- Email: [email protected]
Paradoxical effect of Helicobacter pylori infection on epigastric pain and heartburn in subjects taking NSAIDs or aspirin: the bristol helicobacter project
631
in duodenum, 4 in antropyloric region; perfnsion and pH probe were in the second duodenum. After a phase Ill of the MMC was recorded, acid solution (pH 2) or saline in a double blind, randomized, crossover protocol was perfused at a rate of 5ml/min. After 30 rain, subjects ate a meal (one egg, two slices of bread, 150 cc of water) and motility registration continued for a further 5-hour period. During fasting and every 15 minutes after the meal, severity of discomfort, fullness, bloating, belching, nausea, heartburn, epigastric burning, satiety and pain were evaluated by visual analog scale. Mean duodenal acid exposure (% time pH<4) in 15-rain periods was also evaluated. Results: During acid perfusion, symptom scores for discomfort, bloating, nausea, eplgastric bummg were significantly higher (p<0.01) compared to saline. Postprandial antral MI was lower (2.96 • 1.8 vs 3.62 + 1.8, p = 0.01) and jejunal MI higher (4.87 + 1.0 vs 4.37 -+ 1.4, p = 0.01) during acid per fusion. Occurrence and duration of phases Ill showed no difference. Conclusions: Duodenal acid perfnsion induces antral hypomorility, jejunal hypercontractflity and causes a sensitization to dyspeptic symptoms. Through these mechanisms, increased duodenal acid exposure may play a role in the pathophysiology of FD symptoms
Screening for Coiorectal Cancer: Direct Comparison of a Brush-Sampling Fecal Immunochemical Test for Hemoglobin with Hemoccuh Stephen Cole, Alicia Smith, Peter Bampton, Jayne Sandford, Joylene Morcom, Graeme P. Young Background: Newer fecal occult blood tests (FOBT) incorporating immunochemical technology reduce barriers to population screening for colorectal cancer by removing need for dietary or drug restrictions (Cole Set al, Med J Aust 2001;175:195). !nSure| is a new fecal immunocbemical test (FIT) that requires just 2 stool samples that are collected using a simple brush. However, performance characteristics of this novel FIT have not been determined relative to a guaiac FOBT. Aim: To compare performance of the guaiac FOBT (HemoccultTM ll Sensar~; HO) with the novel FIT, !nSure, in various settings where colonoscopy was subsequently performed. Methods: Patients sampled consecutive stools with both !nSure and HO sampling devices while following dietary restrictions appropriate for HO. !nSure samples were taken from 2 separate stools immersed in toilet bowl water using a brush, while HO samples were taken from 3 stools using a spatula. Patient populations were: an average risk screening cohort (n = 284, median age 67, range 56-74), a high risk surveillance cohort (n= 158, median age 65, range 34-86) and a symptomatic diagnostic group (n = 18, median age 63, range 40-82). Outcome measures: Sensitivity for cancer, for cancer plus adenomas -> 10ram (significant neop[asia) or for cancer plus all adenomas (all neoplasla); positive predictive value (PPV); false positive rate (FPR); tests compared by paired 2x2 tests (with 95% confidence interval (CI) of difference) or g2. Results: !nSure was sigmficanfly better at detecting cancers, significant neoplasia or all neoplasm (see Table for sensitivity for prevalent lesions). PPVs (for all neoplasia) were not significantly different: !nSure 30/69 (43.5%), HO 21/61 (34.4%), X2= 2.11 p=0.29. FPR (for all neoplasia) were similar: !nSure 15/344 (4.4%), HO 14/344 (4.1%). Conclusions: !nSure provides significantly better sensitivity for co[orectal neoplasia without any loss of specificity when compared to HO. Combined with its novel and simpler sampling plus the ability of FIT technology to reduce barriers to screening, !nSure represents an improved alternative to Hemoccult Sensa for screening.
Tests InSure Flemocc=lt Senu 95% CI of dlffereoce
Cancers 11/13 (84,6%) 5/13 (38.5%) 12.0%-64.9%
SIRnlflcantneolflallia 17/22 (77.3%) 11/22 (50%) 4,8%-49,7%
637 G-Protein Mediated Receptor-Cell-Coupling as a Predictor for the Long Term Response to Treatment in Patients with Functional Dyspepsia Gerald Holtmann, Winfried Siffert, Elisabeth Grote, Sebastian Haag, Ute Braun-Lang, Mathias Langkafel, Nicholas Talley Background: Very little is known regarding factors that influence the long term outcome of patients with functional dyspepsia. G-proteins are essential for stimulus-response coupling of receptors which are linked to intracellular effector systems such as the adenylcyclases, the phosphoinositide system, ion channels, as well as various protein kinases and transcription factors. Thus polymorphisms of specific G-protein may influence functions that are linked to the development of symptoms. Aims: To study the role G-protein protein GNB3 for the long term outcome of FD patients adjusting for symptom pattern and concomitant psychiatric disturbances. Methods: We recruited 80 patients with chronic or relapsing symptoms (> 5 years) that were referred to a tertiary referral center for evaluation and treatment of nonresponsive symptoms. All patients had predominantly upper abdominal symptoms with the final diagnosis of functional dyspepsia after extensive diagnostic work up. Presence of anmety and depressive disorders were clinically judged by a trained physician. Genomic DNA was isolated from buccal swabs and genotyping of the C825T/C polymorphisms was performed by PCR and restriction analysis. All patients were treated based upon the predominant symptom pattern utilizing PPI, prokinetics, spasmolytics and low does tricyclic antidepressants as indicated. In addition, most patients received behavinural and relaxation therapy. After 12 month patients were categorized based upon their judgment as respond,ers ( complete or sufficient relief of symptoms) or non responders ( ~ only moderate improvement, no change or deterioration of symptoms). Results: After 12 month 23 out of 80 patients were categorized as responders (R + ) while 57 patients were categorized as non-responders (NR). The GNB3 CC polymorphism was found in 56 % of patients and was univariately associated with R + (p<0.02), while dysmotility-type (p<0.02), concomitant IBS-symptoms (p<:0.05) and the presence of an anxiety disorders (p<005) were associated with NR. Logistic regression analysis revealed a signtficant (p<0.05) association between the R+ arid the CC polymorphisms while there was a trend for a negative association between dysmotilitysymptoms. Conclusions: Molecular variants of the GNB3 that modulate receptor cell-coupling, influence outcome and response to medical therapy in functional dyspepsia.
All neoplasia 30/44 (68,2%) 22/44 (50%) 1.2%-35.2%
635 Relation between Partial Gastric Volumes and Upper Gastrointestinal Sensations in Patients with Functional Dyspepsia and Healthy Volunteers Measured with 3Dimensional Ultrasonography Marco W. Mundt, Andre J. P. Smout, Melvin Samsom 3D ultrasound is a non-invasive techmque to measure gastric volume. Aim of this study was to investigate the relation between total and partial gastric volume changes and sensations in patients with functional dyspepsia and healthy volunteers. METHODS: 12 patients with functional dyspepsia (5 male, age 40.7 +_ 14, range 21-69) and 15 healthy volunteers (6 male, age 26.8 +- 7, range 20-39) participated. 2D ultrasonographic images of the total stomach were acquired during a sweep (approximately 300 images within 20 sec). A pulsemagnetic field generator and a probe sensor enabled 3D orientation. Sensations (epigastric pain, fullness, nausea, and hunger) were scored using a VAS. Subjects ingested a 500 ml liquid meal (200 ml Nutridrink + 300 ml water, 300 kCal) within 3 rain. Data were acquired at t = 0 and 5, 15, 30, 45, 60 min postprandially. The gastric wall was outlined manually using 3D analysis software and total gastric volume was calculated, subsequently proximal gastric volume (10 cm downward from diaphragm) and distal gastric volume (between pyloms and antral area landmarks) were calculated from total 3D gastric volumes. Relationships were assessed using partial correlation, controlling for subjects. RESULTS: Mean fasting gastric volume in patients (37.0 +- 7.7 ml) was comparable to healthy volunteers (32.5 +- 2.5 ml, p = NS). In addition, no differences in gastric volume were observed 5 rain postprandially (506.7+-6.9 nfl vs. 494.6+-6.4 ml, p=NS) and gastric volume linearly decreased during the first postprandial hour. The increase in total gastric volume was related to the increase in fullness, both in patients (r=0.47, p<0.O01) and healthy volunteers (r= 0.53, p
638 Functional Dyspepsia : Cholinergic or Nitrergic Disorder? Mickael Bouin, France Lupien, Pierre Poitras Background : In patients with functional dyspepsia (FD), tolerance to gastric fundus distension is frequently compromised. Based upon the fact that acetylcholine and nitric oxide (NO) are major contributors in balance for respectively the contraction and the relaxation of the stomach fundus, we tested the contribution of the cholinergic or nitrergic pathways in this disorder. Methods : FD patients with impaired tolerance (i.e. maximum tolerated volume less than 600 ml of distension as found in normal healthy volunteers) to gastric distension were included in this study. Gastric distension studies where done by inflating a fundic balloon with progressive amount of air until the maximum tolerated volume of distension was reached by the patient. Gastric distension was first evaluated in basal control conditions before repeating the test after the injection of the anticholinergic hyoscine (Buscopan 20 rag IV) or following the administration of NO donor nitroglycerin (Nitrolingual 1.2 mg sl). Results : 11 patients were included in both treatment groups. Hyoscine improved tolerance to gastric balloon distension in 73% of patients (from 459 +A 28 ml to 595 +/48 nil; p < 0.01). Nitroglycerin was effective in only 9% of the patients (409 +/- 38 rnl to 431 +/- 44 ml; ns); when hyoscine was added in nitroglycerin non responsive patients, tolerance to distension was then improved in 75% of the cases (418 +/- 40 ml to 556 +/58 ml; p < 0.01). Conclusion : Under these experimental conditions, the cholinergic rather than the nitrergic pathway seem to be a predominant factor involved in the tolerance to distension in patients with functional dyspepsia
636 Effect of Acid Perfusion of Duodenum on Induction of Dyspeptic Symptoms in Healthy Volunteers Michele Di Stefano, Rita Vos, Jozef Janssens, Jan F. Tack
639 Paradoxical Effect of Helicobacter pylori Infection on Epigastric Pain and Heartburn in Subjects Taking NSAIDs or Aspirin: the Bristol Helicobacter Project Anne McCune, Richard Harvey, Athene Lane, Liam Murray, lan Harvey, Prakash Nair, Jenny Donovan
Background and Aims: Recently, we reported increased duodenal acid exposure associated with increased symptom severity in a subset of functional dyspepsia (FD) patients (Lee, 2002), but its pathogenetic role is still unclear. To evaluate involvement of duodenal acid exposure in symptom generation, we induced a hyperacidity status of the duodenum in healthy volunteers (HV) and assessed its influence on symptoms. Patients and Methods: Nine HV (4m, 22-33 yrs) underwent 2 studies. After an overnight fast, a 7-channel waterperfnsed catheter, an infusion catheter and a pH probe were positioned under fluoroscopic control: the most distal manometric channel was placed after Treitz ligament, 2 channels
AGA
Abstracts
Background: Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are the most important causes of peptic ulcer disease. We have studied the interaction of H.pylor/ infection with dyspeptic symptoms in subjects taking NSAIDs or aspirin. Methods: The Bristol Helicobacter project is a large community-based prospective randomised controlled
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thai of the effects of H.pylori infection and its eradication. 10,537 people gave informed consent to take part in the study, had a 13C-urea breath test and completed a detailed questionnaire, including details of any medications they were taknig. The symptoms of all I634 subjects whose 13C-urea breath test was positive for H. pylori infection were compared with twice that number (3268) of randomly selected H. pylori negative subjects (total 4902). Results: 17.7% of the study population were taking NSAIDs at least once a momh, 12.8% aspirin and 2 1% both. Eptgastric pain was commoner in those taking NSAIDs than in nonusers, but less so in H.pylori positive subjects: OR 1.19 (0.92,1.54) than in H.pylori negative subjects: OR 1.37 (1.17,1.61). Similarly, heartburn was increased less in H.pylori positive subjects: OR 1.31 (1.03,1.68) than in H.pylori negative subjects: OR 1.53 (1.31,1.79). Similar results were found in those taking aspinn, but not in those taking other analgesics. Conclusion: NSAIDs increase dyspeptic symptoms less in the presence of H.pylori infection, which may make anticipation of ulcer complications more difficult.
Rhlk of H, pyk>rl IrlfecUon in ofrlpdna by parents' region of b{rth
~%
~% "
9 H D~ori + t~ Age-Aqusted (5-ye~r d fferonce)
35% 9
{ 3o~ 2S%
.v # m% 15%
640 Discrepancy Between Epidemiological Data and Frequency of Diagnosis of Dyspepsia and Functional Dyspepsia in the Clinical Setting Ernst-Gunther Hagenmeyer, Gerald Hohmann, Ariane Hoer, Jean-Francois Rico, Bertram Haassler
I
Offlpdna: LIItlnAmedea
,
Parent: Latin Amedclt
P-~@ionof birth
Purpose Population-based studies report a prevalence of dyspepsia of 15-20%, with half of the subjects suffering from functional dyspepsia (FD). The aims of the study were to assess the prevalence of dyspepsia and FD and to estimate frequency and level of heahhcare utilization of FD patients (pts) compared with that of pts with irritable bowel syndrome (IBS) and pts with peptic ulcer disease(PUD). Methods Retrospective cross-sectional and longnudinal analyses from government and private sources were linked: the 1998 German NationalHealth Examination Survey, 1997 panel data of statutory health insurance physicians for outpatient care, and the German federal statistics on inpatient stays. Exact cases of FD were identified with full-text strings or the presence of an ICD-9 for 536.8, 536.9, or 5379 or an ICD-10 for K300 or K31.9. A sensitivity analysis was conducted by varying the case dehnition to include probable FD cases using alternative text strings or ICD codes. A similar dichotomization (exact/probable) was performed for 1BS and PUD cases. Resuhs About 26% of the German population (16.7 million people) between the ages of 18 and 79 experience pare in the upper abdomen at least once per year. Only 7% of the population (4.5 million 2eople) consult a physician for evaluation of their symptoms and 1% (0.7 million) receive a diagnosis of FD by an office-based physician and most (> 90%) are treated by GPs or office-basedinternists. Sixty percent of the patients diagnosed with FD are females compared to 46% of PUD pts, and 68% of 1BS pts. Physicians annually send 6.2 million claims to the statutoryhealth insurance for reimbursement of services for pts with dyspepsia. One- fourth of these claims (1.5 million) are for pta with FD. In all, FD pts account for 042% of all casestreated in outpatient set,aces. This is slightly more than IBS pts (0.38%) but less than PUD pts (0.61%). There are very few hospital stays related to FD compared to PUD (0.2 vs 5.3 hospitahzations per 1,000 pt years). Conclusion Dyspepsia and FD are frequent medical conditions in Germany. The small fraction of consulters receiving a diagnosis of FDcontrasts with population surveys that show that FD accounts for 50 to 60% of all cases of dyspepsia. This strongly suggests that FD is mis- and under-diagnosed which may result m unnecessary diagnostic and/or therapeutic interventions. Measures to appropriately diagnose and treat pts with functional Gt disorders may help to utihze heahhcare resources more effectively.
642 Is The Prevalence of GERD Symptoms Lower in Blacks? a Population-Based Study Hashem B. El-Serag, Linda Rabeneck, Robert M. Genta, Nancy Petersen, David Y. Graham Background Caucasians in the United States have a 5-fold greater incidence rate of esophageal adenocarcinoma and 2-3 times greater prevalence of Barrett's esophagus than blacks. It is unknown whether this ethnic discrepancy reflects lower prevalence of GERD symptoms in blacks, or lesser esophageal damage for the same degree of symptoms. Methods We carried out a population-based study among the ethnically diverse population (55% black) of VA employees at the Houston VAMC. Gastroesophageal Reflux Questionnaires (GERQ) were distributed. The prevalence and frequency of heartburn and/or acid regurgitation were calculated and age-adjusted according to the US general population for 2000. The association between ethnicity and heartburn and/or regurgitation was analyzed in logistic regression analyses that adjusted for age, gender, body mass index (BMI), educational level, smoking, alcohol drinking, and intake of ASA, NSAIDs, or calcium channel blockers. Resulfs Out of 1000 targeted, 915 individuals were verfied to have received the study questionnaires and of those, 520 (57%) returned complete and interpretable forms. The mean age of participants was 45 years (18-75); 65% were women, 41% were blacks, and 34% were white. Irrespective of ethnicity, persons reporting frequent heartburn had a mean BMI of 29.3 (sd 6.3) while those without heartburn had a BMI of 27.7 (6.1), p =0.02. Heartburn occurring at least monthly, or frequently (> 1/week) was reported in 52% and 27% of blacks and in 54% and 23% of whites, respectively Regurgitation occumng monthly, or frequently was reported in 52% and 16% of blacks and in 56% and 15% of whites, respectively. All comparisons were not statistically significant. Similarly, the age-adjusted prevalence rates were not significantly different between blacks and whites. Ethnicity was not a significant predictor of heartburn, or regurgitation in a logistic regression that controlled for age, gender, medications, BMI, and education. In these models, BMI>25 was a significant risk for frequent heartburn (adjusted OR: 1.97, 95% CI: 1.17-3.32, p=0.01), while lower education (below college level) was negatively associated with frequent heartburn (0.24, 0.27-26.48, p<0.001). Conclnsions 1. Blacks and whites in the US have a similar prevalence of GERD symptoms 2. Further studies should examine the role of environmental and genetic factors to explain the lower frequency of Barrett's esophagus and esophageal adenocarcinoma in blacks. 3. Overweight is an independent risk factor of GERD symptoms.
641 Prevalence of H. pylod Infection In a Transitional Generation of Latino Offspring RosarioL Villacorta, Sharon Perry', Luz Sanchez, Shu-Fang Yang, Julie Parsonnet Background:Prevalence of H. pylon infection is declining in industrialized countries. Whether nsk of infection is transitional in U.S. immigrant communities is unknown. Objective. We examinedprevalence of infection among U.S. and foreign-born offspring by parents' country d ongin. Methods. Bay area households referred by community health care providers based on an index case of infectious gastroenteritis were invited to he tested for H. pylori infection and "s'ere interviewed to determine household pedigree structure and country of birth. H. ,0vlortinfection status was determined by serum ELISA. Analysis. Offspring were classified as g S.-bom with U S.-bom parents (2 ~"+ generation); U.S.-born with parents born in Latin Amenca (LA) (P generation); and LA-born with parents born in LA (Immigrant). Logistic regressionwas used to assess risk of H. pylon infection in each group and to adjust for age and other factors. Results Of 908 offspring (average age: 6 years) with participating parents (average age: 30 years), i88 (20%) were born in LA, 67% in the U.S. of parents born in L~. and 115 (13%) in the U.S. of parents born in the U.S. Risk of H. pylori infection ~s 31%, 10%, and 5% [Immigrant generation, P' generation, 2~d+ generation offspring respectively]. Adjusting for age, household size, and parental infection status the adjusted odds of bl. priori infection was 5.9 (95% Ci 2.1-16.6) (Immigrant vs. 2nJ+ generation), and 31 (95% CI: 1.1-89) (V generation vs 2~ generation), and 0.52 (95% CI: .32-.85) (i': generation vs. Immigrant). Having at least one positive parent was independently associated with a 2.5-fold increase in risk of H. pylon infection (95% CI 1.5-4.2) Conclusion: In this senes, U.S.-born offspnng of Latmo immigrant parents exhibit a transitionmg risk of ft. pylon infection. Both current household exposure and host country environment are likely to contribute to these trends
643 Sociodemographic Barriers To Colorectal Cancer Screening M. Rosario Ferreira, June Lee, Nancy C. Dolan, Marian L. Fitzgibbon, Terry C. Davis, Charles L Bennett Background: Despite current evidence supporting colorectal cancer (CRC) screening arid existing screening guidelines, less than 45% of Americans age 50 and older undergo screening. Screening rates are even lower among minority and lower socioeconomic groups. The objectives of this study were to evaluate whether CRC screening recommendations and adherence vary according to sociodemographic characteristics, m the equal access VA system. Methods: We interviewed 294 male patients, age 50 and older, followed at a VA primary care clinic, who had not received CRC screening, and obtained age, race and educational level Patient charts were reviewed for physician CRC screening recommendations and for patient adherence to screening (fecal occult blood test, flexible sigmoidoscopy or colonoscopy) within up to 12 months of the interview. Results: Overall, 75% of all patients received a recommendation for CRC screening. African American patients were significantly less likely to receive a screening recommendation (67% vs 82% for whites, p<0.01). Less educated patients (<12th grade education) were also less likely to receive a screening recommendation (58% vs. 79% for more educated patients, p<0.01). Recommendation rates were similar among patients 50-64 years (76%) and 6574 years (82%), but lower for patients 75 years and older (66%, p = 0.05). In a multivariate regression analysis, including age, race and educational level, whites were more likely to receive a screening recommendation compared to African-Americans (OR = 2.3, 95%CI 1.34.2), and patients with a 12th grade education and above were more likely to receive a screening recommendation, compared to less educated patients (OR = 2.6, 95%CI 1.3-5.3). Data collection on adherence to screening is ongoing, but preliminary results show that among patients who received a CRC sereenmg recommendation, 23% underwent screening.
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AGA Abstracts
in duodenum, 4 in antropyloric region; perfnsion and pH probe were in the second duodenum. After a phase Ill of the MMC was recorded, acid solution (pH 2) or saline in a double blind, randomized, crossover protocol was perfused at a rate of 5ml/min. After 30 rain, subjects ate a meal (one egg, two slices of bread, 150 cc of water) and motility registration continued for a further 5-hour period. During fasting and every 15 minutes after the meal, severity of discomfort, fullness, bloating, belching, nausea, heartburn, epigastric burning, satiety and pain were evaluated by visual analog scale. Mean duodenal acid exposure (% time pH<4) in 15-rain periods was also evaluated. Results: During acid perfusion, symptom scores for discomfort, bloating, nausea, eplgastric bummg were significantly higher (p<0.01) compared to saline. Postprandial antral MI was lower (2.96 • 1.8 vs 3.62 + 1.8, p = 0.01) and jejunal MI higher (4.87 + 1.0 vs 4.37 -+ 1.4, p = 0.01) during acid per fusion. Occurrence and duration of phases Ill showed no difference. Conclusions: Duodenal acid perfnsion induces antral hypomorility, jejunal hypercontractflity and causes a sensitization to dyspeptic symptoms. Through these mechanisms, increased duodenal acid exposure may play a role in the pathophysiology of FD symptoms
Screening for Coiorectal Cancer: Direct Comparison of a Brush-Sampling Fecal Immunochemical Test for Hemoglobin with Hemoccuh Stephen Cole, Alicia Smith, Peter Bampton, Jayne Sandford, Joylene Morcom, Graeme P. Young Background: Newer fecal occult blood tests (FOBT) incorporating immunochemical technology reduce barriers to population screening for colorectal cancer by removing need for dietary or drug restrictions (Cole Set al, Med J Aust 2001;175:195). !nSure| is a new fecal immunocbemical test (FIT) that requires just 2 stool samples that are collected using a simple brush. However, performance characteristics of this novel FIT have not been determined relative to a guaiac FOBT. Aim: To compare performance of the guaiac FOBT (HemoccultTM ll Sensar~; HO) with the novel FIT, !nSure, in various settings where colonoscopy was subsequently performed. Methods: Patients sampled consecutive stools with both !nSure and HO sampling devices while following dietary restrictions appropriate for HO. !nSure samples were taken from 2 separate stools immersed in toilet bowl water using a brush, while HO samples were taken from 3 stools using a spatula. Patient populations were: an average risk screening cohort (n = 284, median age 67, range 56-74), a high risk surveillance cohort (n= 158, median age 65, range 34-86) and a symptomatic diagnostic group (n = 18, median age 63, range 40-82). Outcome measures: Sensitivity for cancer, for cancer plus adenomas -> 10ram (significant neop[asia) or for cancer plus all adenomas (all neoplasla); positive predictive value (PPV); false positive rate (FPR); tests compared by paired 2x2 tests (with 95% confidence interval (CI) of difference) or g2. Results: !nSure was sigmficanfly better at detecting cancers, significant neoplasia or all neoplasm (see Table for sensitivity for prevalent lesions). PPVs (for all neoplasia) were not significantly different: !nSure 30/69 (43.5%), HO 21/61 (34.4%), X2= 2.11 p=0.29. FPR (for all neoplasia) were similar: !nSure 15/344 (4.4%), HO 14/344 (4.1%). Conclusions: !nSure provides significantly better sensitivity for co[orectal neoplasia without any loss of specificity when compared to HO. Combined with its novel and simpler sampling plus the ability of FIT technology to reduce barriers to screening, !nSure represents an improved alternative to Hemoccult Sensa for screening.
Tests InSure Flemocc=lt Senu 95% CI of dlffereoce
Cancers 11/13 (84,6%) 5/13 (38.5%) 12.0%-64.9%
SIRnlflcantneolflallia 17/22 (77.3%) 11/22 (50%) 4,8%-49,7%
637 G-Protein Mediated Receptor-Cell-Coupling as a Predictor for the Long Term Response to Treatment in Patients with Functional Dyspepsia Gerald Holtmann, Winfried Siffert, Elisabeth Grote, Sebastian Haag, Ute Braun-Lang, Mathias Langkafel, Nicholas Talley Background: Very little is known regarding factors that influence the long term outcome of patients with functional dyspepsia. G-proteins are essential for stimulus-response coupling of receptors which are linked to intracellular effector systems such as the adenylcyclases, the phosphoinositide system, ion channels, as well as various protein kinases and transcription factors. Thus polymorphisms of specific G-protein may influence functions that are linked to the development of symptoms. Aims: To study the role G-protein protein GNB3 for the long term outcome of FD patients adjusting for symptom pattern and concomitant psychiatric disturbances. Methods: We recruited 80 patients with chronic or relapsing symptoms (> 5 years) that were referred to a tertiary referral center for evaluation and treatment of nonresponsive symptoms. All patients had predominantly upper abdominal symptoms with the final diagnosis of functional dyspepsia after extensive diagnostic work up. Presence of anmety and depressive disorders were clinically judged by a trained physician. Genomic DNA was isolated from buccal swabs and genotyping of the C825T/C polymorphisms was performed by PCR and restriction analysis. All patients were treated based upon the predominant symptom pattern utilizing PPI, prokinetics, spasmolytics and low does tricyclic antidepressants as indicated. In addition, most patients received behavinural and relaxation therapy. After 12 month patients were categorized based upon their judgment as respond,ers ( complete or sufficient relief of symptoms) or non responders ( ~ only moderate improvement, no change or deterioration of symptoms). Results: After 12 month 23 out of 80 patients were categorized as responders (R + ) while 57 patients were categorized as non-responders (NR). The GNB3 CC polymorphism was found in 56 % of patients and was univariately associated with R + (p<0.02), while dysmotility-type (p<0.02), concomitant IBS-symptoms (p<:0.05) and the presence of an anxiety disorders (p<005) were associated with NR. Logistic regression analysis revealed a signtficant (p<0.05) association between the R+ arid the CC polymorphisms while there was a trend for a negative association between dysmotilitysymptoms. Conclusions: Molecular variants of the GNB3 that modulate receptor cell-coupling, influence outcome and response to medical therapy in functional dyspepsia.
All neoplasia 30/44 (68,2%) 22/44 (50%) 1.2%-35.2%
635 Relation between Partial Gastric Volumes and Upper Gastrointestinal Sensations in Patients with Functional Dyspepsia and Healthy Volunteers Measured with 3Dimensional Ultrasonography Marco W. Mundt, Andre J. P. Smout, Melvin Samsom 3D ultrasound is a non-invasive techmque to measure gastric volume. Aim of this study was to investigate the relation between total and partial gastric volume changes and sensations in patients with functional dyspepsia and healthy volunteers. METHODS: 12 patients with functional dyspepsia (5 male, age 40.7 +_ 14, range 21-69) and 15 healthy volunteers (6 male, age 26.8 +- 7, range 20-39) participated. 2D ultrasonographic images of the total stomach were acquired during a sweep (approximately 300 images within 20 sec). A pulsemagnetic field generator and a probe sensor enabled 3D orientation. Sensations (epigastric pain, fullness, nausea, and hunger) were scored using a VAS. Subjects ingested a 500 ml liquid meal (200 ml Nutridrink + 300 ml water, 300 kCal) within 3 rain. Data were acquired at t = 0 and 5, 15, 30, 45, 60 min postprandially. The gastric wall was outlined manually using 3D analysis software and total gastric volume was calculated, subsequently proximal gastric volume (10 cm downward from diaphragm) and distal gastric volume (between pyloms and antral area landmarks) were calculated from total 3D gastric volumes. Relationships were assessed using partial correlation, controlling for subjects. RESULTS: Mean fasting gastric volume in patients (37.0 +- 7.7 ml) was comparable to healthy volunteers (32.5 +- 2.5 ml, p = NS). In addition, no differences in gastric volume were observed 5 rain postprandially (506.7+-6.9 nfl vs. 494.6+-6.4 ml, p=NS) and gastric volume linearly decreased during the first postprandial hour. The increase in total gastric volume was related to the increase in fullness, both in patients (r=0.47, p<0.O01) and healthy volunteers (r= 0.53, p
638 Functional Dyspepsia : Cholinergic or Nitrergic Disorder? Mickael Bouin, France Lupien, Pierre Poitras Background : In patients with functional dyspepsia (FD), tolerance to gastric fundus distension is frequently compromised. Based upon the fact that acetylcholine and nitric oxide (NO) are major contributors in balance for respectively the contraction and the relaxation of the stomach fundus, we tested the contribution of the cholinergic or nitrergic pathways in this disorder. Methods : FD patients with impaired tolerance (i.e. maximum tolerated volume less than 600 ml of distension as found in normal healthy volunteers) to gastric distension were included in this study. Gastric distension studies where done by inflating a fundic balloon with progressive amount of air until the maximum tolerated volume of distension was reached by the patient. Gastric distension was first evaluated in basal control conditions before repeating the test after the injection of the anticholinergic hyoscine (Buscopan 20 rag IV) or following the administration of NO donor nitroglycerin (Nitrolingual 1.2 mg sl). Results : 11 patients were included in both treatment groups. Hyoscine improved tolerance to gastric balloon distension in 73% of patients (from 459 +A 28 ml to 595 +/48 nil; p < 0.01). Nitroglycerin was effective in only 9% of the patients (409 +/- 38 rnl to 431 +/- 44 ml; ns); when hyoscine was added in nitroglycerin non responsive patients, tolerance to distension was then improved in 75% of the cases (418 +/- 40 ml to 556 +/58 ml; p < 0.01). Conclusion : Under these experimental conditions, the cholinergic rather than the nitrergic pathway seem to be a predominant factor involved in the tolerance to distension in patients with functional dyspepsia
636 Effect of Acid Perfusion of Duodenum on Induction of Dyspeptic Symptoms in Healthy Volunteers Michele Di Stefano, Rita Vos, Jozef Janssens, Jan F. Tack
639 Paradoxical Effect of Helicobacter pylori Infection on Epigastric Pain and Heartburn in Subjects Taking NSAIDs or Aspirin: the Bristol Helicobacter Project Anne McCune, Richard Harvey, Athene Lane, Liam Murray, lan Harvey, Prakash Nair, Jenny Donovan
Background and Aims: Recently, we reported increased duodenal acid exposure associated with increased symptom severity in a subset of functional dyspepsia (FD) patients (Lee, 2002), but its pathogenetic role is still unclear. To evaluate involvement of duodenal acid exposure in symptom generation, we induced a hyperacidity status of the duodenum in healthy volunteers (HV) and assessed its influence on symptoms. Patients and Methods: Nine HV (4m, 22-33 yrs) underwent 2 studies. After an overnight fast, a 7-channel waterperfnsed catheter, an infusion catheter and a pH probe were positioned under fluoroscopic control: the most distal manometric channel was placed after Treitz ligament, 2 channels
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Abstracts
Background: Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are the most important causes of peptic ulcer disease. We have studied the interaction of H.pylor/ infection with dyspeptic symptoms in subjects taking NSAIDs or aspirin. Methods: The Bristol Helicobacter project is a large community-based prospective randomised controlled
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thai of the effects of H.pylori infection and its eradication. 10,537 people gave informed consent to take part in the study, had a 13C-urea breath test and completed a detailed questionnaire, including details of any medications they were taknig. The symptoms of all I634 subjects whose 13C-urea breath test was positive for H. pylori infection were compared with twice that number (3268) of randomly selected H. pylori negative subjects (total 4902). Results: 17.7% of the study population were taking NSAIDs at least once a momh, 12.8% aspirin and 2 1% both. Eptgastric pain was commoner in those taking NSAIDs than in nonusers, but less so in H.pylori positive subjects: OR 1.19 (0.92,1.54) than in H.pylori negative subjects: OR 1.37 (1.17,1.61). Similarly, heartburn was increased less in H.pylori positive subjects: OR 1.31 (1.03,1.68) than in H.pylori negative subjects: OR 1.53 (1.31,1.79). Similar results were found in those taking aspinn, but not in those taking other analgesics. Conclusion: NSAIDs increase dyspeptic symptoms less in the presence of H.pylori infection, which may make anticipation of ulcer complications more difficult.
Rhlk of H, pyk>rl IrlfecUon in ofrlpdna by parents' region of b{rth
~%
~% "
9 H D~ori + t~ Age-Aqusted (5-ye~r d fferonce)
35% 9
{ 3o~ 2S%
.v # m% 15%
640 Discrepancy Between Epidemiological Data and Frequency of Diagnosis of Dyspepsia and Functional Dyspepsia in the Clinical Setting Ernst-Gunther Hagenmeyer, Gerald Hohmann, Ariane Hoer, Jean-Francois Rico, Bertram Haassler
I
Offlpdna: LIItlnAmedea
,
Parent: Latin Amedclt
P-~@ionof birth
Purpose Population-based studies report a prevalence of dyspepsia of 15-20%, with half of the subjects suffering from functional dyspepsia (FD). The aims of the study were to assess the prevalence of dyspepsia and FD and to estimate frequency and level of heahhcare utilization of FD patients (pts) compared with that of pts with irritable bowel syndrome (IBS) and pts with peptic ulcer disease(PUD). Methods Retrospective cross-sectional and longnudinal analyses from government and private sources were linked: the 1998 German NationalHealth Examination Survey, 1997 panel data of statutory health insurance physicians for outpatient care, and the German federal statistics on inpatient stays. Exact cases of FD were identified with full-text strings or the presence of an ICD-9 for 536.8, 536.9, or 5379 or an ICD-10 for K300 or K31.9. A sensitivity analysis was conducted by varying the case dehnition to include probable FD cases using alternative text strings or ICD codes. A similar dichotomization (exact/probable) was performed for 1BS and PUD cases. Resuhs About 26% of the German population (16.7 million people) between the ages of 18 and 79 experience pare in the upper abdomen at least once per year. Only 7% of the population (4.5 million 2eople) consult a physician for evaluation of their symptoms and 1% (0.7 million) receive a diagnosis of FD by an office-based physician and most (> 90%) are treated by GPs or office-basedinternists. Sixty percent of the patients diagnosed with FD are females compared to 46% of PUD pts, and 68% of 1BS pts. Physicians annually send 6.2 million claims to the statutoryhealth insurance for reimbursement of services for pts with dyspepsia. One- fourth of these claims (1.5 million) are for pta with FD. In all, FD pts account for 042% of all casestreated in outpatient set,aces. This is slightly more than IBS pts (0.38%) but less than PUD pts (0.61%). There are very few hospital stays related to FD compared to PUD (0.2 vs 5.3 hospitahzations per 1,000 pt years). Conclusion Dyspepsia and FD are frequent medical conditions in Germany. The small fraction of consulters receiving a diagnosis of FDcontrasts with population surveys that show that FD accounts for 50 to 60% of all cases of dyspepsia. This strongly suggests that FD is mis- and under-diagnosed which may result m unnecessary diagnostic and/or therapeutic interventions. Measures to appropriately diagnose and treat pts with functional Gt disorders may help to utihze heahhcare resources more effectively.
642 Is The Prevalence of GERD Symptoms Lower in Blacks? a Population-Based Study Hashem B. El-Serag, Linda Rabeneck, Robert M. Genta, Nancy Petersen, David Y. Graham Background Caucasians in the United States have a 5-fold greater incidence rate of esophageal adenocarcinoma and 2-3 times greater prevalence of Barrett's esophagus than blacks. It is unknown whether this ethnic discrepancy reflects lower prevalence of GERD symptoms in blacks, or lesser esophageal damage for the same degree of symptoms. Methods We carried out a population-based study among the ethnically diverse population (55% black) of VA employees at the Houston VAMC. Gastroesophageal Reflux Questionnaires (GERQ) were distributed. The prevalence and frequency of heartburn and/or acid regurgitation were calculated and age-adjusted according to the US general population for 2000. The association between ethnicity and heartburn and/or regurgitation was analyzed in logistic regression analyses that adjusted for age, gender, body mass index (BMI), educational level, smoking, alcohol drinking, and intake of ASA, NSAIDs, or calcium channel blockers. Resulfs Out of 1000 targeted, 915 individuals were verfied to have received the study questionnaires and of those, 520 (57%) returned complete and interpretable forms. The mean age of participants was 45 years (18-75); 65% were women, 41% were blacks, and 34% were white. Irrespective of ethnicity, persons reporting frequent heartburn had a mean BMI of 29.3 (sd 6.3) while those without heartburn had a BMI of 27.7 (6.1), p =0.02. Heartburn occurring at least monthly, or frequently (> 1/week) was reported in 52% and 27% of blacks and in 54% and 23% of whites, respectively Regurgitation occumng monthly, or frequently was reported in 52% and 16% of blacks and in 56% and 15% of whites, respectively. All comparisons were not statistically significant. Similarly, the age-adjusted prevalence rates were not significantly different between blacks and whites. Ethnicity was not a significant predictor of heartburn, or regurgitation in a logistic regression that controlled for age, gender, medications, BMI, and education. In these models, BMI>25 was a significant risk for frequent heartburn (adjusted OR: 1.97, 95% CI: 1.17-3.32, p=0.01), while lower education (below college level) was negatively associated with frequent heartburn (0.24, 0.27-26.48, p<0.001). Conclnsions 1. Blacks and whites in the US have a similar prevalence of GERD symptoms 2. Further studies should examine the role of environmental and genetic factors to explain the lower frequency of Barrett's esophagus and esophageal adenocarcinoma in blacks. 3. Overweight is an independent risk factor of GERD symptoms.
641 Prevalence of H. pylod Infection In a Transitional Generation of Latino Offspring RosarioL Villacorta, Sharon Perry', Luz Sanchez, Shu-Fang Yang, Julie Parsonnet Background:Prevalence of H. pylon infection is declining in industrialized countries. Whether nsk of infection is transitional in U.S. immigrant communities is unknown. Objective. We examinedprevalence of infection among U.S. and foreign-born offspring by parents' country d ongin. Methods. Bay area households referred by community health care providers based on an index case of infectious gastroenteritis were invited to he tested for H. pylori infection and "s'ere interviewed to determine household pedigree structure and country of birth. H. ,0vlortinfection status was determined by serum ELISA. Analysis. Offspring were classified as g S.-bom with U S.-bom parents (2 ~"+ generation); U.S.-born with parents born in Latin Amenca (LA) (P generation); and LA-born with parents born in LA (Immigrant). Logistic regressionwas used to assess risk of H. pylon infection in each group and to adjust for age and other factors. Results Of 908 offspring (average age: 6 years) with participating parents (average age: 30 years), i88 (20%) were born in LA, 67% in the U.S. of parents born in L~. and 115 (13%) in the U.S. of parents born in the U.S. Risk of H. pylori infection ~s 31%, 10%, and 5% [Immigrant generation, P' generation, 2~d+ generation offspring respectively]. Adjusting for age, household size, and parental infection status the adjusted odds of bl. priori infection was 5.9 (95% Ci 2.1-16.6) (Immigrant vs. 2nJ+ generation), and 31 (95% CI: 1.1-89) (V generation vs 2~ generation), and 0.52 (95% CI: .32-.85) (i': generation vs. Immigrant). Having at least one positive parent was independently associated with a 2.5-fold increase in risk of H. pylon infection (95% CI 1.5-4.2) Conclusion: In this senes, U.S.-born offspnng of Latmo immigrant parents exhibit a transitionmg risk of ft. pylon infection. Both current household exposure and host country environment are likely to contribute to these trends
643 Sociodemographic Barriers To Colorectal Cancer Screening M. Rosario Ferreira, June Lee, Nancy C. Dolan, Marian L. Fitzgibbon, Terry C. Davis, Charles L Bennett Background: Despite current evidence supporting colorectal cancer (CRC) screening arid existing screening guidelines, less than 45% of Americans age 50 and older undergo screening. Screening rates are even lower among minority and lower socioeconomic groups. The objectives of this study were to evaluate whether CRC screening recommendations and adherence vary according to sociodemographic characteristics, m the equal access VA system. Methods: We interviewed 294 male patients, age 50 and older, followed at a VA primary care clinic, who had not received CRC screening, and obtained age, race and educational level Patient charts were reviewed for physician CRC screening recommendations and for patient adherence to screening (fecal occult blood test, flexible sigmoidoscopy or colonoscopy) within up to 12 months of the interview. Results: Overall, 75% of all patients received a recommendation for CRC screening. African American patients were significantly less likely to receive a screening recommendation (67% vs 82% for whites, p<0.01). Less educated patients (<12th grade education) were also less likely to receive a screening recommendation (58% vs. 79% for more educated patients, p<0.01). Recommendation rates were similar among patients 50-64 years (76%) and 6574 years (82%), but lower for patients 75 years and older (66%, p = 0.05). In a multivariate regression analysis, including age, race and educational level, whites were more likely to receive a screening recommendation compared to African-Americans (OR = 2.3, 95%CI 1.34.2), and patients with a 12th grade education and above were more likely to receive a screening recommendation, compared to less educated patients (OR = 2.6, 95%CI 1.3-5.3). Data collection on adherence to screening is ongoing, but preliminary results show that among patients who received a CRC sereenmg recommendation, 23% underwent screening.
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AGA Abstracts