cholecystokinin and Failure-to-Thrive

Direct measurement of pancreatic enzymes is the gold standard in the evaluation of exocrine pancreatic function. The purpose of our study was to evaluate the use of cholecystokinin as a single-agent secretagogue for pancreatic drainage studies. Twenty pediatric patients received cholecystokinin (group 1) and 40 patients received either secretin plus placebo (group 2) or secretin plus cholecystokinin (group 3). Duodenal fluid was collected for measurement of lipase, amylase, trypsin, chymotrypsin. The mean lipase and amylase activities were higher in group 3 and the mean trypsin and chymotrypsin activities were higher in group 1, but none of these observations were statistically significant. Group 3 had more patients with all four enzymes being normal (75%) compared to groups 1 (60%) and 2 (50%) (P = 0.262). Patients in all three groups had at least one normal enzyme. Cholecystokinin is useful as a single agent for direct pancreatic enzyme measurements in the absence of commercially available secretin.

Topics: Adolescent; Amylases; Child; Child, Preschool; Cholecystokinin; Chymotrypsin; Diagnosis, Differential; Drug Synergism; Failure to Thrive; Female; Humans; Infant; Lipase; Malabsorption Syndromes; Male; Pancreatic Function Tests; Pancreatic Juice; Pilot Projects; Prospective Studies; Secretin; Trypsin

Severe congenital diarrhea occurs in approximately half of patients with Aristaless-Related Homeobox (ARX) null mutations. The cause of this diarrhea is unknown. In a mouse model of intestinal Arx deficiency, the prevalence of a subset of enteroendocrine cells is altered, leading to diarrhea. Because polyalanine expansions within the ARX protein are the most common mutations found in ARX-related disorders, we sought to characterize the enteroendocrine population in human tissue of an ARX mutation and in a mouse model of the corresponding polyalanine expansion (Arx).. Immunohistochemistry and quantitative real-time polymerase chain reaction were the primary modalities used to characterize the enteroendocrine populations. Daily weights were determined for the growth curves, and Oil-Red-O staining on stool and tissue identified neutral fats.. An expansion of 7 alanines in the first polyalanine tract of both human ARX and mouse Arx altered enteroendocrine differentiation. In human tissue, cholecystokinin, glucagon-like peptide 1, and somatostatin populations were reduced, whereas the chromogranin A population was unchanged. In the mouse model, cholecystokinin and glucagon-like peptide 1 populations were also lost, although the somatostatin-expressing population was increased. The ARX protein was present in human tissue, whereas the Arx protein was degraded in the mouse intestine.. ARX/Arx is required for the specification of a subset of enteroendocrine cells in both humans and mice. Owing to protein degradation, the Arx mouse recapitulates findings of the intestinal Arx null model, but is not able to further the study of the differential effects of the ARX protein on its transcriptional targets in the intestine.

Topics: Adolescent; Animals; Cell Differentiation; Cholecystokinin; Chromogranin A; Diarrhea; Disease Models, Animal; Duodenal Diseases; Duodenum; Enteroendocrine Cells; Failure to Thrive; Female; Glucagon-Like Peptide 1; Homeodomain Proteins; Humans; Intestinal Pseudo-Obstruction; Male; Mice; Mice, Inbred C57BL; Mutagenesis, Insertional; Peptides; Somatostatin; Steatorrhea; Transcription Factors