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sgroups. Two further discriminant models were created using these 35 VOCs comparing CDwith normal and UC with normal both of which achieved excellent discrimination. On crossvalidation using 80:20 split of data arbitrarily on 8 occasions and averaging the results, thisapproach appears to have excellent stability, the average area under the curve for the CDmodel is 0.95 test sets and 0.80 for the validation sets, and the UC models give 0.94 and0.86 respectively. Conclusion: This preliminary data demonstrates the potential of patternanalysis of faecal VOC in patients with IBD may provide a non-invasive method in thediagnosis of IBD.

W1909

Glt-1 Over-Expression Attenuates Bladder Nociception and ColonicInflammation-Induced Cross-Organ Sensitization but Not Local Inflammation-Altered Urodynamic Function; Possible Role of a MAP Kinase PathwayMin Yang, Dong-feng Chen, Kenny Roman, Robert L. Stephens

Visceral pain, defined as pain associated with the internal organs, is a major clinical problemaffecting up to 25% of the general US population. Therapeutic options are limited largelyto symptomatic relief, without attending to the underlying etiology. Since glutamate is amajor excitatory neurotransmitter released in the first central synapse of the pain-transmittingafferent neurons, strategies to decrease glutamate availability may have utility in pain manage-ment strategies. Recent data in our laboratory suggests that transgenic animals over-expressingthe predominant glutamate transporter GLT-1, responsible for glutamate removal, show a53%-64% reduction in nociception due to colon distension. The effects of increased GLT-1 expression on nociception elicited from other visceral organs is unknown. Thus, this studyexamined nociception associated with urinary bladder distension (UBD) in a mouse model.The data show that distension-induced bladder nociception measured by the visceromotorresponse was inhibited 57-64% by enhanced GLT-1 expression induced by 7 day ceftriaxonetreatment. Pretreatment with dihydrokainate, a selective GLT-1 blocker, one hour beforebladder distension reversed this response. Moreover, GLT-1 over-expression attenuatedchanges in bladder urodynamic function (bladder contraction frequency and voiding pres-sure) caused by colon inflammation induced by mustard oil. However, changes in bladderurodynamic function caused by vesicular bladder acrolein-induced inflammation was notaltered by GLT-1 over-expression. Given the emerging role of the MAP kinase pathway innociceptive processes, and the significant role of glutamate receptor activation to generateactivated MAP kinases, experiments were performed examining the effect of GLT-1 over-expression on pERK and pMEK generation. The data revealed that GLT-1 over-expressionsignificantly reduced constitutive pERK1/2 (16% decrease in the thoracolumbar (TL), 13%decrease in the lumbosacral (LS), and 27% decrease in the DRGs) and to a lesser extentpMEK1/2 generation in these same tissues (5% - 10%). After distension, pERK was decreased20% by GLT-1 over-expression (TL, LS, DRG) and pMEK was decreased 40% in thalamictissues. Thus, GLT-1 over-expression was found effective to mitigate bladder nociceptionand cross-organ sensitization, reduced activation of the MAP kinase pathway may be respons-ible for the observed effects. The findings support a novel mechanistic target to alleviatevisceral pain. Supported by NIH DK 071839 and by the National Natural Science Foundationof China (No.30700362).

W1910

Chronic Idiopathic Enterocolitis (Cie): Maintaining a Corticosteroid FreeResponse With Immunosuppressive TherapyDaniel J. Stein, Benson T. Massey, Thangam Venkatesan, Richard Komorowski, Walter J.Hogan

Introduction: CIE is a rare intestinal inflammatory condition manifested by the acute onsetof profuse, watery diarrhea of unknown etiology. Early clinical recognition is unusual andthe problem becomes chronic often resulting in protracted hospitalization and morbidity.Effective treatment of CIE requires corticosteroids (CS) to induce clinical response; howeverthe use of immunosuppressant therapies to successfully maintain response and wean CShas not been detailed. The aim of our study was to evaluate the effectiveness of differentimmunosuppressive therapies at maintaining CS free response in a group of CIE patients.Methods: A retrospective chart review was performed for patients meeting criteria for CIE(partial or total villous atrophy, neutrophilic infiltration of the small bowel, negative celiacmarkers, and normal immunoglobulins). Six patients (4 males, 2 females; age range 26 to72; mean 50 years), fulfilled the criteria for CIE were identified at our center over the last3 years, mean follow up of 10.3 months (2-22). The type and duration of immunosuppressanttherapy is reported. Results: At presentation, frequency of stools averaged 13.3 per day.Stool weight (measured in 3 pts) per 24 hours averaged greater than 3000 grams and 48.9grams of fat. Three of the 6 CIE pts were hospitalized for an average of 30 days (all 3requiring repeat hospitalization). No coexisting autoimmune or pancreatic disorders werepresent. Three pts required I.V. CS therapy (average equivalent of 40 mg prednisone daily),all 3 pts all failed an initial course of oral prednisone (average dose 40mg prednisone) andrequired a second course of I.V. CS. A gluten-free diet was attempted in 4 pts and failedin all 4. Five pts had complete resolution of their diarrhea and 1 had partial improvementon prednisone alone. Subsequently, five pts were successfully weaned off prednisone. Twopatients failed 5-aminosalicylic acid products therapy. Budesonide (Entocort) was usedsuccessfully for prednisone weaning in 3 of 4 pts. Two of 3 pts were switched successfullyto azathioprine. Infliximab was used successfully in one patient. Currently, all patients arecontinued on immunosuppressive therapy for the duration of follow up. Conclusions: Allpatients in this case series had resolution of diarrhea with CS which is characteristic forCIE. Five patients were successfully tapered off CS and maintained, prednisone free, usingazathioprine, budesonide or infliximab. Patients who require hospitalization for IV CS havea high likelihood of relapse and readmission. The duration of immunosuppressive therapyin CIE has yet to be determined.

S-764AGA Abstracts

W1911

Effect of Immunomodulator and Anti-TNF Therapy in Inflammatory BowelDisease on Colonoscopy Findings Among Indigent Patients in the UnitedStatesSelvi Thirumurthi, Jason Hou, Hoda M. Malaty

Background: Disease processes can vary between racial/ethnic groups and these differencescan guide therapy. Few studies have evaluated treatment disparities in non-Caucasian patientswith inflammatory bowel disease (IBD). Aims: To assess for differences in drug therapy andcolonoscopy findings among a multi-ethnic population of patients with IBD from a CountyHospital. Methods: A retrospective chart review was conducted on a cohort of patients aged20 to 70 with Crohn's disease (CD) and ulcerative colitis (UC) between 2000 and 2006.The diagnosis of IBD was confirmed based on clinical, radiologic, endoscopic and histologicdata. Demographic and prescription data and colonoscopy findings were recorded. Drugtherapy was classified into 5 categories: ASA, steroids, antibiotics (ciprofloxacin and metronid-azole), immunomodulators (IMM [methotrexate, 6 mercaptopurine and azathioprine]), andanti-TNF (infliximab, adalimumab, certolizumab pegol). An abnormal colonoscopy wasdefined by the presence of at least one of the following: polyp, ulcer, erosion or granularity.The data were analyzed using the Chi-Square, Fisher exact and Student t-tests. Results: Thestudy cohort included 279 patients with 54% female, 30% Caucasian, 44% African Americanand 26% Hispanic, 54% of patients had CD and 46% UC. The mean age at diagnosis was40 +/- 14 years and was similar between CD and UC. Patients with CD were 5 times morelikely to be prescribed anti-TNF therapy (22% vs. 5%, OR=5.8; 95% CI=2.8-14.3; p=0.0001)and twice as likely for IMM therapy (48% vs. 29%, OR=2.2; 95% CI=1.4-3.6; p=0.002)than patients with UC. Prescription of drugs in all categories were similar among racial/ethnic groups or male and female patients. Younger patients had a greater likelihood oftherapy with anti-TNF (20% vs. 9%; OR 2.5; 95% CI=1.2-5.2, p=0.01) and IMM (55% vs.30%; OR 1.9; 95% CI=0.8-3.1; p=0.07) than elderly patients. Although the rate of normalcolonoscopies was similar among patients with CD regardless of drug prescribed, normalcolonoscopies were most prevalent among patients with UC prescribed steroid therapy.Conclusions: Patients with CD had a higher likelihood of anti-TNF and IMM therapy thanthose with UC. Older patients were less likely to be prescribed these agents which may bedue to disease comorbidity or less severe IBD. There was no significant difference in the 5drug categories across racial/ethnic groups. Patients with UC who were prescribed steroidshad a higher rate of normal colonoscopies. Further study of the effect of race/ethnicity andage on the selection of pharmacotherapy are warranted.

W1912

Efficacy of Shortening the Dosing Interval to Once in Six Weeks in Crohn'sDisease Patients That Failed the Standard Maintenance Dose of InfliximabUri Kopylov, Konstantinos Katsanos, Lior H. Katz, Simon Bar-Meir, Epameinondas V.Tsianos, Eran Israeli, Shomron Ben-Horin

Background & aims: Significant proportion of patients treated with Infliximab for Crohn'sdisease (CD) require intensified dosage due to loss of response to maintenance regimen of5 mg/kg/8 weeks. However, there are no comparative data regarding the efficacy of doublingthe dose versus shortening dosing interval (DI) to once every 6 weeks. Methods: A retrospect-ive review of all CD patients treated with Infliximab in the participating centers between2000-2009 was performed. The study cohort consisted of patients who required treatmentescalation as per their physician decision. The outcome of patients whose Infliximab wasintensified to 5 mg/kg/6w (6-week-group) was compared to the outcome of patients whodouble-dosed to 10 mg/kg/8w or 5 mg/kg/4w (Double-dose group) . Results: Thirty sevenpatients (mean age 32.6) were included in the study, of whom 27 (73%) were in the 6-week-group and 10 (27%) were from the double-dose-group. Early clinical response to thefirst intensified dose occurred in 16/27 (59.3%) of the 6-week group versus 6/10 (60%) inthe double-dose group (p=NS). Regained response was maintained for 12 months in 11/27(40.1%) patients compared to 2/10 (20%) patients, respectively (p=NS). No significantdifference concerning age, disease duration and perianal involvement was demonstratedbetween the two groups. Conclusion: In CD patients who lost response to standard Infliximabdose , shortening the dosing interval to every 6 weeks appears to be at least as effective asthe customary strategy of shortening the interval to every 4 weeks or doubling the dose.

W1913

Distinct Expression Patterns of Md2 in Ulcerative Colitis and Crohn's DiseaseHumaira Hashmi

Background: The etiology of inflammatory bowel disease (IBD) is not known. It is hypothes-ized that inappropriate activation of mucosal immunity by environmental factors in geneticallypoised individuals is the major cause for inflammation. Toll-like receptors (TLRs) are themajor innate immune surveillance, recognition and response receptors in the intestinalmucosa. Increased TLR4 has been observed in inflamed colonic mucosa of pediatric patients,suggesting a role for TLR4 mediated signaling in the pathogenesis of ulcerative colitis (UC).Here we tested the hypothesis that TLR4 signaling is up-regulated in Crohn's disease (CD).Method: Complementary DNA was prepared from intestinal biopsy specimens from ulcerativecolitis, crohn's disease and normal control subjects. Quantitative real-time PCR analysis wasperformed to compare gene expression of MD2, a key component in TLR4 signaling. Results:Consistent with previous report, increased expression of MD2 was observed in the inflamedtissue of UC patients, comparing to normal controls and the non-inflamed tissues from CDpatients. In contrast, the MD2 expression in inflamed terminal ileum of CD patients wasnot up-regulated comparing to normal controls or non-inflamed terminal ileum from UCpatients. Conclusion: Since all CD patients included in this study had inflammation in ileum,but not in colon, the distinct expression pattern of MD2 between UC and CD suggest thatTLR4 signaling participated in the colonic inflammation, but not in ileum inflammation.While it is confirmed that TLR4 signaling is involved in the inflammation of UC, furtherstudies are required to ascertain whether TLR4 signaling is involved in the colonic inflamma-tion of CD.