Optimierte Cholesterinsenkung

Ezetimibe is a recently developed compound, which inhibits intestinal cholesterol absorption. Because there are hints for an increase of cholesterol absorption during statin therapy, the combination of Ezetimibe with a statin seems to be appropriate. This dual approach — inhibition of intestinal cholesterol absorption and hepatic cholesterol synthesis — offers a very potent reduction of cholesterol. The combination of statins with Ezetimibe leads to a further reduction of LDL-cholesterol up to 12–21%. The dual inhibition causes a more effective reduction of LDL-cholesterol than a statin monotherapy. LDL treatment goals can be reached more easily, and possible side effects of otherwise necessary high doses of statins can be avoided. Clinical endpoint studies with Ezetimibe are underway.     

Prevalence of HLA-DRB1 genotype and altered Fas/Fas ligand expression in adrenocortical carcinoma

A distinctive feature of malignant adrenocortical neoplasms is decreased major histocompatibility complex (MHC) class II molecule expression. However, it is unknown whether there exists a restriction to certain MHC genotypes and whether this involves alterations of the Fas/Fas ligand system and thereby affects tissue homeostasis. Therefore, MHC class II phenotype and genotype and expression patterns of the Fas/Fas ligand system were investigated in 24 adrenocortical tumors (n(Adenomas) = 14, n(Carcinomas) = 10) and an adrenal cancer cell line (NCI-H295). No MHC class II antigen expression was detected in carcinomas. The DRB1*01 genotype was found in 54.5% of patients with carcinoma (P = 0.046). No prevalence of any genotype could be detected in patients with adenomas, which exhibited varying levels of antigen expression. Fas receptor expression was 75.0% in adenomas compared with 20.0% in carcinomas (P = 0.0196), whereas ligand expression was 37.7% in adenomas and reached almost 100% in the carcinomas investigated in this study (P = 0.0033). In summary, the DRB1*01 genotype may be correlated to a higher risk for malignancy. Additional studies on MHC class II genotype and phenotype and the altered Fas/Fas ligand system in adrenal neoplasms may help to identify mechanisms of immune escape and suggest new diagnostic approaches.     

A homocysteine metabolism-related dietary pattern and the risk of coronary heart disease in two independent German study populations

A biomarker profile of high folate and vitamin B-12 and low plasma homocysteine concentrations reduces the risk of coronary heart disease (CHD) and may be linked to diet. The objectives of the present study were to identify a food pattern related to these biomarkers and to examine its association with CHD risk. Dietary patterns related to biomarker plasma concentrations were constructed from data obtained in the Coronary Risk Factors for Atherosclerosis in Women (CORA) Study (200 cases; 255 controls) using the reduced rank regression statistical method. Risks for CHD with relation to the identified pattern were estimated in the CORA study and in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study with 157 cases of incident myocardial infarction among 26,795 participants. In these 2 German study populations, whole-grain bread, fresh fruit, olive oil, mushrooms, cruciferous vegetables, wine, and nuts contributed the most positively and fried potatoes the most negatively to a dietary pattern that was directly associated with both plasma folate and vitamin B-12 concentrations, but inversely with plasma homocysteine. Multivariate-adjusted relative risks for CHD across increasing quintiles of the food pattern score were 1.0, 0.55, 0.52, 0.58, 0.39 (P for trend = 0.05) in the case-control sample and 1.0, 0.95, 0.75, 0.56, 0.72 (P for trend = 0.041) in the prospective study. The combination of a high intake of whole-grain bread, fresh fruit, olive oil, mushrooms, cruciferous vegetables, wine, and nuts with a low intake of fried potatoes was associated with a favorable biomarker profile of homocysteine metabolism and reduced risk of CHD.     

Mediators of inflammatory and ischemic renal damage: the role of neoangiogenesis

Neoangiogenesis is at the forefront of research in a number of fields that are of interest to the nephrologist, ranging from the development of the kidney and glomerulus to microvascular injury and its repair. The molecular mechanisms have recently been elucidated to a considerable extent. They are relevant for understanding the link between endothelial cells and podocytes, which underlie the glomerular barrier function. For reasons poorly understood capillarogenesis is defective in renal failure.     

The clinical management of hyperphosphatemia

As renal function declines in patients with end-stage renal disease (ESRD), excess dietary phosphorus accumulates in the bloodstream. Routine dialysis removes up to 70% of absorbed phosphorus; therefore, hyperphosphatemia is found in the majority of patients with ESRD. The consequences of this imbalance include secondary hyperparathyroidism and osteodystrophy. Recent studies have also documented that hyperphosphatemia can lead to soft-tissue and vascular calcification; the latter is strongly associated with cardiovascular disease and, thus, increased mortality and morbidity. The reduction of phosphorus levels is, therefore, an important therapeutic target in this patient group. Management of hyperphosphatemia using conventional phosphate binders is not always successful. However, emerging therapies aim to reduce the incidence of hyperparathyroidism, bone disease, and calcification in this patient population. In this article, the consequences of hyperphosphatemia are reviewed, and recent developments in the treatment of the condition are discussed.     

Detection of consciousness by electroencephalogram and auditory evoked potentials

BACKGROUND: A set of electroencephalographic and auditory evoked potential (AEP) parameters should be identified that allows separation of consciousness from unconsciousness (reflected by responsiveness/unresponsiveness to command). METHODS: Forty unpremedicated patients received anesthesia with remifentanil and either sevoflurane or propofol. With remifentanil infusion (0.2 microg . kg . min), patients were asked every 30 s to squeeze the investigator's hand. Sevoflurane or propofol was given until loss of consciousness. After intubation, propofol or sevoflurane was stopped until patients followed the command (return of consciousness). Thereafter, propofol or sevoflurane was started again (loss of consciousness), and surgery was performed. Return of consciousness was observed after surgery. The electroencephalogram and AEP from immediately before and after the transitions were selected. Logistic regression was calculated to identify models for the separation between consciousness and unconsciousness. For the top 10 models, 1,000-fold cross-validation was performed. Backward variable selection was applied to identify a minimal model. Prediction probability was calculated. The digitized electroencephalogram was replayed, and the Bispectral Index was measured and accordingly analyzed. RESULTS: The best full model (prediction probability 0.89) contained 15 AEP and 4 electroencephalographic parameters. The best minimal model (prediction probability 0.87) contained 2 AEP and 2 electroencephalographic parameters (median frequency of the amplitude spectrum from 8-30 Hz and approximate entropy). The prediction probability of the Bispectral Index was 0.737. CONCLUSIONS: A combination of electroencephalographic and AEP parameters can be used to differentiate between consciousness and unconsciousness even in a very challenging data set. The minimal model contains a combination of AEP and electroencephalographic parameters and has a higher prediction probability than Bispectral Index for the separation between consciousness and unconsciousness.