Effect of Ramadan fasting on intragastric pH recorded during 24 hours in healthy subjects

OBJECTIVES: Lifestyle changes during Ramadan as the meals are taken exclusively in the evening, and nightly sleep is often delayed and shortened. The wake/sleep cycle is also modified. The aim of this study was to evaluate the influence of Ramadan on gastric acidity in healthy volunteers. METHODS: Nine healthy volunteers had 24-hour measurement of the gastric pH; 4 periods were compared: one week prior to Ramadan, day 10 and day 24 during Ramadan, and one month after Ramadan. The pH profiles and the [H+] activity (area under the curve) were measured during 24 hours, the night phase (5PM-8AM) and diurnal phase (8AM-5PM). RESULTS: The diurnal variations of the pH profile were more significant; the median pH was 2.3 prior to Ramadan, 1 at day 10 and day 24 and 1.6 one month after Ramadan. The 24-hours [H+] activity increased by 45% at day 10 of Ramadan compared with its level prior to Ramadan. This increase was mostly diurnal (+122%) and also nightly (+25%). The activity [H+] was steady during Ramadan. One month after Ramadan, the 24-hours [H+] activity was 23% higher than the one noted before Ramadan. CONCLUSIONS: This study shows that the conditions of feeding imposed by Ramadan are associated with an increase of the gastric acidity mainly in diurnal phase. These results do not explain the origin of the healthy volunteer digestive symptoms encountered during Ramadan.     

Effect of benzbromarone in 100mg and 50mg doses on healthy subjects

After oral application of 100mg of Benzbromarone a significant decrease of the uric acid concentration in the serum up to the 14th day after beginning of the treatment to a mean value of 1,7 mg/100 ml is achieved; while the application of 50 mg of Benzbromarone reduces the uric acid concentration only to a value of 3,4 mg/100 ml. Thereby the differences amounts to about 1,7 mg/100 ml. The urate elimination increases after 100 as well as after 50 mg of Benzbromarone. Only initially an increased uric acid elimination could be observed. In the further course the uric acid elimination remains increased despite reduced serum concentrations.     

Maintenance treatment for gastro-oesophageal reflux disease. A placebo-controlled evaluation of 10 milligrams omeprazole once daily in general practice

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a frequent cause for consultation in general practice and is a chronically relapsing disease. METHODS: This general practice study was a 6-month randomized, double-blind parallel-group placebo-controlled assessment of the efficacy and safety of continuous treatment with 10 mg omeprazole every morning after initial symptom control in 495 patients with GORD but without erosive oesophagitis. RESULTS: On the basis of life-table estimates for cumulative relapse rates, patients in the placebo group (52%) were almost twice as likely as those in the omeprazole group (27%) to discontinue therapy before 24 weeks because of inadequate relief of heartburn or for other reasons including adverse events (all-patients-treated analysis, log rank test, P = 0.0001). CONCLUSIONS: This study has shown that 10 mg omeprazole once daily is an effective and well-tolerated treatment strategy in general practice for the long-term management of symptoms of GORD in patients without erosive oesophagitis.     

Effect of ranitidine on intragastric pH in clinically normal neonatal foals

OBJECTIVE: To determine intragastric pH in newborn foals and to examine the effect of i.v. or oral administration of an H2-receptor antagonist on intragastric pH. DESIGN: Prospective controlled study. ANIMALS: 6 healthy mixed-breed neonatal foals. PROCEDURE: Intragastric pH was measured, using an antimony electrode. Foals were monitored on days 2, 4, and 6 after birth, and each received 3 treatments. The pH was recorded for 4 hours before treatment and for 10 hours after ranitidine administration (2 mg/kg [0.91 mg/lb] of body weight, i.v.; 6.6 mg/kg [3 mg/lb], PO) or 20 hours after corn syrup administration. Mean and median pH and percentage of time pH was > or = 4 were calculated. RESULTS: Mean intragastric pH significantly increased for 5 hours after i.v. administration of ranitidine, compared with baseline data. Percentage of time intragastric pH was > or = 4 increased significantly for 4 hours after ranitidine administration, and median pH increased significantly for hours 2 to 4 after administration. Oral administration of ranitidine significantly increased mean and median pH for hours 2 to 8 after administration and percentage of time pH was > or = 4 for hours 2 to 7 after administration. CLINICAL IMPLICATIONS: Neonatal foals have highly acidic gastric fluid. Intravenous or oral administration of ranitidine significantly increased intragastric pH for 4 and 8 hours, respectively. Suckling affected intragastric pH and underscored the need for frequent feeding of neonatal foals.     

Omeprazole 10 milligrams once daily, omeprazole 20 milligrams once daily, or ranitidine 150 milligrams twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal reflux disease in general practice

BACKGROUND: The efficacy of omeprazole, 20 mg once daily, in the treatment of reflux oesophagitis and the therapeutic advantages over the histamine H2 receptor antagonists are well documented. This study assessed 20 mg omeprazole daily (OM20), 10 mg omeprazole daily (OM10), and 150 mg ranitidine (RAN) twice daily for symptom relief in gastro-oesophageal reflux disease (GORD). METHODS: Patients (n = 994) presenting with heartburn to their general practitioner underwent endoscopy to exclude peptic ulcer disease and were randomized into a UK, multicentre, parallel-group, double-blind comparison of the three treatments for 4 weeks. Symptoms were assessed at clinic visits after 2 and 4 weeks. RESULTS: Symptom relief after 4 weeks was achieved by 61% (OM20), 49% (OM10), and 40% (RAN) patients (OM20 versus OM10, P < 0.0167; OM20 versus RAN, P < 0.0001; OM10 versus RAN, P < 0.01). Among the patients (32%) with erosive reflux oesophagitis, symptom relief was achieved in 79% (OM20), 48% (OM10), and 33% (RAN) (OM20 versus OM10, P < 0.0001; OM20 versus RAN, P < 0.0001; OM1O versus RAN, NS). CONCLUSION: Omeprazole, 20 mg, is the most effective initial therapy for relief of GORD symptoms.     

Minimal daily variations of plasma and urinary endothelin-1 in healthy subjects

The daily profiles of both the plasma level and the urinary excretion rate of endothelin-1 were examined in 13 healthy volunteers (9 males and 4 females, aged 22 +/- 1 [SEM]). Plasma endothelin-1 (PET) was measured after a one-hour recumbency every 6 hours at 8 a.m., 2 p.m., 8 p.m. and 2 a.m. and the urinary excretion rate of endothelin-1 (UET) was determined in the urine collected every 6 hours. PET was found to be quite stable throughout the day, being 1.57 +/- 0.25 pg/ml at 8 a.m., 1.88 +/- 0.21 at 2 p.m., 2.2 +/- 0.24 at 8 p.m. and 1.90 +/- 0.20 at 2 a.m. After a one-hour ambulation, PET showed no statistical difference. UET also remained unchanged for each 6-hour collecting period, measuring 4.61 +/- 0.69, 3.98 +/- 0.46, 4.63 +/- 0.73 and 3.42 +/- 0.49 ng/hr, respectively. The absence of any daily variations in either PET or UET thus suggests that apparently no specific considerations need be applied regarding the time of taking samples to measure the plasma and urinary endothelin-1.     

Effect of intragastric or intraduodenal administration of a polymeric diet on gallbladder motility, small-bowel transit time, and hormone release

OBJECTIVE: During postpyloric tube feeding, GI intolerance is observed more frequently than during prepyloric feeding, possibly by evoking a stronger GI response. METHODS: We investigated the effect of intragastric and intraduodenal administration of a polymeric diet (125 kcal/h) on gallbladder motility (by ultrasonography), duodeno-cecal transit time (by lactulose H2 breath test), and GI hormone release (including cholecystokinin, pancreatic polypeptide, and gastrin). Six healthy subjects (two male, four female; mean age 22 yr, range 18-27 yr) were studied on two separate occasions in random order during 6 h of continuous administration of the diet through either the gastric or duodenal port of a two-lumen tube. RESULTS: Intraduodenal feeding resulted in a more rapid contraction of the gallbladder, from 32 +/- 4 to 23 +/- 4 cm3 at 10 min (p < 0.05), reaching a minimum of 6 +/- 1 cm3, in contrast to intragastric feeding (31 +/- 4 to 19 +/- 3 cm3 at 60 min, p < 0.05; minimum 14 +/- 1 cm3). The gallbladder remained contracted during the 6-h study period during both intraduodenal and intragastric feeding. Small-bowel transit time was significantly accelerated during intraduodenal compared with intragastric feeding (51 +/- 12 vs 81 +/- 9 min; p = 0.003). Plasma cholecystokinin secretion was significantly (p < 0.05) increased during intraduodenal compared with intragastric feeding (848 +/- 107 vs 279 +/- 89 pmol x L(-1) x 360 min). The same was true for pancreatic polypeptide secretion. However, gastrin release was significantly (p < 0.05) higher during intragastric feeding. CONCLUSIONS: Intraduodenal feeding elicited a stronger GI response than intragastric feeding, as demonstrated by accelerated small-bowel transit time, more rapid and stronger gallbladder contractions, and increased cholecystokinin and pancreatic polypeptide release. Gastrin release, on the other hand, was stronger during intragastric feeding.     

Effect of different levels of hyperoxia on breathing in healthy subjects

We have recently shown that breathing 50% O2 markedly stimulates ventilation in healthy subjects if end-tidal PCO2 (PETCO2) is maintained. The aim of this study was to investigate a possible dose-dependent stimulation of ventilation by O2 and to examine possible mechanisms of hyperoxic hyperventilation. In eight normal subjects ventilation was measured while they were breathing 30 and 75% O2 for 30 min, with PETCO2 being held constant. Acute hypercapnic ventilatory responses were also tested in these subjects. The 75% O2 experiment was repeated without controlling PETCO2 in 14 subjects, and in 6 subjects arterial blood gases were taken at baseline and at the end of the hyperoxia period. Minute ventilation (VI) increased by 21 and 115% with 30 and 75% isocapnic hyperoxia, respectively. The 75% O2 without any control on PETCO2 led to 16% increase in VI, but PETCO2 decreased by 3.6 Torr (9%). There was a linear correlation (r = 0.83) between the hypercapnic and the hyperoxic ventilatory response. In conclusion, isocapnic hyperoxia stimulates ventilation in a dose-dependent way, with VI more than doubling after 30 min of 75% O2. If isocapnia is not maintained, hyperventilation is attenuated by a decrease in arterial PCO2. There is a correlation between hyperoxic and hypercapnic ventilatory responses. On the basis of data from the literature, we concluded that the Haldane effect seems to be the major cause of hyperventilation during both isocapnic and poikilocapnic hyperoxia.     

Identical effects of indomethacin on renal function in healthy uninephrectomized subjects and in healthy control subjects

1. Animal studies have shown that prostaglandins are important for renal function after unilateral nephrectomy. In order to investigate the importance of prostaglandins for renal function in the fully adapted remnant kidney in healthy uninephrectomized subjects, the acute effects of indomethacin on renal haemodynamics, lithium clearance, urinary excretion rates of prostaglandin E2, sodium and water, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured in 14 healthy uninephrectomized subjects (median time after nephrectomy 1.7 years) and in 14 matched healthy control subjects. In addition, nine healthy control subjects were studied without indomethacin and served as a time-control group. 2. Before indomethacin ingestion there was a significantly higher single-kidney urinary excretion rate of prostaglandin E2 in the uninephrectomized group (uninephrectomized group, 349.2 fmol/min; control group, 76.6 fmol/min; time-control group, 96.3 fmol/min). 3. Indomethacin ingestion resulted in equal changes in all parameters in both groups. These were significant decreases in glomerular filtration rate (-11.3% versus -14.6%), renal plasma flow (-6.5% versus -13.0%), urinary flow rate (-49.8% versus -49.4%), fractional sodium excretion (-44.5% versus -47.4%), lithium clearance (33.2% versus -23.8%) and urinary excretion rate of prostaglandin E2 (-93.8% versus -86.7%) (uninephrectomized versus control subjects, values are medians). In the time-control group no changes were observed in these parameters. 4. It is concluded that healthy uninephrectomized subjects with a fully adapted remnant kidney have a normal renal response to acute indomethacin-induced inhibition of prostaglandin synthesis.     

Effect of a single high-fat meal on endothelial function in healthy subjects

Incorporation and metabolism of exogenous GM3 in human myelogenous leukemia HL-60 cells were analyzed using 3H-labeled GM3 ([3H]GM3). [3H]GM3 was rapidly internalized into the cells (trypsin-resistant fraction) 8 times more than the control, 3H-labeled GM1 ([3H]GM1). In addition, not only incorporation but also metabolism of [3H]GM3 was more rapid than [3H]GM1 in HL-60 cells. Moreover, one of the metabolites was found to co-migrate with ceramide in thin-layer chromatography analysis and ceramide formation from exogenous GM3 is more rapid than that from exogenous GM1. These results suggested that there would be some preferential mechanism to produce ceramide from differentiation-inducible GM3 in HL-60 cells rather than from non-inducing GM1.     

Effect of acute dietary fibre supplementation on colonic pH in healthy volunteers

Two patients presented with a tumor involving mainly the supplementary motor area or the premotor cortex. Shortly after tumor resection, each developed transient impairment of voluntary movements. An electromyogram, with the skin electrodes placed over the muscles of the upper arms and forearms, demonstrated aberrant ipsilateral, contralateral or bilateral muscle activation during unilateral motor tasks in both patients. The bilateral activation was more prominent in the patient who had an intact dominant hemisphere. The present study suggests for the first time the importance of non-primary motor areas of the human brain in activating the proper set of muscles on the proper side of the body.     

A comparison of fluticasone propionate, 1 mg daily, with beclomethasone dipropionate, 2 mg daily, in the treatment of severe asthma. International Study Group

Cytochrome P450 1A1 was localized immunohistochemically and benzo[a]pyrene hydroxylase activity was identified in situ by means of fluorescence histochemistry in the nasal mucosa of untreated, 3-methylcholanthrene-treated or Aroclor 1254-treated rats. Cytochrome P450 1A1 was localized predominantly within Bowman's glands, with considerably less staining occurring in the olfactory epithelium of untreated rats. Similarly, benzo[a]pyrene was hydroxylated to the greatest extent in Bowman's glands and, to a lesser extent, in olfactory epithelial cells. Pre-treatment of tissue sections of nasal mucosa with anti-P450 1A1 inhibited most of the benzo[a]pyrene hydroxylase activity present. Although 3-methylcholanthrene treatment did not affect either cytochrome P450 1A1 or hydroxylase activity in the nasal mucosa, a single intraperitoneal injection of Aroclor 1254 significantly increased anti-P450 1A1 binding in Bowman's glands and in the olfactory and respiratory epithelia, and dramatically enhanced benzo[a]pyrene hydroxylase activity in the epithelia and the subepithelial ducts and glands in both the olfactory and respiratory regions. In contrast to its effects on cytochrome P450 1A1, Aroclor 1254 produced a considerably greater induction of hydroxylase activity in the respiratory region, especially in the seromucous glands, than in the olfactory region. These results suggest that Aroclor 1254 treatment also induces other forms of cytochrome P450 in the respiratory region of the nasal mucosa.     

Comparison of the effect of lansoprazole and omeprazole on intragastric acidity and gastroesophageal reflux in patients with gastroesophageal reflux disease

A prospective study of the pharmacokinetics of itraconazole solution was performed in 11 patients who underwent allogeneic BMT (day of BMT = day 0) after a conditioning regimen including total body irradiation (TBI). Itraconazole solution (400 mg once a day) was given 7 days before BMT and continued up to the end of neutropenia unless another antifungal treatment was necessary. Blood samples were collected before itraconazole intake (Cmin) and 4 h later (Cmax) every other day for assays of itraconazole (ITRA) and its active metabolite hydroxy-itraconazole (OH-ITRA). The mean values of Cmin ITRA and OH-ITRA, respectively, were 287 +/- 109 ng/ml and 629 +/- 227 ng/ml at day -1 and 378 +/- 147 ng/ml and 725 +/- 242 ng/ml at day +1. The maximum Cmin values were observed at day +3. Six patients at day -1 (54%) and 8 at day +1 (72%) had satisfactory residual plasma concentrations of at least 250 ng/ml of unchanged ITRA. From day +1 to day +9, eight patients discontinued the itraconazole treatment, five of them had satisfactory plasma residual concentrations at this time. This work shows a good bioavailability of itraconazole oral solution during the early phase after allogeneic BMT, but more data are needed for the late phases.     

Comparison of ceftibuten once daily and amoxicillin-clavulanate three times daily in the treatment of acute exacerbations of chronic bronchitis

In medical practice, antibiotics are generally given empirically for the treatment of acute exacerbations of chronic bronchitis (AECB). To be effective, antibiotic therapy should be broad in spectrum, and it should also cover the common beta-lactamase-producing pathogens. In this multicenter, randomized, investigator-masked study, 469 patients with AECB were randomized (in a ratio of 2:1) to receive 400-mg oral ceftibuten capsules once daily or 500-mg amoxicillin-clavulanate tablets three times daily for 5 to 15 days. Patients receiving ceftibuten were further divided into those who took the capsule with a meal (fed) and those who took the capsule 1 hour before a meal (fasted). Clinical and microbiologic responses were evaluated after treatment at 0 to 6 days (end of treatment) and 7 to 21 days (follow-up). Overall clinical success was determined by cure/improvement of signs and symptoms of AECB at the end of treatment and at follow-up. Overall microbiologic assessment was graded as eradication, persistence, relapse, reinfection, colonization, superinfection, or unassessable. Tolerability was evaluated by grading observed adverse events. The mean duration of treatment was 10.4 days for patients who received ceftibuten and 10.1 days for patients who received amoxicillin-clavulanate. A total of 252 patients receiving ceftibuten and 117 patients receiving amoxicillin-clavulanate were evaluable for clinical efficacy, and 55 patients were evaluable for microbiologic response. Both treatments improved the signs and symptoms of bronchitis, and overall clinical success rates were equivalent for patients treated with ceftibuten (211 of 252 [84%]) and amoxicillin-clavulanate (93 of 117 [79%]) (95% confidence interval [CI], -4.5% to 13.6%). Overall microbiologic eradication rates were also similar for patients treated with ceftibuten (36 of 37 [97%]) and amoxicillin-clavulanate (12 of 14 [86%]) (95% CI, -5.2% to 21.2%). The most frequently reported treatment-related adverse events were gastrointestinal disturbances, which occurred in 15% (47 of 316) and 24% (36 of 152) of patients treated with ceftibuten and amoxicillin-clavulanate, respectively. No significant difference was observed in the ceftibutenfed and ceftibuten-fasted groups in overall clinical assessments of the clinical efficacy population and safety population. In conclusion, 400 mg oral ceftibuten once daily has a similar clinical success rate to 500 mg amoxicillin-clavulanate three times daily, with a trend toward fewer gastrointestinal side effects, in the treatment of patients with AECB.     

Effect of intraduodenal magnesium sulphate on pancreas and gallbladder of man

Magnesium sulphate has previously been used as a purgative in a test involving the measurement of the faecal excretion of pancreatic enzymes. In order to validate the use of magnesium sulphate for this purpose, in 18 individuals the pancreatic and biliary response to intravenous infusion of secretin (1 CU/kg-h) plus CCK(1IU/kg-h) were compared with the responses to one of three dose-rates of magnesium sulphate infused into the duodenum. The effect of magnesium sulhphate was also studied during the coincident intravenous administration of the hormones. Intraduodenal magnesium sulphate did not stimulate the secretion of bicarbonate into the duodenum but did evoke the secretion of pancreatic enzymes and discharge of bile. The pancreatic response to the exogenous hormones was not altered by coincident intraduodenal infusion of magnesium sulphate. We conclude that magnesium sulphate is a satisfactory purgative for speeding the intestinal transit of pancreatic enzymes.     

Effect of granulocyte macrophage-colony stimulating factor on Langerhans cells in normal and healthy atopic subjects

We conducted a reproducibility study of the alternating breath test (ABT) for assessing peripheral chemoreceptor function in infants. The ABT delivers a rapid hypoxic stimulus to the peripheral chemoreceptors with breath-by-breath alternations of the inspired O2 fraction. The reproducibility of the ABT performed on a single occasion has not been extensively studied in infants. Eight unsedated infants (postnatal age, 22+/-19 d; weight, 3.2+/-0.4 kg) were studied in standardized conditions: morning naps, supine position, room temperature 22-24 degrees C, quiet sleep, and face mask attached to a pneumotachograph connected to a two-way electric valve. Respiratory gases were analyzed by mass spectrometer. Two ABTs were performed. Each included a 2-min control run (CR) alternating between air and air, and a 2-min test run (TR) alternating between air and 0.15 O2. After data preprocessing, on average 13+/-11% of the data were rejected because of sighs, apneas, and cycles with the fraction of inspired oxygen above 0.17. Using the remaining validated breaths, the response to ABT was calculated for the CR, for all breaths in the TR (TR(T)), and for the first 50 breaths of the TR (TR50). During the ABTs oxygen saturation did not fall below 96%, and heart rate was not affected. Inspired and end-tidal CO2 fractions remained unchanged during the ABTs. FetO2 oscillated in TRs at a lower values than in CRs and differed significantly between breaths of air and hypoxic breaths of TRs. All infants responded to ABT with percentage alternation coefficients of TRs significantly greater than those of CRs for all respiratory variables. The values of the coefficients were not significantly different between both ABT, and between TR50 and TR(T). The greatest values of the coefficients were for timing variables compared with flows and volume. We conclude that the ABT is a reproducible test of peripheral chemoreceptor function under standardized conditions.     

Effects of indomethacin on intragastric pH and meal-stimulated serum gastrin secretion in rheumatoid arthritis patients

The effects of oral indomethacin on intragastric pH and serum gastrin were investigated in rheumatoid arthritis patients. Nine patients (1 male, 8 female) without a history of peptic ulcer disease and 6 patients with a history of peptic ulcer disease (5 male, 1 female) were studied. To obviate Helicobacter pylori infection as a confounding factor, only patients with positive H. pylori serology were included. After a 5-day period of placebo treatment and after a 5-day period of indomethacin (50 mg t.d.s.; total dose 750 mg), 24-h intragastric pH and basal and meal-stimulated serum gastrin levels were measured in a double-blind placebo controlled cross-over study. There were no differences in the median 24-h pH values between placebo and indomethacin users irrespective of peptic ulcer disease history. Indomethacin resulted in a higher basal and stimulated gastrin response than placebo in patients with a history of peptic ulcer disease. The basal and incremental responses were lower in patients with a history of peptic ulcer disease than in patients without a history of peptic ulcer disease, both during indomethacin and placebo. The same basal and stimulated incremental serum gastrin responses were found during placebo and indomethacin treatment in patients without a history of peptic ulcer disease. No correlation was established between median 2-h post-prandial intragastric pH and post-prandial incremental serum gastrin concentration. We conclude that indomethacin does not influence the intragastric pH of rheumatoid arthritis patients irrespective of history of peptic ulcer disease.     

Effects of hostility on ambulatory blood pressure and mood during daily living in healthy adults.

This study (a) tested the effects of hostile attributes on ambulatory blood pressure (BP), heart rate, and mood monitored repeatedly over 3 days in 100 healthy men and women and (b) determined whether the cardiovascular effects of trait hostility were moderated by mood. Multilevel random-coefficients regression analyses showed that hostile individuals exhibited higher systolic and diastolic BP and rated their current moods as more negative and less positive throughout the monitoring. Individuals low in hostility exhibited high BP only during the few occasions when they experienced negative mood. However, these patterns were true only when participants were classified by Potential for Hostility ratings from the Structured Interview (R. H. Rosenman, 1978), not by the Cynical Hostile Attitudes score derived from the Cook-Medley scale. Results provide convergent and ecological validity of interview rating of hostility and illuminate one possible dynamic mechanism by which overt hostile behaviors might contribute to the rates of increased cardiovascular morbidity and mortality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of once-daily doses of omeprazole (40 and 20 mg) and placebo in the treatment of benign gastric ulcer: a multicenter, randomized, double-blind study

OBJECTIVE: The purpose of this multicenter, randomized, double-blind study, conducted in 520 patients, was to compare the efficacy and safety of omeprazole (40 and 20 mg once daily) with placebo in the treatment of benign gastric ulcer. METHODS: Treatment with omeprazole or placebo lasted 4 wk; those whose ulcers remained unhealed continued the same treatment regimen for an additional 4 wk. The effects of therapy were determined by endoscopy and assessment of GI symptoms. Safety and tolerability were evaluated through reported adverse events, physical examinations, and laboratory tests. RESULTS: At weeks 4 and 8, the proportion of patients with healed ulcers was significantly greater in the omeprazole 40- and 20-mg groups than in the placebo group (p < 0.01). At week 8, the healing rate was significantly greater in the 40-mg group than in the 20-mg group (82.7 vs 74.8%, p < 0.05). In patients with large ulcers (>1 cm), the 40-mg regimen was associated with a significantly higher healing rate (78.9%) than both the 20-mg regimen (61.4%) and placebo (34.6%) at week 8 (p < 0.05 vs omeprazole 20 mg; p < 0.01 vs placebo). Healing rates in patients with small ulcers were similar for the 40- and 20-mg groups. Omeprazole was well tolerated, with no significant differences versus placebo in the overall incidence of clinical or laboratory adverse events. CONCLUSIONS: Omeprazole 40 and 20 mg, administered once daily, healed a significantly greater proportion of patients than did placebo. The 40-mg regimen offered significant advantages over the 20-mg regimen in patients with large ulcers.