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Background: Although the Rome criteria define a number of individual functional gastrointestinal disorders, people may have symptoms of multiple disorders at the same time. In addition, therapies may be effective in subsets of people with specific disorders, yet at the same time help people with multiple disorders., Aim: To estimate the prevalence of combinations of gastrointestional (GI) symptom complexes., Methods: A valid self report questionnaire which records GI symptoms was mailed to an age- and gender-stratified random sample of Olmsted County, MN residents aged 30-64 years. Standard definitions were used to identify people with gastro-oesophageal reflux, dyspepsia, irritable bowel syndrome (IBS), constipation and diarrhoea. The prevalence of people meeting multiple symptom complexes was estimated. Specifically, combinations of dyspepsia, IBS and constipation were compared to dyspepsia, IBS and diarrhoea., Results: A total of 657 (69%) of 943 eligible subjects responded; 643 provided data for each of the necessary symptom questions. Each two-way combination of symptom group was present in between 4 and 9% of the population; each three-way combination was present in 1-4% of the population. The overlap between dyspepsia, IBS and constipation was similar to dyspepsia, IBS and diarrhoea, except body mass index was higher in the diarrhoea overlap group (P = 0.03)., Conclusion: Symptom complex overlap is common in the community; for each condition, the majority of sufferers reported an additional symptom complex. This overlap of symptoms challenges the current paradigm that functional GI disorders represent multiple discreet entities.

Background: The health-related quality of life is impaired in patients with functional gastrointestinal disorders seen in referral centres., Aim: To determine whether the health-related quality of life is impaired in subjects with functional disorders in the community and whether any differences can be explained by psychological co-morbidity., Methods: In a population-based, nested, case-control study, subjects reporting symptoms of either dyspepsia or irritable bowel syndrome and healthy controls were interviewed and completed a battery of psychological measures plus a validated, generic, health-related quality of life measure (Medical Outcomes Study 36-item short form health survey, SF-36). The association between irritable bowel syndrome and dyspepsia and the physical and mental composite scores of SF-36 were assessed with and without adjustment for psychological state., Results: One hundred and twelve cases (30 dyspepsia, 39 irritable bowel syndrome, 32 dyspepsia and irritable bowel syndrome and 11 gastrointestinal symptoms but not dyspepsia or irritable bowel syndrome) and 110 controls were enrolled. In the unadjusted linear regression models, irritable bowel syndrome (but not dyspepsia) was negatively associated with the physical composite score (P < 0.05); in an adjusted model, the association between the physical health-related quality of life and irritable bowel syndrome was explained by the Symptom Checklist-90 somatization score alone. In unadjusted models, irritable bowel syndrome and dyspepsia were each negatively associated with the mental composite score (P < 0.05). The association between the mental health-related quality of life and dyspepsia remained after adjusting for psychological covariates, but the association between this and irritable bowel syndrome was not significant after adjustment., Conclusions: In the community, health-related quality of life is impaired in subjects with irritable bowel syndrome and dyspepsia; however, much of this association can be explained by psychological factors.

Background: We tested the hypothesis that subjects with relatives who suffered from abdominal pain or bowel dysfunction would be at an increased risk of more persistent irritable bowel syndrome., Methods: A valid, self-report questionnaire was mailed to an age- and gender-stratified random sample of residents, aged 30-64 years, in Olmsted County, MN, USA, on three occasions over a 4-year period. Persistent irritable bowel syndrome was defined as the presence of irritable bowel syndrome on at least two of the three surveys, and fluctuating irritable bowel syndrome was defined as the presence of irritable bowel syndrome on only one of the surveys., Results: Subjects were less likely to have persistent irritable bowel syndrome over the age of 50 years [odds ratio (OR), 0.20; 95% confidence interval (CI), 0.09, 0.47]. A positive family history was reported by 23%. A family history of gastrointestinal symptoms was independently associated with persistent irritable bowel syndrome (vs. no irritable bowel syndrome: OR, 2.5; 95% CI, 1.3, 4.9) and fluctuating irritable bowel syndrome (vs. no irritable bowel syndrome: OR, 2.4; 95% CI, 1.3, 4.4). However, subjects reporting a positive family history were not more likely to report persistent vs. fluctuating irritable bowel syndrome (OR, 1.2; 95% CI, 0.5, 2.9). The use of non-steroidal anti-inflammatory drugs (OR, 2.3; 95% CI, 1.2, 4.3) and a history of food sensitivity (OR, 3.6; 95% CI, 1.9, 6.9) were the only other predictors of persistent irritable bowel syndrome., Conclusions: A history of abdominal pain or bowel troubles in first-degree relatives appears to be independently associated with both persistent and fluctuating irritable bowel syndrome.

Objective: The aim of this study was to estimate the prevalence of irritable bowel syndrome using different standard definitions (Rome and Manning criteria) and to determine the degree of agreement between these definitions., Methods: A population-based, cross-sectional survey study was conducted by mailing a valid, reliable questionnaire to an age- and gender-stratified random sample of residents of Olmsted County, MN, aged 30-69 yr. The threshold for a positive diagnosis of irritable bowel was varied from two to four of the six Manning criteria and from two to three of the five defecation disorders in the Rome criteria. Unadjusted as well as age- and gender-adjusted prevalence rates were calculated for each of the five definitions of IBS. Percent agreement and kappa statistics were calculated to assess agreement between the definitions., Results: Questionnaires were returned by 643 of 892 eligible subjects (72% response rate). The age- and gender-adjusted prevalence of IBS varied from 20.4% using a threshold of two symptoms in the Manning criteria to 8.5% using a threshold of three defecation disorders in the Rome criteria. The percent agreement for each comparison of Manning and Rome definitions was always >90%. The kappa values ranged from 0.55 to 0.78, with the best agreement occurring between a threshold of three symptoms of Manning and two defecation disorders in Rome., Conclusions: The prevalence of IBS varied substantially depending on the specific definition of IBS used. The range of prevalence estimates in Olmsted County was similar to other published figures when IBS definition was accounted for. These findings are useful in interpreting epidemiological and clinical studies of IBS.

Objective: To evaluate the association between functional gastrointestinal (GI) symptoms and a family history of abdominal pain or bowel problems., Subjects and Methods: A valid self-report questionnaire that records GI symptoms and spouse's and first-degree relatives' history of abdominal pain or bowel troubles and includes the psychosomatic symptom checklist (a measure of somatization) was mailed to an age- and sex-stratified random sample of Olmsted County, Minnesota, residents aged 30 to 64 years. A logistic regression model that adjusted for age, sex, and somatic symptom score was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of a positive family history for each functional GI disorder., Results: Six hundred forty-three (72%) of 892 eligible subjects returned the survey. Reporting a first-degree relative with abdominal pain or bowel problems was significantly associated with reporting of irritable bowel syndrome (OR, 2.3; 95% CI, 1.3-3.9) and dyspepsia (OR, 1.8; 95% CI, 1.05-3.0) but not constipation, diarrhea, or gastroesophageal reflux. The reporting of a spouse with abdominal pain or bowel problems was not associated with any of these disorders., Conclusions: A history of abdominal pain or bowel troubles in first-degree relatives was significantly associated with irritable bowel syndrome and dyspepsia. Whether the familial associations represent similar exposures in a shared environment, heightened familial awareness of GI symptoms (reporting bias), or genetic factors remains to be determined.

Rationale: Visceral sensation and motility are important in functional gut disorders and are partly controlled by adrenergic innervation., Objectives: To characterize the alpha2-adrenergic control of motor and sensory function of descending colon and rectum., Methods: In 32 healthy volunteers, we assessed compliance, fasting and postprandial tone, and sensations of gas, urgency and pain during phasic distentions. Each subject received one agent at clinically approved doses: clonidine (0.05, 0.1, 0.2 or 0.3 mg p.o. ); or the alpha2 antagonist yohimbine (0.0125 mg, 0.05 mg, 0.125 mg or 0.2 mg intravenously and infusion over 2.5 h)., Results: Clonidine increased colonic and rectal compliance, and reduced tone, pain, gas sensation and rectal urgency. Clonidine showed large pairwise differences in sensation and motility between 0.05 and 0.1 mg doses, which did not interfere with the colon's motor response to feeding. Conversely, yohimbine dose-dependently altered the compliance curve, increased tone and sensations of gas, pain and urgency. Drug effects in the colon were more marked at low distensions; alpha2 modulation of rectal sensation was observed at all levels of distension., Conclusions: alpha2-adrenergic mechanisms modulate colorectal sensations and motility; at doses as low as 0.05 mg, clonidine reduced colorectal sensation while the tone response to feeding was preserved. These studies provide insight into the potential use of alpha2 agents in disease states.

Objective: Symptoms of irritable bowel syndrome (IBS) are reported by 10% of the general population; however, evaluation of traditional risk factors has not provided any insight into the pathogenesis of this condition. The objective of this study was to identify additional risk factors for irritable bowel syndrome., Methods: A valid self-report questionnaire that records the gastrointestinal (GI) symptoms required for a diagnosis of IBS, self-reported measures of potential risk factors, and a psychosomatic symptom checklist was mailed to an age-and gender-stratified random sample of Olmsted County, Minnesota residents aged 30-64 yr. A logistic regression model that adjusted for age, gender, and psychosomatic symptom score was used to identify factors significantly associated with IBS., Results: A total of 643 (72%) of 892 eligible subjects returned the survey. IBS symptoms were reported by 12% of the respondents. IBS was significantly associated with use of analgesics (acetaminophen, aspirin, or nonaspirin nonsteroidal antiinflammatory drugs) for reasons other than IBS, reporting a food allergy or sensitivity, and ratings of somatic symptoms. No association was detected for age, gender, body mass index, smoking history, alcohol use, educational level, exposure to pets in the household, or water supply. Among subjects reporting the use of just one type of analgesic, IBS was associated with acetaminophen but not aspirin or nonaspirin nonsteroidal antiinflammatory drugs used alone. The odds of having IBS were higher among subjects reporting more reasons for taking analgesics and intolerance to a higher number of foods., Conclusions: IBS is significantly associated with analgesic use. However, this is confounded by other somatic pain complaints. IBS symptoms are associated with the reporting of many food allergies or sensitivities. The role of food-induced symptoms in IBS requires further investigation.

Background: Although patients with gastroesophageal reflux are often instructed to change their lifestyle, population-based data on the risk factors for reflux in the United States are lacking., Methods: We performed a cross-sectional study in an age- and gender-stratified random sample of the population of Olmsted County, Minnesota. Residents aged 25 to 74 years were mailed a valid self-report questionnaire that measured reflux symptoms and potential risk factors. Logistic regression was used to estimate the odds ratios (OR) with 95% confidence intervals (CI) for reflux symptoms (heartburn or acid regurgitation) associated with potential risk factors., Results: Overall, 1,524 (72%) of 2,118 eligible subjects responded. A body mass index >30 kg/m2 (OR = 2.8; CI, 1.7 to 4.5), reporting an immediate family member with heartburn or disease of the esophagus or stomach (OR = 2.6; CI, 1.8 to 3.7), a past history of smoking (OR = 1.6; CI, 1.1 to 2.3), consuming more than seven drinks per week (OR = 1.9; Cl, 1.1 to 3.3), and a higher psychosomatic symptom checklist score (OR per 5 units = 1.4; CI, 1.3 to 1.6) were independently associated with frequent (at least weekly) reflux symptoms., Conclusion: Obesity is a strong risk factor for gastroesophageal reflux, although the value of weight reduction remains to be proven. That family history was also a risk factor suggests that there may be a genetic component to the disorder.

Background: During the 1980s, mortality from coronary artery disease (CAD) decreased markedly in the United States. This raises the question of whether a parallel decrease occurred in excess mortality due to CAD in patients undergoing surgical correction of valvular regurgitation., Methods and Results: Survival of 752 patients (age, 64 +/- 13 years) with isolated left-sided valvular regurgitation operated on from 1980 to 1991 was analyzed. Of 242 patients with CAD (stenosis > or = 70%), 208 had coronary artery bypass grafting. Multivariate analysis identified CAD as an independent predictor of operative mortality (odds ratio [OR] = 2.35, P = 0.012), overall (hazard ratio [HR] = 1.65, P < 0.0001) and late mortality (HR = 1.57, P = 0.0006), and postoperative congestive heart failure (HR = 2.35, P = 0.0001). Comparison of patients operated on in 1980 to 1985 with those operated on in 1986 to 1991, excess of operative, overall, and late mortality and postoperative congestive heart failure (adjusted for age and gender) related to associated CAD did not decrease significantly (P = 0.23, P = 0.64, P = 0.90, and P = 0.61, respectively). Overall survival was better for patients receiving an internal mammary artery graft than those receiving vein grafts only (HR = 0.57, P = 0.011)., Conclusions: In contrast to the secular trend for decreased mortality from CAD, excess mortality related to associated CAD after surgery for valvular regurgitation has not decreased. Internal mammary artery grafts were associated with improved outcome. In patients with valvular regurgitations, these results support continued active search of associated CAD, wide use of internal mammary artery graft, and vigorous efforts for secondary prevention of complications of CAD.

Objectives: We sought to determine the reliability of the proximal isovelocity surface area (PISA) method for calculation of effective regurgitant orifice (ERO) of aortic regurgitation (AR)., Background: The ERO area can be calculated by the PISA method, but this method has not been validated in AR., Methods: ERO calculation by the PISA method was undertaken prospectively in 71 consecutive patients with isolated AR and achieved in 64 and compared with two simultaneous reference methods (quantitative Doppler and quantitative two-dimensional echocardiography). In addition, this method was compared with angiography in 12 patients, with surgical assessment in 18 patients and with ventricular volumes in all patients., Results: Good correlations between PISA and reference methods were obtained (both r=0.90, both p < 0.0001), but a trend toward underestimation of the ERO by the PISA method was noted (24+/-19 vs. 26+/-22 mm2 and 27+/-23 mm2, respectively, both p=0.04). However, this trend was confined to five patients with an obtuse flow convergence angle (>220 degrees), and on multivariate analysis this variable was the only independent determinant of underestimation of the ERO. In contrast, in 59 patients with a flat flow convergence (< or =220 degrees ), the PISA method, in comparison with reference methods, showed excellent correlations, with a narrow standard error of the estimate (r=0.95, SEE 5.4 mm2, and r=0.95, SEE 5.8 mm2; all p < 0.0001) and no trend toward underestimation (22+/-18 vs. 23+/-16 mm2, p=0.44, and vs. 23+/-18 mm2, p=0.34)., Conclusions: In patients with AR, the PISA method can be used to measure the ERO with reasonable feasibility. Underestimation of the ERO by PISA may occur in patients with an obtuse flow convergence angle. However, in most patients with appropriate flow convergence, PISA provides reliable measurement of the ERO of AR.

Effects of the nonbenzamide 5-hydroxytryptamine4 agonist SDZ HTF 919 on gastrointestinal motility are unclear. Our aim was to assess the in vivo effects on gastrointestinal and colonic transit of radiolabeled residue and on colonic phasic contractility. In six female dogs, transit was measured over a period of 2 days by radioscintigraphy and colonic motility was measured by pneumohydraulic perfusion manometry of the proximal and distal colon. SDZ HTF 919 was administered initially by bolus i.v. infusion, followed by s.c. injection 8 and 16 hr later. Doses tested were 0.03, 0.1 and 0.3 mg/kg, and isotonic saline and vehicle served as controls in each dog. Stomach and small bowel transit was not significantly altered by SDZ HTF 919. Overall, i.v. SDZ HTF 919 accelerated colonic transit during the first 1 hr, compared with controls. These effects were significant even with the lowest dose of SDZ HTF 919. Responses to higher infusion doses were more variable. SDZ HTF 919 did not cause significant changes in quantitative pressure indices, such as amplitude or motor index, in the small bowel or colon. Prolonged postprandial colonic contractions, each lasting >30 sec, were noted after each i.v. agent and were significantly more frequent with the 0.03 mg/kg dose than with control (vehicle) treatment. Thus, SDZ HTF 919 accelerates canine colonic transit in vivo during the first 1 hr after i.v. administration. SDZ HTF 919 appears to be a promising agent for stimulation of mammalian colonic transit.

Objective: A link between functional bowel disease and sexual, physical, emotional, or verbal abuse remains controversial. We aimed to determine whether abuse is associated with functional bowel disease in outpatients., Methods: A consecutive sample of outpatients completed a validated questionnaire; 997 responded. Using standard criteria, we obtained data on symptoms, psychosocial factors, and abuse (sexual, physical, and emotional or verbal). Logistic regression analysis was used to determine whether abuse was associated with functional bowel disease (versus organic disease) and with irritable bowel syndrome (IBS)-type symptoms defined by the Manning criteria. Adjustments were made for age, gender, marital status, education level, psychological distress, and social support., Results: Of those with a physician-based diagnosis of functional bowel disease (n = 440), 22% reported some form of abuse (13% sexual and/or physical abuse), compared with those with organic disease (n = 557), 16% of whom reported some form of abuse; this difference was not significant. However, abused patients were significantly more likely to report IBS-type symptoms than those who did not report a history of abuse (odds ratio = 1.7, 95% confidence interval = 1.2, 2.5)., Conclusion: Outpatients who report abuse are more likely to have IBS-type symptoms.

Background/aims: A link between abuse and irritable bowel syndrome (IBS) has been reported in outpatients but remains controversial. No population-based studies have investigated this issue. The aim of this study was to determine the prevalence of abuse and its association with symptoms in a representative community sample., Methods: An age- and sex-stratified random sample of residents of Olmsted County, Minnesota ranging in age from 30 to 49 years was mailed a valid self-report symptom questionnaire. Abuse was assessed by standard published criteria., Results: Of the 919 responders (74%), the age-adjusted prevalence of any abuse was 41% in women and 11% in men, resulting in an age- and sex-adjusted prevalence of 26%. Symptoms of IBS, dyspepsia, and frequent heartburn were reported by 14%, 23%, and 12%, respectively. There was a significant association between IBS and sexual abuse, emotional or verbal abuse, and abuse in childhood and adulthood. Similarly, dyspepsia and heartburn were both significantly associated with abuse. In the population, 31% had visited a physician for gastrointestinal symptoms; the odds of visiting a physician were highest in those reporting abuse in adulthood and childhood., Conclusions: Self-reported abuse is common in middle-aged subjects; those who report abuse are more likely to have symptoms consistent with IBS, dyspepsia, or heartburn and to visit a physician for bowel symptoms.