Nadeau, Ashley

SummaryBackgroundOlmesartan‐associated enteropathy (OAE) is characterised by diarrhoea, nausea, vomiting, abdominal pain, weight loss and severe sprue‐like enteropathy, all of which are resolved after discontinuation of olmesartan medoximil.AimTo determine the mechanistic similarities of OAE with coeliac sprue.MethodsDuodenal biopsies were extracted from OAE patients before (n = 11) or after (n = 17) discontinuation of olmesartan medoxomil (on or off olmesartan medoxomil). There were seven ‘on/off’ paired samples. Formalin‐fixed biopsies were stained for CD8, CD4, FoxP3, IL‐15R and psmad 2/3. Caco2 cells (human colonic epithelial line) were treated with olmesartan medoxomil and stained for IL‐15, IL‐15R and ZO‐1.ResultsIn the ‘on olmesartan medoxomil’ duodenal biopsies, a significant increase in the numbers of CD8+ cells and the number of cells that are FoxP3+ (a regulatory T‐cell marker) are present in the duodenum as compared to the duodenal biopsies from patients who discontinued olmesartan medoxomil. IL15R expression is also increased with olmesartan medoxomil use. Evaluation of the effect of olmesartan medoxomil upon Caco‐2 cells demonstrated that IL15 expression is increased in response to olmesartan medoxomil treatment. Further, ZO‐1, a tight junction protein, is disrupted in olmesartan medoxomil‐treated Caco‐2 cells.ConclusionsOlmesartan‐associated enteropathy shares many features with coeliac disease, including symptoms and immunopathogenic pathways, such as increased numbers of CD8+ cells and corresponding overexpression of IL15 by epithelial cells. Taken together, the treatment of epithelial cells with olmesartan medoxomil induces a response by intestinal epithelial cells that is similar to the innate effects of gluten upon the epithelium of coeliac patients.

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.

Abstract Background There is little information regarding gender‐specific measurements of colonic transit and anorectal function in patients with defecation disorders ( DD ). To compare overall colonic transit by gender in DD . Methods In 407 patients with constipation due to DD diagnosed by a single gastroenterologist (1994–2012), DD was characterized by anorectal manometry, balloon expulsion test, and colonic transit by scintigraphy. The primary endpoint was overall colonic transit (geometric center, GC ) at 24 h ( GC 24). Effects of gender in DD on colonic transit, and comparison with transit in 208 healthy controls were assessed by Mann–Whitney rank sum test. Secondary endpoints were maximum anal resting ( ARP ) and squeeze ( ASP ) pressures. We also tested association of the physiological endpoints among DD females by pregnancy history and among DD patients by colectomy history. Key Results The DD patients were 67 males (M) and 340 females (F). Significant differences by gender in DD patients were observed in GC 24 (median: M: 2.2; F: 1.8; P = 0.01), ARP (median: M: 87.8 mmHg; F: 82.4 mmHg; P = 0.04), and ASP (median: M: 182.4 mmHg; F: 128.7 mmHg; P < 0.001). GC 24 was slower in DD compared with same‐gender healthy controls. GC 24 did not differ among DD females by pregnancy history. Anorectal functions and upper GI transit did not differ among DD patients by colectomy history. Conclusions & Inferences Patients with DD have slower colonic transit compared with gender‐matched controls. Among DD patients, males have higher ARP and ASP , and females have slower colonic transit. Although the clinical significance of these differences may be unclear, findings suggest that interpretation of these tests in suspected DD should be based on same‐gender control data.