & Fraser, 1967). A similar effect has also been reported following treatment with ethacrynic acid (Lebacq & Marcq, 1967;Andersen & Persson, 1968) or frusemide (Toivonen & Mustala, 1966;Jones & Pickens, 1967;Hutcheon & Leonard, 1967), although reports to the contrary appear in relation to both drugs (Dige-Petersen, 1966;Ozen, Sandalci & Berker, 1966;Feldman & Diamond, 1967;Jackson & Nellen, 1966;Schaefer, 1964;Mor6t, 1966;McKenzie, Fairley & Baird, 1966). Attempts have been made to investigate these effects using single dose administration in the experimental animal.…”

Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid.

“…However, he excluded patients in whom the glucose tolerance test taken before treatment suggested the presence of latent diabetes mellitus. Jackson and Nellen (1966) are the only workers who have carried out comparative studies of two compounds-namely, frusemide and chlorothiazide-in the same group of patients. They found no evidence of deterioration in either glucose tolerance test or tolbutamide test in any of the 19 patients investigated.…”