A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients.

UNLABELLED: BACKGROUND/ OBJECTIVES: The relationship between the enteroendocrine hormone glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2 promotes mucosal growth, decreases permeability and reduces inflammation in the intestine; physiological stimulation of GLP-2 release is triggered by nutrient contact. The authors hypothesized that ileal Crohn disease (CD) affects GLP-2 release. METHODS: With ethics board approval, pediatric patients hospitalized with CD were studied; controls were recruited from local schools. Inclusion criteria were endoscopy-confirmed CD (primarily of the small intestine) with a disease activity index >150. Fasting and postprandial GLP-2 levels and quantitative urinary recovery of orally administered 3-O-methyl-glucose (active transport) and lactulose/mannitol (passive) were quantified during the acute and remission phases. RESULTS: Seven patients (mean [± SD] age 15.3 ± 1.3 years) and 10 controls (10.3 ± 1.6 years) were studied. In patients with active disease, fasting levels of GLP-2 remained stable but postprandial levels were reduced. Patients with active disease exhibited reduced glucose absorption and increased lactulose/mannitol recovery; all normalized with disease remission. The change in the lactulose/mannitol ratio was due to both reduced lactulose and increased mannitol absorption. CONCLUSIONS: These findings suggest that pediatric patients with acute ileal CD have decreased postprandial GLP-2 release, reduced glucose absorption and increased intestinal permeability. Healing of CD resulted in normalization of postprandial GLP-2 release and mucosal functioning (nutrient absorption and permeability), the latter due to an increase in mucosal surface area. These findings have implications for the use of GLP-2 and feeding strategies as a therapy in CD patients; further studies of the effects of inflammation and the GLP-2 axis are recommended.

Therapeutic applications of octreotide in pediatric patients.

BACKGROUND/AIM: We report our experience with the use of octreotide as primary or adjunctive therapy in children with various gastrointestinal disorders. PATIENTS AND METHODS: A pharmacy database identified patients who received octreotide for gastrointestinal diseases. Indications for octreotide use, dosing, effectiveness, and adverse events were evaluated by chart review. RESULTS: A total of 21 patients (12 males), aged 1 month to 13 years, were evaluated. Eleven received octreotide for massive gastrointestinal bleeding caused by portal hypertension-induced lesions (n=7), typhlitis (1), Meckel's diverticulum (1), and indefinite source (2). Blood transfusion requirements were reduced from 23 ± 9 mL/kg (mean ± SD) to 8 ± 15 mL/kg (P<0.01). Four patients with pancreatic pseudocyst and/or ascites received octreotide over 14.0 ± 5.7 days in 2 patients. In 3 children, pancreatic pseudocyst resolved in 12 ± 2 days and pancreatic ascites resolved in 7 days in 2. Three patients with chylothorax received octreotide for 14 ± 7 days with complete resolution in each. Two infants with chronic diarrhea received octreotide over 11 ± 4.2 months. Stool output decreased from 85 ± 21 mL/kg/day to 28 ± 18 mL/kg/day, 3 months after initiation of octreotide. The child with dumping syndrome responded to octreotide in a week. Adverse events developed in 4 patients: Q-T interval prolongation and ventricular fibrillation, hyperglycemia, growth hormone deficiency, and hypertension. CONCLUSION: Octreotide provides a valuable addition to the therapeutic armamentum of the pediatric gastroenterologist for a wide variety of disorders. Serious adverse events may occur and patients must be closely monitored.

Kabuki syndrome and Crohn disease in a child with familial hypocalciuric hypercalcemia.

BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) results from a mutation of the calcium sensing receptor (CASR) gene and typically presents as asymptomatic hypercalcemia with inappropriately low urinary calcium excretion and normal or mildly elevated levels of parathyroid hormone. OBJECTIVE: To describe a case of FHH associated with Kabuki syndrome and Crohn disease. METHOD: Genomic DNA was screened for CASR mutations and a retrospective chart review was performed. RESULTS: Heterozygosity was observed in exon 3, which encodes a portion of the extra-cellular domain. Sequencing revealed a n.476T>G nucleotide transversion, predicting a non-conservative substitution of arginine for leucine at codon 159 (p.L159R). CONCLUSION: An association between Kabuki syndrome and autoimmune disease has been described in the literature, which may explain the connection between Kabuki syndrome and Crohn disease. However, it remains unclear if there is a link between FHH, Kabuki syndrome and Crohn disease in this case.

Consumption of pure oats by individuals with celiac disease: a position statement by the Canadian Celiac Association.

The treatment of celiac disease is a strict adherence to a gluten-free diet for life. In the past, oats were considered to be toxic to individuals with celiac disease and were not allowed in a gluten-free diet. However, recent evidence suggests that oats that are pure and uncontaminated with other gluten-containing grains, if taken in limited quantities, are safe for most individuals with celiac disease. For adults, up to 70 g (1/2 to 3/4 cup) of oats per day and for children, up to 25 g (1/4 cup) per day are safe to consume. These oats and oat products must fulfill the standards for a gluten-free diet set by the Canadian Food Inspection Agency and Health Canada. The Canadian Celiac Association, in consultation with Health Canada, Agriculture & Agri-Food Canada and the Canadian Food Inspection Agency, has established requirements for growing, processing, and purity testing and labelling of pure oats. These strategies have led to the production of pure, uncontaminated oats for the first time in Canada. Oats and oat products that are safe for consumption by individuals with celiac disease and dermatitis herpetiformis are now commercially available in Canada.

The burden of large and small duct primary sclerosing cholangitis in adults and children: a population-based analysis.

OBJECTIVES: The epidemiology of primary sclerosing cholangitis (PSC) has been incompletely assessed by population-based studies. We therefore conducted a population-based study to determine: (a) incidence rates of large and small duct PSC in adults and children, (b) the risk of inflammatory bowel disease on developing PSC, and (c) patterns of clinical presentation with the advent of magnetic resonance cholangiopancreatography (MRCP). METHODS: All residents of the Calgary Health Region diagnosed with PSC between 2000 and 2005 were identified by medical records, endoscopic, diagnostic imaging, and pathology databases. Demographic and clinical information were obtained. Incidence rates were determined and risks associated with PSC were reported as rate ratios (RR) with 95% confidence intervals (CI). RESULTS: Forty-nine PSC patients were identified for an age- and gender-adjusted annual incidence rate of 0.92 cases per 100,000 person-years. The incidence of small duct PSC was 0.15/100,000. In children the incidence rate was 0.23/100,000 compared with 1.11/100,000 in adults. PSC risk was similar in Crohn's disease (CD; RR 220.0, 95% CI 132.4-343.7) and ulcerative colitis (UC; RR 212.4, 95% CI 116.1-356.5). Autoimmune hepatitis overlap was noted in 10% of cases. MRCP diagnosed large duct PSC in one-third of cases. Delay in diagnosis was common (median 8.4 months). A minority had complications at diagnosis: cholangitis (6.1%), pancreatitis (4.1%), and cirrhosis (4.1%). CONCLUSIONS: Pediatric cases and small duct PSC are less common than adult large duct PSC. Surprisingly, the risk of developing PSC in UC and CD was similar. Autoimmune hepatitis overlap was noted in a significant minority of cases.