Students coached for an admission test perform less well throughout a medical course.

BACKGROUND: Undertaking commercial coaching to improve one's chance of selection into medical school is widespread. Although its effect on selection test performance appears to be relatively minimal, its impact on the predictive validity of the tests is unknown. AIMS: To examine whether commercial coaching for the Undergraduate Medical and Health Sciences Admissions Test (UMAT) changes its ability to predict the subsequent academic performance of medical students. METHODS: The first two cohorts to enrol in a new Australian medical school provided information at the time of their selection interview about whether or not they had undertaken a commercial coaching course to help prepare for the UMAT. Final academic grades for each year of the degree and overall grade point average (GPA) of coached students were compared with those of non-coached students. Moderated regression analyses examined differences in the relationship between UMAT scores and examination results while controlling for entry UMAT scores and past academic performance. RESULTS: Coached students had a lower GPA than those who were not coached. In cohort 1, coached students performed more poorly than non-coached students in every year of their degree. This effect, while similar, was not statistically significant in cohort 2. CONCLUSIONS: Differences in selection process and learning context between the two cohorts may explain why coaching was only significantly related to the performance of one cohort. Further research is required to ascertain if coached students develop a learning style that hinders ongoing acquisition of knowledge, which might have serious implications for job performance after graduation.

Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial.

AIM: To evaluate GI safety of celecoxib compared with 2 nonselective (ns) NSAIDs, as a secondary objective of a large trial examining multiorgan safety. METHODS: This randomised, double-blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100-200 mg b.d., ibuprofen 600-800 mg t.d.s. or naproxen 375-500 mg b.d. plus esomeprazole, and low-dose aspirin or corticosteroids if already prescribed. Clinically significant GI events (CSGIE-bleeding, obstruction, perforation events from stomach downwards or symptomatic ulcers) and iron deficiency anaemia (IDA) were adjudicated blindly. RESULTS: Mean treatment and follow-up durations were 20.3 and 34.1 months. While on treatment or 30 days after, CSGIE occurred in 0.34%, 0.74% and 0.66% taking celecoxib, ibuprofen and naproxen. Hazard ratios (HR) were 0.43 (95% CI 0.27-0.68, P = 0.0003) celecoxib vs ibuprofen and 0.51 (0.32-0.81, P = 0.004) vs naproxen. There was also less IDA on celecoxib: HR 0.43 (0.27-0.68, P = 0.0003) vs ibuprofen; 0.40 (0.25-0.62, P < 0.0001) vs naproxen. Even taken with low-dose aspirin, fewer CSGIE occurred on celecoxib than ibuprofen (HR 0.52 [0.29-0.94], P = 0.03), and less IDA vs naproxen (0.42 [0.23-0.77, P = 0.005]). Corticosteroid use increased total GI events and CSGIE. H. pylori serological status had no influence. CONCLUSIONS: Arthritis patients taking NSAIDs plus esomeprazole have infrequent clinically significant gastrointestinal events. Co-prescribed with esomeprazole, celecoxib has better overall GI safety than ibuprofen or naproxen at these doses, despite treatment with low-dose aspirin or corticosteroids.

Efficacy of esomeprazole for resolution of symptoms of heartburn and acid regurgitation in continuous users of non-steroidal anti-inflammatory drugs.

BACKGROUND: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal symptoms such as heartburn and acid regurgitation. AIM: To assess the efficacy of esomeprazole 20 and 40 mg for resolution of heartburn and acid regurgitation in continuous NSAIDs. METHODS: A post hoc analysis of five clinical trials was performed. Two identically designed, placebo-controlled, 4-week studies (NASA1, SPACE1) enrolled non-ulcer, NSAIDs-treated patients with upper abdominal pain, discomfort or burning. PLUTO and VENUS were identically designed, placebo-controlled, 6-month studies that enrolled patients at risk of NSAIDs-induced ulcers. Study 285 was an 8-week comparative study with ranitidine (300 mg/day) in patients with NSAIDs-induced gastric ulcers. Resolution of investigator-assessed heartburn and acid regurgitation was defined as symptom severity of 'none' in the last 7 days. RESULTS: In NASA1/SPACE1, heartburn resolved in 61% and 62% of patients taking esomeprazole 20 and 40 mg, respectively (vs. 36% on placebo, P < 0.001), and acid regurgitation resolved in 65% and 67% (vs. 48%, P < 0.001). Resolution of both symptoms was greater with esomeprazole than with placebo in PLUTO/VENUS (P

Systematic review with meta-analysis: fundic gland polyps and proton pump inhibitors.

BACKGROUND: A causal association between proton pump inhibitor (PPI) use and fundic gland polyps has been suggested, but the data are conflicting. AIM: To clarify the relationship through a meta-analysis of the existing data. METHODS: A systematic retrieval and selection of records was performed. The main inclusion criteria were original studies reporting the prevalence of fundic gland polyps in PPI users or the reverse, compared to controls. Key outcomes were the odds ratios (OR) for fundic gland polyp prevalence in association with PPI use, prevalence of PPI use amongst subjects with fundic gland polyps and fundic gland polyp prevalence among PPI users. Statistical analysis was performed using Mix 2.0 Pro. RESULTS: The initial search using electronic databases and manual searching retrieved 339 peer-reviewed articles and abstracts. Twenty articles met all inclusion and exclusion criteria, with a total of 40 218 subjects included. The meta-analysis of 12 studies revealed an increase in fundic gland polyps amongst PPI users compared to controls (OR 2.46, 95% CI 1.42-4.27, P = 0.001), particularly among individuals taking PPIs for at least 6 months (OR: 4.71, 95% CI 2.22-9.99, P < 0.001) or 12 months (OR: 5.32, 95% CI 2.58-10.99, P < 0.001). CONCLUSIONS: Proton pump inhibitor usage is associated with a significantly increased prevalence of fundic gland polyps, and there is a trend for this to increase with longer length of PPI exposure. However, the meta-analysis is limited mainly to cohort studies.

Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin.

BACKGROUND: Aspirin is valuable for preventing vascular events, but information about ulcer frequency is necessary to inform risk-benefit decisions in individual patients. AIM: To determine ulcer prevalence and incidence in a population representative of those given aspirin therapy and evaluate risk predictors. METHODS: Patients taking aspirin 75-325 mg daily were recruited from four countries. Exclusions included use of gastroprotectant drugs or other non-steroidal anti-inflammatory drugs. We measured point prevalence of endoscopic ulcers, after quantitating dyspeptic symptoms. Incidence was assessed 3 months later in those eligible to continue (no baseline ulcer or reason for gastroprotectants). RESULTS: In 187 patients, ulcer prevalence was 11% [95% confidence interval (CI) 6.3-15.1%]. Only 20% had dyspeptic symptoms, not significantly different from patients without ulcer. Ulcer incidence in 113 patients followed for 3 months was 7% (95% CI 2.4-11.8%). Helicobacter pylori infection increased the risk of a duodenal ulcer [odds ratio (OR) 18.5, 95% CI 2.3-149.4], as did age >70 for ulcers in stomach and duodenum combined (OR 3.3, 95% CI 1.3-8.7). CONCLUSIONS: Gastroduodenal ulcers are found in one in 10 patients taking low-dose aspirin, and most are asymptomatic; this needs considering when discussing risks/benefits with patients. Risk factors include older age and H. pylori (for duodenal ulcer).

Trefoil peptides are early markers of gastrointestinal maturation in the rat.

Trefoil peptides are members of a unique family of proteins found predominately throughout the gastrointestinal tract, whose proposed functions include mucus stabilization, stimulation and/or differentiation of epithelial cells during wound repair. Recent trefoil knockout studies have reported delays in epithelial cell migration or maturation pathways together with almost a complete lack of mucus. In order to fully explore the role of trefoil peptides in gastrointestinal maturation, these studies were undertaken to accurately characterize the expression of trefoil peptides in the developing rat gut. The results of RPA suggest that trefoil mRNA's are expressed as early as 15 days post coitus (dpc) in the intestine and stomach. Proteins are detected at 17 dpc by radioimmunoassay and immunohistochemical studies, which localize trefoil peptide expression to the lumenal surface of epithelial cells. At 17 dpc the gut is lined by pseudo-stratified, undifferentiated epithelial cells. Polarized, columnar cells are not detected until at least 18 dpc, with sparse mucus staining and parietal cell markers not being detected until 18 and 19 dpc respectively. This data demonstrates that trefoil peptides are early markers of epithelial cell maturation in the developing rat gut. The time course of their expression, well before the mucus cell type is specified, suggests a potential role in epithelial cell differentiation.

Hepatic Kupffer cell function: the efficiency of uptake and intracellular degradation of 14C-labelled mitochondria is reduced in aged rats.

Uptake from the circulation and subsequent intracellular degradation of foreign and potentially harmful substances are key functions of hepatic Kupffer cells. While ageing is generally associated with decreased clearance by the reticulo-endothelial system, the effect of ageing on specific Kupffer cell functions is poorly understood. This study measured the ability of Kupffer cells of isolated perfused rat livers from young and old rats to both phagocytose and subsequently degrade exogenous radiolabelled mitochondria. Using electron microscopy and stereological techniques it was determined that there was no change in the volume density of Kupffer cells between 2 and 24 months, implying that the size of the Kupffer cell population increased (along with the total liver size) with age. However, despite this increase size there was no parallel increase in the capacity of the liver to take up or degrade radiolabelled mitochondria, implying that, in aged rats, Kupffer cell uptake and intracellular degradation was less efficient.

Approaches to healing and prophylaxis of nonsteroidal anti-inflammatory drug-associated ulcers.

Treating and preventing peptic ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDs) calls for clinical judgment. Physicians must weigh their patients' need for anti-inflammatory therapy against their individual risks for ulcer development; their likelihood of coping with an ulcer complication if it should develop; and the economics, efficacy, and tolerability of various treatment and prevention options. This article considers some general strategies common to both treatment and prevention. Data from randomized trials that can guide clinicians and their patients as they attempt to heal an established NSAID ulcer or prevent one occurring in the future are also reviewed.

New data on healing of nonsteroidal anti-inflammatory drug-associated ulcers and erosions. Omeprazole NSAID Steering Committee.

A total of 1,456 patients were available for the All Patients Treated analysis of two large, randomized, double-blind, multicenter, controlled studies (Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment [ASTRONAUT] and Omeprazole versus Misoprostol for NSAID-Induced Ulcer Management [OMNIUM]). These studies examined the efficacies of omeprazole, 20 and 40 mg once daily (both studies), ranitidine, 150 mg twice daily (ASTRONAUT), and misoprostol, 200 microg four times daily (OMNIUM), for the healing of gastric ulcer, duodenal ulcer, or erosions, and the relief of dyspeptic symptoms. At entry, patients were receiving, and continued to receive, nonsteroidal anti-inflammatory drugs (NSAIDs), and had a gastric or duodenal ulcer, and/or >10 erosions in the stomach or duodenum at initial endoscopy. Patients were randomized to blinded treatment for 4/8 weeks until treatment success, which was defined as the healing of ulcer(s), <5 erosions at any site, and not more than mild dyspeptic symptoms. The proportions of patients reaching treatment success by 8 weeks were 77% with both doses of omeprazole, 63% with ranitidine, and 71% with misoprostol. In patients who initially had a gastric ulcer, more ulcers were healed at 8 weeks with omeprazole, 20 (83%) and 40 mg once daily (82%), than with ranitidine (64%) or misoprostol (74%). In patients who initially had a duodenal ulcer, 93% were healed at 8 weeks with omeprazole, 20 mg once daily, compared with 88% for omeprazole, 40 mg once daily, 79% for ranitidine, and 79% for misoprostol. Erosions healed slightly faster at 4 weeks with misoprostol, compared with the other regimens, but by 8 weeks most patients had <5 erosions per gastroduodenal region in each treatment group. Diarrhea and abdominal pain were more common in patients taking misoprostol, as were adverse events leading to withdrawal. Patients with duodenal ulcer or erosions at entry and the presence of Helicobacter pylori were good prognostic factors for overall treatment success. Using a model that included only patients with ulcers, those with smaller ulcers also had a higher likelihood of achieving treatment success. Against the background of these new data, omeprazole is the treatment of choice for healing NSAID-associated ulcers, on the basis of its efficacy and tolerability, and the optimal dose appears to be 20 mg once daily.

Personal review: alarmism or legitimate concerns about long-term suppression of gastric acid secretion?

This article responds to controversial issues about the long-term use of acid suppression raised in a recent article in this journal by Waldum & Brenna. Although rebound acid secretion occurs following proton pump inhibitor therapy, the clinical significance of this is unclear, but the proposal that this is a major driver of acid-related diseases is considered implausible. The polypoid deformity of the gastric corpus that can occur with long-term proton pump inhibitor therapy is not neoplastic, and therefore has no bearing on other issues raised about proton pump inhibitor therapy and gastric malignancy. Current data in humans suggest that the magnitude of serum gastrin elevation from proton pump inhibitor treatment of up to 10 years, and any theoretical risks from this, have been overstated by Waldum & Brenna. Pernicious anaemia is a model of very doubtful validity for the risks of proton pump inhibitor therapy on several grounds. The proposal that diffuse gastric carcinoma arises from acid suppression-induced stimulation of enterochromaffin-like cells is challenged vigorously, because this is based on an implausible and substantially criticized interpretation of histopathology. It is agreed that it is appropriate to be cautious about the safety of long-term acid suppression, because no data are available for lifelong treatment in humans. Such caution should be tempered by a critical assessment of the benefits of this treatment in relation to any possible risks. The substantial data that now exist from long-term treatment of humans with proton pump inhibitors has not thus far revealed any definite risks. The risk of death from anti-reflux surgery, although small, would seem to far exceed any possible risks associated with long-term proton pump inhibitor use. Available data suggest that denial of the benefits of effective acid suppressant therapy to patients with clear-cut troublesome acid related disorders is an overreaction to concerns about the biological effects of inhibiting acid secretion with proton pump inhibitors.

Randomized trial of omeprazole and metronidazole with amoxycillin or clarithromycin for Helicobacter pylori eradication, in a region of high primary metronidazole resistance: the HERO study.

BACKGROUND: The efficacy of omeprazole-based eradication therapies has been determined mostly in populations with low to moderate prevalence of metronidazole resistant Helicobacter pylori, yet resistance is high in many regions. AIM AND METHODS: The H. pylori eradication and duodenal ulcer healing rates after 1 week of either omeprazole 40 mg mane, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. (OAM) or omeprazole 20 mg b.d., metronidazole 400 mg b. d. and clarithromycin 250 mg b.d. (OMC) were compared in a randomized trial in Australia and New Zealand. Patients had a further 1 week of omeprazole 20 mg. Outcome was assessed at 6 weeks with stringent criteria (endoscopy, biopsies and 13C-urea breath test). RESULTS: Of 220 subjects randomized, the H. pylori eradication rates (all patients treated/per protocol) were 82%/85% for OMC and 58%/63% for OAM (P= 0.001). Pre-treatment metronidazole resistance was present in 56% and clarithromycin resistance in 6%. The eradication rate for primary metronidazole resistance isolates treated with OMC was 80% (CI: 65-90%) compared with 45% (CI: 29-62%) for OAM, whereas for sensitive organisms, the eradication rates were 94% (CI: 79-99%) and 79% (CI: 62-91%), respectively. Duodenal ulcer healing was 96% for OMC and 87% for OAM. Compliance was excellent and both treatments were well-tolerated. CONCLUSIONS: OMC is a well-tolerated, effective therapy for H. pylori eradication and duodenal ulcer healing in this region despite the high metronidazole resistance rate. OAM is less effective, largely due to the impact of metronidazole resistance.

Gastric microbleeding following single and repeated dosing with naproxen.

BACKGROUND: Adaptation to gastric damage from nonsteroidal anti-inflammatory drugs (NSAID) has been observed during ongoing dosage in rats and humans. However, this does not always occur, and our previous data suggest that NSAID half-life may be a determining factor. AIM: To investigate whether adaptation occurs during 1 week of naproxen administration in humans. SUBJECTS: Thirteen healthy volunteers were studied at baseline, and after one or seven daily doses of naproxen 750 mg. Gastric microbleeding was measured 4 h after naproxen in gastric washings collected during a 30-min period. Serum thromboxane B concentrations were also assayed, as a marker of cyclo-oxygenase inhibition. RESULTS: Mean blood loss after placebo was 0.60 microL/10 min (95% CI: 0.21-0.98). This rose to 2.15 (0.73-3.57) and 1.75 (0.74-2.76) microL/10 min after one and seven daily doses of naproxen, respectively (P < 0.05 vs. baseline; day 1 vs. 7 not significant). Thromboxane B concentrations were < 10% of control at both day 1 and 7 of dosing. CONCLUSION: In accord with our findings in rats, adaptation to this moderately long acting NSAID in humans was not apparent. We conclude that any adaptation to naproxen is unlikely to be clinically important.

Gastric acid secretory capacity falls after repeated within-day pentagastrin testing in fed subjects.

Between-day pentagastrin testing yields highly reproducible stimulated gastric acid output values, but little is known of the reproducibility of repeated within-day pentagastrin tests. We have performed three pentagastrin tests within the 1 day in nine healthy subjects. Within-day tests were 6 hours apart; the first followed an overnight fast and the second and third were both 4 hours after a substantial meal. A further test was performed the following morning, again after an overnight fast, which allowed comparison of within-day and between-day testing. In the second and third within-day tests there was a marked decrease of stimulated gastric acid output, with both maximal and peak acid output decreased to approximately half of the value of the first test (P less than 0.01). By contrast there were no significant differences in the acid output values obtained in between-day tests (both following an overnight fast). Possible mechanisms for the decreased output on repeated within-day testing include alterations in the sensitivity of the gastrin receptor, or some neurohumoral influence secondary to the preceding meal. Future studies of the duration of action of drugs affecting acid secretion may need to take account of these findings.

Prevention of the gastrointestinal adverse effects of nonsteroidal anti-inflammatory drugs: the role of proton pump inhibitors.

The associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and the presence and complications of gastroduodenal erosions and ulcers are well established. Evidence that acid aggravates NSAID-induced injury provides a rationale for minimising such damage by acid suppression. Other strategies discussed include avoidance of NSAIDs or minimising their dosage, selecting NSAIDs known to cause less damage, and co-prescription of various agents. Cytoprotection with misoprostol, a prostaglandin analogue, has been shown to be effective in reducing NSAID-related peptic ulcers and their complications. Unfortunately, adverse effects may limit compliance in some patients. Histamine H2 antagonists have only limited efficacy in the prevention of NSAID-induced ulcers in humans, particularly in the stomach, except at higher than standard dosages. This may relate to their relatively modest effect in elevating gastric pH, especially in comparison with proton pump inhibitors. Several studies now confirm the efficacy of proton pump inhibitors in the short and longer term prevention of NSAID-induced upper gastrointestinal injury. Placebo-controlled studies suggest reductions of over 70% in gastric and duodenal ulcer rates over 3 to 6 months. The recent ASTRONAUT (Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment) study documented the greater prophylactic efficacy of omeprazole over ranitidine at standard dosages for 6 months. The OMNIUM (Omeprazole versus Misoprostol for NSAID-Induced Ulcer Management) study showed omeprazole to be slightly more effective overall than misoprostol in preventing the upper gastrointestinal adverse effects of NSAIDs, with both substantially more effective than placebo, although misoprostol was somewhat less well tolerated. Although substantial reductions in NSAID ulceration are now achievable when co-therapy with a proton pump inhibitor is given, a few patients will still develop ulcers and their complications. Hence the judicious use of NSAIDs in the first instance cannot be overemphasised.

Critical issues in the pathophysiology and management of peptic ulcer disease.

OBJECTIVE: To discuss some of the critical issues in the pathophysiology and management of peptic ulcer disease. OPINION: Peptic ulcer disease has multiple causes, although gastric acid has traditionally been considered the primary aggressive factor. Helicobacter pylori infection is established as a major causative factor, but some aspects of the mechanisms by which H. pylori causes peptic ulceration remain unclear. Treatment with proton pump inhibitors (PPIs) is the most effective means of healing peptic ulcers. In addition to healing a higher proportion of ulcers than H2-receptor antagonists, PPIs provide faster healing and relief of symptoms. The ability of PPIs to produce effective and sustained inhibition of gastric acid secretion suggests that they may also become the treatment of choice for gastric ulcers caused by non-steroidal anti-inflammatory drugs. However, eradication of H. pylori infection is more effective than maintenance therapy with antisecretory agents in reducing the rate of recurrence of peptic ulcers initially healed using antisecretory therapy. H. pylori eradication is therefore the optimal, and almost certainly the most cost-effective, approach to the long-term management of patients with peptic ulcer disease. Despite the fact that 90-95% of patients with demonstrable duodenal ulceration are probably infected with H. pylori, it is recommended that, in routine clinical practice, infection is diagnosed before eradication therapy is instituted. H. pylori testing 4-6 weeks after the completion of eradication therapy is also recommended to check that the infection has been successfully cured. For routine clinical practice, the highly sensitive and specific rapid urease test is probably the most useful diagnostic approach. The most appropriate H. pylori eradication regimen remains to be defined. However, 1-2 weeks of treatment with a combination of a PPI and two antimicrobial agents achieves eradication rates in excess of 90%, which are similar to those attained using standard triple therapy, but with the advantage of better patient compliance and greater tolerability. Preliminary evidence also suggests that H. pylori eradication prevents the recurrence of peptic ulcer bleeding, although further studies are required. CONCLUSION: H. pylori eradication by 1-2 weeks' treatment with a combination of a PPI and two antimicrobial agents appears to be the optimal (and probably the most cost-effective) approach to the long-term management of patients with peptic ulcer disease, and represents a major advance in the management of such patients.

Small intestinal malabsorption of vitamin B(12) in iron-deficient rats.

Rats were rendered iron deficient by a combination of diet and bleeding to study its effects on vitamin B(12) absorption. Small intestinal loops were isolated in vivo and the absorption of -57Co-vitamin B(12) bound to a known quantity of intrinsic factor was measured. Iron deficiency resulted in the impairment of both uptake and transport of B(12). This malabsorption was corrected within 5 days by parenteral iron repletion. The findings were not due to a non-specific effect of anaemia since no correlation existed between haemoglobin levels and B(12) absorption in rats anaemic as a result of acute blood loss. No evidence was found for an altered small-intestinal microflora, bacterial counts being similar in iron-deficient and control rats. It is concluded that iron deficiency in the rat results in impaired absorption of B(12) by the small intestine, probably as a result of some defect produced in the enterocyte.

Aspirin-induced glandular dysplasia of the stomach: histologic and histochemical studies in rats.

Stomachs of 22 rats treated with aspirin for six months were examined histologically at times ranging from 6 to 18 months after completion of treatment. Healed chronic gastric ulcers were found in 20 rats. Glandular dysplasia was present at the sites of healed ulcers in 12 rats, the glands extending into the submucosa, muscularis propria, and even subserosal fat. The apparent lack of progression with time and the absence of metastases suggest that the changes are not neoplastic but are a consequence of repeated injury and regeneration, with entrapment of glands below the level of the muscularis mucosae. The lesions in the aspirin-treated animals closely resemble those of gastritis cystica polyposa and colitis cystica profunda in the human subject.

Pharmacokinetic and gastric secretory studies of ranitidine in man.

A sensitive and specific high pressure liquid chromatographic procedure for ranitidine estimation is described and pharmacokinetic studies in six healthy volunteers reported. Each subjects received 20 mg of ranitidine i.v.; 20 mg, 40 mg and 100 mg orally having fasted overnight and 100 mg with a standard meal. Following the i.v. dose, ranitidine plasma concentrations fell biexponentially with a distribution half-life of 6.1 +/- 0.9 min and a terminal elimination half-life of 1.9 +/- 0.1 h. The volume of distribution was 115 +/- 7 1 and the systemic plasma clearance 709 +/- 62 ml/min. After 20 mg oral doses the systemic availability was high (88 +/- 10%). Bioavailability was unaffected by food and AUC increased linearly with dose to 100 mg. Renal excretion of unchanged ranitidine was between 50 and 70% and a further 1-3% was excreted as desmethylranitidine. In separate studies, the inhibitory action of cimetidine and ranitidine on pentagastrin stimulated gastric acid output was compared in seven duodenal ulcer patients. Results so far indicate that ranitidine 150 mg i.v. produces a more pronounced and more prolonged suppression of pentagastrin stimulated gastric acid output than cimetidine 200 mg i.v. (p less than 0.001). Ranitidine produced a sustained near total (greater than 90%) suppression in acid output in the period 60 to 120 min after drug administration, whereas acid output with cimetidine was less and fell from 82 to 54% in the same period.

Predictors of gastroduodenal erosions in patients taking low-dose aspirin.

BACKGROUND: Gastroduodenal ulcers are common in patients taking low-dose aspirin. However, the factors predisposing to mucosal erosions, the precursor lesions, are not well known. AIMS: To examine the potential risk factors for the development of erosions in patients chronically taking low-dose aspirin. METHODS: Patients included were taking aspirin 75-325 mg daily for >28 days. Exclusion criteria included use of nonsteroidal anti-inflammatory and ulcer-healing drugs. Demographic data were collected at baseline, prior to endoscopy to determine the frequency and number of erosions and Helicobacter pylori status. In those without ulcer or other exclusions, endoscopy was repeated at 3 months. RESULTS: Fewer patients had gastric erosions if they were H. pylori +ve (48.5% vs. 66.4% in H. pylori-ve patients at baseline, P = 0.17; 40.0% vs. 64.1% at 3 months, P = 0.029). If gastric erosions were present, they were also less numerous in H. pylori +ve patients (3.61 +/- 0.83 vs. 4.90 +/- 0.53 at baseline, P = 0.026; 2.17 +/- 0.68 vs. 5.68 +/- 0.86 at 3 months, P = 0.029). There was a trend (0.1 > P > 0.05) for more gastric erosions in those taking >100 mg/day aspirin. Males had more duodenal erosions at baseline (25.2% vs. 7.5%, P = 0.016). Patient age did not affect the presence or number of erosions. H. Pylori was not significantly associated with duodenal erosion numbers. CONCLUSIONS: Helicobacter pylori infection may partially protect against low-dose aspirin-induced gastric erosions; damage to the stomach appears weakly dose-related; and older age does not increase the risk of erosions.