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Background & Aims: Tricyclic antidepressants are effective in reducing symptoms of functional dyspepsia (FD). We performed a post hoc analysis of data from a previous randomized clinical trial to determine whether the benefits of an antidepressant on gastrointestinal symptoms in patients with FD were mediated by improving sleep or reducing anxiety. We explored the relationships between psychological measures, quality of sleep, and relief of symptoms., Methods: We analyzed data from a multicenter, double-blind trial that evaluated the efficacy of antidepressants on symptoms of FD, from October 2006 through October 2012. Patients (n = 292) were randomly assigned to groups given 50 mg amitriptyline, 10 mg escitalopram, or placebo for 12 weeks. During the study, participants completed the following validated psychological questionnaires: Symptom Check List 90, Symptom Somatic Checklist, Hospital Anxiety Depression Scale, Profile of Mood States, State Trait Anxiety Inventory, and Pittsburgh Sleep Quality Index at baseline and 12 weeks following treatment., Results: Baseline scores for the psychological and sleep measures were similar among groups; after 12 weeks there were no significant differences in scores among groups. Baseline mean global Pittsburgh Sleep Quality Index scores indicated poor sleep quality in all groups at baseline and after 12 weeks. Overall, antidepressants affected sleep duration scores: patients given amitriptyline had lower (better) scores than patients given placebo or escitalopram (P = .019). In all groups, responders had decreased anxiety and improvements in some sleep components., Conclusions: In a post hoc analysis of data from a clinical trial that evaluated the effects of antidepressants in patients with FD, amitriptyline was found to reduce symptoms of FD, but its mechanism is unlikely to involve reductions in psychological distress. The drug may modestly improve sleep. Clinicaltrials.gov no: NCT00248651., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Use of immunosuppressants and inflammatory bowel disease (IBD) may increase the risk of pneumonia caused by Pneumocystis jirovecii (PJP). We assessed the risk of PJP in a population-based cohort of patients with IBD treated with corticosteroids, immune-suppressive medications, and biologics., Methods: We performed a population-based cohort study of residents of Olmsted County, Minnesota, diagnosed with Crohn's disease (n = 427) or ulcerative colitis (n = 510) from 1970 through 2011. Records of patients were reviewed to identify all episodes of immunosuppressive therapies and concomitant PJP prophylaxis through February 2016. We reviewed charts to identify cases of PJP, cross-referenced with the Rochester Epidemiology Project database (using diagnostic codes for PJP) and the Mayo Clinic and Olmsted Medical Center databases. The primary outcome was risk of PJP associated with the use of corticosteroids, immune-suppressive medications, and biologics by patients with IBD., Results: Our analysis included 937 patients and 6066 patient-years of follow-up evaluation (median, 14.8 y per patient). Medications used included corticosteroids (520 patients; 55.5%; 555.4 patient-years of exposure), immunosuppressants (304 patients; 32.4%; 1555.7 patient-years of exposure), and biologics (193 patients; 20.5%; 670 patient-years of exposure). Double therapy (corticosteroids and either immunosuppressants and biologics) was used by 236 patients (25.2%), with 173 patient-years of exposure. Triple therapy (corticosteroids, immunosuppressants, and biologics) was used by 70 patients (7.5%) with 18.9 patient-years of exposure. There were 3 cases of PJP, conferring a risk of 0.2 (95% CI, 0.01-1.0) to corticosteroids, 0.1 (95% CI, 0.02-0.5) cases per 100 patient-years of exposure to immunosuppressants, 0.3 (95% CI, 0.04-1.1) cases per 100 patient-years of exposure to biologics, 0.6 (95% CI, 0.01-3.2) cases per 100 patient-years of exposure to double therapy, and 0 (95% CI, 0.0-19.5) cases per 100 patient-years of exposure to triple therapy. Primary prophylaxis for PJP was prescribed to 37 patients, for a total of 24.9 patient-years of exposure., Conclusions: In a population-based cohort of patients with IBD treated with corticosteroids, immunosuppressants, and biologics, there were only 3 cases of PJP, despite the uncommon use of PJP prophylaxis. Routine administration of PJP prophylaxis in these patients may not be warranted, although it should be considered for high-risk groups, such as patients receiving triple therapy., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Bile acids (BAs) are passively absorbed to a different extent along the mammalian colon, so that levels are lower in the feces than in proximal colon. Our aim was to explore associations among total, primary, and secretory BA in stool and colonic transit in patients with irritable bowel syndrome-diarrhea (IBS-D) without overt BA malabsorption (BAM)., Methods: In a cross-sectional observational study of 116 patients with IBS-D recruited from local communities in Minnesota, we measured total and individual main fecal BA excretion, fecal fat and fecal weight over 48 hours, fasting serum levels of C4 (surrogate for BA synthesis), and overall colonic transit by scintigraphy (geometric center at 24 hours and 48 hours). Patients without overt BAM were assigned to groups based on total fecal BA level below 2337 μmol/48 hours (n = 86) or serum levels of C4 below 47.1 ng/mL (n = 91). We used Spearman correlations to test study hypotheses with correction for 14 correlations tested (P < .0036). Data from 30 healthy volunteers were used as control subjects., Results: Patients with IBS-D who had increased or normal total BA excretion in stool or BA synthesis had higher stool proportions of primary BAs (especially chenodeoxycholate), compared with healthy control subjects. In patients with IBS-D without overt BAM (normal 48-hour total fecal BA or serum C4), there were significant positive correlations between total fecal BA, fecal primary and secretory BA, fecal weight, and increased geometric center at 24 and 48 hours (P < .0036). Normal and slightly increased levels of total fecal BA have greatest effects on colonic transit at 48 hours., Conclusions: In the absence of overt BAM, the total, primary, and secretory BAs in stool contribute to the acceleration of colonic transit and fecal weight in the diarrhea of patients with IBS-D., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Contrary to conventional wisdom, the rectoanal gradient during evacuation is negative in many healthy people, undermining the utility of anorectal high-resolution manometry (HRM) for diagnosing defecatory disorders. We aimed to compare HRM and magnetic resonance imaging (MRI) for assessing rectal evacuation and structural abnormalities., Methods: We performed a retrospective analysis of 118 patients (all female; 51 with constipation, 48 with fecal incontinence, and 19 with rectal prolapse; age, 53 ± 1 years) assessed by HRM, the rectal balloon expulsion test (BET), and MRI at Mayo Clinic, Rochester, Minnesota, from February 2011 through March 2013. Thirty healthy asymptomatic women (age, 37 ± 2 years) served as controls. We used principal components analysis of HRM variables to identify rectoanal pressure patterns associated with rectal prolapse and phenotypes of patients with prolapse., Results: Compared with patients with normal findings from the rectal BET, patients with an abnormal BET had lower median rectal pressure (36 vs 22 mm Hg, P = .002), a more negative median rectoanal gradient (-6 vs -29 mm Hg, P = .006) during evacuation, and a lower proportion of evacuation on the basis of MRI analysis (median of 40% vs 80%, P < .0001). A score derived from rectal pressure and anorectal descent during evacuation and a patulous anal canal was associated (P = .005) with large rectoceles (3 cm or larger). A principal component (PC) logistic model discriminated between patients with and without prolapse with 96% accuracy. Among patients with prolapse, there were 2 phenotypes, which were characterized by high (PC1) or low (PC2) anal pressures at rest and squeeze along with higher rectal and anal pressures (PC1) or a higher rectoanal gradient during evacuation (PC2)., Conclusions: In a retrospective analysis of patients assessed by HRM, measurements of rectal evacuation by anorectal HRM, BET, and MRI were correlated. HRM alone and together with anorectal descent during evacuation may identify rectal prolapse and large rectoceles, respectively, and also identify unique phenotypes of rectal prolapse., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Little is known about the cumulative extent of bowel resection among patients with Crohn's disease., Methods: Using the resources of the Rochester Epidemiology Project, we identified a cohort of 310 incident cases of Crohn's disease from Olmsted County, Minnesota who were diagnosed between 1970 and 2004. Operative and pathology reports were reviewed for bowel resection length. Median bowel resection lengths (with interquartile range [IQR]) were calculated per resection, cumulatively, and as a rate per year of follow-up., Results: One hundred forty-seven patients underwent 1 or more bowel resections. The median follow-up time per patient was 13.6 years (range, 0.2-39 years). Among the 141 patients with resection data available, 211 resections were performed (100 patients with 1 resection, 24 with 2 resections, 9 with 3 resections, 6 with 4 resections, 1 with 5 resections, and 1 patient with 7 resections). The median length of bowel resected was 40 cm (IQR, 22-65 cm) at any resection. The median cumulative length of bowel resected was 64 cm (38-93 cm) during the follow-up period. The median (IQR) rate of bowel resected was 4.2 cm total bowel annually (2.8-7.7 cm). The median length resected was highest for the first resection (52 cm; IQR, 32-71 cm). A mixed regression analysis showed that the length of the first resection was significantly greater than that of the second (P = .002), without significant differences between the second and third or subsequent resections., Conclusions: In a population-based cohort of patients with Crohn's disease, the median cumulative length of total bowel resected was 64 cm during the follow-up period; the median rate of bowel loss due to resection was 4.2 cm annually., Competing Interests: No conflicts for Peyrin-Biroulet, Harmsen, Tremaine, or Zinsmeister., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Patients with inflammatory bowel disease (IBD) may be at higher risk for hidradenitis suppurativa (HS). We studied the risk and clinical characteristics of HS in a population-based cohort of patients with IBD., Methods: We identified all cases of HS (confirmed by biopsy and/or dermatologic evaluation) in a population-based inception cohort of Olmsted County, Minnesota, residents diagnosed with IBD between 1970 and 2004 and followed up through August 2013. We estimated the incidence rate ratio of HS in patients with IBD compared with the general population, and described the clinical characteristics, risk factors, and management of HS., Results: In 679 IBD patients followed up over a median of 19.8 years, we identified 8 patients with HS (mean age, 44.4 ± 8.3 y; 7 women; 6 obese). Compared with the general population, the incidence rate ratio of HS in IBD was 8.9 (95% confidence interval, 3.6-17.5). The 10- and 30-year cumulative incidence of HS was 0.85% and 1.55%, respectively. Five patients had Crohn's disease, 4 of whom had perianal disease; of 3 patients with ulcerative colitis, 2 had undergone ileal pouch-anal anastomosis. Axillae, groin, and thighs were the most common sites of involvement. Six patients had Hurley stage 2 disease (recurrent abscesses with sinus tracts and scarring, involving widely separated areas), and required a combination of antibiotics and surgery; none of the patients were treated with anti-tumor necrosis factor-α agents., Conclusions: In this population-based study, patients with IBD were approximately 9 times more likely to develop HS than the general population, with a female predisposition., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Ghrelin receptors are located in the colon. Relamorelin is a pentapeptide selective agonist of ghrelin receptor 1a with gastric effects, but its effects in the colon are not known. We aimed to evaluate the effects of relamorelin on bowel movements (BMs) and gastrointestinal and colonic transit (CT) in patients with chronic constipation., Methods: We performed a study of 48 female patients with chronic constipation who fulfilled the Rome III criteria and had 4 or fewer spontaneous BMs (SBMs)/wk. In a randomized (1:1), double-blind, parallel-group, placebo-controlled trial, the effects of relamorelin (100 μg/d, given subcutaneously) were tested during 14 days after a 14-day baseline, single-blind phase in which patients were given placebo at 2 Mayo Clinic sites. The participants' mean age was 40.6 ± 1.5 y, with a mean body mass index of 25.7 ± 0.6 kg/m(2), with 1.7 ± 0.1 SBM/wk, and a mean stool consistency of 1.2 ± 0.1 on the Bristol scale during this baseline period. The effect of treatment on transit was measured in 24 participants with colonic transit of less than 2.4 (geometric center at 24 h) during the baseline period. Gastric emptying, small-bowel transit, and CT were measured during the last 2 days that patients received relamorelin or placebo. Bowel function was determined from daily diaries kept by patients from days 1 through 28. Study end points were time to first BM, SBMs/wk, complete SBMs/wk, stool form, and ease of stool passage. Effects of relamorelin were assessed by analysis of covariance., Results: Compared with placebo, relamorelin accelerated gastric emptying half-time (P = .027), small-bowel transit (P = .051), and CT at 32 hours (P = .040) and 48 hours (P = .017). Relamorelin increased the number of SBMs (P < .001) and accelerated the time to first BM after the first dose was given (P = .004) compared with placebo, but did not affect stool form. Adverse events associated with relamorelin included increased appetite, fatigue, and headache., Conclusions: Relamorelin acts in the colon to significantly reduce symptoms of constipation and accelerate CT in patients with chronic constipation, compared with placebo. ClinicalTrial.Gov registration number: NCT01781104., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The anal sphincters and puborectalis are imaged routinely with an endoanal magnetic resonance imaging (MRI) coil, which does not assess co-aptation of the anal canal at rest. By using a MRI torso coil, we identified a patulous anal canal in some patients with anorectal disorders. We aimed to evaluate the relationship between anal sphincter and puborectalis injury, a patulous anal canal, and anal pressures., Methods: We performed a retrospective analysis of data from 119 patients who underwent MRI and manometry analysis of anal anatomy and pressures, respectively, from February 2011 through March 2013 at the Mayo Clinic. Anal pressures were determined by high-resolution manometry, anal sphincter and puborectalis injury was determined by endoanal MRI, and anal canal integrity was determined by torso MRI. Associations between manometric and anatomic parameters were evaluated with univariate and multivariate analyses., Results: Fecal incontinence (55 patients; 46%) and constipation (36 patients; 30%) were the main indications for testing; 49 patients (41%) had a patulous anal canal, which was associated with injury to more than 1 muscle (all P ≤ .001), and internal sphincter (P < .01), but not puborectalis (P = .09) or external sphincter (P = .06), injury. Internal (P < .01) and external sphincter injury (P = .02) and a patulous canal (P < .001), but not puborectalis injury, predicted anal resting pressure. A patulous anal canal was the only significant predictor (P < .01) of the anal squeeze pressure increment., Conclusions: Patients with anorectal disorders commonly have a patulous anal canal, which is associated with more severe anal injury and independently predicted anal resting pressure and squeeze pressure increment. It therefore is important to identify a patulous anal canal because it appears to be a marker of not only anal sphincter injury but disturbances beyond sphincter injury, such as damage to the anal cushions or anal denervation., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: YKP10811, a selective agonist of the serotonin 5-hydroxytryptamine-4 receptor, increases gastrointestinal (GI) motility. We investigated the safety and effects of YKP10811 on GI and colonic transit and bowel movements (BMs) in patients with functional constipation in a randomized, double-blind, placebo-controlled study., Methods: Patients with functional constipation, based on the Rome III criteria, were assigned randomly to groups given YKP10811 10 mg (n = 15), 20 mg (n = 16), 30 mg (n = 15), or placebo (n = 11) daily for 8 days. Transit of solids was measured by validated scintigraphy at baseline and on days 7 to 9. Patients kept diaries on days 1 to 9, recording time to first BM, number of BMs/day, and stool consistency (based on the Bristol Stool Form Scale). To evaluate safety, we collected data on adverse events and clinical laboratory test and electrocardiograms results. The primary efficacy end points were determined from an intent-to-treat analysis assessing colonic transit at 24 hours and the half-time (t1/2) of gastric emptying, using analysis of covariance models. Secondary efficacy end points included measures of colonic transit (geometric center at 4 and 24 hours), small-bowel transit (based on colon filling at 6 hours), t1/2 of ascending colon emptying, and bowel functions. We used the Dunnett test to compare the effects of each dose with placebo. A per-protocol analysis (PPA) assessed the t1/2 of gastric emptying and time to first BM using proportional hazards models., Results: Fifty-five participants completed the study. YKP10811 was associated with a significant acceleration in colon filling at 6 hours (P < .05), t1/2 of ascending colon emptying, and colonic transit at 24 and 48 hours, as well as increased stool consistency over 8 days (based on intent-to-treat analysis). In general, the 10-mg and 20-mg doses were the most effective in accelerating colonic transit. No serious adverse events were observed., Conclusions: YKP10811, a selective agonist of the serotonin receptor 5-hydroxytryptamine-4, accelerates GI and colonic transit and improves bowel functions in patients with functional constipation, compared with placebo. ClinicalTrial.Gov: NCT01523184., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Superficial (T1) esophageal adenocarcinoma (EAC) commonly is treated by endoscopic resection, yet little is known about factors that predict outcomes of this approach. We assessed clinical and histologic variables associated with the overall survival times of patients with T1 EAC who received therapy., Methods: In a retrospective analysis, we collected data from patients who underwent endoscopic mucosal resection (EMR) for T1 EAC (194 patients with T1a and 75 patients with T1b) at the Mayo Clinic, from 1995 through 2011. EMR specimens were reviewed systematically for depth of invasion, presence of lymphovascular invasion, grade of differentiation, and status of resection margins. Kaplan-Meier curves and proportional hazards regression models were used in statistical analyses., Results: Demographic characteristics were similar between patients with T1a and T1b EAC. Overall survival at 5 years after EMR was 74.4% for patients with T1a (95% confidence interval [CI], 67.6%-81.8%) and 53.2% for patients with T1b EAC (95% CI, 40.3%-70.1%). Of surviving patients with T1a EAC, 94.1% remained free of cancer (95% CI, 89.8%-98.5%), and 94.7% of surviving patients with T1b EAC remained free of cancer (95% CI, 85.2%-100%). A multivariable model associated older age (per 10-year increment), evidence of lymphovascular invasion, and deep margin involvement with reduced overall survival in patients with T1 EAC., Conclusions: Systematic assessment of EMR specimens can help predict mortality and potentially guide treatment options for patients with T1 EAC., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Little is known about progression of ischemic colitis (IC) among unselected patients. We aimed to estimate the incidence, risk factors, and natural history of IC in a population-based cohort in Olmsted County, Minnesota., Methods: We performed a retrospective population-based cohort and nested case-control study of IC. Each IC case was matched to 2 controls from the same population on the basis of sex, age, and closest registration number. Conditional logistic regression, the Kaplan-Meier method, and proportional hazards regression were used to assess comorbidities, estimate survival, and identify characteristics associated with survival, respectively., Results: Four hundred forty-five county residents (median age, 71.6 years; 67% female) were diagnosed with IC from 1976 through 2009 and were matched with 890 controls. The age-adjusted and sex-adjusted incidence rates of IC nearly quadrupled from 6.1 cases/100,000 person-years in 1976-1980 to 22.9/100,000 in 2005-2009. The odds for IC were significantly higher among subjects with atherosclerotic diseases; odds ratios ranged from 2.6 for individuals with coronary disease to 7.9 for individuals with peripheral vascular disease. Of IC cases, 59% survived for 5 years (95% confidence interval, 54%-64%), compared with 90% of controls (95% confidence interval, 88%-92%). Age >40 years, male sex, right-sided colon involvement, concomitant small bowel involvement, and chronic obstructive pulmonary disease were all independently associated with mortality (P < .05)., Conclusions: The incidence of IC increased during the past 3 decades in a population-based cohort in Minnesota. IC typically presents in older patients with multiple comorbidities and is associated with high in-hospital mortality (11.5%) and rates of surgery (17%)., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Acute hyperglycemia delays gastric emptying in patients with diabetes. However, it is not clear whether improved control of glycemia affects gastric emptying in these patients. We investigated whether overnight and short-term (6 mo) improvements in control of glycemia affect gastric emptying., Methods: We studied 30 patients with poorly controlled type 2 diabetes (level of glycosylated hemoglobin, >9%). We measured gastric emptying using the [(13)C]-Spirulina platensis breath test on the patients' first visit (visit 1), after overnight administration of insulin or saline, 1 week later (visit 2), and 6 months after intensive therapy for diabetes. We also measured fasting and postprandial plasma levels of C-peptide, glucagon-like peptide 1, and amylin, as well as autonomic functions., Results: At visit 1, gastric emptying was normal in 10 patients, delayed in 14, and accelerated in 6; 6 patients had gastrointestinal symptoms; vagal dysfunction was associated with delayed gastric emptying (P < .05). Higher fasting blood levels of glucose were associated with shorter half-times of gastric emptying (thalf) at visits 1 (r = -0.46; P = .01) and 2 (r = -0.43; P = .02). Although blood levels of glucose were lower after administration of insulin (132 ± 7 mg/dL) than saline (211 ± 15 mg/dL; P = .0002), gastric emptying thalf was not lower after administration of insulin, compared with saline. After 6 months of intensive therapy, levels of glycosylated hemoglobin decreased from 10.6% ± 0.3% to 9% ± 0.4% (P = .0003), but gastric emptying thalf did not change (92 ± 8 min before, 92 ± 7 min after). Gastric emptying did not correlate with plasma levels of glucagon-like peptide 1 and amylin., Conclusions: Two-thirds of patients with poorly controlled type 2 diabetes have mostly asymptomatic yet abnormal gastric emptying. Higher fasting blood levels of glucose are associated with faster gastric emptying. Overnight and sustained (6 mo) improvements in glycemic control do not affect gastric emptying., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The increasing incidence of microscopic colitis has been partly attributed to detection bias. We aimed to ascertain recent incidence trends and the overall prevalence of microscopic colitis in a population-based study., Methods: Using data from the Rochester Epidemiology Project, we identified residents of Olmsted County, Minnesota, who were diagnosed with collagenous colitis or lymphocytic colitis from January 1, 2002, through December 31, 2010, based on biopsy results and the presence of diarrhea (N = 182; mean age at diagnosis, 65.8 years; 76.4% women). Poisson regression analyses were performed to evaluate associations between incidence and age, sex, and calendar period., Results: The age- and sex-adjusted incidence of microscopic colitis was 21.0 cases per 100,000 person-years (95% confidence interval [CI], 18.0-24.1 cases per 100,000 person-years). The incidence of lymphocytic colitis was 12.0 per 100,000 person-years (95% CI, 9.6-14.3 per 100,000 person-years) and collagenous colitis was 9.1 per 100,000 person-years (95% CI, 7.0-11.1 per 100,000 person-years). The incidence of microscopic colitis and its subtypes remained stable over the study period (P = .63). Increasing age (P < .001) and female sex (P < .001) were associated with increasing incidence. On December 31, 2010, the prevalence of microscopic colitis was 219 cases per 100,000 persons (90.4 per 100,000 persons for collagenous colitis and 128.6 per 100,000 persons for lymphocytic colitis)., Conclusion: The incidence of microscopic colitis in Olmsted County residents has stabilized and remains associated with female sex and increasing age., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Some women with urge-predominant fecal incontinence (FI) have diarrhea-predominant irritable bowel syndrome and a stiffer and hypersensitive rectum. We evaluated the effects of the α2-adrenergic agonist clonidine on symptoms and anorectal functions in women with FI in a prospective, placebo-controlled trial., Methods: We assessed bowel symptoms and anorectal functions (anal pressures, rectal compliance, and sensation) in 43 women (age, 58 ± 2 y) with urge-predominant FI, randomly assigned to groups given oral clonidine (0.1 mg, twice daily) or placebo for 4 weeks. Before and after administration of the medication, anal pressures were evaluated by manometry, and rectal compliance and sensation were measured using a barostat. Anal sphincter injury was evaluated by endoanal magnetic resonance imaging. Bowel symptoms were recorded in daily and weekly diaries. The primary end point was the FI and Constipation Assessment symptom severity score., Results: FI scores decreased from 9.1 ± 0.3 to 7.6 ± 0.5 among subjects given placebo and from 8.1 ± 0.4 to 6.5 ± 0.6 among patients given clonidine. Clonidine did not affect FI symptom severity, bowel symptoms (stool consistency or frequency), anal pressures, rectal compliance, or sensation compared with placebo. However, when baseline data were used to categorize subjects as those with or without diarrhea, clonidine reduced the proportion of loose stools in patients with diarrhea only (P = .018). Clonidine also reduced the proportion of days with FI in patients with diarrhea (P = .0825)., Conclusions: Overall, clonidine did not affect bowel symptoms, fecal continence, or anorectal functions, compared with placebo, in women with urge-predominant FI. Among patients with diarrhea, clonidine increased stool consistency, with a borderline significant improvement in fecal continence. ClinicalTrials.gov, Number NCT00884832., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Common risk factors for obstructive sleep apnea (OSA) and Barrett's esophagus (BE) include obesity and gastroesophageal reflux disease (GERD). The aims of this study were to assess the association between OSA and BE and to determine whether the association is independent of GERD and body mass index (BMI)., Methods: Patients who had undergone a diagnostic polysomnogram and esophagogastroduodenoscopy were identified by using Mayo Clinic (Rochester, Minnesota) databases from January 2000-November 2011. They were randomly matched for age, sex, and BMI at time of polysomnogram into the following groups: BE but no OSA (n = 36), OSA but no BE (n = 78), both (n = 74), or neither (n = 74). Clinical and demographic variables were abstracted from medical records. The association between OSA and BE was assessed by using a multiple variable logistic model that incorporated age, sex, BMI, clinical diagnosis of GERD, and smoking history., Results: Subjects with OSA had an 80% increased risk for BE compared with subjects without OSA (odds ratio, 1.8; 95% confidence interval, 1.1-3.2; P = .03). These findings were independent of age, sex, BMI, GERD, and smoking history. Increasing severity of OSA, measured by using the apnea-hypopnea index, was associated with an increased risk of BE (odds ratio, 1.2 per 10-unit increase in apnea-hypopnea index; 95% confidence interval, 1.0-1.3; P = .03)., Conclusions: In this case-control study, OSA was associated with an increased risk of BE, potentially through BMI and GERD independent mechanisms. Patients with OSA may benefit from evaluation for BE., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE., Methods: In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m(2)) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale)., Results: At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (Δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P = .005) and 2 hours (P = .019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P = .026); NVFP scores were lower on RM-131 (P = .041). There were no significant adverse effects., Conclusions: RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Clostridium difficile infection (CDI) can cause life-threatening complications. Severe-complicated CDI is characterized by hypotension, shock, sepsis, ileus, megacolon, and colon perforation. We created a model to identify clinical factors associated with severe-complicated CDI., Methods: We analyzed data from 1446 inpatient cases of CDI (48.6% female; median age, 62.5 years; range, 0.1-103.7 years) at the Mayo Clinic from June 28, 2007, to June 25, 2010. Patients with severe-complicated CDI (n = 487) were identified as those who required admission to the intensive care unit or colectomy, or died, within 30 days of CDI diagnosis. Logistic regression models were used to identify variables that were independently associated with the occurrence of severe-complicated CDI in 2 cohorts. One cohort comprised all hospitalized patients; the other comprised a subset of these inpatients who were residents of Olmsted County, Minnesota to assess the association of comorbid conditions with the development of severe-complicated infection in a population-based cohort. The linear combinations of variables identified by using logistic regression models provided scores to predict the risk of developing severe-complicated CDI., Results: In a multivariable model that included all inpatients, increasing age, leukocyte count >15 × 10(9)/L, increase in serum level of creatinine >1.5-fold from baseline, and use of proton pump inhibitors or narcotic medications were independently associated with severe-complicated CDI. In the secondary analysis, which included only patients from Olmsted County, comorbid conditions were not significantly associated with severe-complicated CDI., Conclusions: Older age, high numbers of leukocytes in blood samples, an increased serum level of creatinine, gastric acid suppression, and use of narcotic medications were independently associated with development of severe-complicated CDI in hospitalized patients. Early aggressive monitoring and intervention could improve outcomes., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: There is an unclear relationship among bowel symptoms, excretion of unconjugated fecal bile acid (UBA), and colonic transit in irritable bowel syndrome (IBS). We measured total and main individual UBA in fecal samples of patients with IBS and assessed relationships among stool frequency or consistency, fecal UBA (total and individual), and colonic transit., Methods: In this study 30 healthy volunteers (controls), 31 subjects with IBS with diarrhea (IBS-D), and 30 with IBS with constipation (IBS-C) were placed on 4-day diets containing 100 g fat; we measured stool characteristics, total fecal UBA and fat levels, and overall colonic transit. We assessed univariate associations of total and individual levels of fecal UBA with phenotype (controls, IBS-D, IBS-C) by using the Kruskal-Wallis test; associations between end points were assessed by using Spearman correlations. With response surface regression models, we assessed relationships between stool, colonic transit, and fecal total and secretory UBA., Results: There was a significant association between total fecal UBA and phenotype (P = .029); the association was greater for IBS-D than IBS-C, compared with controls. Fecal levels of primary UBAs (cholic and chenodeoxycholic acids) were higher in subjects with IBS-D, compared with controls (both P < .01). Levels of fecal secretory UBAs (chenodeoxycholic acid, P = .019; deoxycholic acid, P = .025) were lower in subjects with IBS-C compared with controls, whereas levels of the nonsecretory UBA, lithocholic acid, were higher (P = .020). There were significant univariate associations between stool number and form and total fecal UBA (including percentages of lithocholic acid, chenodeoxycholic acid and cholic acid), fecal fat, and colonic transit at 24 and 48 hours after eating. In the regression models, the relative contribution of colonic transit was consistently greater and largely independent of the contribution of bile acids., Conclusions: Measurements of individual UBAs identify changes associated with stool characteristics in patients with IBS; these effects are independent of the effects of colonic transit., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Endoscopic healing is likely to become an important goal for treatment of patients with ulcerative colitis (UC). A simple validated endoscopic index is needed. We validated the previously developed UC Colonoscopic Index of Severity (UCCIS)., Methods: In a prospective study, 50 patients with UC were examined by colonoscopy; we analyzed videos of rectum and sigmoid, descending, transverse, and cecum/ascending colon. Eight gastroenterologists blindly rated 4 mucosal lesions (for vascular pattern, granularity, friability, ulceration) and severity of damage to each segment and overall. The global assessment of endoscopic severity (GAES) was based on a 4-point scale and 10-cm visual analogue scale. Correlation of the UCCIS score with clinical indexes (clinical activity index and simple clinical colitis activity index), patient-defined remission, and laboratory measures of disease activity (levels of C-reactive protein, albumin, and hemoglobin and platelet counts) were estimated by using the Pearson (r) or Spearman (r(s)) method., Results: Interobserver agreement was good to excellent for the 4 mucosal lesions evaluated by endoscopy and the GAES. The UCCIS calculated for our data accounted for 74% (R(2) = 0.74) and 80% (R(2) = 0.80) of the variation in the GAES and visual analogue scores, respectively (P < .0001). The UCCIS also correlated with clinical activity index (r = 0.52, P < .001), simple clinical colitis activity index (r = 0.62, P < .0001), and patient-defined remission (r = 0.43, P < .01). The UCCIS also correlated with levels of C-reactive protein (r(s) = 0.56, P < .001), albumin (r = -0.55, P < .001), and hemoglobin (r = -0.39, P < .01). A rederivation of the equation for the UCCIS by using the data from a previous study combined with those of the current study (n = 101) yielded similar results., Conclusions: The UCCIS is a simple tool that provides reproducible results in endoscopic scoring of patients with UC., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Crohn's disease often involves the terminal ileum (TI), but skipping of the distal TI can occur. This can lead to negative results from ileocolonoscopy. We analyzed advanced cross-sectional images to determine how frequently this occurs., Methods: We analyzed data from 189 consecutive patients (55% women) with Crohn's disease, evaluated in 2009 by computed tomography enterography (CTE) and ileocolonoscopy. The discharge impression of the gastroenterologist who treated the patients was used as the reference standard for Crohn's disease activity., Results: Of the patients evaluated, 153 underwent TI intubation during endoscopy; 67 of these (43.8%) had normal results from ileoscopy, based on endoscopic appearance. Despite their normal results from ileoscopy, 36 of these patients (53.7%) had active, small-bowel Crohn's disease. The ileum appeared normal at ileoscopy because the disease had skipped the distal ileum of 11 patients (30.6%), developed only in the intramural and mesenteric distal ileum of 23 patients (63.9%), and appeared only in the upper gastrointestinal region of 2 patients (5.6%). These patients had a shorter duration of disease (61.1% for less than 5 years) compared with those found to have Crohn's disease based on ileoscopy (41.1% for less than 5 years; P < .05). CTE detected extracolonic Crohn's disease in 26% of patients; 14% of patients were found to have disorders unrelated to inflammatory bowel disease that warranted further investigation or consultation (including 4 cancers)., Conclusions: Ileoscopy examination can miss Crohn's disease of the TI because the disease can skip the distal ileum or is confined to the intramural portion of the bowel wall and the mesentery. CTE complements ileocolonoscopy in assessing disease activity in patients with Crohn's disease., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Variations in genes that regulate bile acid (BA) synthesis are associated with colonic transit in patients with irritable bowel syndrome (IBS). We investigated features of BA synthesis and excretion and genetic features of patients with different types of IBS., Methods: In 26 healthy volunteers, 26 patients with IBS and constipation (IBS-C), and 26 with IBS and diarrhea (IBS-D), we measured serum levels of 7α-hydroxy-4-cholesten-3-one (C4; a surrogate for BA synthesis) and fibroblast growth factor (FGF) 19 (an ileal hormone that downregulates BA synthesis). For stool samples, we measured concentration of BA, weight, and amount of fat when participants were given high-fat diets. Spearman correlations were used to explore relationships among factors. We analyzed 1 polymorphism in Klotho-β (KLB) and 3 in fibroblast growth factor receptor-4 (FGFR4) for all members of each group using analysis of covariance., Results: The concentration of BA in stool was associated with group (for a comparison of 3 groups; P = .057); it was higher in patients with IBS-D than IBS-C (P = .017). The serum level of C4 was higher in patients with IBS-D than IBS-C (P = .02) or healthy volunteers (P = .01); 38% of patients with IBS-D had increased serum levels of C4, compared with healthy volunteers. Serum level of C4 correlated with stool concentration of BA (rs = 0.606; P < .001), serum FGF19 (rs = -0.324; P = .007), and stool weight (rs = 0.366; P = .003). Stool concentration of BA correlated with weight (rs = 0.737; P < .001) and level of fat (rs = 0.528; P < .001). Body mass index correlated with serum level of C4 (rs = 0.423, P < .001) and stool concentration of BA (rs = 0.507, P < .001), and was higher in patients with IBS-D compared with other groups (overall P = .036). FGFR4 rs1966265 was associated with stool level of BA (P = .032)., Conclusions: Patients with IBS-D have greater body mass index and synthesize and excrete higher levels of BA than individuals with IBS-C or healthy volunteers. Serum levels of C4 might be used to identify patients with IBS-D who have BA malabsorption; studies are needed to determine if some patients have a genetic predisposition to this disorder., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The prevalence of chronic constipation (CC) has been reported to be as high as 20% in the general population, but little is known about its natural history. We estimated the natural history of CC and characterized features of persistent CC and nonpersistent CC, compared with individuals without constipation., Methods: In a prospective cohort study, we analyzed data collected from multiple, validated surveys (minimum of 2) of 2853 randomly selected subjects, over a 20-year period (median, 11.6 years). Based on responses, subjects were characterized as having persistent CC, nonpersistent CC, or no constipation. We assessed the association between constipation status and potential risk factors using logistic regression models, adjusting for age and sex., Results: Of the respondents, 84 had persistent CC (3%), 605 had nonpersistent CC (21%), and 2164 had no symptoms of constipation (76%). High scores from the somatic symptom checklist (odds ratio [OR] = 2.1; 95% confidence interval [CI], 1.3-3.4) and frequent doctor visits (OR = 2.0; 95% CI, 1.0-3.8) were significantly associated with persistent CC, compared with subjects with no constipation symptoms. The only factor that differed was increased use of laxatives or fiber among subjects with persistent CC (OR = 3.0; 95% CI, 1.9-4.9)., Conclusions: The prevalence of constipation might be exaggerated-the proportion of the population with persistent CC is low (3%). Patients with persistent and nonpersistent CC have similar clinical characteristics, although individuals with persistent CC use more laxatives or fiber. CC therefore appears and disappears among certain patients, but we do not have enough information to identify these individuals in advance., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Upper abdominal pain (UAP) in patients with gallstones is often treated by cholecystectomy but it frequently persists. We aimed to identify symptoms associated with relief., Methods: We followed 1008 patients who received cholecystectomy for gallstones and UAP at the Mayo Clinic (Rochester, Minnesota) or Kaiser Permanente (San Diego, California) for 12 months. A validated, self-completed biliary symptoms questionnaire identified features of UAP, gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS); the questionnaire was given initially and 3 and 12 months after cholecystectomy, to identify features that predicted sustained relief of UAP., Results: Five hundred ninety-four patients (59%) reported relief from UAP. Factors associated univariately (P < .05) with relief included frequency of UAP ≤1 per month, onset ≤1 year preoperatively, usual duration (30 minutes to 24 hours, most often in the evening or night), and severity >5/10. Compared to no features, multiple predictive features of UAP (frequency, onset, duration, or timing) were associated with increasing odds ratios (95% confidence interval) for relief: 1, 2, or 3 features (4.2 [1.1-16]; P = .03) and 4 features (6.3 [1.6-25]; P = .008). Negative univariate associations included lower abdominal pain (LAP), usual bowel pattern, nausea ≥1 per week, often feeling bloated or burpy, GERD, and/or IBS. There was an inverse association between relief and somatization; relief was not associated with postprandial UAP. Multivariable logistic regression analysis revealed independent associations (P < .05) with UAP frequency, onset, and nocturnal awakening, but inverse associations with lower abdominal pain, abnormal bowel pattern, and frequent bloated or burpy feelings., Conclusions: UAP features and concomitant GERD, IBS, and somatization determine the odds for relief from UAP after cholecystectomy., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Eosinophilic gastroenteritis (EG) is a rare disorder characterized by eosinophilic infiltration of the gastrointestinal (GI) tract. Despite the increasing prevalence of eosinophilic GI disorders, the epidemiology of EG has not been well studied. We evaluated the clinical spectrum of EG., Methods: We reviewed data from patients diagnosed with EG, allergic gastroenteropathy, or eosinophilia and referred to gastroenterologists from 1987 to 2007 (n = 59; 52 with mucosal, 3 with muscularis, and 4 with subserosal disease). The study included subjects diagnosed with EG and those with a history that suggested EG, defined by GI symptoms; eosinophilic infiltration of the GI tract, eosinophilic ascites, or characteristic radiographic findings with eosinophilia; and no parasitic or extraintestinal disease. Findings were compared with those from patients with unexplained GI symptoms and peripheral eosinophilia (n = 11)., Results: Associations between clinical variables and EG subgroups did not differ between patients with EG and peripheral eosinophilia. Fifty percent of patients with EG who underwent food allergy testing had a positive test result; only 32% of those with EG who underwent radiographic imaging had positive test results. Patients with EG received steroid therapy; 75% with mucosal, 67% with muscle, and 100% with subserosal disease received prednisone. Eighty-eight percent of patients who received only steroids (mean follow-up period, 7 mo) and 94% of patients who received steroids in combination with another therapy (mean follow-up period, 4 mo) had improved or resolved disease., Conclusions: Unlike eosinophilic esophagitis, EG is rare. Results from this large study suggest that EG disease type has shifted toward that of the mucosal layer., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Di-alpha hydroxy bile salt, sodium chenodeoxycholate (CDC), and bile acid binding have unclear effects on colonic transit in health and disease., Methods: We performed 2 randomized, double-blind, placebo-controlled studies. In healthy volunteers (20 per group), we evaluated the effects of oral placebo, 500 mg, or 1000 mg of CDC (delayed-release, each given for 4 days) on gastrointestinal and colonic transit. A second trial compared the effects of colesevelam (1.875 g, twice daily) versus placebo in 24 patients (12 per group) with diarrhea-predominant irritable bowel syndrome (IBS-D) on transit, daily bowel frequency and consistency, and colonic mucosal permeability. Serum fasting 7alpha-hydroxy-4-cholesten-3-one (7alphaC4) was measured to screen for bile acid malabsorption. Effects of treatments on transit were compared using analysis of covariance with body mass index and 7alphaC4 as covariates., Results: In healthy volunteers, CDC significantly accelerated colonic transit (at 24 and 48 hours, P = .01 and P < .0001, respectively), increased stool frequency and ease of passage (both P < .001), and evacuation (P = .02), and decreased stool consistency (P < .001). Four of the 24 IBS-D patients had increased serum 7alphaC4 levels. In IBS-D, colesevelam modestly affected overall colonic transit (24 h; P = .22). Emptying of the ascending colon took an average of 4 hours longer in patients given colesevelam compared with placebo; treatment effect was associated with baseline serum 7alphaC4 levels (P = .0025). Colesevelam was associated with greater ease of stool passage (P = .048) and somewhat firmer stool consistency (P = .12). No effects on mucosal permeability or safety were identified., Conclusions: Sodium chenodeoxycholate in health and colesevelam in IBS-D patients have opposite effects on colonic transit and fecal parameters., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Data on secular trends and outcomes of eosinophilic esophagitis (EE) are scarce. We performed a population-based study to assess the epidemiology and outcomes of EE in Olmsted County, Minnesota, over the last 3 decades., Methods: All cases of EE diagnosed between 1976 and 2005 were identified using the Rochester Epidemiology Project resources. Esophageal biopsies with any evidence of esophagitis and/or eosinophilic infiltration were reviewed by a single pathologist. Clinical course (treatment, response, and recurrence) was defined using information collected from medical records and prospectively via a telephone questionnaire. Incidence rates per 100,000 person years were directly adjusted for age and sex to the US 2000 population structure., Results: A total of 78 patients with EE were identified. The incidence of EE increased significantly over the last 3 of the 5-year intervals (from 0.35 [95% confidence interval (CI)], 0-0.87] per 100,000 person-years during 1991-1995 to 9.45 [95% CI, 7.13-11.77] per 100,000 person-years during 2001-2005). The prevalence of EE was 55.0 (95% CI, 42.7-67.2) per 100,000 persons as of January 1, 2006, in Olmsted County, Minnesota. EE was diagnosed more frequently in late summer/fall. The clinical course of patients with EE was characterized by recurrent symptoms (observed in 41% of patients)., Conclusions: The prevalence and incidence of EE is higher than previously reported. The incidence of clinically diagnosed EE increased significantly over the last 3 decades, in parallel with endoscopy volume. Seasonal incidence was greatest in late summer and fall. EE also appears to be a recurrent relapsing disease in a substantial proportion of patients.

Background & Aims: It is not clear what proportion of synchronous or metachronous colorectal cancers (CRCs) are associated with DNA mismatch repair (MMR) alterations or unsuspected Lynch syndrome. On the basis of tissue analyses, the aims were to evaluate DNA MMR expression in metachronous, synchronous, and isolated sporadic CRCs and to assess within-patient concordance of MMR expression in metachronous and synchronous CRCs., Methods: Tissue was evaluated from 34 patients with metachronous CRC, 34 matched solitary CRC patients, and 40 patients with synchronous CRCs. Subjects with known hereditary CRC were excluded. Immunohistochemical staining for MLH1 and MSH2 was performed on all tissues., Results: Absent MLH1 or MSH2 staining of the initial metachronous tumor was observed in 27% compared with 21% of control CRCs, P = .58. The odds of metachronicity with absent immunostaining were 1.33 (95% confidence interval, 0.46-3.84). Loss of MMR expression was observed in at least one cancer in 30% of patients with synchronous CRC. MMR expression loss was discordant in 70% of metachronous CRCs and 50% of synchronous CRCs. Lynch syndrome was subsequently diagnosed in 2 patients with synchronous CRCs, both with concordant tumor MMR loss but in no patient with metachronous CRC., Conclusions: Among those without known Lynch syndrome, development of multiple primary CRCs appears to be due largely to somatic events and often occurs via different molecular pathways within the same patient. Altered MMR expression in sporadic CRC has low predictive value for metachronicity. MMR expression analysis in cases of multiple primary CRC might identify a small number of patients with unsuspected Lynch syndrome.

Background & Aims: The quantitative relationships between instruments and assays that measure clinical, endoscopic, and biologic disease activity in patients with Crohn's disease are poorly characterized. This study evaluated the correlations between the Crohn's Disease Activity Index (CDAI), the Simple Endoscopic Score for Crohn's Disease (SES-CD), serum high-sensitivity C-reactive protein (hsCRP) (both phenotype and genotype) and interleukin-6 (IL-6), and fecal calprotectin and lactoferrin., Methods: A total of 164 patients with Crohn's disease undergoing colonoscopy were enrolled. The CDAI and SES-CD scores, serum hsCRP and IL-6, CRP and IL-6 genotypes, and fecal calprotectin and lactoferrin were measured., Results: There were no significant associations between the CDAI and SES-CD scores (Spearman rank correlation coefficient, 0.15) or between the CDAI scores and the serum concentrations of hsCRP and IL-6, or the fecal concentrations of calprotectin and lactoferrin. In contrast, the serum hsCRP and IL-6 concentrations and the fecal calprotectin and lactoferrin concentrations were significantly higher in patients with more severe endoscopic disease activity (SES-CD score > 7 points) (P < .001 for all comparisons). The CRP 717 mutant homozygote and heterozygote status was associated with significantly lower concentrations of hsCRP (P = .02). There was a trend toward higher hsCRP concentrations in the CRP 286 heterozygous adenine mutant-type mutant genotype, but this did not reach statistical significance., Conclusions: Serum and fecal biomarker concentrations are associated with endoscopic but not clinical disease activity in patients with Crohn's disease. Stimulated hsCRP concentration is affected significantly by select genetic polymorphisms.

Background & Aims: There is an elevated prevalence of celiac disease (CD) in family members (FMs) of CD patients, but most prior studies have been done on selected populations. Our aim was to determine the clinical, serologic, and genetic predictors of CD in FMs of a population-based cohort of index cases., Methods: Index cases from southeast Minnesota provided contact information for their first-degree relatives. FMs were examined for endomysial antibodies (EMAs), tissue transglutaminase antibodies (tTGAs), and HLA-DQ genotyping. Two questionnaires were applied, Bowel Disease Questionnaire and Short Form Health Survey. Intestinal biopsies were offered if there were any positive autoantibody or seronegative FMs with gastrointestinal symptoms and HLA-DQ at risk for CD., Results: We recruited 111 index cases that had 579 FMs, of whom 344 (59%) were investigated. The average screening rate among families was 65%. A positive tTGA test was found in 47 (14%), 33 with a positive EMA test. CD was diagnosed in 39 (21 males), with an estimated prevalence of 11% (lambda(R) = 16.1). All affected FMs carried the at-risk genotypes. Twenty-one (54%) had "silent" disease, most with severe intestinal villous atrophy. Carrying HLA-DQ2 (odds ratio, 16.1; 95% confidence interval, 2.1-123) and being a sibling (odds ratio, 2.5; 95% confidence interval, 1.1-5.8) are high-risk factors for CD., Conclusions: CD is more common in first-degree relatives than previously reported in the United States, with siblings having the greatest risk. There is male preponderance of new cases, and many had silent disease despite severe histologic injury. A more proactive case-finding strategy in FMs might improve the diagnostic rate of CD in North America.

Background & Aims: The aim of this study was to assess pathophysiology in irritable bowel syndrome (IBS)., Methods: A total of 122 IBS patients (3 male) and 41 healthy females underwent the following: questionnaires (symptoms, psychology), autonomic function, gut transit, gastric volumes, satiation, rectal compliance, and sensation (thresholds and pain ratings) testing. Proportions of patients with abnormal (<10th and >90th percentiles) motor or sensory functions according to bowel symptoms (constipation [C], diarrhea [D], mixed [M),) pain/bloat, and number of primary symptoms were estimated., Results: IBS subgroups (C, D, M) were similar in age, gastric and small-bowel transit, satiation, gastric volumes, rectal compliance, sensory thresholds, and pain ratings. IBS was associated with body mass index, somatic symptoms, and anxiety and depression scores. Significant associations were observed with colonic transit (IBS-C [P = .078] and IBS-D [P < .05] at 24 h; IBS-D [P < .01] and IBS-M [P = .056] at 48 h): 32% of IBS patients had abnormal colonic transit: 20.5% at 24 hours and 11.5% at 48 hours. Overall, 20.5% of IBS patients had increased sensation to distensions: hypersensitivity (<10th percentile thresholds) in 7.6%, and hyperalgesia (pain sensation ratings to distension >90th percentile for ratings in health) in 13%. Conversely, 16.5% of IBS patients had reduced rectal sensation. Pain greater than 6 times per year and bloating were not associated significantly with motor, satiation, or sensory functions. Endorsing 1 to 2 or 3 to 4 primary IBS symptoms were associated with abnormal transit and sensation in IBS., Conclusions: In tertiary referral (predominantly female) patients with IBS, colonic transit (32%) is the most prevalent physiologic abnormality; 21% had increased and 17% had decreased rectal pain sensations. Comprehensive physiologic assessment may help optimize management in IBS.

Background & Aims: The aim of this study was to validate a [13C]-Spirulina platensis gastric emptying (GE) breath test (GEBT) with a standardized meal., Methods: Thirty-eight healthy volunteers and 129 patients with clinically suspected delayed GE underwent measurements at 45, 90, 120, 150, 180, and 240 minutes after a 238 kcal meal labeled test with 100 mg [13C]-S platensis and 0.5 mCi 99mTc. We established normal ranges for scintigraphy with this test meal, intraindividual and interindividual coefficients of variation (COVs), and the ability of the [13C] GEBT breath percent dose excreted *1000 values to predict scintigraphic half-life and to categorize GE as delayed, normal, or accelerated., Results: In health, the 10th and 90th percentiles of half-life for scintigraphic GE with this meal were 52 and 86 minutes; intraindividual COVs for scintigraphy and the GEBT were, respectively, 31% and 27% at 45 minutes, 17% and 21% at 90 minutes, 13% and 16% at 120 minutes, 10% and 13% at 150 minutes, and 8% and 12% at 180 minutes. Interindividual COVs at each time for the [13C] GEBT and scintigraphy were typically approximately 1%-4% lower than intraindividual COVs. Individual breath samples at 45, 150, and 180 minutes predicted GE category; at 80% specificity, 45- and 180-minute samples combined were 93% sensitive to identify accelerated GE, and 150- and 180-minute combined were 89% sensitive for delayed GE., Conclusions: [13C]-S platensis GEBT is as reproducible as scintigraphy; imprecision with both tests reflects physiologic variation. With 4 breath samples, this method with an off-the-shelf meal is valid to assess GE in clinic and in research.

Background & Aims: Wireless capsule endoscopy provides an opportunity to study the macroscopic features in celiac disease by providing a magnified view of the intestinal mucosa. In this study, we evaluated the following: (1) the distribution of atrophy in untreated celiac disease, (2) the correlation between extent of changes and clinical manifestations, (3) the accuracy and interobserver agreement of wireless capsule endoscopy assessment, and (4) the effect of gluten withdrawal., Methods: Thirty-eight consecutive patients with untreated biopsy-proven celiac disease underwent wireless capsule endoscopy. Each subject was invited to undergo repeat testing after at least 6 months of gluten withdrawal. The video images of each patient were reviewed independently by 2 investigators., Results: Thirty-five (92%) subjects had visible atrophy detected by capsule endoscopy. Twenty-two (59%) subjects showed an extensive enteropathy, 12 (32%) had enteropathy limited to the duodenum, and only 1 had a jejunal enteropathy. No association was shown between the extent of the lesion and clinical manifestations. Capsule endoscopy had a better overall sensitivity for the detection of atrophy as compared with upper endoscopy (92% vs 55%, P = .0005), with a specificity of 100%. The overall interobserver agreement for the 2 reviewers was relatively high (% total agreement, 86.5%). After gluten withdrawal, the extent and the pattern of atrophy improved both qualitatively and quantitatively., Conclusions: Celiac disease affects a highly variable portion of the small intestine starting at the duodenum. The extent of visible enteropathy does not explain differences in clinical presentation. Most subjects with visually detected villous atrophy showed a clinically significant improvement after gluten withdrawal.

Background & Aims: Celiac disease (CD) is a chronic inflammatory disorder of the small intestine that is strongly associated with certain HLA molecules encoded by DQA and DQB genes. The aim of this study was to examine the role of DQA and DQB alleles in determining the risk for and the age of onset and severity of CD in an American population., Methods: High-resolution class 2 HLA genotyping was performed in a population-based sample (n = 84) of southeastern Minnesota residents with CD and a comparable control group (n = 102) to determine the contribution of DQA and DQB alleles to disease risk. Logistic regression modeling was used to examine the relative and absolute risks of CD., Results: Ninety-seven percent of CD patients carried both of the HLA alleles, DQA1*05 and DQB1*02. Those who carried a second allele of DQB1*02 were 5 times more likely to have CD than those with just one (95% confidence interval, 1.4-18.1). The carriage of 2 copies of DQB1*02 did not predict either an earlier age of onset or severity of disease., Conclusions: Both HLA alleles DQA1*05 and DQB1*02 are associated with a greatly increased risk of CD, although the latter has the greater effect. Carrying 2 copies of DQB1*02 was associated with an even greater risk for disease but did not predict an earlier age of onset and diagnosis or disease severity. Assessing the copy number of the DQB1*02 allele might allow for the stratification of disease risk.

Background & Aims: In experimental animal models of irritable bowel syndrome (IBS) and human studies, peripheral kappa opioid agonists have been shown to decrease sensation to colonic distention. The aim of this study was to compare the effects of the kappa opioid agonist, asimadoline, and placebo on episodes of abdominal pain in patients with IBS., Methods: After a 2-week run-in period, 100 patients with IBS were randomized (3:2 ratio) to receive asimadoline, up to 1 mg 4 times daily, or placebo for 4 weeks in a double-blind study. Pain was scored by daily diary using a 100-mm visual analogue scale. During pain episodes, patients recorded the pain severity, took study medication, and recorded their pain score 2 hours later. The primary end point was the average reduction in pain severity 2 hours after treatment., Results: The average pain reduction 2 hours posttreatment was not significantly different between the groups. Post hoc analyses suggest asimadoline was effective in mixed IBS (P = .003, unadjusted), but may be worse in diarrhea-predominant IBS (P = .065 unadjusted). The anxiety score was reduced modestly by asimadoline (P = .053). No significant adverse effects were noted., Conclusions: An on-demand dosing schedule of asimadoline was not effective in reducing severity of abdominal pain in IBS. Further studies in visceral pain and IBS appear warranted.

Background & Aims: Functional abnormalities of the duodenum have been observed in non-ulcer dyspepsia. We aimed to identify whether eosinophils in the upper gastrointestinal tract are a biomarker for non-ulcer dyspepsia., Methods: A random sample of an adult Swedish population (n = 1001; mean age, 54 y; 51% female) underwent upper endoscopy. Non-ulcer dyspepsia cases (n = 51, Rome II) and randomly selected controls (n = 48) were identified. Two blinded independent observers assessed the gastroduodenal eosinophil counts. Eosinophils were quantified by counting the number per 5 high-power fields at each of 5 sites (cardia, body, antrum, D1 duodenal bulb, and D2 second portion of duodenum), and total counts were summed over the 5 fields at each site., Results: The odds ratio for non-ulcer dyspepsia (vs asymptomatic controls) in subjects with high duodenal bulb eosinophil counts (median, >/=22, relative to <22) was 11.7 (95% confidence interval, 3.9-34.9), adjusting for age, sex, and H pylori; similar results were observed in D2 (odds ratio = 7.3; 95% confidence interval, 2.9-18.1). A significant association with the number of eosinophil clusters was detected in the duodenum, with higher values in non-ulcer dyspepsia (P < .01). By immunostaining with major basic protein antibody in a subset of duodenal biopsy specimens, eosinophil degranulation was observed in non-ulcer dyspepsia (7 of 15 vs 0 of 5 controls; P = .11). Gastric eosinophil counts were overall not significantly increased in non-ulcer dyspepsia vs controls. Early satiety was associated with eosinophilia in D1 (P = .01) and D2 (P = .02), adjusting for age, sex, and H pylori., Conclusions: Duodenal eosinophilia may characterize a subset of adults with non-ulcer dyspepsia.

Background & Aims: It is unclear whether weight loss with the noradrenergic (norepinephrine) and serotonergic (5-hydroxytryptamine) reuptake inhibitor, sibutramine, is associated with altered stomach functions and whether genetics influence treatment response., Methods: Forty-eight overweight and obese but otherwise healthy participants were randomized to placebo or sibutramine (15 mg/day for 12 weeks). At baseline and posttreatment we measured the following: gastric emptying for solids and liquids by scintigraphy, gastric volumes by single-photon emission computed tomography, maximum tolerated volume and 30-minute postnutrient challenge symptoms, and selected gastrointestinal hormones. All participants received structured behavior therapy for weight management. The influence of candidate gene polymorphisms involved in norepinephrine and 5-hydroxytryptamine or receptor function (phenylethanolamine N-methyltransferase, guanine nucleotide binding protein beta polypeptide 3, alpha2A adrenoreceptor, and solute carrier family 6 [neurotransmitter transporter, serotonin] member 4 [homo sapiens] [SLC6A4]) on weight loss and gastric functions was evaluated., Results: The overall average weight loss posttreatment was 5.4 +/- 0.8 (SEM) kg with sibutramine and 0.9 +/- 0.9 kg with placebo (P < .001). The sibutramine group showed significant retardation in gastric emptying of solids (P = .03), reduced maximum tolerated volume (P = .03), and increased postprandial peptide YY compared with the placebo group. Obese females showed greater effects of sibutramine on weight loss and gastric emptying of solids and liquids. Gastric volumes and postchallenge symptoms were not significantly different in the 2 treatment groups. The LS/SS genotype of the promoter for SLC6A4 was associated with enhanced weight loss with sibutramine., Conclusions: Weight reduction with sibutramine is associated with altered gastric functions and increased peptide YY and is significantly associated with SLC6A4 genotype. The role of genetic variation in SLC6A4 on weight loss in response to sibutramine deserves further study.

Background & Aims: Guidelines for reporting Barrett's esophagus and hiatal hernia measurements and reflux esophagitis grades have been developed to improve consistency, communication, and, ultimately, patient care. Our aims were to assess the percentage of cases in which findings were reported in accordance with guidelines and to assess the impact of education and feedback on reporting behavior., Methods: Prospective cross-sectional study design was used. Chart reviews were performed for all adult patients who underwent esophagogastroduodenoscopy at a tertiary care center during three 2-month time periods during a 12-month interval: Time 1 (March 1, 2004-April 30, 2004), Time 2 (July 1, 2004-August 31, 2004), and Time 3 (March 1, 2005-April 30, 2005). Standardized educational sessions began 2 years before Time 1. No intervention took place between Time 1 and Time 2; data were collected to examine secular change. Between Time 2 and Time 3, individual and group feedback and refresher sessions were given., Results: Five thousand six hundred nine eligible esophagogastroduodenoscopies were performed, of which 2675 demonstrated Barrett's esophagus, hiatal hernia, and/or reflux esophagitis. At baseline, Barrett's esophagus and hiatal hernia measurements were dictated correctly in a median of 67% and 86% of cases, respectively, improving to 100% (P < .05) and 98% (P < .01) of cases, respectively. The Los Angeles Classification system was used in a median of 100% of cases at baseline and at follow-up., Conclusions: Anonymous individual and group feedback, in combination with brief, structured didactic educational sessions, significantly improves compliance with established guidelines for the reporting of Barrett's esophagus and hiatal hernia. Once successfully incorporated into clinical practice, adherence to the esophagitis Los Angeles Classification System is easy to maintain.

Background & Aims: Assessments of symptom severity are necessary to guide therapy in fecal incontinence (FI). However, there is no consensus on how self-reported symptom severity in FI should be measured for this purpose, and the relationship between symptoms of FI and its impact on quality of life (QOL) is not known., Methods: A questionnaire was mailed to an age-stratified random sample of 5300 women identified through the Rochester Epidemiology Project. Symptom severity was assessed by a validated scale (Fecal Incontinence and Constipation Assessment [FICA]), and impact on 15 domains of QOL was evaluated for subjects who had any FI during the past year. The scale incorporated the type, frequency, and amount of FI, as well as the circumstances surrounding FI (ie, urge or passive FI). A QOL-weighted symptom severity score was derived by weighting the responses for these characteristics, in each subject, by the average QOL impact for all subjects who reported that specific symptom characteristic. The relationship between symptom severity and the QOL-weighted symptom severity score was assessed by Spearman rank correlation., Results: Altogether, 2800 of 5300 (53%) women responded to the survey. FI symptoms were mild (45%), moderate (50%), or severe (5%). Among women with FI, the FICA symptom severity scale was strongly correlated (r(s) = 0.92, P < .0001) with the QOL-weighted symptom severity score., Conclusions: Among unselected women in the community, self-reported symptom severity, rated by the FICA scale, was strongly correlated with the impact of FI on QOL, supporting the use of this scale to assess symptom severity in FI.

Background & Aims: Altered postprandial satiation influences food intake in obesity. The aim of this study was to evaluate the contribution of gastric motor functions to intra- and postprandial symptoms in obese, otherwise healthy, people., Methods: In a randomized, parallel-group, double-blind design, 40 obese (body mass index>30 kg/m2) healthy volunteers (n=10/group) received intravenous saline (placebo), atropine (.02 mg/kg), or erythromycin (1 or 3 mg/kg) to alter gastric volume and emptying after liquid nutrient meals, measured by validated imaging methods. The nutrient drink test assessed the volume ingested at maximum satiation, and intra- and early postprandial symptoms. Relationships between gastric motor functions, meal size, and symptoms were assessed by using multiple regression. Circulating levels of candidate upper-gut hormones involved in satiation were measured., Results: Relative to placebo, atropine retarded gastric emptying and increased gastric volumes; erythromycin accelerated gastric emptying and reduced gastric volumes during fasting. Although similar maximal tolerated volumes were recorded across treatments, intra- and immediate postprandial symptoms were increased by these perturbations, particularly nausea and bloating. Upper-gut hormonal profiles generally reflected changes in gastric emptying. Regression analysis showed that fasting predrug gastric volume was a significant predictor of intra- and postprandial bloating. Change in gastric volume postdrug or postmeal did not contribute additionally to predicting intra- or postprandial symptoms. There was significant (negative) association between gastric emptying and fullness score, and significant (positive) association with hunger score 30 minutes postprandially., Conclusions: In obese individuals, fasting gastric volumes and gastric emptying, but not postprandial gastric volumes, were associated with intra- and postprandial symptoms. Understanding the determinants of gastric volume may provide insights on mechanisms controlling satiation.

Unlabelled: background & aims: Opiate bowel dysfunction is a significant clinical problem. Our aim was to evaluate the ability of a peripheral mu-opioid antagonist, alvimopan, to reverse the effect of codeine on gastric, small-bowel, and colonic transit time in healthy volunteers., Methods: Seventy-four healthy participants (43 women) were randomized in a double-blind, placebo-controlled manner to 1 of 4 groups: alvimopan 12 mg twice daily in the presence and absence of codeine sulfate 30 mg 4 times/day, or codeine or placebo alone. Gastric emptying, small-bowel, and colonic transit were measured by scintigraphy using a 99m-labeled technetium egg meal and 111-labeled indium charcoal delivered to the proximal colon via a delayed-release capsule. The primary end points for colonic transit were geometric center of the colonic counts at 24 hours and time for 50% ascending colon emptying. Analysis of covariance was used to assess the significance of the primary and secondary end points., Results: Codeine delayed gastric, small-bowel, proximal, and overall colonic transit (P < .05). Alvimopan reversed codeine's effect on small bowel and colon (ascending colon and overall colonic transit). Alvimopan also accelerated overall colonic transit compared with placebo. Thus, the mean colonic geometric center at 24 hours was 2.33 with placebo/placebo, 3.25 with alvimopan/placebo (P < .05), 1.5 with placebo/codeine (P < .05), and 2.63 with alvimopan/codeine. Alvimopan did not reverse codeine's delay of gastric emptying., Conclusions: Alvimopan reverses codeine's inhibitory effect on small-bowel and colon transit and has potential for treatment of opiate bowel dysfunction. Alvimopan alone accelerates colonic transit, suggesting that mu-opiate mechanisms participate in the physiologic control of colonic transit.

Background & Aims: Colorectal cancer (CRC) screening has been advocated increasingly during the past 2 decades, but there is little direct evidence that it has affected cancer incidence or presentation at the population level. This study assessed concurrent trends in CRC incidence, presentation, survival, mortality, and polypectomies in Olmsted County, Minnesota., Methods: Longitudinal observational study was conducted of all Olmsted County residents with colorectal adenocarcinoma first diagnosed in 1980-1999., Results: Altogether, 889 invasive CRCs were diagnosed among Olmsted County residents from 1980 through 1999. Annual age- and sex-adjusted CRC incidence rates decreased significantly during this period (P = .02) with a 23% decline from 60 per 100,000 in 1980-1984 to 46 per 100,000 in 1995-1999. This was primarily accounted for by a 40% reduction in left-sided CRC (P < .001). The incidence of right-sided CRC remained unchanged, but the proportion of right-sided CRC increased from 46% to 58%. Cancer stage shifted downward, and survival improved over time. The overall proportion of screen-detected CRC rose from 8% to 17%. Annual adjusted adenomatous polypectomy rates increased dramatically from 86 to 320 per 100,000 (P < .001)., Conclusions: The incidence of CRC in Olmsted County has declined in recent years. An impact of screening is suggested by the observed upward trend in screen-detected cases, a favorable stage shift, and a concurrent rise in polypectomy rates. However, the incidence of right-sided cancer remains unaltered and might be less affected by historically used screening interventions. Most CRCs still present symptomatically, and more effective population screening is needed.

Background & Aims: Dyspepsia is common in clinical practice and in the community. The relationship of the symptoms to meals and the pathophysiology in community dyspeptic patients is unclear. The purpose of this study was to measure symptoms, demographic features, and gastric motor and sensory functions associated with dyspepsia in the community., Methods: A Modified Bowel Disease Questionnaire was mailed to a random sample of Olmsted County, MN, residents. Dyspeptic patients and healthy controls identified among community respondents completed further questionnaires, Helicobacter pylori serology, gastric emptying by scintigraphy, gastric accommodation by 99mTc-single-photon emission computed tomography imaging, and postprandial symptoms and satiation by a nutrient drink test., Results: A total of 34.1% of community respondents reported dyspepsia within the past year, frequent (at least 25% of the time in the past year) in 17.5%, and 18.4% reported meal-related dyspepsia. Dyspepsia was frequent and related to meals in 10.8% of respondents. Compared with nondyspeptic controls, community dyspepsia was associated with higher aggregate symptom scores and bloating after a fully satiating meal. Community dyspepsia also was associated with higher somatization scores (P = .001), reporting of other somatic symptoms (P = .07), and general severity score on the symptom checklist 90 (P = .01), but not with disordered motor or sensory function. Gastric volumes, gastric emptying, and maximum tolerated volumes were not significantly different between community controls and dyspeptic patients., Conclusions: Meal-related dyspepsia is an important component of dyspepsia in the community. Community dyspeptic patients have higher symptom scores after a fully satiating meal, consistent with gastric hypersensitivity. This is associated with higher somatization scores rather than disorders of gastric emptying or volumes.

Background & Aims: The aim of this study was to evaluate the dose-ranging pharmacodynamic effects of renzapride, a 5-hydroxytryptamine 4 (5-HT4) receptor full agonist/5-HT3 receptor antagonist, on gastrointestinal transit and symptoms in patients with constipation-predominant irritable bowel syndrome (C-IBS)., Methods: Forty-eight patients (46 women) with C-IBS underwent recording of baseline symptoms for 1 week. Twelve patients per group were randomized (double-blind, parallel design) to 11-14 days of renzapride (1, 2, or 4 mg) or placebo, once daily. Daily bowel habits and weekly satisfactory relief of IBS symptoms were recorded. At the end of treatment, gastric emptying (GE), small bowel transit (SBT), and colon transit (CT) were measured by scintigraphy. The relationship between CT and bowel function was evaluated., Results: A statistically significant linear dose response to renzapride was detected for CT (GC8 h, P = 0.004; GC24 h, P = 0.056), and ascending colon (AC) emptying t1/2 (P = 0.019), but not for GE (t1/2, P = 0.088; or SBT, P = 0.41). AC half-time transit (t1/2) for placebo and 4 mg of renzapride were (median) 17.5 vs. 5.0 hours, respectively. Improved bowel function scores (stool form and ease of passage, but not frequency) were significantly (P < 0.05) associated with accelerated CT. Pharmacokinetic analysis showed linear kinetics of renzapride with a mean t1/2 in plasma of 10 hours. Bowel function and satisfactory relief were not significantly altered by renzapride, although a type II error cannot be excluded. No significant adverse clinical, laboratory, or electrocardiogram (ECG) effects were observed., Conclusions: Renzapride causes clinically significant dose-related acceleration of CT, particularly ascending colonic emptying; this acceleration of transit is associated with improvement of bowel function in female C-IBS patients.

Background & Aims: The impact of education on irritable bowel syndrome (IBS) is not well known. This study evaluated the effect of a onetime group education program on patient-based outcomes in IBS., Methods: All adults referred by Mayo Clinic physicians to the Gastroenterology Division with a diagnosis of IBS between May 1997 and March 1998 were asked to participate. Questionnaires were administered at baseline and 6 months. Symptom resolution, change in pain severity, quality of life, Health-Promoting Lifestyle Profile score, overall patient satisfaction, and health care utilization were compared among those patients who attended the multidisciplinary class and those who did not., Results: Of the 506 patients approached, 403 (80%) agreed to participate. The clinical diagnosis was confirmed in 344 patients (85%) on chart review; 211 patients (61%) subsequently completed a follow-up questionnaire. Overall, 29% of class attendees who met Rome criteria for IBS at baseline no longer met Rome criteria at follow-up, compared with 7% of nonattendees. By multivariate analysis, class attendance predicted higher odds of not meeting Rome criteria at follow-up in individuals meeting Rome criteria at baseline (odds ratio, 7.91; 95% confidence interval, 0.97-64.41) than in nonattendees, but the opposite effect was seen with class attendance in those not meeting Rome criteria at baseline. This interaction between baseline Rome status and class attendance was significant (P < 0.05). Class attendance was associated with improvement in Health-Promoting Lifestyle Profile scores (P < 0.05) but not with change in pain, quality of life, satisfaction, or health care utilization., Conclusions: A onetime, multidisciplinary class for patients with IBS was associated with improvement in symptoms and health-promoting lifestyle behavior.

Background & Aims: We have shown that venlafaxine-XR, a serotonin (5-HT) and norepinephrine reuptake inhibitor, enhanced gastric accommodation, whereas buspirone, a 5-HT(1A) receptor agonist, reduced postprandial symptoms after a fully satiating meal. Our aim was to compare the effects of venlafaxine, buspirone, and placebo on colonic sensorimotor functions in healthy adults., Methods: In this randomized, double-blind, parallel-group, placebo-controlled trial of 60 healthy adults, we assessed the effects of oral venlafaxine, 150 mg; buspirone, 20 mg; and placebo on colonic sensorimotor functions., Results: Venlafaxine increased colonic compliance relative to placebo; thus it decreased the intracolonic balloon pressure at half-maximum volume (P = 0.001) and altered the overall shape of the compliance curve, beta (P = 0.01). Venlafaxine also decreased fasting colonic tone (P = 0.02) and the tonic response to a meal (P = 0.003) compared with placebo; no differences in high amplitude phasic contractile events were observed. Pressure thresholds for first sensation (P = 0.1) and gas (P = 0.07) were not statistically significant with venlafaxine. The increase in pain scores per unit pressure during phasic distentions were affected by treatment (P = 0.02), with smallest changes on venlafaxine and highest on placebo. Buspirone did not significantly alter colonic compliance, tone, or sensation relative to placebo., Conclusions: Venlafaxine alters colonic compliance and tone, and tends to reduce sensation during colonic distention in healthy humans. These data support the need for further clinical and physiologic studies of venlafaxine in colonic disorders affecting motor and possibly sensory functions.

Background & Aims: The aim of this study was to evaluate the efficacy and tolerability of the alpha-2 adrenoreceptor agonist, clonidine, in patients with diarrhea-predominant irritable bowel syndrome (D-IBS) in a double-blind, randomized, parallel-group, placebo-controlled trial., Methods: A 2-week run-in evaluated baseline symptoms. Patients received 0.05, 0.1, or 0.2 mg clonidine or placebo twice a day for 4 weeks. We evaluated satisfactory relief of IBS by weekly question and stool parameters with a daily diary. Satisfactory relief and overall bowel function were primary end points. Secondary end points were stool frequency, consistency, and ease of passage; gut transit; and fasting and postprandial gastric volumes. Analysis followed intention-to-treat principles., Results: Forty-four D-IBS patients participated; there were 4 treatment-related dropouts: 2/2 in the 0.2-mg and 2/12 in the 0.05-mg clonidine groups. Proportion with satisfactory relief of IBS was 0.46, 0.42, and 0.67 with placebo, 0.05 mg, and 0.1 mg clonidine, respectively. Relief was sustained through 4 weeks of treatment, and bowel dysfunction (firmer stools and easier stool passage [P < 0.05]) was reduced with clonidine, 0.1 mg twice a day. Clonidine did not significantly alter gastrointestinal transit or gastric volumes. Drowsiness, dizziness, and dry mouth were the most common adverse events with the 0.1-mg dose; severity of adverse effects subsided after the first week of treatment. A trial to replicate 20% or more responders with clonidine will require 95 patients per treatment arm., Conclusions: Clonidine, 0.1 mg twice a day for 4 weeks, relieves bowel dysfunction and appears promising for relief of D-IBS; these effects are unassociated with significant alterations in transit.

Background and Aims: Celiac disease is considered rare in North America. However, an increasing incidence and widening clinical spectrum have been reported in many countries, and serologic screening suggests a higher prevalence of minimally symptomatic disease. This study reports temporal trends in the incidence of celiac disease in Olmsted County, Minnesota., Methods: All county residents diagnosed with celiac disease between 1950 and 2001 were identified through the Rochester Epidemiology Project. Incidence rates were calculated assuming a Poisson distribution, and changes in incidence by calendar year, age, and gender were assessed by using Poisson regression., Results: Altogether, 82 new cases of celiac disease were identified during the 50-year period. There was a marked female predominance (P < 0.005), and the incidence rates increased with age (P < 0.001) and calendar period (P < 0.001). The overall annual incidence of celiac disease was 2.1 per 100,000 (95% confidence interval [CI], 1.7-2.6) but increased from 0.9 per 100,000 (CI, 0.5-1.2) in 1950-1989 to 3.3 per 100,000 (95% CI, 2.2-4.4) in the 1990s. The incidence was 9.1 per 100,000 (95% CI, 5.2-13.0) in the final 2 years of the study. Serology prompted biopsy in a substantial proportion of recent diagnoses. Clinical features also changed over time, with less diarrhea and weight loss at presentation., Conclusions: Celiac disease has increased recently in this well-characterized population. Milder clinical features and use of serology suggest an increased detection rate, although a true increase in incidence may have also occurred. Celiac disease is not rare in North America.