bismuth-tripotassium-dicitrate and Stomach-Ulcer

Studies of the role of H. pylori (Hp) in etiopathogenesis of a number of common diseases of the upper gastrointestinal tract changed traditional approaches to their management with emphasis on antibiotic therapy. Positive effect of Hp eradication was confirmed in numerous randomized clinical studies. Bismuth-containing drugs have been used for a long time to treat gastrointestinal disorders. To-day, bismuth tri-potassium di-citrate (de---nol) is considered to be an optimal tool for different schemes of eradication therapy (triple and quadruple therapy of the first and second lines) and recommended to improve its efficiency by overcoming resistance of Hp to antibiotics. The overall efficacy of anti-helicobacterial therapy using bismuth tri-potassium di-citrate amounts to 81-98%. This compound has cytoprotective effect on gastric and duodenal mucosa, besides antibacterial action. All these properties characterize de-nol as a single universal preparation for the treatment of erosive ulcers in the gastrointestinal tract.

Topics: Anti-Ulcer Agents; Bismuth; Duodenal Ulcer; Humans; Intestinal Mucosa; Organometallic Compounds; Stomach Ulcer; Treatment Outcome

taking into account the small amount of infection eradication treatments carried out in our country and some characteristics arising from the resistances to some antibiotics, the Spanish Club for the Study of Helicobacter pylori decided to organize a Spanish Consensus Conference to clarify the use of the different infection diagnostic tests, to establish the exact indications of its diagnosis and treatment, to recommend the best treatment guidelines for our country and to promote the use of eradication treatments in adequate indications.. on April 23, 1999 in Madrid, physicians who were experts in infection by Helicobacter pylori representing the different Scientific Societies of our country were gathered. Prior to this, three work areas, diagnosis, indications and treatments, were created and the participants freely joined them. One month before the conference, all of the participants were sent the questions which would be debated. An 80% consensus level, always based on scientific evidence, was required for a recommendation. In the first session, a meeting by work areas was held and in a second session, all of the recommendations were voted on in the meeting of the representatives.. the conference recommends the eradication of the infection in all the gastric or duodenal ulcers, in the erosive duodenitis, in the MALT lymphomas and in gastrectomized patients due to gastric cancer with residual stomach. In the de novo diagnoses of gastroduodenal ulcer, the rapid test of urease is recommended, and a histological study is recommended only if it is negative. In the case of a history of ulcers and also to know the eradication treatment result, the C13 urea breath test is recommended. The culture is reserved for primary treatment and rescue treatment failures so as to select the adequate antibiotic. The primary treatment regimes recommended for our country mean the combination of amoxicillin, clarithromycin and any proton pump inhibitor or with Ranitidine bismuth citrate. If there is allergy to penicillin, amoxycillin will be substituted by metronidazol.

Topics: Amoxicillin; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Clarithromycin; Duodenal Ulcer; Duodenitis; Gastrectomy; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Lymphoma, B-Cell, Marginal Zone; Organometallic Compounds; Penicillins; Proton Pump Inhibitors; Ranitidine; Stomach Neoplasms; Stomach Ulcer

Topics: Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Duodenal Ulcer; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Stomach Ulcer

Helicobacter pylori is becoming increasingly important as a gastrointestinal pathogen and aetilogical agent in several disease states. This review attempts to clarify the role of Helicobacter pylori and importantly, simplify treatment options.

Topics: Amoxicillin; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Dyspepsia; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Organometallic Compounds; Penicillins; Stomach Neoplasms; Stomach Ulcer; Tetracycline; Time Factors

The relationship between Helicobacter pylori (HP) and gastric ulcer therapy is examined by analyzing both the data that suggest that eradication of HP renders the gastric mucosa less susceptible to development of gastric ulcer as well as the substantial body of evidence that does not support this contention. The results reported in clinical trials with colloidal bismuth citrate, antimicrobial agents (furazolidone), and combinations of anti-ulcer and antimicrobial agents (H2-antagonist+cefixime, H2-antagonist+metronidazole) are reviewed. Also analyzed is the relationship between HP eradication and ulcer recurrence. Only one study is available on this aspect, and the limited evidence it provides in favour of a prophylactic effect of eradication therapy is not entirely convincing. The authors conclude that there is no reasonable case for the dogmatic assumption that eradication of HP facilitates either acute healing or long-term prophylaxis of gastric ulcer, though certain subgroups of gastric ulcer patients may benefit from eradication therapy.

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Cefixime; Cefotaxime; Cimetidine; Drug Therapy, Combination; Furazolidone; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Stomach Ulcer

Many endoscopically controlled comparisons with H2-blockers have widely documented that site- and cytoprotective drugs constitute effective and safe agents for the short-term treatment of gastric and duodenal ulcer. Their efficacy however, is counter-acted by the need for multiple daily administration which requires greater patient compliance. Due to its ability to eradicate Helicobacter pylori (HP) from the gastric antrum and retard relapses, colloidal bismuth may be the first choice anti-ulcer drug for those HP positive patients who do not accept continuous maintenance treatment after healing. A specific subgroup of duodenal ulcer patients who may particularly benefit from a short-term treatment with such agents (namely colloidal bismuth) are the non-responders to an 8-week course of H2-antagonists; conversely, actual evidence does not support the hypothetical superiority of such agents over H2-blockers in the treatment of cigarette smokers or chronic consumers of NSAIDs.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bismuth; Drug Administration Schedule; Duodenal Ulcer; Gastric Mucosa; Helicobacter pylori; Histamine H2 Antagonists; Humans; Organometallic Compounds; Smoking; Stomach Ulcer

Topics: Campylobacter Infections; Duodenal Ulcer; Humans; Long-Term Care; Omeprazole; Organometallic Compounds; Ranitidine; Stomach Ulcer

The healing properties of colloidal bismuth subcitrate (CBS) on peptic ulcer are well established and several studies have shown that healing with CBS is associated with a lower relapse rate than that produced by H2-receptor antagonists. The recent observation that CBS is effective against Campylobacter pylori has shed light on this because recent studies have shown that eradication of C. pylori by CBS leads to resolution of the associated gastritis and this may explain the low relapse rates. CBS is also effective in C. pylori positive patients with non ulcer dyspepsia (NUD) in whom clearance of these organisms from the stomach is associated with significant improvement of the associated gastritis and symptoms.

Topics: Cimetidine; Duodenal Ulcer; Dyspepsia; Gastritis; Humans; Organometallic Compounds; Peptic Ulcer; Recurrence; Stomach Ulcer

Topics: Anti-Ulcer Agents; Duodenal Ulcer; Humans; Organometallic Compounds; Stomach Ulcer

Campylobacter pyloridis is a spiral bacterium which was seen by histopathologists several years before it was cultured in 1982 in Perth, Western Australia. It has unique cellular fatty acids, predominantly tetradecanoic acid and cis-11, 12 methylene octadecanoic acid. It also has a unique ultrastructure which is different from that of other campylobacters. C pyloridis possesses a powerful urease enzyme and produces large amounts of extracellular catalase. Both these features may be important virulence factors, allowing it to occupy a protected niche in the stomach below the mucus layer but above the gastric mucosa. Specific lesions are found in the gastric mucosa, and ultrastructural studies show the presence of adherence pedestals identical with those found with enteropathogenic Escherichia coli of the intestine. Histological examination of gastric biopsy tissue has shown that C pyloridis is strongly associated with active chronic gastritis, when polymorphonuclear leucocytes are present, and is not found on normal mucosa except when a biopsy specimen from elsewhere in the stomach shows active chronic gastritis. When patients with symptoms caused by gastritis are identified dual antibacterial treatment, combining the action of bismuth in the stomach with a systemic antibiotic, can eradicate C pyloridis, with remission of symptoms and restoration of normal epithelial morphology. Most peptic ulcers relapse after modern acid reducing treatment, and antibacterial treatment may be beneficial in preventing relapse.

Topics: Amoxicillin; Animals; Anti-Ulcer Agents; Antibodies, Bacterial; Bismuth; Campylobacter; Campylobacter Infections; Duodenal Ulcer; Escherichia coli Infections; Female; Gastric Mucosa; Gastritis; Humans; Male; Microscopy, Electron; Middle Aged; Organometallic Compounds; Rabbits; Stomach Ulcer

Reduction of gastric acidity by the inhibition of secretion or neutralization is the therapeutic principle most widely used in peptic ulcer disease. From a pathophysiological standpoint, this does not appear logical, because in a majority of patients gastric acid secretion is not increased. In addition, there is some concern about the consequences of a reduction in gastric acidity, especially in the long term. And finally, all available inhibitors of gastric acid secretion have a systemic action and may thus cause systemic side effects. Carbenoxolone, sucralfate, and tri-potassium dicitrato bismuthate have been shown to accelerate healing of ulcers without appreciable acid inhibition. Despite an apparently different mode of action, the healing rates are similar to those of commonly used acid inhibitors. Several possible mechanisms of action have been claimed for each of these agents, but none has been convincingly demonstrated to be essential in ulcer healing. This may reflect ignorance of the relevant events rather than an action by a combined principle.

Topics: Anti-Ulcer Agents; Carbenoxolone; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acid; Humans; Organometallic Compounds; Stomach Ulcer; Sucralfate

To study efficacy of a combination of proton pump inhibitor (PPI) and bismuth tripotassium dicitrate (BTD) in gastric ulcers (GU) induced by non-steroid anti-inflammatory drugs (NSAD) in rheumatic patients with factors affecting PPI efficacy.. Fifty rheumatic patients entered the study (5 males and 45 females, mean age 63.5 +/- 6.2 years) with NSAD-induced GU. Criteria of participation in the study: ulcer size > 1.0 cm, 2 and more ulcers, administration of glucocorticoids (GC) and/or cytotoxic drugs. The patients were divided into two groups. Group 1 patients received omeprasol 20 mg twice a day + BTD 240 mg twice a day; group 2 patients received omeprasol alone 20 mg twice a day. The groups were matched by demographic and clinical parameters, consisted mainly of women with rheumatoid arthritis, most of the patients took GC, methotrexate or leflunamid. The result of the treatment was evaluated by the findings of endoscopic examination 4 and 8 weeks after treatment.. Three patients from group 1 and 2 patients from group 2 were withdrawn from the study. For 4 weeks ulcer heeling was achieved in 15 patients of group 1 (68.2%) and 8 patients of group 2 (34.8%), p = 0.038. On week 8 ulcers healed in 86.3 and 78.3% patients, respectively. Severe side effects were absent.. Combination of omeprasol with BTD stimulated heeling of NSAD-induced gastric ulcer.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Omeprazole; Organometallic Compounds; Proton Pump Inhibitors; Stomach Ulcer; Treatment Outcome

The purpose of the present paper was to evaluate the efficacy and tolerability of amoxicillin-clavulanate and tetracycline-based quadruple therapy as an alternative second-line treatment for H. pylori infection.. The study subjects consisted of 54 patients infected with H. pylori, in whom initial triple therapy had failed. Subjects were randomized to receive the following 7-day therapies: (i) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., amoxicillin-clavulanate 1000 mg b.i.d., and tetracycline 500 mg q.i.d. (PBAT); or (ii) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. (PBMT). Eradication rates based on antibiotic susceptibility, drug compliance and side-effect rates were evaluated and compared.. The H. pylori eradication rates were 16.0%/17.4% with PBAT and 65.5%/70.4% with PBMT by intention-to-treat (P<0.001) and per-protocol analyses (P<0.001), respectively. In patients who received PBAT, the eradication rates were only 16.7% (2/12) for both amoxicillin and tetracycline-susceptible H. pylori strains. Drug compliance and side-effect rates were similar in the two groups.. Despite high individual in vitro antimicrobial activity, amoxicillin-clavulanate and tetracycline-based quadruple therapy showed low eradication rates, which strongly suggests that it should not be considered as a therapeutic option for H. pylori eradication.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Ulcer Agents; Biopsy; Bismuth; Contraindications; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Pantoprazole; Pyloric Antrum; Stomach Ulcer; Tetracycline; Treatment Failure

To evaluate efficiency of colloid bismuth subcitrate (CBS) in gastropathies induced by nonsteroid anti-inflammatory drugs (NSAID).. 45 patients with rheumatic diseases (RD) taking NSAID with gastric and/or duodenal up to 1 cm in size or multiple (more than 10) gastric mucosa erosions detected at esophagogastroduodenoscopy were randomized into two groups. Patients of group 1 (n = 30) received CBS (240 mg twice a day + amoxicillin 2 g/day and furozolidon 400 mg/day--subgroup 1a, n = 10 or CBS monotherapy in the same dose--subgroup 1b, n = 20). Patients of group 2 (n = 15) received ranitidine 150 mg twice a day. Older women, RA patients, patients with gastric ulcer prevailed. H. pylori was detected in 73.3 and 90% patients, respectively. Dispepsia and heartburn occurred in 90 and 93.3%, respectively. The efficacy was assessed after 4 weeks of therapy.. Healing of ulcers and erosions were achieved in 22 of 26 patients of group 1 (84.6%) and in 7 of 14 (50%) of group 2 (p = 0.036, chi-square). After therapy dyspepsia persisted in 4 patients of group 1 and 9 patients of group 2. Side effects were in 3 patients on CBS. Untiulcer effect did not differ between the subgroups (88.8 and 82.4%, respectively) and was effective in 6 of 7 HP-negative patients (85.7%) and in 8 of 10 HP-positive patients (80%).. De-Nol is effective in NSAID-induced gastropathies. Its action is not related with influence on HP.

Topics: Aged; Anti-Infective Agents, Local; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Diarrhea; Drug Administration Schedule; Duodenal Ulcer; Duodenoscopy; Esophagoscopy; Female; Furazolidone; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Prevalence; Ranitidine; Severity of Illness Index; Sex Distribution; Stomach Ulcer

The eradication rate of Helicobacter pylori (H pylori) shows variation among countries and regimens of treatment. We aimed to study the eradication rates of different regimens in our region and some factors affecting the rate of eradication.. One hundred and sixty-four H pylori positive patients (68 males, 96 females; mean age: 48+/-12 years) with duodenal or gastric ulcer without a smoking history were included in the study. The patients were divided into three groups according to the treatment regimens. Omeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1 g were given twice daily for 1 week (Group I) and 2 weeks (Group II). Patients in Group III received bismuth subsitrate 300 mg, tetracyline 500 mg and metronidazole 500 mg four times daily in addition to Omeprazole 20 mg twice daily. Two biopsies each before and after treatment were obtained from antrum and corpus, and histopathologically evaluated. Eradication was assumed to be successful if no H pylorus was detected from four biopsy specimens taken after treatment. The effects of factors like age, sex, H pylori density on antrum and corpus before treatment, the total H pylori density, and the inflammation scores on the rate of H pylori eradication were evaluated.. The overall eradication rate was 42%. The rates in groups II and III were statistically higher than that in group I (P<0.05). The rates of eradication were 24.5%, 40.7% and 61.5% in groups I, II and III, respectively. The eradication rate was negatively related to either corpus H pylori density or total H pylori density (P<0.05). The median age was older in the group in which the eradication failed in comparison to that with successful eradication (55 yr vs 39 yr, P<0.001). No correlation between sex and H pylori eradication was found.. Our rates of eradication were significantly lower when compared to those reported in literature. We believe that advanced age and high H pylori density are negative predictive factors for the rate of H pylori eradication.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Ulcer Agents; Clarithromycin; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Stomach Ulcer; Tetracycline; Treatment Outcome; Turkey

Clinical and instrumental-laboratory investigations have been conducted in 372 patients with chronic antral gastritis (CAG, n = 131), diffuse gastritis (DG, n = 108) and ulcer disease (UD, n = 135). Immunomodulators tactivin and levamisol were added to standard treatment of 75 CAG, 63 DG and 85 UD patients. Healing of the lesions was observed, on the average, on the treatment day 24.3 +/- 0.5 and 18.4 +/- 0.6 in the standard treatment and with the added immunomodulator, respectively. Adjuvant levamisol diminished the number of recurrences of chronic gastritis and UD.

Topics: Adjuvants, Immunologic; Anti-Infective Agents; Chronic Disease; Drug Administration Schedule; Drug Therapy, Combination; Duodenoscopy; Gastritis; Gastroscopy; Humans; Levamisole; Organometallic Compounds; Peptides; Stomach Ulcer; Thymus Extracts

The increase of the contents of serum IgA, IgG, IgM on the edge of long non-cicatrizing gastric ulcer was determined. At the same time the level of SIgA decreased in comparison with unaltered gastric mucosa. It is shown that the immunoglobulin content in the healed ulcer cicatrice depended on treatment method. The medicamentous therapy was accompanied by lowering of the contents of IgG, IgA, SIgA and by some increase of IgM level. The laser therapy is characterized by lowering of IgA, IgG, IgM level on a background of significant increase of SIgA content. The local humoral immunity after laser therapy was the same as in persons with unaltered gastric mucosa.

Topics: Adult; Aged; Antacids; Anti-Ulcer Agents; Antibody Formation; Combined Modality Therapy; Gastric Mucosa; Histamine H2 Antagonists; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Low-Level Light Therapy; Middle Aged; Organometallic Compounds; Stomach; Stomach Ulcer

To analyze cost-effectiveness of two different strategies to treat H. pylori infection in peptic ulcer in the primary care setting.. Consecutive patients with endoscopic diagnosis of peptic ulcer were randomized to one of two strategies: a) treatment during 7 days with omeprazole, tetracycline, metronidazole and bismuth subcitrate ("quadruple" therapy) and if failure second-line treatment with omeprazole, amoxycillin and clarithromycin during 7 days (OCA7), and b) initial treatment with OCA7 and if failure treatment with "quadruple therapy". End point was eradication 8 weeks after last treatment dose. Direct and indirect costs were estimated (euros, 1997) and a cost-effectiveness analysis using a decision-tree model was undertaken after real clinical data. 95% confidence intervals are given.. After screening 255 patients, 97 were finally included. 48 patients were given strategy a and 49 strategy b. Eradication was obtained (intention-to-treat) in 72.9% (CI 95%: 58.2-84.7) in group a versus 91.8% (CI 95%: 80.4-97.7) (p < 0.05) in group b. Mean cost per case treated was lower in group a (237 versus 268 euros) but cost per case eradicated was lower in group b (320 versus 296 euros). The cost was primarily determined by efficacy.. Treatment with OCA7 followed by rescue with "quadruple" therapy if failure is more efficient in our area that the inverse strategy. Efficiency is mostly determined by efficacy.

Topics: Adolescent; Adult; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Cost-Benefit Analysis; Data Interpretation, Statistical; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Penicillins; Primary Health Care; Prospective Studies; Stomach Ulcer; Tetracycline; Time Factors

To test the usefulness of a twice-a-day, simplified quadruple therapy to cure Helicobacter pylori infection.. Helicobacter pylori-positive ulcer patients were treated with omeprazole 20 mg twice a day (b.d.), amoxicillin 1 g b.d., tinidazole 500 mg b.d. and bismuth subcitrate 240 mg b.d. for 7 days in an experimental, noncomparative pilot study.. The gastroenterology unit of a county hospital.. Forty-four consecutive patients with peptic ulcer disease and H. pylori infection.. Cure was tested by either endoscopy or breath test after 2 months, and by urea breath test 6 months after therapy.. One patient was lost to follow-up. Of the remaining 43, 37 were cured at the first control, giving an intention-to-treat cure rate of 84.1% (95% CI 69-93%) and a per protocol cure rate of 86% (95% CI 71-94%). Thirty-three cured patients agreed to return for a six-month breath test. All but one were cured (long-term per protocol cure rate 82.1%; 95% CI 66-92%).. This particular quadruple therapy is well tolerated and easy to comply with. However, cure rates did not reach 90%.

Topics: Adult; Aged; Amoxicillin; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Organometallic Compounds; Pilot Projects; Stomach Ulcer; Tinidazole; Treatment Outcome

To compare the efficacy of cimetidine and tripotassium dicitrato bismuthate (TDB) in arthritic patients who had developed gastric (GU) or duodenal (DU) ulceration while taking non-steroidal anti-inflammatory drugs (NSAIDs).. Eighty-six rheumatoid arthritis (RA) patients affected by endoscopically proven DU (n = 44) or GU (n = 42), and on chronic NSAID therapy which was not suspended during anti-ulcer therapy, were randomized to cimetidine (400 mg t.d.s.) or TDB (120 mg q.d.s.). A repeat endoscopy was planned after 4 weeks (and 8 weeks, in case of failed healing). The patients who were unhealed after 8 weeks of therapy were allocated to the alternative anti-ulcer drug for a further 8 weeks without interrupting the anti-inflammatory therapy.. At week 4 of therapy. 14/24 (58%) DU and 9/20 (45%) GU patients treated with cimetidine were healed, compared with 12/20 (60%) and 10/22 (45%) TDB-treated patients (N.S.). At week 8 of therapy, the DU healing rates were 15/24 (63%) with cimetidine and 14/20 (70%) for TDB. The corresponding GU healing rates were 12/20 (60%) with cimetidine and 13/22 (60%) for TDB (N.S.). At week 16, complete healing with cimetidine was observed in 67% of DU and 57% of GU patients unhealed with TDB; the corresponding figures in the patients crossed to TDB were 83% for DU and 63% for GU patients (N.S. vs. cimetidine).. No statistically significant difference was found between the healing activities of cimetidine and TDB in rheumatoid arthritis patients with peptic ulcer who did not interrupt their NSAID treatment for arthritis. This trial showed that the continued consumption of NSAIDs appears to slow the ulcer healing process, especially in GU patients.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Cimetidine; Double-Blind Method; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Organometallic Compounds; Stomach Ulcer; Treatment Outcome

To compare cure rates of Helicobacter pylori (H. pylori) infection, ulcer healing, and side effects of three simplified regimens of triple therapy in patients with peptic ulcer disease.. Two hundred thirty-one patients were prospectively randomized to receive either regimen OAM (omeprazole 20 mg b.i.d., amoxicillin 750 mg b.i.d., and metronidazole 400 g b.i.d.), OCM (omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d., and metronidazole 400 mg b.i.d.), or BCM (bismuth subcitrate 240 mg b.i.d., clarithromycin 250 mg b.i.d., and metronidazole 400 mg b.i.d.), all for 10 days. Side effects were reported immediately afterward in a self-administered questionnaire. Upper endoscopy was carried out before treatment and 2 months after treatment. Three antral and three corpus biopsy specimens were analyzed microbiologically and with rapid urease test to determine the presence of H. pylori. Altogether 143 patients (62%) had an active ulcer at start of treatment. Metronidazole resistant (M-R) H. pylori strains were found in 30% of patients, while none had clarithromycin resistant (C-R) strains.. According to intention-to-treat analysis, H. pylori cure rates were 91, 95, and 95% with OAM, OCM, and BCM, respectively (p = 0.63). In patients with metronidazole-sensitive (M-S) strains versus M-R strains, the cure rates were 96 versus 77% with OAM (p = 0.025), 94 versus 94% with OCM, and 94 versus 96% with BCM. Ulcer healing rates were 95, 94, and 92%, respectively (p = 0.91). There were no significant differences in side effects between the regimens, and only five patients (2%) had to stop the treatment prematurely.. All treatment regimens were highly effective for cure of H. pylori infection and for ulcer healing. Metronidazole resistance reduced the efficacy of OAM, but was of no importance for the efficacy of OCM or BCM. Side effects were of minor importance.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Drug Resistance; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Norway; Omeprazole; Organometallic Compounds; Penicillins; Prospective Studies; Stomach Ulcer

One-week bismuth triple therapy has been established to be highly effective in curing H. pylori infection, but patient compliance has been the major factor of success in therapy. For patients hospitalized for ulcer bleeding, an effective regimen that can completed before discharge will ensure full compliance.. To compare 2-day versus 1-wk bismuth triple therapy plus omeprazole in curing H. pylori infection and bleeding peptic ulcers.. 100 patients with non-actively bleeding duodenal (DU) or gastric ulcers (GU) and confirmed H. pylori infection were randomized to receive either bismuth subcitrate 120 mg, tetracycline 500 mg, and metronidazole 400 mg four times daily for 1 wk (OBTM-7) or bismuth subcitrate 240 mg, tetracycline 500 mg, and metronidazole 400 mg four times daily for 2 days (OBTM-2). Both groups of patients also received omeprazole 20 mg twice daily for the first week. In the OBTM-2 group, the anti-Helicobacter therapy was finished during hospitalization. Endoscopy was repeated 5 wk after randomization to monitor ulcer healing and determine H. pylori status. Side effects related to the anti-Helicobacter therapy was graded as follows: A, mild discomfort, which did not affect daily activity; B, moderate discomfort affecting daily activity; and C, severe discomfort and patients discontinued therapy.. Forty-six patients in the OBTM-2 group and 50 in the OBTM-7 group returned for follow-up endoscopy. With an intention-to-treat analysis, ulcer healing was achieved in 44 of 46 patients (95.7%) in the OBTM-2 group versus 49 of 50 (98%) in the OBTM-7 group, p = 0.61. H. pylori eradication was successful in 35 of 46 patients (76.1%) in the OBTM-2 and in all 50 patients (100%) in the OBTM-7 group, p = 0.00024. There was no difference in the severity of side effects experienced by the patients in the OBTM-2 group than in the OBTM-7 group (19 vs 32%, p = 0.16). None of the patients had rebled during the period of follow-up.. Despite similar efficacy in ulcer healing, the 2-day quadruple therapy is less effective than the 1-wk regimen in curing H. pylori infection.

Topics: Activities of Daily Living; Adult; Aged; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Administration Schedule; Duodenal Ulcer; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Hospitalization; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Patient Compliance; Peptic Ulcer Hemorrhage; Stomach Ulcer; Tetracycline

Helicobacter pylori infection is common in patients with peptic ulcers caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs). But the pathogenic role of H pylori in this disease is controversial. We studied the efficacy of eradication of H pylori in the prevention of NSAID-induced peptic ulcers.. We recruited patients with musculoskeletal pain who required NSAID treatment. None of the patients had previous exposure to NSAID therapy. Patients who had H pylori infection but no pre-existing ulcers on endoscopy were randomly allocated naproxen alone (750 mg daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, each given orally four times daily) before administration of naproxen (750 mg daily). Endoscopy was repeated after 8 weeks of naproxen treatment or when naproxen treatment was stopped early because of bleeding or intractable dyspepsia. All endoscopic examinations were done by one endoscopist who was unaware of treatment assignment. The primary endpoint was the cumulative rate of gastric and duodenal ulcers.. 202 patients underwent endoscopic screening for enrolment in the trial, and 100 eligible patients were randomly assigned treatment. 92 patients completed the trial (47 in the naproxen group, 45 in the triple-therapy group). At 8 weeks, H pylori had been eradicated from no patients in the naproxen group and 40 (89%) in the triple-therapy group (p < 0.001). 12 (26%) naproxen-group patients developed ulcers: five had ulcer pain and one developed ulcer bleeding. Only three (7%) patients on triple therapy had ulcers, and two of these patients had failure of H pylori eradication (p = 0.01). Thus, 12 (26%) patients with persistent H pylori infection but only one (3%) with successful H pylori eradication developed ulcers with naproxen (p = 0.002).. Eradication of H pylori before NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Bismuth; Drug Administration Schedule; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Naproxen; Organometallic Compounds; Prospective Studies; Stomach Ulcer; Tetracycline

Our objective was to assess the effectiveness of therapy for Helicobacter pylori (HP) on the prevention of recurrent bleeding in patients with recent upper gastrointestinal hemorrhage from peptic ulcers.. We performed a prospective follow-up study without randomization on 125 consecutive patients (83 males and 42 females) who had presented with their first major episode of upper gastrointestinal hemorrhage from peptic ulcer (22 gastric and 103 duodenal ulcers). All 125 patients were HP-positive. During the acute phase of bleeding, all patients were treated with standard supportive measures. After the acute bleeding phase, patients were allocated to two treatment groups: 1) antimicrobial therapy-84 patients received one of the following three regimens: 1) amoxicillin 500 mg t.i.d. for 10 days + omeprazole 20 mg b.i.d. for 30 days; 2) clarythromycin 500 mg t.i.d. for 12 days + omeprazole 20 mg b.i.d. for 30 days; or 3) amoxicillin 500 mg t.i.d. for 10 days + metronidazole 500 mg t.i.d. for 10 days + colloidal bismuth subcitrate 240 mg b.i.d. for 30 days. For long-term antisecretion maintenance treatment, 41 patients were allocated to either omeprazole 20 mg once a day or ranitidine 150 mg once a day, for 1 yr.. During the follow-up period, peptic ulcers recurred in six patients in the antibiotic group (7.14%) and 13 patients in the maintenance group (31.7%) (p < 0.001). The fraction of patients without recurrent bleeding was greater in the antibiotic group than in the maintenance group. Two patients in the antibiotic group (2.3%) and five in the maintenance group (12.1%) had recurrent hemorrhages (p < 0.1).. Cure of HP infection reduces the recurrence of peptic ulcer and of rebleeding from ulcer disease more effectively than does long-term maintenance therapy.

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Drug Therapy, Combination; Duodenal Ulcer; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Peptic Ulcer Hemorrhage; Prospective Studies; Ranitidine; Recurrence; Stomach Ulcer; Time Factors

The aim of this study was to compare the healing effect of a gastroprotective agent and antisecretory drugs in gastric body ulcer where failure of the mucosal defense might be an important factor. Eighty-five patients with benign gastric ulcer were divided into four groups: treated with antacids (I), cimetidine (II), ranitidine (III), and colloidal bismuth subcitrate (De-Nol) (IV). Endoscopically confirmed complete healing was achieved in 57, 61, and 63% in groups I, II, and III, respectively, and in 88% in group IV (P < 0.05). Gastric secretion did not change significantly. Relapses during the next three years occurred several times more frequently in groups I, II, and III than in group IV. Helicobacter pylori was positive in about half the relapsing patients in groups I, II, and III but negative in those of group IV. It is concluded that De-Nol treatment of gastric body ulcer was more efficient than antisecretory drugs both initially and in reducing relapses.

Topics: Adult; Antacids; Anti-Ulcer Agents; Bismuth; Cimetidine; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Organometallic Compounds; Ranitidine; Recurrence; Stomach Ulcer; Time Factors

The effect of Helicobacter pylori eradication on ulcer healing and the relapse rate were investigated in a multicentre trial of 239 gastric ulcer patients. Patients with H pylori positive gastric ulcer were randomly assigned to one of three groups: (A) 10 days' treatment with metronidazole and eight weeks' treatment with colloidal bismuth subcitrate (CBS) (84 patients); (B) 10 days' treatment with metronidazole placebo and eight weeks with CBS (73 patients); or (C) ranitidine (82 patients). At 12 weeks in 210 patients, gastric ulcer was present in three (9%) of 35 H pylori negative patients, and in 45 (26%) of 175 H pylori positive patients (p < 0.05). Results after one year of follow up were available for 205 patients. Between 12 and 52 weeks, two (7%) ulcer relapses occurred in 29 H pylori negative patients and in 60 (47%) of 128 H pylori positive patients (p < 0.001). After two weeks of open triple therapy (CBS 120 mg four times daily, amoxicillin 500 mg four times daily, and metronidazole 400 mg three times daily), given to the patients with ulcer relapse, only one (an NSAID user) of 55 successfully treated patients had an ulcer relapse during the one year follow up. Healing of gastric ulcer is rapid and recurrence is infrequent after successful H pylori eradication. H pylori eradication changes the natural history of the gastric ulcer disease.

Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Prospective Studies; Ranitidine; Recurrence; Stomach Ulcer

There is a strong association between infection with Helicobacter pylori and gastric ulcers that are unrelated to the use of nonsteroidal antiinflammatory medications. We studied the efficacy of antibacterial therapy without medication to suppress gastric acid for the treatment of patients with H. pylori infection and gastric ulcers unrelated to the use of nonsteroidal agents.. Patients with gastric ulcers seen on endoscopy and with H. pylori infection confirmed by smear or culture were randomly assigned to receive either a one-week course of antibacterial agents (120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, each given orally four times a day) or a four-week course of omeprazole (20 mg orally per day). Follow-up endoscopies were performed after five and nine weeks. The patients and their physicians were aware of the treatment assignments, but the endoscopists were not.. A total of 100 patients were randomly assigned to treatment, and 85 completed the trial. At five weeks, H. pylori had been eradicated in 41 of the 45 patients in the antibacterial-treatment group (91.1 percent; 95 percent confidence interval, 82.9 to 99.3) and in 5 of the 40 in the omeprazole group (12.5 percent; 95 percent confidence interval, 2.3 to 22.7; P < 0.001). The gastric ulcers were healed in 38 of the patients treated with antibacterial drugs (84.4 percent; 95 percent confidence interval, 73.9 to 95.0) and in 29 of those treated with omeprazole (72.5 percent; 95 percent confidence interval, 58.6 to 86.4; P = 0.28). At nine weeks, ulcer healing was confirmed in 43 of the patients receiving antibacterial therapy and in 37 of those receiving omeprazole (P = 1.0). The mean (+/- SD) duration of pain during the first week of treatment was 1.9 +/- 2.6 days in the omeprazole group, as compared with 3.6 +/- 3.0 days in the antibacterial-treatment group (P = 0.004). One year after treatment, recurrent gastric ulcers were detected in 1 of 22 patients (4.5 percent) in the antibacterial-treatment group and in 12 of 23 (52.2 percent) in the omeprazole group (P = 0.001). H. pylori was detected in the 1 patient with a recurrent ulcer who had received antibacterial treatment and in 10 of the 12 patients with recurrent ulcers who had received omeprazole.. In patients with H. pylori infection and gastric ulcers unrelated to the use of nonsteroidal antiinflammatory drugs, one week of antibacterial therapy without acid suppression heals the ulcers as well as omeprazole and reduces the rate of their recurrence.

Topics: Adult; Aged; Anti-Bacterial Agents; Anti-Ulcer Agents; Confidence Intervals; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Recurrence; Stomach Ulcer; Tetracycline

Two 4-week triple-therapy treatment regimens, metronidazole+tetracycline+bismuth subcitrate and omeprazole+amoxycillin+bismuth subcitrate, were compared in a randomly allocated double-blind trial for their efficacy in eradicating Helicobacter pylori from the gastric mucosa of patients with gastritis and/or peptic ulcer disease.. The presence of gastritis and/or peptic ulcers was confirmed by endoscopy in all patients included in the study. To evaluate drug effects, we used the urease test on gastric mucosa, and haematoxylin-eosin and specific Giemsa stains on biopsy tissues obtained by endoscopic procedures; we also evaluated the improvement in clinical symptoms before and after the 4-week treatments.. Among 164 patients with gastritis and/or peptic ulcers, H. pylori infection was confirmed in 93.9% (154 patients) by the urease test and in 87.8% (144 patients) by haematoxylin-eosin stain. Following 4 weeks of treatment with both combination regimens, negative conversion rates by the urease test and haematoxylin-eosin staining and rates of recovery from clinical symptoms were similar in both regimens (metronidazole+tetracycline+bismuth subcitrate: 82.3, 72.9 and 73.9%; omeprazole+amoxycillin+bismuth subcitrate: 89.6, 83.4 and 76.1%, respectively). Also, the extent of inflammatory activity and the H. pylori score by the Giemsa method indicated high rates of recovery, with improvements to grade 0 (lowest grade) from higher grades with both combination regimens (60.4 and 66.7% of patients taking metronidazole+tetracycline+bismuth subcitrate and 64.6 and 83.3 of those taking omeprazole+amoxycillin+bismuth subcitrate). However, the prevalence of side effects during the 4 weeks of treatment was doubled in the former group compared to the latter (25.5 versus 12.5% of patients).. Significant improvements in biochemical and histopathological findings and in the clinical symptoms of gastritis and/or peptic ulcer disease in patients with a high rate of H. pylori infection were observed equally with both regimens. However, there were notably fewer side effects in patients treated with omeprazole+amoxycillin+bismuth subcitrate. We therefore recommended this regimen in preference to metronidazole+tetracycline+bismuth subcitrate for the treatment of H. pylori-related gastritis and peptic ulcer disease.

Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Double-Blind Method; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Peptic Ulcer; Stomach Ulcer; Tetracycline; Treatment Outcome

One hundred consecutive patients with Helicobacter pylori infection, as proven by culture, were treated with 120 mg colloidal bismuth subcitrate (CBS) four times daily, 250 mg tetracycline four times daily, and 250 mg metronidazole four times daily during 15 days. The patients were amply instructed in how to take the medicine and strongly urged to complete the prescribed course. In 66 of the 100 patients pretreatment metronidazole susceptibility was determined. Endoscopy was performed 3 months after cessation of treatment to check for H. pylori eradication by culture, urease testing, and histology. Side effects of the treatment were registered and classified into five groups on the basis of severity. Eradication was achieved in 93 of 100 patients (93%), in 61 of 62 patients with a metronidazole-sensitive strain (98.4%), and in 2 of 4 patients with a metronidazole-resistant strain (50%). Eighty-two per cent of the patients experienced no or just minor side effects; 15% had moderate side effects, and just 3% had severe side effects. Non-ulcer dyspepsia patients reported significantly more side effects than patients with peptic ulcer disease. With proper patient instruction, this treatment regimen is well tolerated and very effective for the eradication of metronidazole-sensitive H. pylori strains.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Administration Schedule; Drug Therapy, Combination; Duodenal Ulcer; Dyspepsia; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Peptic Ulcer; Stomach Ulcer; Tetracycline; Treatment Outcome

The relationship between Helicobacter pylori (HP) and gastric ulcer therapy is examined by analyzing both the data that suggest that eradication of HP renders the gastric mucosa less susceptible to development of gastric ulcer as well as the substantial body of evidence that does not support this contention. The results reported in clinical trials with colloidal bismuth citrate, antimicrobial agents (furazolidone), and combinations of anti-ulcer and antimicrobial agents (H2-antagonist+cefixime, H2-antagonist+metronidazole) are reviewed. Also analyzed is the relationship between HP eradication and ulcer recurrence. Only one study is available on this aspect, and the limited evidence it provides in favour of a prophylactic effect of eradication therapy is not entirely convincing. The authors conclude that there is no reasonable case for the dogmatic assumption that eradication of HP facilitates either acute healing or long-term prophylaxis of gastric ulcer, though certain subgroups of gastric ulcer patients may benefit from eradication therapy.

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Cefixime; Cefotaxime; Cimetidine; Drug Therapy, Combination; Furazolidone; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Stomach Ulcer

Both misoprostol (synthetic PGE1 analog) and De-Nol (factor releasing endogenous prostaglandins in the gastric mucosa) can be useful in the treatment of patients with gastric ulcer resistant to cimetidine according to their gastroprotective properties. 64 patients whose gastric ulcer had not healed after 6 weeks of therapy with cimetidine in daily dose of 1000 mg were treated in a comparative short-term trial to assess the relative efficacy of misoprostol (Cytotec; Searle) in daily dose of 800 micrograms (I group; n = 32) and colloidal bismuth subcitrate (De-Nol; Gist-Brocades), four times a day in dose of 5 ml diluted with 15 ml of water (II group; n = 32). Both groups of patients were comparable according to age, sex, duration of ulcer disease, smoking habits, gastric acid secretion, ulcer size and localization in the stomach. The ulcer healing was controlled endoscopically after 2 and 4 weeks of the treatment. Healing rates after 2 weeks of therapy appeared to be 47% for misoprostol and 34% for De-Nol. After 4 weeks of therapy the healing rates were 72% with misoprostol and 63% with De-Nol. No statistically significant differences in the therapeutic efficacy were observed between two groups of the patients. No correlation was found between the ulcer healing rates and size of ulcer, its localization or smoking habits. The moderate side effects (transient diarrhea) were observed in 22% of patients treated with misoprostol. These findings suggest that misoprostol is as effective as De-Nol in the treatment of gastric ulcers resistant to cimetidine.

Topics: Adult; Aged; Alprostadil; Anti-Ulcer Agents; Cimetidine; Clinical Trials as Topic; Drug Resistance; Female; Humans; Male; Middle Aged; Misoprostol; Organometallic Compounds; Stomach Ulcer

110 patients with benign gastric ulcer and concomitant joint diseases (rheumatoid arthritis, osteoarthrosis) were treated in a comparative short-term clinical trial to assess the relative efficacy of calcitonin (daily 100 MRC of salmon calcitonin intramuscularly), cimetidine (daily 1000 mg orally) and colloidal bismuth subcitrate (De-Nol-four times a day in doses of 5 ml diluted with 15 ml of water). Groups of patients were comparable according to age, sex, duration of ulcer disease, smoking habits, gastric acid secretion and mean ulcer size. The ulcer healing was controlled endoscopically after 2 and 4 weeks of the treatment. There was no significant difference in the ulcer healing rate between three groups neither after 2 weeks (calcitonin-36.7% of healed ulcers, cimetidine-37.5% and De-Nol-35.0% nor after 4 weeks respectively (76.7%, 72.5% and 77.5%). In the calcitonin group a gradual joint pain relief was observed in 84% of patients who complained arthralgia. The moderate side effects (headache, nausea, flush) were observed only in the patients treated with calcitonin (8 subjects). We suggest that calcitonin may be considered as a valid anti-ulcer drug in the peptic ulcer patients with concomitant rheumatological diseases especially with osteoporosis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Arthritis, Rheumatoid; Calcitonin; Cimetidine; Clinical Trials as Topic; Female; Gastroscopy; Humans; Injections, Intramuscular; Male; Middle Aged; Organometallic Compounds; Osteoporosis; Random Allocation; Stomach Ulcer; Wound Healing

To determine the clinical importance of Campylobacter pyloridis infection, its association with gastric inflammation, and the response to drug therapy, patients with a duodenal or gastric ulcer (n = 63), patients with nonulcer dyspepsia (n = 240), and asymptomatic volunteers (n = 34) were studied. In a prospective longitudinal study, the type, intensity, and distribution of inflammation in antral biopsy specimens were correlated with the presence of C. pyloridis. Campylobacter pyloridis was cultured from antral biopsy specimens in 98% of the ulcer patients, 70% of the nonulcer dyspepsia patients, and 20% of the asymptomatic volunteers. The dependency of chronic active gastritis on the presence of C. pyloridis was shown by an association of gastritis with positive culture and healing of gastritis with negative culture after various therapeutic regimens. Spontaneous disappearance of C. pyloridis never occurred. Colloidal bismuth subcitrate, amoxicillin, and the combination of colloidal bismuth subcitrate and amoxicillin were effective therapies in eradicating C. pyloridis. Recolonization with the same bacterial subtype and recurrence of gastritis frequently occurred within 1 mo after initial eradication. In this study we demonstrate ultimate normalization of gastric mucosa after successful eradication of C. pyloridis. Especially complete normalization of gastric mucosa after amoxicillin monotherapy provides additional strong evidence for a true cause-effect relationship between C. pyloridis colonization and gastritis.

Topics: Adult; Amoxicillin; Anti-Ulcer Agents; Campylobacter; Campylobacter Infections; Duodenal Ulcer; Dyspepsia; Female; Gastritis; Humans; Longitudinal Studies; Male; Middle Aged; Organometallic Compounds; Prospective Studies; Stomach Ulcer

Topics: Adult; Aged; Anti-Ulcer Agents; Female; Humans; Male; Middle Aged; Organometallic Compounds; Ranitidine; Recurrence; Stomach Ulcer

Colloidal bismuth subcitrate (CBS) in the form of a chewable tablet has been compared with ranitidine in the short-term treatment of benign gastric ulcers. Eighty patients were admitted to this randomised single blind study. Endoscopic control was carried out after 4 weeks, and after 8 weeks when healing was incomplete or had not occurred at the 4-week examination. After 1 month of therapy the healing rates were 70% with CBS and 62.5% with ranitidine (P = not significant). At two months the corresponding cure rates were 87.5% and 79%, respectively (P = not significant). Antacid consumption was higher in the group treated with ranitidine, but the difference was not statistically significant. Patient cooperation was good and similar in the two groups. These findings confirm that CBS, in tablet form, is at least as effective as ranitidine in the acute treatment of benign gastric ulcers.

Topics: Adult; Bismuth; Female; Gastroscopy; Humans; Male; Middle Aged; Organometallic Compounds; Random Allocation; Ranitidine; Stomach Ulcer

The pharmacological mechanism of ulcer coating and cytoprotection associated with colloidal bismuth have important therapeutic implications for the management of peptic ulcer disease. While the short-term healing rate is similar to that obtained by the H2 antagonists, the relapse rate appears lower.

Topics: Anti-Ulcer Agents; Bismuth; Clinical Trials as Topic; Duodenal Ulcer; Humans; Organometallic Compounds; Peptic Ulcer; Stomach Ulcer

The pathophysiology of gastric ulcer and gastritis has been related to an increase in damaging factors such as duodeno-gastric reflux and anti-inflammatory drugs. A decreased capacity for mucosal prostaglandin generation is highly likely. Acid secretion is usually normal or even reduced. Colloidal bismuth subcitrate (CBS) has been shown to increase gastric mucosal defence. In controlled trials a clear superiority over placebo has been demonstrated. Amalgamation of the data shows an average healing rate of about 70% in gastric ulcer, which is statistically significantly higher than that for cimetidine in comparative trials. The therapeutic gain (the difference between the healing rate of drug and placebo in a direct comparison) of CBS is high compared with other anti-ulcer agents. In campylobacter gastritis we have shown that the microorganism is very sensitive to CBS, and its eradication results in histological improvement.

Topics: Bismuth; Campylobacter; Clinical Trials as Topic; Gastritis; Humans; Organometallic Compounds; Stomach Ulcer

Topics: Aluminum; Bismuth; Carbenoxolone; Clinical Trials as Topic; Duodenal Ulcer; Humans; Organometallic Compounds; Placebos; Prostaglandins; Stomach Ulcer; Sucralfate

The gastric cytoprotective effects of vitamin A, De-Nol and sucralfate were compared with the effectiveness of pirenzepine in healing ulcer in patients with chronic gastric ulcer. A total of 100 patients was randomized into different groups: the patients were treated with antacids, vitamin A (3 X 50.000 IU), De-Nol liquid (4 X 5 ml), sucralfate (4 X 1 g) or pirenzepine (3 X 50 mg). The treatment was continued for 4 weeks. At the beginning, 2 and 4 weeks after starting treatment the patients were subjected to endoscopy and the size of the ulcer was measured planimetrically. The ulcer-healing effect of De-Nol liquid was significantly better than that of the antacids (p less than 0.01). Ulcer size was reduced significantly in all groups (p less than 0.01), however, at the end of the study the gastric ulcers were smallest in the De-Nol treated group (p less than 0.001). The dynamics of ulcer healing in the second week was most favourable in the patients receiving vitamin A (p less than 0.01). The present data point to the cytoprotective effects of De-Nol liquid, vitamin A and sucralfate and to their ability of healing chronic gastric ulcers.

Topics: Adolescent; Adult; Aged; Aluminum; Antacids; Anti-Ulcer Agents; Benzodiazepinones; Bismuth; Clinical Trials as Topic; Female; Gastric Mucosa; Humans; Male; Middle Aged; Organometallic Compounds; Pirenzepine; Stomach Ulcer; Sucralfate; Vitamin A; Wound Healing

One hundred ambulant outpatients with active, endoscopically proven peptic ulceration entered a double-blind trial of either tripotassium-dicitratobismuthate or placebo. Thirty-four patients had gastric ulceration, 56 had duodenal ulceration, three had both gastric and duodenal ulcers, and two had stomal ulceration. Five patients with gastric ulceration were withdrawn from the trial. Three patients with both gastric and duodenal ulceration and two patients with stomal ulceration were excluded from statistical analysis. After 28 days of tripotassium-dicitratobismuthate 94% of gastric ulcer patients had significant endoscopic healing (P less than 0.01). Although 75% of duodenal ulcers healed after 28 days of tripotassium-dicitratobismuthate, this was not statistically significant because of a 60% rate of healing with placebo. Tripotassium-dicitratobismuthate produced a significantly quicker symptomatic response in duodenal ulcer patients (P less than 0.01). No serious side effects were recorded, and patient acceptability was high. It is concluded that tripotassium-dicitratobismuthate is an effective agent for promoting gastric ulcer healing and for symptomatic relief in duodenal ulceration.

Topics: Adult; Aged; Bismuth; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Organometallic Compounds; Palliative Care; Peptic Ulcer; Prospective Studies; Random Allocation; Stomach Ulcer

The efficacy of local-acting De-Nol liquid (tripotassium dicitrato bismuthate) was investigated in patients with endoscopically verified gastric ulcer. In a prospective-type clinical trial, 16 outpatients received De-Nol and 24 outpatients received an antacid mixture (sodium bicarbonate, calcium carbonate, magnesium trisilicate in equal parts). The period of study was 4 weeks, the endoscopy being performed on the 14th and 28th day after commencement of treatment. We Registration was made of the degree of ulcer healing (ulcer is healed, or not healed but reduced by 50%, or slightly healed, or unchanged), the degree of pain (0 = none, 1 = slight, 2 = moderate, 3 = severe), body weight, different biochemical and haematological examinations, side-effects and some other parameters. Of those patients given De-Nol treatment, the ulcer healed in 69% within four weeks, as compared with 33% of those given antacid therapy. There was also a significant (p less than 0.001, p less than 0.02) difference between the two groups in the size of the ulceration which remained and in the decrease of pain. Side-effects were not recorded. These data suggest the beneficial effect of De-Nol liquid in the treatment of patients with gastric ulceration.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Bismuth; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Organometallic Compounds; Stomach Ulcer

Topics: Adult; Aged; Antacids; Anti-Ulcer Agents; Bismuth; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Female; Guanidines; Humans; Male; Middle Aged; Organometallic Compounds; Pain; Placebos; Recurrence; Stomach Ulcer

Topics: Antacids; Anti-Ulcer Agents; Bismuth; Clinical Trials as Topic; Disease Models, Animal; Duodenal Ulcer; Gastrointestinal Hemorrhage; Humans; Organometallic Compounds; Peptic Ulcer; Recurrence; Stomach Ulcer

Fifty patients with endoscopically proven gastric ulcers completed a one month double-blind randomised trial of tripotassium dicitrato bismuthate (TBD) (DeNol) compared with an identical placebo. Ulcer healing occurred in 18 (72%) of the 25 patients given TDB and in nine (36%) of the patients given placebo. The TDB group experienced significantly less pain than the placebo group. During a follow-up of 29 patients with healed ulcers for up to 44 months, relapse occurred in 13 (45%). It was highest in the first three months (27%) and had risen to 41% at two years.

Topics: Anti-Ulcer Agents; Bismuth; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Organometallic Compounds; Random Allocation; Recurrence; Stomach Ulcer

Sixty patients with benign chronic gastric ulcer were treated in a controlled clinical trial to assess the relative efficacy of cimetidine and tri-potassium di-citrato bismuthate (De-Nol). Patients were assigned at random either to cimetidine or to De-Nol treatment after initial endoscopic diagnosis. Healing was assessed endoscopically after six weeks by an endoscopist who had no knowledge of the patients' treatment. Consumption of analgesic preparations (both for medical and for non-medical reasons), of other anti-inflammatory agents, and of alcohol and cigarettes was recorded. Of the 57 patients who were reassessed at six weeks, 30 had been assigned to De-Nol and 20 of these patients (66%) had completely healed; 27 patients had been assigned to cimetidine and 17 of these (63%) had also completely healed. Those patients who regularly ingested more than four analgesic preparations a day healed less frequently, but this effect was not statistically significant. There was no significant difference between cimetidine and De-Nol in the initial healing of chronic gastric ulceration. The choice of therapy for chronic gastric ulceration will depend on cost, patient acceptance, and data from studies of more complex therapeutic regimens.

Topics: Analgesics; Anti-Inflammatory Agents; Bismuth; Chronic Disease; Cimetidine; Citrates; Female; Gastroscopy; Guanidines; Humans; Male; Organometallic Compounds; Prospective Studies; Random Allocation; Stomach Ulcer

THE AIM OF INVESTIGATION: To study the effect of schemes second line quadruple therapy on the state of gastric mucosal barrier and NO formation in experimental ulcer.. The study included 60 white male rats weighing 150-190 gr, mixed population. The effect of the standard second-line regimens on the content of the fractions of insoluble glycoproteins, on indicators of NO formation and anaerobic glycolysis in gastric mucosal tissue in experimental ulcer.. Quadruple therapy consisting of omeprazole, de-nol, amoxicillin and tetracycline stimulates mechanisms of protective barrier, which has a positive effect on the mechanisms of NO formation. Scheme with omeprazole, de-nol, tetracycline and metronidazole inhibits the synthesis of mucosal barrier, the key mechanisms of NO formation.. In the plan of correction of mechanisms of cytoprotection in the gastric mucosal tissue quadruple therapy with omeprazole, de ethanol, amoxicillin, and tetracycline is considered to be effective.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Disease Models, Animal; Drug Therapy, Combination; Gastric Mucosa; Male; Nitric Oxide; Omeprazole; Organometallic Compounds; Rats; Stomach Ulcer; Tetracycline

Diclofenac-bismuth complexation was attempted by mixing diclofenac sodium (Na) and bismuth-subcitrate aqueous solutions at diclofenac:bismuth molar ratio of 3:1. A solid precipitate was obtained and isolated. The precipitate was characterized for stoichiometric ratio of diclofenac-bismuth complexation using capillary electrophoresis, which showed 1:1 complexation. In addition, nuclear magnetic resonance and Fourier transform infrared analysis were performed for the isolated solid complex and indicated that bismuth was in coordinate bond formation with the carboxylate group of diclofenac. In comparison with diclofenac Na powder, the complex was evaluated as an aqueous suspension for in vitro drug dissolution. The complex exhibited a faster dissolution rate than and similar dissolution extent as diclofenac Na. In comparison with an aqueous solution of diclofenac Na and an aqueous suspension of physical mixture of diclofenac acid (suspended) and bismuth-subcitrate (dissolved), the aqueous complex suspension was evaluated for ulcerogenic effect in rats upon oral administration. The complex led to more gastric ulceration than diclofenac Na, which was not in accordance with the antiulcer properties of bismuth. This antiulcer effect was shown as the physical mixture administration was accompanied with lower gastric ulceration than diclofenac Na administration. These gastric ulceration results were explained in terms of the difference in particle size between solid diclofenac acid formed as a result of the complex breakdown in an acidic medium (0.1 M HCl to simulate the gastric fluid) and that formed as a result of diclofenac Na neutralization. Diclofenac acid particles formed from the complex breakdown were of average size, three times smaller of those formed as a result of diclofenac Na protonation. This difference in particle size was correlated with the higher gastric ulceration associated with the complex than with diclofenac Na in terms of higher coverage of the gastric mucosa with diclofenac, and consequently, higher local ulceration.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Chemical Precipitation; Diclofenac; Electrophoresis, Capillary; Magnetic Resonance Spectroscopy; Male; Organometallic Compounds; Particle Size; Rats; Rats, Wistar; Solubility; Spectroscopy, Fourier Transform Infrared; Stomach Ulcer; Suspensions

Bacopa monniera is an Indian tratidional medicine widely used to improve intellectual functions. Earlier, we had reported the prophylactic and curative effects of standardized extract of Bacopa monniera (BME) in various gastric ulcer models. The effect was due to augmentation of the defensive mucosal factors like increase in mucin secretion, life span of mucosal cells and gastric antioxidant effect rather than on the offensive acid-pepsin secretion. The present study includes evaluation of standardized BME (bacoside A content--35.5 +/- 0.9) on other contributing factors towards ulcerogenesis. BME in the dose of 1000 microg/ml showed anti-Helicobacter pylori activity in vitrol and in the dose of 10 microg/ml increased in vitro of prostanoids (PGE and PGI2) in human colonic mucosal incubates. It may be concluded that these factors may contribute to antiulcerogenic activity of BME.

Topics: Anti-Infective Agents; Bacopa; Epoprostenol; Helicobacter Infections; Helicobacter pylori; Humans; India; Intestinal Mucosa; Medicine, Traditional; Microbial Sensitivity Tests; Organometallic Compounds; Phytotherapy; Plant Extracts; Prostaglandins E; Stomach Ulcer

Comparative assessment of treatment results in 618 patients with gastroduodenal ulcer (GDU) was carried out. 3 groups of patients were compared. Different combinations of drugs were used in 384 patients, 234 patients have undergone open resections of the stomach or organsaving operations, 83 patients--analogous laparoscopic operations. Immediate and long-term results of the treatment were studied. After drug therapy, including antihelicobacter drugs, healing of ulcers was achieved in 96.9-97.9% cases. 1 year after drug therapy the recurrence of CDU is revealed in 16.2-20.3% patients, rate of the recurrence increases with years. After surgical treatment of CDU (more often in complicated course of the disease) rate of recurrences is 2-3 times lower (6.5-7.4% cases). Laparoscopic resections of the stomach and organsaving operations are atraumatic, accompanied by physiologic course of postoperative period and reduction of postoperative complication rate.

Topics: Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Drug Therapy, Combination; Duodenal Ulcer; Follow-Up Studies; Gastrectomy; Helicobacter Infections; Helicobacter pylori; Humans; Laparoscopy; Metronidazole; Omeprazole; Organometallic Compounds; Peptic Ulcer; Postoperative Complications; Ranitidine; Recurrence; Stomach Ulcer; Tetracycline; Time Factors

Topics: Amoxicillin; Anti-Bacterial Agents; Case-Control Studies; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Rosacea; Severity of Illness Index; Stomach Ulcer

Topics: Abdominal Pain; Adolescent; Adult; Age Factors; Amoxicillin; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Antibodies, Bacterial; Child; Chronic Disease; Clarithromycin; Clinical Trials as Topic; Drug Therapy, Combination; Duodenal Ulcer; Endoscopy; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Organometallic Compounds; Penicillins; Recurrence; Risk Factors; Stomach Ulcer

Under observation there were 82 patients operated on for ulcer disease of the stomach and duodenum. Dissemination of the mucosa with Helicobacter pylori (HP) was studied by means of using the urease test. Before the operation the positive result of the study was obtained in 73 patients (89%). In 1-6 months after the operation the HP infection was found in 29 patients (39.7%). The HP persistence retained in 39.7% of the patients subjected to resection of the stomach in spite of the preoperative treatment including De-nol and Metronidazole. Post-resectional reflux-gastritis and anastomositis were more pronounced in HP carriers. The antireflux variants of anastomoses (transversal, terminolateral gastroduodenal anastomosis and gastrojejunal anastomosis by Roux) were followed by much less HP persistence and less frequent cases of anastomositis and gastritis of the gastric stump.

Topics: Adult; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Duodenal Ulcer; Evaluation Studies as Topic; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Stomach Ulcer

In the present study, the effectiveness of a triple therapy for eradication of Helicobacter pylori was evaluated. Therapy consisted of 120 mg tripotassium dicitrato bismuthate q.d.s. for four weeks, 500 mg amoxycillin q.d.s. and 500 mg metronidazole t.d.s. for two weeks. In 77 Helicobacter pylori-positive patients with duodenal ulcers (n = 32), gastritis (n = 18) and after gastric resection (n = 7), rapid urease-based test, culture, histology and serology were used to confirm the eradication, or relapse. The overall eradication rate was 75.3%, ulcers were healed in 82.1% and an improvement of the endoscopic gastritis was observed in 75.3% of the patients. The eradication rates were not statistically different among the subgroups. 1-3 months after the treatment IgG titres had fallen by 25% and over in 67.5% of the patients irrespective of the success of bacterial eradication. Side effects, particularly diarrhoea and nausea, were common (53.2%) but mild. Only 6.5% of the patients' had to discontinue the treatment because side effects became intolerable.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Stomach Ulcer; Treatment Outcome

Topics: Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Duodenal Ulcer; Duodenitis; Evaluation Studies as Topic; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Peptic Ulcer; Stomach Ulcer; Time Factors

In a prospective study designed to assess the effect of Helicobacter pylori eradication on peptic ulcer healing, 85 consecutive patients with H. pylori-positive peptic ulcer disease were treated with a triple therapy regimen consisting of colloidal bismuth subcitrate 120 mg four times daily for 28 days, with metronidazole 400 mg three times daily and tetracycline 500 mg three times daily for the first seven days of treatment. H. pylori status was assessed by CLO test and histology at least four weeks after completing therapy. Of 75 patients (88%) H. pylori-negative after therapy, 69 (92%) had healed ulcers compared with only five of 10 patients (50%) who remained H. pylori-positive (p = 0.003). Cigarette smoking had no significant effect on ulcer healing. Our results suggest that H. pylori eradication may accelerate ulcer healing and provide further evidence that an effective helicobactericidal regimen is the treatment of choice in H. pylori-positive peptic ulcer.

Topics: Adult; Aged; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Peptic Ulcer; Prospective Studies; Smoking; Stomach Ulcer; Tetracycline

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Stomach Ulcer

Topics: Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Stomach Ulcer

Topics: Anti-Bacterial Agents; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Organometallic Compounds; Stomach Ulcer

In this study we measured phospholipase A (PLA) and C (PLC) activity of media filtrates and French Press lysates of the gastritis-inducing bacteria Helicobacter pylori. We report here that both H. pylori lysates and filtrates contain PLA1, PLA2, and C enzymes, which readily hydrolyze a radiolabeled dipalmitoylphosphatidylcholine (DPPC) and phosphorylcholine substrates, respectively. The specific activity of both PLA and C enzymes were greatest in the 6.5-7.0 and 8.4-8.8 pH ranges, respectively. Colloidal bismuth subcitrate (CBS) induced a dose-dependent inhibition of PLA2 and C activity of both H. pylori lysates and filtrates. This inhibitory effect of CBS on PLA2 was antagonized in a dose-dependent fashion by the addition of CaCl2 to the incubation mixture, suggesting that calcium and bismuth may be competing for the same site on the enzyme. In contrast, the ability of bismuth salts to inhibit PLC activity of H. pylori lysates was not antagonized by CaCl2. Employing a biophysical assay system for surface wettability, it was determined that H. pylori lysates had the capacity to remove a synthetic phospholipid monolayer off a glass in a dose-dependent fashion. This ability of the bacterial lysates to catalyze the transformation of a hydrophobic surface to a wettable state was significantly attenuated in the presence of bismuth salts. Our experimental results are, therefore, consistent with the possibility that H. pylori colonization compromises the stomach's barrier to acid by eroding a phospholipid lining, possibly a monolayer, on the surface of the gastric mucus gel and that this process is blocked in response to bismuth therapy.

Topics: Anti-Bacterial Agents; Bismuth; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Organometallic Compounds; Phospholipases A; Phospholipases A1; Phospholipases A2; Stomach Ulcer; Type C Phospholipases

The efficacy of vinpocetine (CAS 42971-09-5) to prevent gastric mucosal damage induced by several noxious agents and its antisecretory effect were studied in rats. Vinpocetine administered orally or intraperitoneally inhibited the development of gastric lesions induced by 96% ethanol in a dose-dependent way. The highest protective activity was observed when vinpocetine was given intraperitoneally 30 min before ethanol, and its effect was still significant when administered 120 min before ethanol exposure. Oral administration of vincamine also displayed gastroprotective action in this model. Pretreatment with indometacin counteracted the protective action of vinpocetine against ethanol-induced damage, suggesting the involvement of a prostaglandin-mediated mechanism. The protective effect of vinpocetine was compared with that of prostaglandin E2, sucralfate, and tripotassium dicitrate bismuthate. The antiulcer activity of vinpocetine was demonstrated also in gastric injury induced by phenylbulazone and in chronic gastric ulcer induced by acetic acid. Histamine-stimulated gastric acid secretion in pylorus-ligated rats was partially inhibited by vinpocetine administered intraduodenally. The activity of vinpocetine established in these experiments is indicative of its potential clinical value as a gastroprotective agent.

Topics: Acetates; Acetic Acid; Administration, Oral; Animals; Anti-Ulcer Agents; Dinoprostone; Ethanol; Female; Gastric Acid; Histamine; Injections, Intraperitoneal; Intubation, Gastrointestinal; Organometallic Compounds; Phenylbutazone; Pylorus; Rats; Rats, Wistar; Stomach Ulcer; Sucralfate; Vinca Alkaloids

Ranitidine bismuth citrate is a novel compound formed from ranitidine and a bismuth citrate complex. In conscious dogs, ranitidine bismuth citrate had similar activity to ranitidine hydrochloride as an inhibitor of histamine-induced gastric acid secretion when oral doses containing equivalent amounts of ranitidine base (0.1 or 0.3 mg/kg) were compared. In the rat, ranitidine bismuth citrate (3-30 mg/kg p.o.) prevented gastric mucosal damage induced by ethanol (fundic damage) and indomethacin (antral damage). Ranitidine hydrochloride and tripotassium dicitrato bismuthate were also effective against indomethacin-induced damage, but were both significantly less potent than ranitidine bismuth citrate in this model. Ranitidine hydrochloride was inactive against ethanol-induced damage. In vitro, ranitidine bismuth citrate (1 mmol/L) inhibited human pepsin isoenzymes 1, 2, 3 and 5. Pepsin 1 was inhibited to a similar extent by ranitidine bismuth citrate, bismuth citrate and tripotassium dicitrato bismuthate at concentrations equivalent to 1 mmol/L bismuth, but ranitidine (1 mmol/L) was inactive. Ranitidine bismuth citrate was more potent than tripotassium dicitrato bismuthate as an inhibitor of pepsins 2, 3 and 5. Ranitidine bismuth citrate inhibited both Helicobacter pylori (effective concentration 4-32 micrograms bismuth/ml) and H. mustelae (1-4 micrograms bismuth/ml); similar results were obtained with tripotassium dicitrato bismuthate. Bismuth citrate was slightly less effective, and ranitidine hydrochloride was inactive (> 125 micrograms/ml). In ferrets naturally colonized with H. mustelae, oral treatment with ranitidine bismuth citrate, 12 or 24 mg/kg twice daily for 4 weeks, caused a dose related clearance of H. mustelae. Qualitatively similar results were obtained in a small study with tripotassium dicitrato bismuthate and bismuth citrate.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Citrates; Dogs; Ethanol; Female; Ferrets; Gastric Acid; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Indomethacin; Isoenzymes; Male; Microbial Sensitivity Tests; Organometallic Compounds; Pepsin A; Ranitidine; Rats; Stomach Ulcer

The presence of Helicobacter was tested on a group with antral or duodenal ulcer with or without gastritis, versus a group without gastric or duodenal pathology. Furthermore an open trial was performed between omeprazole and colloidal bismuth subcitrate (CBS) on patients similarly affected by peptic disease. Although CBS did eliminate Helicobacter in more than a half of patients, what was not obtained by omeprazole, this result did not mean a better control of peptic disease: in fact the omeprazole was remarkably more active in our series on clinical and endoscopic ground, whether the Helicobacter was present or not, and further studies are required to assess the real significance of Helicobacter pylori in the above conditions.

Topics: Adult; Aged; Anti-Ulcer Agents; Colloids; Drug Evaluation; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Organometallic Compounds; Stomach Ulcer

We have performed a retrospective study of 103 patients with either peptic ulcer or non-ulcer dyspepsia, infected with metronidazole-sensitive strains of Helicobacter pylori (H. pylori), who were treated with a combination of tripotassium dicitrato bismuthate and metronidazole for a period of at least two weeks. Dual therapy with tripotassium dicitrato bismuthate plus metronidazole showed similarly high eradication rates (greater than or equal to 80%) of H. pylori from patients irrespective of age, gender or clinical diagnosis. Most importantly, dual therapy achieved a similar eradication rate of H. pylori infection in 41 patients who had previously been treated with tripotassium dicitrato bismuthate alone or in combination with an antibiotic other than metronidazole. It therefore appears that H. pylori does not become resistant to treatment with tripotassium dicitrato bismuthate.

Topics: Adult; Aged; Drug Administration Schedule; Drug Resistance, Microbial; Duodenal Ulcer; Dyspepsia; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Retrospective Studies; Stomach Ulcer

The belief that blood flow plays a central role in cytoprotection and there being no data available, at present, regarding the possible action of Colloidal bismuth subcitrate (CBS-DENOL) on the gastric mucosal blood flow (GMBF), led us to investigate its influence on mucosal hemodynamics in the rat stomach. Measurements of GMBF were performed in 32 male Wistar rats, treated by either CBS or placebo in drinking water for a 3-wk period, by the use of a laser-Doppler flowmeter, at 14 defined points of the stomach. CBS treated animals revealed a highly statistically significant increase (P less than 0.0005, upaired t-test) of GMBF in comparison with the placebo treated. These findings lead us to suggest that CBS exerts its antiulcer action via the mechanism of increased gastric mucosal blood flow. Additionally the increased blood flow may be associated with the previous findings of increased synthesis of prostaglandins, gastric mucus and bicarbonate secretion by CBS.

Topics: Animals; Anti-Ulcer Agents; Gastric Mucosa; Hemodynamics; Male; Microcirculation; Organometallic Compounds; Rats; Rats, Inbred Strains; Regional Blood Flow; Stimulation, Chemical; Stomach Ulcer

The purpose of this study was to determine the changes in rat gastric functional morphology that take place with age and to study the action of colloidal bismuth subcitrate on the age related degeneration of the stomach. At 95 weeks of age erosions were apparent over 80% of the gastric mucosa and this was associated with a significant decline in the numbers and mucus content of the mucosal epithelial cells. The rate of stem cell proliferation in the neck region was also significantly lower than that found in 9 week old animals. The administration of 50 mg/kg colloidal bismuth subcitrate for 14 days to 9 week old animals resulted in slight hypertrophy of the mucosal epithelial cells. When 95 week animals were placed on the same regimen there was a decline in the number of deep erosions in the mucosa and an increase in the number and mucin content of the mucosal epithelial cells. A significant increase in the proliferation of the stem cell population was also observed after colloidal bismuth subcitrate administration. It is suggested that colloidal bismuth subcitrate may ameliorate the increased susceptibility to harmful agents that occurs with age.

Topics: Age Factors; Aging; Animals; Bismuth; Cell Count; Cell Division; Disease Models, Animal; Epithelium; Gastric Mucosa; Male; Organometallic Compounds; Rats; Rats, Inbred Strains; Stem Cells; Stomach; Stomach Ulcer

Altogether 89 patients with long non-healing gastric ulcers were examined for Campylobacter pylori (CP) and mucous microflora. It is shown that in patients with long non-healing gastric ulcers, CP was only demonstrable in 19.8% of cases whereas pathological microflora (Candida and microbial associations) in 72.3% of cases. In patients with CP, the administration of de-nol, metronidazole and ampicillin were not sufficiently effective.

Topics: Adult; Ampicillin; Anti-Ulcer Agents; Campylobacter; Chronic Disease; Female; Gastric Mucosa; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Stomach Ulcer; Wound Healing

This study was designed to investigate the protective effect of colloidal bismuth subcitrate (CBS) on aspirin-induced gastric mucosal lesion 20 patients with arthralgia were allocated into this study. All of them were free of gastrointestinal symptom and their gastric mucosa were nearly normal under gastroendoscopic observation. The first group of 10 patients received orally aspirin 1.5 qid for 4 days. The second group also of 10 patients was treated with CBS 120 mg qid and after 2 days they received aspirin and CBS simultaneously in the dosage mentioned above for another 4 days. Before and after treatment, the patients of both groups were examined endoscopically. After treatment, the mucosal inflammation was much less in the second group than that in the first group. The prostaglandin E2 concentration of antral mucosa in the first group was reduced significantly after administration of aspirin alone, while that in the second group was slightly increased after a combined treatment of aspirin and CBS. The results demonstrate that CBS is an effective agent in prevention of gastric lesion induced by aspirin and prostaglandin E may be involved in this mucosal protective effect.

Topics: Adolescent; Adult; Anti-Ulcer Agents; Aspirin; Dinoprostone; Female; Gastric Mucosa; Humans; Male; Organometallic Compounds; Stomach Ulcer

Topics: Administration, Oral; Bismuth; Campylobacter Infections; Dose-Response Relationship, Drug; Gastritis; Humans; Organometallic Compounds; Salicylates; Stomach Ulcer

Topics: Anti-Ulcer Agents; Bismuth; Campylobacter Infections; Humans; Organometallic Compounds; Stomach Ulcer

Topics: Anti-Ulcer Agents; Campylobacter Infections; Drug Therapy, Combination; Follow-Up Studies; Gastritis; Humans; Metronidazole; Organometallic Compounds; Stomach Ulcer

This study compares the gastroprotective effects of colloidal bismuth subcitrate (De-Nol) with those of sucralfate and a methylated analogue of prostaglandin E2 (PGE2) against acute gastric lesions induced by acidified aspirin and absolute ethanol in rats. Both De-Nol and sucralfate given orally prevented dose dependently the formation of gastric lesions by these ulcerogens, De-Nol being, respectively, twice and seven times more potent, on a weight basis, than sucralfate. As the gastroprotective activities of both De-Nol and sucralfate on ethanol lesions can be reversed by pretreatment with indomethacin and as De-Nol and sucralfate increase the mucosal generation and luminal release of PGE2, we postulate that mucosal prostaglandins may be involved in the mechanism of action of these drugs on the gastric mucosa.

Topics: Animals; Aspirin; Dinoprostone; Ethanol; Gastric Juice; Gastric Mucosa; Organometallic Compounds; Prostaglandins E; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stomach Ulcer; Sucralfate

We evaluated the gastric mucosal protective properties of the anti-ulcer drug, colloidal bismuth subcitrate (CBS; DE-NOL), and its ability to stimulate mucosal synthesis of PGE2 in the rat. Gastric lesions were induced by ethanol and quantified by a visual scoring procedure. CBS was about 3-4 times more protective than sucralfate at reducing lesions. PGE2 displayed potent activity in this model, though cimetidine displayed only weak activity. Increasing the concentration of a standard dose of CBS in the rat stomach enhanced the protective activity against ethanol lesions. Pretreatment of rats with CBS led to complete, partial and no protection at 0.25, 8 and 16 h respectively. PGE2 generation in gastric mucosa biopsies was dose-dependently increased by oral CBS and peak synthesis occurred at 0.25 h. Although partial protection against ethanol lesions was found 8 h after CBS, basal levels of PGE2 generation had already returned at 4 h. Indomethacin blocked CBS-stimulated generation of PGE2, but only partially blocked the protection against ethanol-induced lesions. These findings indicated that CBS protects the rat gastric mucosa against ethanol lesions and both prostaglandin- and non-prostaglandin-mediated mechanisms could contribute to this protection.

Topics: Animals; Anti-Ulcer Agents; Dinoprostone; Ethanol; Female; Gastric Mucosa; Indomethacin; Male; Organometallic Compounds; Prostaglandins E; Rats; Rats, Inbred Strains; Stomach Ulcer; Sucralfate

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Cimetidine; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Organometallic Compounds; Stomach Ulcer

Peptic ulcer disease occurs when there is an imbalance between aggressive factors and mucosal resistance. Mucus plays a key role in mucosal resistance. The mucus layer is relatively resistant to peptic digestion, it provides a layer through which there is a movement of hydrogen ions from the parietal cell to the lumen but a resistance to back-diffusion of hydrogen ions in the opposite direction. It maintains a pH gradient by 'sequestering' secreted bicarbonate and by its resistance to H+ back-diffusion. Colloidal bismuth subcitrate (De-Nol) binds to mucus to stabilize the mucous layer and increase the resistance to back-diffusion of hydrogen ions without significantly modifying the ion-exchange properties of mucus.

Topics: Adult; Aged; Animals; Anti-Ulcer Agents; Duodenal Ulcer; Gastric Mucosa; Guinea Pigs; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Ion Exchange; Microscopy, Electron, Scanning; Middle Aged; Mucus; Organometallic Compounds; Stomach Ulcer; Time Factors

We investigated the gastroprotective effects of colloidal bismuth subcitrate (CBS, De-Nol) in comparison with agents such as sucralfate and methylated PGE2. Both CBS and sucralfate given orally prevented dose dependently the formation of gastric lesions by acidified aspirin, ethanol and restraint stress, CBS being more potent on a weight-to-weight basis than sucralfate. CBS and sucralfate were also equally effective in enhancing the healing rate of chronic gastric and duodenal ulcer induced by serosal application of acetic acid, while methylated PGE2 was completely ineffective in this model. Non-colloidal bismuth subnitrate, in contrast to CBS, was ineffective against stress-induced lesions. CBS stimulated mucosal generation and luminal release of PGE2 dose dependently.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Anti-Ulcer Agents; Aspirin; Immersion; Organometallic Compounds; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological; Sucralfate

Mucosa protective drugs are thought to have an important role in the treatment of both duodenal (DU) and gastric ulcer (GU) disease by means of correcting the disturbed defensive factors. Sucralfate as well as colloidal bismuth subcitrate (CBS) form a layer on the ulcer base and in this way protect the ulcer from acid, peptic activity and bile. In duodenal ulcer sucralfate and CBS have shown a significant difference in healing rate compared with placebo. The same holds true for gastric ulcer. When compared with H2-receptor antagonists the healing rates obtained with sucralfate are rather similar. The data obtained with CBS tend to be superior. Also the scores for symptomatic improvement are indistinguishable compared to that seen with H2-receptor antagonists. Especially after CBS the relapse rates of both DU and GU appear less and delayed. Mucosa protective agents are to be considered as valid alternatives to the H2-receptor antagonists.

Topics: Cimetidine; Duodenal Ulcer; Gastric Mucosa; Humans; Intestinal Mucosa; Organometallic Compounds; Peptic Ulcer; Recurrence; Stomach Ulcer; Sucralfate; Wound Healing

Colloidal bismuth subcitrate (CBS) precipitates in an acid environment, adheres to mucus, blocks pepsin activity, retards hydrogen-ion back diffusion and stimulates prostaglandin synthesis. The average healing rate after 4 weeks' treatment with CBS is 78% in duodenal ulcer versus 67% with cimetidine. A direct comparison with ranitidine gives healing rates of 78% (CBS) as opposed to 78% with ranitidine. The corresponding figures in gastric ulcer are 68% (CBS) and 54% (cimetidine). The percentage of relapse-free patients is substantially higher after CBS ulcer healing than after H2-blockers. Bismuth subsalicylate eliminates Campylobacter pylori in 71% after 4-weeks' therapy. Parallel to this elimination a decrease and normalization of the acute inflammatory process can be seen in antral mucosa.

Topics: Anti-Ulcer Agents; Bismuth; Campylobacter Infections; Chronic Disease; Duodenal Ulcer; Gastritis; Humans; Organometallic Compounds; Peptic Ulcer; Salicylates; Stomach Ulcer

Basal and pentagastrin stimulated gastric secretion was measured in seven patients with duodenal, and six with gastric ulcers before and after four weeks' treatment with colloidal bismuth subcitrate (as De-Nol), one tablet four times a day. Each duodenal and all but one of the gastric ulcers healed. After De-Nol there were no significant changes in basal, or pentagastrin stimulated volume, acid output, or primary parietal component. There were marked decreases in basal (duodenal ulcer -25%; gastric ulcer -16%) and pentagastrin stimulated total pepsin outputs, (duodenal ulcer -42%, gastric ulcer -36%). There were insignificant decreases in basal output of mucus, but postpentagastrin stimulated mucus output was significantly inhibited (p less than 0.05) in patients with duodenal (-16%) and with gastric ulcer (-27%). The drop in gastric proteolysis after De-Nol is unlikely to be because of the healing of the ulcers and is more likely to be because of the drug. The ulcer healing efficacy of De-Nol may be related to this decline in the proteolytic action of gastric juice, but is unlikely to be because of a quantitative change in mucus, or in acid secretion.

Topics: Adult; Aged; Bismuth; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Humans; Male; Middle Aged; Mucus; Organometallic Compounds; Pepsin A; Stomach Ulcer

This study was designed to compare the gastroprotective effects of colloidal bismuth subcitrate (CBS) with those of sucralfate and methylated analog of prostaglandin E2 (PGE2) against acute gastric lesions induced by absolute ethanol, acidified aspirin (ASA), and water immersion and restraint stress in rats. When given orally, both CBS and sucralfate prevented in a dose-dependent way the formation of gastric lesions induced by all three ulcerogens, CBS being about 7, 2, and 20 times more potent, respectively on a weight-to-weight basis than sucralfate. Methylated PGE2 was also highly effective against these ulcerogens. Bismuth subnitrate was ineffective against acute gastric lesions induced by stress conditions. The protection of both CBS and sucralfate was reversible when the animals were pretreated with indomethacin to suppress the generation of endogenous prostaglandins. Since CBS and sucralfate increased the production of PGE2 in the gastric mucosa, we postulate that their gastric protective action may be mediated, at least partly, by mucosal prostaglandins.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Bismuth; Dinoprostone; Gastric Mucosa; Organometallic Compounds; Prostaglandins E; Rats; Rats, Inbred Strains; Stomach Ulcer; Sucralfate

Topics: Adult; Anti-Ulcer Agents; Bismuth; Cimetidine; Female; Humans; Male; Middle Aged; Organometallic Compounds; Stomach Ulcer

Topics: Aluminum; Antacids; Anti-Ulcer Agents; Benzimidazoles; Bismuth; Carbenoxolone; Critical Care; Gastritis; Histamine H2 Antagonists; Humans; Omeprazole; Organometallic Compounds; Peptic Ulcer Hemorrhage; Prostaglandins; Risk; Stomach Ulcer; Stress, Physiological; Sucralfate

This study establishes that real differences between relapse rates exist, and confirmed previous observations by Pounder et al. that relapse rates influence clinical outcomes in ulcer populations. The results make it clear that the way in which a drug influences relapse is an important determinant of therapeutic efficiency, additional to the requirement for healing efficiency. Cytoprotective agents as a group appear to be associated with lower relapse rates than cimetidine. It is not known whether the differences are peculiar to cimetidine, specific to the blockade of H2-histamine receptors, or whether they relate to the process of inhibition of secretory processes generally. Clearly, further comparisons are needed; however, conventional clinical trials are not designed to provide the necessary information. For the healing of peptic ulcers, lower relapse rates appear to provide therapeutic advantage to members of the cytoprotective group when compared with agents acting via anti-secretory mechanisms, in addition to that associated with the local (non-systemic) mode of action where applicable.

Topics: Aluminum; Antacids; Bismuth; Carbenoxolone; Cimetidine; Duodenal Ulcer; Humans; Organometallic Compounds; Peptic Ulcer; Recurrence; Stomach Ulcer; Sucralfate

Topics: Aluminum; Anti-Ulcer Agents; Bismuth; Carbenoxolone; Drug Evaluation; Gastric Acid; Gastric Mucosa; Gastritis; Humans; Organometallic Compounds; Prostaglandins; Stomach Ulcer; Sucralfate

The effects of tripotassium dicitrato bismuthate (TDB) on gastric acid, pepsin and mucoprotein secretion in rats and on hydrochloric-peptic secretion and plasma gastrin levels in dogs were investigated. In Shay rats, TDB did not affect acid secretion but significantly lowered pepsin concentration and increased the amount of bound mucoproteins. In addition, gastric mucosal lesions were significantly prevented by the drug. In dogs, chronically fitted with both gastric fistulae and Heidenhain pouches, acid secretion and plasma gastrin levels stimulated by a meat meal were unaffected by TDB, while pepsin concentration and pepsin output were significantly decreased. On the basis of these results, the antiulcer activity of TDB appears to be ascribed to the protection of the gastric mucosa through an increase in mucoprotein synthesis and a decrease of pepsin activity.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Dogs; Female; Gastric Acid; Gastric Mucosa; Gastrins; Mucoproteins; Organometallic Compounds; Pepsin A; Rats; Rats, Inbred Strains; Species Specificity; Stomach Ulcer; Time Factors

Topics: Adult; Aged; Bismuth; Drug Evaluation; Drug Tolerance; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Organometallic Compounds; Ranitidine; Stomach Ulcer

Tri-potassium di-citrato bismuthate given intragastrically to rats 60 min before administration of necrotizing agents such as 85% ethanol, 0.2 N sodium hydroxide or acidified indomethacin, reduced the formation of mucosal lesions dose-dependently. Prostaglandin I2 (PGI2)-like material, determined by bioassay, was higher in the gastric mucosa of animals treated with bismuth subcitrate complex than in control animals.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Epoprostenol; Ethanol; Gastric Mucosa; Indomethacin; Male; Organometallic Compounds; Rats; Rats, Inbred Strains; Sodium Hydroxide; Stomach Ulcer

The mechanism of action of ulcer drugs without acid inhibition appears to involve improvement of defensive factors of the gastroduodenal mucosa. The concept of ulcer healing without acid inhibition is attractive for theoretical reasons, because doubts have arisen about the safety of elevation of intragastric pH, especially in long-term treatment of peptic ulcer disease. Ulcer drugs that do not affect gastric acidity may therefore be preferred, provided they compare favorably to the best acid inhibitors available in terms of efficacy, adverse effects and other requirements. Among these drugs, sucralfate fulfills these criteria to a large extent.

Topics: Aluminum; Anti-Ulcer Agents; Bismuth; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Humans; Organometallic Compounds; Recurrence; Stomach Ulcer; Sucralfate

Topics: Adult; Aged; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Humans; Middle Aged; Organometallic Compounds; Stomach Ulcer

Topics: Anti-Ulcer Agents; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Organometallic Compounds; Stomach Ulcer

Topics: Aged; Anti-Ulcer Agents; Bismuth; Female; Humans; Male; Middle Aged; Mucus; Organometallic Compounds; Stomach Ulcer

The mode of action of colloidal bismuth subcitrate (CBS), a colloidal bismuth preparation often used in the treatment of gastroduodenal ulcers, is unknown. The precipitation characteristics of CBS were determined by titration with hydrochloric acid and gastric juice. The precipitation pH were 4.0 and 3.5 respectively. Preoperative administration of CBS resulted in a preferential accumulation of bismuth in chronic gastric ulcers as determined by tissue bismuth assays. CBS and gastric glycoprotein formed an in vitro complex which markedly retarded the migration of H+. One of the mechanisms by which CBS promotes ulcer healing is through its behaviour as a diffusion barrier to hydrochloric acid.

Topics: Anti-Ulcer Agents; Bismuth; Diffusion; Electrochemistry; Gastric Acid; Glycoproteins; Humans; Hydrogen-Ion Concentration; Mucus; Organometallic Compounds; Stomach Ulcer

Controlled clinical trials have shown that tripotassium dicitrato bismuthate healed duodenal and gastric ulcers significantly better than placebo. One mechanism suggested is that it forms a protective coat at the ulcer base. We studied this coating action in rats with chronic gastric ulcers produced by a standardized technique for mucosal wounding at the fundoantral junction. Bismuth was identified by histochemical staining using Castel's reagent, the specificity of which was verified in vitro against 13 other metallic compounds and chemicals. Our results showed that tripotassium dicitrato bismuthate had a coating affinity for the ulcer base, but not for the adjacent normal mucosa. All rats treated with tripotassium dicitrato bismuthate 1, 2, 4, and 6 h previously, but not the control rats treated with water or those treated with four other bismuth compounds, manifested a layer of bismuth that coated the ulcer base. Light and electron microscopy of the tripotassium dicitrato bismuthate-treated ulcers--but not their controls-revealed an abundance of macrophages, which had ingested the bismuth. This unique bismuth coat may insulate the ulcer base from acid-pepsin digestion, while the influx of macrophages may expedite reparative processes.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Gastric Mucosa; Macrophages; Male; Microscopy, Electron; Organometallic Compounds; Rats; Rats, Inbred Strains; Stomach Ulcer

Topics: Bismuth; Citrates; Duodenal Ulcer; Gastric Mucosa; Humans; Organometallic Compounds; Stomach Ulcer