Chang, Howard Y.

ABSTRACTObjectiveMost Helicobacter pylori infections are acquired during childhood. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) recently published practice guidelines for managing pediatric H. pylori infection. Before this publication, the authors conducted a survey to assess pediatric gastroenterologists' knowledge and practices regarding H. pylori.MethodsOne hundred nine of 514 NASPGHAN members completed an Internet‐based questionnaire on H. pylori infection.ResultsEighty‐two percent of respondents performed outpatient testing for H. pylori. Of these, only 31% restricted testing to children aged >5 years. Most recommended testing for H. pylori in guideline‐recommended conditions; some would not treat infected patients. Ninety‐seven percent would test for H. pylori in a child with new duodenal ulcer (DU), 79% in a child with a history of DU, and 91% in a child with new gastric ulcer. However, only 86%, 60%, and 91%, respectively, would treat H. pylori infection in those conditions. A proton pump inhibitor (PPI)‐based triple regimen was the first‐choice therapy for 78% of respondents. Correct estimates of rates of resistance to amoxicillin, clarithromycin, metronidazole, and tetracycline were 10%, 17%, 43%, and 12%, respectively. Eighty‐six percent believed there was insufficient research on H. pylori in children.ConclusionsNorth American pediatric gastroenterologists seem well informed about H. pylori infection in children despite the lack of published guidelines at the time of survey. Knowledge about antibiotic resistance rates was deficient. Most offered some outpatient testing for H. pylori and would test children with ulcer disease. However, some would not treat patients based on a positive result.

The Ca(2+)- and calmodulin-dependent protein phosphatase calcineurin is inhibited by the immunosuppressant drug cyclosporin A in the presence of cyclophilin A or B. Of the two isoforms, cyclophilin B is more potent by a factor of 2-5 when either the phosphoprotein [32P]casein or the [32P]phosphoserine [Ser(32P)] form of the 19-residue bovine cardiac cAMP-dependent protein kinase regulatory subunit peptide RII, [Ser(32P)15]RII, is used as substrate. With [Ser(32P15]RII as substrate, the concentrations of the cyclosporin A.cyclophilin A and cyclosporin A.cyclophilin B complexes, which cause 50% inhibition of calcineurin activity, are 120 and 50 nM, respectively. Lowering the concentration of calcineurin 80% with [32P]casein as substrate lowered the apparent inhibition constant for each complex even further; 50% inhibition of calcineurin was observed at 40 nM for cyclosporin A.cyclophilin A, whereas it was less than 10 nM for cyclosporin A.cyclophilin B. In all inhibition assays with [32P]casein or [Ser(32P)15]RII, the concentration of calcineurin required for measurable phosphatase activity is such that these complexes behave as tight-binding inhibitors of calcineurin, and steady-state kinetics cannot be used to assess inhibition patterns or Ki values. Limited trypsinization of calcineurin produces a fragment that is still inhibited, indicating that the interaction of cyclosporin.cyclophilin with calcineurin does not require either calmodulin or Ca2+.