Does treatment with cimetidine extended beyond initial healing of duodenal ulcer reduce the subsequent relapse rate?

Cimetidine 1 g daily is often continued for a fixed period beyond the time of healing of duodenal ulcer on the assumption that it might reduce the subsequent relapse rate. To test this, 194 patients whose ulcers had healed after one month of cimetidine 1 g daily were allocated at random to three groups for further treatment with cimetidine 1 g daily for two months (n = 63) or five months (n = 66) or placebo (n = 65). Thereafter all patients received placebo. Endoscopy was done routinely every three months, or earlier if symptoms recurred. During follow-up in the placebo phase, which lasted for up to 25 months, the estimated total proportions of patients in the three groups with symptomatic recurrences of ulcer were 80%, 90%, and 77%, respectively; the corresponding proportions with silent plus symptomatic relapses were 92%, 90%, and 100%. The relapse rates were also similar in all three groups. Statistical analysis showed a significant variation in relapse rate but the differences were regarded as clinically unimportant. These findings show that full-dose cimetidine continued for several months beyond the time of healing of duodenal ulcer dose not decrease the risk of subsequent relapse.     

Stimulation of HCO3- secretion by the prostaglandin E2 analog enprostil: studies in human stomach and rat duodenum

This study investigated the action of enprostil, a synthetic analog of PGE2, on gastric HCO3- secretion in humans and on duodenal HCO3- secretion in the anesthetized rat. A previously validated 2-component model was used to calculate gastric HCO3- and H+ secretion in 10 human subjects. Compared to placebo, a single 70 micrograms oral dose of enprostil increased basal gastric HCO3- secretion from 1810 +/- 340 to 3190 +/- 890 mumol/hr (P less than 0.05). In addition, enprostil reduced basal gastric H+ secretion from 5240 +/- 1140 to 1680 +/- 530 mumol/hr (P less than 0.02). Enprostil also increased HCO3- secretion and reduced H+ secretion during intravenous pentagastrin infusion. In the rat, duodenal HCO3- secretion was measured by direct titration in situ using perfused segments of duodenum just distal to the Brunner gland area and devoid of pancreatic and biliary secretions. Addition of enprostil (10 micrograms/ml) to the duodenal bathing solution increased duodenal HCO3- secretion from 6.3 +/- 1.3 to 15.1 +/- 2.0 mumol/cm X hr (P less than 0.01, n = 6). The stimulatory action of enprostil on duodenal HCO3- secretion at 10 micrograms/ml was comparable in magnitude and duration to that of 10 micrograms/ml natural PGE2. In summary, the PGE2 analog enprostil stimulated gastroduodenal HCO3- secretion, effects which may be beneficial in protection of the gastroduodenal mucosa against luminal acid.     

An Alternative Non-Macrolide, Non-Imidazole Treatment Regimen for Curing Helicobacter pylori and Duodenal Ulcers: Ranitidine Bismuth Citrate Plus Amoxicillin

Background. Because patients who fail to be cured of H. pylori infection following macrolide or imidazole therapy are difficult to treat, there is a clear need for a reasonably effective and simple second-line treatment regimen. The purpose of these two studies was to evaluate the efficacy of ranitidine bismuth citrate (RBC) plus amoxicillin for the cure of H. pylori infection and for healing duodenal ulcers and preventing ulcer relapse.
Materials and Methods. Two identically designed randomized, double-blind, double-dummy studies were conducted in patients with an H. pylori -associated duodenal ulcer. Patients were treated with either RBC 400 mg bid for 4 weeks plus amoxicillin 500 mg qid for 2 weeks, RBC 400 mg bid for 4 weeks and placebo qid for 2 weeks, placebo bid for 4 weeks and amoxicillin 500 mg qid for 2 weeks, or placebo bid for 4 weeks and placebo qid for 2 weeks. Patients with healed ulcers after 4 weeks of treatment were eligible for entry into a 24-week observation phase for the assessment of H. pylori status (culture, histology, and CLOtest^TM) and ulcer relapse.
Results. A total of 229 patients with confirmed H. pylori infection at baseline were evaluated. Of these, 132 whose ulcers had healed entered the 24-week posttreatment observation phase. The combination of RBC plus amoxicillin resulted in higher H. pylori cure rates (55%) and higher duodenal ulcer healing (74%) than did either treatment alone. All treatments were well tolerated.
Conclusions. The combination of ranitidine bismuth citrate plus amoxicillin cures H. pylori infection in more than half of the patients treated. This treatment regimen shows promise as the basis for future non-macrolide, non-imidazole triple therapy regimens for curing H. pylori infection. Such regimens may be appropriate second-line treatment for patients who are resistant to or who are unable to tolerate macrolide- or imidazole-containing therapies.     

Serum concentration of prolactin, gastrin and glycocholic acid in patient with peptic ulcer treated with ranitidine

In 66 patients with peptic ulcer (11 with gastric ulcer, 55 with duodenal ulcer, 19 women, 47 men) the serum concentrations of prolactin, dehydrocholic acid and gastrin were determined. The studies were repeated after treatment with ranitidine: in 50 patients after three weeks and in 40 patients after another 30 days. During the first period ranitidine 2 x 150 mg was administered, while during the second period the dose was 1 x 150 mg. The results were compared with those obtained from 120 healthy subjects. Before starting the treatment prolactin levels were significantly higher than those in the control group. During the treatment a significant decrease of the levels was observed. Similar changes of prolactin concentrations were found in the group of 39 men with duodenal ulcer isolated from the studied patients, who were compared with a group of 50 healthy men. It was not found that the development of peptic ulcer and the treatment with ranitidine exerted and effect on the changes of gastrin and dehydrocholic acid concentrations.     

Recurrent peptic ulcers in patients following successful Helicobacter pylori eradication: a multicenter study of 4940 patients

Objective. Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection. Methods. This was a multicenter study involving 4940 peptic ulcer patients who were H. pylori negative after successful eradication treatment and were followed for up to 48 months. The annual incidence of ulcer relapse in H. pylori‐cured patients, background of patients with relapsed ulcers, time to relapse, ulcer size, and site of relapsed ulcers were investigated. Results. Crude peptic ulcer recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric, duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively. Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5% and 1.3%, respectively. The recurrence rate was significantly higher in gastric ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs were significantly higher in those with gastric ulcer recurrence compared to duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at the same or adjacent sites as the previous ulcers). Conclusions. Curative treatment of H. pylori infection is useful in preventing ulcer recurrence. Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer tended to recur at the site of the original ulcers.     

Effectiveness and tolerance of selected Polish antacids in the therapy of duodenal ulcer disease. A placebo- and ranitidine-controlled study

In a randomized, open clinical trial we compared the efficiency of selected Polish antacids Alugastrin, Gastrin and Wikalina with ranitidine and placebo in the healing of duodenal ulcer, pain relief and drug toleration. One hundred and ten outpatients completed the study. The trial showed that antacids and ranitidine had similar rates of duodenal ulcer healing which were significantly better than placebo. After 4 weeks of treatment with Alugastrin, Gastrin, Wikalina and ranitidine the healing rates were 70%, 76%, 71% and 81%, respectively, compared to placebo 44%. Efficiency of antacids in pain relief was similar to placebo and slightly lower than ranitidine. Antacids were well tolerated, except for hypermagnezemia and urine alkalization caused by Gastrin and Wikalina. We conclude that studied antacids are as effective as ranitidine in promoting healing of duodenal ulcer, but because of side effects they are not recommended for maintenance therapy.     

Antiulcer activity of Andrographis paniculata (Burm.f.) wall. against cysteamine-induced duodenal ulcer in rats

Antiulcer activity of Andrographis paniculata was evaluated by cysteamine induced duodenal ulcer model in rats. Male albino Wistar rats were pre-administered with 200 mg/kg body wt. of hydroalcoholic extact of Andrographis paniculata (HAEAP) orally, for 30 days prior to i.p. administration of 420 mg/kg body wt. of cysteamine as a single dose. Rats preadministered with 30 mg/kg body wt. of ranitidine served as standard drug. Ulcer index, thiobarbituric acid reactive substances, mucin, glutathione peroxidase and myeloperoxidase activities, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, glycoproteins and membrane bound enzyme activities were measured in duodenum of experimental animals. The ulcer score and myeloperoxidase activity were significantly minimized in rats treated with HAEAP. Mucin content was found to be preserved in rats treated with the extract. GSH/GSSG ratio and glutathione peroxidase activities were found to be maintained by the HAEAP. Level of lipid peroxidation products was found to be significantly low in HAEAP treated rats compared to ulcer control rats. The basolateral and brush border membrane bound enzyme activities which were depleted significantly in ulcer control rats were found to be maintained in rats pre-treated with the extract. The ulcer preventing effect was comparable to that of ranitidine treated rats. Level of glycoproteins was also found to be preserved in rats treated with the extract. The normal rats treated with the HAEAP did not show any abnormal alterations in the parameters studied. Histopathological observations also showed the ulcer preventing effect of the HAEAP. It is suggested that the ulcer preventing effect may be due to its mucin preserving and antioxidant nature.     

Resistance to medical ulcer therapy--possible reasons and management.

In 112 patients with duodenal ulcer (males, mean age 29, range 18-35) with a history of at least 3 years, and never being treated with H2-antagonists, maintenance therapy with Tagamet was started. All of them had ulcer recurrence when entering the study. The first two months a full dose was applied, after this bedtime doses up to 24 months. Endoscopy was performed at the beginning, after the first and second months and then every two-month period. Gastric secretion was measured every 2-3 months. A resistant ulcer was defined as one 1/not healing within the two initial months, 2/recurring on maintenance treatment. RESULTS: in 78% the ulcer was healed within one month, in 96% within two months, in the rest within the following 3-4 weeks. Relapses occurred in 21 patients, altogether 27 times. Factors likely to contribute to recurrence included a large ulcer size, longer duration, an inflamed mucosa and--most frequently--heavy smoking. Patients with relapses had higher initial secretory values and smaller decrease during maintenance treatment. Helicobacter pylori (examined in a subgroup) was not clearly associated with ulcer recurrence.     

Behavior of thyrotropic, triiodothyronine, thyroxine and cortisol hormone levels in blood serum of patients with duodenal ulcer treated with ranitidine]

Blood serum concentrations of thyrotropic hormone (TSH), triiodothyronine (T3), thyroxine (T4) and cortisol have been measured in 50 patients with duodenal ulcer. The determinations were repeated after a specific time of treatment with ranitidine: in 45 patients after 3 weeks and in 37 after additional 30 days of treatment. During the first period of treatment ranitidine was administered at a dose of 300 mg divided into two daily doses and during the second period of treatment at a single daily dose of 150 mg. A small but statistically significant changes, an increase in T3 and a decrease in TSH concentration, were observed before the treatment. No changes concerning these two parameters were found as an effect of the treatment. A decrease in the concentration of T4 was found, on the other hand, after three weeks of ranitidine administration. This decrease persisted after further 30 days of chronic treatment with ranitidine. No significant changes concerning blood serum cortisol concentration were found in any of the studied groups.     

Gastric antisecretory and antiulcer activity of oxytocin in rats and guinea pigs.

The effect of oxytocin (1 mg/kg s.c) on gastric acid secretion and on different experimentally induced gastric and duodenal ulcers was studied. The acute gastric ulcer models used were pylorus ligation, indomethacin, ethanol and histamine induced acute gastric ulcers. Chronic gastric ulcers were induced using acetic acid and duodenal ulcers by cysteamine hydrochloride. Oxytocin showed significant antisecretory and antiulcer activity in pylorus ligated rats. Similarly oxytocin reduced the ulcer index in histamine induced gastric ulcers in guinea pigs and cysteamine induced duodenal ulcers in rats. The antiulcer and antisecretory effect was comparable to that of ranitidine (50mg/kg, i.p) though less in intensity. However, it did not show any gastric cytoprotective effect in ethanol and indomethacin induced ulcer models but ranitidine showed protection (p<0.05) in later model. Oxytocin enhanced gastric ulcer healing in acetic acid induced chronic gastric ulcer model. The reversal of oxytocin effect by atosiban, an oxytocin receptor antagonist indicates a role for oxytocin receptors. The antiulcer activity of oxytocin can be attributed to its antisecretory effect.     

Inhibition of leukocyte migration after concanavalin A and phytohemagglutinin in patients with ulcers]

An attempt of the assessment of T-cells function in patients with gastric or duodenal ulcer has been undertaken. The studies involved 60 patients with gastric or duodenal ulcers and 47 individuals of the control group. Lymphocyte reactivity to different concentrations of concanavalin A and phytohemagglutinin has been assessed with leukocyte migration inhibition test. Lymphocyte T function has been examined also in patients with gastric or duodenal ulcers in reference to the theophylline-dependent and theophylline-sensitive subpopulation of T-cells. Leukocyte migration index values after phytohemagglutinin and concanavalin A did not differ significantly in patients with gastric or duodenal ulcers and theophylline-sensitive T-cells. Differences have been noted in the migration inhibition deficits. This phenomenon has been least frequent in case of phytohemagglutinin in the control group (5.8%) and most frequent in patients with gastric ulcer (62%). Percentage of patients responding to higher concanavalin A concentration (40 micrograms/ml) with leukocyte migration inhibition has been the highest in patients with duodenal ulcer. This index value has been significantly lower (p < 0.05) only in patients with duodenal ulcer and increased number of theophylline-dependent lymphocytes T. Increased reactivity of T-cells to higher concanavalin A concentration in patients with duodenal ulcer with theophylline-dependent T-cells in peripheral blood probably indicates increased the suppressor lymphocytes activity.     

Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine.

OBJECTIVE: To evaluate the prophylactic effect of ranitidine 150 mg twice daily in patients requiring one of the following non-steroidal anti-inflammatory drugs: naproxen, piroxicam, diclofenac, and indomethacin. In addition, risk factors were studied in order to help in targeting of such treatment to specific groups of patients. DESIGN: Double blind, placebo controlled, randomised, parallel group with endoscopic assessments at 0, 4, and 8 weeks. SETTING: Multicentre outpatient study at secondary referral centres in five European countries. PATIENTS--297 patients with rheumatoid arthritis or osteoarthritis over the age of 18 without lesions in the stomach and duodenum at baseline endoscopy (after one week without taking non-steroidal anti-inflammatory drugs). Those taking other antirheumatic agents, concomitant ulcerogenic drugs, or treatment for peptic ulcers within the previous 30 days were excluded. Age, sex, arthritic disease, and type of non-steroidal anti-inflammatory drug used were comparable in the two treatment groups. In all, 263 patients completed the trial. INTERVENTIONS: Ranitidine 150 mg twice daily or placebo (plus the selected non-steroidal anti-inflammatory drug) was prescribed within five days after the baseline endoscopy for two consecutive periods of four weeks. Paracetamol was permitted during the study, but not antacids. Patients were withdrawn if the most severe grade of damage (including ulceration) was found at the four week endoscopy or when indicated, or with lesser damage at the investigator''s discretion. END POINT: Frequency of gastric and duodenal ulceration or lesions, or both. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of peptic ulceration by eight weeks was 10.3% (27/263); 2 out of 135 (1.5%) developed duodenal ulceration in the ranitidine group, compared with 10 out of 126 (8%) taking placebo. The frequency of gastric ulceration was the same (6%) for the two groups at eight weeks. Though significantly fewer gastric lesions developed in the ranitidine group by eight weeks. The frequency of non-ulcerative lesions in the duodenum did not differ greatly for the two groups at either time point. Twelve out of 75 (16%) patients taking piroxicam developed peptic ulceration, of whom two thirds had duodenal ulceration. Patients with a history of peptic ulcer were particularly susceptible to recurrent ulceration, against which ranitidine offered some protection. CONCLUSIONS: Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.     

Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.

OBJECTIVE--To determine whether azathioprine can prevent relapse in ulcerative colitis. DESIGN--One year placebo controlled double blind trial of withdrawal or continuation of azathioprine. SETTING--Outpatient clinics of five hospitals. SUBJECTS--79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo. MAIN OUTCOME MEASURE--Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance. RESULTS--For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal. CONCLUSIONS--Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.     

Gastrointestinal complications of renal transplantation. 1. The upper gastrointestinal tract.

In 95 consecutive cases of cavaderic renal transplantation followed up for 1 to 83 months (mean 23.1 months) 17 complications developed in the upper gastrointestinal tract of 15 patients; these included duodenal ulcer in 12 and gastric ulcer, esophagitis, hemorrhagic gastritis, small-bowel obstruction and small-bowel perforation in 1 each. The occurrence of a complication was not related to the patient''s age, sex, blood group or use of cigarettes or alcohol, the duration of hemodialysis before transplantation, the tissue match or the number of infusions of immunosuppressive medication. One patient died of the complication. The peptic ulcers that developed after transplantation were successfully managed conservatively in 69% of cases. Since surgical treatment in patients whose immune response has been suppressed is associated with an increased frequency of complications such as disruption of suture lines, it is preferable to reserve it for those in whom complications develop that are unresponsive to conservative measures.     

Intermittent treatment of duodenal ulcer with cimetidine.

Intermittent treatment with short courses of cimetidine given only when symptoms recurred was assessed in patients with duodenal ulcer as an alternative to maintenance treatment. Their progress was followed up for up to 22 months. Gastroscopy was carried out in most attacks to confirm recurrence of the ulcer and subsequent healing. Out of 125 patients treated, 83 relapsed, of whom 21 defaulted. After retreatment 36 patients relapsed again. The pattern of relapse and remission for the group as a whole was similar after both courses of treatment, indicating an unchanged natural history. Nevertheless, wide variation occurred in individual patients, so that the pattern of relapse could not be predicted by the duration of the initial remission. Most patients had one or two or rarely three symptomatic relapses a year, which were rapidly treated successfully with cimetidine. Therefore, unless the necessity for long-term maintenance treatment is established, intermittent treatment provides an adequate alternative in most patients with duodenal ulcer.     

Randomised double blind controlled study of recurrence of gastric ulcer after treatment for eradication of Helicobacter pylori infection.

OBJECTIVE: To determine whether eradication of Helicobacter pylori infection reduces recurrence of benign gastric ulceration. DESIGN: Randomised, double blind, controlled study. Patients were randomised in a 1:2 ratio to either omeprazole 40 mg once daily for eight weeks or the same treatment plus amoxycillin 750 mg twice daily for weeks 7 and 8. A 12 month untreated follow up ensued. SETTING: Teaching and district general hospitals between 1991 and 1994. SUBJECTS: 107 patients with benign gastric ulcer associated with H pylori. MAIN OUTCOME MEASURES: Endoscopically confirmed relapse with gastric ulcer (analysed with life table methods), H pylori eradication, and healing of gastric ulcers (Mantel-Haenszel test). RESULTS: 172 patients were enrolled. Malignancy was diagnosed in 19; 24 were not infected with H pylori; four withdrew because of adverse events; and 18 failed to attend for start of treatment, leaving 107 patients eligible for analysis (35 omeprazole alone; 72 omeprazole plus amoxycillin). In the omeprazole/amoxycillin group 93% (67/72; 95% confidence interval 84% to 98%) of gastric ulcers healed and 83% (29/35; 66% to 94%) in the omeprazole group (P = 0.103). Eradication of H pylori was 58% (42/72; 46% to 70%) and 6% (2/35; 1% to 19%) (P < 0.001) and relapse after treatment was 22% (16/72) and 49% (17/35) (life table analysis, P < 0.001), in the two groups, respectively. The recurrence rates were 7% (3/44) after successful H pylori eradication and 48% (30/63) in those who continued to be infected (P < 0.001). CONCLUSIONS: Eradication of H pylori reduces relapse with gastric ulcer over one year. Eradication rates achieved with this regimen, however, are too low for it to be recommended for routine use.     

Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding

AIM: To evaluate the effect of Helicobacter pylori eradication on ulcer bleeding recurrence in a prospective, long-term study including more than 400 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. H. pylori infection was confirmed by rapid urease test, histology or (13)C-urea breath test. Several eradication regimens were used. Ranitidine 150 mg was administered daily until eradication was confirmed by breath test 8 weeks after completing eradication therapy. Patients with therapy failure received a second or third course of therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy, and were controlled yearly with a repeated breath test. RESULTS: Four hundred and twenty-two patients were followed up for at least 12 months, with a total of 906 patient-years of follow up. Mean age was 59 years, and 35% were previous nonsteroidal anti-inflammatory drug (NSAID) users. Sixty-nine percent had duodenal, 24% gastric, and 7% pyloric ulcer. Recurrence of bleeding was demonstrated in two patients at 1 year (incidence: 0.22% per patient-year of follow up), which occurred after NSAID use in both cases. CONCLUSION: Peptic ulcer rebleeding does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved.     

The H2-receptor antagonist era in duodenal ulcer disease.

This paper reviews the remarkable impact of H2-receptor antagonists on duodenal ulcer management. The development and the scientific rationale of these agents are presented, and efficacy and safety aspects in the short- and long-term treatment of duodenal ulcer disease discussed. Attention is focused on the possible role of "acid rebound" in ulcer relapse following the withdrawal of therapy and on the clinical relevance of prolonged suppression of acid secretion in patients on long-term therapy.     

Effect of 16,16-dimethyl PGE2 on renal papillary necrosis and gastrointestinal ulcerations (gastric, duodenal, intestinal) produced in rats by mefenamic acid

Mefenamic acid, given orally to rats at a single dose of 1200 mg/kg, produced renal papillary necrosis (RPN) in 63% of animals. The incidence was reduced to 27% by 16,16-dimethyl PGE2 (dmPGE2), given at an oral dose of 0.75 mg/kg t.i.d. RPN is likely to be caused by the renal prostaglandin depletion elicited by mefenamic acid, an inhibitor of prostaglandin cyclooxygenase. Substitution with dmPGE2 reduces RPN presumably by preventing the prostaglandin depletion. We conclude that the prostaglandin used is cytoprotective for the kidney. Mefenamic acid, like most nonsteroidal anti-inflammatory compounds (NOSAC), produced ulcerations of the small intestine (jejunum and ileum). These were prevented by dmPGE2 (intestinal cytoprotection). Unlike most other NOSAC, however, mefenamic acid produced duodenal ulcers in nearly all animals (80%). Of these ulcers, 88% were perforated. Twenty-five of the twenty-six animals that died had a perforated ulcer. These duodenal ulcers were also prevented by dmPGE2. Mefenamic acid-induced ulcers could be used as an experimental model for testing agents with a potential for preventing or healing duodenal ulcers.     

Omeprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial

One hundred and sixty two patients with endoscopically proved reflux oesophagitis stratified for severity, 66 with grade 1 disease (erythema and friability) and 96 with grade 2 or 3 disease (including erosions or ulcerations), were allocated at random to double blind treatment with omeprazole 40 mg in the morning or ranitidine 150 mg twice daily for up to 12 weeks. A patient could be evaluated sooner if symptomatic relief and endoscopically normal mucosa (grade 0) were noted after four to eight weeks'' treatment. Patients treated with omeprazole responded significantly more rapidly than those treated with ranitidine (p<0.0001), cumulative healing rates at four, eight, and 12 weeks being 90%, 100%, and 100% respectively for those with grade 1 disease and 70%, 85%, and 91% respectively for those with grade 2 or 3 disease in the omeprazole group. Corresponding rates in the ranitidine group were 55%, 79%, and 88% (grade 1) and 26%, 44%, and 54% (grade 2 or 3). Relief of the major symptoms of heartburn, regurgitation, and dysphagia and improvements in the histological appearance of the mucosa occurred earlier and were again more pronounced during treatment with omeprazole than with ranitidine.This observed superiority of omeprazole 40 mg in the morning over ranitidine 150 mg twice daily in the short term treatment of reflux oesophagitis was obtained without major clinical or biochemical side effects, but further research is needed into longer term use of omeprazole and the effects of the acid inhibition it induces.