AGA Abstracts This is suggestive of an active uptake of the compound in neural cells, a hypothesis confirmed by the observation that AZD3355, but not baclofen, was actively taken up in brain slices (uptake of AZD3355 and baclofen after 60 min of incubation at 0.1 μM: 2.23±0.03 and 0.20±0.01 μmol/kg, respectively). AZD3355, in contrast to baclofen, inhibited GABA binding to the GABA carrier in rat brain membranes (IC 50 =670 μM). The racemate of AZD3355 concentration-dependently reduced firing of gastric vagal mechanoreceptors. Conclusion: AZD3355, but not baclofen, is a substrate for the GABA carrier, which serves to maintain CNS extracellular levels low. This fundamental difference explains i) why baclofen is much more potent in producing CNS side effects and ii) the previously reported biphasic dose- response curve for AZD3355 with respect to TLESR inhibition. At low doses, central GABA B receptors are not activated by AZD3355 due to inactivation via the GABA carrier. At very high doses, the uptake system is overwhelmed, and central effects occur. With this favorable profile, AZD3355 holds promise to be the first reflux inhibitor, a new generation of GERD treatments. W1790 Body Mass Index Is Associated Through Common Genetic Pathways with Symptomatic Gastro-Esophageal Reflux Disease (GERD): A U.S. Co-Twin Study Mike Jones, Anthony Lembo, Nicholas J. Talley BACKGROUND: A genetic component in GERD has been previously established. Body mass index (BMI) is linked to GERD but whether this is due to a common genetic factor is unknown. Whether psychological factors are associated with GERD is controversial, and whether any link is explained by inheritance is also unknown. We aimed to examine if there is a genetic component that explains the frequent co-occurrence of GERD with BMI and psychological pathology in a co-twin study (controlling for genetic factors). METHODS: A nested case-control and co-twin control analysis in Minnesota twins. Both members completed validated questionnaires; GERD was defined by classical heartburn or acid regur- gitation (≥2 times/week). Measures included SCL-90, Eysenck Personality Questionnaire (neuroticism), BMI, smoking, alcohol, and education. Case-control analysis included indi- viduals with complete covariate information, adjusted for twin pair, age and sex. Co-twin control analysis considered monozygotic twin pairs discordant for GERD. RESULTS: 481 monozygotic (MZ) pairs [mean (s.d.) age 53 +/- 5.8 years] and 505 dizygotic pairs (mean age 54 +/- 5.6). Independent positive risk factors for GERD were BMI, somatization and neuroticism; anxiety and paranoia were negatively associated with GERD after adjusting for confounders (table). In the co-twin analysis (MZ alone), the OR for neuroticism substantially increased, while the OR for BMI and somatization tended towards unity (table). CONCLU- SIONS: GERD is strongly and independently associated with BMI and psychological factors. The data strongly indicate a common genetic link between GERD and BMI, suggest a possible genetic link with somatization, but strongly point against a genetic link with neuroticism, anxiety and paranoia. Case-control and co-twin analysis of risk factors for GERD (# multivariate) W1791 Prevalence of Dyspepsia Symptoms in Patients with Non Erosive Reflux Disease (NERD) Subclassified Using 24-Hour Ambulatory Intraluminal pH- Impedance Edoardo Savarino, Daniel Pohl, Luca Sconfienza, Patrizia Zentilin, Pietro Dulbecco, Radu Tutuian, Vincenzo Savarino Introduction: Functional dyspepsia and gastroesophageal reflux disease (GERD) are among the most prevalent upper gastrointestinal disorders. Non Erosive Reflux Disease (NERD) incorporates subgroups which differ significantly in terms of presentation, pathophysiology and management. There is accumulating evidence to indicate an overlap between NERD and functional dyspepsia. Aim: To evaluate the prevalence of dyspepsia symptoms in patients with NERD subclassified into three distinct groups using 24-hour multichannel-impedance pH-metry (MII-pH). Methods: We evaluated 109 consecutive patients with NERD using MII-pH. At the time of examination patients were off PPI therapy for at least 30 days. During ambulatory MII-pH refluxate presence was measured at 3, 5, 7, 9, 15 and 17 cm and esophageal pH at 5 cm above the LES. We calculated distal esophageal acid exposure (%time pH<4), number of impedance detected reflux episodes (acid, nonacid) and symptom association using the symptom index (SI). A validated Dyspepsia Questionnaire was used to quantify individual patients symptoms before the exam Results: Of 109 patients (63F, median age 48 yrs; range 18-78), 44 (40%) had an abnormal distal acid exposure. Out of 65 (60%) subjects with normal distal acid exposure, 34 (31%) had a positive SI for acid and/or non-acid reflux. In the pH-metry neg/SI neg subgroup (classified as Functional Heartburn, FH) symptoms such as nausea, abdominal pain, postprandial fullness and bloating were more frequent compared to the pHmetry pos and pH-metry neg/SI pos subgroups (table 1). Female were more often classified in to the functional heartburn group (p<0.01). Conclusions: MII-pH identifies NERD patients whose symptoms are neither related to symp- tomatic reflux nor abnormal distal esophageal acid exposure and should be labelled as functional heartburn. The highest prevalence of dyspepsia symptoms in this subgroup indicate that these patients should be included in the overall population with functional GI disorder and not remain a GERD subgroup. Table 1: Individual patients symptoms and NERD classification (n=109) A-716 AGA Abstracts W1792 The Role of Gastro-Esophageal Pressure Gradient On Esophageal Peristalsis in GERD Patients Fernando Fornari, Carlos Augusto S. Madalosso, Richard R. Gurski Background: Gastro-esophageal pressure gradient (GEPG) offers resistance to esophageal transit and may interfere with the performance of esophageal peristalsis. Aims: 1. To assess the role of GEPG on esophageal peristalsis in GERD patients with a wide range of body mass index (BMI); 2. To compare GEPG between GERD patients with normal esophageal peristalsis, ineffective esophageal motility (IEM) and nutcracker esophagus (NE). Methods: One-hundred and twenty-one consecutive GERD patients (38% male; 42 ± 12.9 years; BMI 19-67 kg/m2) underwent solid-state esophageal manometry and 24h pH-metry off PPI. GERD was confirmed by increased esophageal acid exposure and/or positive symptom index for heartburn at pH-metry. Patients with manometry findings other than normal peristalsis (n = 92), IEM (n = 12) and NE (n = 17) were excluded. Patients were further classified according with BMI in three categories: non-obese (BMI < 30; n = 46), obese (BMI 30-40; n = 26) and morbidly obese (BMI > 40; n = 49). GEPG was measured as the difference between gastric and esophageal basal pressures, whereas the performance of esophageal peristalsis was assessed by distal esophageal amplitude (DEA). GEPG was analyzed taking into account BMI, DEA and manometry findings. Results: GEPG was progressively higher comparing non-obese, obese and morbidly obese patients (6.4±2.4 vs. 9.7±2.7 vs. 13.3±2.6 mm Hg; P < 0.001). There was a strong correlation between GEPG and BMI (r = 0.82; P < 0.0001) and a weak but significant correlation between GEPG and DEA (r = 0.39; P < 0.0001). GEPG was significantly higher in patients with NE when compared to those with normal peristalsis and IEM (12.9±3.6 vs. 9.6±3.8 vs. 8.2±3.9; P < 0.01). NE patients showed significantly higher BMI (44±13.3 vs. 35.9±10.2 vs. 32.2±10.5; P < 0.05) compared to the other groups, and was more frequent in morbidly obese than in obese and non-obese patients (25% vs. 8% vs. 6%; P < 0.05). Conclusions: GEPG is clearly influenced by BMI and seems to interfere with the performance of esophageal peristalsis. Severe overweight might overdiagnose NE at manometry testing. W1793 Identification of Impaired Bolus Transit and Clearance By Secondary Peristalsis in Patients with Non-Obstructive Dysphagia Chien-Lin Chen, Michal M. Szczesniak, Taher Omari, Ian J. Cook Background/aim: Evidence exists suggesting that secondary peristalsis may be impaired in non-obstructive dysphagia (NOD). The relationship between such changes and alterations in bolus transport, if any, has not been studied. We investigated the hypothesis that triggering of secondary peristalsis and its effectiveness in esophageal bolus clearance are impaired in patients with NOD. Methods: Eleven healthy volunteers and 10 consecutive patients under- went combined impedance and manometry. Secondary peristalsis was stimulated by rapid mid-esophageal injections of saline (20 ml). Impedance measured bolus presence time (BPT) at each of the recording sites and bolus transit time. Bolus transit was considered to be complete when impedance defined complete bolus clearance at all recording sites. Results: Secondary peristaltic responses traversing the entire esophagus were triggered in NOD patients in only 15% of the stimuli compared with 78% of stimuli in controls (p < 0.001). The proportion of secondary peristaltic sequences demonstrating complete bolus transit was lower in NOD patients (10%) when compared with controls (76%)( p < 0.001). Esophageal bolus transit time, in response to secondary peristalsis, was longer in patients than controls (p = 0.005), as was the dwell time (BPT) at each recording site (p < 0.05). When compared with controls, NOD patients demonstrated a higher proportion of incomplete bolus transit in response to secondary peristaltic sequences that traversed the entire esophagus (p < 0.05). The between-group difference in the proportion of incomplete bolus transit was also noted during aberrant secondary peristaltic responses (ineffective or synchronous). Conclusions: In patients with NOD, triggering of secondary peristalsis is impaired, and impedance measures demonstrate impaired bolus clearance by both morphologically normal and aberrant second- ary peristaltic sequences. Abnormal secondary peristalsis with impaired bolus clearance may explain, in part, the dysphagia in NOD. W1794 Patients with Primary (Idiopathic) Achalasia Have Circulating Peripheral Blood Mononuclear Immune Cells That Are Hyper- Reactive to the Herpes- Simplex -1 Virus Kar W. Lau, Conall McCaughey, Peter V. Coyle, Liam J. Murray, Brian T. Johnston INTRODUCTION: Achalasia is the best characterized oesophageal motor disorder but the aetiology is unknown. The pathology seen in achalasia consists of a decrease in nitric oxide- producing neurones and the presence of an activated T-cell inflammatory infiltrate in the myenteric plexus (1). Certain Human Leucocyte Antigen (HLA) class II alleles are also more prevalent in patients with primary achalasia (1). These factors suggest that an autoimmune mechanism may be involved in the pathogenesis of primary achalasia. The stimulus initiating