We studied the influence of cholestyramine (24 g per day) on receptor-mediated and receptor-independent low-density-lipoprotein catabolism in five women with heterozygous familial hypercholesterolemia. Cholestyramine lowered the level of circulating low-density-lipoprotein apoprotein by doubling (P less than 0.01) its fractional clearance via the receptor path, but fractional catabolism by the receptor-independent route remained unchanged. Moreover, although the absolute rate of catabolism of the apoprotein was not affected by treatment, the amounts handled by each pathway altered. Catabolism via the physiologically controllable receptor route increased by 71 per cent (P less than 0.05), but there was a 12 per cent drop in clearance by the nonreceptor pathway. These data demonstrate the utility of cholestyramine in promoting low-density-lipoprotein catabolism via its specific physiologic clearance pathway. They also show that heterozygotes with familial hypercholesterolemia can increase the activity of their low-density-lipoprotein receptors when presented with an appropriate stimulus.

The isolation and identification of cholesterol α‐oxide, coprostanol, β‐sitosterol, cholest‐4‐en‐3‐one and cholesta‐4, 6‐dien‐3‐one from human serum are reported. Compounds were isolated by thin layer chromatography and were identified by gas liquid chromatography and gas chromatography‐mass spectrometry (GC‐MS). Data for standard sterols are also reported. The possible origins of these minor components and the significance of their presence are discussed.

The effects of a new steroid anaesthetic agent (CT1341) were studied in twenty volunteers divided into three groups. In group I, serial measurements were made of heart rate, blood pressure and respiratory rate. In group II, detailed haemodynamic studies were made in patients undergoing diagnostic cardiovascular investigations. These studies included measurement of cardiac output, stroke volume and arterial blood gases. In group HI, time from induction to "true recovery" was measured following a single intravenous injection of the drug. This agent produced a stable anaesthetic state in all cases. Anaesthesia was characterized by a rise in respiratory rate and pulse rate with a slight fall in systolic and diastolic blood pressure. A significant fall in Pa<>, occurred in those patients breathing air. The mean recovery time in six patients was 24.3 min. CT1341 produced safe and stable anaesthesia in all twenty cases and is worthy of further clinical trial. • CT1341 is manufactured by Glaxo Laboratories Limited, Greenford, Middlesex. 3a-hydroxy-5a-pregnane-ll,20 dione 0.9% w/v 21-acetoxy-3a-hydroxy-5o pregnane-11,20 dione 0.3% w/v Cremophor EL 20% w/v Sodium chloride 0.25% w/v Water for injection BP to 100% Throughout this paper the dosage of CT1341 will be expessed as ml of the above formulation. This paper reports the findings of a preliminary and limited clinical investigation conducted with the approval of the Committee on Safety of Drugs.

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