Intestinal Guanylate Cyclase-C mRNA Expression in Duodenum and Colon of Children.

OBJECTIVES: Guanylate cyclase-C (GC-C) agonists, which increase intestinal secretion and accelerate transit, are used to treat chronic constipation and constipation-predominant irritable bowel syndrome and are being evaluated for pediatric use. Prior studies suggest GC-C receptor density may be higher in young children, potentially amplifying GC-C agonism with treatment implications. We aimed to quantitate duodenal and colonic GC-C mRNA expression in children. METHODS: Mucosal biopsies were obtained from subjects aged 6 months to 18 years during clinically indicated upper, that is, esophago-gastro-duodenal, and/or colonic endoscopy. Tissue samples without histologic abnormalities were grouped by subject age (<24 months, 24 months to <6 years, 6 to <12 years, and 12 to <18 years) and analyzed for GC-C mRNA expression by qPCR. The relationship between GC-C mRNA levels and age was modeled using regression analyses. RESULTS: Ninety-nine subjects underwent upper endoscopy/colonoscopy; 93 had evaluable samples. Mean relative GC-C mRNA expression was 2.36 (range 2.21-2.46) for duodenal samples and 1.56 (range 1.22-1.91) for colonic samples. Predicted and observed normalized GC-C mRNA expression in each region were comparable among age groups. Pooled expression by region demonstrated lower expression in colonic versus duodenal samples. CONCLUSIONS: Uniform levels of GC-C mRNA expression were detected in children aged >6 months in the duodenum and >12 months in the colon. Higher expression was observed in all age groups in duodenal versus colonic samples, indicating regional variability in GC-C receptor density. These data are reassuring for further studies of GC-C agonists in children.

Comorbidities in patients with irritable bowel syndrome with constipation or chronic idiopathic constipation: a review of the literature from the past decade.

BACKGROUND: Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are common functional bowel disorders. Patients with IBS-C or CIC often present with ≥ 1 comorbidity that coincides with either of these conditions. These comorbidities may make underappreciated contributions to the patient's overall disease burden. OBJECTIVE: To identify the comorbidities that are the most frequently reported in patients with IBS-C or CIC in the medical literature. METHODS: A literature search (January 2001-March 2012) was performed using the Medline and Medline In-Process databases. Studies of adult patients with IBS-C or CIC were selected, and the prevalence rates of the comorbidities were extracted and analyzed according to the body system affected. RESULTS: A total of 70 distinct comorbidities were identified from 35 published studies. These comorbidities involved several body systems, including the gastrointestinal, genitourinary, psychiatric, endocrine, and allergic or immunologic systems. Functional dyspepsia and depression were the most common comorbidities in patients with IBS-C, whereas functional dyspepsia, diabetes, and depression were the most common comorbidities in patients with CIC. CONCLUSION: Patients with IBS-C or CIC frequently experience a wide range of comorbidities that contribute to their disease burden. Thus, we believe that medical professionals should consider common comorbidities when diagnosing and treating patients with IBS-C or CIC.