Su1619 Analysis on Understanding of Functional Dyspepsia (FD) and Attitude Toward FD Among Japanese Internists by the Self-Administered Questionnaires

after a 15 minute preincubation. The inhibition of acid secretion remained for over 25 minutes in the continued presence of the secretagogue carbachol demonstrating the potent inhibitory effect dopamine has on gastric glands. DISCUSSION: The hyper secretion of acid affects over 25 million patients worldwide. In an effort to suppress acid secretion drugs have been designed to bind directly to the proton pump to stop the secretion of acid. Unfortunately, recent data show that these drugs lose potency over time, resulting in recurring disease. In the present study we show that a single exposure to dopamine is sufficient to block carbachol induced acid secretion. We speculate that these direct effects of dopamine are mediated via ghrelin secreting cells located in the gastric gland resulting in ghrelin release that can directly suppress acid secretion. These results provide a new molecular target for drug development to prevent the hyper secretion of acid that may supplement or replace classical acid suppression therapy.

Effect of Intravenous Proton-Pump Inhibitor (Omeprazole) on Intra-Gastric pH in Thai Healthy Volunteers With Extensive Metabolizing CYP2C19 Genotype: Comparison Between Intermittent Bolus (Low Dose) and Continuous Infusion (Standard Recommended Dose) Kanita Chattrasophon, Sutep Gonlachanvit BACKGROUNDS AND AIMS: Proton-pump inhibitor is more effective for gastric acid control in Asian than Western population possible because of high prevalence of poor metabolizing CYP2C19 genotype in Asian people. The aim of this study was to evaluate the effect of low dose intravenous (IV) bolus vs. standard recommended dose continuous IV infusion of omeprazole in Thai healthy volunteers with extensive metabolizing CYP2C19 genotype. METHODS: 8 healthy subjects (age 30±6yr, 5 F, BMI 24±3 kg/m2) with extensive metabolizing CYP2C19 genotype were randomized to receive either omeprazole 80mg IV bolus followed by 40 mg IV bolus every 12 hr or omeprazole 80mg IV bolus followed by 8mg/ hr continuous infusion for 48 hr. The gastric pH was monitored by a pH catheter with a data logger (DIGITRAPPER pH 400, Medtronic A/S) for 2 days during the omeprazole treatment peroids. The gastric pH sensor was positioned at 10 cm below the lower esophageal sphincter located by esophageal manometry. All subjects were allowed to consume 3 standard meals/day. RESULTS : The mean gastric pH for IV bolus was significantly lower than continuous infusion only on day 1 [6.2±1.0 vs. 7.1±0.6 (p<0.05)]. Percent time pH>6 for IV bolus was also significantly lower compared to continuous infusion only on day 1(66.2±22.7% vs. 84.7±17.3%)(p<0.05).The % time pH >6 for the entire 48-hr study was significantly lower for IV bolus compared to continuous infusion (69.9±12.6% vs. 83.0±13.8%, p<0.05). 2 subjects developed gastric acid break through during the IV. bolus treatment. In contrast, no subject had gastric acid break through during the continuous IV infusion of omeprazole. Subjects with BMI < 24 and > 24 had similar intragastric pH during both IV bolus and IV continuous infusion of omeprazole (IV bolus, BMI < 24 vs. >24: 6.4±0.9 vs. 6.3±0.4) (continuous drip; 7.1±0.3 vs. 6.8±0.6)(p>0.05). CONCLUSION: Continuous IV infusion of standard recommended dose of omeprazole provided better gastric acid control compared to lower dose IV bolus only during the first day but not on the second day. Although the continuous IV infusion was more effective both standard dose continuous IV infusion and low dose IV bolus omeprazole was effective for gastric pH control in Thai healthy volunteers with extensive metabolizing CYP2C19 genotypes. The better gastric acid control compared to those reported in healthy volunteers in Western countries suggests the role of other factor(s), beside the CYP2C19 genotype, on gastric acid inhibition effect of IV omeprazole.

Su1618 ROME III Criteria-Based Prevalence of Dyspepsia Symptoms in General Populations in Six Countries in Latin America (SWOG Trial S0701) Ricardo Dominguez, Douglas R. Morgan, Rachael Sexton, Edgar M. Peña, E. R. Greenberg, Antonio Rollan, William D. Chey BACKGROUND: The functional gastrointestinal disorders and dyspepsia are common abdominal pain syndromes which have an important health care burden. Knowledge of the epidemiology of uninvestigated and functional dyspepsia in Latin America is limited. METHODS: Healthy adult volunteers were recruited from the general populations (ages 2165) years in Colombia (Túquerres), Costa Rica (Guanacaste), Nicaragua (León), Honduras (Copán), México (Obregon and Tapachula), and Chile (Santiago) as part of a large H. pylori eradication trial.[1] The participants were Hispanic mestizo, except for the predominantly indigenous population of Obregon, and were selected using several strategies: A census of households, door-to-door recruitment, and public health clinic registries. H .pylori prevalence among sites was similar (mean 79.4%) as assessed by the urea breath test. Upon enrollment to the trial participants completed the Rome III Diagnostic Questionnaire (R3DQ), which provided the basis to assess the prevalence of uninvestigated dyspepsia symptoms, including the subsets of postprandial distress syndrome and epigastric pain syndrome. The Spanish R3DQ has been previously translated and validated in a multinational study in Latin America and Spain.[2] The threshold criteria of 3 months duration with onset over 6 months prior was used. RESULTS: We interviewed 1859 adults (ages 21-65 years) with the R3DQ. The overall prevalence of univestigated dyspepsia was 25.1% (F 29.5%, M 18.5%). Dyspepsia was not associated with H. pylori infection (odds ratio, 95%CI =1.07, 0.82-1.39) or age (odds ratio, 95% CI =0.97, 0.89-1.06, per decade). There was significant variation in prevalence among sites (p=0.004), ranging from 15.8% in Leon to 37.4% in Obregon. In a multivariate model adjusted for age and study site, dyspepsia was significantly associated with female gender (odds ratio, 95% CI =1.64, 1.30-2.08). Postprandial distress syndrome was a relatively frequent subset, 16.7% (women 20.5%, men 12.9%), while the epigastric pain syndrome was uncommon, 0.3% (women 0.2%, men 0.4%). CONCLUSIONS: In this large multi-center study among diverse Latin American communities, symptom-defined dyspepsia based upon the Rome III criteria was relatively common, and especially so among women. Differences in site prevalence may reflect environmental and cultural issues, and specific study populations. Gender was the strongest determinant of dyspepsia prevalence, while no association was noted with H. pylori infection. REFERENCES: [1] Greenberg ER, et.al. Lancet 2011. [2] Morgan D et al. Multinational validation of the Spanish Rome III Adult Diagnostic Questionnaire. Gastroenterology 2010;38(Suppl.1):S386 SUPPORT: The Bill & Melinda Gates Foundation grant #43930 and National Cancer Institute grant # CA037429.

Su1616 The Inappropriate Prescription of Proton Pump Inhibitor Therapy in a Hospital Setting Orlaith B. Kelly, Catherine Dillane, Gavin C. Harewood, Stephen Patchett, Frank Murray Background: Proton pump inhibitors (PPIs) provide an important pharmacological means of prevention and treatment of gastro-esophageal reflux and peptic ulcer disease. Their widespread use and perceived safety have however, led to much inappropriate prescription which is not without effect, both in terms of adverse events and financial cost. Aims: To assess current level and appropriate nature of oral PPI prescription in a hospital setting. Methods: A prospective hospital audit was performed to assess PPI prescription. Standards of practice were based on current prescribing guidelines. Statistical analyses were performed using non-parametric testing. Relative risks (RR) and odds ratios (OR) were calculated. p values <0.05 were deemed significant. Results: 447 inpatients were included. Over half (57.5%) were prescribed PPIs. Of these, 26.8% prescriptions were for an inappropriate or unclear indication and 68.4% had been inappropriately dosed. 41.6% could have undergone dose reduction, while 26.5% could have discontinued therapy altogether. Age, gender and length of stay had no significant effect on PPI prescription. Aspirin use was significantly associated with PPI prescription (RR: 1.8, 95% confidence interval 1.127-3.69; p< 0.05) and also with inappropriate prescription (p<0.001). Patients admitted surgically were more likely to commence PPI therapy and also more likely to be inappropriately dosed (p<0.001). Omeprazole and Lansoprazole had a higher probability of inappropriate prescription than other PPI types (p<0.01, p<0.001 respectively). One patient inappropriately prescribed PPI in this study developed Clostridium difficile associated diarrhea. Conclusion: Inappropriate use of PPI therapy is a widespread problem in hospital practice. Targeted education programmes dealing with prescription and multidisciplinary medicine reconciliation strategies may provide cost effective strategies in addressing this issue.

Su1619 Analysis on Understanding of Functional Dyspepsia (FD) and Attitude Toward FD Among Japanese Internists by the Self-Administered Questionnaires Hiroshi Kaneko, Hirohito Tsuboi Background: Functional dyspepsia (FD) is one of the commonest diseases in the field of Internal Medicine. The Japanese Society of Gastroenterology (JSGE) has been enlightening the term and concept of FD for last few years in accordance with the worldwide spread of enlightenment on functional gastrointestinal disorders by Rome committee (Rome criteria). Aim: The purpose of this survey was to elucidate understanding status of FD and Rome criteria and attitude toward FD. Participants and Methods: Data were collected at the time of lifelong education course for certified members of Japanese Society of Internal Medicine in 2009. Educational programs were held in three places of Japan. Self-administered questionnaires were delivered to the medical doctors prior to the lectures; out of 4,262 attendees, 1,659 doctors agreed to full fill the questionnaire, which includes demographic variables, understanding of the medical terms (FD, two FDs in Japanese translation, chronic gastritis), the way to explain the disorder to patients, attitude toward the patients, and understanding and application of Rome criteria. Data were analyzed utilizing the PASW Statistics software ver.17. Results: Analysis subjects were 1,641 (24-90 yo; Tokyo, n=851; Osaka, n=535, Sendai, n=255) internists among 1,659 medical doctors. 1) 72.3% of internists understand the term ‘FD', and 94.9% comprehend ‘chronic gastritis'. Participants in Tokyo and Osaka (urban areas) exhibited significantly higher rate of understanding or FD, but not chronic gastritis, than those in Sendai (suburban area) (p<0.05). Logistic linear regression analysis revealed that factors affecting the understanding of FD were age, area (urban or suburban), working style (practitioner or hospital doctor), JSGE specialist or not. 2) Internists who understand FD inform FD patients about the diagnosis as chronic gastritis (56.8%), FD (37.1%), FD in Japanese Kanji character (57.9%), no worry (11.0%) and just imagination (0.7%), etc. 3) Percentage of enthusiastic, general or unwilling to care the patients was 19.4%, 70.8% and 3.2%, respectively. Logistic regression model displayed that attitude toward treatment depends on age, gender, specialty, working style. 4) 36.7% understand the existence of Rome criteria and 32.1% out of them put it to practical use. Positive factor for the application were certificated by JSGE specialist. Conclusion: Understanding of FD appears to spread from urban cities. Explanation for FD to patients is not unified (either

Su1617 Dopamine Can Directly Inhibit Gastric Acid Secretion Sabine Schmidt, Peter J. Geibel, Sascha Kopic, Markus Ritter, John P. Geibel Previous studies in whole animals suffering from gastric cancer and hyper-secretory disease showed that either IV or gavage with dopamine resulted in a reduction in acid secretion. It was speculated that the effects of dopamine were related to central nervous system inhibition of acid secretion. More recent studies have shown that dopamine can have a direct effect on ghrelin secretion. In the present study we investigated if exposure to dopamine in isolated gastric glands that were stimulated with carbachol can result in a direct inhibition of acid secretion. METHODS: Hand-dissected rat gastric glands were loaded with the fluorescent pH indicator dye BCECF-AM, following loading the single gastric glands were exposed to a NH4Cl prepulse to further acidify the parietal cells. To monitor intracellular pH BCECF was excited at 490 ± 10 nm and 440 ± 10 nm, respectively, and the emission intensity recorded at 530 ± 10 nm. Raw data were converted to pH using the High K+/nigericin calibration technique. To induce acid secretion all glands were exposed to 100uM carbachol, a potent secretagogue that is known to elevate intracellular calcium. In one series of glands prior to or concurrently with carbachol the glands were exposed to 100uM dopamine in the perfusion buffer. RESULTS: Dopamine exposure led to a marked and significant suppression in carbachol induced acid secretion in glands. The effects of dopamine were apparent

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chronic gastritis or FD in Japanese). For the spread of standard FD care, education on young and old doctors and doctors in less urban area might be effective.

and the initial gradient is higher than in the control group. It was found that FD patients have higher stomach sensitivity and higher gastric tone than controls. It was also found that there are different responses to IGP change depending on the type of medication.

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Su1622 Mast Cells in the Gastric Antrum, Its Relation With Functional Dyspepsia. a Multicenter Study in a South-American Country Susana B. Pignataro, Teresa Barcia, Esteban H. Campitelli, Adriana M. Cea, Daniela Ibarra, Alicia M. Paszkiewich, Flavio O. Pere, Santiago J. Regnasco, Horacio W. Rubio, Emilia C. Saa, Claudia Casco, Maria J. Jaroslavsky, María L. Racca, Ruben D. Ronchetti

Gastrointestinal Symptoms in Patients With Diabetes Mellitus and the Correlation With Mental and Physical Health Jan Brun, Gisela Ringstrom, Stig Attvall, Christina Brock, Magnus Simren, Eva A. Olausson Background: A large proportion of patients with diabetes mellitus (DM) suffer from gastrointestinal (GI) symptoms. A wide spectrum of symptoms has been reported, even though nausea and frequent vomiting often receives the greatest attention in research and clinical practice. Moreover, the association between GI symptoms and mental and physical health in DM is incompletely understood. Aims: To illustrate the spectrum of GI symptoms in DM and how this correlates with physical and mental health. Methods: Validated questionnaires were sent to all patients with DM treated with insulin attending two diabetes outpatient clinics in our region. 801 patients were invited to participate and were asked to complete a questionnaire to rate the severity of twenty GI symptoms during the previous two weeks (Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), divided into six summary scores. They also completed questionnaires to assess quality of life (SF-36: physical component summary (PCS) and mental component summary (MCS), anxiety and depression (Hospital Anxiety and Depression scale (HAD). Results: A total of 475 patients returned completed questionnaires (response rate 59%) (age 49±15 (mean±SD) years; 266 males). In the group who did not return the questionnaires a larger male predominance was observed (65 vs. 56%; p= 0.009), but there was no age difference between responders and non-responders. 75 (16%) reported no GI symptoms at all, and the majority of patients reported very mild or mild symptoms. Using “at least moderate symptom severity” as a cut-off, the most prevalent GI symptoms were stomach fullness (29.4%), visible abdominal distension (20.5%), feeling excessively full after a meal (17.3%), bloating (17.3%) and loss of appetite (10.8%), whereas nausea and vomiting of at least moderate severity was reported by 8.6% and 4% of the patients, respectively. The distribution of the summary scores is shown in table 1, and postprandial fullness/early satiety and bloating were most commonly reported. The severities of the GI symptom summary scores were associated with impaired physical and mental QOL (SF-36) and more severe anxiety and depression. Of the GI symptoms, the magnitude of the correlations with SF-36 and HAD scores were quite similar, whereas anxiety demonstrated stronger correlations than depression with the GI symptoms, and the same was seen for mental vs. physical QOL (SF-36) (table 2). Conclusion: GI symptoms in general are common in patients with DM treated with insulin, and postprandial fullness, early satiety and bloating are particularly common, but the vast majority of diabetic patients with GI symptoms report mild symptom severity. GI symptoms in DM are associated with impaired physical and mental health and paying attention to and treating these symptoms seems to be clinically important. Table 1. Distribution of PAGI-SYM summary scores.

INTRODUCTION:Mast cells might be involved in the pathogenesis of FD, but is still unclear how to evaluate their presence in the gastric mucosa,and their association with FD and H. pylori infection. AIM: to assess the presence of an increased number of mast cells in gastric mucosa (antrum) of patients with FD subtype postprandial distress, based on Rome III criteria, with and without HP infection. MATERIAL AND METHODS: an observational multicenter study, 53 patients were enrolled consecutively, 20(38%) male, mean age 52 years, who underwent an upper endoscopy to be compared with control group (n=56). For mast cells count, biopsy samples were taken from the antrum and they were detected by Giemsa stain, and HP status was defined as a positive urease test or histologic finding.Two blinded independent pathologists assessed the mast cells number, an a third one was called when in disagreement or when the difference of mast cells number was ≥4.Statistical analysis: X2test was used to compare proportions, and the Mann-Whitney test to compare numerical variables in both groups.Odds ratios (OR)were calculated using logistic regression with a significance level of 0.05 in all cases. RESULTS:see Table I and II Forward Stepwise Multiple Logistic Regression was used to identify better predictors of mast cells> 6 among the following variables: age<45,sex male, H. pylori status and dyspepsia symptoms.This model included the age(OR=8,55; p=0,005) and dyspepsia(OR=7,19; p=0,013) CONCLUSION: an increased number of mast cells in the gastric antrum ,seems to be more related to age, to functional dyspepsia symptoms than to H. pylori infection.However furher studies are necessary to confirm these findings including a higher number of cases 1FD:Functional dyspepsia 2.HP: Helicobacter pylori Results: Case group vs Control Group

14 cases with mast cells>6 and a random samples of control with mast cells <7 were taken to the case- control ratio was in average 1:4

N/V=Nausea/Vomiting; PF/ES=Postprandial Fullness / Early Satiety; Bloat=Bloating; U/L Abd Pain=Upper/Lower Abdominal Pain; H/R=Heartburn / Regurgitation. Score: 0=No symptoms; 5=Severe symptoms. Table 2. Correlation between PAGI-SYM summary scores, and SF-36 and HAD scores. Su1621 Intragastric Pressure Measurement Using Air Insufflation During Gastroscopy to Assess the Effect of Glucagon or Prifinium Bromide on Functional Dyspepsia Satoru Kawachi, Tsuyoshi Suzuki, Keiji Ogura Aims: We have reported previously the relationship between the sensitivity of the stomach to air insufflation during gastroscopy and the hypersensitivity of functional dyspepsia (Gastroenterol. 136(5), A438, 2009). FD patients and healthy volunteers may have different responses to the intragastric pressure (IGP) change and pressure threshold. To investigate this hypothesis, we measured responses to air insufflation during gastroscopy in FD patients and in healthy controls. In addition, we analyzed the effect on IGP change of prifinium bromide or glucagon to investigate differences between the two groups due to medication. Subjects: Twenty four FD patients (mean age 44 years, 8 male, 16 female) and 34 healthy volunteers (mean age 56 years, male 9, female 25). Methods: During gastroscopy, air was insufflated into the stomach at a rate of 20 mL/sec, and the change in IGP was measured until patients felt discomfort. Time to the threshold IGP (sec), gradient of IGP during the first 5 seconds (initial gradient, mmHg/sec), and gradient of IGP at the threshold (gastric tone, mmHg/sec) were measured. After the first tests, glucagon (1mg: for 16 patients, mean age 42 years, 4 male, 12 female) or prifinium bromide (7.5 mg: for 8 patients, mean age 50 years, 4 male, 4 female) was administered and insufflation tests were performed again. Results: (1) Time to threshold: The time to reach threshold pressure was significantly shorter in the FD group than in the control group (P<0.05). Initial gradient: The initial gradient was significantly higher in the FD group than in the control group (P<0.05). Gastric tone: Gastric tone was higher in the FD group than in the control group. (2) Taking medication (FD group): There was no significant difference in the time to threshold and gastric tone between the glucagon group and prifinium bromide group. The initial gradient, however, was significantly lower in the glucagon group than in the prifinium bromide group (P<0.05). Conclusions: The results in this study suggest that there are different responses to IGP change between FD patients and controls. In the FD group, the time to threshold is shorter

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** p-value<0.0001 for all the correlations. Su1623 Measurement of Time to Threshold of Discomfort Using Air Insufflation During Gastroscopy to Determine Functional Dyspepsia (FD) and Non-Erosive Reflux Disease (NERD) Satoru Kawachi, Tsuyoshi Suzuki, Keiji Ogura Aims: It has been debated that gastrointestinal hypersensitivity and insufficient gastric relaxation may cause functional dyspepsia (FD). We have reported previously the relationship between stomach hypersensitivity or gastric tone determined by measuring intragastric pressure using air insufflation during gastroscopy and symptomatic gastrointestinal diseases (Gastroenterol. 136(5), A438, 2009 ). In this study, we evaluated the usefulness of “time to threshold” of discomfort due to air insufflation to diagnose FD. In addition, we examined the change in the time to threshold with medication. Subjects: Fifty-four FD patients (mean age 49 years, 16 male, 38 female), 25 NERD patients (mean age 54 years, 16 male, 9 female) and 34 healthy volunteers (mean age 56 years, 9 male, 25 female) . Methods: During

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