Ameliorated course of glucose-6-phosphate isomerase (G6PI)-induced arthritis in IFN-γ receptor knockout mice exposes an arthritis-promoting role of IFN-γ

The absence of IFN-γ signaling leads to an increased inflammatory response in many murine models of autoimmune diseases induced by a CFA-assisted immunization schedule. We investigated the role of endogenous IFN-γ in arthritis induced by immunization with glucose-6-phosphate isomerase (G6PI) in CFA in DBA/1 mice. Surprisingly, and in contrast to our previous findings in collagen-induced arthritis (CIA), G6PI-induced arthritis was found to be reduced in IFN-γ receptor-deficient (IFN-γR KO) mice, demonstrating a proinflammatory role for IFN-γ in this model. Milder disease in IFN-γR KO mice was associated with less vigorous innate and adaptive immune responses early (day 9) after immunization: less proliferation of myeloid cells in the spleen, less osteoclast formation, less G6PI-reactive Th cells (as measured by ex vivo stimulation and flow cytometry and by in vivo skin reactivity to G6PI) and lower G6PI-specific immunoglobulin serum levels. Surprisingly, on day 21, despite continued milder disease in IFN-γR KO mice, their Th cell responses were no longer diminished but augmented as compared to wild-type mice, and their numbers of immature myeloid splenocytes were also more increased. These data reveal that IFN-γ signaling is critical for the induction of the early immune responses which trigger G6PI-induced arthritis. The strikingly different clinical consequences of absent IFN-γ signaling in G6PI-induced arthritis compared with the very similarly induced CIA emphasize that the role of a single cytokine in experimentally induced arthritis depends critically on the very nature of the inciting (auto)antigen and in particular on the kinetics of the disease manifestation elicited by the antigen.     

Secular trends in mortality associated with new therapeutic strategies in surgical critical illness

BACKGROUND: Since 1999 randomized controlled trials have shown that new therapeutic strategies, such as strict glycemic control, increased use of noninvasive ventilation and of lung-protective ventilation, and early goal-oriented shock therapy, may reduce mortality in selected groups of critically ill patients. Whether these benefits can be translated to a surgical clinical setting is unclear. We wanted to evaluate longitudinally the successive routine implementation of new therapeutic measures and its effect on postsurgical patients admitted to the intensive care unit. METHODS: We performed a retrospective analysis on data collected prospectively from March 1, 1993 through February 28, 2005. RESULTS: A cohort of 1,802 consecutive cases requiring intensive care therapy for more than 4 days was analyzed. A significant decrease in mortality was observed in the last years of the study. With adjustment for relevant covariates, treatment after the implementation of new therapeutic strategies was identified as an independent factor linked with a reduced risk of death (odds ratio [OR] .518; 95% confidence interval [CI] .337-.796), whereas older age (OR 1.030; 95% CI 1.015-1.045), a high severity score on admission (OR 1.155; 95% CI 1.113-1.198) or during intensive care unit stay (OR 1.187; 95% CI 1.145-1.231), a high number of failing organs (OR 1.918; 95% CI 1.635-2.250), and peritonitis (OR 3.277; 95% CI 2.046-5.246) were independently associated with death. CONCLUSIONS: Implementing of a variety of new therapeutic measures into routine care of critically ill surgical patients was associated with improved survival after 2001.     

Do physicians improve their communication skills between finishing medical school and completing internship? A nationwide prospective observational cohort study

Objective

To test whether young physicians improve their communication skills between graduating from medical school and completing clinical internship, and to explore contributing background and/or internship factors.

Methods

Norwegian medical students graduating June 2004 were invited to take part in a videotaped standardized patient interview February 2004. Of the 111 students who originally participated, 62 completed a second interview February 2006. Observed communication skills were assessed with the Arizona Communication Interview Rating Scale (ACIR).

Results

The level of communication skills increased significantly during the period for participants overall; and for females but not males. General social skills reached significantly higher levels than specific professional skills, both types of skill improving during the study. Independent predictors were working in local hospitals, learning atmosphere and low stress.At school completion, 50% reached a level defined as ‘advanced beginner’. Towards the end of the internship, 58% reached ‘capable’ and 27% ‘competent’ levels of communication skills.

Conclusions

Female physicians improved most in communication skills, the gender difference being multivariate mediated through low stress levels and learning atmosphere. The findings support the division of communication skills into general social and specific professional skills.

Practice implications

The relatively low proportion of young physicians, especially males, developing the capability to practise independently at internship completion indicates a need for more effective training in communication skills, during both medical school and internship.     

Very early premature ovarian failure in two sisters compound heterozygous for the FMR1 premutation

Expansion of the CGG trinucleotide repeat in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene within the premutation range is one of the known genetic factors associated with premature ovarian failure and earlier age at menopause. Studies have shown that approximately 16–26% of female carriers will develop premature ovarian failure, and current research is focussed on the identification of molecular factors that predict its occurrence in female carriers. In this report we present two sisters who are compound heterozygous for a premutation, and who were referred because of very early menopause, occurring at the age of 17 years in the youngest sister. Premature ovarian failure associated with FMR1 premutation at such an early age has not been reported in the literature before.     

Medizin darf nicht verstummen

best practice onkologie -     

Effects of dietary supplementation with the green tea polyphenol epigallocatechin-3-gallate on insulin resistance and associated metabolic risk factors: randomized controlled trial

Animal evidence indicates that green tea may modulate insulin sensitivity, with epigallocatechin-3-gallate (EGCG) proposed as a likely health-promoting component. The purpose of this study was to investigate the effect of dietary supplementation with EGCG on insulin resistance and associated metabolic risk factors in man. Overweight or obese male subjects, aged 40-65 years, were randomly assigned to take 400 mg capsules of EGCG (n 46) or the placebo lactose (n 42), twice daily for 8 weeks. Oral glucose tolerance testing and measurement of metabolic risk factors (BMI, waist circumference, percentage body fat, blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG) was conducted pre- and post-intervention. Mood was evaluated weekly using the University of Wales Institute of Science and Technology mood adjective checklist. EGCG treatment had no effect on insulin sensitivity, insulin secretion or glucose tolerance but did reduce diastolic blood pressure (mean change: placebo - 0.058 (se 0.75) mmHg; EGCG - 2.68 (se 0.72) mmHg; P = 0.014). No significant change in the other metabolic risk factors was observed. The EGCG group also reported feeling in a more positive mood than the placebo group across the intervention period (mean score for hedonic tone: EGCG, 29.11 (se 0.44); placebo, 27.84 (se 0.46); P = 0.048). In conclusion, regular intake of EGCG had no effect on insulin resistance but did result in a modest reduction in diastolic blood pressure. This antihypertensive effect may contribute to some of the cardiovascular benefits associated with habitual green tea consumption. EGCG treatment also had a positive effect on mood. Further studies are needed to confirm the findings and investigate their mechanistic basis.     

Intra-individual variability in ADHD, autism spectrum disorders and Tourette's syndrome

The potential for response variability to serve as an endophenotype for attention deficit hyperactivity disorders (ADHD) rests, in part, upon the development of reliable and valid methods to decompose variability. This study investigated the specificity of intra-individual variability (IIV) in 53 children with ADHD by comparing them with 25 children with high functioning autism (HFA), 32 children with autism spectrum disorders (ASD), who also were comorbid for ADHD (ASD+ADHD), 21 children with Tourette's syndrome (TS), and 85 typically developing controls (TD). In order to decompose the variability of the reaction times, we applied three distinct techniques: ex-Gaussian modeling, intra-individual variability analysis, and spectral analysis. Our data revealed that children with HFA and children with ASD+ADHD exhibited substantial IIV compared with ADHD and TD children. We argue that: (1) all three methods lead to a single consistent conclusion; (2) careful documentation of the analytic steps used in spectral analysis is mandatory for comparison between studies; (3) the presence of comorbidities may constitute an important factor in the observed response variability in previous studies of ADHD.