Cardiovascular morbidity and endothelial dysfunction in chronic haemodialysis patients: is homocyst(e)ine the missing link?

BACKGROUND: Haemodialysis patients exhibit an excessive burden of atherothrombotic disease, which is not explained adequately by traditional risk factors. Hyperhomocyst(e)inaemia, a consistent finding in uraemic patients, is now widely recognized as an independent risk factor for vascular disease. The aim of this study was to examine the hypothesis that hyperhomocyst(e)inaemia is associated with cardiovascular complications in dialysed patients. METHODS: In a cohort of 63 stable chronic haemodialysis patients, we examined the causal relationship between hyperhomocyst(e)inaemia and vascular endothelial and haemostatic function. All their markers were determined before and after an 8-week course of a 10 mg per day oral folate supplementation, a manoeuvre known to decrease hyperhomocyst(e)inaemia in uraemic patients. RESULTS: History of at least one cardiovascular atherothrombotic event was present in 47.6% of the haemodialysed patients, and radiographic evidence of vascular calcifications in 70%. Hyperhomocyst(e)inaemia was found in all patients, averaging 3.5-fold the upper limit of normal values (P<0.001), despite the lack of clinical and biological evidence of malnutrition. Fibrinogen, von Willebrand factor and plasminogen activator inhibitor type 1, but not endothelin 1, were significantly higher in haemodialysis patients than in controls. After adjustment for all variables, past history of cardiovascular events was independently associated with higher levels of homocyst(e)inaemia only (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01-1.12; P<0.026). The presence of aortic calcifications was independently and significantly associated with age (OR 1.37; 95% CI 1.07-1.75; P<0.025), homocyst(e)inaemia (OR 1.14; 95% CI 1.02-1.27; P<0.05) and fibrinogen concentration only (OR 9.74; 95% CI 1.25-75.2; P<0.05). None of the endothelial haemostatic factors was, however, related to homocyst(e)ine levels. Mid-term folate supplementation decreased plasma homocyst(e)ine levels significantly without achieving normal values. No significant change of endothelial-haemostatic markers was observed, however, despite the drop in plasma homocyst(e)ine. CONCLUSIONS: Hyperhomocyst(e)inaemia is associated with increased cardiovascular risk in haemodialysis patients. Folate supplementation was partially effective in lowering hyperhomocyst(e)inaemia, but its usefulness in terms of reduction in cardiovascular morbidity and mortality remains to be determined in prospective trials.

Bioavailability of escin after administration of two oral formulations containing aesculus extract.

In a steady-state cross-over study in 18 healthy volunteers, the relative bioavailability of beta-escin (CAS 11072-93-8) after oral administration of a new immediate release enteric-coated test formulation containing aesculus extract was evaluated in comparison with a prolonged-release reference preparation. The subject received the test and the reference preparation in randomised sequence for 7 days each with no washout period in between. The daily dose was 50 mg escin b.i.d. Blood samples for pharmacokinetic profiling were taken on the 7th treatment day of each period over a full 24-h cycle of two successive dosing intervals. For the determination of beta-escin serum concentrations, a highly specific radioimmunoassay (RIA) was used. Generally, escin serum concentrations were lower during the second dosing interval (night) than during the first interval, probably indicating a drug by food interaction. (The morning dose was given after overnight fasting whereas the evening dose was given between meals). Test and reference demonstrated bioequivalence with regard to the extent of absorption; for the AUC (0-24 h p.a.), the 90% confidence interval ranged from 84% to 114% (point estimate: 98%). The differences observed for rate parameters can be disregarded due to the generally slow elimination and the wide therapeutic concentration range of escin.

Reproductive health in Europe. In every country -- for every age group.

PIP: This editorial (September 1996 issue of "Entre Nous") presents the view that reproductive health is appropriate for all stages of the life cycle. Europe comprises about 50 different countries and 850 million people. Reproductive health concerns vary between regions and countries. The World Health Organization definition indicates that reproductive health refers to a state of complete physical, mental, and social well-being. Reproductive health implies that people are able to have a responsible, satisfying, and safe sex life. This means access to effective, affordable, and acceptable methods of fertility regulation, health services for safe pregnancies and deliveries, treatment of reproductive diseases and cancers, and care during and after menopause. This issue of the magazine includes a variety of perspectives on reproductive health. There is an article on the rise of sexually transmitted diseases in the Newly Independent States of the former USSR. Other articles address the health needs of older women in European developed countries, changes in contraceptive needs as women age, and the suffering of women due to reproductive health problems. The world focus on maternal and child health draws attention away from a holistic or comprehensive perspective. Although many women in developing countries suffer from reproductive tract infections, little attention is given to these common problems that have serious social and health implications. Dr. Nafis Sadik affirms the importance of women's empowerment and couples' and individuals' rights to decide freely and responsibly the number and spacing of children and to have the access and means to act. The principle of reproductive health is important for all women, all people, and all nations.^ieng

[Pharmaokinetics of beta-escin after administration of various Aesculus extract containing formulations]. / Pharmakokinetik von beta-Aescin nach Gabe verschiedener Aesculus-Extrakt enthaltender Formulierungen.

With a specific radioimmunoassay the pharmacokinetics and relative bioavailability of escin was measured after administration of different formulations containing Aesculus-extract. Of special interest was the relative bioavailability of escin after administration of a newly developed film-coated tablet with sustained release in comparison to a reference formulation. In a cross-over steady-state study in 24 volunteers bioequivalence of test and reference preparation could be demonstrated. The 90% confidence interval of the AUC (O-tau) was 98.3 to 120.9%.

[Nutrition, metabolic and endocrine complications during extrarenal dialysis]. / Nutrition, complications métaboliques et endocriniennes au cours de l'épuration extra-rénale.

Patients with chronic renal failure treated by maintenance dialysis often have nutritional disorders, metabolic disorders concerning lipids, proteins and carbohydrates, and disorders of endocrine systems involved in the regulation of these metabolisms. These disorders are difficult to diagnose, as their clinical symptoms are few and of little pathognomonic value. Hence the need for anthropometric measurements as well as biochemical and physiological exploration of metabolic pathways for intermittent overall evaluation and longitudinal follow-up. These patients have reduced subcutaneous fat reserves, intolerance to carbohydrates by resistance to insulin (partially corrected by haemodialysis), low levels of plasma aminoacids, notably valine, type IV hyperlipidaemia with low levels of essential fatty acids, fragile immune system and increased requirements for vitamins B, especially B6. Dietary recommendations include: food energy 35 kiloCal/kg bodyweight/day; proteins 1 to 1.2 g/kg bodyweight/day (50 p. 100 of which must be complete proteins) and supplements of vitamins. Dialysis must be optimal for clearance of nitrogen compounds and body homeostasis.