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There are indications that treatment of hypercholesterolemia by means of drugs reduce risk of atherosclerosis in patients with increased concentrations of atherogenic lipoproteins. Such therapy should be initiated only after satisfactory exclusion of secondary causes of hyperlipoproteinemia, and should be regarded as an adjunct to appropriate dietary therapy. Drug therapy should be strongly considered in patients with total cholesterol above 8-9 mmol/l on diet therapy only. Drug therapy should be considered at even lower concentrations of cholesterol when coronary heart disease is present and in familial forms of hyperlipidemia when increased risk of atherosclerosis has been documented. In patients with increased plasma concentrations of total cholesterol the drugs of choice are agents which enhance the rate of LDL catabolism (resins) or reduce the rate of LDL synthesis (nicotinic acid). Fibrates should be used when triglycerides and cholesterol are both increased. HMG CoA reductase inhibitors offer considerable promise in the therapy of patients with primary hypercholesterolemia. Probucol may be used in combination with other drugs, particularly when xanthomas are present in patients with familial hypercholesterolemia.

We describe the clinical findings and natural history of an autosomal dominant form of partial lipodystrophy found in four affected individuals from three generations in the same family. The lipodystrophy was present from infancy/early childhood, involved primarily the face and local areas on the buttocks, and was nonprogressive. Affected individuals also had the Rieger anomaly, midface hypoplasia, short stature, retarded bone age, and hypotrichosis. An affected woman developed insulinopenic diabetes mellitus at 39 yr and another had glucose intolerance at 55 yr.

Binding, uptake, and degradation of 125I-labelled HDL were measured in isolated rat non-parenchymal cells in vitro. The binding exhibited saturation kinetics and was inhibited to various degrees with other unlabelled lipoproteins such as VLDL, LDL, and HDL, but the uptake was not reduced by heat and formaldehyde-denatured albumin. The binding could be reduced by pronase treatment of the cells. Acetylated 125I-labelled HDL were more effectively taken up and degraded by non-parenchymal cells than unmodified 125I-labelled HDL. The Kupffer cells were able to take up two to three times as much HDL per cell as the endothelial cells. 125I-labelled HDL bind to the plasma cell membrane and can be dissociated by addition of unlabelled HDL. Relatively more labelled HDL dissociate at 4 degrees C than at 37 degrees C. The non-parenchymal cells also internalize 125I-labelled HDL at 37 degrees C, and the lysosomotropic drug chloroquine inhibits partly the degradation of accumulated 125I-labelled HDL.

Five children are reported with dolichocephaly (with sagittal suture synostosis in three), sparse, slow-growing, fine hair, epicanthal folds, hypodontia and/or microdontia, short span, brachydactyly and brachypodia, and narrow thoraces. Radiologic abnormalities were noted chiefly in the skull, chest, and limbs. Intelligence was normal. The pattern of inheritance is compatible with an autosomal recessive trait.

The association of 125I-labelled rat high density lipoproteins (125-I-HDL) to suspended rat hepatocytes was studied at 4 degrees C. 125 I-HDL associated to isolated hepatocytes by two processes-one of high and one of low affinity. The cell-association of 125I-HDL exhibited saturation kinetics and was inhibited to varying degrees with both rat and human lipoproteins such as VLDL, LDL and HDL but not by lipoprotein deficient serum or asialo-fetuin. The cell-association of 125I-HDL did not require divalent cations and could be reduced by pronase treatment of the cells. The binding site was clearly different from the receptor for LDL in extrahepatic cells since heparin and apolipoprotein E did not compete and cholesterol ester labelled HDL. The number of binding sites for HDL at 4 degrees C was 2.2 X 10(6) per cell and the association constant (Ka) 8.2 X 10(6) (mol/l)-1. Experiments with HDL labelled with [3H] cholesterol by means of lecithin: cholesterol acyltransferase (LCAT, EC 2.3.1.43) in the cholesterol ester moiety suggested that the same mechanism was responsible for the cell-association of HDL prepared this way.