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1056 Reduced Symptoms and Visceral Sensitivity Is Related to Menstrual Cycle Changes in IBS
AGA Abstracts
1055 Non-Specific Abdominal Pain and Air Pollution: A Novel Association Gilaad G. Kaplan, Brian H. Rowe, Martin Storr, Mieczyslaw Szyszkowicz
1057
Background: Non-specific abdominal pain (NSAP) is one of the most common discharge diagnoses from the emergency department (ED). In many patients an underlying disease is never discovered and the symptoms are often considered functional. NSAP has been associated with depression and headaches, which have both been shown to be exacerbated by exposure to air pollutants. Aim: We studied whether acute exposure to air pollution was independently associated with ED visits for NSAP. Methods: We identified 95,173 patients who visited an Edmonton area ED between April 1, 1992 and March 31, 2002 and were recorded with an ICD-9 code for NSAP (789.0X). We replicated our study by identifying 25,852 ED visits for NSAP at the Jewish General Hospital in Montreal between January 1, 1997 and December 31, 2002. Environmental data were used to calculate the daily mean concentrations for ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and particles <10 (PM10) and <2.5 (PM2.5) micrometers. We performed a timeseries analysis using generalized linear mixed hierarchical models to estimate the percentage value of changes in the relative risk (%RR) with 95% confidence intervals (CI) associated with an increase in the interquratile range (IQR) of SO2, NO2, CO, O3, PM10, and PM2.5 after adjusting for temperature and humidity. Estimates whose 95% CI did not cross 0 were significant. Stratified analyses investigated differential effects by age and gender. Findings: Nearly 2/3 of ED visits for NSAP were by women and the majority of women presented in adolescence and early adulthood. PM10 was significantly associated with NSAP patients aged 15 to 24 years in both Edmonton (%RR = 3.2; 95% CI: 1.1, 5.4) and Montreal (%RR = 8.0; 95% CI: 2.8, 13.5). In women aged 15 to 24 years CO, NO2, and PM10 were positively associated with NSAP in Edmonton [%RR=2.5 (95% CI: 0.4, 4.5); %RR=3.2 (95% CI: 0.4, 6.0); and %RR=3.2 (95% CI: 0.8, 5.6), respectively] and Montreal [%RR =6.0 (95% CI: 2.4, 9.8); %RR=8.2 (95% CI: 2.8, 13.8); and %RR=9.2 (95% CI: 3.4 15.4), respectively]. In contrast, O3 was negatively associated with NSAP in women aged 15 to 24 years in Edmonton (%RR=-4.7; 95% CI: -8.0, -1.4) and Montreal (%RR=-10.6; 95% CI: -16.7, -4.0). Interpretation: Women aged 15 to 24 years were more likely to present to EDs with NSAP when ambient concentrations of CO, NO2, and PM10 were elevated. In contrast, O3 exposure appeared to be negatively associated with NSAP. These findings were identified in two geographically distinct metropolitan Canadian cities.
A Prospective Study of Autonomic Nerve Function in Adults with Cyclic Vomiting Syndrome Thangam Venkatesan, Alexandru Barboi, Thomas Prieto, Walter J. Hogan, Abigail Schroeder, B. U. Li, Safwan Jaradeh Background: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that is characterized by recurrent, stereotypical, discrete episodes of intense nausea and vomiting interspersed with varying symptom-free intervals. There are several postulated mechanisms involved in its pathogenesis and one potential explanation for this disorder may be linked to autonomic dysfunction. Aims and methods: The aim of our study was to prospectively evaluate autonomic nerve function in patients with CVS. The sympathetic nervous system was tested through postural changes in heart rate and blood pressure and the thermoregulatory sweat test. The heart rate response to deep breathing (R-R variability on EKG) was performed to screen for abnormalities of the parasympathetic nervous system. Results: A total of 20 patients who met Rome III criteria for CVS: 15 (75%) women and 5 (25%) men were enrolled in the study. The mean age was 31.6±6.4 years with median duration of disease of 7 years (range 1-30 years). Family history of migraines was elicited in 12(60%) patients and 7(35%) had a personal history of migraine. 12 patients (60%) had evidence of orthostatic tachycardia with an average increase in heart rate of 30 beats/minute without a demonstrable decline in blood pressure in the upright posture. Of these 12 patients, 7 reported symptoms during the test including nausea, abdominal and chest pain, dizziness, fatigue, black floaters, and hypersalivation. On thermoregulatory sweat testing, 18 patients (90%) had abnormalities in sudomotor function with sweat loss involving 5-35% of the body surface area. All 20 patients had abnormal sympathetic nerve function with either postural tachycardia, sweat loss or both. In contrast, 19 patients (95%) had no abnormalities in parasympathetic function with a normal heart rate response (R-R variability on EKG) to deep breathing. Conclusions: The results of this study suggest that patients with CVS have impairment of the sympathetic nervous system while parasympathetic nerve function appears to be intact. These findings of dysautonomia in CVS have implications in both the diagnosis and treatment of these patients. 1058
1056
Differentiation of Gastric ECL Cells in CCK 1+2 Receptor Double Knockout Mice Chun-Mei Zhao, Yosuke Kodama, Arne Sandvik, Duan Chen
Reduced Symptoms and Visceral Sensitivity Is Related to Menstrual Cycle Changes in IBS Miranda A. Van Tilburg, Marsha J. Turner, Olafur S. Palsson, Motoyori Kanazawa, William E. Whitehead
Background/aim: Differentiation of gastric ECL cells is known to be altered in CCK2 receptor knockout (KO) mice. This study investigates the ECL cells in CCK1 receptor KO and CCK1+2 receptor double KO mice, in addition to CCK2 receptor KO mice. Methods: CCK1 receptor KO and CCK2 receptor KO mice were generated by targeted gene disruption as described previously. CCK1+2 receptor double KO mice were generated by intercrossing mice that were homozygous for both mutations. Age/sex-matched wild-type (WT) mice were included. All mice used were 3-4 months of age. Fasted mice were deprived of food for 24 h. Hormones were measured by RIA and the ECL cells were analyzed by immunocytochemistry and electron microscopy. Results: General characteristics in terms of body weight, weights of heart, liver, kidney, pancreas and stomach, lengths of small and large intestine were not different among the 4 strains of the mice neither in freely fed nor in fasted state. Plasma carboxyamidated gastrin concentration was elevated in both CCK2 and CCK1+2 receptor KO mice in fasted state and even more so in freely fed states, but it was not elevated at all in CCK1 receptor KO mice. The elevated plasma gastrin levels in CCK1+2 receptor KO mice were about 30% less than that in CCK2 receptor KO mice in both fasted and fed states. Plasma gly-extended gastrin and progastrin levels were also elevated in both CCK2 and CCK1+2 receptor KO mice in freely fed state but not in fasted state. There was no difference with respect to the plasma levels of carboxyamidated CCK among the 4 strains neither in freely fed nor in fasted state. In CCK1 receptor KO mice, the ECL cells in terms of number and volume density were reduced when visualized by histamine immuno-staining but unchanged by pancreastatin immuno-staining. In CCK2 receptor KO mice, the ECL cells disappeared when stained for histamine but appeared unchanged when stained for pancreastatin. In CCK1+2 receptor KO mice, the ECL cells remained but had a reduced number when stained either for histamine or pancreastatin. Ultrastructure of the ECL cells was apparently normal in CCK1 receptor and CCK1+2 receptor KO mice but markedly altered by a lack of electron-lucent secretory vesicles in the cytoplasm in CCK2 receptor KO mice. In addition, somatostatin-producing D cells were unchanged in all 3 mutant mouse strains compared with WT. Conclusion: CCK1+2 receptor double KO mice displayed a different phenotype of ECL cells compared with CCK2 receptor KO mice, suggesting a possible role of CCK1 receptor in differentiation of the ECL cells.
Background: It has been reported that IBS symptoms increase during menses (Gastroenterol 1990; 98, 1485-89; and 1992; 102: 505-13) but not all women report such an association. We aimed to investigate what variables (psychological distress, visceral hypersensitivity, and motility) are associated with reporting of menstrual cycle variations in IBS. Methods: 156 Female patients (mean age=30.2 years) with IBS (Rome II criteria + physician diagnosis) completed the IBS Severity Scale (IBS-SS; APT 1997;11:395-402), IBS-QOL (Dig Dis Sci. 1998;43:400-11) and a measure of psychological distress (anxiety, depression and somatization, BSI-18 (NCS Pearson, Inc.) and a questionnaire on changes in diarrhea, constipation, pain, bloating and urge during menses. Balloon distensions in the descending colon were performed using a G&J electronic barostat to assess pain thresholds by ascending method of limits. Colonic phasic motility was determined with the motility index (MI, average area under the curve of phasic contractions). All women were tested on non-menses days. Ttest and Chi2 were used to compare women who reported changes in symptoms versus those who did not report changes. Results: Most women reported changes in at least one IBS symptoms during menses (N=113; 72.4%) especially in pain, bloating and diarrhea (see Table 1). Motility, psychological distress, and IBS subtype did not distinguish women who reported increased IBS symptoms during menses versus those women who did not. AML threshold (corrected for Individual operating pressure) was higher in women who reported changes in IBS symptoms during menses (30.06 vs 21.7; p=.02) and IBS severity was lower (236.7 vs 275.9, p=.02). Conclusions: Exacerbation of IBS symptoms during menses is not related to psychological distress or motility disturbance but shows an association with reduced pain sensitivity and reduced symptoms on non-menses days compared to women who do not report menstrual cycle variations in IBS. Prospective studies are needed to investigate if menstrual related exacerbation is identifying a subgroup of patients who have IBS symptoms primarily during menses and not at other times. [Supported by R01 DK31369, R24 DK067674, RR00046 and U54RR024383] Percentage of women reporting changes in symptoms
AGA Abstracts
A-162
1055 Non-Specific Abdominal Pain and Air Pollution: A Novel Association Gilaad G. Kaplan, Brian H. Rowe, Martin Storr, Mieczyslaw Szyszkowicz
1057
Background: Non-specific abdominal pain (NSAP) is one of the most common discharge diagnoses from the emergency department (ED). In many patients an underlying disease is never discovered and the symptoms are often considered functional. NSAP has been associated with depression and headaches, which have both been shown to be exacerbated by exposure to air pollutants. Aim: We studied whether acute exposure to air pollution was independently associated with ED visits for NSAP. Methods: We identified 95,173 patients who visited an Edmonton area ED between April 1, 1992 and March 31, 2002 and were recorded with an ICD-9 code for NSAP (789.0X). We replicated our study by identifying 25,852 ED visits for NSAP at the Jewish General Hospital in Montreal between January 1, 1997 and December 31, 2002. Environmental data were used to calculate the daily mean concentrations for ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and particles <10 (PM10) and <2.5 (PM2.5) micrometers. We performed a timeseries analysis using generalized linear mixed hierarchical models to estimate the percentage value of changes in the relative risk (%RR) with 95% confidence intervals (CI) associated with an increase in the interquratile range (IQR) of SO2, NO2, CO, O3, PM10, and PM2.5 after adjusting for temperature and humidity. Estimates whose 95% CI did not cross 0 were significant. Stratified analyses investigated differential effects by age and gender. Findings: Nearly 2/3 of ED visits for NSAP were by women and the majority of women presented in adolescence and early adulthood. PM10 was significantly associated with NSAP patients aged 15 to 24 years in both Edmonton (%RR = 3.2; 95% CI: 1.1, 5.4) and Montreal (%RR = 8.0; 95% CI: 2.8, 13.5). In women aged 15 to 24 years CO, NO2, and PM10 were positively associated with NSAP in Edmonton [%RR=2.5 (95% CI: 0.4, 4.5); %RR=3.2 (95% CI: 0.4, 6.0); and %RR=3.2 (95% CI: 0.8, 5.6), respectively] and Montreal [%RR =6.0 (95% CI: 2.4, 9.8); %RR=8.2 (95% CI: 2.8, 13.8); and %RR=9.2 (95% CI: 3.4 15.4), respectively]. In contrast, O3 was negatively associated with NSAP in women aged 15 to 24 years in Edmonton (%RR=-4.7; 95% CI: -8.0, -1.4) and Montreal (%RR=-10.6; 95% CI: -16.7, -4.0). Interpretation: Women aged 15 to 24 years were more likely to present to EDs with NSAP when ambient concentrations of CO, NO2, and PM10 were elevated. In contrast, O3 exposure appeared to be negatively associated with NSAP. These findings were identified in two geographically distinct metropolitan Canadian cities.
A Prospective Study of Autonomic Nerve Function in Adults with Cyclic Vomiting Syndrome Thangam Venkatesan, Alexandru Barboi, Thomas Prieto, Walter J. Hogan, Abigail Schroeder, B. U. Li, Safwan Jaradeh Background: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that is characterized by recurrent, stereotypical, discrete episodes of intense nausea and vomiting interspersed with varying symptom-free intervals. There are several postulated mechanisms involved in its pathogenesis and one potential explanation for this disorder may be linked to autonomic dysfunction. Aims and methods: The aim of our study was to prospectively evaluate autonomic nerve function in patients with CVS. The sympathetic nervous system was tested through postural changes in heart rate and blood pressure and the thermoregulatory sweat test. The heart rate response to deep breathing (R-R variability on EKG) was performed to screen for abnormalities of the parasympathetic nervous system. Results: A total of 20 patients who met Rome III criteria for CVS: 15 (75%) women and 5 (25%) men were enrolled in the study. The mean age was 31.6±6.4 years with median duration of disease of 7 years (range 1-30 years). Family history of migraines was elicited in 12(60%) patients and 7(35%) had a personal history of migraine. 12 patients (60%) had evidence of orthostatic tachycardia with an average increase in heart rate of 30 beats/minute without a demonstrable decline in blood pressure in the upright posture. Of these 12 patients, 7 reported symptoms during the test including nausea, abdominal and chest pain, dizziness, fatigue, black floaters, and hypersalivation. On thermoregulatory sweat testing, 18 patients (90%) had abnormalities in sudomotor function with sweat loss involving 5-35% of the body surface area. All 20 patients had abnormal sympathetic nerve function with either postural tachycardia, sweat loss or both. In contrast, 19 patients (95%) had no abnormalities in parasympathetic function with a normal heart rate response (R-R variability on EKG) to deep breathing. Conclusions: The results of this study suggest that patients with CVS have impairment of the sympathetic nervous system while parasympathetic nerve function appears to be intact. These findings of dysautonomia in CVS have implications in both the diagnosis and treatment of these patients. 1058
1056
Differentiation of Gastric ECL Cells in CCK 1+2 Receptor Double Knockout Mice Chun-Mei Zhao, Yosuke Kodama, Arne Sandvik, Duan Chen
Reduced Symptoms and Visceral Sensitivity Is Related to Menstrual Cycle Changes in IBS Miranda A. Van Tilburg, Marsha J. Turner, Olafur S. Palsson, Motoyori Kanazawa, William E. Whitehead
Background/aim: Differentiation of gastric ECL cells is known to be altered in CCK2 receptor knockout (KO) mice. This study investigates the ECL cells in CCK1 receptor KO and CCK1+2 receptor double KO mice, in addition to CCK2 receptor KO mice. Methods: CCK1 receptor KO and CCK2 receptor KO mice were generated by targeted gene disruption as described previously. CCK1+2 receptor double KO mice were generated by intercrossing mice that were homozygous for both mutations. Age/sex-matched wild-type (WT) mice were included. All mice used were 3-4 months of age. Fasted mice were deprived of food for 24 h. Hormones were measured by RIA and the ECL cells were analyzed by immunocytochemistry and electron microscopy. Results: General characteristics in terms of body weight, weights of heart, liver, kidney, pancreas and stomach, lengths of small and large intestine were not different among the 4 strains of the mice neither in freely fed nor in fasted state. Plasma carboxyamidated gastrin concentration was elevated in both CCK2 and CCK1+2 receptor KO mice in fasted state and even more so in freely fed states, but it was not elevated at all in CCK1 receptor KO mice. The elevated plasma gastrin levels in CCK1+2 receptor KO mice were about 30% less than that in CCK2 receptor KO mice in both fasted and fed states. Plasma gly-extended gastrin and progastrin levels were also elevated in both CCK2 and CCK1+2 receptor KO mice in freely fed state but not in fasted state. There was no difference with respect to the plasma levels of carboxyamidated CCK among the 4 strains neither in freely fed nor in fasted state. In CCK1 receptor KO mice, the ECL cells in terms of number and volume density were reduced when visualized by histamine immuno-staining but unchanged by pancreastatin immuno-staining. In CCK2 receptor KO mice, the ECL cells disappeared when stained for histamine but appeared unchanged when stained for pancreastatin. In CCK1+2 receptor KO mice, the ECL cells remained but had a reduced number when stained either for histamine or pancreastatin. Ultrastructure of the ECL cells was apparently normal in CCK1 receptor and CCK1+2 receptor KO mice but markedly altered by a lack of electron-lucent secretory vesicles in the cytoplasm in CCK2 receptor KO mice. In addition, somatostatin-producing D cells were unchanged in all 3 mutant mouse strains compared with WT. Conclusion: CCK1+2 receptor double KO mice displayed a different phenotype of ECL cells compared with CCK2 receptor KO mice, suggesting a possible role of CCK1 receptor in differentiation of the ECL cells.
Background: It has been reported that IBS symptoms increase during menses (Gastroenterol 1990; 98, 1485-89; and 1992; 102: 505-13) but not all women report such an association. We aimed to investigate what variables (psychological distress, visceral hypersensitivity, and motility) are associated with reporting of menstrual cycle variations in IBS. Methods: 156 Female patients (mean age=30.2 years) with IBS (Rome II criteria + physician diagnosis) completed the IBS Severity Scale (IBS-SS; APT 1997;11:395-402), IBS-QOL (Dig Dis Sci. 1998;43:400-11) and a measure of psychological distress (anxiety, depression and somatization, BSI-18 (NCS Pearson, Inc.) and a questionnaire on changes in diarrhea, constipation, pain, bloating and urge during menses. Balloon distensions in the descending colon were performed using a G&J electronic barostat to assess pain thresholds by ascending method of limits. Colonic phasic motility was determined with the motility index (MI, average area under the curve of phasic contractions). All women were tested on non-menses days. Ttest and Chi2 were used to compare women who reported changes in symptoms versus those who did not report changes. Results: Most women reported changes in at least one IBS symptoms during menses (N=113; 72.4%) especially in pain, bloating and diarrhea (see Table 1). Motility, psychological distress, and IBS subtype did not distinguish women who reported increased IBS symptoms during menses versus those women who did not. AML threshold (corrected for Individual operating pressure) was higher in women who reported changes in IBS symptoms during menses (30.06 vs 21.7; p=.02) and IBS severity was lower (236.7 vs 275.9, p=.02). Conclusions: Exacerbation of IBS symptoms during menses is not related to psychological distress or motility disturbance but shows an association with reduced pain sensitivity and reduced symptoms on non-menses days compared to women who do not report menstrual cycle variations in IBS. Prospective studies are needed to investigate if menstrual related exacerbation is identifying a subgroup of patients who have IBS symptoms primarily during menses and not at other times. [Supported by R01 DK31369, R24 DK067674, RR00046 and U54RR024383] Percentage of women reporting changes in symptoms
AGA Abstracts
A-162