An exploratory study of the association of adrenergic and serotonergic genotype and gastrointestinal motor functions.

Adrenergic and serotonergic mechanisms alter human gut motor functions. Genotype variation influences phenotype. Our aim was to test the hypothesis that variation in genes that control these functions is associated with gastrointestinal (GI) motor functions in humans with functional GI disorders (FGID). A database of 251 people was assembled by combining genotype data with measurements of gut transit and gastric volumes. Genetic variations evaluated were: alpha(2A) adrenergic (C-1291G), alpha(2C) (Del 332-325), 5-HT transporter (SLC6A4) and GNbeta3 (C825T). We sought associations between motor function or disease groups and genotypes, adjusting for age, gender and body mass index. Among 251 participants, 82 were healthy, 20 with irritable bowel syndrome (IBS) with mixed bowel habit, 49 with constipation-predominant IBS, 67 with diarrhoea-predominant IBS and 33 with functional dyspepsia. For all candidate genes, there was no significant association between motor function and wildtype vs non-wildtype gene status. There were significant interactions between genotype and motility phenotype, specifically GNbeta3 and alpha(2A) and gastric emptying at 4 h. Borderline associations were noted for SCL6A4 and alpha(2A) and postprandial gastric volume, and for alpha(2C) and gastric emptying at 2 h. We conclude that genotype variation may affect gastric motor functions in different FGID phenotypes. However, these candidate genes account for only a limited amount of the variance in gastric function of patients with FGID.

Appetite and obesity: a gastroenterologist's perspective.

This review focuses on the gastrointestinal tract's control of appetite and interventions directed to the gut that are effective in the treatment of obesity. It examines the evidence linking gut hormones to the control of both appetite and upper gastrointestinal motility, the evidence that stomach function is altered and contributes to satiation in obesity and outlines the principles of therapy for obesity which are directed at the gastrointestinal tract. These therapies impair fat absorption or alter stomach functions through pharmacological, device, endoscopic, or surgical approaches. Gastroenterologists need to understand the role of factors controlling appetite in order to effectively manage the increasing number of obese patients and the ways the gut function may be altered as a result of the treatments and their complications.

Effect of a proton pump inhibitor on postprandial gastric volume, emptying and symptoms in healthy human subjects: a pilot study.

BACKGROUND: In consensus guidelines, proton pump inhibitors (PPIs) are recommended for the treatment of functional dyspepsia. It is unclear whether PPIs change gastric volume or emptying. AIM: To assess the effect of a PPI, rabeprazole, on gastric volume and emptying and postprandial symptoms. METHODS: In a double-blind, parallel-group placebo-controlled trial, 13 healthy participants were randomized to rabeprazole, 20 mg b.d., or placebo. On day 3, fasting gastric volume was measured using intravenous (99m)Tc-pertechnate and single photon emission computed tomography (SPECT). After the last dose of study medication, an (111)In-chloride egg meal (300 kcal) was ingested, and postprandial gastric volume and emptying were measured by SPECT. Symptom ratings using a visual analogue scale (fullness, nausea, bloating, abdominal pain, aggregate score) were obtained at baseline and 15, 30, 45, 60 and 75 min postprandially. Group comparisons were performed using Mann-Whitney rank sum test. RESULTS: There were no statistically significant differences in gastric volume or emptying in the two groups. However, there was a borderline increase in gastric volume with rabeprazole compared with placebo. Rabeprazole treatment reduced aggregate postprandial symptoms, particularly fullness, 30 min after the meal (P = 0.01). CONCLUSIONS: In healthy participants, rabeprazole, 20 mg b.d., did not significantly change gastric emptying, but reduced symptoms and had a borderline effect on gastric volume postprandially. The mechanism of reduced postprandial symptoms with a PPI requires further study.

Validation of the Mayo Dysphagia Questionnaire.

While multiple instruments characterize upper gastrointestinal symptoms, a validated instrument devoted to the measurement of a spectrum of esophageal dysphagia attributes is not available. Therefore, we constructed and validated the Mayo Dysphagia Questionnaire (MDQ). The 27 items of the MDQ underwent content validity, feasibility, concurrent validity, reproducibility, internal consistency, and construct validity testing. To assess content validity, five esophageal subspecialty gastroenterologists reviewed the items to ensure inclusion of pertinent domains. Feasibility testing was done with eight outpatients who refined problematic items. To assess concurrent validity, 70 patient responses on the MDQ were compared to responses gathered in a structured patient-physician interview. A separate group of 70 outpatients completed the MDQ twice to assess the reproducibility of each item. A total of 148 patients participated in the validation process (78 [53%] men; mean age 62). On average, the MDQ took 6 minutes to complete. A single item (odynophagia) tested poorly with a kappa value of <0.4. Otherwise, the majority of concurrent validity kappa values were in the good to excellent range with a mean of 0.63 (95% CI 0.22-0.89). The majority of reproducibility kappa values were also in the good to excellent range with a median kappa value of 0.76 (interquartile range: 0.67-0.81). Cronbach's alpha values were excellent in the range of 0.86-0.88. Spearman rank correlation coefficients to assess construct validity were also excellent in the range of 0.87-0.98. Thus, the MDQ is a concise instrument that demonstrates overall excellent concurrent validity, reproducibility, internal consistency, and construct validity for the features of esophageal dysphagia.

Black esophagus: report of six cases and review of the literature, 1963-2003.

Black esophagus is the uncommon endoscopic finding of extensive black discoloration of the esophageal mucosa, usually from acute esophageal necrosis. Six cases of black esophagus were seen at Mayo Clinic (Rochester, Minnesota, USA) from 1997 through 2003, and 46 cases were reported in the English-language literature from 1963 through 2003. We studied the demographics, clinical features, and outcomes of these 52 cases of black esophagus. Age and sex were known for 50 patients: the mean (SD) age was 65 years (19), and 42 patients (84%) were men. Symptoms were known for 51 patients: the most common symptom was upper gastrointestinal tract bleeding, occurring in 40 patients (78%). All 52 patients had at least one comorbid condition (with most having two or more), including duodenal ulcer in 17 (33%), cancer in 15 (29%), renal insufficiency in 15 (29%), and diabetes mellitus in 14 (28%). The suspected cause of black esophagus was reported for 40 patients: ischemia in 22 (55%); massive gastroesophageal reflux in seven (18%); and esophageal infection (Lactobacillus acidophilus, herpes simplex, Candida albicans) in four (10%). Most patients received supportive therapy, particularly acid suppression therapy. Of the 47 patients for whom outcomes were known, 17 (36%) died. There were no statistically significant differences between survivors and non-survivors. Black esophagus typically occurs in older men with at least one comorbid condition; a substantial number of patients die. Although the underlying mechanism leading to black esophagus is unknown, clinicians caring for patients with black esophagus should focus on optimizing perfusion, minimizing acid reflux, and treating esophageal infection if present.