Search

Purpose: Our aim was to evaluate the usefulness of the 13C-urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, for assessment of the efficacy of eradication therapy, and for post-treatment follow-up in children.Methods: Seventy-two patients who underwent endoscopy for symptoms related to the upper gastrointestinal tract were examined by rapid urease test, histology, and culture. The patients were also studied with serology and UBT.Results: Forty-seven of the 72 patients were diagnosed with H. pylori infection, based on the results of biopsy-based tests and serology. As an initial diagnostic test to detect H. pylori infection, the sensitivity of the UBT was 95%, which was comparable with that of histology (94%), rapid urease test (96%), and serology (91%) and was greater than that of culture (79%). The specificity of the UBT was 100%, which was comparable with that of the other four tests. The efficacy of eradication therapy was assessed by biopsy-based tests and the UBT in 24 H. pylori-positive patients. For this purpose, the sensitivities of UBT and histology were 100%, while the sensitivities of culture and the rapid urease test were 88%. The specificity was 100% for all of these tests. Eleven patients were assessed by biopsy-based tests and UBT after more than 6 months of post-treatment follow-up. There were no discordances between the results of the UBT and those of the biopsy-based tests in any of the patients.Conclusions: The UBT may be useful for detecting H. pylori infection in children with upper gastrointestinal tract symptoms, for assessment of the efficacy of eradication therapy, and for the follow-up evaluation of patients after the therapy. [ABSTRACT FROM AUTHOR]

Background & Aims: Adenosine has been implicated as an important regulator of the inflammatory response. Four subtypes of adenosine receptors (A 1 , A 2A , A 2B , and A 3 ) have been described, of which A 2A potentially inhibits inflammation. The aim of this study was to investigate the role of A 2A in mucosal inflammation by administering a selective A 2A agonist (ATL-146e) to experimental models of inflammatory bowel disease., Methods: The anti-inflammatory effects of ATL-146e were studied in the acute and chronic rabbit formalin-immune complex models of colitis and the SAMP1/YitFc mouse model of spontaneous ileitis., Results: ATL-146e significantly reduced the acute inflammatory index and tissue necrosis compared with vehicle ( P < .01) in the acute model of rabbit immune colitis. In the chronic rabbit immune colitis model, ATL-146e significantly suppressed inflammatory cell infiltration into the colonic mucosa ( P < .05) and prevented mortality. The administration of ATL-146e significantly decreased the chronic inflammatory index ( P < .01) and villus distortion index ( P < .01) in the ileum of SAMP1/YitFc mice, and ameliorated adoptively transferred ileitis in severe combined immunodeficient mice injected with CD4 + T cells from SAMP1/Yit mice ( P < .05). Tumor necrosis factor, interferon gamma, and interleukin 4 concentrations were significantly suppressed by ATL-146e treatment in supernatants from cultures of mesenteric lymph node cells of SAMP1/YitFc mice ( P < .05 vs vehicle-treated mice)., Conclusions: A 2A adenosine receptor activation by ATL-146e significantly reduced inflammation in the intestinal mucosa. This effect was associated with decreased leukocyte infiltration and inhibition of proinflammatory cytokines. Activation of A 2A by selective agonism may therefore serve as a novel therapy for the treatment of inflammatory bowel disease.

Background and Aims: Genetic predisposition is implicated strongly in Crohn's disease. Disease-associated mutations in NOD2/CARD15 , the best-studied susceptibility gene in this disorder, explain only a small fraction of the heritability. The SAMP1/YitFc (SAMP1/Fc) mouse strain expresses many features of Crohn's disease in humans. We bred SAMP1/Fc to disease-resistant AKR mice to identify additional susceptibility genes that may play a role in human disease., Methods: Linkage disequilibrium mapping was performed in an (AKR x SAMP1/Fc) backcross to SAMP1/Fc, followed by sequencing, expression analysis using reverse transcription polymerase chain reaction (PCR) and immunohistochemistry, and functional testing in vivo of the regional candidate gene encoding the peroxisome proliferator-activated receptor gamma ( Pparg ). A cohort-based association study was performed in humans., Results: We show that ileitis is blocked in SAMP1/Fc mice by inheritance of AKR alleles on chromosome 6 in the region of Pparg . Major differences in Ppargamma expression in the parental mouse strains are found specifically in the crypts of the small intestine, and treatment of ileitis-prone mice with a Ppargamma agonist decreased disease severity in susceptible mice expressing low levels of the protein. Rare alleles of PPARG are associated significantly with Crohn's disease in humans., Conclusions: We have identified Pparg as a susceptibility gene in both the SAMP/Yit mouse and in human Crohn's disease. Similarities between Crohn's disease and the SAMP1/Fc model suggest that the effect of this gene in humans may be mediated through regulation of PPARgamma activity in the crypts of the small intestine.

Background & Aims: The SAMP1/Yit mouse strain develops spontaneous ileitis with histologic features of Crohn's disease. Disease expression in the SAMP1/YitFc subline (SAMP1/Fc) is partially inhibited by outcross to C57BL/6J (B6) mice, suggesting complex genetic control of disease susceptibility with both dominant and recessive determinants. We performed a genetic analysis of a (B6 x SAMP1/Fc)F(2) cross to localize the genes regulating intestinal inflammation in this model., Methods: A genome-wide scan was performed using a panel of microsatellite loci determined to be informative for this cross. Quantitative trait loci were identified with Map Manager QT using a serial regression approach. Positional candidate genes were selectively sequenced at the genomic level to identify potential susceptibility genes for functional screening., Results: A genome-wide scan of (B6 x SAMP1/Fc)F(2) mice identified a SAMP-derived quantitative trait loci with additive effects on chromosome 9 in a region likely to have been inherited from the AKR mouse strain. The candidate interval contains several genes of interest because of their potential role in either immune system function, intestinal epithelial function, or both. Suggestive evidence for additional loci was also observed on chromosomes 6 and X., Conclusions: The SAMP1/Fc allele for a locus, designated Ibdq1, promotes inflammation-associated epithelial damage in these mice. Consistent with persistent mild ileitis in (B6 x SAMP1/Fc)F(1) mice, this locus appears to function in an additive fashion. Two genes in this interval, encoding the interleukin 10 receptor alpha chain and interleukin 18, are excellent candidates for Ibdq1.

We describe here the immunologic characterization of a new mouse strain, SAMP1/Yit, which spontaneously develops a chronic intestinal inflammation localized to the terminal ileum. The resulting ileitis bears a remarkable resemblance to human Crohn's disease. This strain of mice develops discontinuous, transmural inflammatory lesions in the terminal ileum with 100% penetrance by 30 weeks of age. The intestinal inflammation is characterized by massive infiltration of activated CD4+ and CD8alpha(+)TCRalphabeta(+) T cells into the lamina propria and is accompanied by a dramatic decrease in the intraepithelial lymphocyte CD8alpha(+)TCRgammadelta(+)/CD8alpha(+)TCRalphabeta(+) ratio. The results of adoptive transfer experiments strongly suggest that CD4+ T cells that produce a Th1-like profile of cytokines, e.g., IFN-gamma and TNF, mediate the intestinal inflammation found in SAMP1/Yit mice. In addition, pretreatment of adoptive transfer recipients with a neutralizing anti-TNF antibody prevents the development of intestinal inflammation, suggesting that TNF plays an important role in the pathogenesis of intestinal inflammation in this model. To our knowledge, these data provide the first direct evidence that Th1-producing T cells mediate intestinal inflammation in a spontaneous animal model of human Crohn's disease.

We present three cases of infants with idiopathic neonatal hepatitis showing diffuse intrahepatic fatty degeneration. Prolonged cholestasis has improved immediately upon intravenous administration of a high-dose gammaglobulin treatment in all three patients. The TT virus (TTV) genome was detectable in the serum of two patients, in the duodenal fluid of one and in the liver of all three. By analyzing sequence homology, we observed that the respective TTV isolated from serum, duodenal fluid and liver tissue were completely identical in cases 2 and 3. These findings suggest that TTV infection was one of the contributing factors for neonatal cholestasis in these patients. TTV was isolated from the serum of two out of the three mothers. The viruses were either completely or almost identical in sequence to those isolated from their respective infants, suggesting that they had been transmitted from mother to infant in these 2 cases. The patients presented here, whose livers were infected with the TTV and showed a favorable response to gammaglobulin therapy, may represent a subset of idiopathic neonatal hepatitis patients., (Copyright 2002 S. Karger AG, Basel)

We present 3 cases of immunocompetent infants with CMV infection who showed prolonged liver dysfunction. In all cases the CMV genome was detectable in hepatocytes using the in situ hybridization method. Combination therapy with ganciclovir (GCV) and hyperimmune gammaglobulin (HGG) was instituted in 2 cases and successfully suppressed the replication of CMV, with sustained improvement in liver function. In 1 of these cases, signals for CMV DNA were undetectable in the liver 12 months after termination of combination therapy. These results help to confirm the etiology of CMV for persistent hepatitis in immunocompetent infants using the in situ hybridization method and also show the efficacy of combination therapy with a virostatic agent, GCV, and an immune-modulating agent, HGG.

We present here three paediatric patients with primary sclerosing cholangitis. In case 1, the serum gamma-glutamyl transpeptidase was decreased only temporarily by ursodeoxycholic acid (UDCA) treatment and 34 months later, sulphasalazine was added because of microscopic colitis. The enzyme level decreased with dual therapy. Similarly, in case 3, first diagnosed as autoimmune hepatitis, the transpeptidase levels remained elevated for 18 months during treatment with UDCA, prednisolone and mizoribin. The enzyme decreased only after a diagnosis of primary sclerosing cholangitis complicated with ulcerative colitis was established and sulphasalazine was introduced. Case 2 also had Crohn's colitis and was put on UDCA and sulphasalazine from the start. The enzyme level was normalized within 1 month and has remained normal for the following 5 years. Liver biopsies were analysed repeatedly in these three patients. In case 1, periductal fibrosis remained unchanged while being treated by UDCA. There appeared to be no progression in liver cirrhosis in case 3 while being treated by UDCA, prednisolone, and mizoribin. In case 2, who has been treated with both UDCA and sulphasalazine from the start, periductal fibrosis and portal fibrosis were remarkably improved 45 months later. We suggest that sulphasalazine in addition to UDCA might be a viable treatment for children with primary sclerosing cholangitis.

Congenital chloride diarrhea (CLD) is an autosomal recessive disease characterized by excretion of watery stool with a high chloride content. Pathogenesis of CLD is a deficient absorption of chloride in exchange for bicarbonate in the ileum and the colon. In 1996, it was reported that 36 patients with CLD had mutations in the down-regulated in adenoma (DRA) gene; 32 Finnish patients had a three base deletion (951delGGT), 2 Polish patients had a one base mutation (371AtoT) and 2 Polish patients had a one base deletion (344delT). In this study we analyzed the DRA gene in a Japanese boy patient with CLD and in members of his family. The patient was found to have a two base deletion (TT) at nucleotide 1526-1527 within codon 509 which results in a frameshift leading to a permature stopping at codon 517. The patient was homozygous for the deletion, his parents and brother were heterozygous, and his sister was normal. This is the first case of CLD identified to carry a mutation of the DRA gene in Asia.

We demonstrate immunoglobulin-complexed aspartate aminotransferase (macro-AST) in a 14-year-old boy with rectitis-type ulcerative colitis by using both gel filtration and electrophoresis methods. The immunoglobulin complexed with AST in this case was identified as an IgG kappa both by electrosyneresis and immunoprecipitation reactions. The present case was noted to have a concomitant elevation of macro-AST associated with deterioration of ulcerative colitis. However, macro-AST has continued to exist when the activity of ulcerative colitis subsided, and the serum level of AST became normal. Thus, macro-AST might be related to an immunological component of ulcerative colitis as well as to the activity of the disease.

We assessed the efficacy of a government-sponsored mass protection program in Osaka, Japan, for perinatal HBV infection in infants born to HBeAg positive HBV carrier mothers. We also evaluated the impact of optional follow-up procedures in such infants, including an evaluation of anti-HBs response and a booster dose of HBV vaccine for poor responders. The results demonstrated that this mass protection program protected 94.4% of the infants from perinatal HBV infection in the Osaka area. However, the proportion of infants with an unprotective level of anti-HBs was higher in the standard group than in the follow-up group both at 1.0 and 1.5 years of age, which was also the case for HBV events. Furthermore, the present study showed that a booster dose of vaccine in poor responders was very effective in promoting an anti-HBs response. In conclusion, we recommend that a follow-up blood test to confirm a response of anti-HBs to HBV vaccine should be performed at 4-8 weeks after the third injection of HBV vaccine in infants born to HBeAg positive HBV carrier mothers. We also recommend that a booster injection of HBV vaccine should be immediately given to poor responding infants who otherwise are at a considerable risk of developing HBV infection in late infancy.

We studied the effect of Sho-saiko-to (Xiao-Chai-Hu-Tang) on HBeAg clearance rate (SN rate) in fourteen children with chronic hepatitis B virus (HBV) infection and with sustained liver disease. Seven of fourteen patients (50.0%) became HBeAg negative in the average observation period of 0.47 years(0.2-0.9 years). Four of those seven patients developed anti-HBe. The annual SN rate in the She-saiko-to treated group was apparently higher than the natural annual SN rate (22.7%) of 22 untreated patients retrospectively reviewed from the onset of hepatitis. Sho-saiko-to seemed to promote clearance of HBeAg in children with chronic HBV infection and with sustained liver disease. Sho-saiko-to may be a useful drug for such patients.