Evaluation of omeprazole as a cost-effective diagnostic test for gastro-oesophageal reflux disease.

BACKGROUND: There is a need for a simple, therapeutic test that is of diagnostic value and can also provide rapid symptom relief in patients who present with classic, mild symptoms suggestive of gastro-oesophageal reflux disease (GERD), when the diagnosis is based on symptom assessment alone. AIM: To assess the diagnostic value of a therapeutic trial of omeprazole 40 mg in a dyspeptic population. METHODS: A total of 90 patients with symptoms suggestive of GERD entered the study. Patients underwent endoscopy and ambulatory oesophageal pH monitoring for 18-24 h. Patients then received omeprazole 40 mg o.m. for 2 weeks. RESULTS: There was a significant correlation between the diagnoses obtained from a trial of omeprazole and the diagnoses obtained from pH monitoring (P < 0. 05). There was no significant correlation between the diagnoses obtained from endoscopy and those obtained from pH monitoring. Both omeprazole and endoscopy were compared to pH monitoring as the 'gold standard' for the diagnosis of GERD and the cost per correct diagnosis with omeprazole was pound47 (95% CI: pound40- pound59) compared to pound480 (95% CI: pound396- pound608) with endoscopy. There was a complete absence of acid-related symptoms in the majority (59%) of patients after 3 days of omeprazole 40 mg therapy and, after 2 weeks, 82% of patients had experienced an improvement in overall symptoms ( 1 grade). CONCLUSIONS: We conclude that omeprazole can be used as a clinically effective tool in the initial management of GERD and that it is of diagnostic value in patients who present with typical symptoms, such as heartburn, when the diagnosis is based on symptom assessment alone.

Omeprazole is more effective than cimetidine in the prevention of recurrence of GERD-associated heartburn and the occurrence of underlying oesophagitis.

BACKGROUND: There is documentation of the long-term use of omeprazole 10 mg o.d. in patients with reflux oesophagitis but not in the large number of gastrooesophageal reflux disease (GERD) patients without oesophagitis. There is also a paucity of data on the long-term use of cimetidine in GERD patients. METHODS: One hundred and fifty-six patients (100 male) who previously had symptomatic non-ulcerative oesophagitis (81%) or symptoms without oesophagitis (19%), were recruited. All patients were in symptomatic remission following 4 weeks of omeprazole 20 mg o.d. or cimetidine 400 mg q.d.s. and, if required, a further 4 weeks of omeprazole 20 mg o.d. Patients were randomized to receive, double-blind, either omeprazole 10 mg o.m. (n = 77) or cimetidine 800 mg nocte (n = 79) for 24 weeks. RESULTS: A greater proportion of patients receiving omeprazole, compared with cimetidine, were in symptomatic remission after 12 (69 vs. 27%) and 24 weeks (60 vs. 24%) (each P < 0.0001). The median time to symptomatic relapse was longer for patients receiving omeprazole (169 vs. 15 days) (P = 0.0001). Of patients leaving the study in symptomatic remission, a greater proportion receiving omeprazole, compared with cimetidine, was free of oesophagitis (84 vs. 53%) (P < 0.05). CONCLUSION: Omeprazole 10 mg o.m. is more effective than cimetidine 800 mg nocte in the prevention of recurrence of GERD-associated heartburn and the occurrence of underlying oesophagitis.

Omeprazole is more effective than cimetidine for the relief of all grades of gastro-oesophageal reflux disease-associated heartburn, irrespective of the presence or absence of endoscopic oesophagitis.

BACKGROUND: Previous studies have demonstrated greater efficacy for omeprazole compared with cimetidine in patients with endoscopically verified oesophagitis, but excluded the substantial group of gastro-oesophageal reflux disease (GERD) patients with reflux symptoms but without endoscopic abnormality. This prospective, randomized, double-blind study compared omeprazole and cimetidine in the treatment of GERD-associated heartburn both in patients with symptomatic non-ulcerative oesophagitis and in those with heartburn but without oesophagitis. METHODS: A total of 221 patients with heartburn and oesophageal mucosa grade 0 (normal, n = 51), 1 (no macroscopic erosions, n = 52), 2 (isolated erosions, n = 97) or 3 (confluent erosions, n = 21) were randomized to receive double-blind either omeprazole 20 mg daily or cimetidine 400 mg q.d.s. for a period of 4 weeks. Those still symptomatic after 4 weeks of treatment received omeprazole 20 mg daily for a further 4 weeks. RESULTS: There was no correlation between severity of heartburn and endoscopic grade at entry (correlation coefficient = 0.196). After 4 weeks of treatment, the proportion of patients in whom heartburn was controlled (no more than mild symptoms on no more than 1 day in the previous 7) on omeprazole (66%; 74/112) was more than double that on cimetidine (31%; 34/109) (P < 0.0001). There was no significant difference between the relief of heartburn in the 47% of patients without unequivocal oesophagitis (endoscopic grade 0 or 1) and in the 53% of patients with erosive oesophagitis (grade 2 or 3) (P = 0.31). Only treatment with omeprazole (P < 0.0001) and lower severity of heartburn at entry (P < 0.01) were significant in predicting heartburn relief. Amongst those patients requiring an additional 4 weeks of treatment with omeprazole, 67% (54/81) reported that their heartburn was controlled after 8 weeks of treatment. CONCLUSION: We conclude that omeprazole is superior to cimetidine for the relief of all grades of heartburn in GERD, whether or not the patient has unequivocal endoscopic oesophagitis.

Reflux symptom relief with omeprazole in patients without unequivocal oesophagitis.

BACKGROUND: As many as 50% of patients with reflux symptoms have no endoscopic evidence of oesophagitis. This multicentre study was designed to assess symptom relief after omeprazole 20 mg once daily in patients with symptoms typical of gastro-oesophageal reflux disease but without endoscopic evidence of oesophagitis. METHODS: Patients (n = 209) were randomized in a double-blind study to receive either omeprazole 20 mg once daily (n = 98) or placebo (n = 111) for 4 weeks. Symptoms were assessed at clinic visits and using daily diary cards, with patient-completed questionnaires providing additional data on symptoms and on psychological disturbance. RESULTS: On completion, symptom relief favoured omeprazole: 57% of patients on omeprazole were free of heartburn (vs. 19% on placebo), 75% were free of regurgitation (47%) and 43% were completely asymptomatic (14%), each with P < 0.0001. Fewer patients in the omeprazole group required alginate/antacid relief medication (P < 0.05). Symptom relief (time to first heartburn-free day) was more rapid with omeprazole (2 vs. 5 days on placebo; P < 0.01). A greater reduction in anxiety occurred in the omeprazole group (P < 0.05). CONCLUSION: Omeprazole 20 mg once daily is effective in providing relief of the symptoms typical of gastro-oesophageal reflux disease in patients with essentially normal oesophageal mucosa.

Symptomatic and endoscopic duodenal ulcer relapse rates 12 months following Helicobacter pylori eradication treatment with omeprazole and amoxycillin with or without metronidazole.

AIM: To determine the effect of Helicobacter pylori eradication with omeprazole and amoxycillin, with or without metronidazole, on the 12-month course of duodenal ulcer disease. METHODS: In a randomized; double-blind study, conducted in 19 hospitals, 105 H. pylori positive duodenal ulcer patients were healed and symptom-free following either omeprazole dual therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s., OA, eradication rate 46%, n = 52) or omeprazole triple therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s.+metronidazole 400 mg t.d.s., OAM, eradication rate 92%, n = 53) for 2 weeks, followed by 2 weeks of omeprazole 20 mg o.m. and a 12-month untreated follow-up period, after which time all patients were endoscoped. Endoscopic and symptomatic relapse rates, and effect on H. pylori status measured using 13C-urea breath test, were determined. RESULTS: During the 12-month untreated follow-up period, the life-table endoscopic relapse rates were 12% (95% CI: 2-22%) and 2% (95% CI: 0-6%) for OA and OAM patients, respectively. By 12 months, life-table symptomatic relapse rates were 22% (95% CI: 13-37%) and 19% (95% CI: 8-30%) for OA and OAM, respectively. In the 12 months untreated follow-up period, 2/69 (3%, 95% CI: 0-7%) patients rendered H. pylori negative had an endoscopic relapse at the end of the 12-month follow-up period, compared with 5/31 (16%, 95% CI: 3-29%) patients remaining H. pylori positive (P = 0.03 between H. pylori positive and negative groups). Twelve of 69 (17%, 95% CI: 8-26%) patients rendered H. pylori negative relapsed symptomatically, compared with 9/31 (29%, 95% CI: 13-45%) patients remaining H. pylori positive (P = N.S. between groups). There was a significant improvement in epigastric pain (P = 0.0001), nausea and vomiting (P < 0.05) between entry to the study and 1, 6 and 12 months post-treatment for both treatment groups. CONCLUSIONS: OAM eradicates H. pylori in significantly more patients than OA, but successful H. pylori eradication with either OAM or OA predisposes to low endoscopic and symptomatic relapse rates for duodenal ulcer patients when followed up for 12 months.

Addition of metronidazole to omeprazole/amoxycillin dual therapy increases the rate of Helicobacter pylori eradication: a double-blind, randomized trial.

AIMS: To compare the efficacy, safety and tolerability of an omeprazole/amoxycillin (OA) dual therapy Helicobacter pylori eradication regimen with an omeprazole/amoxycillin/metronidazole (OAM) triple therapy regimen. METHODS: In this double-blind trial, conducted in 19 hospitals, 119 patients with symptomatic duodenal ulcer disease were randomized to receive either 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and placebo followed by a further 14 days' treatment with omeprazole 20 mg daily (n = 59) or 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s., followed by a further 14 days' treatment with omeprazole 20 mg daily (n = 60). H. pylori status was assessed by 13C-urea breath test at entry and at 4 weeks post-treatment. RESULTS: H. pylori infection was eradicated in 46% of the OA treated patients and in 92% of the OAM treated patients, a mean difference of 46% (P < 0.0001, 95% CI for the difference: +30 to +62). In only one patient was the duodenal ulcer not endoscopically healed after 4 weeks of treatment (OA 100%; OAM 98% healed). There were no significant differences in speed of symptom relief or improvement in symptoms between the two groups. Both regimens were well tolerated, with 96% of patients completing the course, and only one patient withdrawing due to an adverse event. The only side-effect with a significantly higher incidence in the OAM group was diarrhoea, which occurred in 36% of patients compared to 16% of patients in the OA group (P < 0.05). CONCLUSIONS: A regimen consisting of omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. for 14 days gives an appreciably higher H. pylori eradication rate than omeprazole and amoxycillin alone, with acceptable tolerability.

Omeprazole 10 mg or 20 mg once daily in the prevention of recurrence of reflux oesophagitis. Solo Investigator Group.

This study determined the optimal maintenance dose of omeprazole in reflux oesophagitis. One hundred and ninety three patients rendered asymptomatic and healed after four or eight weeks omeprazole were randomised double blind to 10 mg omeprazole once daily (n = 60 evaluable), 20 mg omeprazole once daily (n = 68), or placebo (n = 62) for one year or until symptomatic relapse. Each omeprazole regimen was superior to placebo in preventing both symptomatic relapse (life table analysis, p < 0.001) and endoscopically verified relapse (p < 0.001). At 12 months, the life table endoscopic remission rates (proportions of patients without grade > or = 2 oesophagitis) were: 50% (95% confidence intervals 34 to 66%) with 10 mg omeprazole once daily, 74% (62 to 86%) with 20 mg omeprazole once daily, and 14% (2 to 26%) with placebo. At 12 months, the life table symptomatic remission rates (proportions of patients asymptomatic or with mild symptoms) were: 77% (64 to 89%) with 10 mg omeprazole once daily, 83% (73 to 93%) with 20 mg omeprazole once daily, and 34% (16 to 52%) with placebo. Both 10 mg and 20 mg omeprazole once daily were effective in prolonging the remission of reflux oesophagitis: 10 mg may be appropriate to start longterm treatment, though the existence of a dose response relation means that 20 mg once daily may be effective in patients for whom 10 mg once daily is suboptimal.

A comparison of omeprazole and ranitidine in the prevention of recurrence of benign esophageal stricture. Restore Investigator Group.

BACKGROUND/AIMS: Dilatation combined with subsequent pharmacological control of gastroesophageal reflux represents a logical but poorly documented approach to the management of benign esophageal stricture. This large trial (366 patients) aimed to assess whether omeprazole as the most effective available medication for gastroesophageal reflux disease prevents recurrent stricture formation. METHODS: Patients (n = 366) were randomized in a double-blind study to undergo either omeprazole (20 mg once daily; 180 evaluable patients) or ranitidine therapy (150 mg twice daily; 185 evaluable patients) for 1 year after dilatation to 12-18-mm diameter (36-54F gauge). Subsequently, endoscopy and dilatation were performed when clinically indicated and endoscopy on completion. Symptoms were assessed at clinic visits every 3 months and using weekly diary cards. RESULTS: Fewer patients undergoing omeprazole therapy required redilatation compared with those on ranitidine (43 of 143 [30%] vs. 66 of 143 [46%] by 12 months; P < 0.01), and patients in the omeprazole group needed fewer redilatations during the year (0.48 vs. 1.08; P < 0.01). On completion, symptom relief favored omeprazole: 76% of patients in the omeprazole group were free of dysphagia (compared with 64% in the ranitidine group; P < 0.05); 83% were able to accept a normal diet (69%; P < 0.01); and 65% were completely asymptomatic (43%; P < 0.001). CONCLUSIONS: Omeprazole, 20 mg once daily, was more effective than ranitidine, 150 mg twice daily, as prophylaxis against stricture recurrence and in providing symptom relief.

Does 40 mg omeprazole daily offer additional benefit over 20 mg daily in patients requiring more than 4 weeks of treatment for symptomatic reflux oesophagitis?

This study was designed to establish whether 40 mg omeprazole once daily exhibits sufficient additional efficacy over that of 20 mg omeprazole once daily in patients with symptomatic reflux oesophagitis requiring more than an initial 4-week course of 20 mg omeprazole once daily (o.m.) to warrant routine use of the higher dose. Three hundred and thirteen patients were randomized to receive either 20 mg omeprazole (4 weeks) then 20 mg (second 4 weeks if not both healed and symptom-free after 4 weeks), or 20 mg omeprazole (4 weeks) then 40 mg omeprazole o.m. (second 4 weeks). One hundred and twenty-seven patients were healed and symptom-free after 4 weeks and left the study at that point. Taking the second treatment period in isolation, the healing rate (64% vs. 45%, P < 0.02) and relief of heartburn (72% vs. 60%, P < 0.002) were greater among patients receiving 40 mg omeprazole o.m., demonstrating the existence of a dose-response relationship for omeprazole. However, on completion, there were no significant differences between the patients randomized to the 20/20 mg (healed 65%, asymptomatic 69%) or the 20/40 mg (healed 74%, asymptomatic 74%: both not significant differences compared with 20/20 mg) regimens. The magnitude of the difference in efficacy between 20 and 40 mg omeprazole in symptomatic reflux oesophagitis is insufficient to warrant the routine use of 40 mg in patients requiring more than 4 weeks' treatment with 20 mg omeprazole o.m.; continued treatment with 20 mg omeprazole for 4-8 weeks is the preferred option.

Comparison of omeprazole and cimetidine in reflux oesophagitis: symptomatic, endoscopic, and histological evaluations.

Symptomatic patients with endoscopically verified reflux oesophagitis were randomised to a double blind trial in which they received either omeprazole (20 mg once daily) or cimetidine (400 mg four times daily) for four, and if necessary, eight weeks. In an 'intention to treat' analysis, oesophagitis was found to have healed after four weeks in 77 of 137 (56%) in the omeprazole group and in 34 of 133 (26%) in the cimetidine group (p less than 0.001). By eight weeks these values were 71% and 35% respectively; p less than 0.001. Histological assessments were available for 73% of the patients. At entry, 63% (66 of 104) in the omeprazole group and 60% (56 of 94) in the cimetidine group (ns) had abnormal histology. After the study, the proportions of patients who initially had had abnormal histology but who then progressed to normal were 67% (44 of 66: omeprazole) and 48% (27 of 56: cimetidine) respectively (p less than 0.001). All patients had reflux symptoms at entry. After four weeks, 46% in the omeprazole group and 22% (p less than 0.001) in the cimetidine group were asymptomatic. Diary cards completed for the first two weeks showed that patients treated with omeprazole experienced fewer reflux symptoms by day and night and used fewer antacids. Omeprazole, 20 mg once a day for four to eight weeks, healed a greater proportion of patients with reflux oesophagitis than cimetidine, 1.6 g per day, assessed endoscopically and histologically, and relieved more patients' symptoms.

Randomised, double blind comparison of omeprazole and cimetidine in the treatment of symptomatic gastric ulcer.

In a randomised, double blind, parallel group study in patients with symptomatic gastric ulcer (94% greater than or equal to 5 mm diameter), 102 received omeprazole 20 mg om and 87 cimetidine 400 mg bd. After four weeks 73% and 58% (p less than 0.05) respectively had healed (eight weeks: 84% and 75%, ns). After four weeks, a greater proportion (81%) of omeprazole treated patients was symptom free than of those receiving cimetidine (60%; p less than 0.01). Over the first two weeks, patients receiving omeprazole had less day pain, less night pain and took fewer antacids than those receiving cimetidine (all p less than 0.05). The difference between omeprazole and cimetidine was not appreciably affected by age, smoking, size of the ulcer and trial centre. Tolerability was similar in the two treatment groups. In the treatment of symptomatic gastric ulcer, omeprazole relieves the symptoms more quickly than cimetidine and heals a greater proportion of ulcers within four weeks.

Symptom relief and duodenal ulcer healing with omeprazole or cimetidine. Opus (Omeprazole Peptic Ulcer Study) Research Group.

In a double-blind parallel-group study, 98 patients with symptomatic duodenal ulcer received omeprazole 20 mg o.m. and 91 cimetidine 800 mg nocte for 2 or, if then not healed, 4 weeks. After 2 weeks the healing rates on an intention-to-treat basis were: for omeprazole 62% and for cimetidine 33% (P less than 0.001), and at 4 weeks 85% and 61%, respectively (P less than 0.001). The proportions symptom-free at 2 weeks were 83% of the omeprazole and 63% of the cimetidine-group (P less than 0.01) and at 4 weeks 84% and 72% (P = 0.01). Patients receiving omeprazole took fewer antacid tablets than those receiving cimetidine. Patient tolerance of both drugs was similar and good. In the treatment of duodenal ulcer, omeprazole 20 mg o.m. gives faster symptom relief than cimetidine 800 mg nocte, as well as healing a greater proportion of ulcers within 2 and 4 weeks.

Endocrine regulation of the form and function of axonal arbors during insect metamorphosis.

By discrete manipulation of the endocrine cues that control insect metamorphosis, it has been possible to examine the mechanisms governing the growth of neural processes during development. During the transition from larva to pupa in the hawkmoth, Manduca sexta, identified sensory neurons reorganize their central projections to evoke a new behavior--the gintrap reflex. Topical application of a juvenile hormone analog to the peripheral cell bodies of these sensory neurons during a critical period of development caused them to retain their larval commitment rather than undergo pupal development with the rest of the animal. The sensory neurons retained the larval arborization pattern within the pupal CNS and were unable to evoke the gin-trap reflex. Thus, the hormonal environment of the cell body is critical for controlling growth and synapse formation by distant axonal processes.

Electrohydrothermoprobe--a simple alternative to laser therapy in the management of acute gastrointestinal haemorrhage.

One hundred and twenty six consecutive patients presenting with upper alimentary bleeding were endoscoped. Seventeen gastric and 11 duodenal lesions with visible blood vessels were identified and cauterised with the electrohydrothermoprobe. One gastric and four duodenal vessels rebled, necessitating surgery. For the gastric vessels this represents about one tenth of the expected rebleeding rate, and is a significant reduction. The technique appears to have no effect on the rebleeding rate in duodenal vessels.

Embryogenesis of an insect nervous system II: a second class of neuron precursor cells and the origin of the intersegmental connectives.

The intersegmental connectives in the locust central nervous system are initiated by the axons of early differentiating neuron trios. Using a combination of electron microscopy and fluorescent dye injection we have shown that the axons of these cells grow out anteriorly and posteriorly in each segment along a basement membrane, and link together at the segment borders to form continuous longitudinal pathways on each side of the developing nervous system. These early neurons are the progeny of a second class of precursor cell, the midline precursors, which are distinct from the segmental neuroblasts. Like the neuroblasts, the midline precursors are arranged in a standard segmentally repeated pattern. This and the standard pattern of axon outgrowth in different segments suggest that the nervous system develops to a common, segmentally repeated programme.