Citations

AbstractBackgroundNausea and vomiting are thought to result from upper gastrointestinal dysfunctions. Our clinical observations led to the hypothesis that colonic motor dysfunction is associated with nausea and vomiting.MethodsWe reviewed electronic medical records (EMR) of 149 patients presenting with complaints of nausea and/or vomiting in a tertiary gastroenterology practice to investigate the association with disorders of colonic motor or evacuation disorders. We extracted demographics, gastric emptying (GEin 149) and colonic transit (CTin 138) of solids, ascending colon emptying half‐time (ACt1/2), rectal evacuation by anorectal manometry (ARM) in 91 and balloon expulsion test (BE) in 55 patients. We estimated the proportions with delayedGEorCT, based on the 5th percentile ofGE(in 319) andCTin 220 healthy volunteers using same method.Key ResultsAmong 11 patients with nausea and/or vomiting with onlyGEmeasured, five had delayed and six normalGE. Among the 149 patients, 77 (52%) patients had evacuation disorders, confirmed by objective tests in 68 patients, and clinical examination in nine patients. In the 138 patients with bothGEandCTmeasured, 106 (76%) had both normalGEandCT, 11 (8%) only delayedGE, 16 (11%) normalGEwith delayedCT, and five (3%) delayedGEandCT. Among 21 patients (15%) with delayedCT, nine had slowACt1/2and 12 evacuation disorder.Conclusions & InferencesIn patients with chronic nausea and/or vomiting in gastroenterology practice, evaluation of colonic motility and rectal evacuation should be considered, since about half the patients have abnormal functions that conceivably contribute to the presenting nausea and/or vomiting.

The contribution of elevated glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism after Roux-en-Y gastric bypass (RYGB) has been the subject of uncertainty. We used exendin-9,39, a competitive antagonist of GLP-1, to examine glucose metabolism, islet hormone secretion, and gastrointestinal transit in subjects after RYGB and in matched control subjects. Subjects were studied in the presence or absence of exendin-9,39 infused at 300 pmol/kg/min. Exendin-9,39 resulted in an increase in integrated postprandial glucose concentrations post-RYGB (3.6 ± 0.5 vs. 2.0 ± 0.4 mol/6 h, P = 0.001). Exendin-9,39 decreased insulin concentrations (12.3 ± 2.2 vs. 18.1 ± 3.1 nmol/6 h, P = 0.002) and the β-cell response to glucose (ϕTotal, 13 ± 1 vs. 11 ± 1 × 10−9 min−1, P = 0.01) but did not alter the disposition index (DI). In control subjects, exendin-9,39 also increased glucose (2.2 ± 0.4 vs. 1.7 ± 0.3 mol/6 h, P = 0.03) without accompanying changes in insulin concentrations, resulting in an impaired DI. Post-RYGB, acceleration of stomach emptying during the first 30 min by exendin-9,39 did not alter meal appearance, and similarly, suppression of glucose production and stimulation of glucose disappearance were unaltered in RYGB subjects. These data indicate that endogenous GLP-1 has effects on glucose metabolism and on gastrointestinal motility years after RYGB. However, it remains uncertain whether this explains all of the changes after RYGB.

AbstractGhrelin is the endogenous ligand for the growth hormone secretagogue‐1a receptor and is a potential target for treatment of gastroparesis. This viewpoint assesses the potential role of ghrelin agonists in the treatment of gastroparesis through a review of the early phase, randomized, controlled trials of ghrelin agonists in patients with diabetes and, either, delayed gastric emptying at the time of the trial or symptoms at the time of the trial, and prior documentation of delayed gastric emptying of solids. Whereas recent experience with ghrelin agonists that have a macrocycle structure (TZP‐101, TZP‐102) has not confirmed earlier promising results, there is little evidence that ghrelin receptors downregulate with repeated treatment, in contrast to motilin receptors. Phase IIa clinical trials performed with a different agent (RM‐131, which is a small molecule ghrelin agonist) suggest that, as a class, ghrelin agonists may be efficacious in stimulating gastric emptying. It is premature to dismiss ghrelin agonists as potential therapies for gastroparesis.

AbstractPurposeThe objective was to review the genetics of human visceral pain with particular emphasis on pain associated with irritable bowel syndrome.BackgroundThe biomarkers most commonly employed in identifying visceral hypersensitivity are sensation ratings and thresholds or brain imaging during viscus (e.g., rectal) distension. Genetic studies suggest that variation in the control of candidate genes involved in ion channel function, neurotransmitter synthesis, reuptake or receptor functions, and inflammatory disease susceptibility loci may impact variations in prevalence of the symptom phenotype of abdominal pain or IBS, or quantitative traits (intermediate phenotypes) of rectal sensation. The candidate genes include SLC6A4, CNR1, and TNFSF15 reflecting serotonin reuptake, cannabinoid receptors, and inflammatory‐barrier functions. However, other than TNFSF15, the other candidate genes are only univariately associated with pain, IBS symptom complex, or quantitative traits of sensation. These data have generated hypotheses and present opportunities for study of mechanisms and treatment of visceral pain in humans, which remains an unmet clinical need in patients with IBS and functional abdominal pain.

Summary Background Daikenchuto, a Japanese herbal medicine used for post‐operative ileus and constipation, dose dependently stimulates gastrointestinal ( GI ) motility and decreases rectal compliance and sensation. Effects of TU ‐100 (commercial form of daikenchuto) in adults with constipation are unknown. Aim To compare the effects of oral TU ‐100, 2.5 g t.d.s. or 5 g t.d.s. and placebo t.d.s. on GI and colonic transit ( CT ), rectal compliance ( RC ) and sensation thresholds ( RST ), anal sphincter pressures ( ASP ) and bowel function in female patients with functional constipation ( FC ). Methods We conducted a single‐centre, randomised, parallel‐group, double‐blind, pharmacodynamic study; 45 female patients with FC without evidence of rectal evacuation disorder were assigned to 28 days' treatment with oral placebo or TU ‐100 (Tsumura USA, Princeton, NJ, USA). Demographic data and CT were measured at baseline and randomisation stratified by baseline CT (GC> or <1.9) and by BMI (<25 or ≥25 kg/m 2 ). At the end of treatment period, we measured GI and CT by scintigraphy, RST and RC by barostat, ASP by manometry, psychosensory sensations, bowel function by daily diary and quality of life ( QOL ). The study had power to detect effect sizes of 33% ( CT ), 40% ( RC ) and 46% ( RST ). Statistical analysis included BMI as covariate. Results TU ‐100 had no significant effects on GI or CT , RC , ASP , recto‐anal pressure difference, or RST . The 5 g t.d.s./day dose was associated with lower RST for first sensation and gas (unadjusted P : 0.045 and 0.024 respectively). There were no treatment effects on psychosensory symptoms, stool frequency, stool consistency or QOL . Conclusion Mechanisms underlying the observed clinical benefit of TU ‐100 remain unclear ( ClinicalTrials.gov NCT01139216).