Lancet
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R 82913, a tetrahydroimidazobenzodiazepinthione (TIBO) derivative with potent activity against human immunodeficiency virus 1 (HIV-1) in vitro, was given to 22 patients with AIDS or AIDS-related complex in a dose-escalating pilot study. Doses of 10 to 300 mg administered daily by intravenous infusion were well tolerated for up to 50 weeks, with no haematological or biochemical evidence of toxicity. ⋯ When the rise in p24 antigen before therapy was compared to the fall during treatment, end-point analysis showed a significant difference (p less than 0.03). The combination of potent antiretroviral activity in vitro and the observed effect on HIV p24 antigen and absence of toxicity in vivo indicate that R 82913 and related TIBO derivatives merit further study in the treatment of retroviral infections.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group.
A randomised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid (one of the vitamins in the B group) or a mixture of seven other vitamins (A,D,B1,B2,B6,C and nicotinamide) around the time of conception can prevent neural tube defects (anencephaly, spina bifida, encephalocele). A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy, were allocated at random to one of four groups--namely, folic acid, other vitamins, both, or neither. 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect; 27 of these had a known neural tube defect, 6 in the folic acid groups and 21 in the two other groups, a 72% protective effect (relative risk 0.28, 95% confidence interval 0.12-0.71). ⋯ There was no demonstrable harm from the folic acid supplementation, though the ability of the study to detect rare or slight adverse effects was limited. Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy, and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid.
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The combination of measurements of regional cerebral blood flow (rCBF) and blood velocity in the middle cerebral arteries (MCA) by transcranial doppler sonography was used to investigate cerebrovascular involvement in migraine. Ten migraine patients with unilateral headache were studied during an attack and when they had been free of attacks for 5 days (non-attack). On both occasions they were given as intravenous infusion of sumatriptan (2 mg), a 5-HT1-like receptor agonist, which relieved the symptoms within 30 min without affecting rCBF. ⋯ The mean MCA diameter increase was estimated to be 20%. Thus, headache was associated with intracranial large arterial dilatation on the headache side. Sumatriptan predominantly had effects on the distended artery, which suggests that the 5-HT receptor system has a role in the pathogenesis of migraine.