Over a period of four years, streptozocin has been used to induce diabetes in 10 baboons, all of whom are insulin dependent. We describe our experience with their husbandry, induction of diabetes, insulin therapy, metabolic control and growth rate. Streptozocin dosage of 60 mg/kg readily induces hyperglycemia with minimal hepatic or renal toxicity. Using a once daily injection of mixed short and intermediate acting insulins at a dosage of 2-4 U/kg, it is possible to maintain a degree of metabolic control similar to that attained in patients.
A selective cell culture medium, D-valine minimal essential medium (92 mg/l), has been developed to inhibit the proliferation of fibroblasts in cell culture (Gilbert & Migeon 1975). Substitution of D-valine for L-valine prevents fibroblast growth due to the absence of D-amino acid oxidase in these cells. Most cell cultures require foetal bovine serum as an essential component of the culture media, however foetal bovine serum contains L-valine, negating the value of D-valine selective media. To overcome this difficulty, we have produced a modified selective media for cell culture, by the dialysis of foetal bovine serum and confirmed its ability to inhibit fibroblast growth whilst still allowing the proliferation of epithelial cells in culture.
A prospective, double-blind, randomized controlled trial was carried out, comparing alpha-methyldopa and clonidine hydrochloride in 100 pregnant women with hypertension. There was no difference in hypotensive effect or reported maternal side effects with either agent. There was one neonatal loss in each group (98% survival). Neither drug caused clinically significant hypotension nor rebound hypertension in the neonates. Clonidine hydrochloride, like methyldopa, appears to be a safe antihypertensive agent in pregnancy.
This study evaluates the outcome of 142 consecutive pregnancies in women in whom hypertension was diagnosed before 32 weeks' gestation and who were managed by a team comprising obstetricians, physicians and perinatologists. Arterial pressure was lowered to 140/90 mmHg or lower with clonidine hydrochloride or methyldopa therapy to which, in most cases, a vasodilator, hydralazine or diazoxide was added. The outcome of patients who were managed by the multidisciplinary team from the clinical onset of their disease was compared to the outcome of those who were transferred after the onset of hypertension from other centres. A greater perinatal mortality rate was found among the infants of patients with pre-eclampsia and patients with essential hypertension in pregnancy when the mothers were referred late for management. Reasons for the difference in pregnancy outcome are not clear. Possible explanations are discussed which emphasize the need for further study to establish optimal management of this common complication of pregnancy.
SUMMARY1. This study evaluates the perinatal outcome of infants born to ninety‐five mothers with hypertension in pregnancy whose blood pressure was treated in a double blind trial comparing clonidine hydrochloride (C) and α‐methyldopa (A).2. There were no fetal deaths and two neonatal deaths, giving a perinatal mortality of 2%. There was no significant difference between Groups C and A with regard to the gestation or weight at birth, incidence of intrauterine growth retardation, or condition at birth as judged by Apgar scores and acid‐base status. No infant in either group developed significant hypotension or rebound hypertension. The blood pressure was not significantly different between Groups C and A, and controls. In each of these three groups there was a similar significant rise in systolic blood pressure with age.
Two hundred and thirty-six pregnant women were referred for assessment and management of hypertension and/or renal disease. A Unit consisting of a physician, an obstetrician and a perinatologist jointly assessed each patient and advised on management. All patients were hospitalized and at bed rest. Drug therapy was clonidine hydrochloride or methyl dopa and in some patients a vasodilator was added. The decision to deliver was dictated by foetal maturity and wellbeing, in conjunction with maternal condition. There was no maternal mortality and the overall perinatal survival was 97%. The outcome of these pregnancies compares favourably with studies previously reported and reflect a successful approach to management of high risk hypertensive pregnancies.