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Biomedical subjects

G Dobrilla

Publications and source records attributed to G Dobrilla.

At least 19 recordsLinked to original sources
PubMed1992

Helicobacter pylori and gastric ulcer therapy: reflections and uncertainties.

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.

Anti-Bacterial Agents↗
PubMed1991

Antisecretory agents, peptic secretion and serum pepsinogen in man.

Less attention has been devoted to the effects of antisecretory agents on pepsin secretion than to those on gastric acid secretion, particularly in human subjects. Moreover, comparison of the various trials is far from being simple and straightforward owing to the fact that the studies available present substantial variability in terms of types of subjects (controls, DU patients), gastric secretion (basal, stimulated), type of stimulation (pentagastrin, histamine, insulin, meals, sham feeding) antisecretory drug administration route (oral, i.v.) and considered parameters (concentration, output). This review of the published data reveals that all antisecretory agents reduce pepsin output, regardless of their sometimes very different mechanism of action. Despite this, there are differences in antisecretory effects according to the agent used to stimulate gastric secretion. Even within a single drug class (H2-antagonists, prostaglandins) there may be differences depending on the potency of the compound used.

Anti-Ulcer Agents↗
PubMed1991

[No acid, no ulcer: such a simple axiom?].

According to the traditional view gastric acid and pepsin are a sine qua non for ulcer development. Acid suppression, however, is far from being the only successful therapeutic approach, and similar healing rates are achieved by drugs with substantially different mechanisms of action--antacids, H2-antagonists, antimuscarinics, cytoprotective and site-protective agents--thus denoting a multifactorial pathogenesis. Even with the antisecretory compounds, the relationship between gastric acid and ulcer healing gives rise to perplexity: antacids prove effective at widely varying doses; pirenzipine and H2-blockers, which are clinically equieffective, differ considerably in antisecretory efficacy; H2-antagonist studies on early vs late postprandial dosing yield contradictory clinical results; morning and bedtime single administrations of H2-antagonists prove equiactive on ulcer healing, leading to a reappraisal of the alleged importance of nocturnal acidity. Ulcer sealants such as colloidal bismuth and sucralfate prove as effective as H2-antagonists despite their total lack of antisecretory activity, thereby apparently undermining the primary pathogenetic role of acid. However, with the spectacular 100% healing rates achieved by the protonpump blocker, omeprazole, the wheel has come full circle, and gastric acid appears to re-emerge as a primary element in pathogenesis. Specific therapy, based on the predominant pathogenetic factor involved, is likely to be a feasible proposition, but, at present, remains little more than a remote possibility.

Animals↗
PubMed1990

Longterm treatment of irritable bowel syndrome with cimetropium bromide: a double blind placebo controlled clinical trial.

The aim of this study was to evaluate the efficacy of cimetropium bromide, a new antimuscarinic compound, in relieving symptoms of patients with irritable bowel syndrome over a three month period. Seventy consecutive outpatients were given cimetropium (50 mg tid) or placebo according to a double blind, randomised, parallel groups design. Symptoms were evaluated initially and at monthly intervals up to the end of the study period. One patient receiving placebo withdrew because of treatment failure. Pain score decreased by 40, 66, 85% in the cimetropium group, at the end of the first, second and third months respectively, compared with 26, 32 and 52% reductions among controls (p = 0.0005). At the end of treatment there was a 86% reduction in the number of abdominal pain episodes per day in the cimetropium group compared with 50% in the placebo group (p = 0.001). Constipation and diarrhoea scores decreased by 59 and 49% in the cimetropium treated patients, compared with 37 and 39% in controls, the differences between being not significant. At the end of the study 89% of the patients treated with cimetropium considered themselves as globally improved as opposed to 69% in the placebo group (p = 0.039). The corresponding 95% confidence intervals for the differences between the proportion of improved patients in the two groups were from 11% to 29%. Six patients taking cimetropium complained of slight dry mouth. The results of this study showed that cimetropium bromide is effective in relieving pain in patients with irritable bowel syndrome.

Adult↗
PubMed1990

Powerful gastric acid inhibition: when is it justified?

Peptic ulcers fail to heal in up to 10% of patients after 8 weeks of therapy with H2-receptor antagonists largely owing to the multifactorial pathogenesis of the disease. Site-protective agents may heal the ulcers in many, but not all, of these non-responders. In ulcers which prove particularly refractory to therapy, only powerful gastric acid inhibition of the type best achieved with omeprazole is capable of healing most, and sometimes even 100% of patients in the short term. Powerful inhibition of gastric acid secretion proves clinically advantageous, in terms both of symptom relief and endoscopic lesions, in severe reflux oesophagitis, characterized, as it is, by erosive and ulcerative lesions. Strong inhibition of acid secretion is, of course, also indicated in Zollinger-Ellison syndrome, the treatment of which has already been revolutionized by the use of H2-antagonists, usually given in very high doses, and appears to have made yet another step forward with the advent of omeprazole thanks to the particularly marked potency and duration of action of this benzimidazole derivative. Powerful inhibition of acid secretion thus seems possible both with high-dose H2-antagonists and, most notably, with omeprazole. Though fully justified in certain classic conditions such as refractory ulcer, erosive-ulcerative oesophagitis and Zollinger-Ellison syndrome, massive antisecretory blockade would not appear to be suitable for indiscriminate use, especially long-term.

Anti-Ulcer Agents↗
PubMed1990

The gastric acid conundrum in peptic ulcer.

According to the traditional view, gastric acid and pepsin are a sine qua non for ulcer development. Acid suppression, however, is far from being the only successful therapeutic approach, and similar healing rates are achieved by drugs with substantially different mechanism of action antacids, H2-antagonists, antimuscarinics, cytoprotective and site-protective agents-thus denoting a multifactorial pathogenesis. Even with the antisecretory compounds, the relationship between gastric acid and ulcer healing gives rise to perplexity: antacids prove effective at widely varying doses; pirenzipine and H2-blockers, which are clinically equieffective, differ considerably in antisecretory efficacy; H2-antagonist studies on early vs late postprandial dosing, yield contradictory clinical results; morning and bedtime single administration of H2-antagonists prove equiactive on ulcer healing, leading to a appraisal of the alleged importance of nocturnal acidity. Ulcer sealants such as colloidal bismuth and sucralfate prove as effective as H2-antagonists despite their total lack of antisecretory activity, thereby reapparently under-mining the primary pathogenetic role of acid. However, with the spectacular 100% healing rates achieved by the proton-pump blocker, omeprazole, the wheel has come full circle, and gastric acid appears to re-emerge as a primary element in pathogenesis. Specific therapy, based on the predominant pathogenetic factor involved, is likely to be a feasible proposition, but, at present, remains little more than a remote possibility.

Gastric Acid↗
PubMed1990

Effects of sucralfate and sulglycotide treatment on active gastritis and Helicobacter pylori colonization of the gastric mucosa in non-ulcer dyspepsia patients.

We conducted a double-blind randomized treatment study on patients affects by non-ulcer dyspepsia in whom multiple biopsy specimens showed active gastritis. Patients were given either 3 g/day of sucralfate (n = 39) or 600 mg/day of sulglycotide (n = 50) for 6 wk, a glycopeptide isolated from pig duodenum constituents. Endoscopy was carried out at baseline and at the end of treatment. We took biopsies from the gastric body (twice) and antrum (six times) at each endoscopy in order to determine grade and extent of gastritis and Helicobacter pylori colonization. Both treatments induced a marked regression of active gastritis (sucralfate group: p less than 0.05 and p less than 0.0001, respectively, in body and in antrum; sulglycotide group: p less than 0.01 and p less than 0.001, respectively). Conversely, Helicobacter pylori colonization remained unchanged at the end of the treatments. At baseline, a close relationship was found between grade of active inflammation in each biopsy and Helicobacter pylori density. After therapy, the association was lost in each treatment group. These results suggest that there can be a remission of active gastritis in patients with non-ulcer dyspepsia even without changes in Helicobacter pylori colonization. This result can be achieved by enhancing the protective properties of the gastric mucosa.

Adult↗
PubMed1989

Drug treatment of functional dyspepsia. A meta-analysis of randomized controlled clinical trials.

The results of therapeutic trials in functional dyspepsia (FD), a frequently encountered condition, are contradictory. Our aim, then, was to produce a pooled estimate, or meta-analysis, of a series of short-term randomized placebo-controlled clinical trials on the pharmacological treatment of FD with antisecretory and gastrokinetic drugs. We retrieved trials for analysis purposes by consulting computerized data bases and by scanning published reviews, Current Contents, and references cited in the individual studies. We also requested bibliographical updates from the medical departments of the manufacturers of the drugs used in the various trials. Of 74 trials retrieved by these means, 23 proved eligible for meta-analysis on the basis of six selection criteria defined a priori. Results were expressed in terms of "therapeutic success" (TS), which includes "symptom-free patients," patients with "significant improvement in symptoms," "excellent results," and so on. The differences in TS rates between the various drugs and placebo were calculated in each trial as the algebraic difference together with the respective 95% confidence interval (95% C.I.); the pooling of results of all eligible trials was done using Cochran's weighted method. With antisecretory drugs, the mean difference in TS rates versus placebo was +20% (95% C.I.: 14-24%). The therapeutic gain for the respective antisecretory agents was 25% (95% C.I.: 14-36%) in the case of pirenzepine and 18% (95% C.I.: 12-24%) in the case of H2 antagonists. Meta-analysis of trials with gastrokinetic drugs also showed superior efficacy of these agents compared with placebo, with a mean difference in TS rates of +46% (95% C.I.: 40-52%).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1989

Campylobacter pylori and non-ulcer dyspepsia. 1. The final results of a double-blind multicentre trial for treatment with pirenzepine in Italy.

In a double-blind multicentre trial to study the effect of pirenzepine in the treatment of non-ulcer dyspepsia, 104 of 128 patients, 52 in each of the study and control groups, completed the 4 weeks of the investigation. There was improvement of the endoscopic and clinical findings but no change of the degree of the mucosal inflammation or the extent of colonisation by campylobacter pylori. The mode of action of pirenzepine in patients with non-ulcer dyspepsia associated with campylobacter related gastroduodenitis remains obscure. Further studies are needed to investigate the possibility of a causal relationship between mucosal colonisation with campylobacter pylori and gastroduodenitis specially in cases of non-ulcer dyspepsia.

Adult↗
PubMed1989

Octatropine-methyl-bromide and sulglycotide salt in the short-term treatment of active duodenal ulcer. A double blind endoscopic study of 40 outpatients.

Forty outpatients with endoscopically confirmed duodenal ulcers were entered in a double blind trial. They were randomly allocated to octatropine-methyl-bromide and sulglycotide salt (GVP) or placebo. The results show that the combination of the two drugs is less efficacious than the two constituent substances taken separately, is not more efficacious than placebo in ulcer healing, and is ineffective with regard to ulcer pain.

Anti-Ulcer Agents↗
PubMed1989

Oxmetidine in the short term treatment of active duodenal ulcer. A review and commentary.

Oxmetidine is an H2-antagonist like cimetidine containing an imidazole ring in its molecule, but differing from cimetidine in that it contains in the side-chain a substituted isocytosine moiety in place of the cyanoguanidine group. Nine controlled clinical trials are critically analysed in detail. The overall results show that the antiulcer activity of oxmetidine is not significantly different from that of cimetidine with mean healing rates by week 4 of 74.9% and 75.3%, respectively. Healing rates proved to be lower in smokers than in non-smokers in all trials but one. Satisfactory response as regards symptoms was obtained both with oxmetidine and cimetidine. A certain degree of variability with regard to the untoward effects was found, but in all cases failed to prove significant from the clinical point of view. However, a better definition of oxmetidine safety requires a study on a large number of patients and for a longer period.

Anti-Ulcer Agents↗
PubMed1989

Management of chronic pancreatitis. Focus on enzyme replacement therapy.

The goals of treatment with pancreatic extracts in patients with chronic relapsing pancreatitis are twofold: pain relief and control of maldigestion caused by exocrine pancreatic insufficiency. Experience with the use of pancreatic enzymes for analgesic purposes suggests that the less severe the pain, the greater the analgesic effect of these enzymes. However, the number of trials, as well as the number of patients treated, is fairly small and more studies in larger patient populations are needed. The use of pancreatic enzymes for maldigestion owing to exocrine pancreatic insufficiency which is secondary to chronic pancreatitis, pancreatectomy, cystic fibrosis, or GI bypass surgery incurs several problems. These problems are primarily caused by gastric inactivation of the enzymes, low enzyme activity of many commercial preparations and/or poor patient compliance. Treatment with conventional enzyme products (powdered extracts, enteric-coated tablets or capsules) has been disappointing. At best, results were inconsistent, showing a high degree of individual variation. The introduction of enzyme preparations in the form of pH-sensitive enteric-coated microspheres in hard gelatin capsules represents a significant advance. These microspheres are superior to conventional enzyme preparations in improving the symptoms of pancreatic insufficiency, particularly steatorrhea, where low doses of microspheres are as effective as large doses of conventional enzyme preparations. Steatorrhea, however, is rarely completely resolved. In cases refractory to therapy, treatment with the combination of pH-sensitive enteric-coated microspheres and H2-antagonists or prostaglandins has met with some success.

Chronic Disease↗
PubMed1988

First-degree atrioventricular block in a young duodenal ulcer patient treated with a standard oral dose of ranitidine.

A 20-year-old male patient on oral treatment with ranitidine 300 mg/day in a single bedtime dose was admitted to hospital for a brief episode of syncope which had occurred 20 min earlier. All clinical, laboratory and instrumental examinations yielded negative findings, except for electrocardiographic evidence of first-degree atrioventricular block. Administration of atropine produced transient disappearance of the block, which disappeared altogether after discontinuing ranitidine treatment. Two separate rechallenges with ranitidine each produced recurrence of (asymptomatic) first-degree atrioventricular block at electrocardiographic examination, but oral treatment with cimetidine (400-800 mg/day) and famotidine (40-80 mg/day) induced no electrocardiographic abnormalities. The hypothesis that this patient may be abnormally susceptible to the cholinergic or cholinergic-like effect of ranitidine, a side effect unrelated to the drug's primary H2-blocking action, would appear to be consistent with evidence of an increased vagal tone of the atrioventricular node as revealed by atrial pacing. However, the ability of ranitidine to release histamine in man and the potential dysrhythmia-inducing effect of histamine should also be taken into consideration.

Administration, Oral↗
PubMed1988

Cisapride versus placebo in reflux esophagitis. A multicenter double-blind trial.

In a 6 to 12-week double-blind trial, the effect of cisapride (10 mg q.i.d.) was compared with that of placebo in 63 patients with esophagitis confirmed by endoscopy and/or biopsy. In only one patient (3%) in the cisapride group but in 43% of the placebo patients (p = 0.001), symptoms had not improved after 6 weeks. Forty patients continued treatment until week 12. At that time, control endoscopy showed a significantly (p = 0.005) higher rate of healing (no erosions, ulcers, or bleeding mucosa) in the cisapride patients (63%) than in the placebo patients (12%). At week 12, only three of the 21 cisapride patients still had moderate reflux symptoms, whereas eight of the 19 placebo patients had moderate or severe symptoms (p less than 0.05). Cisapride patients also took significantly (p less than 0.001) less antacids during the trial. These results show that cisapride, 10 mg q.i.d., heals esophagitis lesions and greatly reduces associated symptoms. The treatment was well tolerated.

Adult↗
PubMed1988

Influence of ulcer healing agents on ulcer relapse after discontinuation of acute treatment: a pooled estimate of controlled clinical trials.

Whether or not the incidence of ulcer relapse varies according to the drug used to produce initial healing is a controversial matter. We tackled this problem using data from 15 eligible trials from 25 published controlled trials in patients followed up for six to 12 months. Pooled estimates of differences in ulcer relapse incidence between patients initially healed with H2-antagonists and patients initially healed with non-H2-antagonist drugs were calculated. The overall incidence of relapse in patients healed with comparator drugs is 11 percentage units lower at six and 12 months, than that observed in H2-antagonist-healed patients. The confidence intervals are +/- 8% at six months and +/- 7% at 12 months. These data suggest the existence of a different effect on relapse incidence for the entire class of comparator drugs taken as a whole, compared with H2-antagonists. On considering the non-H2-antagonists singly, this conclusion holds good only in the case of tripotassium dicitrato bismuthate.

Anti-Ulcer Agents↗