signaling and TRPV1 channels were performed using rectum.RESULTS: In DSS induced colitis model mice, disease activity index, tissue inflammation and amount of 5-HT was gradually increased during 7 days of DSS treatment.The visceral hyperalgesia to mechanical distension was observed on day 7 but not on day 4.The number of 5-HT3 receptorexpressing nerve fibers is significantly increased in mucosa on day 7. On the other hand, number of the 5-HT4 receptor-expressing nerve fibers is significantly decreased on day 7.No significant alteration in the number of 5-HT3 and 5-HT4 receptors was detected on day 4. Progress of the inflammation led to down regulation of SERT immunoreactivities with concomitant increases in 5-HT-and TPH-1-positive cell numbers.5-HT-and TPH-1-positive cells were widely distributed in whole mucosa on day 0 and 4. On day 7, these cells were mainly detected in upper part of mucosa.A significant 2-fold increase in number of TRPV1expressing nerve fibers was found in mucosa on day 7. Non-neuronal TRPV1-immunopositive cells were observed on day 7.There is no clear alteration of the immunoreactivities of the 5-HT signaling and the TRPV1 channels in muscle layers of rectum in colitis model mice.CONCLUSION: These results suggest that increased 5-HT, 5-HT3 receptors, TRPV1 channels and decreased 5-HT4 receptors are associated with the pathological conditions of the inflammatory bowel disease.

Introduction/Aims: Post-infectious irritable bowel syndrome (PI-IBS) may develop in 4% to 30% of affected patients following bacterial gastroenteritis (GE), but limited information is available on outcome of viral GE. During summer 2009 a massive outbreak of viral GE associated with contamination of municipal drinking water (Norovirus and Enterovirus) occurred in San Felice del Benaco (Lake Garda, Italy) [1]. In order to investigate the natural history of a community outbreak of viral GE and to assess the incidence of functional gastrointestinal disorders and PI-IBS, we carried out a prospective population-based cohort study with control group. Methods: Baseline questionnaires were administered to the resident community within one month of the outbreak. Follow-up questionnaires of the Italian version of Gastrointestinal Symptom Rating Scale (GSRS, a 15 item survey scored according to a 7-point Likert scale) were mailed to all patients responding to baseline questionnaire at 3 and 6 months and to a cohort of unaffected controls, living in the same geographical area, at 6 months after the outbreak. GSRS itemwere grouped into five dimensions: abdominal pain, reflux, indigestion, diarrhea and constipation. At month 12 all patients and controls were interviewed by an health assistant in order to verify Rome III criteria of IBS. T-test and χ2 or fisher's exact test were used as appropriate. Results: Baseline questionnaires were returned by 348 patients: mean age ± SD 45 ± 22 years, 53% female. At outbreak nausea (scored ≥4), vomiting and diarrhea lasting 2-3 days or more were reported by 66%, 60% and 77% of patients, respectively. Fifty percent reported fever and 19% referred weight loss (mean 3 Kg). Follow-up surveys were returned at month 6 by 185 patients and 168 controls: mean of GSRS score for each dimension is reported in the figure. At month 12 we identified 40 patients with a new diagnosis of IBS (Rome III criteria), in comparison with 3 subjects in the control cohort (p<0.0001; OR 11.40, 3.44-37.82, 95%CI). The 40 cases of PI-IBS, according to the subclassification of IBS by predominant stool pattern [2], were subtyped as follow: 4 IBS with constipation, 7 IBS with diarrhea, 16 with mixed IBS and 13 with unsubtyped IBS. Conclusion: Our study provides evidence that mixed Norovirus and Enterovirus GE may lead to post-infectious gastrointestinal disordes which persist for at least 12 month after infection. PI-IBS following viral infections develops in a substantial proportion of patients (22%) similar to that reported after bacterial GE. References: 1) Scarcella et al. Eurosurveillance 2009 2) Longstreth et al, Gastroenterology 2006.

Objectives: Manifestations of gastroparesis are heterogeneous and clinical complications are poorly defined. Misconceptions of gastroparesis may be common. The objective was to determine physicians' perception of gastroparesis and identify areas that need further research and education. Methods: A physician survey was prospectively developed and tested. The survey included questions on the etiology, symptoms, management and perceived complications of gastroparesis. Physicians' feedback included rated responses by Likert scale and ranked responses by priority. A total of 3658 surveys were mailed to gastroenterologists and general practitioners using an online physician directory and a local medical society directory. Analysis of variance and t test were utilized. Results: A total of 397 surveys were returned. 85.9% of responses were from the national survey and 14.1% were local. Physicians ranked diabetes (70%) as the most common cause of gastroparesis, followed by idiopathic (21%) and postsurgical (9%). Postprandial epigastric pain (61%) was ranked as the most frequent symptom of gastroparesis, followed by retching/vomiting (20%) and heartburn/regurgitation (19%). 60% believed scintigraphy t1/2 is an accurate measurement of gastric emptying. Only one-third believed gastric electrical stimulation was effective as treatment of gastroparesis. Physicians rated abdominal pain as the most clinically significant complication of gastroparesis surpassing weight loss, hospitalization for dehydration, and malnutrition (P < 0.01). There were small but statistically significant differences between gastroenterologists versus general practitioners and private versus academic physicians. Conclusion: More physician awareness and education is needed on gastroparesis and the standardized four-hour gastric scintigraphy method, as well to clarify the management strategy for this condition.

Aim: Symptoms of gastroparesis are very diverse. Classifying patients by predominant symptom may improve management strategy.Goal: To validate a new symptom-predominant classification for gastroparesis using symptom severity and quality-of-life measures.Study: Subjects with gastroparesis for > 2 months were prospectively enrolled. A physician classified each subject into one of the following: vomiting-predominant, dyspepsia-predominant, or regurgitation-predominant gastroparesis. Subjects also classified themselves independently from the physician. Each subject completed a Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) and SF-12v2 Health-Related Quality-Of-Life survey. Receiver operating characteristic curves were constructed with sensitivity and specificity of each PAGI-SYM subscale to differentiate subjects into symptom-predominant subgroups. Area under the curve (AUC) was used to compare the receiver operating characteristic curves. Analysis of variance, Cohen's kappa (kappa) statistic, student t test, and Pearson correlation (r) were used.Results: One hundred subjects (87 females, mean 48 y) were enrolled. There was a 78% concordance between physician and subject's classification of gastroparesis with substantial correlation (kappa=0.64). PAGI-SYM nausea/vomiting subscale (AUC = 0.79) and PAGI-SYM heartburn/regurgitation subscale (AUC = 0.73) were the best in differentiating subjects into vomiting-predominant and regurgitation-predominant gastroparesis, respectively. No subscale was adequate to differentiate dyspepsia-predominant gastroparesis. SF-12v2 total scores significantly correlated with worsening of the total PAGI-SYM scores (r = - 0.339 to - 0.600, all P < 0.001).Conclusions: There was a substantial agreement between physician and patient using a symptom-predominant gastroparesis classification. Results suggest that a predominant-symptom classification is a valid means to categorize subjects with vomiting-predominant and regurgitation-predominant gastroparesis. Patients with dyspepsia and delayed gastric emptying need further research.

Purpose: Domperidone has been shown to be effective in treating gastroparesis, but it is not approved in the U.S. However, FDA recognized some patients with refractory gastroparesis or GI motility disorder may benefit from domperidone. Aim of Study: To review our clinical experience with domperidone through the FDA Investigational New Drug (IND) program. Methods: Indications for domperidone were symptoms of gastroparesis or small bowel dysfunction refractory to conventional therapy. To enroll into the study, patients must have at least one of following: abnormal gastric scintigraphy, food bezoars during EGD, or abnormal antroduodenal/small bowel manometry. Patients with ECG QTc interval >450 msec for men and >470 msec for women were excluded. Demographics, presentation (vomiting, dyspepsia, or regurgitation-predominant), and etiologies were reviewed. Dose of domperidone was increased if necessary. Maximal allowable dose was 30 mg qac and qhs. Treatment outcome was classified as responder (symptoms improved/resolved) or non-responder (symptoms same/worse). Side effects data were collected prospectively. Analysis of variance and SPSS software was utilized. Results: 305 subjects (81% females, mean age 51 yrs) signed informed consent during a 32-month period. 26% of subjects had domperidone before. 33%, 46%, and 21% of subjects presented with vomiting, dyspepsia, and regurgitation-predominant symptoms, respectively. Etiologies were idiopathic (48%), diabetic (21%), post-surgical (21%), and miscellaneous (10%). In the 192 subjects who started domperidone, mean follow-up of 11 months were obtained. 124 subjects (65%) were responders (see Table). Except for age, there were no differences in gender, symptom presentation, and etiologies between reponders and non-responders of domperidone. Only 10 subjects (5%) were able to stop domperidone without recurrence, and 28% were able to lower the dose. 22% of subjects reported side effects (11% breast symptoms, 7% CNS symptoms similar to metoclopramide, and 3% diarrhea). Only 2 subjects (0.7%) reported chest pain or palpation. No one suffered a cardiovascular complication. Domperidone was stopped in 13% of subjects for no symptom improvement and in 6% for side effects. Conclusion: 1) Domperidone was effective in two-thirds of patients in our open-label program through the FDA. 2) However, only one-third of patients were able to lower the dose or stop domperidone. 3) Presentation and etiology did not predict efficacy, but responders were older than non-responders.Table

and post-treatment in responders showed a significant difference (p<0.001), while nonresponders displayed no difference (p=0.86).A receiver operator characteristics (ROC) test was performed on those with two consecutive tests and the AUC was 0.72±0.5.At a cutoff of 22.5 ppm the sensitivity was 72% and specificity 62%.Evaluation of AUC showed controls to have 824±672 ppm*min, while responders 1127±795 were different from responders follow-up 532±647 (p<0.001),non-responders 916±878 were unchanged compared to follow-up 1133±1128.The ROC test of the AUC showed equal results as the peak values; 0.72±0.5.At a cut-off of 1000 ppm*min the sensitivity was 70% and specificity 64%.IBS patients responding to antibiotics displayed higher peak values (32±16) compared to healthy controls (p<0.001),while those not responding to treatment were similar to controls.Conclusion: Using appropriate cut-off levels, HBT can be used for determining bacterial overgrowth providing basis for treatment.A subgroup of IBS patients are identified with bacterial overgrowth thus responding to treatment.