Aim: Genome‐wide association studies have described variants within the interleukin‐23 receptor (IL23R) locus to be associated with Crohn’s disease (CD) and ulcerative colitis (UC). We investigated ...the association of rs11209026 (p.Arg381Gln) and rs7517847 (c.799‐3588T>G) into German paediatric inflammatory bowel disease (IBD) patients and analysed IL23R transcriptional activity in colonic tissues.
Methods: The rs11209026 and rs7517847 nucleotide substitutions were determined in 353 German children with IBD (221 CD, 132 UC) and 253 controls using pre‐designed TaqMan® SNP genotyping assays. In selected IBD patients and controls, IL23R mRNA expression was measured using real‐time PCR.
Results: The prevalence of the rs11209026 A allele was lower in CD patients, but not in UC patients, when compared with controls (1.8% vs 7.1%, p < 0.01). The rs7517847 variant, in contrast, was associated neither with CD nor with UC. IL23R expression was variable in IBD patients compared with controls without significant overexpression or downregulation.
Conclusion: Our study provides additional support for the strong protection of the rs11209026 (p.Arg381Gln) variant against paediatric CD. IL23R was expressed in both CD and UC with a great variability. However, expression levels showed no significant association with the disease.
Aplastic anaemia can coincide with non-A-E hepatitis. Treatment follows a standardised study protocol of the German Society of Paediatric Oncology and Haematology (GPOH). Patients receive ...immunosuppression and/or bone marrow transplantation. We present six cases of aplastic anaemia after non-A-E hepatitis with different courses. In four of these children illness first presented with acute gastroenteritis. Five out of six children fully recovered, two of these with immunosuppression alone, three after bone marrow transplantation. One patient died due to complications of the bone marrow transplantation. In two patients steroid therapy was carried out to treat the hepatitis. This did not have any effect on the course of their aplastic anemia. We emphasise this common combination of aplastic anemia following non-A-E hepatitis. This overview underlines the necessity of regular blood testing after non-A-E hepatitis. Often gastroenteritis seems to precede illness thus perhaps indicating an infectious trigger.
Leptin plays an important role in reproductive function. In patients with acute anorexia nervosa, serum leptin levels have repeatedly been shown to be lower than in age-matched controls. We have ...previously hypothesized that the amenorrhea characteristic of anorexia nervosa is related to this low leptin secretion. In an attempt to address this hypothesis, serum levels of leptin and follicle stimulating hormone (FSH) and luteinizing hormone (LH) of 16 female inpatients with anorexia nervosa or an eating disorder not otherwise specified (atypical anorexia nervosa) were measured on a biweekly basis during weight gain. We hypothesized that a serum leptin level of 1.85 microg L(-1) would be associated with gonadotropin levels at or above the minimal level observed during the menstrual cycle in healthy adult fertile females. Our results revealed that increments of LH levels generally tracked increments of leptin levels during the first weeks of treatment. Similarly, in those patients with low referral leptin levels, FSH initially also tracked leptin levels. In contrast, a relationship between gonadotropin levels and leptin secretion was no longer discernible after LH and FSH levels had peaked. Those patients with exceedingly low leptin levels upon admission revealed a slow increase of gonadotropin levels. Our hypothesis of a threshold leptin level of 1.85 microg L(-1) was supported for LH only.
Peginterferon plus ribavirin is standard therapy for adults with chronic hepatitis C. As no data are available for children, the aim of the study was to evaluate the efficacy and tolerability of ...peginterferon alfa-2b in combination with ribavirin in chronically infected children. Genotypes, alanine aminotransferase levels, and different routes of viral transmission were considered. In an open-labeled, uncontrolled pilot study, 62 children and adolescents (range, 2-17 years) were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 microg/kg body weight once per week plus oral ribavirin (15 mg/kg x day) for 48 weeks. Sixty-one patients completed the study. Twenty-three children discontinued therapy after 6 months according to study protocol. Sustained viral response was documented in 22 (47.8%)of 46 patients with genotype 1, in 13 (100%) of 13 with genotype 2 or 3, in 1 of 2 with genotype 4, in 19 (70.4%) of 27 children with parenteral, in 12 (48%) of 25 with vertical, and in 5 of 9 with unknown route of infection. Overall, treatment was well tolerated. Nevertheless, some side effects were present in all treated patients. Eighty-three percent had leucopenia, but only 3 individuals required dose reduction and 10.3% developed thyroid autoantibodies and thyroid dysfunction. In conclusion, combination treatment of peginterferon alfa-2b with ribavirin showed encouraging results and was well tolerated in children and adolescents with chronic hepatitis C. Weekly dosing of peginterferon alfa-2b is a considerable advance for this age group. The treatment is not approved for children. Further controlled trials are needed.
Mutations in the leptin gene can result in profound obesity in both rodents and humans. In humans, serum leptin levels correlate with body mass index (BMI: kg m(-2)). However, in patients with ...anorexia nervosa (AN) leptin levels are lower than in BMI-matched healthy controls. We had previously argued that genes involved in weight regulation should be considered as candidate genes for AN. To investigate this hypothesis we screened the coding region of the leptin gene and part of the leptin gene linked upstream region (LEGLUR) in 49 patients with AN and 315 children and adolescents with extreme obesity. Two novel mutations in the coding region (Ser-91-Ser; Glu-126-Gln), each found in a single proband, and a novel polymorphism in the LEGLUR (position -1387 G/A; frequency of both alleles approximately 0.50) were identified. Tests for association of LEGLUR polymorphism alleles were negative by comparing allele frequencies between 115 AN patients, 71 bulimia nervosa patients, 315 extremely obese children and adolescents, 141 healthy underweights and 50 controls that were not selected for body weight. Tests for transmission disequilibrium were also negative. Hence, an influence of variations in the leptin gene on eating disorders or extreme early onset obesity could not be detected.
Low leptin levels are an endocrinological hallmark of acute anorexia nervosa (AN); a subthreshold leptin secretion in adipocytes as a consequence of a reduced energy intake is presumed to be the ...major trigger of the adaptation of an organism to semistarvation. The aim of the current study is to define symptoms of AN that are potentially linked to low leptin levels. For this purpose, quantitative somatic and psychopathological variables were obtained in 61 inpatients with acute AN (study group 1) upon referral for inpatient treatment, and they were concomitantly blood sampled to allow determination of serum leptin levels. Correlations between these variables and logarithmic transformed (lg10) leptin levels were descriptively assessed. Apart from the well-known correlations between leptin levels and anthropometric measurements, the strongest correlation was observed between lg10 serum leptin levels and expert ratings of motor restlessness (r = −0.476; nominal P = 0.003) upon use of visual analog scales. We thus generated the hypothesis that physical activity levels in AN patients are related to serum leptin levels. This hypothesis was tested in an independent study group of 27 adolescent inpatients (study group 2) who were also assessed upon referral. Physical activity levels, which, in this study group, were assessed with the activity module of the expert rating form of the Structured Inventory for Anorexic and Bulimic Syndromes, were significantly correlated with lg10 leptin levels (r = −0.51; one-sided P = 0.006). A regression model based on the independent variables body mass index and lg10 leptin levels explained 37% of the variance of physical activity (R2 = 0.37; P = 0.003); only the lg10 leptin levels contributed significantly to the variance (P = 0.003). Our results suggest that, similar to semistarvation-induced hyperactivity in rats, hypoleptinemia in patients with AN may be one important factor underlying the excessive physical activity.
The aim of this study was to test the association between farm animal contact in infancy and the development of juvenile Crohn disease and ulcerative colitis.
A case-control study was conducted in 13 ...children's hospitals by using a mailed questionnaire. Case subjects with Crohn disease or ulcerative colitis who were registered in these hospitals were eligible (response rate: 90%). Children who underwent strabismus surgery at 11 of the 13 centers served as control subjects (response rate: 85%). All children 6 to 18 years of age who were born in Germany without malformations were included (444 case subjects with Crohn disease, 304 case subjects with ulcerative colitis, and 1481 control subjects).
Regular contact with farm animals during the first year of life was associated inversely with Crohn disease and ulcerative colitis. In addition, regular contact with cats in infancy was linked inversely with case status. Allergic rhinitis was correlated significantly with Crohn disease but not with ulcerative colitis.
Contact with farm environments in infancy might decrease the risk of juvenile Crohn disease and ulcerative colitis.
Rapid, patient near tests for detecting antibodies against Helicobacter pylori are offered for clinical use. We evaluated the BM-Test (Boehringer Mannheim, Germany; identical to the Helisal Rapid ...Blood Test) in children with recurrent abdominal pain.
The BM-Test and 13C-urea breath test (UBT) were performed in 195 children (4-18 years). Symptoms were assessed using a 4-week diary. Upper endoscopy was performed in all UBT-positive children and in UBT-negative children with symptoms suggestive of organic disease. H. pylori status was considered positive if at least two of three methods (UBT, histology or rapid urease test) or culture were positive.
After exclusion of children with previous H. pylori therapy (n = 8) and undetermined H. pylori status (n = 1), 61/186 (33%) children were H. pylori positive. The BM-Test in relation to H. pylori status revealed a sensitivity of 54%, specificity of 90%, a likelihood ratio of 5.2 for a positive, and of 0.4 for a negative test result. Accuracy of the test was independent of ethnicity, gender, age, family history for ulcer disease, frequency or severity of abdominal symptoms, epigastric tenderness, type of blood sampling (capillary versus venous) and DOB values of the UBT. In eight previously treated children, the test gave one false-positive and three false-negative results.
Almost half of H. pylori-infected children and 10% of non-infected children were misclassified by the BM-Test. False-negative results are not related to young age or certain ethnic groups. The poor performance makes the test unsuitable for epidemiological and clinical use in children.
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