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Tu1434 Autonomic Response to a Visceral Stressor is Dysregulated in Irritable Bowel Syndrome and Correlates With Visceral Perception
glucose tolerance test (GTT) in CD patients with megacolon with and without constipation. Material and methods: 10 Healthy volunteers (HV) and 20 patients with Chagas' disease (CD) and (18y or more) were included. All patients underwent a clinical examination, barium enema, 5-day colonic transit marker test and serology for CD . Patients with upper gut surgeries in the past, taking drugs that could affect gastrointestinal motility and having any kind of organic disease other than CD were excluded. According to symptoms and serology, they were divided in 3 groups: 1-Control group (CG): 10 HV; 2-Chagasic with megacolon without constipation group ChnonCM: 10; 3-Chagasic constipated and megacolon group (ChCMG): 10 patients. All patients and HV were submitted to OCTT and GTT. OCTT was measured using the lactulose hydrogen (H2) breath test. After intake of lactulose(15 mg); H2 was measured at baseline(0), 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140,160 and 180 min. OCTT was defined as the time from baseline when there was a rise in H2 levels of >20 ppm over baseline or >10 ppm over baseline sustained over 2 consecutive time points. GTT were calculated after intake glucose (75mg). Blood glucose (BG) was measured at 0, 30, 60, 90 and 120 min. OCTT and GTT were compared among the three groups; for statistical analyses were used ANOVA with Tukey test. Results: ChCMG showed significantly higher blood glucose levels as compared to the CG at 30min(p = 0.01), 60min(p= 0,005) and 90min(p=0,003).There was no statistically significant difference between ChCMG and ChnonCMG.OCTT was statistically significant slower in ChCMG as compared with ChnonCMG and CG at 110 min: p= 0,004; at 120min:p=0,002; at140min:p=0,001 at160min,p=0,002;and at 180 min:p=0,002.There was no statistically significant difference on OCTT between ChnonCM and CG.Mean OCTT was >180min in ChCMG, 100min in ChnonCMG and 80min in CG. Conclusion: CD patients presenting with megacolon and constipation have slow orocecal transit time and an increased blood glucose levels.Patients with megacolon without Constipation had an increased blood glucose levels but normal orocecal transit time.Constipation in Chagas' disease is not related to megacolon but to slow orocecal transit time. References:1.Rev Soc Bras Med Trop, 17(supl):23,1984 2 .Rev Soc Bras Med Trop, 19(supl II):29,1986 3.Gut;14,1973.4.Rev Soc Bras Med Trop.37(3): 2004
Gluten Sensitization May Be a Possible Pathogenic Factor for IBS in a Chinese Population Wei Lu, Kok-Ann Gwee, Kewin Tien Ho Siah, Ru Min Lee, Cecilia Cheng Lai Ngan Background: In western populations where there is a high prevalence of celiac disease (CD), serological and tissue markers were found to be more common in patients with irritable bowel syndrome (IBS) phenotype. While CD is believed to be uncommon in Chinese, there is a report from China suggesting that this association may also exist. Aim: To study the prevalence of celiac disease markers in patients with IBS criteria and of Chinese ethnicity from Singapore, where there has been increasing wheat consumption. Method: We explored this association in a cohort of ethnic Chinese patients with IBS by Rome III criteria, who had all undergone IgA anti-gliadin antibody (AGA) and IgA anti-endomysial antibody (EMA) serology testing and duodenal biopsies as part of their clinical workup. In addition, we recalled patients with positive serology for further test of human leukocyte antigens HLADQ2 and HLA-DQ8, which are known to be associated with celiac disease. Result: In 106 patients of Chinese ethnicity who fulfilled Rome III IBS criteria 16 (15.1%) were tested positive for AGA, and 7 (6.6%) had intra-epithelial lymphocytosis reported in duodenal biopsies. None of the patients was positive for EMA. The prevalence of intra-epithelial lymphocytosis (IEL) was numerically higher in patients with positive AGA than negative AGA serology, with 3 (18.8%) and 4 (4.4%) respectively (p=0.105). Similarly, villous atrophy was numerically more common in AGA positive than AGA negative group with 8(50%) and 30(33.3%) respectively (p=0.20). None of these patients had more than mild villous atrophy. The prevalence of Helicobacter pylori infection in AGA positive and AGA negative groups were 18.8% and 28.9% respectively (p=0.40). Nine of the 16 patients in the AGA positive group agreed to undergo HLA-DQ2/8 genotyping, and only 2 patients were positive for HLA-DQ8. These two HLA-DQ positive patients are sisters whose parents had emigrated from the northern part of China where the traditional dietary staple was wheat. Neither of them had villous atrophy, but one had IEL. The other 7 patients who were HLA-DQ2/8 genotype negative were descended from tribes in the southern part of China; one of the patients had concurrent systemic lupus erythematosus (SLE). Five of the 7 patients had villous atrophy, while two of the 7 patients had IEL. Conclusion: Our observations suggest that celiac disease could be present in some ethnic Chinese patients with IBS criteria. However there is a subset of Chinese patients with positive anti-gliadin serology who do not have the full histologic features for celiac disease and were HLA haplotype negative, suggesting that these patients could IBS associated with an immune sensitization to gluten not amounting to celiac disease.
Tu1434 Autonomic Response to a Visceral Stressor is Dysregulated in Irritable Bowel Syndrome and Correlates With Visceral Perception Paul Cheng, Melissa Alberto, Wendy Shih, Angela P. Presson, Arlene Licudine, Emeran A. Mayer, Bruce D. Naliboff, Lin Chang BACKGROUND: Autonomic nervous system (ANS) dysregulation of the gut may play a pathophysiologic role in irritable bowel syndrome (IBS). Previous studies reported altered ANS responses in IBS at baseline or following colonic distension, a meal or mental stress but there is little data to suggest these changes correlate with visceral perception. This is the first study to examine ANS response in IBS during a visceral stressor, a flexible sigmoidoscopy, and its association to visceral perception. AIMS: 1)To compare heart rate variability (HRV) and skin conductance (SC) at rest and during a visceral stressor in IBS patients and healthy controls (HCs) and 2)To examine the effects of sex, psychological symptoms and perceptual ratings of the visceral stressor on ANS function. METHODS:Male and female Rome III positive IBS patients and HCs completed questionnaires to measure GI and psychological (HAD) symptoms. ECG and SC measurements at rest and during a visceral stressor (sigmoidoscopy) were acquired using the BioPac system (BioPac Inc.) for HRV autoregression spectral analysis. Immediately following the procedure, a validated VDVAS (0-20 cm) was used to measure perceptual ratings to the visceral stressor. Linear mixed models using the SAS v9.2 Mixed procedure, Wilcoxon Rank Sum test, Fisher Exact test, and Spearman correlation were used with significance level of 0.05. RESULTS: 36 IBS patients (53% F, mean age 37.89 yrs) and 31 HCs (62% F, mean age 37.26 yrs) participated. IBS bowel habit subtypes were 39% IBS-D, 31% IBS-C, 28% IBS-M, and 3% IBS-U. Compared to HCs, IBS patients had higher HAD anxiety (6.4±0.9 vs. 2.5±0.4, p=0.002) and depression (3.3±0.6 vs. 0.9±0.3, p=0.005) scores but they were in normal range and did not significantly affect ANS responses. IBS and HCs had similar baseline ANS measures. During the visceral stressor, HCs showed an increase in cardiosympathetic tone and a decrease in cardiovagal tone. However, IBS patients had significantly less cardiosympathetic (p=0.012) and cardiovagal (p=0.009) responsiveness vs. HCs. Although SC increased in both IBS and HCs in anticipation to the procedure, it decreased afterwards in HCs but remained elevated in IBS (p=0.017). The change in SC following the visceral stressor positively correlated with unpleasantness ratings of the visceral stressor in IBS (r=0.40, p=0.017) but not in HCs. Men had higher cardiosympathetic tone (p=0.001) and lower cardiovagal tone (p<0.001) than women at rest. Bowel habit was not associated with ANS response. CONCLUSION: IBS have dysregulated non-GI ANS responses to a visceral stressor vs. HCs. In IBS patients, higher sympathetic arousal during sigmoidoscopy was associated with higher perceived unpleasantness of the procedure, suggesting that sympathetic nervous system activation may be an objective physiological correlate of visceral hypersensitivity in IBS.
Tu1432 A Longitudinal Study of Clinical Parameters and Cytokine Profiles in IBS Orla F. Craig, Timothy G. Dinan, Eamonn M. Quigley Background: Immune dysfunction has been postulated to be important in IBS pathogenesis; previous studies have suggested that IBS is characterised by a distinctive pro-inflammatory cytokine profile; it is not known whether the cytokine profile of IBS varies over time. Aim: To characterise the clinical and cytokine profile of IBS over time. Methods: Patients with a clinical diagnosis of a functional bowel disorder were recruited from a specialty outpatient clinic. 58 patients completed a baseline visit, 30 returned for a second visit two months later and 19 for a third visit 6 months after the baseline visit. At each visit they completed the Rome III questionnaire, the patient health questionnaire (PHQ) and the hospital anxiety and depression scale (HAD) and provided a plasma sample. Cytokine production (IFN-γ, TNF-α, IL-8, IL-6, IL-13, IL-10 and IL-12p70) was measured by enzyme-linked immunoabsorbent assay. 19 healthy controls completed 1 visit. Results: 50/58 patients (7 IBS-C, 4 IBS-D, 39 IBS-M) met Rome III criteria for IBS at visit 1. 23/30 (3 IBS-C, 6 IBS-D, 14 IBSM) met the criteria at visit 2 and 15/19 (1 IBS-C, 0 IBS-D, 14 IBS-M) at visit 3. 8/14 meeting criteria for IBS on all three visits had the same IBS subtype at each of the three visits, all IBS-M. Those with IBS-C and IBS-D alternated with IBS-M but not with each other. Of those with IBS 7/50, 4/23 and 2/15 were depressed at visits 1, 2 and 3 respectively as per the HAD scale. 1/14 was depressed at all three visits. 23/50, 12/23 and 6/15 had anxiety at visits 1, 2 and 3. 5/14 had anxiety at all three visits. None of the healthy controls had depression and two had anxiety. While, IFN-γ varied significantly over time, there was no significant variation for the remaining cytokines over the three visits. IFN-γ (p=0.03) and TNF-α (p=0.04) were both lower in those with IBS compared to healthy controls. Looking at IBS sub-types, IFN-γ (p=0.01) and TNF-α (0.04) were lower in IBS-C only; but no significant difference, in comparison to controls, was seen for the other subtypes. IL-6 was numerically higher in IBS but reached statistical significance, in comparison to controls, only for those with IBS and depression (Figure), regardless of whether the HAD questionnaire (p=0.05) or the PHQ (p=0.02) was used. The HAD score for depression was moderately associated with IL-6. (ρ=0.28 CI 0.04-0.49). Over the three-month period co-existent depression was associated with higher levels of IL-6 in those with IBS (p=0.0003). Conclusion: Symptoms of IBS remain stable in terms of bowel pattern and coexistent anxiety over a 6month period; however, depressive symptoms vary. The cytokine profile of IBS sufferers is for the most part stable over time and differs from healthy controls but does not appear to be exclusively pro-inflammatory. Depressive symptoms in IBS are characterised by higher levels of IL-6.
Tu1435 IBS-D and Postprandial Distress Syndrome (PDS) According to ROME III Criteria are More Prevalent Among Patients With History of Cholecystectomy. a Case-Control Study. Amyra A. Azamar Jacome, Federico B. Roesch, Jose M. Remes Troche Background/Aim: Relationship between the development of functional gastrointestinal disorders and cholecystectomy is controversial. For example, it is unclear if irritable bowel syndrome (IBS) is a risk factor for cholecystectomy, or if biliary disease and cholecystectomy predisposes to IBS. Furthermore, the prevalence of IBS and functional dyspepsia (FD) according to Rome III criteria among cholecystectomized patients is not known. Thus, our aim was to compare the prevalence of IBS (and its subtypes) and FD (epigastric pain syndrome, EPS and postprandial distress syndrome (PDS)) among a cohort of cholecystectomized patients and a control group. Material and Methods: In a cross-sectional study 61 patients (mean age 51.4 years, 87% female) with history of cholecystectomy over 2 years were evaluated using the Rome III modular questionnaire Spanish version to assess the prevalence of IBS, FD, EPS, PDS and functional heartburn (FH). Also Bristol stool scale was used. As a control group, 234 subjects (mean age 43.6years, 69% female without history
Tu1433 Constipation in Chagas Disease is Not Related to Megacolon Mauro Bafutto, Alejandro Luquetti, Salustiano Gabriel, Joffre Rezende Filho, Enio C. Oliveira Background:Chaga's disease (CD) may present with constipation, that has been considered only related to megacolon. However, 35-50% of chagasic patients with megacolon do not have constipation(1,2). Small bowel motor disorders and an increase of glucose absorption have been reported in CD patients(3,4) .The role of megacolon and constipation in Chaga's disease is not completely understood. Aim: To evaluate orocecal transit time (OCTT) and
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AGA Abstracts
AGA Abstracts
Tu1431
Gluten Sensitization May Be a Possible Pathogenic Factor for IBS in a Chinese Population Wei Lu, Kok-Ann Gwee, Kewin Tien Ho Siah, Ru Min Lee, Cecilia Cheng Lai Ngan Background: In western populations where there is a high prevalence of celiac disease (CD), serological and tissue markers were found to be more common in patients with irritable bowel syndrome (IBS) phenotype. While CD is believed to be uncommon in Chinese, there is a report from China suggesting that this association may also exist. Aim: To study the prevalence of celiac disease markers in patients with IBS criteria and of Chinese ethnicity from Singapore, where there has been increasing wheat consumption. Method: We explored this association in a cohort of ethnic Chinese patients with IBS by Rome III criteria, who had all undergone IgA anti-gliadin antibody (AGA) and IgA anti-endomysial antibody (EMA) serology testing and duodenal biopsies as part of their clinical workup. In addition, we recalled patients with positive serology for further test of human leukocyte antigens HLADQ2 and HLA-DQ8, which are known to be associated with celiac disease. Result: In 106 patients of Chinese ethnicity who fulfilled Rome III IBS criteria 16 (15.1%) were tested positive for AGA, and 7 (6.6%) had intra-epithelial lymphocytosis reported in duodenal biopsies. None of the patients was positive for EMA. The prevalence of intra-epithelial lymphocytosis (IEL) was numerically higher in patients with positive AGA than negative AGA serology, with 3 (18.8%) and 4 (4.4%) respectively (p=0.105). Similarly, villous atrophy was numerically more common in AGA positive than AGA negative group with 8(50%) and 30(33.3%) respectively (p=0.20). None of these patients had more than mild villous atrophy. The prevalence of Helicobacter pylori infection in AGA positive and AGA negative groups were 18.8% and 28.9% respectively (p=0.40). Nine of the 16 patients in the AGA positive group agreed to undergo HLA-DQ2/8 genotyping, and only 2 patients were positive for HLA-DQ8. These two HLA-DQ positive patients are sisters whose parents had emigrated from the northern part of China where the traditional dietary staple was wheat. Neither of them had villous atrophy, but one had IEL. The other 7 patients who were HLA-DQ2/8 genotype negative were descended from tribes in the southern part of China; one of the patients had concurrent systemic lupus erythematosus (SLE). Five of the 7 patients had villous atrophy, while two of the 7 patients had IEL. Conclusion: Our observations suggest that celiac disease could be present in some ethnic Chinese patients with IBS criteria. However there is a subset of Chinese patients with positive anti-gliadin serology who do not have the full histologic features for celiac disease and were HLA haplotype negative, suggesting that these patients could IBS associated with an immune sensitization to gluten not amounting to celiac disease.
Tu1434 Autonomic Response to a Visceral Stressor is Dysregulated in Irritable Bowel Syndrome and Correlates With Visceral Perception Paul Cheng, Melissa Alberto, Wendy Shih, Angela P. Presson, Arlene Licudine, Emeran A. Mayer, Bruce D. Naliboff, Lin Chang BACKGROUND: Autonomic nervous system (ANS) dysregulation of the gut may play a pathophysiologic role in irritable bowel syndrome (IBS). Previous studies reported altered ANS responses in IBS at baseline or following colonic distension, a meal or mental stress but there is little data to suggest these changes correlate with visceral perception. This is the first study to examine ANS response in IBS during a visceral stressor, a flexible sigmoidoscopy, and its association to visceral perception. AIMS: 1)To compare heart rate variability (HRV) and skin conductance (SC) at rest and during a visceral stressor in IBS patients and healthy controls (HCs) and 2)To examine the effects of sex, psychological symptoms and perceptual ratings of the visceral stressor on ANS function. METHODS:Male and female Rome III positive IBS patients and HCs completed questionnaires to measure GI and psychological (HAD) symptoms. ECG and SC measurements at rest and during a visceral stressor (sigmoidoscopy) were acquired using the BioPac system (BioPac Inc.) for HRV autoregression spectral analysis. Immediately following the procedure, a validated VDVAS (0-20 cm) was used to measure perceptual ratings to the visceral stressor. Linear mixed models using the SAS v9.2 Mixed procedure, Wilcoxon Rank Sum test, Fisher Exact test, and Spearman correlation were used with significance level of 0.05. RESULTS: 36 IBS patients (53% F, mean age 37.89 yrs) and 31 HCs (62% F, mean age 37.26 yrs) participated. IBS bowel habit subtypes were 39% IBS-D, 31% IBS-C, 28% IBS-M, and 3% IBS-U. Compared to HCs, IBS patients had higher HAD anxiety (6.4±0.9 vs. 2.5±0.4, p=0.002) and depression (3.3±0.6 vs. 0.9±0.3, p=0.005) scores but they were in normal range and did not significantly affect ANS responses. IBS and HCs had similar baseline ANS measures. During the visceral stressor, HCs showed an increase in cardiosympathetic tone and a decrease in cardiovagal tone. However, IBS patients had significantly less cardiosympathetic (p=0.012) and cardiovagal (p=0.009) responsiveness vs. HCs. Although SC increased in both IBS and HCs in anticipation to the procedure, it decreased afterwards in HCs but remained elevated in IBS (p=0.017). The change in SC following the visceral stressor positively correlated with unpleasantness ratings of the visceral stressor in IBS (r=0.40, p=0.017) but not in HCs. Men had higher cardiosympathetic tone (p=0.001) and lower cardiovagal tone (p<0.001) than women at rest. Bowel habit was not associated with ANS response. CONCLUSION: IBS have dysregulated non-GI ANS responses to a visceral stressor vs. HCs. In IBS patients, higher sympathetic arousal during sigmoidoscopy was associated with higher perceived unpleasantness of the procedure, suggesting that sympathetic nervous system activation may be an objective physiological correlate of visceral hypersensitivity in IBS.
Tu1432 A Longitudinal Study of Clinical Parameters and Cytokine Profiles in IBS Orla F. Craig, Timothy G. Dinan, Eamonn M. Quigley Background: Immune dysfunction has been postulated to be important in IBS pathogenesis; previous studies have suggested that IBS is characterised by a distinctive pro-inflammatory cytokine profile; it is not known whether the cytokine profile of IBS varies over time. Aim: To characterise the clinical and cytokine profile of IBS over time. Methods: Patients with a clinical diagnosis of a functional bowel disorder were recruited from a specialty outpatient clinic. 58 patients completed a baseline visit, 30 returned for a second visit two months later and 19 for a third visit 6 months after the baseline visit. At each visit they completed the Rome III questionnaire, the patient health questionnaire (PHQ) and the hospital anxiety and depression scale (HAD) and provided a plasma sample. Cytokine production (IFN-γ, TNF-α, IL-8, IL-6, IL-13, IL-10 and IL-12p70) was measured by enzyme-linked immunoabsorbent assay. 19 healthy controls completed 1 visit. Results: 50/58 patients (7 IBS-C, 4 IBS-D, 39 IBS-M) met Rome III criteria for IBS at visit 1. 23/30 (3 IBS-C, 6 IBS-D, 14 IBSM) met the criteria at visit 2 and 15/19 (1 IBS-C, 0 IBS-D, 14 IBS-M) at visit 3. 8/14 meeting criteria for IBS on all three visits had the same IBS subtype at each of the three visits, all IBS-M. Those with IBS-C and IBS-D alternated with IBS-M but not with each other. Of those with IBS 7/50, 4/23 and 2/15 were depressed at visits 1, 2 and 3 respectively as per the HAD scale. 1/14 was depressed at all three visits. 23/50, 12/23 and 6/15 had anxiety at visits 1, 2 and 3. 5/14 had anxiety at all three visits. None of the healthy controls had depression and two had anxiety. While, IFN-γ varied significantly over time, there was no significant variation for the remaining cytokines over the three visits. IFN-γ (p=0.03) and TNF-α (p=0.04) were both lower in those with IBS compared to healthy controls. Looking at IBS sub-types, IFN-γ (p=0.01) and TNF-α (0.04) were lower in IBS-C only; but no significant difference, in comparison to controls, was seen for the other subtypes. IL-6 was numerically higher in IBS but reached statistical significance, in comparison to controls, only for those with IBS and depression (Figure), regardless of whether the HAD questionnaire (p=0.05) or the PHQ (p=0.02) was used. The HAD score for depression was moderately associated with IL-6. (ρ=0.28 CI 0.04-0.49). Over the three-month period co-existent depression was associated with higher levels of IL-6 in those with IBS (p=0.0003). Conclusion: Symptoms of IBS remain stable in terms of bowel pattern and coexistent anxiety over a 6month period; however, depressive symptoms vary. The cytokine profile of IBS sufferers is for the most part stable over time and differs from healthy controls but does not appear to be exclusively pro-inflammatory. Depressive symptoms in IBS are characterised by higher levels of IL-6.
Tu1435 IBS-D and Postprandial Distress Syndrome (PDS) According to ROME III Criteria are More Prevalent Among Patients With History of Cholecystectomy. a Case-Control Study. Amyra A. Azamar Jacome, Federico B. Roesch, Jose M. Remes Troche Background/Aim: Relationship between the development of functional gastrointestinal disorders and cholecystectomy is controversial. For example, it is unclear if irritable bowel syndrome (IBS) is a risk factor for cholecystectomy, or if biliary disease and cholecystectomy predisposes to IBS. Furthermore, the prevalence of IBS and functional dyspepsia (FD) according to Rome III criteria among cholecystectomized patients is not known. Thus, our aim was to compare the prevalence of IBS (and its subtypes) and FD (epigastric pain syndrome, EPS and postprandial distress syndrome (PDS)) among a cohort of cholecystectomized patients and a control group. Material and Methods: In a cross-sectional study 61 patients (mean age 51.4 years, 87% female) with history of cholecystectomy over 2 years were evaluated using the Rome III modular questionnaire Spanish version to assess the prevalence of IBS, FD, EPS, PDS and functional heartburn (FH). Also Bristol stool scale was used. As a control group, 234 subjects (mean age 43.6years, 69% female without history
Tu1433 Constipation in Chagas Disease is Not Related to Megacolon Mauro Bafutto, Alejandro Luquetti, Salustiano Gabriel, Joffre Rezende Filho, Enio C. Oliveira Background:Chaga's disease (CD) may present with constipation, that has been considered only related to megacolon. However, 35-50% of chagasic patients with megacolon do not have constipation(1,2). Small bowel motor disorders and an increase of glucose absorption have been reported in CD patients(3,4) .The role of megacolon and constipation in Chaga's disease is not completely understood. Aim: To evaluate orocecal transit time (OCTT) and
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AGA Abstracts
AGA Abstracts
Tu1431