Utility of Diagnostic Studies for Upper Gastrointestinal Symptoms in Children with Orthostatic Intolerance.

OBJECTIVE: To assess the utility of gastrointestinal (GI) diagnostic studies in the evaluation of patients with orthostatic intolerance. STUDY DESIGN: Medical records of 103 consecutive children/young adults with orthostatic intolerance and gastrointestinal symptoms were reviewed. All patients had undergone antroduodenal manometry in conjunction with the tilt table test, autonomic testing, and upper gastrointestinal endoscopy (EGD). A gastric emptying study (GES) was performed in 81 patients. RESULTS: The median age of the cohort was 17 years (IQR, 15-19) with a female predominance (females:males, 3:1). As expected, the tilt table test was abnormal in all patients. Antroduodenal manometry was abnormal in 83 of 103 patients (81%), showing neurogenic intestinal dysmotility in 50%, rumination in 20%, and visceral hyperalgesia in 10%. The GES results were abnormal in 23 of 81 patients (28.4%), mostly (21 of 23) with delayed GES. None of the tilt table test or autonomic results were predictive of abnormal antroduodenal manometry or GES. Analysis of EGD biopsy samples revealed nonspecific esophagitis and/or gastritis in 16 of 103 patients (15%). CONCLUSIONS: Antroduodenal manometry with the tilt table test were the most insightful investigations in adolescents and young adults with orthostatic intolerance and gastrointestinal symptoms. GES and EGD provided limited information. Gastrointestinal symptoms were related more to functional rather than mucosal or organic etiologies, suggesting a limited role of endoscopy alone in evaluating patients with orthostatic intolerance presenting with gastrointestinal symptoms.

Chemoreception regulates chemical access to mouse vomeronasal organ: role of solitary chemosensory cells.

Controlling stimulus access to sensory organs allows animals to optimize sensory reception and prevent damage. The vomeronasal organ (VNO) detects pheromones and other semiochemicals to regulate innate social and sexual behaviors. This semiochemical detection generally requires the VNO to draw in chemical fluids, such as bodily secretions, which are complex in composition and can be contaminated. Little is known about whether and how chemical constituents are monitored to regulate the fluid access to the VNO. Using transgenic mice and immunolabeling, we found that solitary chemosensory cells (SCCs) reside densely at the entrance duct of the VNO. In this region, most of the intraepithelial trigeminal fibers innervate the SCCs, indicating that SCCs relay sensory information onto the trigeminal fibers. These SCCs express transient receptor potential channel M5 (TRPM5) and the phospholipase C (PLC) beta2 signaling pathway. Additionally, the SCCs express choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) for synthesizing and packaging acetylcholine, a potential transmitter. In intracellular Ca2+ imaging, the SCCs responded to various chemical stimuli including high concentrations of odorants and bitter compounds. The responses were suppressed significantly by a PLC inhibitor, suggesting involvement of the PLC pathway. Further, we developed a quantitative dye assay to show that the amount of stimulus fluid that entered the VNOs of behaving mice is inversely correlated to the concentration of odorous and bitter substances in the fluid. Genetic knockout and pharmacological inhibition of TRPM5 resulted in larger amounts of bitter compounds entering the VNOs. Our data uncovered that chemoreception of fluid constituents regulates chemical access to the VNO and plays an important role in limiting the access of non-specific irritating and harmful substances. Our results also provide new insight into the emerging role of SCCs in chemoreception and regulation of physiological actions.