This study examined the prevalence of upper gastrointestinal (GI) symptoms and symptom groupings ... more This study examined the prevalence of upper gastrointestinal (GI) symptoms and symptom groupings and determined impact on disability days in a nationally representative US sample. A telephone survey of 21,128 adults was conducted including questions about the presence of upper GI symptoms during the past 3 months. Respondents were categorized as symptomatic (ie, reported GI symptoms once per month) or asymptomatic. The survey included questions about missed work, leisure activity, or household activity days. Symptom groupings were identified by using factor analysis, and cluster analysis was used to assign respondents into distinct groups on the basis of these symptom groupings. The prevalence of an average of 1 or more upper GI symptoms during the past 3 months was 44.9%. The most common symptoms experienced during the past 3 months were early satiety, heartburn, and postprandial fullness. Factor analysis identified 4 symptom groupings: (1) heartburn/regurgitation; (2) nausea/vomiting; (3) bloating/abdominal pain; and (4) early satiety/loss of appetite. Five respondent clusters were identified; the largest clusters were primarily early satiety/fullness (44%) and gastroesophageal reflux disease-like symptoms (28%). Two small clusters reflected nausea and vomiting (7%) and a heterogeneous symptom profile (4%). Symptomatic respondents reported significantly more missed work, leisure, and household activity days than asymptomatic respondents (all P < .0001). Factor analysis separated GI symptoms into groupings reflecting gastroesophageal reflux disease and dyspepsia: early satiety, postprandial fullness, and loss of appetite; bloating and abdominal pain/discomfort; and nausea and vomiting. These upper GI symptoms were associated with significant loss of work and activity days.
Dietary fiber is a term that reflects a heterogeneous group of natural food sources, processed gr... more Dietary fiber is a term that reflects a heterogeneous group of natural food sources, processed grains, and commercial supplements. Several forms of dietary fiber have been used as complementary or alternative agents in the management of manifestations of the metabolic syndrome, including obesity. Not surprisingly, there is a great variation in the biological efficacy of dietary fiber in the metabolic syndrome and body weight control. Diverse factors and mechanisms have been reported as mediators of the effects of dietary fiber on the metabolic syndrome and obesity. Among this array of mechanisms, the modulation of gastric sensorimotor influences appears to be crucial for the effects of dietary fiber but also quite variable. This report focuses on the role, mechanism of action, and benefits of different forms of fiber and supplements on obesity and the metabolic syndrome, glycemia, dyslipidemia, and cardiovascular risk and explores the effects of dietary fiber on gastric sensorimotor function and satiety in mediating these actions of dietary fiber.
The performance characteristics of colonic sensation and motility measurements are unclear. To co... more The performance characteristics of colonic sensation and motility measurements are unclear. To compare left colon compliance, tone, and sensation in males and females and to evaluate inter and intra-individual coefficients of variation (COV) in these measurements. Data were acquired using standard barostat methods, by one technologist, in 72 human volunteers (38 males, 18-65 years). We measured compliance, fasting tone, and sensation during baseline and post-placebo; postprandial (PP) tone was measured only post-placebo. Compliance and thresholds for first sensation, gas, and pain were measured using ascending method of limits; sensory ratings (0-100 mm VAS) using random phasic distensions at 8-36 mmHg above baseline operating pressure. Change in PP tone was measured by barostat balloon volume for the first 30 min after a 1000-kcal meal. Inter-COV was calculated as 100 (SD/mean), and intra-COV as (100 x SD delta/overall mean). There were no statistically significant associations with gender for most sensory or motor data at baseline. A modest association of fasting colonic tone and gender was observed. COV are lower (20-35%) for compliance, fasting tone, pain threshold, and sensation ratings than for PP tone and threshold for first or gas sensation (>45%). COV data are similar in males and females; sensation COVs appear smaller in females than in males. Testing of compliance, tone and pain, and gas sensation in left colon performs adequately to assess these functions in humans. Lower COV for sensation tests among females is relevant to plan studies of drugs intended for functional GI disorders.
Ghrelin is a peptide hormone that possesses unique orexigenic properties. By acting on the growth... more Ghrelin is a peptide hormone that possesses unique orexigenic properties. By acting on the growth-hormone secretagogue receptor 1a, ghrelin induces a short-term increase in food consumption, which ultimately induces a positive energy balance and increases fat deposition. Reduced ghrelin levels have been observed in obese patients and after bariatric surgery. In particular, bariatric procedures that involve gastric resection or bypass lead to reduced ghrelin levels. Administration of physiological doses of exogenous ghrelin to humans does not significantly alter gastric motility; however, administration of high doses stimulates gastric motility, with increased gastric tone and emptying, and increased activity of migrating motor complexes in the small bowel. The potential of ghrelin agonists to be used as prokinetics is being tested in patients with gastroparesis and postoperative ileus. Ghrelin acts directly on pancreatic islet cells to reduce insulin production. Findings from studies in animals have revealed that small-molecule ghrelin antagonists favorably influence glucose tolerance, appetite suppression and weight loss. Other studies have demonstrated that ghrelin antagonists retard gastric emptying only at very high doses, which suggests that these agents will probably not induce upper gastrointestinal symptoms. The potential of this new class of therapeutic agents to influence appetite and glycemic control strongly indicates that they should be tested in clinical trials.
IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so... more IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotr...
Psychosensory stimulation increases the perception of stimuli in different regions of the human c... more Psychosensory stimulation increases the perception of stimuli in different regions of the human colon. The aim of this study was to determine the perception of pain and gas during distention of two colonic regions in healthy volunteers during stress and relaxation. Methods: In 22 healthy subjects, phasic distentions of transverse and sigmoid colon were performed using infinitely compliant balloons, and symptoms were measured before and during one of three randomized treatments: sham or active relaxation or mental stress. Anxiety ratings and somatic cold-pain sensitivity were included in a multivariate regression model. Results: Mental stress increased levels of anxiety (P < 0.05) and the sensation of gas (P < 0.01), but not pain (P = NS), during transverse colon distentions and the sensations of gas and pain during sigmoid distentions (P < 0.05). Active relaxation reduced only sensation of gas in the sigmoid colon. Somatic pain sensitivity and pretreatment colonic sensory scores were significantly associated with the sensory scores during treatments. Conclusions: Psychosensory stimulation increases colonic sensation during shortterm distention in two regions of the human colon; relaxation alone exerts a smaller influence on sensations arising in the sigmoid colon. Address requests for reprints to: Michael Camilleri, M.D., Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota 55905. Fax: (507) 255-6318.
This study examined the prevalence of upper gastrointestinal (GI) symptoms and symptom groupings ... more This study examined the prevalence of upper gastrointestinal (GI) symptoms and symptom groupings and determined impact on disability days in a nationally representative US sample. A telephone survey of 21,128 adults was conducted including questions about the presence of upper GI symptoms during the past 3 months. Respondents were categorized as symptomatic (ie, reported GI symptoms once per month) or asymptomatic. The survey included questions about missed work, leisure activity, or household activity days. Symptom groupings were identified by using factor analysis, and cluster analysis was used to assign respondents into distinct groups on the basis of these symptom groupings. The prevalence of an average of 1 or more upper GI symptoms during the past 3 months was 44.9%. The most common symptoms experienced during the past 3 months were early satiety, heartburn, and postprandial fullness. Factor analysis identified 4 symptom groupings: (1) heartburn/regurgitation; (2) nausea/vomiting; (3) bloating/abdominal pain; and (4) early satiety/loss of appetite. Five respondent clusters were identified; the largest clusters were primarily early satiety/fullness (44%) and gastroesophageal reflux disease-like symptoms (28%). Two small clusters reflected nausea and vomiting (7%) and a heterogeneous symptom profile (4%). Symptomatic respondents reported significantly more missed work, leisure, and household activity days than asymptomatic respondents (all P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). Factor analysis separated GI symptoms into groupings reflecting gastroesophageal reflux disease and dyspepsia: early satiety, postprandial fullness, and loss of appetite; bloating and abdominal pain/discomfort; and nausea and vomiting. These upper GI symptoms were associated with significant loss of work and activity days.
Dietary fiber is a term that reflects a heterogeneous group of natural food sources, processed gr... more Dietary fiber is a term that reflects a heterogeneous group of natural food sources, processed grains, and commercial supplements. Several forms of dietary fiber have been used as complementary or alternative agents in the management of manifestations of the metabolic syndrome, including obesity. Not surprisingly, there is a great variation in the biological efficacy of dietary fiber in the metabolic syndrome and body weight control. Diverse factors and mechanisms have been reported as mediators of the effects of dietary fiber on the metabolic syndrome and obesity. Among this array of mechanisms, the modulation of gastric sensorimotor influences appears to be crucial for the effects of dietary fiber but also quite variable. This report focuses on the role, mechanism of action, and benefits of different forms of fiber and supplements on obesity and the metabolic syndrome, glycemia, dyslipidemia, and cardiovascular risk and explores the effects of dietary fiber on gastric sensorimotor function and satiety in mediating these actions of dietary fiber.
The performance characteristics of colonic sensation and motility measurements are unclear. To co... more The performance characteristics of colonic sensation and motility measurements are unclear. To compare left colon compliance, tone, and sensation in males and females and to evaluate inter and intra-individual coefficients of variation (COV) in these measurements. Data were acquired using standard barostat methods, by one technologist, in 72 human volunteers (38 males, 18-65 years). We measured compliance, fasting tone, and sensation during baseline and post-placebo; postprandial (PP) tone was measured only post-placebo. Compliance and thresholds for first sensation, gas, and pain were measured using ascending method of limits; sensory ratings (0-100 mm VAS) using random phasic distensions at 8-36 mmHg above baseline operating pressure. Change in PP tone was measured by barostat balloon volume for the first 30 min after a 1000-kcal meal. Inter-COV was calculated as 100 (SD/mean), and intra-COV as (100 x SD delta/overall mean). There were no statistically significant associations with gender for most sensory or motor data at baseline. A modest association of fasting colonic tone and gender was observed. COV are lower (20-35%) for compliance, fasting tone, pain threshold, and sensation ratings than for PP tone and threshold for first or gas sensation (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;45%). COV data are similar in males and females; sensation COVs appear smaller in females than in males. Testing of compliance, tone and pain, and gas sensation in left colon performs adequately to assess these functions in humans. Lower COV for sensation tests among females is relevant to plan studies of drugs intended for functional GI disorders.
Ghrelin is a peptide hormone that possesses unique orexigenic properties. By acting on the growth... more Ghrelin is a peptide hormone that possesses unique orexigenic properties. By acting on the growth-hormone secretagogue receptor 1a, ghrelin induces a short-term increase in food consumption, which ultimately induces a positive energy balance and increases fat deposition. Reduced ghrelin levels have been observed in obese patients and after bariatric surgery. In particular, bariatric procedures that involve gastric resection or bypass lead to reduced ghrelin levels. Administration of physiological doses of exogenous ghrelin to humans does not significantly alter gastric motility; however, administration of high doses stimulates gastric motility, with increased gastric tone and emptying, and increased activity of migrating motor complexes in the small bowel. The potential of ghrelin agonists to be used as prokinetics is being tested in patients with gastroparesis and postoperative ileus. Ghrelin acts directly on pancreatic islet cells to reduce insulin production. Findings from studies in animals have revealed that small-molecule ghrelin antagonists favorably influence glucose tolerance, appetite suppression and weight loss. Other studies have demonstrated that ghrelin antagonists retard gastric emptying only at very high doses, which suggests that these agents will probably not induce upper gastrointestinal symptoms. The potential of this new class of therapeutic agents to influence appetite and glycemic control strongly indicates that they should be tested in clinical trials.
IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so... more IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotr...
Psychosensory stimulation increases the perception of stimuli in different regions of the human c... more Psychosensory stimulation increases the perception of stimuli in different regions of the human colon. The aim of this study was to determine the perception of pain and gas during distention of two colonic regions in healthy volunteers during stress and relaxation. Methods: In 22 healthy subjects, phasic distentions of transverse and sigmoid colon were performed using infinitely compliant balloons, and symptoms were measured before and during one of three randomized treatments: sham or active relaxation or mental stress. Anxiety ratings and somatic cold-pain sensitivity were included in a multivariate regression model. Results: Mental stress increased levels of anxiety (P < 0.05) and the sensation of gas (P < 0.01), but not pain (P = NS), during transverse colon distentions and the sensations of gas and pain during sigmoid distentions (P < 0.05). Active relaxation reduced only sensation of gas in the sigmoid colon. Somatic pain sensitivity and pretreatment colonic sensory scores were significantly associated with the sensory scores during treatments. Conclusions: Psychosensory stimulation increases colonic sensation during shortterm distention in two regions of the human colon; relaxation alone exerts a smaller influence on sensations arising in the sigmoid colon. Address requests for reprints to: Michael Camilleri, M.D., Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota 55905. Fax: (507) 255-6318.
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