A158 AGA ABSTRACTS G0644 EFFECT OF T-593, A NEW H2-BLOCKER, ON INTRAGASTRIC pH. M. Inoue1), T. Shimatanil), Y. Horikawa 1), Y. KawaiO, C. Tao 1), G. Kajiyama 1), K. Tamaki 2), S. Kimura3), M. Nakamura 4), H. Mieno 5), T. Shirakawa 6) and H. Yokoya7) 1st Department of Internal Medicine, Hiroshima University School of Medicine 1), Chugoku Rosai Hospital 2), Saiseikai Kure Hospital 3), Nagashio Hospital 4), Hiroshima Railway Hospital 5), Seno Shirakawa Hospital 6) and Joge Hospital 7), Japan BACKGROUND AND AIMS: T-593 (( +_)-(E)-l-[2-hydroxy-2-(4hydroxyphenyl) ethyl]-3-[2-[[[5-(methylamino) methyl-2-furyl] methyl] thio] ethyl]-2-(methylsulfonyl) guanidine), a newly developed H2-receptor blocker, has been characterized as a potent and persistent inhibitor of gastric acid secretion, as having a potent anti-ulcer action and as protecting the gastric mucosa in fundamental studies. In this study, we examined the effects of T593 on gastric acid secretion in humans by 24-hour intragastfic pH monitoring. SUBJECTS AND METHODS: Six healthy males were used in each experiment. The pH monitoring was performed using a pH determination device of Chemical Co., Ltd. (pH-101Z, Tokyo, Japan). A glass electrode was inserted into the stomach and the intragastric pH was measured before and after administration of T-593. The experiments were as follows: (1) A comparison of dosage (100rag, 200rag and 400rag twice daily) (2) A comparison between 400rag once daily and 200rag twice daily. The results are expressed as the means +- S.E. of the values. RESULTS: (1) The pH 3 holding time during 24 hours was dose-dependently prolonged by administration of T-593 (Control: 331.2 +-51.8 rain (23.0_+ 3.6%), 200rag/day: 614.9_ 97.9min (42.7 + 6.8%), 400 rag/day: 828.0 +- 131.0 rain (57.5 +-9.1%), 800rag/day: 983.5 +- 149.8 rain (68.3 -+ 10.4%)). (2) With the pH 3 holding time during the whole day, there were no significant differences between the groups administered 400rag once daily and 200rag twice daily (616.3 _+72.0 rain (42.8 +- 5.0%), 564.5 +_141.1 rain (39.2 +-9.8%), respectively). CONCLUSION: T-593 demonstrated a potent action of inhibiting acid secretion in humans, and is considered highly useful in the treatment of acidrelated diseases. G0645 CISAPRIDE AND RANITIDINE IN THE ACUTE TREATMENT OF 470 PATIENTS WIT/./ GERD AND DIFFERENT DEGREE OF ESOPHAGITIS. G.I.S.U. (Interdisciplinary group for Ulcer Study). Italy. Background: it is not well established whether the treatment with cisapride might be really effective in different grades of gastro-esophageal reflux disease (GERD) when it is administered in alternative or in addition to H2blockers; moreover scanty data are present in the literature about the influence that sex, age, grade of esophagitis, smoking, alcoho L typical and atypical symptoms of GERD might have on short term treatment of reflux disease. Aims: 1) to investigate the role of C in comparison to ranitidine in the acute treatment of patients with grade 0-1 esophagitis 2) to establish whether C could be able to improve the healing of moderate-severe esophagitis when added to high dose of R; 3) to identified the influence of various endogenous and exogenous factors on short term therapy of GERD. Methods: 470 consecutive outpatients, aged 18 to 70 years, with GERD symptoms from at least 4 weeks, entered the study. They were stratified in two groups according to their degree of esophagitis (Savary - Miller): group A (0-I°) (316 pts, 179 M, 137 F, mean age 46; gr. 0 51 pts, gr. I° 265 pts.) was randomly treated with C10 mg x 3/die or with R300 mg/nocte (R300), group B (II°-IV°)(154 pts, 108 M, 46 F, mean age 54; gr. II ° 75 pts, gr. Ill ° 42 pts, gr. IV° 23 pts, not specified grade 14 pts), was randomly treated with R 300 mg x 2/die (R600) alone or by R600 plus C 10 mg x 3/die. Smoking habit, alcohol consumption and symptoms (retrosternal and epigastric pyrosis, regurgitation, belching, pain, bitter taste, nausea, vomiting, dysphagia) have been accurately monitored at the admission and after 4 and 8 weeks of therapy. Endoscopic control was performed 8 weeks after the admission. Statistics: Mann Whitney U-test, multivariate analysis. Results: Intention to Treat analysis of endoscopic healing did not show any difference between C and R300 in group A (72.8% vs 77.2%; p: NS) and between C-R600 and R600 in group B (65% vs 70.1%; p:NS). In group A both C and R300 were able to significantly improve specific and aspecific symptoms already after 4 weeks of therapy. Similar results were obtained in group B by C+R600 and by R600 alone. Multivariate analysis showed that only the grade of esophagitis could predict a poor clinical and endoscopic outcome of GERD. Conclusions: C is a valid alternative to R300 in the short term treatment of patients with grade 0-I ° esophagitis, but its addition to high doses of R (600rag/die) does not offer any therapeutic gain in patients with grade II°-IV° esophagitis. Only the initial degree of esophagitis predicts the short term outcome of GERD.
GASTROENTEROLOGYVol. 114, No. 4 • G0646 INDUCTION OF MUCOSAL DAMAGE OF STOMACH BY INOCULATION OF PLASMID DNA ENCODING INTERFERON-7. A. Irisawa, A. Saito, Y. Sato, K. Obara, T. Nishimaki, R. Kasukawa. Department of Internal Medicine II, Fukushima Medical College, Fukushima 960-12, Japan Recent studies have shown that Helicobacter pylori (I-IP)-specific immune responses display a predominant Thl phenotype. However, it remains unclear whether IFN-'t produced by Thl cells has a pathogenic or prospective role in the HP-related gastritis. To address this question, we injected directly Balb/C mouse stomach with naked plasmid DNA (pDNA) encoding either IFN-T (pCMV-IFN-T) or IL-4 (pCMV-IL-4) because direct injection of naked pDNA to the tissues has been shown to cause transfection of cells at the injected site through an unknown mechanism, and induce prolonged expression of proteins encoded by the pDNA. To confirm the expression of pDNA-encoded protein at the gastric mucosa after direct injection of pDNA to the stomach, we also injected [~ - galactosidase ([3 -gal)-encoding pDNA, pACB-Z, and the stomach was examined for 13 -gal expression by an enzymatic approach. 13 -galexpressing ceils were demonstrated in mucosal epithelial cells in the stomach afer injection of pACB-Z. One month after intragastric injection of pCMVIFN- ~, or PCMV-IL-4, the stomachs were macroscopically or histologically examined. Macroscopically the mucosa of pCMV-IFN-T-injected stomach had severe erosion and moderate hemorrhage whereas that of pCMV-IL-4-injected stomach had no pathogenic change. Histological examination of pCMV-IFN"/-injected stomach showed muccosal damage and moderate infiltration of mononuclear cells into the mucosal epithelium. These results showed that expression of IFN-T at the mucosal epithelium directly cause mucosal damage and suggested that HP-specific Thl cells may cause destruction of mucosal cells and contribute m the gastritis via production of IFN-'¢. G0647 THE COMPARISON WITH RAPID UREASE TEST AND HISTOLOGICAL EXAMINATION IN DETECTION OF HELICOBACTER PYLORI. M. Ishida. *M. Tabuchi, **K. Sakuma, K. Hirabayashi, Y. Ueda, T. Fujimoti and **A. Terano. Department of Pathology, Dokkyo University School of Medicine, Tochigi, Japan. *Nakameguro Digestive Organs Clinic. **2nd Department of Internal Medicine, Dokkyo University School of Medicine. The correlation of the detected efficiency of Helicobacter pylori (fl. pylori) between Rapid Urease Test (RUT) and histological examination was investigated with 351 cases, using upper digestive tract endoscopy. 44.2% (155/351) were found positive by RUT. 11. pflori rates in H.E. and Giemsa stainings were 92.3% (1431155) and 99.4% (154/155) respectively. WarthinStarry method and immunohistochemical staining were additionally carried out in the 28 RUT positive cases that developed neutral tints. The detected rates of/-/, pylori were 100% (28128) in both H.E. and Giemsa stainings. However, the detected rates were significantly lower, 47.8% (11/28) in the Warthin-Statry method and 78.6% (22128) in immunohistochemicai staining. Though RUT is a useful detecting method, superior in time consumption, handling and cost, we found that it is not sufficient for the cases of low germ rates and neutral tints. We conclude that, as routine, histological examinations, both H.E. staining and Giemsa staining methods are also essential for H. pylvri detection and for evaluation after eradication. • G0648 A SIALYL LEWIS X ANALOGUE ATTENUATES GASTRIC EROSIONS INDUCED BY THERMAL INJURY IN RATS. H. Ishikawa M. Yoshida, G. Wakabayashi, Y. Otuni, M. Shimazu, T. Kubota, K. Kumai, M. Kitajima; Dept. of Surgery, School of Medicine, Keio University, Tokyo JAPAN Sialyl Lewis X (sLex) is known as a ligand of selectin family. For purpose of clinical use, we have developed a novel selectin antagonist; sLex analogue. In the present study, the role of selectin on gastric mucosal lesion formation induced by thermal injury was studied using this sLex analogue. < Methods > (1) Male Wistar rats were anesthetized and a 30% full skinthickness dorsal burn was inflicted. The animal experimentation guidelines of the Keio University School of Medicine were followed. The sLex analogue group (4 mg / kg body weight, injected into jugular vein 30 minutes before and 2.5 hours after the bum) and the saline group (administrated in the same manner with sLex analogue) were studied. Luminol-dependent zymosanstimulated chemiluminescence (ChL) activity generated by leukocytes from jugular vein were measured. (2) Saline or sLex analogue was added to whole blood obtained from jugular vein, and luminol-dependent zYm0san-stirnulated ChL :activity was measured in vitro. < Results > (1) Total length of gastric erosions of the sLex analogue group was significantly shorter (1.75 +- 1.06 mm) than that of the saline group (7.29 +_.4.23mm) 5 hours after thermal injury. ChL activity generated by leukocytes after thermal injury was higher than that before thermal injury in both the sLex analogue group and the saline group. In addition, the increase in ChL activity of the sLex analogue group was significantly (p < 0.05) lower than that of the saline group. (2) The sLex analogue did not decrease ChL activity generated by leukocytes in vitro. < Conclusion > The protective effects of the sLex analogue on gastric