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the child's G1, cold, and SZ symptoms. Differences between prepubertal children (ages 710) and adolescents (ages 13-17) were assessed. Results: (1) For GI symptoms, children of mothers with IBS (case children) report more symptoms than control children (p<.001) and girls report more GI symptoms than boys (p = .04), but there was no age difference and no interaction between age and gender. (2) For SZ symptoms, case children report more symptoms than controls (p<.001), girls report more symptoms than boys (p =.04), and adolescents report more symptoms than children (p <.001 ). Consistent with our hypothesis, there was a significant interaction between age and gender (p = .05). Post-hoc tests showed that adolescent girls report more symptoms than adolescent boys (p = .02% but there was no gender difference for children. (3) For cold symptoms, there were no differences between cases and controls, but girls reported more cold symptoms than boys (p = .001), adolescents reported more cold symptoms than children (p = .04), and there was a significant interaction between age and gender (p= .01). Post-hocs indicated that adolescent girls reported more cold symptoms than adolescent boys (p<.001), but there was no gender difference for young children. (4) Similar results were obtained when parent's report of symptoms was used in analyses. Conclusions: Results suggest that children of mothers with 1BS are at increased risk for GI symptoms throughout childhood and adolescence. The hypothesis that male-female differences in symptom reporting emerge after puberty was confirmed for SZ and cold symptoms. For GI symptoms, girls report more symptoms than boys independent of age. Supported by RO1 HD36069.
Synergistic Induction of Cyclooxygenase-2 by Gastrin and EGF in Intestinal Epithelial Cells Ji-Zhong Cheng, Yan-Shi Guo, Mark R. Hellmich, Courtney M. Townsend Jr Cyclooxygenase-2 (COX-2) is aberrantly overexpression in gastrointestinal cancers and has been implicated in carcinogenesis and cancer progression; but the regulation of COX-2 expression has not been well defined. EGF is an inducer of COX-2 expression. We recently reported that gastrin stimulates the expression of COX-2 mRNA, protein and its promoter activity in intestinal epithelial cells (Guo et al, J Binl Chem 2002, in press). The purpose of this study was to determine whether gastrin collaborates with EGF to synergistically induce COX-2 gene expression in RIE/CCKBR cells, and if so, what mechanisms are involved. METHODS. RIE/CCKBR cell line, denved from rat intestine epithelial cells (RIE- 1), possesses native EGF receptor (EGFR) and was stably transfected with CCK-B receptor. The COX-2 mRNA, protein and promoter activity were determined by Northern blot, Western blot and luciferase analyses, respectively. The phnsphorylation of extracellular signal-regulated kinase (ERK) was examined using anti-active ERK1/2 antibody. Tyrnsine phosphorylation of EGER was determined by immunoprecipitating with anti-EGFR and blotting with anti-phosphotyrosine antibodies. RESULTS. Gastrin (100 nM) or EGF (20 ng/ml) alone induced a timedependent increase of COX-2 protein levels (3 to 5 folds) in RIE/CCKBR cells. The combination of both peptides synergistically stimulated the COX-2 protein expression (10 to 30 folds), and increased the COX-2 mRNA abundance and COX-2 promoter activity. The synergistic effect was significantly suppressed by AG-1478, a selective inhibitor of EGFR tyrosine kinase activity; whereas gastrin induced a EGF-independent phnsphorylation of EGFR. The synergistic induction of COX-2 also was partially blocked by donnnant negative Src construct and the selective Src inhibitor PP2. Moreover, the combination of gastrni and EGF elicited a synergistic increase of ERK1/2 phosphorylation, whereas PD98059, a specific inhibitor of MEK/ERK pathway, significantly inhibited the induction of COX-2 in response to combined gastrin and EGF. CONCLUSION. Gastrin may collaborate with EGF to synergistically induce COX-2 expression in intestinal epithelial cells. The synergistic induction of COX-2 requires the gastrin-mediated transactivation of EGFR, and the activation of Src and ERK kinases. These findings provide a better understanding of the regulating mechanisms of COX-2 in intestinal epithelial cells.
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Visceral Hypersensitivity and Relation to Symptoms in the Irritable Bowel Syndrome (IBS) Iris Posserud, Gisela Ringstrom, Pia Agerforz, Einar S. Bjomsson, Hasse Abrahamsson, Magnus Simren Visceral hypersensitivity is an important factor in IBS. However, the relationship between visceral sensory dysfunction and symptoms is unclear. AIMS: Investigate the correlations between colorectal sensitivity and symptoms in IBS patients. METHODS: Sixty-one healthy controls (HC) (39 females; mean age 33, range 20-70) and 109 IBS patients (27 constipation predominant, 51 diarrhea predominant, 31 alternating IBS) (81 females; mean age 40, range 19-71) were studied. Twenty-four HC and 72 patients underwent sigmoid colon balloon distensions and 37 HC and 37 pauems underwent rectal distensions Sensory thresholds (mmHg) for discomfort and pain were determined. Hypersensitivity was defined as the mean threshold for discomfort and pain in HC -2 SD. Patients completed a symptom questionnaire (12 bowel related, 6 dyspeptic and 10 extraintestinal symptoms). Symptoms were labeled as being absent, present or relevant/severe and correlated to colorectal sensitivity. RESULTS: A total of 54% of the patients were hypersensitive to colorectal distensions (colon 50%,vs. rectum 62%; p>0.20). In a univariate analysis, presence of fatigue, depression, anxiety, sleeping difficulties and absence of relevant/severe symptoms of infrequent stools were more common in hypersensitive patients (p<0.05). Using a logistic regression analysis, the presence of anxiety (OR 2.75, 95% CI 1.02-7.41; p<0.05) and absence of relevant/severe symptoms of infrequent stools (OR 0.22, 95% C1 0.06-084; p<0.03) were found to be independently associated with visceral hypersensitivity. Lower sensory thresholds for discomfort and pain were observed in patients that underwent colonic distensions and suffered from relevant/severe symptoms of pain and abdominal distension, as well as relevant/severe extraintestinal symptoms, such as fatigue, depression, anxiety and sleeping difficulties. [n patients that underwent rectal distensions, relevant/severe symptoms of infrequent and hard stools were associated with higher sensory thresholds for discomfort and pain. Hypersensitivity was unrelated to IBS-subgroups and gender. CONCLUSION: Visceral hypersensitivity relates to extraintestina] symptoms and some, but not the majority of, bowel related symptoms seen in IBS. This suggests that the link between visceral hypersensitivity and symptoms in IBS is complex and that there is no clear direct cause-effect relationship. Our findings also indicate regional differences in the relation between visceral sensitivity and symptoms.
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Comparison of Irritable Bowel Syndrome (IBS) Patients in Gastroenterology and Primary Care Clinics Olafur S. Palsson, Andrew D. Feld, Rona L Levy, Michael Von Korff, Victoria E. Barghout, Marsha J. Turner, William E. Whitehead IBS patients who see G1 specialists are often thought to have more severe symptoms and greater psychopathology than those seen in primary care. However, no published U.S. data comparing IBS patients in the two settings exist to evaluate this notion. Aims: To compare IBS symptoms and demographic and psychological characteristics of patients in gastroenterology (G1) and primary care (PC) clinics in the same geographical area. Methods: Consecutive patients diagnosed with IBS, functional diarrhea, constipation or abdominal pain visiting the GI and PC clinics of a large northwestern health maintenance organization (HMO) were invited to participate in a mail survey. Sixteen hundred and three patients completed questionnaires including demographic questions, the Rome Modular Diagnostic Questionnaire for 1BS, the IBS-QOL (Dig Dis Sci. 1998;43:400-11), the IBS Severity Questionnaire (Aliment Pharmacol Ther 1997;11:395-402), Brief Symptom Inventory-18 (NCS Pearson, Inc.), and the Recent Physical Symptoms Questionnaire (RPSQ) and Comorbid Medical Conditions Questionnaire (Gastroenterol 2002;122(Suppl 1):A502). Data from the 145 GI patients and the 650 PC patients who met Rome I[ cnteria for IBS were compared. Results: GI clinic patients were significantly (p<.05) older and had more formal education than PC patients PC and GI patients did not differ in overall scores on the 1BS Severity Index (mean +/- S.E: 298.78 +/- 5.24 v~s. 295.13 +/- 10.66; n.s.) nor in their ratings of abdominal pain severity (56.57 +A 1.07 vs. 52.73 +/- 2.34; n.s.) or frequency (# of days out of 10 days: 5.66 +A 0.16 vs. 5.40 +/- 0.31; n.s.). Contrary to hypothesis, PC patients scored significantly higher (p< 05) on all scales of the Brief Symptom Inventory: anxiety (4.20 +A 0.18 vs. 341 +/- 0 32),-depression (4.03 +/- 0.18 vs. 3.13 +/- 0.34), somatization (5.00 +/- 0 1 7 v s , 4.13 +/- 0.32), and overall psychological symptom severity (13.12 +A 0 4 6 vs. 10.52 +/- 079). PC patients did not differ from GI patients in 1BS-QOL scores, number of co-morbid medical conditions or RPSQ somatization scores. Conclusions: Neither of our a priori hypotheses was confirmed. IBS patients in GI and PC clinics have equivalent IBS symptoms and comparable health-related quality of life and medical comorbidity; and patients seen in primary care have higher (not lower) average levels of psychological symptoms. (Supported by RO1 DK31369, RO1 HD36069 and a grant from Novartis Pharmaceuticals Corp.)
125 Is Abdominal Bloating Related to Physical Distension in Patients with Irritable Bowel Syndrome (IBS)? Richard Lea, Lesley A. Houghton, Brian Redly, Peter J. Whorwell Abdominal bloating and distension are frequently reported symptoms in patients with IBS, but it is unknown whether they are related. Previous studies have attempted to quantify distension using a tape measure (1,2), but this is prone to patient and/or investigator bias, and only allows static measurements at specific times. We have recently validated the technique of Ambulatory Abdominal Inductance Plethysmography (ALP)to objectively assess abdominal girth (3), and it was the aim of this study to use this technique to assess whether (i) IBS patients distend more than healthy volunteers, and (ii) physical distension is related to subjective reports of abdominal bloating. Methods: Abdominal girth was recorded for 24 hours in 21 patients meeting Rome II Criteria for 1BS (aged 18-59yrs yrs; 2 male) and 9 healthy female volunteers (aged 29-67 yrs). All subjects were encouraged to pursue normal daily activities, and the symptom of abdominal bloating was scored on a 0-3 scale, where 3 =severe bloating. Results: In patients with IBS, abdominal girth was significantly greater at the end compared with the beginning of the day 1 (end: 93.1cm (85.4, 100.8)cm, mean (95%CI) v beginning: 89.7cm (83.2, 96.2)cm; p = 0.008). On waking the following morning (day 2), girth had significantly decreased (87.9cm (81.3, 94.6)cm; p<0.0001). In healthy volunteers, there were no significant changes in girth throughout the 24 hours (beginning of day 1: 90.7cm (83.2, 98.1)cm, end of day h 91.0cm (83.0, 99.0)cm, waking on day 2: 89.8cm (82.3, 97.3)cm). Comparing IBS patients with volunteers, the changes in girth from the beginning to end of day 1 (patients + 3.4cm (1.0, 58)cm v volunteers + 0.3cm (-4.4, 5.1)cm; p=0.18) and from the end day 1 to waking on day 2 (- 5.1cm (-3.0, -7.3)cm v1.2cm (2.6, -5.1)cm; p<0.05) were greater in the patients. Lastly, the change in girth from the beginning to the end of the day, directly correlated with the patients subjective reporting of their abdominal bloating on that day (r = 0.48; p = 0.03). Conclusions: These are the first objective data showing that IBS patients do experience progressive abdominal distension throughout the day and that this is related to their subjective reports of abdominal bloating.
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Age and Gender Effects on Pediatric Gastrointestinal Symptoms Lynn S. Walker, Rnna L Levy, Andrew Eeld, Michael Von Korff, Dennis Christie, William Whitehead Functional gastrointestinal (GI) symptoms and somatization (SZ) symptoms are more common in women than men. Both types of symptoms aggregate in families and may, in part, be learned during childhood. It is not known when the gender difference emerges. Aim: We tested the hypothesis that pre-puberta[ girls and boys would not differ on GI or SZ symptoms, but among adolescents, girls would exhibit more GI and SZ symptoms than boys, particularly if the mother had a functional GI disorder (FGID). Cold symptoms, which are less likely to be influenced by social learning, were not expected to differ by child age, gender, or maternal FGID. Methods: Subjects were 296 children of mothers with IBS (case children) and 335 children of mothers without IBS (controls), mean age 11.8 years, 51% female. The Child Symptom Checklist was completed by children and parents describing
AGA Abstracts
A-14