Nitric oxide mechanisms in protection afforded by L-arginine in ibuprofen induced gastric toxicity

A1252 AGA ABSTRACTS

GASTROENTEROLOGY Vol. 118, No.4

5729 FAST TRACK THERAPY FOR GASTRO-OESOPHAGEAL REFLUX (GORD) AND DYSPHAGIA: THE TECHNICIAN'S ROLE. W. Jackson, J. Vasani, H. H. Tsai, K. R. Wedgwood, Castle Hill Hosp, Cottingham, United Kingdom. Introduction: Oesophageal manometry and 24hr pH studies are used to assess patients with symptoms of GORD and non-mechanical dysphagia. After investigation patients may not commence therapy until review in the out patient clinic which may involve a variable delay. Aim: To assess the role of the or physiology technician in data analysis and administration of therapy directly from written protocol. Method: Patients with GORD+/non mechanical dysphagia underwent oesophageal manometry and pH studies. Therapy was administered directly from the GI physiology laboratory and consisted of Cisapride (C) 20mg BD for oesophageal dysmotility and normal pH values, or C and Lansoprazole (L)30mg daily for oesophageal dysmotility and abnormal pH study. Therapy was given for a 2-week period. Patients then underwent repeat studies on medication to monitor clinical, symptomatic and physiological responses, after which they had out patient review by a consultant. Results: 38 patients underwent testing and primary therapy (25M: 13F age range 24-76 years), 17 were treated with C and 21 with C and L, and symptoms and physiological responses shown. Conclusions: The Gl physiology technician was capable of data analysis and therapy administration from protocol. This administration minimised delays in treatment, and provided clinical and physiological data pre and post therapy without delaying the patients consultant review. C

Patients' responses

C&L

10 4

asymptomatic and improved physiology symptoms same- improved physiology symptoms same - deteriorating physiology symptoms worse - deteriorating physiology taken from study - other medical conditions

16 2 1

1

0 2

1

1

5730 OESOPHAGITIS AND BARRETT'S OESOPHAGUS-ARE THEY RELATED TO THE PATTERN OF GASTRO-OESOPHAGEAL REFLUX? P. K. Jalal, A. D. Dwarakanath, A. R. Tanner, ST JAMES'S Univ Hosp, Leeds, United Kingdom; NORTH TEES Hosp, Stockton On Tee, United Kingdom. Aims: To evaluate any relationship between the diurnal variation of gastrooesophageal reflux measured by ambulatory pH studies and the development of various grades of oesophagitis and Barrett's oesophagus. Patients and Methods: Patients with symptoms of gastro-oesophageal reflux (n= 116) who had undergone 24-hour ambulatory pH monitoring of oesophagus were analyzed to define the diurnal pattern of the reflux. An upper gastro-intestinal endoscopy had been undertaken within one month of the pH study; the results were then analyzed to evaluate the possible relationship between oesophagitis (Savary-Miller classification), Barrett's oesophagus (classical long-segment with intestinal metaplasia on histology)and the pattern of reflux. Results: 24-hr pH-metry was abnormal in 67 patients; 32(47.6%)had predominant upright reflux, 2 had reflux predominantly in supine posture and the remaining 33 (49.2%) had reflux in both positions (bipositional). 20 of 67 patients (30%) had oesophagitis on endoscopy; 8 had mild oesophagitis (grade 1) and 12 had moderate to severe oesophagitis(grade 2 or more). In the mild oesophagitis group, 6 (75%) had upright reflux and 2 had reflux in both positions. In the group with moderate to severe oeophagitis,IO out of 12 patients (83%) had bipositional reflux. A total of 7 patients (10.4%) had Barrett's oesophagus and 3 of them had associated moderate oesophagitis. 6 patients with Barrett's oesophagus had bipositional reflux. Patients with bipositional reflux had a greater degree of oesophagitis than the upright group (p<0.05).The magnitude of reflux as judged by the DeMeester scoring system showed that bipositional group had a higher reflux than the upright group (p<0.005). Conclusion: Patients with bipositional reflux have more severe damage to the oesophageal mucosa and increased occurrence of Barrett's oesophagus. The pattern of reflux is an indicator to the clinical severity of the disease.

5731 DIAGNOSIS OF DYSPEPTIC SYMPTOMS: IMPACT OF DIET AND MALABSORPTION. Peter Janetschek, Friedericke Gantert, Ulrich Boeckmann, Day Clin North, Munich, Germany. BACKGROUND and AIMS: Dyspeptic symptoms, afflicting the intestinal tract, producing symptoms of pain, nausea, vomiting, bloating, belching, diarrhea, halitosis or any combination may impact daily life severe. When traditionally search for inflammatory, infectious, neoplastic and other structural abnormalities is done in vain, patients are diagnosed as having functional symptoms and are treated symptomatically. As these symptoms could possibly be explained by the dynamics of intestinal gas production, modified by diet, we studied the impact of malabsorption in dyspepsia as a putative missing link of NUD-diagnosis particularly since very few data are existing regarding dyspepsia and diet. METHODS: Absorption of

lactose, sorbitol and fructose were investigated in 823 adults with at least I of 7 NUD-symptoms by means of the hydrogen breath test ( Bedfont EC 60, England ). 10 g sorbitol, respectively 50 g fructose and 50 g lactose were given diluted in 100 ml water after a 10 hour fasting period. Malabsorption was judged by a peak breath H2 excretion of or > 20 ppm. RESULTS: 23,5 % of all 823 patients with a minimum of 2 of 7 NUDsymptoms malabsorbed sorbitol, 29,3 % malabsorbed fructose, 16,3% lactose, 11,3 % two of three substates, 5,6 % all three substrates (all p<0.005). During the test symptoms developed in 12,8% of the patients. Avoiding the non-absorbed component of diet, 65,5 % of the dyspeptic patients improved considerable (p<0.05). CONCLUSION: These results show the highly relevant impact of diet in dyspepsia due to malabsorption. Food anamnesis, diagnosis and therapy by avoiding malabsorbed agents is simple, effective and cost-effective. Malabsorption seems to be an important link in diagnosis and therapy of non ulcer dyspepsia symptoms.

5732 IS VECTOR MANOMETRY OF THE LOWER ESOPHAGEAL SPHINCTER USEFUL IN THE CLINICAL SETTING? Andrew D. Jenkinson, S. Mark Scott, Sritharan S. Kadirkamanathan, David F. Evans, or Physiology Unit, The Royal London Hosp, London, United Kingdom. Background: Vector manometry of the lower esophageal sphincter (LES) has been advocated as superior to station manometry in the assessment of patients with gastroesophageal reflux disease (GERD). However, its use in the clinical setting has yet to be fully established. Aim: To determine whether the identification of a manometrically defective LES by vector manometry in GERD patients is of use in the prediction of surgical outcome. Method: Rapid pull-through vector manometry (8-channel catheter, 0.5 ern/sec speed) of the LES and 24 hour esophageal pH measurement were performed on 59 patients before and 6 - 8 weeks after laparoscopic Nissen fundoplication. Results were compared with those of 17 healthy, asymptomatic volunteers. For the purposes of this study, a mechanically defective LES was defined as a vector volume below the normal range in control subjects. Postoperative outcome was compared in patients with and without defective sphincters. Results: All patients had pathological reflux confirmed on pre-operative pHmetry (total reflux time >4%). Median vector volume increased from 734 mm.rnmllg' pre-operatively, to 3452 mrn.mmllg" following surgery. Twenty-eight patients (48%) had a mechanically defective LES prior to surgery (VV below the lower limit of normal: 708 mm.mrnl-lg''). There was no difference in post-operative outcome between patients with defective and normal sphincters in terms of median total time esophageal pH<4 (0.5% versus 0.3%, p = ns). Three patients in each group had total pH times >4% following surgery. All patients with residual reflux had a substantial increase in vector volume following surgery. Conclusion: Reflux patients with a mechanically defective LES, as identified by vector manometry, are just as likely to benefit from antireflux surgery as those with a mechanically normal LES. Patients should continue to be selected for surgery primarily on the basis of pHmetry, endoscopy and symptoms. Based upon the results of this study, pre-operative vector manometry affords little or no diagnostic benefit.

5733 NITRIC OXIDE MECHANISMS IN PROTECTION AFFORDED BY L-ARGININE IN IBUPROFEN INDUCED GASTRIC TOXICITY. Dolores Jimenez, David POlO, Catalina Alarcon de la Lastra, Jose Esteban, Bruseghini Leo, Antonio Esteras, Juan Manuel Herrerias, Maria Jose Martin, Virginia Motilva, Faculty of Pharmacy, Seville, Spain; Faculty of Medicine, Cadiz, Spain; Zambon S A Lab, Barcelona, Spain; Virgen Macarena Hosp, Seville, Spain. Background: the labile endogenous vasodilator nitric oxide (NO) formed from L-arginine (L-arg) by a constitutive enzyme plays a modulator role in the regulation of gastric blood flow and mucosal integrity. However, an excessive production of NO by inducible NOS activity may lead to injury under certain pathological conditions. Recent data have indicated that NO-NSAID can inhibit expression of inducible NO synthase, which is up-regulated during injury and inflammation. Previous studies have suggested that oral administration of L-arg reverses the deleterious gastric effect of ibuprofen (ibp) improving different parameters related to oxygen free radicals and vascular state. Aim: to investigate the role of gastric NO (NOS activity and expression, and cGMP production) in the protection afforded by oral L-arg in experimental NSAID gastric toxicity induced by ibp. Method: Wistar rats were given oral dose of ibp and L-arg (100 mg/Kg b.w., respectively) and 6 h after were sacrificed. Gastric levels of cGPM were assayed by a competitive immunoassay, NOS activity by measuring the production of '4C-L-citruline in a radioenzymatic assay and expression of mRNA iNOS by reverse transcriptase-polymerase chain reaction (RTPCR). The intensity of PCR-products were quantified by densitometry, and compared with that of GADPH as an internal control. Results: gastric cGMP contents were significantly greater in ibplL-arg groups (90 min and 6 h, p
AGAA1258

April 2000

co mparing with ibp alone group s. Conclusions: The protective activ ity of L-arg, that previou s studies have associa ted with its hyperemic respon se, co uld be partl y explained by an actu ation of the vasodilator NO liberated by the constitutive NOS enz yme using the substrate L-arg, as the increased in cGPM has demon strated. Furtherm ore, the increa sed expression of iNOS, connected with damage by ischemia and inflammation and promoted by the NSAID , is partially revert ed by the amino-acid. 5734 IS BARRETT'S ESOPHAGUS BECOMING MORE FREQUENT? Philippe Jorn od, Gian O. Dorta , Draha Pantoflickova, Chri stian Felley, Jean -Jacques Gonvers, Philippe Monnier, Andre L. Blum, Jean-Baptiste Ollyo, Div of Gastroenterology CHUVIPMU, Lausanne, Switzerland; Divison of Gastroenterology, CHUVIPMU, Lausanne , Switzerland; Dept of Otorhinolaryngology and Head and Neck Surg , Lausanne, Switzerland; CHUV , Lausanne, Switzerland. Backround : It has been claimed that reflux esophagitis and Barrett's esophagus (BE) are becomin g more frequent. Aim : To analyse the prevalence of BE in Lausanne in the last 30 years. Meth ods : We analyzed all upper gastrointestinal endos cop ies performed from 1969 to 1998 and assessed the prevalence of pepti c esophagitis and BE during the three decade s (1969-1978, 1979-198 8 and 1989·1998). One individual (180) prospectively collected all endoscopic data during this time period. We different iated between finger-like BE (FBE) and circumferential BE of at least 3 ern of length (CBE). Results : A total of 62 '124 endoscopies were perform ed during the 30 years period . At first endoscopy peptic esophagitis was found in 7204 patients and BE in 1300 patients , respectively. FBE was found in 750 patients and CBE in 550 patients , respectively. Additional 389 BE were found in 1631 patients with reflux esophagitis who had follow-up endoscopies. The table gives the prevalence of initial BE for each decade . Sex and age distribution of peptic esophagitis and BE did not change durin g the three decades. Late FBE were found in 8/190 (4.2%) from 1969-197 8. The corre spondin g numbe rs in the next two decades were 57/590 (9.6%) and 155/851 (18 .2%), respectively. Late CBE were found in 17/190 follow-up endo scopi es (8.9%) from 1969-1978. The corresponding numbers in the next two decades were 56/590 (9.5%) and 66/851 (7.7%), respectively. Conclusions : The number of BE diagnosed in our unit has increased over the last 30 years. Th is increase is paralleled by an increase of reflux esophagitis. The proporti on of patient s with reflux esophagitis and early or late CBE tend s to decrea se while the proportion of FBE increa ses. This may be due to a wider indicati on of endoscopy and a better awarne ss of FBE .

Peptic esophagitis FBE CBE BE (Total)

1969·1978

1979 - 1988

n ("!o)

n (%)

1989 -1998 n ("!oj

1446

2372 185 (7.8%) 185 (7.8%) 370(15.6%)

3386 436(12.9%) 220 (6. 5%) 656 (19.4%)

129 (8.9%) 145(1 0%) 274 (189%)

5735 CORRELATION OF SERUM GASTRIN TITER, HISTOLOGIC SCORING, AND HELICOBACTER PYLORI INFECTIVITY ACCORDING TO GASTRODUODENAL DISEASE ENTITIES. Woon-Tae Jung , Sung-Hwa Lee, Eul-Jo Jung , Joong-Hyun Cho , Gyeongsang National Univ Hosp, Chinju , South Korea . Backgr ound s/Aims: There were report s that serum gastrin titer was more increased in the patients with H. pylori infection than in asymptomatic person s who were uninfected. The aim of this study is to investigate the correlation of serum gastrin titer, histologic sco ring, and H. pylori infectivity accord ing to gastroduodenal disease entitie s in Koreans. Methods: Ninety-nin e patients who were infected with and 35 patients who were uninfeeted with H. pylori (62, 23 of chronic gastriti s, 22, 8 of gastri c ulcer , 8, 2 of duodenal ulcer, and 7. 2 of advanced gastric cancer , respectivel y) were measured serum gastrin titer by I 25l-radioimmunoassay. The presence of H. pylori infection was assessed by rapid urease test and histologi c evaluation including H. pylori colonization density and the degree of lymph ocyt ic and neutrophilic infiltration was assessed using endoscopic biopsied samples. Results: I) No significant difference of serum gastrin titer was noted between infected and uninfected groups (53.1::'::44.9 vs 52.7::'::46.lpg/ml, p=0.48). This result was similar after stratification into each disease entities (p> 0.05). 2) In both infected and uninfected group s, serum gastrin titer was significantl y increased in cases of high chroni c lymphocytic infiltration score than in cases of low that score in the fundus (55.1:t45.8 vs 22.9::':: 15.0pg/ml in infected group , 66.4::'::48.8 vs 39.8::'::40.4pg/ml in uninfected group , p<0.05 for each) . This finding was more prominent in patients with gastritis. 3) Serum gastrin titer was significantly increased in cases of high activity score than in cases of low that score in the fundus (124.3::'::58.7 vs 46.0:':39.5pglml, p<0.05). This finding was more prominent in patients with gastritis. 4) In comparison after grouping with patients of same histologi c score, serum gastrin titer was not significantly different between infected and uninfected groups . Conclu sions: Serum gastrin titer was significantly increased in cases of high histologic score, especially in the fundu s, in the patients of chronic gastrit is. But hypergastrinemia is not correlated with infection of H. pylori.

5736 ASSESSMENT OF CLINICAL SIGNIFICANCE IN ENDOSCOPY NEGATIVE HEARTBURN. Ola Junghard, Rolf Carl sson, Goran Hasselgren, Nicholas J. Talley, Ingela K. Wiklund , AstraZeneca R&D Molndal , Molndal , Sweden ; Nepean Hosp, Penrith , NSW, Australia. Background : Heartburn is the primary symptom in patients with GERD . In clinical studies the severity is routinely measured on a four-graded scale. The clinical significance of a one grade change in this scale is unknown but of major methodological rele vance. The aim was to assess the perceived magnitude and importance of a one-grade improvement. Method s: Patients with heartburn as their main symptom and with a macroscopically normal esoph ageal mucosa were treated with proton pump inhibitors in a 4 week study (n= 1282 in ITT anal ysis) performed in Canada, UK and Ireland . All patients had symptoms of heartburn at least 4 of the last 7 days prior to the baseline visit and a history of heartburn of 6 months or more . Severity (none, mild, moderate, severe) and frequency (number of days) of heartburn were assessed by the investigator at each clinical visit, referring to the 7-day period prior to the visit. At the 2 and 4 weeks visits the patients were asked to classify their heartburn as unchanged. worse or better (hardly better/worse at all, a little , somewhat, moderately, a good deal, a great deal, a very great deal better/worse) compared to baseline. Furthermore, the importance of this change in heartburn for carrying out daily activities was rated as not important, slightly, somewhat, moderately important, important, very important or extremely important. The percentage of patient s rating their heartburn as at least a good deal better (GDB) and the percentage who rated the improvement as at least important (IMP) were used as markers of perceived magnitude and importance of improvement in heartburn . Results : Among the 377 patients with a decrease from baseline to 4 weeks of one severity grade , GDB was 71 % and IMP 64 %. The ratings were dependent on the basel ine severity: in patients improving one severity grade from mild (n= 157), from moderate (n = 196) and from severe (n = 24), GDB was 89% , 62 % and 29%, and IMP 75%, 58 % and 46% , respectively. Change in frequenc y of heartburn affected the ratings : among patients with no change in severity grade, but with a decrease of I (n= IS), 2-4 (n = 48) and 5-6 (n=23) days with heartburn, GDB was 27%. 50% and 78% and IMP 27%, 44% and 78%. Overall, in the 668 patients with complete relief of heartburn at 4 weeks GDB was 94% and IMP 8 1%. Conclu sion: Most patien ts rate a one grade decrease in heartburn severity as being at least a good deal better as well as being at least import ant for carry ing out daily activitie s. The rating is dependent of the baseline severity of heartburn . A decrease in heartburn frequency alone is also of value. 5737 CETRAXATE IN COMBINATION WITH OMEPRAZOLE, AMOXICILLIN AND CLARITHROMYCIN INCREASES THE ERADICATION RATE OF HELICOBACTER PYLORI IN SMOK· ERS. Tomoari Kamada, Ken Harum a, Eiji Miyoshi, Xing Chen, Hiroshige Hamada, Soichiro Kido , Mitsuhiro Mihara, Yasuhiko Kitadai , Masah aru Yoshihara, Koji Sumii, Goro Kajiyama, Yuzuru Kawamura, Hiroshima Univ Sch of Med, Hiroshima, Japan ; Kawamura Hosp, Hiroshima, Japan . Background: Our previous study have indicated that the eradication rate of Helicobacter pylori (H. pylori) in smokers is less effective than in nonsmokers (Helicobacter 1999; 4: 204) . Cetraxate is a gastric mucosal protective agent which increases gastric mucosal blood flow remarkably. The aim of this study was to evaluate the effect of cetraxate in combination with omeprazole, amoxicillin and clarithromycin on the eradication of H. pylori in smokers. Methods : The study group consisted of 102 patient s with H. pylori-positive smokers (83 males; 19 female s; mean age, 49 yrs; 44 duoden al ulcer s; 29 gastric ulcers ; 29 non-ulcer dyspepsia ). H. pylori infection status was determined by histology , serology, and the l3C-urea breath test (UBT) . 52 patients were treated with a one-week regimen comprising OAC , and 50 patients were treated with a one-week regimen comprising OAC + CET (0 = omeprazole 20 mg once daily , A = amo xicillin 500 mg thrice daily. C = clarithromycin 200 mg thrice daily. CET= cetraxate 200 mg thrice daily). The success of the treatment was evaluated by histology and the l 3C-UBT 4 weeks after the completion of the treatment. Results: The erad ication rates of H. pylori were evaluated by per protocol analysis. The eradicati on of H. pylori was successful in 30 of 52 patients (57.5%) with OAC therap y, and in 47 of 50 patients (94%) with OAC + CET therap y. The addition of cetraxate to omeprazole, amoxicillin and c1arithromycin significantl y increased the eradication rate of H. pylori in smokers (P< 0.01). Adverse effects noticed with OAC + CET therapy were diarthea or loose stool (5/50, 10%) and taste disturbance (1/50, 2%). Conclu sion: Cetraxate in combination with the new triple therap y for one week is safe and effective for the eradication of H. pylori in smokers.