Effects of conventional and aggressive statin treatment on markers of endothelial function and inflammation

BACKGROUND: Atherosclerosis is considered to be a chronic inflammatory disorder. Several large-scale clinical studies demonstrate that markers of inflammation, such as high-sensitivity C-reactive protein (hsCRP), fibrinogen, and soluble CD40 ligand, are potent and independent predictors of vascular risk. HYPOTHESIS: The study was undertaken to investigate the effect of increasing the statin dose from conventional to aggressive treatment on lipids levels, inflammation, and endothelial function in patients with coronary artery disease (CAD). METHODS: We randomized 97 patients to either 20 mg simvastatin or 80 mg atorvastatin. Plasma levels of lipids, hsCRP, fibrinogen, soluble adhesion molecules, and nitric oxide-total were analyzed at baseline and after 6 months of treatment. RESULTS: Lipid values were significantly reduced in both treatment groups, but with significantly greater reduction in the aggressively treated group. Furthermore, aggressive statin treatment significantly decreased hsCRP and fibrinogen, while only small reductions were seen in the conventionally treated group, resulting in significant differences between the two treatment groups (p < 0.001). Nitric oxide-total increased significantly in both treatment groups, although the increase was more pronounced in the aggressively treated group (22.6 vs. 15.6%). CONCLUSION: Aggressive statin treatment significantly improved lipid status and reduced markers of inflammation and improved endothelial function compared with conventional treatment in patients with CAD. No interaction was observed, and high-dose treatment did not offer additional benefit compared with standard-dose treatment with respect to soluble adhesion molecules.     

Plasma concentrations during naltrexone implant treatment of opiate-dependent patients

AIMS: To evaluate individual variations in plasma concentrations over time in patients with naltrexone implants. METHODS: Ten opioid-dependent patients received up to four implants. Plasma samples were collected regularly for the analyses of naltrexone and the metabolite beta-naltrexol. RESULTS: The median naltrexone C(max) was 12.3 (range 5.8-22.1) ng ml(-1), the median T(max) was 1 day (range 3 h to 35 days), and the median length of time that plasma concentrations were above 1 ng ml(-1) was 55 (range 30-80) days. Two patients reported heroin use without experiencing any effect. Tissue reactions were recorded in two patients after repeated implantation. CONCLUSION: Marked individual and intraindividual variations in naltrexone concentrations were observed. Further studies should be performed to evaluate the need for therapeutic drug monitoring during naltrexone implant treatment.     

Untersuchungen der Cerebrospinalflüssigkeit mit besonderer Berücksichtigung der Pandyschen Reaktion

Ohne ZusammenfassungProfessor Dr. Sänger gewidmet aus Anlass seiner 25jährigen Tätigkeit im Krankenhause St. Georg.     

Organic leachables from polymer-based dental filling materials

Results are reported from a study on the in vitro separation and identification of leachables from three different polymer-based dental filling materials by using a combined method of gas chromatography and mass spectrometry. The median number of separable organic leachables in these materials was between 14 and 22. Of these organic leachables the following were identified and quantified: DL-camphorquinone, 4-dimethylaminobenzoic acid ethyl ester (DMABEE), drometrizole, 1,7,7-trimethylbicyclo[2,2,1]heptane, 2,2-dimethoxy[1,2] diphenyletanone (DMBZ), ethyleneglycol dimethacrylate (EGDMA), and triethyleneglycol dimethacrylate (TEGDMA). Three of the leachables have previously been shown to provoke allergy. The range of log P(ow) values (representing the lipophilicity of these compounds) varied between 1.09 and 4.20. By multivariate data analysis, selected leachables from the tested materials were shown to separate into characteristic patterns. The results contribute to a characterization of potential hazardous compounds in polymer-based dental filling materials.     

Development of working alliance over the course of psychotherapy

Objectives. The goal was to investigate patients' rating of working alliance in longer‐term individual psychotherapy (N=201), in order to determine different patterns of development and predictors of positive versus negative development. Design. The study explored patient factors that might be associated with positive versus negative development of the alliance, from early in treatment until the end. Subgroups of patients with different alliance development were compared, in order to identify predictors of these groups. Methods. The data analyses identified patients who demonstrated significant change in the perceived quality of alliance using the reliable change index. Most patients were expected to have a stable alliance, and fewer were expected to have improving or deteriorating alliance. Results. We found three patterns: stable alliance, improving alliance, and deteriorating alliance. Seventy per cent of the therapies had a stable alliance, which was maintained throughout the treatment, supporting the assumption that the quality of the early alliance is important for the therapy process. We observed different pre‐treatment scores of Target Complaint and Expectation of Change in Target Complaint between the subgroups with different development of the working alliance. Higher Expectation of Change was associated with improving alliance, whereas the combination of higher Target Complaint scores and lower Expectation of Change was associated with deteriorating alliance. Also, lower score on Global Assessment Scale (<50) was associated with deteriorating alliance. Clinical case vignettes illustrate the developments of improving and deteriorating alliance. Conclusion. Several pre‐treatment patient characteristics were associated with development of alliance in positive versus negative directions. Clinical implications are discussed.     

OCT2, SSX and SAGE1 reveal the phenotypic heterogeneity of spermatocytic seminoma reflecting distinct subpopulations of spermatogonia

Spermatocytic seminoma (SS) is a rare testicular neoplasm that occurs predominantly in older men. In this study, we aimed to shed light on the histogenesis of SS by investigating the developmental expression of protein markers that identify distinct subpopulations of human spermatogonia in the normal adult testis. We analysed the expression pattern of OCT2, SSX2-4, and SAGE1 in 36 SS cases and four intratubular SS (ISS) as well as a series of normal testis samples throughout development. We describe for the first time two different types of SS characterized by OCT2 or SSX2-4 immunoexpression. These findings are consistent with the mutually exclusive antigenic profile of these markers during different stages of testicular development and in the normal adult testis. OCT2 was expressed predominantly in A(dark) spermatogonia, SSX2-4 was present in A(pale) and B spermatogonia and leptotene spermatocytes, whilst SAGE1 was exclusively present in a subset of post-pubertal germ cells, most likely B spermatogonia. The presence of OCT2 and SSX2-4 in distinct subsets of germ cells implies that these markers represent germ cells at different maturation stages. Analysis of SAGE1 and SSX2-4 in ISS showed spatial differences suggesting ongoing maturation of germ cells during progression of SS tumourigenesis. We conclude that the expression pattern of OCT2, SSX2-4, and SAGE1 supports the origin of SS from spermatogonia and provides new evidence for heterogeneity of this tumour, potentially linked either to the cellular origin of SS or to partial differentiation during tumour progression, including a hitherto unknown OCT2-positive variant of the tumour likely derived from A(dark) spermatogonia.