Prediction of phenotype for acetylation and for debrisoquine hydroxylation by DNA-tests in healthy human volunteers

Summary The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of DNA by the polymerase chain reaction (PCR), which also allow for identification of heterozygous carriers of one mutant allele.In the present study, the results of genotyping of 81 healthy European volunteers were compared with the phenotype obtained by the classical biochemical approach using debrisoquine and caffeine as probe drugs.Genotyping correctly predicted all 73 extensive metabolisers (EMs) and 6 out of 8 poor metabolisers (PMs) of debrisoquine. All 48 rapid acetylators and 33 of 35 slow acetylators were predicted.Overall, the DNA analysis result matched the in vivo phenotype in 97.5 % of individuals.     

Alterations within pp59v-rel-containing protein complexes following the stimulation of REV-T-transformed lymphoid cells with zinc.

pp59v-rel exists in association with specific cellular proteins within lymphoid cells transformed by reticuloendotheliosis virus (REV-T). These include the cellular rel homolog (p75c-rel) as well as a 40-kDa avian homolog to I kappa B. The brief exposure of REV-T-transformed lymphoid cells to micromolar concentrations of ZnSO4 induces profound alterations within these protein complexes. Most of the constituents of the rel protein complexes (to include pp59v-rel, p75c-rel, and p115) translocate from the cytosol to the nucleus. This system has been used to characterize the molecular events that accompany the activation of rel protein complexes. The level of phosphorylation increases on three proteins within these complexes: pp59v-rel, p75-c-rel, and pp40. The degree of phosphorylation on pp59v-rel is such that its relative mass increases 3 to 6 kDa when resolved by SDS-polyacrylamide gel electrophoresis. pp59v-rel is phosphorylated on serine and threonine residues predominantly within a single domain of 17.5 kDa. Similarly, p75c-rel exhibits a corresponding increase in its relative mass with increased phosphorylation. The increased phosphorylation of pp40 is accompanied by its dissociation from the cytosolic rel protein complexes. These observations draw parallels with the induction of the NF-kappa B trans-activating factor.     

Ein Beitrag zur aktuellen Antidementivadiskussion in Deutschland

In Germany, the role of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease (AD) has become a topic of recent discussion. The present article addresses issues which, in the opinion of the authors, have not received sufficient attention. These include the distinction between statistical and clinical significance, outcome parameters, the duration of clinical trials, variability in treatment response and the definition of treatment responders. The authors argue that these issues need to be considered in an in-depth evaluation of acetylcholinesterase inhibitors in the treatment of AD.     

Inzidentalome der Nebenniere

Adrenal incidentalomas are clinically inapparent masses detected incidentally with imaging studies conducted for other reasons. They are relatively common and require structured diagnostic workup. In many cases surveillance is warranted. The diagnostic workflow has to reveal whether the mass is hormonally functioning and/or if there is evidence of malignancy. If the tumor is functionally silent and not larger than 4 cm, surveillance is warranted. Functioning tumors and masses larger than 6 cm have to be resected. Fine-needle aspiration biopsy is indicated in very rare cases, but pheochromocytoma has to be ruled out first.     

Regulation der Laktation

At birth the human newborn is immature and has not yet acquired fully competent organ functions. During lactation especially the digestive tract and the immune system gain competence. Lactation is regulated by a complex interaction of numerous hormonal factors. Most important are probably prolactin and oxytocin—two hormones produced and secreted in the pituitary. The production and secretion of these two hormones is again regulated by several factors in the central nervous system and these mechanisms can be disturbed by a variety of exogenous factors such as drugs and any other substances interacting with dopamine metabolism in the brain. It is important to know these physiological interactions to be able to understand the regulation of lactation and to be able to assess which factors could interfere with this process.     

Total-videoendoskopische Strumaresektion via“axillobilateral breast approach”

BACKGROUND: The axillobilateral breast approach (ABBA) is a procedure allowing thyroid resection without scarring at the neck. We operated on a series of 26 patients with this technique. METHOD: Via incisions at the edge of the mamilla and axilla, trocars are placed subcutaneously under the platyma. Dissection is performed bluntly and with an ultrasonographic scalpel under videoscopic control. The procedure itself corresponds to conventional surgery. The specimen is removed through the axillary trocar. RESULTS: Twenty-six female patients underwent thyroid resection using the ABBA technique. Subtotal resection was performed in 24. Mean operation times were 111 min (unilateral) and 187 min (bilateral). In none of these cases was conversion necessary. One transient recurrent laryngeal nerve palsy and one paresis of the arm plexus were found postoperatively. CONCLUSION: In selected patients the ABBA technique is feasible and safe with the mandatory radicalness. The primary aim of this method is the cosmetic result.     

Endoprothesenlockerungen

The life time of hip endoprostheses is in part limited by aseptic loosening. The aim of this study was to produce a digital system for recording shaft loosening in such endoprostheses using acceleration sensors. Four identical prosthetic shafts were each set with 3.2-axial acceleration sensors and placed in artificial femurs. In order to simulate a firm fit, one prosthesis was fixed with bone cement; a loose fit was fixed with a surrounding silicon shell 0.5 mm thick. Simulation of the transition from firm to loose in the other two prostheses was attained by the distal 2/3 or 1/3 being cemented, with the rest surrounded by a silicone shell. A weak oscillation was initiated via a damped falling weight. Using a fast Fourier transformation it was possible to make a global evaluation of the measurement curves. A wavelet transformation could be used to differentiate firm or loose prostheses. A third order Daubechies filter recognized the deviation in the main oscillation, made visible by an increase in amplitude. The results encourage the development of an implantable, telemetrically functioning total system which would allow digital quality assurance when integrated into the endoprosthesis.