Association of Filaggrin loss-of-function-mutations with atopic dermatitis and asthma in the Early Treatment of the Atopic Child (ETAC) population

Many candidate gene studies for atopic dermatitis (AD) and associated phenotypes have been conducted so far, but replication of significant results has been a major problem. Two loss of function polymorphisms FLG R501X- and 2282del4, in the Filaggrin ( FLG ) gene encoding for an epidermal barrier protein were recently identified. They were reported to be predisposing factors for AD and concomitant asthma. Several groups confirmed the initial results in independent populations. The aim of this study is to further investigate the importance of these FLG variants in the development of AD and subsequent asthma symptoms in pre-school children, we investigated children and parents of the Early Treatment of the Atopic Child (ETAC)-trial. We genotyped 496 children and 488 parents of the ETAC population for the two FLG variants, evaluating an association by family based analysis (transmission disequilibrium test). We found a highly significant association of the FLG null variants R501X- and 2282del4 with AD (combined genotype p < 0.0001) and asthma (combined genotype p < 0.0001). The replication and its statistical significance underlines the importance of the FLG polymorphisms and the importance of the skin barrier function in the development of AD and subsequent asthma.     

AIDS AS A CHALLENGE FOR THE DEVELOPMENT OF THE TREATMENT OF OPIOID DEPENDENTS IN CHINA Report on the 9th National Conference on Drug Dependence, MMT and HIV Prevention in Sanya/Hainan (VR China), 1-5 November 2006

Nearly 100 experts from all over China attended the Chinese National Conference on Drug Dependence in Sanya/Hainan. The participants came from drug abuse treatment centers, methadone clinics and drug research institutes. The conference's focus was on the question how drug abuse treatment shall and might be part of HIV prevention. CHINALi xiao(The Federal Drug Commissioner with the Federal Ministry of Health, Berlin)     

Pattern of serum autoantibodies allows accurate distinction between a tumor and pathologies of the same organ

PURPOSE: Recent studies impressively showed the diagnostic potential of seroreactivity patterns for different tumor types, offering the prospect for low-cost screening of numerous tumor types simultaneously. One of the major challenges toward this goal is to prove that seroreactivity profiles do not only allow for identifying a tumor but also allow for distinguishing tumors from other pathologies of the same organ. EXPERIMENTAL DESIGN: We chose glioma as a model system and tested 325 sera (88 glioma, 95 intracranial tumors, 60 other brain pathologies, and 82 healthy controls) for seroreactivity on a panel of 35 antigens. RESULTS: We were able to discriminate between glioma and all other sera with cross-validated specificity of 86.1%, sensitivity of 85.2%, and accuracy of 85.8%. We obtained comparably good results for the separation of glioma versus nontumor brain pathologies and glioma versus other intracranial tumors. CONCLUSION: Our study provides first evidence that seroreactivity patterns allow for an accurate discrimination between a tumor and pathologies of the same organ even between different tumor types of the same organ.     

Prenatal diagnosis of genetic disease by chorionic villi sampling

Chorionic villi sampling at week 9–11 of gestation is increasingly applied as a new method in prenatal diagnosis of genetic disorders. Cytogenetical, biochemical or recombinant DNA methods have been used successfully in more than 6000 pregnancies at risk. Different obstetric techniques for sampling chorionic villi using a catheter or a biopsy forceps, both under ultrasound guidance only, are practised so far. At the present stage of experience main problems of this method seem to be the risk of foetal loss, diagnostic errors caused by maternal cell contamination, as well as the difficulty in the interpretation of chromosomal mosaicism.     

Results of proximal metaphyseal fractures in children

BACKGROUND: The aims of the present study were: determining the extent of the two typical outcomes (valgus deformity and leg overgrowth); examining the extent, limits and duration of possible spontaneous corrections; and analysing the consequences of different types of therapy. METHODS: Metaphyseal tibial fractures in children are rare (incidence 5.6:100,000). Seven children were retrospectively re-examined by their medical records and roentgenograms. The patients' ages at the time of the accident ranged from 1 year 10 months to 10 years 2 months, and the average observation period was 34 months. RESULTS: All the patients experienced a subjective recovery, with the exception of one child who had minor functional problems. All of them were able to move their knee joint freely. Six patients developed a genu valgum (proximal tibia angle between 6 degrees and 16 degrees ); each of them was treated conservatively. Only two patients--both under the age of 5--experienced a partial spontaneous correction. Overgrowth on the side of the fracture was observed in four cases, varying from 0.5 cm to 1.5 cm, most pronounced after complete reduction and stable osteosynthesis. CONCLUSIONS: We recommend surgical correction and osteosynthesis as the preferred method of treatment, even with the increased likelihood of overgrowth. This is based on our observation of valgus deformity occurring in all cases after conservative treatment, with partial remodelling seen only in children up to the age of 5.     

Registration of drug-associated lesions of the mucosa of the upper gastrointestinal tract. The problem of characterizing the health status of healthy subjects

BACKGROUND AND AIM: Investigations with regard to toxic effects of drugs on the upper gastrointestinal tract depend on healthy volunteers with normal mucosal conditions. Because of the high prevalence of Helicobacter pylori infection it is mandatory to exclude infected volunteers without abdominal history as early as possible. This study was to compare the power of non-invasive and invasive tests in the selection of volunteers without gastric disease. METHOD: 85 healthy volunteers (age 18-35 years) without abdominal history underwent both gastroduodenoscopy and specific tests for Helicobacter pylori infection (IgA- and IgG-antibodies, ureasetest, culture, HE-staining). In the case of pathological findings, the biopsies were performed without including the subjects into the study with a non-steroidal anti-inflammatory drug (NSAIDs) (Diclofenac, CAS 15307-86-5). The invasive tests of volunteers, who were selected, were performed at the end of drug period, because biopsies would influence the outcome of a 7-day treatment with diclofenac RESULT: Initially 25/85 volunteers without any history of abdominal disease must be excluded. In 15 subjects there were abnormal concentrations of IgG- and/or IgA- antibodies against Helicobacter pylori. Endoscopically in 10 persons severe lesions were found (6 ulcer and/or erosions and/or reflux disease). In 18 subjects histologically the Helicobacter pylori infection was confirmed. At the end of the treatment period in 17/60 volunteers a positive Helicobacter pylori staining was found. Comparing five Helicobacter pylori tests there were no significant correlations between non-invasive and invasive procedures. CONCLUSION: The endoscopic investigation (gastroduodenoscopy) was the only valid method to differentiate between healthy volunteers and subjects with mucosal lesions. With regard to Helicobacter pylori infection neither the non-invasive nor the invasive tests were significantly correlated. Therefore, in investigations on the toxic effect of drugs the infection rate must be determined after treatment to prove the homogeneity of and between the groups. Most important is a subtile endoscopic technique which depends on high resolution video-endoscopes, chromoscopy as well as inter- and intra-observer variation procedures.     

Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin

AIMS: The primary aims of these two single-centre, randomized, evaluator-blind, placebo/positive-controlled, parallel-group studies were to evaluate the potential for pharmacodynamic and pharmacokinetic interaction between ezetimibe 0.25, 1, or 10 mg and simvastatin 10 mg (Study 1), and a pharmacodynamic interaction between ezetimibe 10 mg and simvastatin 20 mg (Study 2). Evaluation of the tolerance of the coadministration of ezetimibe and simvastatin was a secondary objective. METHODS: Eighty-two healthy men with low-density lipoprotein cholesterol (LDL-C) >or=130 mg dl-1 received study drug once daily in the morning for 14 days. In Study 1 (n=58), five groups of 11-12 subjects received simvastatin 10 mg alone, or with ezetimibe 0.25, 1, or 10 mg or placebo. In Study 2 (n=24), three groups of eight subjects received simvastatin 20 mg alone, ezetimibe 10 mg alone, or the combination. Blood samples were collected to measure serum lipids in both studies. Steady-state pharmacokinetics of simvastatin and its beta-hydroxy metabolite were evaluated in Study 1 only. RESULTS: In both studies, reported side-effects were generally mild, nonspecific, and similar among treatment groups. In Study 1, there were no indications of pharmacokinetic interactions between simvastatin and ezetimibe. All active treatments caused statistically significant (P<0.01) decreases in LDL-C concentration vs placebo from baseline to day 14. The coadministration of ezetimibe and simvastatin caused a dose-dependent reduction in LDL-C and total cholesterol, with no apparent effect on high-density lipoprotein cholesterol (HDL-C) or triglycerides. The coadministration of ezetimibe 10 mg and simvastatin 10 mg or 20 mg caused a statistically (P<0.01) greater percentage reduction (mean -17%, 95% CI -27.7, -6.2, and -18%, -28.4, -7.4, respectively) in LDL-C than simvastatin alone. CONCLUSIONS: The coadministration of ezetimibe at doses up to 10 mg with simvastatin 10 or 20 mg daily was well tolerated and caused a significant additive reduction in LDL-C compared with simvastatin alone. Additional clinical studies to assess the efficacy and safety of coadministration of ezetimibe and simvastatin are warranted.