Novel non-steroidal anti-inflammatory drugs: what we have learned from animal studies.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) is frequently associated with serious adverse effects related to the inhibition of cyclooxygenase (COX) in tissues where prostanoids exert physiological effects, such as gastric mucosal defence, renal homeostasis and platelet aggregation. The discovery of a second COX isoform (COX-2) specifically induced in pathological tissues led to the development of selective COX-2 inhibitors, believed to have an improved safety profile compared to traditional NSAIDs. Animal studies, however, have revealed a protective role for the COX-2 enzyme in the stomach, kidney, heart, vasculature and reproductive system, and therefore, the safety of COX-2 selective inhibitors needs to be reassessed. On the other hand, new therapeutic indications have emerged as a result of the role played by COX-2 overexpression in cancer or Alzheimer's disease. A second approach aimed at obtaining safer NSAIDs is based on the gastroprotective effects of nitric oxide (NO). Traditional NSAIDs chemically linked to NO-releasing moieties retain the therapeutic efficacy, but not the adverse effects, of the parent NSAIDs. Moreover, additional therapeutic applications in cardiovascular diseases, Alzheimer's disease and cancer have been suggested. Animal data, however, need to be confirmed in large clinical trials. Finally, the increase in endogenous NO via a selective increase in inducible NO synthase in the gastric mucosa is the mechanism underlying the good gastric tolerability and the gastroprotective effects of the non-selective NSAID amtolmetin guacyl, documented to date in the rat.

[Nitric oxide and gastroduodenal damage caused by NSAIDs. Recent findings and clinical implications]. / Nitrossido e danno gastroduodenale indotto da FANS. Recenti acquisizioni ed implicazioni cliniche.

A significant role of nitric oxide (NO) is being acknowledged gastroduodenal mucosa defense mechanism(s) against the injurious effect of NSAIDs. Many of the NO effects recall those of prostaglandins, such as direct protection of epithelial cells, mucus release, repair of mucosal erosions or ulcerations, mast cell degranulation. Other co-effects prove to be the inhibition of neutrophil adherence to the vascular endothelium, also associated with an improved mucosal blood flow. NO may also act by scavenging oxygen-derivedfree radicals. Consequently, in order to reduce the NSAID gastrotoxicity has been proposed: a) the linking of a NO-releasing mojety to these agents (NSAID NO-donors); b) the use of amtolmetin guacyl (AMG), a drug which induces an increase in the gastric mucosa NO concentration via direct stimulation of the local endogenous synthesis of this gas. Clinical studies on the efficacy and tolerability have been carried out with AMG versus other NSAIDs (diclofenac, indomethacin, piroxicam, naproxen) in patients with osteoarthritis, rheumatoid arthritis and a number of post-traumatic arthropathies. As far as clinical symptoms are concerned AMG proves to be equally effective, but significantly better as far as gastroscopic lesions are concerned. NONSAIDs and AMG may play an important role among the long-term treatment of chronic inflammatory osteoarticular and rheumatic diseases.

[Lansoprazole: an analysis of the clinical trials in the 3 years of 1997-1999]. / Lansoprazolo: analisi delle esperienze cliniche nel triennio 1997-1999.

Aim of this overview was to evaluate the main clinical trials with lansoprazole published from 1997 to 1999 in English-language journals, regarding gastroesophageal reflux disease, peptic ulcer, NSAID-induced ulcer, and ZES. Results of clinical trials for therapy and prevention of lesions/symptoms have been evaluated separately. In direct comparisons, lansoprazole alone (not combined with antibiotics) proves to be equieffective to other PPI and more effective than H2-RA in both therapy and prevention of GERD, peptic ulcer (a part from anti-Hp regimens) and NSAID-induced ulcer. Among Hp-eradicating regimens in patients with peptic ulcer or functional dyspepsia, lansoprazole-based triple therapy is equal in efficacy to other PPI-based or RBC-based triple therapies and, in any case, significantly better than dual therapies. The in vitro anti-Hp activity of lansoprazole, more marked than with other PPI, does not seem to effort clinical advantages. Safety of lansoprazole is largely satisfactory and no different from other PPI and H2-RA.

[Functional dyspepsia in the aged]. / La dispepsia funzionale nell'anziano.

Functional dyspepsia (FD) is a very common syndrome in general population which does not spare the elderly. To define the pathophysiology of FD (GI secretion and motility, visceral sensitivity, psyche) in the elderly proves to be a difficult task, because it is hard enough in itself to discriminate between troubles due to "normal" ageing and manifestations of diseases to which the elderly are particularly susceptible. At any event, unlike in non-elderly dyspeptics, in elderly patients thorough GI investigations are always absolutely mandatory. Dietary recommendations should be simple and reasonable. Drug therapy by antisecretory and prokinetic agents should not be too strong, because the elderly are particularly sensitive to drugs, and are often taking other drugs for extra-intestinal pathology.

[NSAID-induced gastroduodenal damage: strategies for prevention]. / Danno gastroduodenale da FANS: strategie di prevenzione.

The improved knowledge of the mechanism by which NSAIDs work and damage the gastrointestinal (GI) mucosal suggested a series of measures for the prevention of NSAIDs-induced GI lesions, apart from the use of those proved to be less toxic. PPI have now been definitively shown to be more effective in the relief of symptoms and in the healing and prevention of ulcers/erosions than H2-antagonists and also better tolerated than misoprostol. Other more innovative approaches include selective and highly selective COX-2 inhibitors, NSAIDs containing NO or stimulating the gastric endogenous biosynthesis of NO, and chiral NSAIDs. Clinical usefulness of other compounds, including NSAIDs associated with zwitterionic phospholipids or fibroblast growth factor, is still under investigation.

Lansoprazole versus omeprazole for duodenal ulcer healing and prevention of relapse: a randomized, multicenter, double-masked trial.

The aim of this randomized, multicenter, double-masked, parallel-group study was to compare the efficacy of lansoprazole with that of omeprazole monotherapy in duodenal ulcer healing and prevention of relapse. A total of 251 patients with duodenal ulcer were treated with either lansoprazole 30 mg/d (n = 167) or omeprazole 40 mg/d (n = 84). Patients with healed ulcers were then randomly allocated to 12 months of maintenance therapy with lansoprazole 15 mg/d (n = 74), lansoprazole 30 mg/d (n = 71), or omeprazole 20 mg/d (n = 73). Healing rates at 4 weeks (intent-to-treat analysis) were 93.9% (95% confidence interval [CI], 90.2% to 97.6%) with lansoprazole and 97.5% (95% CI, 93.7% to 100%) with omeprazole; there were no significant differences between groups. Endoscopic relapse rates after 6 months were 4.5% (95% CI, 0% to 10.6%) with lansoprazole 15 mg, 0% with lansoprazole 30 mg, and 6.3% (95% CI, 1.5% to 12.5%) with omeprazole 20 mg, compared with 3.3% (95% CI, 0% to 8.2%), 0%, and 3.5% (95% CI, 0% to 8.8%), respectively, at 12 months. Again, there were no significant differences between groups. The incidence of adverse events during acute treatment was 6.0% and 7.1% in the lansoprazole and omeprazole groups, respectively; during maintenance therapy, the incidences were 12.2% (lansoprazole 15 mg), 5.6% (lansoprazole 30 mg), and 11.0% (omeprazole 20 mg). Within treatment groups, pain was significantly ameliorated after the acute phase but not after maintenance therapy (P < 0.05); no differences were observed between groups. Gastrin values increased significantly after acute therapy (P < 0.05), persisted at these increased levels during maintenance therapy, and returned to normal after 6-month follow-up. Both lansoprazole and omeprazole were highly effective and well tolerated in the treatment of duodenal ulcer; relapse rates were similar for all doses studied. Thus no additional benefit is to be gained from using a proton-pump inhibitor at a dose > 15 mg lansoprazole to prevent relapse.

[Peptic ulcer, functional dyspepsia, Helicobacter pylori: a 1998 stock-taking on the topic of their correlation and therapeutic strategies]. / Ulcera peptica, dispepsia funzionale, Helicobacter pylori: bilancio 1998 in tema di correlazione e di strategie terapeutiche.

While the correlation between Helicobacter pylori and peptic ulcer is accepted worldwide, the role of Hp in functional dyspepsia is still a debatable issue. Therefore, Hp eradication in all dyspeptic patients has both supporters and opponents. In contrast, anti-Hp regimens are increasingly well defined, most convincing treatments being triple therapies consisting of one proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antimicrobials. Duration of anti-Hp regimens varies from 2 weeks (more usually adopted in USA) and 1 week (more usually adopted in Europe). Due to the short and simple anti-Hp triple therapies, side effects prove to be few and negligible and patient compliance is significantly better. By contrast, Hp resistance to extensively used antimicrobials, such as metronidazole and clarithromycin, is more than an emerging problem causing significantly lower eradication rates. Very recent data indicate that RBC-based triple therapy is much less affected by the helicobacterial resistance, and is also effective in non-responders to a PPI-based triple therapy.

[NSAID-induced gastrointestinal diseases: recent data on pathogenesis and prevention]. / Patologia gastrointestinale da FANS. Dati recenti in tema di patogenesi e di prevenzione.

Our knowledge of the mechanism by which aspirin and traditional NSAIDs work and damage the gastrointestinal mucosa, recently markedly improved, has suggested a number of measures for the prevention of the NSAID-induced GI lesions. Among these, perhaps the most innovative approach seems to be the nitric oxide-releasing NSAIDs or compounds, like amtolmetin guacyl, that work by increasing the endogenous biosynthesis of NO selectively at gastric mucosa level. Further data, stemming from large RCTs and confirming the results of experimental studies and the initial clinical experiences, are needed to better define the true clinical impact of this approach.

Ranitidine bismuth citrate with either clarithromycin 1 g/day or 1.5 g/day is equally effective in the eradication of H. pylori and healing of duodenal ulcer.

BACKGROUND: No randomized double-blind studies have been performed to compare clarithromycin 1 g/day with higher doses of the macrolide (1.5 g/day) when combined with ranitidine bismuth citrate (RBC). AIM: To compare H. pylori eradication and ulcer healing rates of RBC 400 mg b.d. for 4 weeks combined for the first 2 weeks either with clarithromycin 500 mg b.d. (Group A) or clarithromycin 500 mg t.d.s. (Group B). METHODS: Two hundred and seventy-three patients with H. pylori-positive active duodenal ulcer were included. H. pylori infection was detected by CLO-test and histology on antral and corpus biopsies before and at least 4 weeks after the end of therapy. Eradication was assumed if both CLO-test and histology results were negative for H. pylori. RESULTS: Eradication/healing rates according to intention-to-treat and per protocol analysis were 76/82% and 87/92% for Group A and 78/85% and 88/95% for Group B, respectively (P = N.S.). Adverse events were reported by 7% and 12% of patients in Groups A and B, respectively, and they were generally mild. CONCLUSIONS: RBC in co-prescription with clarithromycin 500 mg b.d. is as effective as RBC plus clarithromycin 500 t.d.s. in eradicating H. pylori and healing duodenal ulcers.

Randomised trial of single and repeated fibrin glue compared with injection of polidocanol in treatment of bleeding peptic ulcer.

BACKGROUND: Although injection treatments for ulcer haemostasis seem to be effective, recurrent bleeding remains a serious problem. Large randomised clinical trials are required to show differences between treatment modalities for gastrointestinal bleeding. The aim of this study was to compare the safety and efficacy of repeated endoscopic injection of fibrin glue (FG) with that of single endoscopic injection of polidocanol in the prevention of recurrent bleeding. METHODS: 854 patients with active gastroduodenal bleeding (spurting, oozing), or ulcers with a visible non-bleeding vessel, were randomly assigned one of three endoscopic treatments: single application of polidocanol 1%, single application of FG, or daily repeated application of FG until the visible vessel had disappeared. All patients were pretreated with local injection of epinephrine (1/10,000), and had daily repeat endoscopies until the vessel observed at initial endoscopy was no longer visible. FINDINGS: Recurrent bleeding rates among the 790 patients in whom the rates could be assessed were 58 (22.8%) of 254 in the polidocranol group, 51 (19.2%) of 266 in the FG-single group, and 41 (15.2%) of 270 in the FG-repeated group. The difference between FG-repeated treatment and polidocanol was significant (p = 0.036). Treatment failed, making other treatments (including surgery) necessary, in 34 (13.0%) of 261 in the polidocanol group, 34 (12.4%) of 274 in the FG-single group, and 21 (7.7%) of 274 in the FG-repeated group. The difference between FG-repeated treatment and polidocanol was significant (p = 0.046). The 30-day-mortality rates were low in all three treatment groups (polidocanol 4.7%; FG-single treatment 5.3%, FG-repeated treatment 4.3%). The safety profiles of the three treatment strategies were similar. INTERPRETATION: Repeated injection with FG glue is significantly more effective than injection with polidocanol 1% in the treatment of bleeding from gastroduodenal ulcers.

[The epidemiology of the gastroduodenal damage induced by aspirin and other nonsteroidal anti-inflammatory drugs]. / Epidemiologia del danno gastroduodenale indotto dall'aspirina e dagli altri farmaci antiinfiammatori non steroidei.

A substantial body of studies (controlled, cohort and case-control studies) now confirm the long established impression that there is an increased prevalence of gastric and duodenal ulcer and of associated complications in subjects treated with aspirin (ASA) or with non-steroidal anti-inflammatory drugs (NSAIDs). The overall percentage of ulcers/erosions in patients treated with ASA ranges from 10 to 50% with a relative risk of bleeding ranging from 1.8 to 15%. The overall relative risk of ulcers/erosions in NSAIDs-treated subjects is around 3%, with complications detectable in 2.4% of cases. The risk of lesions and complications associated with ASA/NSAIDs is more marked in patients aged over 65, in those with a previous history of ulcer (both symptomatic and silent), in those treated with substantial doses or with combinations of NSAIDs and in those concomitantly using anticoagulants and/or steroids. The epidemiological data highlight the importance of implementing ASA/NSAIDs therapy only when strictly necessary as well as the advisability of adopting as broad a range of measures as possible to reduce the tissue-damaging effects of these pharmacological agents.

[The medical therapy of chronic pancreatitis. Problems, progress and outlook]. / La terapia medica della pancreatite cronica. Problemi, progressi e prospettive.

The aims of medical therapy in chronic pancreatitis are mainly to relieve the recurrent pain and to correct any malabsorption secondary to digestive insufficiency resulting from deficient exocrine pancreatic function. The treatment of the pain initially involves the use of dietary measures and analgesic drugs. The results of the use of pancreatic extracts and somatostatin reported in the literature are controversial, as are those of coeliac plexus block. Of unquestionable efficacy, at least in the short to medium term, are surgical decompression interventions in patients, with pain refractory to these measures and who present significant dilation of Wirsung's duct at ERCP. Endoscopic decompression constitutes an alternative to surgical decompression. In view of the transitory results of endoscopic decompression, which, in any event, should be implemented only by endoscopists possessing the necessary experience and expertise, the use of this technique may perhaps be targeted at carefully selected patients to be submitted to surgical decompression. As far as maldigestion is concerned, which occurs only when the pancreatic functional deficit reaches 90% or more, replacement therapy with pancreatic extracts must be resorted to. Multi-Unit Dose preparations are to be preferred, consisting in gastro-protected microspheres measuring not more than 2 mm in diameter and containing high doses of lipase, since at least 30,000 I.U. of lipase are required in the post-prandial phase for reasonably satisfactory correction of the steatorrhoea. Should this fail to prove effective, it is good policy to add antisecretory drugs (H2-antagonists, proton-pump inhibitors).

[The eradication of Helicobacter pylori and the prevention of ulcer recurrence. The certainties and the open problems]. / Eradicazione di Helicobacter pylori e prevenzione della recidiva ulcerosa. Certezze e problemi aperti.

Maintenance treatment with antisecretory agents, and above all with H2-RA, is a therapeutic option still largely favoured by physicians. However, in the last decades the pathogenetic role of Helicobacter pylori (Hp) in duodenal and gastric ulcer has met with increasingly convincing confirmation. Actually, Hp eradication brings about a dramatic and persistent decrease in ulcer relapse rate. At present, there is a general agreement that Hp-positive patients, with ulcer whether ab initio or recurrent, need to be treated with anti-Hp regimens. The first choice therapy, according to some clinicians, should be the classic triple therapy (colloidal bismuth, metronidazole and tetracicline or amoxicillin) associated or not with a proton pomp inhibitors (PPI) or H2-RA. Though supported by other gastroenterologists, dual therapy with a PPI plus amoxicillin raises some perplexity due to the unpredictable variability of the results. Non-bismuth triple therapy, consisting in 2 antimicrobial and 1 antisecretory agent, for which a duration of only 1 week would seem sufficient even at low dosage, is currently meeting with greater favour. The FDA approval is probably imminent for 2 anti-Hp regimens consisting in clarithromycin plus a PPI or the complex salt ranitidine-bismuth citrate.

[Diet and drugs in the therapy of nonorganic dyspepsia: the hypothesis and factual data]. / Dieta e farmaci nella terapia della dispepsia non organica: ipotesi e dati di fatto.

Non-organic dyspepsia, although not frequently reported, is still a disorder which is difficult to classify in nosographic and physiopathological terms, a fact which inevitably influences the indications for its treatment. Non-pharmacological treatment of non-organic dyspepsia includes changes in dietary and behavioural habits which, even if established on empirical grounds, play a far from ancillary role. When considered appropriate, pharmacological treatment must be formulated solely on the basis of controlled clinical trials vs placebo given the well-known significance of the placebo effect in this and other so-called "functional" diseases. The therapeutic strategies which are most subject to verification are based on the one hand on the neutralisation or inhibition of gastric acid secretion and, on the other, on the improvement of gastrointestinal motility. Surprisingly, the widely used antacid drugs are among those which have been less well studied and show the lowest efficacy. Among the anti-secretory drugs, pirenzepine is approximately 25% more effective than placebo. H2-antagonists, the drugs which have been most closely studied both in terms of the number of trials and the size of the sample populations studied, produce contradictory results. However, a meta-analysis of the trials shows an overall 18% improvement in efficacy compared to placebo. The overall results of studies on prokinetic compounds are "good" in meta-analytical terms, with an improved efficacy of 50% compared to placebo. This is not necessarily due to the superiority of prokinetic compared to anti-secretory drugs and can be explained by the reduced placebo effect in trials using prokinetic drugs or a greater presence in the latter of dyspepsia which is physiopathologically correlated to motor discord. Among the future drugs still being studied, it is particularly worth mentioning fedotozine, a specific K opioid receptor agonist which appears to have provided extremely interesting results in preliminary studies. The role of barrier drugs, such as sucralfate and colloidal bismuth, continues to remain unclear and in particular the latter might be of increased use if evidence of a relationship between Helicobacter pylori and non-organic dyspepsia were reinforced; this relationship may in fact not exist in all dyspeptic patients but only in a subgroup. Lastly, the problem of the duration of pharmacological treatment still remains unsolved, as do the questions of whether longterm treatment should be conceived once acute symptoms have disappeared and whether it is possible to hypothesise differentiated pharmacological treatment depending on the clinical variants of functional dyspepsia which have been defined with greater attention over the course of the past decade.

Extracorporeal shock wave lithotripsy (ESWL) of gallbladder stones: experience in Bolzano.

During a period of 24 months, 115 patients with symptomatic gallbladder stones (77 females, 38 males; median age 46 years, range 22-87) were treated by extracorporeal shock wave lithotripsy with a Lithostar Plus. Concomitant bile acid dissolution therapy (ursodeoxycholic acid + chenodeoxycholic acid 7.5 mg/kg/day each or tauroursodesoxycholic acid 5-10mg/kg/day) was administered until 3 months after total fragment clearance. Complete clearance of all fragments was obtained after 6, 9, 12, 18 and 24 months in, respectively, 30, 45, 51, 62 and 72%. Life table analysis of the subgroups showed significantly better clearance results in patients with fragments < 5mm at the first extracorporeal shock wave lithotripsy session (67%) than in patients with larger fragments (39%) (p < 0.01). Patients with solitary stones < 20mm cleared their fragments better (58%) at 12 months than those with multiple stones (49%), but the differences were not statistically significant. Stone recurrence was 6% at 1 year and was lower in patients with solitary stones (3%) than in those with multiple stones (12%). Major side effects consisted in 2 cases of mild acute pancreatits and 19% of biliary colics.

Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patients.

BACKGROUND: In a significant number of patients affected by the irritable bowel syndrome, an adverse reaction to food is proposed to be a causative factor. A diet that eliminates the offending foods is the obvious treatment for such adverse reactions. Compliance with a dietetic regimen is often poor and sometimes not completely free from risks. METHODS: Since the diarrheic type of irritable bowel syndrome seems mainly affected by food intolerance, and previous observations suggested that oral cromolyn sodium is effective in such patients, a multicenter therapeutic trial in the diarrheic type of irritable bowel syndrome was carried out in 346 of 409 patients with this disease, to evaluate the effects of oral cromolyn sodium and compare its efficacy with that of an elimination diet. RESULTS: Symptoms related to the irritable bowel syndrome improved in 60% of patients treated with elimination diet and in 67% of those treated with oral cromolyn sodium (1500 mg/day) for 1 month. Moreover, in both groups clinical results were significantly better in the patients positive to the skin prick test than in the negative ones. CONCLUSIONS: These results confirm the high prevalence of adverse reactions to foods in diarrheic irritable bowel syndrome and the usefulness of cromolyn sodium treatment in these patients.

Chronic gastritis, intestinal metaplasia, dysplasia and Helicobacter pylori in gastric cancer: putting the pieces together.

Chronic gastritis may favour the development of gastric cancer more as a condition than as precancerous lesion. Since, in most cases, it is pathologically correlated with Helicobacter pylori infection, it is reasonable to postulate at least an indirect role for this organism in the pathogenesis of gastric cancer. H. pylori, however, is only one of the risk factors involved, in that additional factors (excess salt, cigarette smoking, deficiency of foodstuffs with an antioxidizing effect) may facilitate the malignant transformation of chronic atrophic gastritis into intestinal-type gastric cancer. Gastric carcinogenesis therefore presents itself as a multifactorial, multistage process, furthered by the occurrence of precancerous lesions which are usually interrelated (type-III intestinal metaplasia, severe dysplasia) and by functional alterations such as achlorhydria, which, though it is not enough in itself to cause gastric cancer, promotes abnormal intragastric bacterial development, a condition which may be followed by abnormal intragastric formation of cancerogenous nitroso compounds. The existence of a close correlation between both gastric cancer and H. pylori infection and low socio-economic and hygienic status of the population lends further strength to the hypothesis that an "H. pylori factor" is involved in gastric carcinogenesis. Consequently, to reduce the risk of gastric cancer, various strategies have been devised to prevent H. pylori infection (improvement in socio-environmental conditions, anti-H. pylori vaccine) and/or to eradicate the organism (by means of therapeutic regimens including antimicrobial agents, which, however, can be implemented only in patients who have not developed diffuse atrophy and/or dysplasia, in whom H. pylori may no longer be detectable). Definitive proof of the real extent of the relationship between H. pylori and gastric cancer and of the efficacy of therapeutic and preventive measures can be provided only by controlled trials in populations with a high prevalence of chronic non-atrophic gastritis which are difficult to organize.

Placebo and placebo effect: their impact on the evaluation of drug response in patients.

Placebo, defined as any therapeutic procedure, without any specific activity, given deliberately to have an effect on a patient, symptom, syndrome or disease, has a great impact in the evaluation of drug response. The possible pathways via which the possible effect brings about clinical and physiological changes remain unknown, but a humoral mechanism seems to be implicated in some placebo effects (e.g. placebo-induced analgesia). The placebo effect depends on many factors, including the type of patient, the personality of the physician, the doctor-patient relationship and the type and even the colour of the drug preparation. Placebo control is important particularly when the disease is characterized by frequent spontaneous periods of acute exacerbation and remission. Functional (such as dyspepsia and irritable bowel syndrome) and organic (such as peptic ulcer and inflammatory bowel disease) gastrointestinal diseases have got great benefit from placebo-controlled clinical trials. In such trials the more effective the placebo is, the more difficult it will be to demonstrate the efficacy of active drug in statistical terms. Nevertheless, provided the use of placebo be ethical for a given condition, placebo-controlled trials are the only objective way of assessing correctly drug response in patients.

[Helicobacter pylori and the treatment of gastric ulcer. Reflections and uncertainties]. / Helicobacter pylori y tratamiento de la úlcera gástrica. Reflexiones e incertidumbres.

The authors examine the relationship between Helicobacter pylori and gastric ulcer therapy, analyzing both the data suggesting that eradication of the organism renders the gastric mucosa less susceptible to development of gastric ulcer and the substantial body of evidence to the contrary. They review the results reported in clinical trials with colloidal bismuth subcitrate, antimicrobial agents (furazolidone), and combinations of antiulcer and antimicrobial agents (H2-antagonist + cefixime, H2-antagonist + metronidazole). Also analyzed is the relationship between Helicobacter pylori 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 Helicobacter pylori facilitates either acute healing or long-term prophylaxis of gastric ulcer, though certain subgroups of gastric ulcer patients may benefit from eradication therapy.