Thiopurine S -methyltransferase polymorphisms: efficient screening method for patients considering taking thiopurine drugs

Objective: More than 11% of the Caucasian population are heterozygous or homozygous carriers of thiopurine S-methyltransferase (TPMT) mutants and are at risk for toxic side effects when treated with thiopurine drugs. Therefore, screening for TPMT polymorphisms in a patient prior to prescribing these agents is recommended. The goal of this study was to determine a cut-off concentration of the TPMT activity assay beyond which genotyping of the TPMT gene should be performed. Methods: The TPMT activity of 240 unrelated Caucasian subjects was measured using high-performance liquid chromatography. Genotyping for the most frequent allelic variants, TPMT*2, *3A, *3B, *3C and *7 was performed by LightCycler technology and sequencing. Results: The inter-individual TPMT activity showed a range from 23nmol MTG/g*Hb*h−1 to 97nmol MTG/g*Hb*h−1 with a median of 56nmol MTG/g*Hb*h−1. Using a cut-off concentration of 45.5nmol MTG/g*Hb*h−1, a test sensitivity of 100% and a specificity of 89% were reached for heterozygous carriers of a TPMT mutation. We identified 1 carrier of TPMT*2, 14 carriers of TPMT*3A and 3 carriers of TPMT*3C, resulting in a TPMT heterozygosity prevalence of 7.5%. Conclusions: This study defines the cut-off value for the TPMT phenotyping assay at 45.5nmol/g*Hb*h−1, beyond which additional genotyping elucidates the individual risk for drug therapy. Using this cut-off concentration, the number of genotyping assays could be reduced by about 60

Can Deliberately Incomplete Gene Sample Augmentation Improve a Phylogeny Estimate for the Advanced Moths and Butterflies (Hexapoda: Lepidoptera)?

This paper addresses the question of whether one can economically improve the robustness of a molecular phylogeny estimate by increasing gene sampling in only a subset of taxa, without having the analysis invalidated by artifacts arising from large blocks of missing data. Our case study stems from an ongoing effort to resolve poorly understood deeper relationships in the large clade Ditrysia ( > 150,000 species) of the insect order Lepidoptera (butterflies and moths). Seeking to remedy the overall weak support for deeper divergences in an initial study based on five nuclear genes (6.6 kb) in 123 exemplars, we nearly tripled the total gene sample (to 26 genes, 18.4 kb) but only in a third (41) of the taxa. The resulting partially augmented data matrix (45% intentionally missing data) consistently increased bootstrap support for groupings previously identified in the five-gene (nearly) complete matrix, while introducing no contradictory groupings of the kind that missing data have been predicted to produce. Our results add to growing evidence that data sets differing substantially in gene and taxon sampling can often be safely and profitably combined. The strongest overall support for nodes above the family level came from including all nucleotide changes, while partitioning sites into sets undergoing mostly nonsynonymous versus mostly synonymous change. In contrast, support for the deepest node for which any persuasive molecular evidence has yet emerged (78–85% bootstrap) was weak or nonexistent unless synonymous change was entirely excluded, a result plausibly attributed to compositional heterogeneity. This node (Gelechioidea + Apoditrysia), tentatively proposed by previous authors on the basis of four morphological synapomorphies, is the first major subset of ditrysian superfamilies to receive strong statistical support in any phylogenetic study. A “more-genes-only” data set (41 taxa×26 genes) also gave strong signal for a second deep grouping (Macrolepidoptera) that was obscured, but not strongly contradicted, in more taxon-rich analyses

Technikgenese: Einflußfaktoren der Technisierung jenseits traditioneller Technikfolgenforschung

Ausgehend davon, daß das Verhältnis von Technikgeneseforschung zu Technikfolgenforschung komplementär sein muß, werden in dem Beitrag die strukturellen, institutionellen und organisatorischen, die kognitiven wie perzeptiven Voraussetzungen dafür untersucht, welche Technikfolgen wie systematisch und rational in frühen Phasen der Technikentstehung wahrgenommen, berücksichtigt und technisch umgesetzt werden und welche nicht, um in der sozialwissenschaftlichen Rekonstruktion der Bedingungen technischer Innovationen die gesellschaftlichen und organisatorischen Einflußparameter, die Selektionsprozesse bei der Neueinführung von Techniken prägen, manifest werden zu lassen. Ziele und Grundlagen der sozialwissenschaftlichen Technikgeneseforschung werden dargestellt. Indem Technikgenese in organisationskulturellen Kontexten analysiert wird, wird ein neuer Forschungsansatz konzipiert, der im Kern beansprucht, das Selektions- und Entscheidungsverhalten von Organisationen mit Hilfe von Erklärungskategorien zu erfassen. Der zentrale Beitrag des organisationskulturellen Forschungsansatzes der Technikgenese liegt in der Möglichkeit, diejenigen Faktoren herauszukristallisieren, die eine Organisation dazu befähigen, innovative Impulse selbst zu generieren oder entsprechende Stimuli aus ihrer Umwelt aufzunehmen und umzusetzen. Abschließend wird das weitere Vorgehen sozialwissenschaftlicher Forschung zur Technikgenese skizziert. (ICA

Analysis of risk factors for low bone mineral density in inflammatory bowel disease

BACKGROUND/AIM: Several risk factors have been suggested for osteoporosis which frequently occurs in inflammatory bowel disease (IBD) patients. We studied prevalence and risk factors for reduced bone mineral density (BMD) in IBD patients at the University Hospital of Zurich, Switzerland. METHODS: The BMD was determined by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck in 88 IBD patients (55 with Crohn's disease, 30 with ulcerative colitis, and 3 with indeterminate colitis). Z scores were obtained by comparison with age- and sex-matched normal values, and T scores by comparison with sex-matched healthy young adults. Osteopenia and osteoporosis were defined according to the WHO guidelines. Predictive factors for BMD were analyzed by group comparison and stepwise regression analysis. RESULTS: Osteopenia was present in 43% of the patients at the lumbar spine and in 42% of them at the femoral neck. Osteoporosis was present in 14% of the patients at the lumbar spine and in 5% of them at the femoral neck. At the lumbar spine, stepwise regression analysis showed that body mass index, age, number of bowel resections, topic steroids, and azathioprine correlated with the Z scores. Cumulative steroid dose, topic steroids, age and bowel resection were found to be predictors for a pathological T score. At the femoral neck, regression analysis showed that body mass index, age, topic steroids, and azathioprine correlated with the Z scores. Only a low body mass index was a significant predictor for pathological femoral T scores. CONCLUSIONS: Osteopenia and osteoporosis are commonly found in IBD patients. Steroid treatment and bowel resection were significant risk factors for osteoporosis of the lumbar spine. However, disease-inherent factors also appear to confer a major risk, indicating that the BMD should be determined in all IBD patients, irrespective of steroid treatment

Verkaeuferinnen im Warenhaus Zum Zusammenhang von Berufssituation und Interessenorientierung von Frauen

Bibliothek Weltwirtschaft Kiel C 151535 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Frauenarbeit im Einzelhandel - das ''Paradies der Damen''?

Bibliothek Weltwirtschaft Kiel C 151530 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman