9 research outputs found
Prolonged intestinal transit and diarrhea in patients with an activating <i>GUCY2C</i> mutation
<div><p>Introduction</p><p>Increased intestinal hydration by activation of the epithelial enzyme linked receptor guanylate cyclase C (GC-C) is a pharmacological principle for treating constipation. Activating mutations in the <i>GUCY2C</i> gene encoding GC-C cause Familial <i>GUCY2C</i> diarrhea syndrome (FGDS) which has been diagnosed with severe dysmotility.</p><p>Aim</p><p>To investigate gut motility and hormones before and after a meal in FGDS patients and compare with healthy controls (HC).</p><p>Subjects and methods</p><p>Bristol stool chart and stool frequency was assessed. Before and after a meal occlusive and non-occlusive contractions were obtained using ultrasound. A wireless motility capsule (WMC) recorded gut transit time, pH, contractions and pressure. Plasma levels of selected gut hormones were measured at different time points.</p><p>Results</p><p>The FGDS patients had 4 (range 1–10) loose stools/day and prolonged total gut transit time compared to HC, 55.5 h vs 28.5 h, respectively,with significantly increased colon transit time. In FGDS patients, pH in duodenum, small bowel and colon was increased and the number of contractions and the intraluminal pressure were significantly decreased, measured by WMC. Ultrasound showed in small bowel increased number of non-occlusive contractions in the FGDS patients. Serotonin (5-HT) plasma levels in the HC peaked 30 min after the meal, while the FGDS patients had no response.</p><p>Conclusion</p><p>Despite having diarrhea, the FGDS patients have prolonged transit time through the gut compared to HC, particularly in colon. The reduced number of intestinal contractions and lack of 5-HT release after a meal in FGDS patients surprisingly resemble colonic motility disturbances seen in patients with constipation.</p></div
Gastrointestinal hormones.
<p>Median plots with IQR (25 and 75 percentiles) for the time course secretion of the different hormones before (baseline) and after a meal. Significant differences were found between FGDS and HC regarding plasma Proguanylin at all time points (baseline, 30 min, 60 min, 120 min and 240 min) and for plasma Serotonin 30 min postprandial (* p< 0.05,**p < 0.01). There were no significant differences in plasma measurements of GLP-1, PYY and Proguanylin between FGDS and HC.</p
Contractions in small bowel obtained by Ultrasound.
<p>Box plots showing the number of non-occlusive ileal and jejunal contractions and the number of occlusive ileal and jejunal contractions pr min obtained by ultrasound for each of the study time points. The median is shown within the box; the box represents the 25 and 75 percentiles and the whiskers 10 and 90 percentiles. The black boxes display FGDS patients, the white boxes the Healthy controls.</p
Pressures obtained by Wireless Motility Capsule (WMC).
<p>Intraluminal pressure parameters in mmHg, median and range obtained with WMC. Colon data from 23 healthy controls and 14 patients are displayed.</p
Number of contractions obtained by Wireless Motility capsule (WMC).
<p>Box plots showing number of contractions per min in stomach, antrum, duodenum, small bowel and colon recorded by WMC. There was no significant difference between the two groups in stomach or antrum. In the duodenum, small bowel and in colon there was significant differences between FGDS and HC. The median is shown within the box; the box represents the 25 and 75 percentiles and the whiskers 10 and 90 percentiles.</p
Gastrointestinal pH measurements.
<p>Box plots showing the elevated pH values in the duodenum, small bowel and colon found in patients with Familial <i>GUCY2C</i> diarrhea syndrome (FGDS) compared to healthy controls (HC). There was no difference in the stomach and antrum. The median is shown within the box; the box represents the 25 and 75 percentiles and the whiskers 10 and 90 percentiles.</p
Interobserver analyses from small bowel.
<p>Scatter plots and Bland-Altman plots with limits of agreement depicting bias and error between observer 1 and observer 2 for detection of small bowel transit time recorded with wireless motility capsule in healthy controls (2A,B) and in patients with Familial <i>GUCY2C</i> Diarrhea Syndrome (2C,D).</p
Fluid- filled small bowel loops.
<p>The number of fluid-filled small bowel loops obtained by ultrasound.There were significant differences between FGDS and HC for all measured points (p<0.001). Error bars are shown as median with IQR (25 and 75 percentiles).</p