Summary Background Nutritional intervention with hydrolysed infant formulas has been shown efficacious in preventing eczema in children predisposed to allergy. However, this preventive effect has never been related to the natural course of eczema in children with or without a family history of allergy. The aim of this study therefore was to compare the course of eczema in predisposed children after nutritional intervention to the natural course of eczema. Method The prospective German birth cohort study GINIplus includes a total of 5991 children, subdivided into interventional and non-interventional groups. Children with a familial predisposition for allergy whose parents agreed to participate in the prospective, double-blind intervention trial (N=2252) were randomly assigned at birth to one of four formulas: partially or extensively hydrolysed whey, extensively hydrolysed casein (eHF-C) or standard cow's milk formula. Children with or without familial predisposition represented the non-interventional group (N=3739). Follow-up data were taken from yearly self-administered questionnaires from 1 up to 6 years. The outcome was physician-diagnosed eczema and its symptoms. The cumulative incidence of eczema in predisposed children with or without nutritional intervention was compared with that of non-predisposed children who did not receive intervention. Cox regression was used to adjust for confounding. Results Predisposed children without nutritional intervention had a 2.1 times higher risk for eczema [95% confidence interval (CI) 1.6-2.7] than children without a familial predisposition. The risk was smaller with nutritional intervention even levelling out to 1.3 (95% CI 0.9-1.9) in children fed eHF-C formula. Conclusion Although direct comparability is somewhat restricted, the data demonstrate that early intervention with hydrolysed infant formulas can substantially compensate up until the age of 6 years for an enhanced risk of childhood eczema due to familial predisposition to allergy.

Background: Prenatal and postnatal tobacco exposure have been reported to be associated with behavioral problems. However, the magnitude of the association with tobacco exposure at specific periods of exposure is unclear.Objective: We assessed the relative risk of behavioral problems in children who had been exposed to tobacco smoke in utero and postnatally.Methods: We analyzed data from a prospective birth cohort study in two cities in Germany: the German Infant Nutrition Intervention. Our sample included 5,991 children born between 1995 and 1998 as well as their parents. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According to prespecified SDQ cutoff values, children were classified as "normal,""borderline," or "abnormal" according to the subscales "emotional symptoms,""conduct problems,""hyperactivity/inattention,""peer-relationship problems," and a total difficulties score. Smoke exposure and further covariates were assessed using parent questionnaires.Results: Compared with children not exposed to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had twice the estimated risk [95% confidence interval (CI), 1.4-3.1] of being classified as abnormal according to the total difficulties score of the SDQ at 10 years of age. Children who were only prenatally exposed had a 90% higher relative risk (95% CI, 0.9-4.0), whereas children who were only postnatally exposed had a 30% higher relative risk (95% CI, 0.9-1.9). These results could not be explained by confounding by parental education, father's employment, child's time spent in front of computer or television screen, being a single father or mother, or mother's age.Conclusions: Prenatal exposure to tobacco smoke is associated with behavioral problems in school-age children. Although our findings do not preclude the influence of postnatal exposure, prenatal exposure seems to be more important. Editor's SummaryTobacco exposure has been associated with behavioral problems in children, but associations with exposures at specific time points have not been established. Rückinger et al.(p. 150) estimated associations between maternal smoking during pregnancy and/or tobacco smoke exposure during childhood with behavioral problems in 2,862 participants in the prospective German Infant Nutrition Intervention study. Exposure was assessed at birth and at periodic follow-up interviews (at least five per subject), and behavioral problems were identified based on parental responses to the Strength and Difficulties Questionnaire (SDQ) at the 10-year follow-up examination; children were classified as normal, borderline, or abnormal for emotional symptoms, conduct problems, hyperactivity/inattention, peer-relationship problems, and total difficulties according to standard SDQ cut points. Adjusted relative risks for abnormal total difficulty scores were increased among children exposed both prenatally and postnatally to tobacco smoke, with similar associations noted for conduct and hyperactivity/inattention subscales. The authors conclude that findings support adverse behavioral effects of tobacco smoke exposure in school-age children.

BACKGROUND: Helicobacter pylori-associated diseases and gastroduodenal ulcer disease are common conditions of major clinical and economic importance. There is thus a need for a guideline that incorporates the scientific knowledge gained in recent years and that takes specific aspects of the situation in Germany into account with regard to epidemiology, resistance status, diagnostic evaluation, and treatment. METHODS: This level-S3 consensus guideline was developed in accordance with the recommendations of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). It was commissioned by the German Association for Digestive and Metabolic Diseases (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten, DGVS) and prepared in cooperation with other scientific societies. After search terms were compiled, a systematic, IT-supported literature search was performed in the PubMed and Cochrane databases. The search was restricted to articles that appeared in German or English from 2000 onward. RESULTS: H. pylori infection can be accurately diagnosed either non-invasively (with a (13)C-urea breath test or a stool antigen test) or invasively (with a rapid urease test, by histology, or by culture). Gastric and duodenal ulcer and gastric MALT lymphoma are absolute indications for eradication therapy; relative indications include functional dyspepsia, the prevention of gastric cancer in persons at risk, the initiation of long-term treatment with non-steroidal anti-inflammatory drugs (NSAID), and the prior occurrence of gastroduodenal complications with the use of either NSAID or acetylsalicylic acid (ASA). First-line therapy consists of a proton-pump inhibitor (PPI) and clarithromycin combined with either metronidazole or amoxicillin, given for at least one week. CONCLUSION: This guideline enables the structured, evidence-based diagnosis and treatment of H. pylori infection and associated conditions, as well as of gastroduodenal ulcer disease.

BACKGROUND: Assays for IgG antibodies against deamidated gliadin (IgG-anti-dGli) are comparable in performance with tests detecting IgA antibodies against tissue transglutaminase (IgA-anti-tTG) in diagnosing celiac disease (CD). IgA-anti-tTG are absent in IgA deficiency, a condition often associated with CD. In IgA deficiency, IgG-anti-tTG, which have a lower overall diagnostic accuracy, are routinely measured. We examined whether IgG-anti-dGli would be useful for diagnosing CD patients with IgA deficiency. METHODS: We studied 34 IgA-deficient CD patients, 185 IgA-competent newly diagnosed children with CD, 316 children without CD, 400 adult blood donors, and 6 control IgA-deficient individuals without CD. Anti-dGli and anti-tTG were measured by ELISA, and endomysium antibodies (EmA) were measured by immunofluorescence on monkey esophagus (IgA as well as IgG class for all antibodies). We calculated diagnostic sensitivity (percentage of patients above cutoff with 95% CIs) according to age-specific cutoffs for 95% diagnostic specificity and according to cutoffs proposed by the manufacturer of the assays. RESULTS: No IgA-deficient CD patients were positive for any IgA-based antibody assay. Diagnostic sensitivity of IgG-anti-tTG was 91.2%(95% CI 76.3%-97.7%) according to age-specific cutoffs and 82.4%(66.1%-92.0%) according to manufacturer cutoffs. The diagnostic sensitivity of IgG-EmA was 75.8%(58.8%-87.4%) and the sensitivity of IgG-anti-dGli was 88.2%(72.8%-95.9%) according to both cutoffs. CONCLUSIONS: IgG-anti-dGli and IgG-anti-tTG have comparable diagnostic sensitivities for IgA-deficient celiac patients. IgG-anti-dGli may be useful for diagnosing CD in IgA-deficient patients.

This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

BACKGROUND: The molecular cause of inflammatory bowel disease is largely unknown. METHODS: We performed genetic-linkage analysis and candidate-gene sequencing on samples from two unrelated consanguineous families with children who were affected by early-onset inflammatory bowel disease. We screened six additional patients with early-onset colitis for mutations in two candidate genes and carried out functional assays in patients' peripheral-blood mononuclear cells. We performed an allogeneic hematopoietic stem-cell transplantation in one patient. RESULTS: In four of nine patients with early-onset colitis, we identified three distinct homozygous mutations in genes IL10RA and IL10RB, encoding the IL10R1 and IL10R2 proteins, respectively, which form a heterotetramer to make up the interleukin-10 receptor. The mutations abrogate interleukin-10-induced signaling, as shown by deficient STAT3 (signal transducer and activator of transcription 3) phosphorylation on stimulation with interleukin-10. Consistent with this observation was the increased secretion of tumor necrosis factor alpha and other proinflammatory cytokines from peripheral-blood mononuclear cells from patients who were deficient in IL10R subunit proteins, suggesting that interleukin-10-dependent "negative feedback" regulation is disrupted in these cells. The allogeneic stem-cell transplantation performed in one patient was successful. CONCLUSIONS: Mutations in genes encoding the IL10R subunit proteins were found in patients with early-onset enterocolitis, involving hyperinflammatory immune responses in the intestine. Allogeneic stem-cell transplantation resulted in disease remission in one patient. Copyright 2009 Massachusetts Medical Society.

The recently updated German S 3-guideline regarding the diagnosis and treatment of Crohn's disease incorporates several changes concerning the radiological approach compared to the former guideline. This article focuses on guideline-based radiological imaging techniques for patients with Crohn's disease. The new guideline is also compared to former European and German guidelines in the context of recently published radiological literature.

A modified version of a rapid office based one-step monoclonal immunoassay for detection of Helicobacter pylori antigen in stool from children was evaluated against biopsy based methods and compared to a monoclonal enzyme immunoassay using the same antigen. Blinded stool samples from 185 children (0.3-18.2 years) were investigated at the time of upper endoscopy prior to anti-H. pylori therapy, 62 children were H. pylori infected and 123 non-infected according to predefined reference standards. Samples obtained 6 - 8 weeks after anti-H. pylori therapy were available from 58 children (3.8-17.7 years) and compared to results of the (13)C-urea breath test (14/58 positive). The rapid stool tests were performed by two independent readers. Of 243 rapid tests performed, 1 (0.4%) was invalid for technical reasons. Equivocal results (very weak line) were reported 16 times by Reader 1, and 27 times by Reader 2. When equivocal results were considered as positive, the two observers agreed in 76 positive and 160 negative results, and disagreed in 7 samples (2.9%). The sensitivity was 90.8% for Reader 1 and 85.5% for Reader 2, the specificity 91.0% and 93.4%, respectively. The monoclonal enzyme immunoassay revealed a sensitivity and specificity of 94.7% and 97.6%, respectively. The modified chromatographic immunoassay is a good alternative in settings or situations when the monoclonal enzyme immunoassay or the (13)C-urea breath test are not available or feasible. In order to improve sensitivity, very weak lines should be considered as positive test results.

The pro-inflammatory cytokine TNF alpha (TNF) has a key position in the pathogenesis of various infectious and inflammatory diseases. Clarification of its pivotal role in the pathogenesis of rheumatoid arthritis, spondyloarthritis, uveitis, psoriasis and inflammatory bowel disease has resulted in the successful development of TNF- blocking therapies, which have disease-modifying properties that exceed the effects of conventional therapeutic options. For this reason data on the concurrence of several chronic inflammatory diseases have led to the hypothesis of common pathogenetic processes of cytokine dysregulation. The acronym TRECID describes this concept of "TNF RElated Chronic Inflammatory Diseases". Physicians of different specialties have integrated new therapeutic options with TNF-blocking therapies into their strategies for the management of the affected patients. Thus the concept of TRECID can be regarded as a role model for a dynamic, interdisciplinary cooperation based on shared pathophysiological aspects.

Antibodies to deamidated gliadin present a new tool in the diagnosis of celiac disease (CD). In children, the ELISA for the determination of IgG antibodies to (deamidated) gliadin-analogous fusion peptides (GAF3X) has a superior performance compared to the ELISA for the determination of antibodies against native gliadin and is comparable to assays for IgA antibodies against tissue transglutaminase (IgA-anti-tTG). The combined investigation of IgG antibodies to GAF3X (IgG-anti-GAF3X) and IgA-anti-tTG significantly increases the fraction of children definitely identified as either CD or non-CD patients. The new IgG-anti-GAF3X ELISA was also able to detect CD in three cases of IgA deficiency and in two cases of latent CD and was also useful in the diagnosis of children younger than 2 years of age.