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Mechanism by which beer and wine stimulates gastric acid secretion in dogs: Role of gastrin
A1286 AGA ABSTRACTS
GASTROENTEROLOGY Vol. 118, No.4
5874 ASSESSMENT OF A DISCRIMINAT PRONOSTIC ANALYSIS FOR PEPTIC ULCER HEMORRHAGE. Antoni Obrador, Juan Vidal, Luis Barranco, Amparo Sapina, Juan Riera, Pere Vaquer, Alfred Llompart, Jaume Gaya, Son Dureta Hosp, Palma, Spain. In a previous study, which included more than 300 patients, we accomplished a logistic regression multivariate analysis of the relapsing factors of the gastroduodenal ulcer hemorrhage. The independent variables were: type of ulcer base, size of the ulcer, endoscopic detection of blood in the explored tract, and clinical signs of low cardiac output. Objective. Assessment of a discriminative analysis for predicting rebleeds due to gastroduodenal ulcer in a prospective series of patients. Patients and methods. The patients who arrived at the hospital for an upper gastrointestinal hemorrhage (after performing a diagnostic endoscopy) were evaluated to estimate the risk of relapse according to the discriminant analysis obtained in the same center. The applied analysis is as follows: Probability = 1/(1+e- Z ) , being e = 2,7183 and z = the sum of the value of the variables in a certain patient. The study was carried out from July 1998 to May 1999. The series was of 172 patients. Results: the following contingence table shows the results of the application of the discriminative function. These data agree to obtain the next parameters: sensibility 13,3%; specificity 99,4%; positive predictive value 66,6; negative predictive value 92,3% and a global efficiency of 91,3%. If we had applied the four criteria in the 13 patients in whom the analysis did not predict the relapse, there had not turned out any error in the prevision. Conclusions. I) The discriminative analysis obtained applied to prospective series yields a small percentage of classification errors in the prediction of rebleeding. 2) The application of the four criteria that integrates the analysis permits the correction of the errors in all the cases. 3) This information is basic to set up a program of early discharge for patients suffering from gastroduodenal ulcer hemorrhage. Contingence table ofreal relapses vs predicted relapses
yes no
total
yes
no
total
2 13 15
1
156 157
3 169 172
Ordinates are the predicted relapses and abscisses are real relapses
5875 OPTIMAL DURATION FOR TRIPLE THERAPY AGAINST NON· RESISTANT STRAINS OF HELICOBACTER PYLORI. Keiji Ogura, Haruhiko Yoshida, Shin Maeda, Yutaka Yamaji, Yuzo Mitsuno, Masao Akanuma, Yoshihiro Hirata, Makoto Okamoto, Takao Kawabe. Yasushi Shiratori, Masao Ornata, The Institute for Adult Diseases, Tokyo, Japan; Dept of Gastroenterology. Univ of Tokyo. Tokyo. Japan; Univ of Tokyo, Tokyo, Japan. BACKGROUND: We reported mixed infection with wild-type (sensitive) and mutant (resistant) Helicobacter pylori strains by using a PCR-based preferential homo-duplex formation assay (PCR-PHFA) to detect 23S rRNA gene mutations associated with clarithromycin resistance (J Clin Microbiol, in press). Half cases with the mixed infection were determined as sensitive by conventional MIC assessment and yet failed in clarithromycin-based therapy. AIM: To assess the efficacy of clarithromycin-based triple therapy in patients infected exclusively with wild-type strains as determined by PCR-PHFA. METHODS: Ninety patients who had pure wild-type H. pylori infection were randomly assigned to take clarithromycin (200 mg b.i.d.), amoxicillin (500 mg q.i.d.), and lansoprazole (30 mg b.i.d.) for either 5 days or 7 days (n = 48 and n = 42, respectively). The outcome of eradication was assessed by [13C] urea breath test. RESULTS: Eradication rates were 36/48 (75%) vs. 39/42 (93%) by intention-to-treat analysis (P =0.022), and 36/45 (80%) vs. 39/40 (98%) by per protocol analysis (P =0.012), for the 5-day and 7-day protocols. respectively. Compliance and the incidence of untoward effects were similar in both groups. CONCLUSIONS: Seven-day administration is necessary and sufficient for the triple therapy with clarithrornycin, amoxicillin, and Iansoprazole in patients with pure wild-type (clarithromycin-sensitive) H. pylori infection.
5876 REGRESSION OF ATROPHIC GASTRITIS AND INTESTINAL METAPLASIA IN PATIENTS FROM WHOM HELICOBACTER PY· LORI WAS ERADICATED MONITORED PROSPECTIVELY FOR AT LEAST ONE YEAR. Toshifumi Ohkusa, Kazuhiko Fujiki, Ichizen Takashimizu, Jiro Kumagai, Toru Tanizawa, Yoshinobu Eishi, Tokyo Med and Dental Univ, Tokyo, Japan. Background: There have been few endoscopic studies during long-term follow-up after eradication of Helicobacter pylori. We examined patients repeatedly by endoscopy and biopsy for at least I year after treatment intended to eradicate the bacterium. Methods: We evaluated 163 infected patients given a proton-pump inhibitor and antibiotics who had at least three endoscopic examinations with antral and corporal biopsies before treatment and again 1-3 and 12-15 months after treatment ended. The
infection was diagnosed if at least two of four tests (culture, histology. rapid urease test. and urea breath test) gave positive results. The endoscopic and histological severity of gastritis was graded by the Sydney system. Statistical analysis was done by the unpaired t-test, Fisher exact test. Wilcoxon rank-sum test, and Wilcoxon signed-rank test. Results: For the liS patients (mean age, 54 years; 84 men and 31 women) treated successfully. the proportions with edema, erythema, friability. exudate, and rugal hypertrophy had decreased by 1-3 months, and the proportions with nodularity had decreased by 12-15 months. Mean neutrophil activity and inflammation decreased by 1-3 months. and both atrophy in the corpus and intestinal metaplasia in the antrum had regressed by 12-15 months. The mean extent of atrophy in terms of Kimura-Takemoto atrophic patterns had decreased by 12-15 months. In the 48 other patients (mean age. 59 years; 30 men and 18 women) in whom the bacterium was not eradicated. there were no clear changes in findings. Conclusion: In long-term follow-up but not short-term follow-up. atrophy and intestinal metaplasia regressed in patients in whom the bacterium was eradicated. Regression of the endoscopic features of edema, erythema. friability, exudate. rugal hypertrophy, and nodularity was related to regression of the histological findings of neutrophil activity and inflammation.
5877 ACTIVATED PROTEIN C INHIBITS THE SECRETION OF TUMOR NECROSIS FACTOR-A INDUCED BY CAG A FROM HEL-
ICOBACTER PYLORI. Satoko Oka, Esteban Cesar Gabazza, Ichiro Imoto, Nagahito Toyoda, Shigehito Nakashima, Michihiko Yamaguchi, Yukiko Taguchi, Yukihiko Adachi, Koji Suzuki. Mie Univ Sch of Medicine. Tsu, Japan. Background/Aim: Activated protein C (APC). besides regulating the activation of the coagulation system, has recently been suggested to modulate the inflammatory response. We previously reported that APC is present at high concentration in the gastric mucosa of patients with Helicobacter pylori (H. pylori) -associated gastritis, and that lipopolysaccharide (LPS), cytotoxin-associated antigen (CagA) and vacuolating cytotoxin from this bacterium increase the formation of APC on the surface of monocytic cells . The secretion of cytokines induced by CagA has been recently reported to play an important role in the mechanism of the gastric mucosal injury. In the present study, we evaluated whether APC inhibits the CagA-induced secretion of cytokines in THP-I cells. Method: The monocytic THP-I cells were culutured using RPMI 1640 medium containing 2.5% fetal bovine serum. For assessing the stimulatory activity of CagA on TNF-asecretion from THP-l cells, the cells (lxlOOOOOO/well) were stimulated with varying concentrations of CagA. The time course of CagA-mediated secretion of TNF-awas also evaluated. For evaluating the inhibitory activity of APC, THP-l cells were cultured in the presence of defined concentrations of CagA and of varying concentrations of APC (0-15/-Lg/ml). Results: CagA significantly (p<0.05) stimulated the secretion of TNF-afrom THP-I cells in a concentration-dependent manner; CagA also time-dependently stimulated the secretion of TNF-afrom these monocytic cells, the secretion reaching a peak at 12 h. Culture of THP-I cells in the presence of APC, significantly inhibited the secretion of CagA-inducedsecretion of TNF-ain a dose-dependent manner. Conclusion: CagA was found to increase the secretion of TNF-afrom monocytic cells. suggesting an important mechanism by which CagA injures the gastric mucosa. In addition. APC was found to inhibit significantly the CagA-mediated stimulation of TNFosecretion. suggesting that APC may play an important role in the protection of the gastric mucosa during H. pylori -associated gastritis.
5878 MECHANISM BY WHICH BEER AND WINE STIMULATES GASTRIC ACID SECRETION IN DOGS: ROLE OF GASTRIN. Susumu Okabe, Tasuku Murai, Kuniharu Matsuno, Atsuko Ono, Kyoto Pharm Univ, Kyoto, Japan. Background/Aim: Oral administration of beer and wine stimulates gastric acid secretion in man and animals, most probably by inducing an increased gastrin release. To confirm the role of circulating gastrin, we examined whether or not (S-0509, a CCK-B/gastrin-receptor antagonist) inhibits the gastric acid secretion stimulated by beer, wine and ethanol in dogs. Materials & Methods: Animals: Ten beagle dogs (10-14 kg) of both sexes, either with a vagally-denervated Heidenhain pouch (n=7) and innervated fistula (n=3), were used in the study. Gastric samples were collected every IS min and analyzed for volume and acid output. Acid secretion was stimulated by beer (50-200 ml), red or white wine (25-100 ml), or 5% ethanol (contained in the beer, 200 ml). S-0509, famotidine or atropine (as reference drugs) was given iv 15 min prior to secretagogues. Results: Beer, wine (red and white) and 5% ethanol significantly stimulated gastric acid secretion in dogs with a Heidenhain pouch and gastric fistula in a volumerelated mannter. Special beer (Root beer), without ethanol, also stimulated the gastric acid secretion which was not different from the normal beer with ethanol. The degree of acid stimulation by 50 ml of red and white wine was much the same. The peak acid outputs were observed 30 min after administration, approx. 0.4 mEq/15 min for beer, 0.2 mEqll5 min for wine and 0.1 mEq/15 min for 5% ethanol. These stimulated secretion returned to the basal level within 60 min. Serum gastrin level significantly increased after the administration of beer and wine, but not after 5% ethanol. S-0509 (0.3, I and 3 mg/kg) significantly inhibited both beer and wine-stimulated acid secretion in a dose-related manner. The duration of antisecretory effect of S-0509 on wine-stimulated secretion was shorter
AGAA1287
April 2000
than that observed with beer. Both famotidine (0.3 mglkg) and atropine (0.1 mglkg) profoundly and persistently inhibited the beer and winestimulated secretion. To note was that 5% ethanol-stimulated acid secretion was not inhibited by S-0509, although it was significantly inhibited by both famotidine and atropine. Conclusion: The mechanism underlying enhanced gastric acid secretion by beer and wine appears to involve the increased level of gastrin in the blood. The mechanism of stimulatory action of 5% ethanol might involve other factors rather than gastrin. 5879 ENDOSCOPIC AND HISTOLOGICAL ESOPHAGITIS IN PATIENTS WITH PHARYNGEAL AND LARYNGEAL PARESTHESIA. Masahiro Okochi, Takashi Joh, Hiromi Kataoka, Hideo Suzuki, Kyouji Seno, Naotsuka Okayama, Yoshihumi Yokoyama, Makoto Itoh, Nagoya City Univ Med Sch, Nagoya, Japan. (Background & Aim) Some studies have suggested that pharyngeal and laryngeal (PhlLa) paresthesia is partly associated with gastric acid regurgitation. Howev.er, the relationship between PhlLa paresthesia and esophagitis has been investigated in less detail. Therefore, this study examined how PhlLa paresthesia is linked to the endoscopic and histological reflux esophagitis. (Method) PhlLa paresthesia, reflux symptoms and abdominal symptoms were evaluated in 500 outpatients referred to the upper gastrointestinal endoscopy by self-administered questionnaires prior to endoscopy. During endoscopic examination, 7 biopsy specimens taken for histological evaluation, which consisted of 2 from the proximal and distal esophagus, and 5 from the antrum, angle, body of the stomach. Prevalence of H. pylori infection was also determined by histology and the H.p serum antibody. TheX2 test was used for statistical analysis. (Results) 1. The frequency of reflux symptoms and PhlLa paresthesia was 24.0 and 34.0%, respectively. 2. The frequency of endoscopic (12.8 vs 9.0%), histological esophagitis (55.9 vs 26.9%, p
5881 CLINICAL PREDICTION OF ENDOSCOPIC HEALING IN RE· FLUX ESOPHAGITIS THE SECOND WEEK OF TREATMENT. Jorge Olmos, Roberto Higa, Jorge Davolos, Alejandro Gards, Hosp Italy, Buenos Aires, AA, Argentina. Introduction: Symptomatic relief and lesion healing are the aim of the treatment of reflux esophagitis. There is a lack of clinical tools to predict the healing probability of this disorder. Aim: To determine the value of a clinical score as predictor of healing in reflux esophagitis patients. Material and methods: Eighty-four patients of both genders were enrolled. They were 18-80 years old and presented reflux esophagitis. Subjects who had received treatment With PPls the last four weeks; those with cancer; postoperative esophagitis; severe renal, hepatic or cardiac failure were excluded. Pregnant women, possibly pregnant women, and women in breast-feeding period were also excluded. Patients were randomized in two groups: 42 to receive lanzoprazole 15 mg (23 F/19 M, age X 52.7 :!:: 14.2) and 42 to receive lanzoprazole 30 mg (16 F126 M, age X 49.7 :!:: 15.4). The diagnosis was confirmed at entrance by endoscopy and healing was controlle? with the same study at the second week, and if necessary at forth and eight weeks of treatment. A basal clinical score was assigned according to the presence of: heartburn, I point; regurgitation, I point; heartburn plus regurgitation, 1.5 points; nocturnal symptoms, 2 points; and symptom frequency: occasional, I point, often, 2 points and frequent, 3 points. Univariate and multivariate logistic regression were applied to validate the results. Results: According to logistic regression the results at the second we~k of treatment are the following: Assuming a cutoff limit of 4.5 points patients have at least 80% probability of healing. The higher the score, the lowest the healing probability (p = <0.05), regardless the treatment received. Clinical score Healing probability 2.0360 94% 2.5213093% 3.0213090% 3.5213087% 4.0213084% 4.5213080% 5.0213074% Conclusions: A symptomatic score based on personal interview is a useful tool to predict early healing regardless the treatment administered is this study. 5882 LANZOPRAZOLE 15 MG IS AS EFFECTIVE AS LANZOPRA· ZOLE 30 MG IN MILD AND MODERATE EROSIVE REFLUX ESOPHAGITIS (ERE). Jorge Olmos, Roberto Higa, Jorge Davolos, Alejandro Gards, Hosp Italy, Buenos Aires, Argentina. Symptomatic relief and healing are the aims of the treatment of ERE. Several reports compare different doses of lanzoprazole. However, no study evaluates the role of a clinical score, an endoscopic score and the measurement of quality of life. Aim: 1. To compare the safety and the efficacy of two different doses of lanzoprazole at weeks 2, 4 and 8 of treatment. 2. To determine if a clinical score and an endoscopic score are good predictors of healing and quality of life improvement at two weeks of treatment. Material and methods: 84 patients, both genders, age 18-80, with ERE grades I to 3 according to Savary-Miller were enrolled. Subjects that had received PPls the last 4 weeks; that consumed NSAID; with esophageal cancer or perforation; postoperative esophagitis; severe renal, hepatic or cardiac failure were excluded. Patients were randomized into two groups: 42 to receive lanzoprazole 15 mg daily (23 FI19 M, age X 52.7 :!:: 14.2) and 42 to receive 30 mg daily (16 F126 M, age X 49.7 :!:: 15.4). The patients were evaluated at entrance and at week 2 by means of an endoscopic score, a clinical score, and a visual analog scale. Quality of life was measured with a validated test. Presence, severity and duration of side effects were recorded. Wilcoxon's test, multiple logistic regression and Schuirmann's test to evaluate efficacy equivalence were used to validate the results. Results:Subgroups Grade 1 Grade 2 Grade 3 L. 15 mg 9 22 II L. 30 mg 12235 Healing 15 mg 30 mg Shuirmann's test week 2 67% vs. 69% p <0.05 (equivalent) week 4 88.1% vs. 78.3% P <0.001 (equivalent) week 8 88.1% vs. 83.3% P <0.001 (equivalent/intention-to-treat analysis) 97.4% vs. 100% P < 0.001 (equivalent/per protocol analysis) The symptomatic score and Visual analog scale predicted a significant improvement after week 2. As for the quality of life score, it diminished from a value of 18 to 4 at week 2 (p <0.001). According to an univariate analysis, the clinical s~ore predicts the heahng at week 2 (p <0.05). Mucosal friability IS a negatrve predictor of heahng at week 2 (p <0.005). Side effects were mild and transient. Conclusions: Lanzoprazole 15 mg is as effective as lanzoprazole 30 mg in healing mild and moderate ERE. A significant rate of healing was achieved at week 2. The small number of patients in this gro~p hinder~d the analysis of grade 3 esophagitis. Symptoms and quality of hfe were significantly Improved after week 2. The clinical score predicts the healing probability at week 2, while friability was a negative predictor. Both drugs demonstrated to be safe.
GASTROENTEROLOGY Vol. 118, No.4
5874 ASSESSMENT OF A DISCRIMINAT PRONOSTIC ANALYSIS FOR PEPTIC ULCER HEMORRHAGE. Antoni Obrador, Juan Vidal, Luis Barranco, Amparo Sapina, Juan Riera, Pere Vaquer, Alfred Llompart, Jaume Gaya, Son Dureta Hosp, Palma, Spain. In a previous study, which included more than 300 patients, we accomplished a logistic regression multivariate analysis of the relapsing factors of the gastroduodenal ulcer hemorrhage. The independent variables were: type of ulcer base, size of the ulcer, endoscopic detection of blood in the explored tract, and clinical signs of low cardiac output. Objective. Assessment of a discriminative analysis for predicting rebleeds due to gastroduodenal ulcer in a prospective series of patients. Patients and methods. The patients who arrived at the hospital for an upper gastrointestinal hemorrhage (after performing a diagnostic endoscopy) were evaluated to estimate the risk of relapse according to the discriminant analysis obtained in the same center. The applied analysis is as follows: Probability = 1/(1+e- Z ) , being e = 2,7183 and z = the sum of the value of the variables in a certain patient. The study was carried out from July 1998 to May 1999. The series was of 172 patients. Results: the following contingence table shows the results of the application of the discriminative function. These data agree to obtain the next parameters: sensibility 13,3%; specificity 99,4%; positive predictive value 66,6; negative predictive value 92,3% and a global efficiency of 91,3%. If we had applied the four criteria in the 13 patients in whom the analysis did not predict the relapse, there had not turned out any error in the prevision. Conclusions. I) The discriminative analysis obtained applied to prospective series yields a small percentage of classification errors in the prediction of rebleeding. 2) The application of the four criteria that integrates the analysis permits the correction of the errors in all the cases. 3) This information is basic to set up a program of early discharge for patients suffering from gastroduodenal ulcer hemorrhage. Contingence table ofreal relapses vs predicted relapses
yes no
total
yes
no
total
2 13 15
1
156 157
3 169 172
Ordinates are the predicted relapses and abscisses are real relapses
5875 OPTIMAL DURATION FOR TRIPLE THERAPY AGAINST NON· RESISTANT STRAINS OF HELICOBACTER PYLORI. Keiji Ogura, Haruhiko Yoshida, Shin Maeda, Yutaka Yamaji, Yuzo Mitsuno, Masao Akanuma, Yoshihiro Hirata, Makoto Okamoto, Takao Kawabe. Yasushi Shiratori, Masao Ornata, The Institute for Adult Diseases, Tokyo, Japan; Dept of Gastroenterology. Univ of Tokyo. Tokyo. Japan; Univ of Tokyo, Tokyo, Japan. BACKGROUND: We reported mixed infection with wild-type (sensitive) and mutant (resistant) Helicobacter pylori strains by using a PCR-based preferential homo-duplex formation assay (PCR-PHFA) to detect 23S rRNA gene mutations associated with clarithromycin resistance (J Clin Microbiol, in press). Half cases with the mixed infection were determined as sensitive by conventional MIC assessment and yet failed in clarithromycin-based therapy. AIM: To assess the efficacy of clarithromycin-based triple therapy in patients infected exclusively with wild-type strains as determined by PCR-PHFA. METHODS: Ninety patients who had pure wild-type H. pylori infection were randomly assigned to take clarithromycin (200 mg b.i.d.), amoxicillin (500 mg q.i.d.), and lansoprazole (30 mg b.i.d.) for either 5 days or 7 days (n = 48 and n = 42, respectively). The outcome of eradication was assessed by [13C] urea breath test. RESULTS: Eradication rates were 36/48 (75%) vs. 39/42 (93%) by intention-to-treat analysis (P =0.022), and 36/45 (80%) vs. 39/40 (98%) by per protocol analysis (P =0.012), for the 5-day and 7-day protocols. respectively. Compliance and the incidence of untoward effects were similar in both groups. CONCLUSIONS: Seven-day administration is necessary and sufficient for the triple therapy with clarithrornycin, amoxicillin, and Iansoprazole in patients with pure wild-type (clarithromycin-sensitive) H. pylori infection.
5876 REGRESSION OF ATROPHIC GASTRITIS AND INTESTINAL METAPLASIA IN PATIENTS FROM WHOM HELICOBACTER PY· LORI WAS ERADICATED MONITORED PROSPECTIVELY FOR AT LEAST ONE YEAR. Toshifumi Ohkusa, Kazuhiko Fujiki, Ichizen Takashimizu, Jiro Kumagai, Toru Tanizawa, Yoshinobu Eishi, Tokyo Med and Dental Univ, Tokyo, Japan. Background: There have been few endoscopic studies during long-term follow-up after eradication of Helicobacter pylori. We examined patients repeatedly by endoscopy and biopsy for at least I year after treatment intended to eradicate the bacterium. Methods: We evaluated 163 infected patients given a proton-pump inhibitor and antibiotics who had at least three endoscopic examinations with antral and corporal biopsies before treatment and again 1-3 and 12-15 months after treatment ended. The
infection was diagnosed if at least two of four tests (culture, histology. rapid urease test. and urea breath test) gave positive results. The endoscopic and histological severity of gastritis was graded by the Sydney system. Statistical analysis was done by the unpaired t-test, Fisher exact test. Wilcoxon rank-sum test, and Wilcoxon signed-rank test. Results: For the liS patients (mean age, 54 years; 84 men and 31 women) treated successfully. the proportions with edema, erythema, friability. exudate, and rugal hypertrophy had decreased by 1-3 months, and the proportions with nodularity had decreased by 12-15 months. Mean neutrophil activity and inflammation decreased by 1-3 months. and both atrophy in the corpus and intestinal metaplasia in the antrum had regressed by 12-15 months. The mean extent of atrophy in terms of Kimura-Takemoto atrophic patterns had decreased by 12-15 months. In the 48 other patients (mean age. 59 years; 30 men and 18 women) in whom the bacterium was not eradicated. there were no clear changes in findings. Conclusion: In long-term follow-up but not short-term follow-up. atrophy and intestinal metaplasia regressed in patients in whom the bacterium was eradicated. Regression of the endoscopic features of edema, erythema. friability, exudate. rugal hypertrophy, and nodularity was related to regression of the histological findings of neutrophil activity and inflammation.
5877 ACTIVATED PROTEIN C INHIBITS THE SECRETION OF TUMOR NECROSIS FACTOR-A INDUCED BY CAG A FROM HEL-
ICOBACTER PYLORI. Satoko Oka, Esteban Cesar Gabazza, Ichiro Imoto, Nagahito Toyoda, Shigehito Nakashima, Michihiko Yamaguchi, Yukiko Taguchi, Yukihiko Adachi, Koji Suzuki. Mie Univ Sch of Medicine. Tsu, Japan. Background/Aim: Activated protein C (APC). besides regulating the activation of the coagulation system, has recently been suggested to modulate the inflammatory response. We previously reported that APC is present at high concentration in the gastric mucosa of patients with Helicobacter pylori (H. pylori) -associated gastritis, and that lipopolysaccharide (LPS), cytotoxin-associated antigen (CagA) and vacuolating cytotoxin from this bacterium increase the formation of APC on the surface of monocytic cells . The secretion of cytokines induced by CagA has been recently reported to play an important role in the mechanism of the gastric mucosal injury. In the present study, we evaluated whether APC inhibits the CagA-induced secretion of cytokines in THP-I cells. Method: The monocytic THP-I cells were culutured using RPMI 1640 medium containing 2.5% fetal bovine serum. For assessing the stimulatory activity of CagA on TNF-asecretion from THP-l cells, the cells (lxlOOOOOO/well) were stimulated with varying concentrations of CagA. The time course of CagA-mediated secretion of TNF-awas also evaluated. For evaluating the inhibitory activity of APC, THP-l cells were cultured in the presence of defined concentrations of CagA and of varying concentrations of APC (0-15/-Lg/ml). Results: CagA significantly (p<0.05) stimulated the secretion of TNF-afrom THP-I cells in a concentration-dependent manner; CagA also time-dependently stimulated the secretion of TNF-afrom these monocytic cells, the secretion reaching a peak at 12 h. Culture of THP-I cells in the presence of APC, significantly inhibited the secretion of CagA-inducedsecretion of TNF-ain a dose-dependent manner. Conclusion: CagA was found to increase the secretion of TNF-afrom monocytic cells. suggesting an important mechanism by which CagA injures the gastric mucosa. In addition. APC was found to inhibit significantly the CagA-mediated stimulation of TNFosecretion. suggesting that APC may play an important role in the protection of the gastric mucosa during H. pylori -associated gastritis.
5878 MECHANISM BY WHICH BEER AND WINE STIMULATES GASTRIC ACID SECRETION IN DOGS: ROLE OF GASTRIN. Susumu Okabe, Tasuku Murai, Kuniharu Matsuno, Atsuko Ono, Kyoto Pharm Univ, Kyoto, Japan. Background/Aim: Oral administration of beer and wine stimulates gastric acid secretion in man and animals, most probably by inducing an increased gastrin release. To confirm the role of circulating gastrin, we examined whether or not (S-0509, a CCK-B/gastrin-receptor antagonist) inhibits the gastric acid secretion stimulated by beer, wine and ethanol in dogs. Materials & Methods: Animals: Ten beagle dogs (10-14 kg) of both sexes, either with a vagally-denervated Heidenhain pouch (n=7) and innervated fistula (n=3), were used in the study. Gastric samples were collected every IS min and analyzed for volume and acid output. Acid secretion was stimulated by beer (50-200 ml), red or white wine (25-100 ml), or 5% ethanol (contained in the beer, 200 ml). S-0509, famotidine or atropine (as reference drugs) was given iv 15 min prior to secretagogues. Results: Beer, wine (red and white) and 5% ethanol significantly stimulated gastric acid secretion in dogs with a Heidenhain pouch and gastric fistula in a volumerelated mannter. Special beer (Root beer), without ethanol, also stimulated the gastric acid secretion which was not different from the normal beer with ethanol. The degree of acid stimulation by 50 ml of red and white wine was much the same. The peak acid outputs were observed 30 min after administration, approx. 0.4 mEq/15 min for beer, 0.2 mEqll5 min for wine and 0.1 mEq/15 min for 5% ethanol. These stimulated secretion returned to the basal level within 60 min. Serum gastrin level significantly increased after the administration of beer and wine, but not after 5% ethanol. S-0509 (0.3, I and 3 mg/kg) significantly inhibited both beer and wine-stimulated acid secretion in a dose-related manner. The duration of antisecretory effect of S-0509 on wine-stimulated secretion was shorter
AGAA1287
April 2000
than that observed with beer. Both famotidine (0.3 mglkg) and atropine (0.1 mglkg) profoundly and persistently inhibited the beer and winestimulated secretion. To note was that 5% ethanol-stimulated acid secretion was not inhibited by S-0509, although it was significantly inhibited by both famotidine and atropine. Conclusion: The mechanism underlying enhanced gastric acid secretion by beer and wine appears to involve the increased level of gastrin in the blood. The mechanism of stimulatory action of 5% ethanol might involve other factors rather than gastrin. 5879 ENDOSCOPIC AND HISTOLOGICAL ESOPHAGITIS IN PATIENTS WITH PHARYNGEAL AND LARYNGEAL PARESTHESIA. Masahiro Okochi, Takashi Joh, Hiromi Kataoka, Hideo Suzuki, Kyouji Seno, Naotsuka Okayama, Yoshihumi Yokoyama, Makoto Itoh, Nagoya City Univ Med Sch, Nagoya, Japan. (Background & Aim) Some studies have suggested that pharyngeal and laryngeal (PhlLa) paresthesia is partly associated with gastric acid regurgitation. Howev.er, the relationship between PhlLa paresthesia and esophagitis has been investigated in less detail. Therefore, this study examined how PhlLa paresthesia is linked to the endoscopic and histological reflux esophagitis. (Method) PhlLa paresthesia, reflux symptoms and abdominal symptoms were evaluated in 500 outpatients referred to the upper gastrointestinal endoscopy by self-administered questionnaires prior to endoscopy. During endoscopic examination, 7 biopsy specimens taken for histological evaluation, which consisted of 2 from the proximal and distal esophagus, and 5 from the antrum, angle, body of the stomach. Prevalence of H. pylori infection was also determined by histology and the H.p serum antibody. TheX2 test was used for statistical analysis. (Results) 1. The frequency of reflux symptoms and PhlLa paresthesia was 24.0 and 34.0%, respectively. 2. The frequency of endoscopic (12.8 vs 9.0%), histological esophagitis (55.9 vs 26.9%, p
5881 CLINICAL PREDICTION OF ENDOSCOPIC HEALING IN RE· FLUX ESOPHAGITIS THE SECOND WEEK OF TREATMENT. Jorge Olmos, Roberto Higa, Jorge Davolos, Alejandro Gards, Hosp Italy, Buenos Aires, AA, Argentina. Introduction: Symptomatic relief and lesion healing are the aim of the treatment of reflux esophagitis. There is a lack of clinical tools to predict the healing probability of this disorder. Aim: To determine the value of a clinical score as predictor of healing in reflux esophagitis patients. Material and methods: Eighty-four patients of both genders were enrolled. They were 18-80 years old and presented reflux esophagitis. Subjects who had received treatment With PPls the last four weeks; those with cancer; postoperative esophagitis; severe renal, hepatic or cardiac failure were excluded. Pregnant women, possibly pregnant women, and women in breast-feeding period were also excluded. Patients were randomized in two groups: 42 to receive lanzoprazole 15 mg (23 F/19 M, age X 52.7 :!:: 14.2) and 42 to receive lanzoprazole 30 mg (16 F126 M, age X 49.7 :!:: 15.4). The diagnosis was confirmed at entrance by endoscopy and healing was controlle? with the same study at the second week, and if necessary at forth and eight weeks of treatment. A basal clinical score was assigned according to the presence of: heartburn, I point; regurgitation, I point; heartburn plus regurgitation, 1.5 points; nocturnal symptoms, 2 points; and symptom frequency: occasional, I point, often, 2 points and frequent, 3 points. Univariate and multivariate logistic regression were applied to validate the results. Results: According to logistic regression the results at the second we~k of treatment are the following: Assuming a cutoff limit of 4.5 points patients have at least 80% probability of healing. The higher the score, the lowest the healing probability (p = <0.05), regardless the treatment received. Clinical score Healing probability 2.0360 94% 2.5213093% 3.0213090% 3.5213087% 4.0213084% 4.5213080% 5.0213074% Conclusions: A symptomatic score based on personal interview is a useful tool to predict early healing regardless the treatment administered is this study. 5882 LANZOPRAZOLE 15 MG IS AS EFFECTIVE AS LANZOPRA· ZOLE 30 MG IN MILD AND MODERATE EROSIVE REFLUX ESOPHAGITIS (ERE). Jorge Olmos, Roberto Higa, Jorge Davolos, Alejandro Gards, Hosp Italy, Buenos Aires, Argentina. Symptomatic relief and healing are the aims of the treatment of ERE. Several reports compare different doses of lanzoprazole. However, no study evaluates the role of a clinical score, an endoscopic score and the measurement of quality of life. Aim: 1. To compare the safety and the efficacy of two different doses of lanzoprazole at weeks 2, 4 and 8 of treatment. 2. To determine if a clinical score and an endoscopic score are good predictors of healing and quality of life improvement at two weeks of treatment. Material and methods: 84 patients, both genders, age 18-80, with ERE grades I to 3 according to Savary-Miller were enrolled. Subjects that had received PPls the last 4 weeks; that consumed NSAID; with esophageal cancer or perforation; postoperative esophagitis; severe renal, hepatic or cardiac failure were excluded. Patients were randomized into two groups: 42 to receive lanzoprazole 15 mg daily (23 FI19 M, age X 52.7 :!:: 14.2) and 42 to receive 30 mg daily (16 F126 M, age X 49.7 :!:: 15.4). The patients were evaluated at entrance and at week 2 by means of an endoscopic score, a clinical score, and a visual analog scale. Quality of life was measured with a validated test. Presence, severity and duration of side effects were recorded. Wilcoxon's test, multiple logistic regression and Schuirmann's test to evaluate efficacy equivalence were used to validate the results. Results:Subgroups Grade 1 Grade 2 Grade 3 L. 15 mg 9 22 II L. 30 mg 12235 Healing 15 mg 30 mg Shuirmann's test week 2 67% vs. 69% p <0.05 (equivalent) week 4 88.1% vs. 78.3% P <0.001 (equivalent) week 8 88.1% vs. 83.3% P <0.001 (equivalent/intention-to-treat analysis) 97.4% vs. 100% P < 0.001 (equivalent/per protocol analysis) The symptomatic score and Visual analog scale predicted a significant improvement after week 2. As for the quality of life score, it diminished from a value of 18 to 4 at week 2 (p <0.001). According to an univariate analysis, the clinical s~ore predicts the heahng at week 2 (p <0.05). Mucosal friability IS a negatrve predictor of heahng at week 2 (p <0.005). Side effects were mild and transient. Conclusions: Lanzoprazole 15 mg is as effective as lanzoprazole 30 mg in healing mild and moderate ERE. A significant rate of healing was achieved at week 2. The small number of patients in this gro~p hinder~d the analysis of grade 3 esophagitis. Symptoms and quality of hfe were significantly Improved after week 2. The clinical score predicts the healing probability at week 2, while friability was a negative predictor. Both drugs demonstrated to be safe.