The usefulness of information on HDL-cholesterol: potential pitfalls of conventional assumptions

Treatment decisions related to disease prevention are often based on two conventional and related assumptions. First, an intervention-induced change in a surrogate marker (such as high-density lipoprotein [HDL]-cholesterol) in the desired direction translates into health benefits (such as reduction in coronary events). Second, it is unimportant which interventions are used to alter surrogate markers, since an intervention benefit is independent of the means by which it is achieved. The scientific foundation for these assumptions has been questioned. In this commentary, the appropriateness of relying on low levels of HDL-cholesterol for treatment decisions is reviewed. The Veterans Affairs - HDL-Cholesterol Intervention Trial (VA-HIT) investigators recently reported that only 23% of the gemfibrozil-induced relative reduction in risk of coronary events observed in the trial could be explained by changes in HDL-cholesterol between baseline and the 1-year visit. Thus, 77% of the health benefit to the participants was unexplained. Other possible explanations are that gemfibrozil has multiple mechanisms of action, disease manifestations are multifactorial, and laboratory measurements of HDL-cholesterol are imprecise. The wisdom of relying on levels and changes in surrogate markers such as HDL-cholesterol to make decisions about treatment choices should questioned. It seems better to rely on direct evidence of health benefits and to prescribe specific interventions that have been shown to reduce mortality and morbidity. Since extrapolations based on surrogate markers may not be in patients' best interest, the practice of medicine ought to be evidence-based.     

Zur Charakteristik der schlesischen Vogelwelt

Ohne Zusammenfassunggehalten in der Sitzung vom 5. Oktober 1891 zu Berlin.     

Arsenic and high affinity phosphate uptake gene distribution in shallow submarine hydrothermal sediments

The toxicity of arsenic (As) towards life on Earth is apparent in the dense distribution of genes associated with As detoxification across the tree of life. The ability to defend against As is particularly vital for survival in As-rich shallow submarine hydrothermal ecosystems along the Hellenic Volcanic Arc (HVA), where life is exposed to hydrothermal fluids containing up to 3000 times more As than present in seawater. We propose that the removal of dissolved As and phosphorus (P) by sulfide and Fe(III)(oxyhydr)oxide minerals during sediment–seawater interaction, produces nutrient-deficient porewaters containing?<?2.0 ppb P. The porewater arsenite-As(III) to arsenate-As(V) ratios, combined with sulfide concentration in the sediment and/or porewater, suggest a hydrothermally-induced seafloor redox gradient. This gradient overlaps with changing high affinity phosphate uptake gene abundance. High affinity phosphate uptake and As cycling genes are depleted in the sulfide-rich settings, relative to the more oxidizing habitats where mainly Fe(III)(oxyhydr)oxides are precipitated. In addition, a habitat-wide low As-respiring and As-oxidizing gene content relative to As resistance gene richness, suggests that As detoxification is prioritized over metabolic As cycling in the sediments. Collectively, the data point to redox control on Fe and S mineralization as a decisive factor in the regulation of high affinity phosphate uptake and As cycling gene content in shallow submarine hydrothermal ecosystems along the HVA.     

Withdrawal of cerivastatin from the world market

Cerivastatin was recently withdrawn from the market because of 52 deaths attributed to drug-related rhabdomyolysis that lead to kidney failure. The risk was found to be higher among patients who received the full dose (0.8 mg/day) and those who received gemfibrozil concomitantly. Rhabdomyolysis was 10 times more common with cerivastatin than the other five approved statins. We address three important questions raised by this withdrawal. Should we continue to approve drugs on surrogate efficacy? Are all statins interchangeable? Do the benefits outweigh the risks of statins? We conclude that decisions regarding the use of drugs should be based on direct evidence from long-term clinical outcome trials.     

Zur Frage der Geschwulstbildung bei Gattungsbastarden der ZahnkarpfenXiphophorus undPlatypoecilus

Ohne ZusammenfassungMit 4 Textfiguren