April 2000

860

THE RELATION OF GASTROINTESTINAL SYMPTOMS TO PSY­caosocnr. CHARACTERISTICS IN A COMMUNITY·BASEDSAMPLE OF CffiLDREN AND ADOLESCENTS.John T. Stutts, Robyn 1. Claar, Lynn S. Walker, Vanderbilt Univ, Nash­viJIe, TN.

We have previously shown that pain intensity in children with recurrentabdominal pain is significantly correlated with symptoms of depression.This is consistent with recent theories that chronic pain is not a simplesensory phenomenon, but is influenced by behavioral, cogitive and emo­tional factors (McGrath, 1990). The purpose of the present, cross-sectionalstudy was to assess the prevalence of gastrointestinal (GI) symptoms in acommunity sample of school children and to identify the psychosocialcharacteristics of children with high levels of GI symptoms. Study subjectsincluded a group of children and adolescents (n=723) in the CheathamCounty Tennessee School System (319 male; 404 female; ages 7 to 16years; mean age=1O.97 years, SD=2.0J). Children completed self-reportprotocol including the Children's Somatization Inventory (CSI)(Walker,1997), the Positive and Negative Affect Scale (Watson and Clark, 1984)and the Perceived Competence Scale for Children (Harter, 1985). GI­related symptoms on the CSI that were endorsed as "some", "alot", or "awhole lot" included: lump in throat (11% of children), nausea (28%),constipation (5%), diarrhea (4%), abdominal pain (22%), difficulty swal­lowing (12%), vomiting (6%), bloating (7%) and food intolerance (14%).Children were then subdivided into two groups: Group 1 = children whoendorsed 4 or more of the 9 GI symptoms (n=57) (i.e., those scoring2:2SD above the mean GI symptom score) and Group 2 = children whoendorsed fewer than 4 GI symptoms (n=666). The subgroups did not differsignificantly from one another with respect to age, race, or gender. Asignificant difference between the two groups was found for all psychos­ocial domains with Group I children reporting higher test anxiety, highernegative affect, lower positive affect, lower self-esteem, and lower per­ceived social and academic confidence (p-values, 0.001 to 0.01). Theexception was decreased maternal support which approached statisticalsignificance (p=0.06). These data support the association between negativepsychosocial factors and the increased frequency of reported GI symptomsin school-aged children and adolescents. These findings further suggest thatpsychosocial factors should be considered in the clinical evaluation andtreatment of children with multiple GI complaints.

861

DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF NON·CONSTIPATED FEMALE IRS PATIENTS IN THE UNITEDSTATES.Nicholas J. Talley, Steve Kong, Patrice C. Ferriola, Allen W. Mangel, Univof Sydney, Penrith, Australia; Glaxo Wellcome, RTP, NC.

Objective: Irritable bowel syndrome (IBS) is characterized by recurrentabdominal pain, discomfort and alterations in bowel functions. Severallarge studies have confirmed that IBS is a female predominant condition.We have conducted three large, multicenter, US-based IBS trials. In thepresent report, we aimed to describe the characteristics of non-constipatedfemale IBS patients. Methods: 3,467 female IBS patients were evaluated.The intended population to be enrolled in the studies (S3BA2001,S3BA300l, S3BA3002) was non-constipated patients with an IBS historyof at least 6 months as determined by the Rome I Criteria. IBS symptomswere gathered during a two week period without IBS treatment. Results:The mean age at time of entry into the studies was 45 years and patientsreported a mean duration of IBS symptoms of 10 years. Overall, theenrolling physicians classified 58% of the patients as diarrhea-predominantand 35% as alternators. Eighty-eight percent of patients were white and,with the exception of mucus, at least 80% of the patients fulfilled each ofthe Rome I Criteria for IBS. Patients reported: moderate severity abdom­inal pain/discomfort; approximately 23% of the days as pain/discomfortfree; an average stool frequency of 2.3 bowel movements per day; approx­imately 60% of the days with urgency; and approximately 70% of the dayswith bloating. A high degree of consistency was shown between the studies(Table below). Conclusions: In the 3 large studies considered, non-consti­pated, female IBS patients showed a high degree of consistency for clinicaland demographic characteristics.

ISS and Demographic Characteristics

AGAA147

862A PATIENT BASED SYMPTOM QUESTIONNAIRE FOR USE INIRRITABLE BOWEL SYNDROME (IRS).Ingela K. Wiklund, Steve Fullerton, Christopher 1. Hawkey, Roger H.Jones, George F. Longstreth, Robert Peacock, Ingalill K. Wilson, Astra­Zeneca R&D Molndal, Molndal, Sweden; Div of Digest Diseases, UCLASch of Medicine, Los Angeles, CA; Div of Gastroenterology, Univ Hosp,Nottingham, United Kingdom; Dept of Gen Practice & Primary Care, GKTSch of Med, London, United Kingdom; Dept of Gastroenterology, KaiserPerrnanente Med Ctr, San Diego, CA.

Background: There is no standard questionnaire that captures differentsymptom clusters in IBS. Therefore, the Gastrointestinal Symptom RatingScale (GSRS) was modified by including symptoms characterising IBSaccording to the Rome criteria. Aim: To describe the development of theGSRS-IBS version and its psychometric properties. Patients and methods:patients (female 77%; mean age 44 yrs), with moderate to severe IBSsymptoms included in a "mock trial" conducted in the UK and the UScompleted the questionnaire at baseline and after 6 and 12 weeks oftreatment (treatment provided at the discretion of the investigator). Themodified GSRS had 22 items using 7-graded Likert scales. Results: Afactor analysis identified 5 symptom clusters explaining 74% of the vari­ance. Symptoms with a high ceiling effect (i.e. representing no problems)and symptoms of the upper GI tract were discarded. The symptom clustershad a high internal consistency: bloating (a=0.79), diarrhoea (a=0.83),constipation (a=0.82), pain (a=0.75) and satiety (a=0.85). The testre-test reliability after 6 weeks ranged from 0.55-0.70. Intercorrelationsbetween the symptom clusters were low, r=0.08 to r=0.51, indicating thatfive separate factors had been distinguished. Pain, bloating and diarrhoeawere the most bothersome clusters. High correlations between pain, bloat­ing and diarrhoea and IBS specific quality of life impairment in terms ofdaily activities, emotional distress and fatigue supported the constructvalidity. In patients identified as treatment responders effect sizes werelarge for pain (>0.80), and moderate for bloating (>0.40), and diarrhoea(>0.40), whilst constipation and satiety showed insignificant change. Con­clusion: The GSRS-IBS version is reliable, valid and responsive to changefor symptom clusters depicting pain, bloating and diarrhoea.

863DIFFERENTIAL ACTIVATION OF MAP KINASES BY ACETYL·CHOLINE (ACH) IN NORMAL AND INFLAMED COLONIC CIR·CULAR MUSCLE CELLS.Irshad Ali, Sushil K. Sarna, Med Coli of Wisconsin and Zablocki VA MedCtr, Milwaukee, WI.

Recent studies show that several cells express multiple families of proteinkinases known as mitogen-activated protein kinases (MAPKs) includingextracellular signal-regulated proteins (ERKs). Their role in the contractionof canine colonic circular muscle cells and its modification during inflam­mation is not fully understood. AIM: Our aim in this study was toinvestigate whether specific MAP kinases are activated by muscarinicreceptor stimulation with ACh and if this activation is modified in inflamedcells. METHODS: Circular muscle cells were enzymatically dissociatedfrom the normal and the inflamed dog colon. Tissues were harvested 48 hafter induction of colonic inflammation by mucosal exposure to ethanoland acetic acid. Western immunoblots using antibodies to phosphorylatedMAPKs were employed to determine the activation of kinases. RESULTS:ACh (1.0 p,M) treatment activated ERKI and ERK2 within 30 sec but themaximum was reached at 5 min (198±45% and 130± 12% of control forERKI and ERK2, respectively, n=5, p<0.05) in normal colon cells. Theactivation of these MAPKs was delayed in inflamed cells to about 5 min(146±9.6 and 155± 12.1% of control, respectively, n=6, p<O.05). ACh­mediated cell contraction was significantly inhibited by 10 p,M genestein(87±7%), a tyrosine kinase inhibitor, as well as by 10 p,M PD98059(85±4%), map Kinase kinase (MEK) inhibitor, at 40 sec in normal cellsbut not in inflamed cells. This is likely due to the delayed activation ofERKI and ERK2 as noted above. ACh treatment of the cells also activatedMAPK p38 at 30 sec (651± 188% of control, n=4, p<0.05) but the peakwas reached at 60 sec (791±265% of control, n=4, p<0.05). p38 kinasewas not activated by ACh in cells from the inflamed colon for up to 5 min.CONCLUSIONS: 1) MAPKs are activated in signalling mechanisms forcontraction of colonic circular muscle cells by ACh. 2) Specific MAPKsactivate at different times and by different amounts. Therefore, they exhibitthe potential to mediate the stimulation of different types of coloniccontractions, such as short and long duration phasic contractions, giantmigrating contractions, and tone. 3) The activation of MAPKs is signifi­cantly delayed and suppressed during inflammation that may, in part,contribute to the alterations in colonic motility seen in inflammation.

Parameter Study I (n=587) Study II(n=1416) Study III(n=1463)

Age (years)Duration of 185 Symptoms (years)StoolS/DIY%Days Urgency%Days Bloating

44.99623

61.3%73.9%

45.811.12.3

62.4%70.3%

45.410.02.3

59.8%69.6%