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A Walan

Publications and source records attributed to A Walan.

At least 19 recordsLinked to original sources
PubMed2001

Quality of life in chronic NSAID users: a comparison of the effect of omeprazole and misoprostol.

OBJECTIVE: To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions. METHODS: Validated baseline and follow-up QoL questionnaires were completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6 months). RESULTS: Patients with arthritis being treated with NSAIDs have a poor QoL. Rheumatoid arthritis causes more joint problems and physical mobility limitations than osteoarthritis. Chronic NSAID use causes heartburn and dyspepsia. QoL improved on both treatments (about equally on two general QOL scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol, particularly reflux, abdominal pain and indigestion symptoms. During maintenance, both treatments maintained QoL, but misoprostol induced diarrhoea. CONCLUSION: QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is superior to misoprostol for relief and prevention of NSAID-associated gastrointestinal symptoms allowing continued NSAID treatment without compromising the patients' QoL.

Adolescent↗
PubMed2000

Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa.

BACKGROUND & AIMS: The efficacy and safety of long-term acid suppression remains a subject for debate. We report data from patients with refractory reflux esophagitis who were undergoing maintenance therapy with >/=20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4-11.2 years). METHODS: Patients with severe reflux esophagitis resistant to long-term therapy with H(2)-receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus. RESULTS: In 230 patients (mean age, 63 years at entry; 36% were >/=70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori-positive and -negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus intestinal metaplasia was rare, and no dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients. CONCLUSIONS: Long-term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis.

Adolescent↗
PubMed2000

Changing patterns of Helicobacter pylori gastritis in long-standing acid suppression.

BACKGROUND: Helicobacter pylori colonization and associated inflammation are influenced by local acid output. Infected subjects with acid-related diseases, such as gastroesophageal reflux disease (GERD) are likely to have an antral-predominant gastritis. We hypothesized that long-term acid suppression would result in relatively greater bacterial colonization in the corpus leading to diffuse or corpus-predominant gastritis and that this would be prevented by prior H. pylori eradication. MATERIALS AND METHODS: To investigate this, we conducted a prospective, double-blind trial of the effect on gastric histology of 12-month maintenance treatment with omeprazole in H. pylori-positive GERD patients randomly assigned to either an eradication or omeprazole-alone regime. A control group of 20 H. pylori-negative GERD patients also received omeprazole throughout the study period. Biopsies taken at baseline and at 12 months were graded "blind" by a single observer according to the updated Sydney System. The 41 H. pylori-positive subjects with grade B or C esophagitis were randomly assigned (20 to omeprazole alone, 21 to eradication) and 33 subjects completed the 12-month study. RESULTS: There was a significant decline in antral chronic inflammation in initially positive patients between baseline and end in both the eradication group (p =.035) and the omeprazole-alone group (p =.008). However, corpus chronic inflammation increased in the omeprazole-alone group (p =.0156) but decreased in the eradication group. The change toward corpus predominance between baseline and end for the omeprazole-alone group is highly significant (p =.0078). Furthermore, 5 of 11 in the omeprazole-alone group developed mild corpus atrophy, compared to 0 of 8 who had undergone H. pylori eradication. The change in frequency of corpus atrophy between the two groups is significant (p =.02). CONCLUSION: In H. pylori-positive subjects with GERD, long-term acid suppression leads to a shift from antral- to corpus-predominant gastritis that can be prevented by prior eradication. The shift is accompanied by an increase in corpus atrophy. H. pylori infection should be eradicated prior to long-term acid suppression with proton pump inhibitors.

Adolescent↗
PubMed1999

Omeprazole and ranitidine in the prevention of relapse in patients with duodenal ulcer disease.

BACKGROUND: Although the eradication of Helicobacter pylori is of primary importance when initiating treatment, it is also important to have a strategy for patients who are H pylori-negative, fail to demonstrate eradication or have a tendency to become re-infected or relapse. PATIENTS AND METHODS: In a double-blind, parallel-group clinical trial of 928 patients (from 70 centres in 16 countries) with duodenal ulcers who after a short term study had relief of symptoms and healed ulcers proved endoscopically, 308 were randomly assigned to receive omeprazole 10 mg in the morning, 308 to receive omeprazole 20 mg in the morning and 312 to receive ranitidine 150 mg at bedtime for up to 12 months. Symptoms were assessed every three months and endoscopy repeated at three, six and 12 months, or more often if indicated by recurrence of symptoms. The safety screening included basal serum gastrin concentrations and gastric mucosal histopathology. RESULTS: The remission rates up to 12 months were 87% for the omeprazole 20 mg group, 71% for the omeprazole 10 mg group and 63% for the ranitidine group. Omeprazole 20 mg differed significantly from both omeprazole 10 mg (P=0.0001, 95% CI 9 to 23) and ranitidine (P=0.0001, 95% CI 17 to 31). There was no statistically significant difference between omeprazole 10 mg and ranitidine over the 12-month period, but the 95% confidence interval allowed differences between 0% and 16% in favour of omeprazole at 12 months. A Cox regression analysis revealed that longer treatment courses to heal, smoking, a long ulcer history and young age negatively contributed to the odds of staying in remission. The treatments were well tolerated. There was a slight increase in basal serum gastrin concentrations, reflecting the different degrees of acid inhibition induced by the three treatments. No dysplastic or neoplastic lesions were found in any biopsies. CONCLUSIONS: More duodenal ulcer patients are maintained in remission with omeprazole 20 mg daily than with omeprazole 10 mg daily or with ranitidine 150 mg at bedtime.

Adolescent↗
PubMed1999

Pharmacoeconomic aspects of non-steroidal anti-inflammatory drug gastropathy.

Non-steroidal anti-inflammatory drugs are commonly used to reduce inflammation and pain associated with arthritis. However, non-steroidal anti-inflammatory drugs induce gastrointestinal side-effects such as dyspeptic symptoms, duodenal or gastric ulcers and, in some cases, serious complications. The aim has been to compare the benefits with the drawbacks of non-steroidal anti-inflammatory drug treatment using a hypothetical population representing patients with arthritis. A problem description was made on the basis of a literature review, and a simple and hypothetical health economic model was constructed. Including direct and indirect costs, the annual total costs in Sweden for gastrointestinal side-effects per non-steroidal anti-inflammatory drug user were estimated to be 3,420 SEK (438 US$), and the approximated costs of arthritis were 60,000 SEK (7,692 US$). The benefits of non-steroidal anti-inflammatory drug treatment were found to outweigh the drawbacks if the patient's arthritis symptoms, expressed as a difference in utility value between having and not having symptoms of arthritis, are improved by 6% or more. Costs for non-steroidal anti-inflammatory drug-induced gastrointestinal side-effects should be evaluated in relation to the benefits of non-steroidal anti-inflammatory drugs in the treatment of inflammation and pain. A simple modelling approach indicated that treatment with non-steroidal anti-inflammatory drugs may be highly cost-effective as both the clinical and economic benefits for patients responding to such treatment out-weighed possible drawbacks.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole.

AIMS: To study the pharmacokinetics of three proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole, as well as any potential influence on CYP1A2 activity (measured by means of rate of caffeine metabolism) of these compounds at single dose and repeated dose administration. METHODS: Fourteen healthy males, classified as 12 extensive metabolizers (EMs) and two poor metabolizers (PMs) according to the urinary S/R mephenytoin ratio, completed this open, randomized, three-way cross-over study. In each of the three 7-day treatment periods either omeprazole (20 mg), lansoprazole (30 mg) or pantoprazole (40 mg) in therapeutically recommended doses was administered once daily, and the pharmacokinetics of the proton pump inhibitors as well as the rate of caffeine metabolism was measured on days 1 and 7. RESULTS: In the EMs there was an increase in AUC from day 1 to day 7 for omeprazole. In the PMs the AUC of both omeprazole and lansoprazole was unchanged during repeated dosing, while for pantoprazole there was a tendency to a slight decrease. The AUC at steady state was for all three proton pump inhibitors 5 fold higher in PMs compared with EMs, indicating that the same proportion of the dose, irrespective of compound, is metabolized by CYP2C19. No induction of CYP1A2 was evident for any of the compounds in either EMs or PMs. CONCLUSIONS: The approximately 5 fold difference in AUC between EMs and PMs indicates that approximately 80% of the dose for all three proton pump inhibitors is metabolized by the polymorphically expressed CYP2C19. None of the three proton pump inhibitors, administered in therapeutically recommended doses, is an inducer of CYP1A2--neither in PMs nor in EMs.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Pathophysiological effects of long-term acid suppression in man.

A critical evaluation has been made of the available evidence in man of the effects of prolonged low acid states on the structure and function of the stomach. Various human models have been examined. 1. Ageing does not affect acid output from the normal male stomach, and there may be an increase in women. With progressive atrophy of the corpus mucosa, which is more frequent and rapid in patients with gastric ulcer, there is an associated loss of secretory function. Chronic gastritis and atrophy are the most important age-related changes, which in many cultures are hypothesized to develop via a prior Helicobacter pylori-related gastritis. However, H. pylori colonization of the mucosa decreases with increasing grades of gastric atrophy probably because intestinal metaplasia provides a hostile environment. Atrophy and intestinal metaplasia are associated with precancerous lesions and gastric cancer. Apparent hyperplasia of the gastric argyrophil endocrine cells is a common and spontaneous phenomenon in patients with atrophic gastritis, which in part may be related to the preferential loss of nonendocrine cells. 2. Pernicious anemia is associated with a complete lack of acid production, marked hypergastrinemia, and endocrine cell hyperplasia in the majority of patients. ECL-cell carcinoids and gastric cancer occur with a prevalence of 3-7%, and endoscopic surveillance in routine clinical practice is not warranted. 3. Gastric ECL-cell carcinoids are rare events that have been described in association with two diseases in man, pernicious anemia and Zollinger-Ellison syndrome as part of multiple endocrine neoplasia syndrome type I, and usually relate to marked hypergastrinemia and the presence of chronic atrophic gastritis with gastric antibodies or a genetic defect rather than the presence or absence of acid. Regression or disappearance of ECL-cell carcinoids, either spontaneously or after removal of the gastrin drive, has been recorded. Lymph node, and rarely hepatic, metastases are documented but death in these cases has been anecdotal. 4. Therapy with H2 antagonists may result in up to a twofold rise in serum gastrin levels but in man no endocrine cell hyperplasia has been recorded. However, the data for H2 antagonists on these aspects are very limited. There is no drug-related risk of gastric or esophageal cancer, although the incidence of the latter may be raised. Long-term treatment with omeprazole is associated with a two- to fourfold increase in gastrin levels over baseline values in one third of patients and apparent endocrine cell hyperplasia in 7% of cases overall.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1994

Long-term consequences with regard to clinical outcome and cost-effectiveness of episodic treatment with omeprazole or ranitidine for healing of duodenal ulcer.

The clinical outcome and cost-effectiveness of episodic treatment of duodenal ulcer with omeprazole and ranitidine were evaluated over a 5-year period. The analysis was based on data from published clinical trials comparing healing rates obtained with omeprazole and with ranitidine, as well as on data from the literature on ulcer recurrence and other clinical events. Patients with an active duodenal ulcer were treated until healed or for a maximum of 24 weeks. Maintenance therapy was instituted in patients with ulcers that were very slow to heal and in patients with frequent relapses after cessation of treatment. Patients who experienced frequent relapses while receiving maintenance therapy, and those whose ulcer had not healed after 24 weeks of continuous treatment, were defined as candidates for surgery. A statistical model was set up and a random number generator used to generate a sequence of clinical events, month by month, over a 5-year period for each patient in a large cohort. Episodic treatment with omeprazole was shown to be more effective in avoiding maintenance treatment and surgery when compared with episodic treatment with ranitidine. Patients who received episodic treatment with omeprazole also spent more time in remission from disease. Using current Swedish cost data, it was found that episodic treatment with omeprazole was more cost-effective than episodic treatment with ranitidine.

Cost-Benefit Analysis↗
PubMed1992

Safety experience from long-term treatment with omeprazole.

Omeprazole was administered for up to 6 years in 859 patients for 'prevention of relapse in patients with poorly responsive peptic ulcer or reflux oesophagitis'. The pattern of adverse events reported during long-term treatment was similar to the adverse-event profile in short-term treatment with omeprazole (n = 2,818), ranitidine (n = 1,572) and cimetidine (n = 891). Omeprazole had essentially the same adverse-event profile as the two H2-receptor antagonists. The adverse-event profile for omeprazole during long-term treatment did not differ from that seen during short-term treatment with either omeprazole or the H2-receptor antagonists. The rate of occurrence of any specific adverse event decreased with time, and no previously unidentified adverse event occurred with long-term omeprazole therapy. There were no serious adverse events that were considered to be causally related to omeprazole therapy. Thus, omeprazole has been shown to be well tolerated in both short- and long-term treatment.

Adolescent↗
PubMed1992

Phagocyte killing of Campylobacter jejuni in relation to oxidative activation.

When studying the interaction between Campylobacter jejuni and human neutrophils, we found that four different clinical isolates showed a great variability in this association. Also the ability to induce neutrophil production of oxidative metabolites, measured as chemiluminescence (CL), differed between the strains. Surprisingly, strain 1, which showed weak interaction with neutrophils and high resistance to killing, induced the highest CL response. All strains evoked an intracellular CL response, and three strains also gave rise to an extracellular response. This extracellular release of toxic oxygen species might contribute to the local tissue damage during infection. There was no clear correlation between association, killing and oxidative response. However, one strain that only evoked an intracellular generation of oxygen metabolites also showed the highest sensitivity to killing. Phagocytosis was increased up to ten times after opsonization with normal human serum. The intracellular CL production increased several fold, whereas the extracellular generation of oxygen species disappeared or was considerably decreased after opsonization. These results indicate that complement-opsonized C. jejuni are phagocytosed and readily attacked by the oxidative defence system within the phagosome.

Campylobacter jejuni↗
PubMed1990

Intravenous omeprazole: effect of a loading dose on 24-h intragastric pH.

To determine the effect of three times daily dosing with intravenous omeprazole on intragastric acidity, 24 h intragastric pH was measured continuously with a monocrystalline antimony electrode system in II patients with inactive duodenal ulceration during fasting conditions. After a baseline investigation, two different dosage regimens of intravenous omeprazole were compared in a double-blind crossover study, with regard to their ability to keep the pH greater than or equal to 4 for as long as possible. Success in the individual patient was defined as pH greater than or equal to 4 for at least 90% over the 24-h period. Two doses of omeprazole [40 mg t.d.s. (120 mg) and 80 mg + 40 mg + 40 mg (160 mg)] were compared. Omeprazole (120 mg) increased the median of individual median intragastric 24-h pH from 1.49 to 6.67. The pH was greater than or equal to 4 for greater than or equal to 90% of the 24 h in three of the 11 patients. With omeprazole, 160 mg (a loading dose of 80 mg), the median of individual median intragastric 24-h pH increased to 7.33. The pH was greater than or equal to 4 for greater than or equal to 90% of the 24 h in seven of the 11 patients. Median time to reach pH 4 was 39 min after 40 mg and 20 min after 80 mg omeprazole. An initial loading dose of 80 mg omeprazole seems preferable to 40 mg to achieve a fast and sustained increase in intragastric pH to above 4 in the fasting patient.

Adult↗
PubMed1990

Clinical development programme for omeprazole.

Omeprazole has been shown to provide more rapid symptom relief and to heal ulcers more quickly and reliably than H2-receptor antagonists in duodenal ulcer, gastric ulcer and reflux oesophagitis. In addition, omeprazole is well tolerated and has a good safety profile. Among the areas for clinical development with omeprazole are the maintenance treatment of duodenal ulcer, treatment of non-steroidal anti-inflammatory drugs (NSAID)-induced gastro-duodenal lesions, maintenance treatment of reflux oesophagitis and the treatment of bleeding ulcer. Two studies of patients with duodenal ulcer have shown that maintenance treatment with omeprazole, 10 mg once daily, was as effective as, or superior to, treatment with omeprazole, 20 mg given on Friday, Saturday and Sunday only, and markedly superior to placebo. In patients with gastric ulcer which developed during treatment with NSAIDs omeprazole, 20 mg once daily, resulted in a higher healing rate than ranitidine, 150 mg b.i.d., both at 4 and at 8 weeks. Reflux oesophagitis is often a persistent condition requiring continuous maintenance treatment. In a recent multicentre trial, a substantially higher proportion of patients remained in remission with omeprazole, 20 mg once daily, than with ranitidine, 150 mg b.i.d. Studies comparing omeprazole and ranitidine (administered intravenously) in patients with bleeding peptic ulcers have also demonstrated the superiority of omeprazole with regard to the control of bleeding and the avoidance of surgery. Further studies are currently underway in this and other related areas.

Drug Administration Schedule↗
PubMed1989

Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer.

Omeprazole blocks the action of H+,K+-ATPase in the gastric mucosa and thus inhibits the secretion of hydrochloric acid. We conducted a double-blind multicenter study (45 centers in 13 countries) of 602 patients with benign gastric or prepyloric ulcers to compare the effectiveness of omeprazole (20 mg once daily, 203 patients, or 40 mg once daily, 194 patients) and ranitidine, an H2-receptor antagonist (150 mg twice daily, 205 patients) in promoting ulcer healing and to evaluate the pattern of ulcer relapse during a six-month follow-up. Healing occurred at four weeks in 80 percent of the patients receiving 40 mg of omeprazole, 69 percent of those receiving 20 mg of omeprazole, 69 percent of those receiving ranitidine. At eight weeks, the corresponding figures were 96, 89, and 85 percent. A multivariate analysis of ulcer healing showed that at four weeks the ulcers of significantly more patients receiving omeprazole had healed as compared with patients receiving ranitidine (omeprazole, 40 mg, vs. ranitidine, P less than 0.0005; omeprazole, 20 mg, vs. ranitidine, P = 0.01). At eight weeks, the 40-mg dose of omeprazole was significantly more effective than ranitidine (P = 0.001) or the 20-mg dose of omeprazole (P = 0.03). Ulcer symptoms were relieved faster with omeprazole. In 68 patients receiving concurrent nonsteroidal antiinflammatory drugs, the healing rates at four weeks were 81 percent in the group receiving 40 mg of omeprazole, 61 percent in the group receiving 20 mg, and 32 percent in the group receiving ranitidine; at eight weeks, the corresponding figures were 95, 82, and 53 percent. During the six-month follow-up period (without treatment), significantly more patients in the omeprazole groups were free of symptoms and ulcers than in the ranitidine group. We conclude that in the dose used, omeprazole is superior to ranitidine in the treatment of benign gastric ulcers.

Adult↗
PubMed1989

The clinical utility and safety of omeprazole.

More than 13,000 individuals with duodenal ulcer, gastric ulcer or reflux oesophagitis have now taken part in controlled clinical studies with omeprazole. In duodenal ulcer, treatment with omeprazole, 20 mg daily or more, has resulted in healing rates of 58%-83% after 2 weeks and 84%-100% after 4 weeks. In all of these studies, healing rates with omeprazole have been higher than with either ranitidine or cimetidine. Omeprazole has also had a more pronounced effect on ulcer symptoms. Although the first comparative study on gastric ulcer showed only marginally higher healing rates with omeprazole than with an H2-receptor antagonist, later studies have all shown significantly higher healing rates with omeprazole. Healing rates of the order of 70% or more have been achieved within 4 weeks, rising to over 88% after 8 weeks. Symptom relief has also been faster with omeprazole. In both duodenal ulcer and gastric ulcer, almost every patient can be healed, including those resistant to treatment with H2-receptor antagonists. The influence of omeprazole on the healing of reflux oesophagitis has been investigated in several studies comparing omeprazole with ranitidine. Healing rates have been markedly higher with omeprazole in all studies. These unprecedentedly high healing rates (81%-96% at 8 weeks) have also been accompanied by rapid symptom relief. In clinical studies with omeprazole, no clinically significant side-effects which could be ascribed to treatment, nor indeed any serious side-effects, have been observed, neither have any clinically significant changes in laboratory variables been seen. Furthermore, no pathological changes of the gastric mucosa have been detected after long-term treatment with omeprazole.

Duodenal Ulcer↗
PubMed1989

Clinical experience with omeprazole: assessment of efficacy and safety.

After pharmacological studies showed that omeprazole had a marked and longlasting inhibitory effect on acid secretion, many clinical studies commenced. In duodenal ulcer, omeprazole in doses of 20-40 mg/day has been shown to give significantly higher healing rates than ranitidine or cimetidine. Omeprazole has given healing rates of 58-83% after treatment for 2 weeks and 84-100% after 4 weeks. A more pronounced effect on the relief of ulcer symptoms has also been observed. Similarly, in gastric ulcer several studies have been performed, all of which have shown higher healing rates with omeprazole both at 4 and 8 weeks. Symptom relief has also been faster and more pronounced with omeprazole. In patients with reflux oesophagitis, omeprazole has been shown to decrease the time with an acid milieu in the oesophagus. In several studies omeprazole in doses of 20-60 mg/day has consistently given healing rates approximately twice those of ranitidine in doses of 150 mg twice daily at 4 and 8 weeks. In addition, there has been a rapid improvement in the symptoms of oesophagitis. Omeprazole has been found to be very effective in the Zollinger-Ellison syndrome, with a prompt effect on acid secretion and symptoms. The accumulated experience exceeds 300 patients. More than 13,000 patients have taken part in the clinical investigations with omeprazole. Neither serious side-effects nor other side-effects which could be ascribed to treatment have been observed. There have not been any clinically significant changes in laboratory variables apart from those which are caused by the decrease in acid secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenal Ulcer↗
PubMed1989

Clinical utility and safety of omeprazole.

Omeprazole inhibits H+,K+-ATPase, the enzyme responsible for the exchange of H+ and K+ in the final step in the acid secretory process within the parietal cell. It has been shown to produce a marked and long-lasting inhibition of acid secretion with a decrease in 24-hour intragastric acidity after repeated daily dosing. Omeprazole has been shown to give significantly higher healing rates than ranitidine or cimetidine in patients with duodenal ulcer and gastric ulcer. Similarly, a more pronounced effect on ulcer symptoms has been observed. In patients with reflux esophagitis, omeprazole has been shown to decrease the time with an acid milieu in the esophagus. Omeprazole has consistently given about twice as high healing rates and faster decrease in symptoms than with ranitidine. In patients with Zollinger-Ellison syndrome, omeprazole has been found to have a rapid and long-lasting effect on acid secretion and acid-induced symptoms.

Animals↗
PubMed1988

Omeprazole.

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Clinical Trials as Topic↗