Tolerance of lleal and colonic gas loads in patients with irritable bowel syndrome and functional bloating

practical use for primary care physicians. Finally, as our study proved only 2 % of the investigated individuals to be 'pure D-lOS patients', the existence of diarrhea-predominant IBS is questionable.

decision only, were documented. Results: Despite an overall improvement of dyspeptic symptoms and 0ol over time, there were subgroups of patients which showed no improvement of 9ol (O-) or dyspeptic symptoms (S-) after 1 year (26.7% and 28.1%) and 2 years (22.4% and 21.0%). Although of similar size these two subgroups were not identical, with about half of each group showing overlap (S-/O- 13.3%, S-/Q + 14.9%, S +/O- 13.4%, S +/Q + 58.4%). Compared with responder (S+/Q+), S-/Q- showed more male (49% vs 39%) and S-/G+ more female (67% vs. 61%). Symptom non-resonders (S-) showed a higher age (52 vs. 48 y.), a lower prevalenceof smoking (22.4 vs. 28.7%), a higher rate of tea consumption (57.5% vs. 49.0%), but no differences in body size, body weight, weight gain/loss over 2 years, consumption of alcohol, history of smoking, or the symptom classification (ulcer-, reflux-, dysmotilify-, undetermined type). They were more likely to have initally severe/very severe dyspeptic symptoms, and during follow up they were more likely to experience their current life situation as continuous stress (S- vs. S +: intial visit 43.4% vs. 47.8%, at t year 41.4% vs. 29.6%, at 2 years 31.9% vs. 26.2%). Management with initial endoscopy was associated with lower rates of non-responders (S-/Q- 8.0%, S-/O+ 11.4%, S+/Q- 11.4%) than initial empirical therapy (S-/O- 13.6%, S-/Q+ 15.0%, S+/Q- 14.1%) or no initial therapy (S-/020.4%, S-/O+ 20.4%, S+/O- t3.0%). Conclusion: Patients with FD not responding with symptom improvement during long term follow up can be subdivided in a group which shows improvement of qualify of life and one which does not. Both clinical management factors as well as individual behaviors of the patients showed characteristic differences betweenresponders and non-responders, but none of this factors alone was able to predict non-responsiveness during the follow up. (Study supported by an educational grant from Janssen Cilag, Germany).

4O56 Reclassification of Functional Bowel Disorders with Rome II Diagnostic Criteria Danilo Badiali, Gala Altobelli, Enrico Corazziari, Dept Science Cliniche, Universita' La Sapienza, Rome Italy Functional bowel disorders (FBD) manifest clinically with the presence of one or more of the following symptoms: abdominal pain, abdominal discomfort and bowel dysfunction in absence of any objective evidence of structural and biochemical alteration. Standardized symptombased diagnostic criteria are therefore the only available means to define and subtype them, A previously standardized definition of FBD (Rome/criteria 1) has been recently revised (Rome //criteria2). Aim of this study was to evaluate how Rome//criteria classify FBD in comparison to Rome (criteria. Two hundred and eighty-one consecutive out-patients (F:188; mean age 42.5 yrs, range:14-77 yrs), referred to our GI clinic, were thoroughly investigated and asked to fill in a validated 43 item questionnaire addressing clinical history, abdominal symptoms, and bowel dysfunction. Results: The final diagnosis was chronic functional GI disorders in 200 pts and organic disease in 62 pts, 19 were unclassified. Patients diagnosed as having IBS according to the Rome I criteria were 67. The Rome II criteria confirmed this diagnosis in 45 pts (67%), and reclassified the remaining 22 pts as: Functional Constipation (FC) (22.5%), Unspecified Functional Bowel Disorders (UFBD) (6%) and Functional Abdominal Bloating (FAB) (4.5%). Patients diagnosed as having UFBD according to the Rome I criteria were 35. The Rome/I criteria confirmed this diagnosis in 25 pts (71%), and reclassified the remaining 10 pts as: lOS (26%) and FC (3%). Patients defined FC with Rome I criteria were 38, and this diagnosis was confirmed in all of them with Rome II criteria. The diagnosis of FAB with the Rome I criteria was made in 11 pts and it was confirmed with the Rome II criteria in all of them. Conclusions. About 33% of patients defined as IBS with the Rome I criteria were reclassified with the Rome/I criteria, and most of them were defined as Functional Constipation. Moreover, 29% of patients defined as Unspecified Functional Bowel Disorder with the Rome / criteria were reclassified, the majority as IBS, with Rome//criteria. These data indicate that, in comparison to Rome I criteria, Rome/I criteria can better discriminate subtypes of Functional Bowel Disorders that appear to comprise more homogenous groups of patients. (1)Thompson WG et al. Irritable bowel syndrome: guidelines for the diagnosis. Gastroenteml Int 1989;2:92 (2)Thompson WG et aL Functional bowel disorders and functional abdominal pain. Gut 1999;45(suppl II):1143

4054 The Role of Gender and Bowel Habit Predominance on Visceral Perception in IBSo Lin Chang, Bruce D. Naliboff, UCLA/CURENeuroenteric Disease Prog, UCLA Sch of Medicine, Los Angeles, CA; Max Schmulson, Dept de Gastroenterology, Inst Nacional, Mexico DF Mexico; Oh Young Lee, Hanyang Univ, Seoul South Korea; Teresa I. Olivas, Emeran A. Mayer, UCLA/CURENeuroenteric Disease Prog, UCLA Sch of Medicine, Los Angeles, CA BACKGROUND: Recent studies suggest that IBS patients show gender and bowel habit differences affect physiologic and treatment responses. However, such differences in visceral perception have not been well studied. AIM: To evaluate the effect of both gender and bowel habit predominance in IBS on perceptual responses to visceral stimulation. METHODS: 58 lOS (mean 42 _+ 1 yrs; 34 males, 24 females) and 26 healthy controls (mean 38 +_ 3 yrs; 9 males, 17 females) underwent recto-sigmoid balloon distention. IBS-D was defined as > 3 BMs/d and/or loose or watery stools and no hard or lumpy stools. IBS-C was defined as < 3 BMs/wk and/or hard or lumpy stools and no loose or watery stools. IBS-A was defined as alternating bowel habits that did not meet IBS-D or IBS-C criteria. There were no significant differences in bowel habit predominance between males [IBS-D (n = 14), IBS-C (n = 6), IBS-A (n = 14)] and females [IBS-D (n = 8), IBS-C (n = 7), IBS-A (n = 9)]. Visceral distention was performed using a double balloon catheter (1 rectal, 1 sigmoid) connected to a barostat. Rectal discomfort thresholds were measured using a randomized, phasic distention (tracking) paradigm before and after noxious sigmoid stimulation (SIC, 60 mmHg intermittent pulses). RESULTS:Comparedto controls, lOS patients had lower rectal discomfort thresholds pre- (34 _+ 2 vs. 41 +_ 3 mmHg) and post-SIG (32 -+ 2 vs. 37 _+ 3 mmHg) (both p < 0.05). With respect to gender, there was significant interaction between males and females (p < 0.05). While there was significant decrease in rectal thresholds from pre- to post-SIC in both control females (45 -+ 4 to 39 _+ 3 mmHg) and lOS females (29 -+ 3 to 25 _+ 2 mmHg)(both p < 0.91), there was no change in thresholds in control males (34 -+ 4 to 34 -+ 4 mmHg) and IBS males (37 _+ 3 to 37 +- 3 mmHg). With regard to bowel habit predominance, IBSC and IBS-A patients had simitar rectal thresholds, which were significantly lower pre- and post-SIG, compared to IBS-D (p < 0.05). Gender and bowel habit were each related to thresholds after controlling for the other. CONCLUSIONS:1) Gender and bowel habit independently influenced visceral sensitivity; 2) Femalecontrols had higher baseline rectal discomfort thresholds compared to males and IBS females; 3) Both female groups demonstrated sensitization following SIC while both male groups did not. In contrast to previously reported greater autonomic (sympathetic) responses to rectosigmoid distention in male subjects, women show greater viscerosensory responses to this paradigm. Supported by NIH #AR41622 (LC), #DK48351 (EAM), AstraZeneca

4057 Physiological Markers For The Rome II Clinical SubgroupsIn Functional Dyspepsia. M Pia Caldarella, Fernando Azpiroz, Hosp Gen Vail d'Hebron, Barcelona Spain; Maria Vilagrasa, Hosp Germans Trias, Barcelona Spain; Juan R. Malagelada, Hosp Gen Vail d'Hebron, Barcelona Spain BACKGROUND.The recognition of subgroups in functional dyspepsia is based on symptoms, but the relevanceof clinical subgroups would be enhanced by objective physiological markers, METHODS.In 30 patients with functional dyspepsia (15 dysmotility-like, 15 ulcer-like classified by Rome II symptom criteria) and 22 healthy subjects we tested the responses to gastric distension using two different paradigms: a) with the subjects in the upright position the proximal and the distal stomach were selectively distended by air-filled and water-filled bags, respectively; b) with the subjects in the right and left lateral decubitus, proximal and distal gastric distension were respectively performed with air-filled bags connected to a tensostat, Perception of gastric distension was measured by a 0 to 6 score scale. RESULTS. Both ulcerand dysmotility-like dyspepsia showed similar increased perception of proximal stomach distension with normal values of compliance. By contrast, fixed volume distension of the antrum showed a significantly more severe intolerance in ulcer-like than in dysmotility-like dyspepsia (discomfort at 86_+14 ml vs 183-+24 ml, respectively; p
4055 Does Diarrhea Predominant Irritable Bowel Syndrome Really Exist? Rodolfo E A Seelis, Gastroenterology, Aachen Germany; Werner Dohmen, Gen Medicine, Aachen Germany Background: The updated 'Rome Ir criteria reflect recent advances in the diagnosis of irritable bowel syndrome (IBS). However, a number of other gastro-intestinal (GI) conditions may have symptoms similar to lOS, especially similar to type I, diarrhea-predominant IBS (D-IBS). Therefore, our aim was to validate the usefullness of the 'Rome I1' criteria in primary care. Method: Following diagnosis of D-IBS as assessed by the 'Rome I1' criteria further diagnostic screening of O-lOS patients was performed in order to exclude possible organic, metabolic, infectious, functional and structural diseases by means of endoscopy of the upper and lower GI-tract (including histology), by blood biochemistry, by stool examination (e.g. elastase I), by tests for carbohydrate malabsorption and by 75-SeHCAT-test. Results: Having excluded infectious and inflammatory bowel disease, finally in 351 general practice patients (age 44.4 + 15.5 years; female : male = 65% : 35% ) D-IBS was diagnosed according to the 'Rome Ir criteria. However, further diagnostic screening of these patients revealed additional GIdisorders as lactose-intolerance (n = 162 patients (p.) = 46%), xylose-intolerance (n = 8tp. = 23%), pancreatic insufficiency (n = 68p. = 19%), pathological bile acid resorption (n = 26p. = 7%), coeliac disease (n = 4p. = 1%), microscopic colitis (n = 2p. = 0.5%), hyperthyroidism ( n = 2p. = 0.5%). In 10 % of the suspected D-IBS patients combinations of up to 3 different GI-disorders were found. In contrast, only 2 % of all suspected D-lOS patients proved negativefor all applied tests. Conclusion: Above listed, additionally discovered GI-disorders of our patients were misdiagnosed as D-IBS by only using the Rome II criteria. Our data suggest, that symptom related classifications, e.g. Rome II criteria, are of limited

4058 Tolerance Of Ileal And Colonic Gas Loads In Patients With Irritable Bowel Syndrome And Functional Bloating. Beatrice Salvioli, Jordi Serra, Fernando Azpiroz, Juan-R Malagelada, Digest System Research Unit, Hosp Vail d'Hebmn, Barcelona Spain BACKGROUND/OBJECTIVES.Using a gas challenge test, we have previously demonstrated that patients with irritable bowel syndrome and functional bloating have impaired intestinal propulsion, and developed gas retention and symptoms in response to infusion of gas into the jejunum. However, the area of the gut responsible for defective propulsion and perception remains unknown. To establish the specific contribution of different gut segments, we have now investigated the responses to distal gas infusion. METHODS. In 6 patients with irritable bowel syndrome and predominant bloating and 6 patients with functional bloating and in 8 healthy subject~ a mixture of gas (N2, 02 and C02 in venous proportions to minimize diffusion) was infused at 12 ml/min for 2 hours either into the ileum (105 cm distal to the angle of Treitz) or the caecum by means of oro-enteric intraluminal catheters positioned under fluoroscopic control. Gas collection was continuously monitored via an intrarectal catheter by means of a barostat, and abdominal perception was measured by a O to 6 score scale at 15 min intervals. Gas was infused into the ileum in 6 patients and 4 healthy controls and into the

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caecum in another 6 patients and 4 controls. RESULTS. Infusion of gas into the caecum failed to produce retention (-143_+88 ml in patients and -25_+39 ml in controls; N.S.), or symptoms (perception score 2.3_+0.5 in patients and 1.0_+0.8 in controls; N.S.). Likewise, infusion of gas into the ileum produced neither retention (61 _+103 ml in patients and 80-+142.5 ml in controls; N.S.) or symptom perception (score 2.5_+0.6 in patients and 1.2_+0.4 in controls; N.S.). Overall no patient developedmore than 400 ml gas retention, and only 1 out of 12 patients reportedsymptoms abovescore 4. CONCLUSION.Normal propulsion and tolerance of distally infused gas suggests that the proximal small bowel is responsable for abnormal propulsive and symptomatic responsesto gas loads in patients with irritable bowel syndrome and functional bloating.

Validation Of Adequate Relief As An EndpointIn Clinical Trials In Functional Dppepsia Mark R. Heath, Teresa B. Perschy, Susan C. Sorrells, Christi S. Kleoudis, George E. Dukes, Allen W. Mangel, Giaxo Wellcome Inc, ResearchTriangle Park, NC Background: Functional dyspepsia (FD) is characterized by persistent or recurrent pain or discomfort cantered in the upper abdomen, no altered bowel function and no evidence of organic disease,Additional symptoms of FD can include early satiety, postprandial fullness, bloating, and nausea.One of the greatestchallengeswhen designing studies for the treatment of FD is to define endpoints that reflect improvement in the multiple symptoms present in FD. In the present study we evaluatedthe adequate relief (AR) of upper abdominal pain or discomfort as an efficacy endpoint in FD patients. Methods: 320 FD patients (220 F, 100 M), as defined by Rome I criteria, were enrolled into a 12-wk study with a novel therapeutic agent ($3B20015). Datafor individual symptoms of FD (upper abdominal pain, early satiety, postprandial fullness, blnating/distension, nauseaand burping/belching) were collected daily as secondary measures using a telephone based diary system. Once every 7 days patients ware asked to respond "Y" or "N" to the AR question, "In the past seven days have you had adequate relief of your upper abdominal pain or discomfort". The correlations between AR and the secondary measures were computed (irrespective of treatment) for each week and the 12-wk averageusing Spearman'sRankCorrelationCoefficient. Improvementsin secondary measures ware based on change from baseline. Results: AR was positively correlated with improvement in % pain free days (wks w/AR 34.9%, wks w/no AR 7.5%), % days with nausea (wks w/AR -30.9%, wks w/no AR -9.7%), % days with bloating/distension (wks w/AR -21.2%, wks w/no AR -4.4%), % days with early satiety (wks w/AR -33.0%, wks w/ no AR -13.2%), % days with postprandialfullness (wks w/AR -33.8%, wks w/no AR -9.5%), % days with burping/belching (wks w/AR -17.4%, wks w/no AR -2.9%). The p-values for all correlations are <0.001. The p-value is based on the correlation between 12-wk average adequate relief and the change from baseline in the 12-wk average symptom. Conclusion: We conclude that AR of upper abdominal pain or discomfort representsa validated endpoint and is positively correlated with improvement in all symptoms characterizing FD.

4O59 Lactose Maldigeotion Does Not Explain Subjective Intolerance For Diap/Products la The Irritable Bowel Syndrome (IBS) Magnus Simren, Agneta Mansson, Dept of internal Medicine, Gothenburg Sweden; Uff Bengtsson, Asthma & Allergy Ctr, Gothenburg Sweden; HasseAbrahamsson, Anders F: Kilander, Einar S. Bjornsson, Dept of Internal Medicine, Gothenburg Sweden Background: Subjective intolerance for diary products is reported by 30% of patients with IBS (Simr~n et al Digestion 2001). The importance of lactose maldigestion for symptoms in IBS is disputed. The aim of the presentstudy was to investigateit iaotose rnatdigestioncauses the subjective intolerancefor diary products in IBS. Methods: 12 women and 6 men with IBS (24-62 years) according to the Rome I criteria participated in the study. All of them reported moderate, severe or very severegastrointestinal symptoms after intake of diary products and a majority of them avoided diary products completely. Constipation was the predominant bowel habit in 6 patients,diarrheain 4 and alternating diarrheaand constipation in 8. Hydrogen breath test was performed double-blind after intake of 500ml milk (25 g lactose; 1.5% fat) one day and another day after 500 ml "low lactose milk" (<4 g lactose; 1.5% fat). Aspartame was addedto the regular milk in order to make it taste like the "low-lactose milk". Symptoms bloating, gas, pain and bowel movements - and breath hydrogen concentrationwere analyzed every 30 minutes for 3 hours after the milk intake. Thereafter only symptoms were reported for the rest of the day. A sustained rise in breath hydrogen of >20ppm above baselinewas considered abnormal and if symptoms occurred at the same time the patients were regarded lactose intolerant. Results: Only one of the 18 patients was iaotose intolerant, having a rise in breath hydrogen 157ppm and gastrointestinal symptoms. No other patient had a rise in breath hydrogen >20ppm. After lactose containing milk 8 patients reported no symptoms at all comparedwith 7 after "low-lactose milk" (ns). Only one patient reported severepain during the investigation and that was after "low-lactose-milk". Light - moderate gas problems were reported by 5 patients both after milk and "low-lactose milk", light - moderate abdominal pain by 6 patients after milk vs 8 after "low-lactose milk" (p=0.17) and light - moderate abdominal distension by 5 patients after milk vs 7 after "low-lactose milk" (p=0.13). Both after milk and "low-lactose milk" only 2 patients had bowel movements during the 3 h test. Results: In a selectedgroup of IBS patientswith subjectiveintolerancefor diary products iaotose maldigestion is uncommon. Their intoleranceis most likely explainedby other mechanisms. In a low prevalencearea for lactose maldigestion this is probably of minor importance for the symptoms in IBS.

Symptom I ~ In Iwitahle Rowel Syndrome (IRa) Patients Mike Markowitz, Priti Jhingran, Art Harris, Alison Wentz, Afsaneh Asghari, Susan H. Gordon, Jean-Francois Ricci, Eric G. Carter, Glaxo Wellcome Inc, ResearchTriangle Park, NC Background:IBS is a highly prevalent disease (15%) with symptom patterns that wax and wane overtime, with a possible profound negative impact on quality of life and productivity. Most IBS researchto date has focused on physiological and psychological interplay between symptoms, but little is Imowo regarding the long-term natural history of symptom patterns in 18S patients. Methods: Patients were screened in primary care and GI specialist practices for IBS according to the Rome II criteria and positive screeners were evaluated for IBS. Confirmed IBS patients were enteredinto a prospectiveobservationalcommunity-basedregistry (current available data on 902 patients). Symptom data were collected weekly using a telephone interactive voice responsesystem (IVRS) questionnaire. Data on age, severity, IBS subtype (diarrhea predominent - D-IBS, constipation predominant - C-IBS, and alternators), and gender ware collected at baseline. These data were analyzed by patterns (frequency, severity, and bothersomeness)of IBS symptoms (pain, bloating, and changes in frequency and consistency of stool) at the mid-point of the baseline period of the registry (Week 6). Results: Overall, patients reportedthat their IBS episodeswere moderatelysevereand moderately or very bothersome. Duration and severity of individual IBS symptoms were similar in the overall population; abdominal pain being the most bothersome of all symptoms. Older patients, however, tended to have the most frequent, most severe, and most bothersome symptoms. Symptoms were more frequent and severe in females (24% reporting severe symptoms versus 9% in males) and 24% of females versus 17% of males reported being extremely or very bothered by their IBS symptoms. The most bothersome symptom for DIBS patients was abdominal pain (42%) whereas alternators and C-IBS patients were most bothered by both abdominal pain and bloating. D-IBS patients also rated their symptoms as severe23% of the time, comparedto 10% of the time for C-IBS patients. Previouslydiagnosed patientsexperiencedseveresymptoms more frequently (23% of the time) than newly diagnosed patients (15% of the time). Conclusions:Durationand severityof IBS symptoms are associated with gender, IBS subtype, and whether a patient is newly or previously diagnosed. Females, patients with severe IBS, D-IBS patients, and previously diagnosed patients tend to exhibit the most severe symptom patterns.

4060 Validation of Global ImprovementScale in Irritable Bowel Syndrome (IBS) Symptoms as an Endpointin IBS Clinical Trials Priti Jhingran, BarbaraA. 8agby, Britt S. Carr, Susan H. Gordon, Michael Markowitz, Eric G. Carter, Glaxo Wellcome Inc, ResearchTriangle Park, NC Background:As suggested by the Rome II criteria, global assessmentsof therapeutic efficacy are valuableto physicians since they are based on the integrated symptoms of patients. The IBS Global Improvement Scale(GIS) assessesmultiple symptoms of IBS in a patient-defined rating. This study evaluatedGIS as an efficacy endpoint and relationships between GIS and clinical, treatment satisfaction, and productivity endpoints were also explored. Methods: Data were collected in a 12-week randomized,double-blind, placebo-controlledstudy of Lotronex lmg twice daily for control of bowel urgency in 801 femaleswith nonconstipated18S.Subjects satisfied screening criteria of at least 50% of the days with lack of satisfactory control of their bowel urgency. Control of bowel urgency was collected daily throughout the study. GIS was rated on a 7-point Likert scale ranging from symptoms substantially improved to substantially worse. Responderswere defined as those patients with substantial or moderate improvement. We compared GIS scores at Weeks 4, 8, and 12 to global patient assessments 3 months prestudy. Results: GIS responders had more days with satisfactory control of urgency, as well as firmer stools, fewer stools per day, and fewer days with incomplete evacuation at Week 12. Substantially more GIS responders (90%) were satisfied or very satisfied with treatment at Week 12 as compared to nonresponders (13%) (r=O.8). Similar trends were observedfor satisfactionwith key medicationattributes (relief of abdominal pain/ discomfort, relief of bowel urgency, relief of other IBS symptoms). In addition, a favorable correlation betweenGIS and Lost Workplace Productivity was observed (r =-0.4). Conclusion: GIS is a valid endpoint for measuring improvement in IBS symptoms and may be a useful tool in future clinical trials to assess efficacy of IBS interventions.

Should GastroeMorologist lhink About Food Allergy In Patients With Functional ,Abdominal Pain? Stephane Nanoey, Dept of Gastroenterology,Lyon-Sud Hosp, Pierre-BeniteFrance; Francoise Andre, Dept of Immunology, Lyon-Sud Hosp, Pierre-BeniteFrance; Sylvette Ciaudel, Dept of Gastroenterology,Lyon-Sud Hosp, Pierre-BeniteFrance; ClaudeAndre, Dept of Immunology, Lyon-Sud Hosp, Pierre-BonitoFrance; Bernard Flourie, Louis Descos, Dept of Gastroenterology,Lyon-Sud Hosp, Pierre-BeniteFrance

TABLE 1: Change(Mean± SEM FromBaseline) Parameter

% of days with s~sfactory control of urgency Stool frequency Stool consistency Incompleteevacuation

Respooders (n--402)

Nonrenpooders (n-t77)

0.59 (±. 014)

0.24 (± .024)

06

-1.28 (± .064) -0.89 (± ,036) -0.40 (± .021)

-0.49 (±. 106) -0.40 (± ,049) -0.16 (± .027)

-0.4 -0.5 -0.4

Fond allergy caused by intestinal IgE-mediated hypersensitivity reactions includes various oropharyngal, cutaneous, pulmonaryand gastrointestinalmanifestationswhosethe respective frequency is not well known. In this work we attemptedto characterizethe clinical manifestations of fond allergy in a well defined cohort of patients with food allergy. Methods : 100 consecutive patients (56 M, 44 F, mean age 41 yrs) suffering from food allergy were studied. Diagnosis of food allergy was based on a combination of clinical and biological parameters (symptoms relatedwith meals, increasedserum specific food IgE and fecal IgE in the absence of fecal blood and parasitosis, positive skin tests) and on the positivity of an oral food challenge (increased intestinal permeability and/or reduced oro-cecal transit time). Results : Haft patients took medical advice mainly because of oropharyngal or skin manifestations

GIS Correlation with Week 12

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