Relationship between cholesteryl ester transfer activity and high density lipoprotein composition in hyperlipidemic patients

Cholesteryl ester transfer from solid-phase bound HDL to endogenous plasma HDL or VLDL/LDL was determined in 50 patients with primary disorders of lipid metabolism and 27 normolipidemic subjects. Transfer to the plasma HDL pool was significantly reduced in familial hypercholesterolemia, familial combined hyperlipidemia, hypoalphalipoproteinemia and dysbetalipoproteinemia. Subfractionation of HDL revealed that the lipid transfer to HDL3 was significantly reduced in all patient groups while transfer to HDL2 was increased in those with dysbetalipoproteinemia and familial hypertriglyceridemia. Transfer to LDL and VLDL was increased only in patients with dysbetalipoproteinemia and hypoalphalipoproteinemia. Reduced transfer to HDL occurred in samples with altered HDL composition; particularly where HDL-triglyceride was significantly increased and HDL-cholesteryl esters were reduced. Transfer of cholesteryl ester to HDL3 was significantly decreased in patients with vascular disease. These findings indicate that impaired interaction of cholesteryl ester transfer protein with the HDL3 pool may contribute to the risk of coronary heart disease in patients with specific plasma lipid abnormalities.     

Breaking the habit: a retrospective analysis of desistance factors among formerly problematic heroin users

Introduction and Aims . The aim of this study was to examine heroin careers among former users to assess desistance factors and explanations for sustained abstinence. Design and Methods . The study surveyed 107 former problematic heroin users who have achieved long‐term abstinence about their experiences of achieving and sustaining abstinence. The cohort was recruited opportunistically from three sources, drawing heavily on former users working in the addictions field. Results . On average, the group had heroin careers lasting for just under 10 years, punctuated by an average of 2.6 treatment episodes and 3.1 periods of abstinence, and had been heroin abstinent for an average of 10 years at the time of completing the survey. The most commonly expressed reason for finally achieving abstinence was ‘tired of the lifestyle followed by reasons relating to psychological health. In contrast, when asked to explain how abstinence was sustained, clients quoted both social network factors (moving away from drug‐using friends and support from non‐using friends) and practical factors (accommodation and employment) as well as religious or spiritual factors. Treatment was not mentioned widely either in achieving or sustaining abstinence, in contrast to 12‐Step, which was endorsed widely. Discussion and Conclusions . The study supports a careers perspective for examining heroin careers and indicates that, while achieving abstinence is possible for chronic opiate users, the path to sustained abstinence is complex and often reliant upon external support systems.     

Methyldopa. Mechanisms and treatment 25 years later

Methyldopa, an adrenergic-inhibiting compound, has been used for over 25 years as a safe and effective antihypertensive agent. The postulated mechanisms for the antihypertensive action of this compound have been varied and parallel our broadening knowledge of the role of the adrenergic nervous system in controlling arterial pressure. This review outlines the mechanisms of adrenergic control of the circulation and how the proposed mechanisms of action of methyldopa (ie, dopa decarboxylation, false neurotransmission, inhibition of renin release, and stimulation of alpha receptor sites in the brain) seem to account for the depressor action of the drug. Physiologic effects as well as immunologic and other clinical effects are also discussed.     

Renal involvement follows cardiac enlargement in essential hypertension

To assess the relationship between early clinically detectable involvement of hypertensive vascular disease in heart and kidneys, we obtained systemic and renal hemodynamic and M-mode echocardiographic measurements in 65 patients with essential hypertension. The results indicate that patients with and without left ventricular hypertrophy had similar renal hemodynamic findings. In contrast, patients with altered renal hemodynamic measurements (ie, reduced renal distribution of cardiac output and, therefore, absolute renal blood flow with increased renal vascular resistance) and increased serum uric acid levels also had increased left ventricular posterior and septal wall thicknesses and mass index. Moreover, these data also demonstrated that in patients with altered renal hemodynamics, the lower the renal distribution of cardiac output and the higher the serum uric acid levels, the greater were the indexes of cardiac enlargement. These results demonstrated that the pathophysiological and hemodynamic effects of essential hypertension in the heart precede those in the kidneys.     

Familial hypoalphalipoproteinemias

The familial hypoalphalipoproteinemias are a heterogeneous group of rare lipoprotein disorders characterized by extremely low levels of plasma high density lipoproteins (HDL) and, in most cases, autosomal recessive inheritance. Most of these conditions present distinctive and diagnostic clinical and laboratory abnormalities. In spite of the marked reductions in HDL, however, many of these conditions are not associated with premature atherosclerosis. This is true of Tangier disease, Fish Eye disease, lecithin: cholesterol acyltransferase deficiency, and of some variants of apo Al. Another condition, defined as a primary and familial decrease in HDL-cholesterol levels in the absence of other lipoprotein abnormalities. that is associated with premature atherosclerosis was originally called Familial Hypoalphalipoproteinemia but is better referred as to Familial Isolated Hypoalphalipoproteinemia. At present, the prevalence, inheritance, and the underlying defect(s) in this disorder are unknown. Decreased or absent synthesis of apo A-I due to a gene defect is the cause of apo A-I/C-III and apo A-I/C-III/A-IV deficiency. However, the etiology of the low levels of HDL is unclear for most of the remaining familial hypoalphalipoproteinemias. Increased catabolism, decreased synthesis and altered equilibration of HDL between intra- and extravascular spaces have all been suggested as underlying causes of low plasma HDL. Whatever their causes, these disorders are associated with altered HDL composition and altered equilibration of cholesterol amongst the various lipoprotein classes. The absence of consistent correlation with premature atherosclerosis in many of these conditions suggests that the protective effect of HDL may reside in a quantitatively small, but metabolically active subfraction of HDL particles.