A non-synonymous coding variant (L616F) in the TLR5 gene is potentially associated with Crohn's disease and influences responses to bacterial flagellin.

BACKGROUND AND OBJECTIVES: Although numerous studies have implicated TLR5, or its ligands, bacterial flagellins, in the pathogenesis of Crohn's disease (CD), genome-wide association studies (GWAS) have not reported associations with the TLR5 gene. We aimed to examine potential CD-associated TLR5 variants and assess whether they modified inflammatory responses to bacterial flagellins. METHODS AND PRINCIPAL RESULTS: A two-stage study was carried out. In stage 1, we genotyped tagging single-nucleotide polymorphisms (tag-SNPs) in the TLR5 gene in a sample of CD cases (<20 years of age, N = 566) and controls (N = 536). Single SNP and haplotype analysis was carried out. In Stage 2, we assessed the functional significance of potential CD-associated variant(s) vis-à-vis effects on the inflammatory response to bacterial flagellin using HEK293T cells. We observed marginal association between a non-synonymous coding SNP rs5744174 (p = 0.05) and CD. Associations between SNP rs851139 that is in high linkage disequilibrium (LD) with SNP rs5744174 were also suggested (p = 0.07). Haplotype analysis revealed that a 3 marker haplotype was significantly associated with CD (p = 0.01). Functional studies showed that the risk allele (616F) (corresponding to the C allele of SNP rs5744174) conferred significantly greater production of CCL20 in response to a range of flagellin doses than the comparator allele (616L). CONCLUSIONS: Our findings suggest that a non-synonymous coding variation in the TLR5 gene may confer modest susceptibility for CD.

Proton pump inhibitors for irritable infants.

QUESTION: Crying is common in infants; however, caring for infants with inconsolable crying, previously also known as colic or reflux, is often extremely distressing for parents. Is there a benefit to using gastric acid suppression (eg, proton pump inhibitors [PPIs]) in these infants? ANSWER: The use of PPIs in infants and children has increased in recent years. The efficacy of proton pump inhibitors has not been demonstrated in the treatment of irritability and excessive crying in otherwise healthy infants younger than 3 months of age. Conversely, while PPIs are generally well tolerated, there is some evidence to link the use of PPIs with increased susceptibility to acute gastroenteritis, community-acquired pneumonia, and disorders of nutrient absorption and utilization. Irrespective of treatment, crying and irritability in infancy generally improve with time. Proton pump inhibitors do not improve symptoms in the interim.

A randomized trial of yoga for adolescents with irritable bowel syndrome.

BACKGROUND: Adolescents with irritable bowel syndrome (IBS) frequently experience interference with everyday activities. Mind-body approaches such as yoga have been recommended as interventions for patients with IBS. Despite promising results among adult samples, there have been limited studies exploring the efficacy of yoga with pediatric patients. OBJECTIVE: To conduct a preliminary randomized study of yoga as treatment for adolescents with IBS. METHODS: Twenty-five adolescents aged 11 to 18 years with IBS were randomly assigned to either a yoga or wait list control group. Before the intervention, both groups completed questionnaires assessing gastrointestinal symptoms, pain, functional disability, coping, anxiety and depression. The yoga intervention consisted of a 1 h instructional session, demonstration and practice, followed by four weeks of daily home practice guided by a video. After four weeks, adolescents repeated the baseline questionnaires. The wait list control group then received the yoga intervention and four weeks later completed an additional set of questionnaires. RESULTS: Adolescents in the yoga group reported lower levels of functional disability, less use of emotion-focused avoidance and lower anxiety following the intervention than adolescents in the control group. When the pre- and postintervention data for the two groups were combined, adolescents had significantly lower scores for gastrointestinal symptoms and emotion-focused avoidance following the yoga intervention. Adolescents found the yoga to be helpful and indicated they would continue to use it to manage their IBS. CONCLUSIONS: Yoga holds promise as an intervention for adolescents with IBS.

Comparison of multidetector CT and barium studies of the small bowel: inflammatory bowel disease in children.

OBJECTIVE: We compared barium studies of the small bowel with multidetector CT (MDCT) in the evaluation of the small bowel during the initial presentation of inflammatory bowel disease in a pediatric population. SUBJECTS AND METHODS: This was a prospective study. Eighteen children undergoing workup for inflammatory bowel disease underwent MDCT, colonoscopy, and barium studies of the small bowel before commencement of therapy. Examinations were independently reviewed. The patients and their guardians completed a questionnaire assessing the acceptability of each study. RESULTS: In 13 of 18 children, the findings of MDCT and barium studies of the small bowel concurred in the evaluation of terminal ileum disease. In three of these children, MDCT detected skip segments of small-bowel disease not detected on barium studies of the small bowel. In two of 18 children, the terminal ileum was not visualized on barium studies of the small bowel, whereas MDCT showed substantial terminal ileum disease in both children. In three of 18 children, there was discordance between the two tests regarding terminal ileum disease. However, these discordant imaging findings were all subtle. In addition, MDCT revealed extraenteric abnormalities, clinically relevant in two children (ureteric obstruction and perirectal abscess), and showed the colon in all children, seven of whom had incomplete colonoscopy. The questionnaire revealed that 16 of 18 patients preferred MDCT to small-bowel barium studies. The reasons given were poor tolerance of oral barium and the long duration of barium studies of the small bowel. CONCLUSION: MDCT can be an alternative to barium studies of the small bowel for evaluation of the small bowel in patients with inflammatory bowel disease. MDCT also offers additional, clinically relevant information not obtained by small-bowel barium studies.

Gastric polyps and nodules in children receiving long-term omeprazole therapy.

OBJECTIVE: Multiple gastric polyps have been reported to occur in adults receiving omeprazole therapy. There are little published data in children. We report our experience in monitoring the gross and histologic appearance of the stomach in children receiving long-term omeprazole therapy. METHODS: This was a retrospective review of the charts of children who received omeprazole for more than 6 months for reflux esophagitis between 1989 and 1998. All patients had repeated endoscopic examinations until healing of the esophagitis was confirmed and then annually thereafter. At endoscopy, gastric mucosal swellings were classified as polyps or nodules based on histology. RESULTS: Thirty-one children had long-term endoscopic follow-up while receiving omeprazole. Seven of 31 children had gastric polyps and/or nodules, noted between 10 and 48 months (mean = 28 months) of omeprazole therapy. Four had nodules only, one had a sessile hyperplastic polyp, and two had both a polyp (one hyperplastic and one fundic gland polyp) and nodules. All lesions were found in the gastric body. Nodules in four of the six children disappeared spontaneously while the children continued to receive omeprazole. The polyps persisted. There were no dysplastic changes in the gastric mucosa or polyps in any of the patients. There were no significant differences between the 7 children with and the 24 without polyps/nodules with respect to age, gastrin concentrations, or dose and duration of omeprazole therapy. CONCLUSIONS: Gastric polyps and nodules may be found in children receiving long-term omeprazole therapy. The gastric changes in our patients were benign during the mean observation period of 31 months.