High rates of fructose malabsorption are associated with reduced liver fat in obese African Americans.

OBJECTIVE: African Americans commonly have lower liver fat accumulation than Hispanics, despite a similar propensity for obesity. Both ethnicities exhibit high consumption of fructose-containing beverages, which has been associated with high liver fat owing to the lipogenic properties of fructose. Therefore, differences in fructose absorption may be an important factor in regulating liver fat deposition. We hypothesized that fructose malabsorption in African Americans may reduce hepatic delivery of fructose, thus contributing to lower liver fat deposition compared to Hispanics. METHODS: Thirty-seven obese young adults aged 21.4 ± 2.1 years (16 African American, 21 Hispanic) underwent a 3-hour hydrogen (H2) breath test to assess fructose malabsorption. Magnetic resonance imaging was used to determine visceral and subcutaneous adipose tissue volume and liver fat. Fructose malabsorption was expressed as an area under the curve for H2 production (H2 AUC). RESULTS: Compared to Hispanics, African Americans had lower liver fat (5.4% ± 5.0% vs 8.9% ± 2.3%, p = 0.02) and a higher prevalence of fructose malabsorption (75.0% vs 42.9%; p = 0.05). Liver fat was negatively related to the extent of fructose malabsorption in African Americans (r = -0.53, p = 0.03), and this relationship was independent of the volumes of total fat and subcutaneous and visceral adipose tissue. There were no significant relationships between liver fat and fructose malabsorption in Hispanics. CONCLUSION: African Americans have both a higher prevalence and a greater magnitude of fructose malabsorption than Hispanics. In African Americans, fructose malabsorption was negatively correlated with liver fat, which may be protective against fatty liver disease.

Prospective open label study of solifenacin for overactive bladder in children.

PURPOSE: We evaluated the effect of solifenacin for urinary incontinence in children with overactive/neurogenic bladder refractory to oxybutynin or tolterodine. MATERIALS AND METHODS: Pediatric patients presenting with refractory overactive bladder with incontinence were offered the opportunity to enter a prospective, open label protocol using adjusted dose regimens of 1.25 to 10 mg solifenacin. Study inclusion criteria were absent correctable neurological anomalies on magnetic resonance imaging, failure of symptoms to improve on intensive behavioral and medical (oxybutynin or tolterodine) therapy, and/or significant side effects of those agents. Followup consisted of a voiding diary, post-void residual urine measurement, urine culture, ultrasound and urodynamics. Families were questioned about continence, side effects, compliance, behavior change and quality of life. The primary end point was efficacy for continence and secondary end points were tolerability and safety. RESULTS: Enrolled in the study were 42 girls and 30 boys. Of the patients 27 with neurogenic bladder, of whom 11 were on clean intermittent catheterization, and 45 with overactive bladder completed a minimum 3-month followup. Patients were on solifenacin a mean of 15.6 months. Mean age at study initiation was 9.0 years. Mean ± SD urodynamic capacity improved from 146 ± 64 to 311 ± 123 ml and uninhibited contractions decreased from 70 ± 29 to 20 ± 19 cm H(2)O (p <0.01). Continence improved in all patients, including 24 who were dry, and 42 and 6 who were significantly and moderately improved, respectively. Of the patients 50 reported no side effects while 15 had mild and 3 had moderate side effects. Four patients withdrew from the protocol due to intolerable side effects. Four patients had significant post-void residual urine (greater than 20 ml). CONCLUSIONS: In children with overactive bladder refractory to oxybutynin or tolterodine solifenacin is an effective alternative to improve symptoms. Tolerability was acceptable and the adjusted dose regimen appeared safe.

Double anticholinergic therapy for refractory overactive bladder.

PURPOSE: Using 2 anticholinergic medications simultaneously (10 to 30 mg oxybutynin, 4 mg tolterodine and/or 5 to 10 mg solifenacin) we optimized the medical therapy for children in whom single agent anticholinergic therapy failed. We evaluated efficacy, tolerability and safety. MATERIALS AND METHODS: Children with refractory overactive bladder and incontinence were included in a prospective, open label protocol. Study inclusion criteria were persistent symptoms on medical and behavioral therapy, absence of correctable neurological anomalies, and partial clinical and urodynamic responses on an optimal dose of 1 well tolerated, long acting anticholinergic. Patients were followed prospectively every 3 months. The primary end point was efficacy for continence and the secondary end points were tolerability and safety. RESULTS: We enrolled 14 girls and 19 boys in the study, and followed 19 patients with neurogenic bladder and 14 with overactive bladder a minimum of 3 months. Mean age at enrollment was 12 years and double medication was given for a mean of 16 months (range 3 to 42). Mean +/- SD urodynamic capacity improved from 192 +/- 92 to 380 +/- 144 ml, no deterioration in compliance was noted and maximal contraction pressure decreased from 77 +/- 27 to 18 +/- 15 cm H(2)O. Continence improved in all patients, of whom 17 were dry, and 14 and 2 were significantly and moderately improved, respectively. No, mild and moderate side effects were reported by 12, 16 and 5 patients, respectively. In 3 of the 17 patients who voided greater than 20% post-void residual urine developed. Blood tests and electrocardiogram remained normal. CONCLUSIONS: In children with refractory overactive bladder double anticholinergic therapy is an efficient and serious alternative to surgery. Patients and families were satisfied with this nonoperative, innovative approach.

Systemic mastocytosis involving the gastrointestinal tract: clinicopathologic and molecular study of five cases.

Systemic mastocytosis is an uncommon condition characterized by abnormal proliferation of mast cells in one or more organ. The specific D816V KIT mutation is present in most cases. Gastrointestinal symptoms occur commonly but histologic characterization of gastrointestinal involvement is incomplete. The purpose of this study was (1) to describe the clinicopathologic features in five patients with systemic mastocytosis involving the gastrointestinal tract and (2) to determine whether gastrointestinal involvement is associated with the usual D816V mutation or a different mutation. Clinical details were obtained from the hospital of origin or referring pathologist. Histologic features were documented in slides stained with hematoxylin and eosin, mast cell tryptase and CD117. Molecular analysis for the D816V KIT mutation was performed on formalin-fixed paraffin-embedded sections. Symptoms included diarrhea/loose stools (n=5), abdominal pain (n=4), vomiting (n=3) and weight loss (n=3). Other findings included cutaneous lesions of mastocytosis (n=4), malabsorption (n=2), hypoalbuminemia (n=2) and constitutional growth delay (n=1). Sites of gastrointestinal involvement included the colon (n=5), duodenum (n=3) and terminal ileum (n=3). Endoscopic/gross findings included mucosal nodularity (n=4), erosions (n=2) and loss of mucosal folds (n=2). In three patients the endoscopic appearance was considered consistent with inflammatory bowel disease. All cases showed increased mast cell infiltration of the lamina propria, confirmed by immunohistochemistry for mast cell tryptase and CD117. In two cases, mast cells had abundant clear cytoplasmic resembling histiocytes. Marked eosinophil infiltrates were present in four patients, in one patient leading to confusion with eosinophilic colitis. Architectural distortion was noted in three cases. The D816V KIT mutation was present in all four cases tested. In conclusion, gastrointestinal involvement by systemic mastocytosis is characterized by a spectrum of morphologic features that can be mistaken for inflammatory bowel disease, eosinophilic colitis or histiocytic infiltrates. Systemic mastocytosis involving the gastrointestinal tract is associated with the usual D816V KIT mutation.

Canadian Helicobacter Study Group Consensus Conference: Update on the approach to Helicobacter pylori infection in children and adolescents--an evidence-based evaluation.

As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of 14 topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The goal was to update guidelines based on the best available evidence using an established and uniform methodology to address and formulate recommendations for each topic. The degree of consensus for each recommendation is also presented. The clinical issues addressed and recommendations made were: population-based screening for H. pylori in asymptomatic children to prevent gastric cancer is not warranted; testing for H. pylori in children should be considered if there is a family history of gastric cancer; the goal of diagnostic interventions should be to determine the cause of presenting gastrointestinal symptoms and not the presence of H. pylori infection; recurrent abdominal pain of childhood is not an indication to test for H. pylori infection; H. pylori testing is not required in patients with newly diagnosed gastroesophageal reflux disease; H. pylori testing may be considered before the use of long-term proton pump inhibitor therapy; testing for H. pylori infection should be considered in children with refractory iron deficiency anemia when no other cause has been found; when investigation of pediatric patients with persistent or severe upper abdominal symptoms is indicated, upper endoscopy with biopsy is the investigation of choice; the 13C-urea breath test is currently the best noninvasive diagnostic test for H. pylori infection in children; there is currently insufficient evidence to recommend stool antigen tests as acceptable diagnostic tools for H. pylori infection; serological antibody tests are not recommended as diagnostic tools for H. pylori infection in children; first-line therapy for H. pylori infection in children is a twice-daily, triple-drug regimen comprised of a proton pump inhibitor plus two antibiotics (clarithromycin plus amoxicillin or metronidazole); the optimal treatment period for H. pylori infection in children is 14 days; and H. pylori culture and antibiotic sensitivity testing should be made available to monitor population antibiotic resistance and manage treatment failures.

Hydrophilic-coated catheter appreciation study in a pediatric population.

OBJECTIVE: The objective of the paper was to compare the satisfaction of hydrophilic-coated catheters (HC) (SpeediCath, Coloplast Canada, Mississauga, ON) versus uncoated catheters in a pediatric neurogenic bladder population, in order to identify a target group for HC. The main hypothesis was that our patients, with regard to their limitations, might have difficulties using the HC. MATERIAL AND METHODS: A comparative prospective study was initiated in one pediatric rehabilitation centre. Out of the 39 patients who tried the HC during a routine clinic visit, 31 patients/parents accepted to participate in a 1-week trial and to answer a satisfaction questionnaire. Their medical records were reviewed for age, neurological disease, intellectual deficit, impaired dexterity and method of catheterization (Mitrofanoff/urethra). RESULTS: Thirty of the 31 patients answered the satisfaction questionnaire. The median age for the 30 patients was 13.5 years (range 6-20 years). Of these patients, 19 were females (63%), 26 performed self-catheterization (87%), and 6 had Mitrofanoff (20%). Ten children (33%) would be ready to proceed with HC and all 10 children would receive catheterization by the urethra. Of these, 9 were females (90%), 8 used compact-HC (80%) and all were self-sufficient. Patients using compact-HC would continue with this catheter. In the patient comments, males catheterizing per-urethra and patients using a continent stoma requiring long catheters had problems with the excess of lubricant. CONCLUSION: Most children preferred their usual uncoated catheter and would not change for HC. Female patients catheterizing per-urethra with a compact-HC seem to benefit most from this catheter.

Role of probiotics in the modulation of intestinal infections and inflammation.

PURPOSE OF REVIEW: Using microorganisms to influence positively the course of an illness caused by injurious microorganisms is an approach with mounting clinical evidence showing efficacy. Whereas antibiotics will remain an important therapeutic option, there are limitations and problems to their increasing and chronic usage, and probiotics offer a strategy to reduce antibiotic usage. Increasingly, it has become clear that the mechanisms whereby probiotics can impact in intestinal diseases involve a large repertoire of responses. This review summarizes recent findings on how probiotics may effect benefit through interactions with host eukaryotic cells. RECENT FINDINGS: Limiting the access of microbes associated with the development of disease to host mucosal surfaces and altering the responses of host to microbial insults are potential mechanisms whereby probiotics can influence the pathogenesis of disease. Evidence is accumulating that live, viable probiotic organisms diminish accessibility to intestinal epithelial cell; however, the mucosal exclusion is not through direct blockage of shared epithelial receptors between probiotic microbes and pathogenic organisms. Modulation of mucosal defenses such as innate protective mechanisms, enhanced epithelial cell survival, and immune responses have all been shown to have potential in aiding in these actions. Intestinal epithelial cell adherence influences response and, as such, appears to be necessary but may not be wholly sufficient, because soluble bacterial factors have been reported to effect modulation of immune and nonimmune responses of eukaryotic cells. SUMMARY: There is a considerable repertoire of responses potentially responsible for the effects of probiotics, and these responses appear to involve a complex interplay between the microbes of the intestinal tract and the cells of the host. Continued work can be expected to further the understanding of the mechanisms involved, and more work is needed to determine the relative clinical importance of each of the phenomena. These studies are expected to help direct the most efficacious use of probiotics for inflammatory conditions arising from the intestinal tract.

Helicobacter pylori activates Toll-like receptor 4 expression in gastrointestinal epithelial cells.

Helicobacter pylori activates the transcription factor NF-kappaB, leading to proinflammatory cytokine production by gastric epithelial cells. However, the receptors for the initial bacterial interaction with host cells which activate downstream signaling events have not been completely defined. Recently, it has been shown that microbial components activate Toll-like receptors (TLRs), thereby leading to AP-1- and NF-kappaB-dependent transcription and resulting in the production of proinflammatory cytokines. The aim of this study was to determine whether H. pylori activates TLR4. Reverse transcription-PCR showed that both type I and type II H. pylori clinical isolates induced TLR4 mRNA expression in AGS cells compared with that by uninfected controls. H. pylori upregulated TLR4 protein expression in two gastric epithelial cell lines (AGS and MKN45) and one intestinal epithelial cell line (T84). Monoclonal TLR4 antibody inhibited lipopolysaccharide-induced interleukin-8 secretion from THP-1 macrophages but not from gastric epithelial cells infected with H. pylori. H. pylori demonstrated increased adherence to CHO TLR4-transfected cells compared with that to both CHO TLR2-transfected and nontransfected CHO cells (P < 0.01). These results indicate that H. pylori activates TLR4 expression in epithelial cells and that TLR4 can serve as a receptor for H. pylori binding.

Glycine conjugation of para-aminobenzoic acid (PABA): a pilot study of a novel prognostic test in acute liver failure in children.

BACKGROUND: Fulminant hepatic failure (FHF) is associated with high mortality; few patients survive without liver transplantation. It is important to have a sensitive, specific early predictor of outcome to distinguish potential survivors (S) from nonsurvivors (NS). OBJECTIVE: Because we had previously shown that glycine conjugation of para-aminobenzoic acid (PABA) quantitatively reflects liver function in children with chronic liver disease, in this pilot study we wanted to determine whether the measurement of the glycine conjugates of PABA could distinguish S from NS in FHF in comparison with standard prognostic indices. METHODS: Twenty-four patients were studied: acute severe hepatitis (n = 7), subfulminant hepatic failure (n = 7), and FHF (n = 10). Assessment of King's College criteria, measurement of factor V and VII levels, PABA testing, and transjugular liver biopsies were performed in almost all patients within 48 hours of admission. Serum PABA and its glycine conjugates (para-aminohippurate (PAHA) and para-acetamidohippurate (PAAHA)) were measured thirty minutes after oral administration by high-pressure liquid chromatography. Poor prognostic categories as previously established in the literature were defined as factor V < 0.20U/ml, factor VII < 0.08 U/ml, % necrosis >70%, hippurate ratio = 0%, and PAHA = 0M. RESULTS: The measurement of PAHA was the best predictor of a poor outcome in patients with acute liver failure with a sensitivity of 92%, and negative predictive value (NPV) of 92% compared with a sensitivity of 54% and a NPV of 63% with King's College criteria. CONCLUSION: Measurement of serum PAHA is the best early prognostic marker of death in children who suffer from FHF.

Altered expression of genes involved in hepatic morphogenesis and fibrogenesis are identified by cDNA microarray analysis in biliary atresia.

Biliary atresia (BA) is characterized by a progressive, sclerosing, inflammatory process that leads to cirrhosis in infancy. Although it is the most common indication for liver transplantation in early childhood, little is known about its etiopathogenesis. To elucidate factors involved in this process, we performed comprehensive genome-wide gene expression analysis using complementary DNA (cDNA) microarrays. We compared messenger RNA expression levels of approximately 18,000 human genes from normal, diseased control, and end-stage BA livers. Reverse-transcription polymerase chain reaction (RT-PCR) and Northern blot analysis were performed to confirm changes in gene expression. Cluster and principal component analysis showed that all BA samples clustered together, forming a distinct group well separated from normal and diseased controls. We further identified 35 genes and ESTs whose expression differentiated BA from normal and diseased controls. Most of these genes are known to be associated with cell signaling, transcription regulation, hepatic development, morphogenesis, and fibrogenesis. In conclusion, this study serves to delineate processes that are involved in the pathogenesis of BA.