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Background: The accidental ingestion of the third larval stage of Anisakis can cause acute clinical symptoms, which are relieved via extraction of the larvae. Although this is a highly effective technique, it can only be practiced when the larvae are found in accessible areas of the gastrointestinal tract, and therefore instead the condition has often been treated using various different drugs., Aims: This study evaluates the effectiveness of gastric acid secretion inhibitors (omeprazole and ranitidine), gastric mucosal protectants (sucralfate) and anthelmintics (mebendazole and flubendazole) in treating anisakiasis in Wistar rats., Methods: Rats were infected with Anisakis-type I larvae and administered the drugs via a gastric probe. Data were recorded regarding the number of live and dead larvae, their location both within the animal and in its feces, and the presence of gastrointestinal lesions. Additionally, gastric pH was measured and histology performed., Results: While rats in all experimental groups exhibited lesions; those treated with ranitidine and mebendazole showed significantly fewer lesions (50% and 35% of rats exhibited lesions, respectively). Histological examination of the gastric lesions revealed infection-induced changes, but no significant differences were observed between the treated and untreated rats., Conclusions: Mebendazole was found to be most efficacious in preventing gastrointestinal lesions, followed by ranitidine, which was the most effective antacid of those studied. Both these drugs could thus be considered as part of the conservative management of anisakiasis.

Background: Gastroesophageal reflux disease (GERD) is a chronic symptomatic condition and may be associated with erosive esophagitis (EE). Considerable data on the long-term maintenance of healing of EE are available, but data on long-term GERD symptom prevention and patient quality of life (QOL) are limited., Aims: To investigate QOL in subjects with healed EE who received 12 months of double-blind maintenance treatment with lansoprazole or ranitidine, followed by long-term open-label lansoprazole therapy to prevent recurrence of EE., Methods: Subjects with healed EE received 12 months of double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily, followed by dose-titrated, open-label lansoprazole therapy for up to 82 months., Results: During double-blind treatment (n = 206), lansoprazole-treated patients showed significantly (P

Objective: This study focused on unhealed gastrocutaneous fistulas to resolve whether standard drugs that promote healing of gastric ulcers may simultaneously have the same effect on cutaneous wounds, and corticosteroid aggravation, and to demonstrate why peptides such as BPC 157 exhibit a greater healing effect. Therefore, with the fistulas therapy, we challenge the wound/growth factors theory of the analogous nonhealing of wounds and persistent gastric ulcers., Methods: The healing rate of gastrocutaneous fistula in rat (2-mm-diameter stomach defect, 3-mm-diameter skin defect) validates macro/microscopically and biomechanically a direct skin wound/stomach ulcer relation, and identifies a potential therapy consisting of: (i) stable gastric pentadecapeptide BPC 157 [in drinking water (10 microg/kg) (12 ml/rat/day) or intraperitoneally (10 microg/kg, 10 ng/kg, 10 pg/kg)], (ii) atropine (10 mg/kg), ranitidine (50 mg/kg), and omeprazole (50 mg/kg), (iii) 6-alpha-methylprednisolone (1 mg/kg) [intraperitoneally, once daily, first application at 30 min following surgery; last 24 h before sacrifice (at postoperative days 1, 2, 3, 7, 14, and 21)]., Results: Greater anti-ulcer potential and efficiency in wound healing compared with standard agents favor BPC 157, efficient in inflammatory bowel disease (PL-14736, Pliva), given in drinking water or intraperitoneally. Even after 6-alpha-methylprednisolone aggravation, BPC 157 promptly improves both skin and stomach mucosa healing, and closure of fistulas, with no leakage after up to 20 ml water intragastrically. Standard anti-ulcer agents, after a delay, improve firstly skin healing and then stomach mucosal healing, but not fistula leaking and bursting strength (except for atropine)., Conclusion: We conclude that BPC 157 may resolve analogous nonhealing of wounds and persistent gastric ulcers better than standard agents.

Up to 20% of patients, or even more, will fail to obtain eradication after a standard triple therapy. The aim of this study is to evaluate the efficacy of moxifloxacine-containing regimens in the first-line treatment of Helicobacter pylori. One hundred and twenty H. pylori-positive patients were randomized into four groups to receive one of the following 14-day treatments: ranitidine bismuth citrate (RBC) 400 mg b.d. plus amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (RAC group, n = 30); RBC 400 mg b.d. plus moxifloxacine 400 mg o.d. and amoxicillin 1,000 mg b.d. (RAM group, n = 30); esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus clarithromycin 500 mg b.d. (EAC group, n = 30); and esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus moxifloxacine 400 mg o.d. (EAM group, n = 30). Eradication was assessed by (13)C urea breath test 8 weeks after therapy. Per-protocol and intention-to-treat eradication was achieved in 23 out of 30 patients (76.7%, 95% confidence interval [CI]: 61-92) in the RAC group, in 20 patients (66.7%, 95% CI: 49-84) in the RAM group, in 16 patients in the EAM group (53.3%, 95% CI: 34-71), and in 19 patients in the EAC group (63.3%, 95% CI: 54-72). Mild or moderate side-effects were significantly more common in the EAM group (70%) compared to the RAC (36.6%), RAM (43.3%), and EAC (56.6%) groups (P = 0.03). From our results, we conclude that moxifloxacine-containing triple therapies have neither eradication nor compliance advantages over standard triple therapies. Further studies with new antibiotic associations are needed for the better eradication of H. pylori in developing regions of the world.

In some patients, proton pump inhibitors do not abolish nocturnal gastric acidity and additional evening antisecretory medication may be required. In 16 subjects with chronic heartburn, 24-hr gastric and esophageal pH were measured at baseline and again after six days of 20 mg omeprazole alone at 08:00 hr followed by placebo, 75 mg ranitidine, or 20 mg omeprazole at 22:00 hr. Integrated acidity was calculated from the cumulative, time-weighted mean acid concentrations (derived from pH values for each second). Baseline integrated gastric acidity increased progressively over 24 hr, whereas integrated esophageal acidity increased only until 22:00 hr. Morning omeprazole nearly abolished 24-hr esophageal acidity and significantly decreased overall gastric acidity but did not abolish nocturnal gastric acidity. Adding evening ranitidine or omeprazole nearly eliminated the nocturnal increase in gastric acidity. Integrated acidity was more sensitive than time pH < 4 in assessing gastric and esophageal acidity as well as their inhibition by omeprazole and ranitidine. In conclusion, integrated acidity provides novel information regarding the synergy of omeprazole plus ranitidine. Adding low-dose ranitidine helps control nocturnal gastric acidity that can occur with conventional omeprazole administration. Although the heartburn patients in the present study had nocturnal gastric acidity without accompanying nocturnal esophageal acid reflux, other patients who do have nocturnal esophageal reflux might profit from addition of bedtime ranitidine or another gastric antisecretory agent.

Eight-hundred forty-nine patients with symptomatic nonerosive GERD from two clinical trials of lansoprazole 15 mg daily (LAN 15) and lansoprazole 30 mg daily (LAN 30) vs ranitidine 150 mg twice a day (RAN 150) completed a health-related quality-of-life (HRQoL) questionnaire at baseline and four and eight weeks after treatment. The questionnaire included the Short-Form 12, GERD symptoms, eating symptoms, social restrictions, problems with sleep, work disability, treatment satisfaction, and associated importance weights items. Both LAN groups reported greater, although not significant, improvement from baseline to week 8 versus RAN 150 in the majority of HRQoL scales. Treatment satisfaction was significantly higher at week 8 in both LAN groups. Quality-days incrementally gained analysis showed that both LAN groups gained significantly more quality days than RAN 150. Patients taking lansoprazole 15 or 30 mg daily reported better outcomes than those receiving ranitidine 150 twice a day over the eight-week study.

Five patients with gastroesophageal reflux disease (GERD), who also had chronic functional diarrhea and postprandial urgency, unexpectedly noted rapid relief of their diarrhea and urgency when they took lansoprazole for their heartburn. To determine if this surprising result was not fortuitous, all 20 patients seen during the next six months for chronic diarrhea and postprandial urgency due to irritable bowel syndrome (IBS) or functional diarrhea were treated with inhibitors of gastric secretion: 14 with proton-pump inhibitors and 6 with H2 blockers. All patients had rapid, marked improvement. Usually within three days, their symptoms abated and they usually had one to three formed stools per day. Relief continued during the one to six months they were followed on therapy. Five patients stopped therapy, had recurrent diarrhea, and rapid relief upon resuming therapy. Thus, inhibition of gastric secretion effectively controls the diarrhea and postprandial urgency associated with IBS or functional diarrhea, probably by diminishing the gastrocolic or gastroenteric reflex.

In most patients duodenal ulcer is a chronic relapsing disease. If no active maintenance treatment or eradication therapy is given after healing, around 70-100% of patients have a relapse during the first year. We conducted a double-blind multicenter study in 472 patients with duodenal ulcer. They were treated with omeprazole 20 mg every morning for four or eight weeks and when healed were randomly allocated to maintenance treatment with either omeprazole 20 mg every morning or ranitidine 150 mg at bedtime for up to six months. The patients were assessed by endoscopy at monthly intervals until healing occurred. Thereafter scheduled endoscopy was carried out after 1, 3, and 6 months of maintenance treatment or immediately in the event of a suspected relapse. Healing status (intention to treat approach) was 87% at four weeks and 93% at eight weeks. At six months the estimated remission rate was 90% for omeprazole and 82% for ranitidine (P = 0.03, 95% CI 1-15%). The incidence of adverse events was similar during the two maintenance treatments. Treatment with omeprazole 20 mg every morning maintained significantly more patients in remission than treatment with ranitidine 150 mg at bedtime.

Stress ulcer prophylaxis protects against clinically important gastrointestinal bleeding and has gained widespread use. This study compares the efficacy of omeprazole to ranitidine for this indication. This was a prospective, randomized clinical trial. Sixty-seven high-risk patients were randomized to receive either ranitidine 150 mg (N = 35) intravenously daily or omeprazole 40 mg (N = 32) daily orally or by nasogastric route. Patients were monitored for clinically important bleeding. There was no statistically significant difference between treatment groups in the number of patients enrolled, gender, race, or age. The study groups were comparable in regard to the severity of illness based on their similar APACHE II score, duration of ICU stay, duration of ventilator dependence, and mortality rate. A significant difference was found only in regard to the number of risk factors per patient. The ranitidine-treated group had 2.7 risk factors per patient while the omeprazole-treated group had 1.9 (P < 0.05). Eleven patients (31%) given ranitidine and two patients (6%) given omeprazole developed clinically important bleeding (P < 0.05). Nosocomial pneumonia developed in five patients (14%) receiving ranitidine and one patient (3%) receiving omeprazole (P > 0.05). We conclude that oral omeprazole is safe, effective, and clinically feasible for stress ulcer prophylaxis.

Gastric ulcer is relatively infrequent, and clinical trails are often based on small-sized samples. The aim of this study was to define the "gold standard" therapy of active gastric ulcer. We included all single- or double-blind clinical trials on the short-term treatment of gastric ulcer. All the articles published over the period 1977-1994 were reviewed. Meta-analysis was done with both fixed and random effect models; results were shown using Galbraith's radial plot. Forty-eight papers comprising 52 studies were evaluated. Cimetidine, ranitidine, and famotidine proved significantly better than placebo [odds ratio (OR) and 95% confidence interval (CI 95%) at four to six weeks were: 2.67 (2.03-3.52), 3.94 (2.28-6.80), 1.76 (1.08-2.88), respectively]. Cimetidine and ranitidine had results comparable with the newer H2 blockers [OR (CI 95%) at four weeks: 1.16 (0.91-1.47), 1.11 (0.80-1.55), respectively]. H2 blockers were proved comparable with either sucralfate [OR (CI 95%) at eight weeks: 0.81 (0.37-1.79)] or bismuth [OR (CI 95%) at four to six weeks: 0.67 (0.37-1.20)]. Omeprazole is more effective than H2 blockers [OR (CI 95%) at four weeks: 2.00 (1.57-2.55)]. It is concluded that H2 blockers are preferred to either a placebo or sucralfate for short-term gastric ulcer treatment; the newer H2 blockers do not have significant advantages over the older types; omeprazole can be regarded as the "gold standard" for active gastric ulcer treatment.

Risk factors of slow healing were previously researched in a large sample of duodenal (DU) and gastric ulcer (GU) patients over 65 years of age; persistence of ulcer symptoms was proven the most reliable factor in predicting nonhealing ulcer, while ulcer size was of importance only for DU. We aimed to complete the analysis, with a more careful evaluation of concomitant diseases and therapies. Ranitidine 300 mg daily was given for four to eight weeks to 310 GU and 699 DU patients. Ninety-three patients dropped out of the study; 79/294 gastric ulcers and 138/635 duodenal ulcers were unhealed after four weeks. Cardiovascular, gastrointestinal, and pulmonary disorders were the most frequent concomitant diseases; NSAIDs, cardiovascular drugs, and antihypertensives were the most frequent concomitant therapies. Esophagitis was diagnosed in 15.5% of patients. Ulcer healing was the major determinant of persistence of ulcer symptoms; esophagitis emerged as an important adjunctive and independent factor. Use of hypoglycemic agents in the whole sample and smoking habit (in GU) may have also a role. With persistence of ulcer symptoms removed from the analysis, ulcer size was the most constant factor affecting ulcer healing. NSAID use, cardiovascular disorders, esophagitis (in GU), and concomitant therapy with cardiovascular drugs (in DU) also play a role. In conclusion, persistence of ulcer symptoms, the major indicator of slow ulcer healing in the elderly, is independently affected also by the presence of esophagitis. Use of hypoglycemic agents and smoking habit may also have a role in persistence of ulcer symptoms. NSAIDs, cardiovascular disorders, cardiovascular drugs, and esophagitis affect ulcer healing, for which the most constant indicators remained persistence of ulcer symptoms and ulcer size.

The aim of this study was to compare the healing effect of a gastroprotective agent and antisecretory drugs in gastric body ulcer where failure of the mucosal defense might be an important factor. Eighty-five patients with benign gastric ulcer were divided into four groups: treated with antacids (I), cimetidine (II), ranitidine (III), and colloidal bismuth subcitrate (De-Nol) (IV). Endoscopically confirmed complete healing was achieved in 57, 61, and 63% in groups I, II, and III, respectively, and in 88% in group IV (P < 0.05). Gastric secretion did not change significantly. Relapses during the next three years occurred several times more frequently in groups I, II, and III than in group IV. Helicobacter pylori was positive in about half the relapsing patients in groups I, II, and III but negative in those of group IV. It is concluded that De-Nol treatment of gastric body ulcer was more efficient than antisecretory drugs both initially and in reducing relapses.

One hundred twenty-four patients with idiopathic gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr) were prospectively evaluated and treated with ranitidine twice a day. Fifty-four patients (44%) required standard doses of ranitidine 300 mg/day for adequate treatment, and the other 70 patients (56%) required increased doses of ranitidine (mean 994 mg/day, range 600-3000 mg/day). Mean basal acid outputs for these two groups were 14.0 and 16.6 meq/hr, respectively, which were not significantly different. Nevertheless, there was a significant correlation between basal acid output and daily ranitidine dose required for therapy (r = 0.18, P = 0.05). The duration of ranitidine therapy consisted of: < 1 year (N = 46), 1 year (N = 16), 2 years (N = 19), 3 years (N = 22), 4 years (N = 15), 5 years (N = 6). Only five patients required progressive increases in ranitidine during the time of treatment, which consisted of an average of 0.5 dose adjustments per year. No side effects occurred with any of these high doses of ranitidine. These results indicate that, as in Zollinger-Ellison syndrome, ranitidine is effective therapy for patients with idiopathic gastric acid hypersecretion; however, markedly increased doses as large as 3000 mg/day may be required.

Pantoprazole is a new substituted benzimidazole, which is a potent inhibitor of gastric acid secretion by its inhibition of H+,K(+)-ATPase. Pantoprazole, 40 mg, was compared with the H2-receptor antagonist ranitidine, 300 mg, in the healing of acute duodenal ulcer. Two hundred seventy-six patients with endoscopically diagnosed duodenal ulcer were studied in this multicenter double-blind study. Patients were reendoscopied after two weeks of treatment, and those patients whose ulcers remained unhealed were also endoscoped after an additional two weeks of treatment. The primary end point was the complete healing of the ulcer. Demographic characteristics were comparable in both treatment groups. After two weeks of treatment, 90/124 (73%) patients in the pantoprazole group had healed ulcers compared with 57/126 (45%) patients in the ranitidine group (P < 0.001, per-protocol analysis). After four weeks, the cumulative healing rates were 92% and 84% in the pantoprazole and ranitidine groups, respectively (P = 0.073). Symptoms were also improved at week 2, with 84% and 72% of patients in the pantoprazole and ranitidine groups, respectively, reporting no ulcer pain (P < 0.05, per-protocol analysis). Both treatments were well tolerated. This study has confirmed the superiority of pantoprazole compared with ranitidine in the healing of duodenal ulcers and pain relief after two weeks of treatment and has shown pantoprazole to be well tolerated in this indication.

We conducted a double-blind, placebo-controlled study to evaluate the effects of ranitidine on intragastric pH and upper gastrointestinal tract bleeding in severe head injury patients. Within 24 hr of the precipitating trauma, 34 adults with Glasgow coma scale scores < or = 10 were randomized to a 6.25 mg/hr ranitidine continuous infusion or placebo for a maximum of 72 hr. Intragastric pH was recorded via an intragastric pH electrode. Patients with hematemesis, hematochezia, bright red blood, or "coffee ground" nasogastric tube aspirates plus a 5% decrease from baseline in hematocrit were considered to have gastrointestinal bleeding. Ranitidine patients maintained a significantly greater mean pH than placebo patients (placebo 2.2, ranitidine 4.1; P < 0.01). All patients had at least two bleeding risk factors at study entry. No ranitidine patients (0/16) developed bleeding compared with five (5/18) placebo patients (P < 0.05). Ranitidine continuous infusion provided consistent intragastric pH control and significant protection from stress-related upper gastrointestinal tract bleeding in a high-risk patient population.

Gastric pseudolymphoma is a rare disorder of unknown etiology that can undergo transformation into malignant lymphoma. This report describes the first case of a gastric pseudolymphoma associated with Helicobacter pylori infection that underwent complete clinical, endoscopic, and histologic resolution following treatment with bismuth subsalicylate, amoxicillin, and metronidazole. The eradication of Helicobacter pylori may have eliminated ongoing antigenic stimulation that has previously been postulated to be responsible for the development and subsequent progression of gastric pseudolymphoma.

The efficacy of omeprazole in preventing gastric mucosal injury induced by hemorrhagic shock in rats and the putative mechanisms involved in this effect were investigated in the present study. Omeprazole did not affect mean arterial blood pressure under both basal conditions and induction of hemorrhagic shock, but it evoked a marked increase in Alcian blue recovery from gastric preepithelial mucus. The morphometric analysis of histological sections revealed that omeprazole caused a significant reduction of hemorrhagic shock-induced damage of gastric mucosa. Ranitidine, used as the reference drug, failed to affect mean arterial blood pressure, Alcian blue recovery from gastric mucus, or hemorrhagic shock-induced damage of gastric mucosa. Both omeprazole and ranitidine exerted a significant inhibition of gastric acid output from anesthetized pylorus-ligated rats. Overall, the present results indicate that omeprazole is effective in protecting gastric mucosa from necrotic damage induced by hemorrhagic shock and suggest that an enhancement of gastric mucus secretion contributes to this protective action.

In a prospective study of the risk factors for duodenal ulcer relapse during maintenance (150 mg daily) ranitidine therapy, 1899 patients with chronic ulcer disease were recruited to a multicenter, German trial. Healing of all ulcers was confirmed endoscopically; endoscopy was also obligatory after one and two years or if the patients presented in the interim with symptoms of ulcer relapse. By the end of the first year, 247 patients had experienced at least one relapse and, by the end of the second year, 432 patients had relapsed at least once. The crude one- and two-year relapse rates were 13.0% (95% CI 11.5-14.5) and 22.7% (20.9-24.6%), respectively. Univariate analysis indicated that all seven prospectively defined risk factors were associated with an increased two-year relapse rate; of these, duodenal erosions distant from the healed ulcer [odds ratio (95% CI): 2.23 (1.59-3.15); P < 0.0001], smoking, past or present [1.46 (1.12-1.90); P = 0.0050], psychological stress [1.38 (1.09-1.74); P = 0.0085], heavy physical labor [1.45 (1.06-1.98); P = 0.0219], and absence of NSAID intake [1.54 (1.01-2.29); P = 0.0464] were independent risk factors on stepwise logistic regression analysis, whereas persistent symptoms at healing [1.29 (1.03-1.62), P = 0.0310] and frequent prior relapses [1.45 (1.01-2.04); P = 0.0454] were not. Multiple relapses in 107 patients [5.63% (4.60-6.67%)] were associated with duodenal erosions, smoking, stress, and heavy physical labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiation-induced esophagitis can cause substantial morbidity. Experiments in lab animals have shown that pretreatment with indomethacin protects the esophagus from radiation damage. We conducted a prospective, double-blind, randomized trial of naproxen vs placebo in patients undergoing thoracic radiation therapy for lung cancer. Twenty-eight patients were enrolled, of which 26 completed the study. Sixteen patients were given a short course of radiation (30 Gy/10 fractions/2 weeks), and 10 patients were given a longer course and a larger dose (40-50 Gy/25 fractions/5 weeks). Half of the irradiated patients were treated with naproxen, 375 mg, taken orally twice a day, and half were given an identical placebo. All patients were given ranitidine 300 mg, taken orally once a day. Study drugs were taken throughout the course of radiation. Endoscopy with esophageal biopsies and brushings was performed before and on the last day of treatment. Patients kept a daily diary for symptom scoring. Symptoms such as chest pain, dysphagia, odynophagia, and/or heartburn were reported in 15 patients from both subgroups, resulting in diet restriction to liquids only in eight patients and requiring temporary discontinuation of radiation therapy in one of them. Approximately half the patients in each subgroup developed esophagitis, usually mild and usually limited to the proximal esophagus. Severity of symptoms was not proportional to the severity of esophagitis. Candidiasis was documented in eight patients, but only four had symptoms that were severe in one. We conclude that acute radiation injury to the esophagus is observed in approximately half the patients receiving radiation therapy and can result in substantial morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to evaluate possible differences in basal gastric acid secretion with regard to severity of gastroesophageal reflux disease. Basal acid output was determined by nasogastric suction in 228 patients with gastroesophageal reflux disease who received upper gastrointestinal endoscopy and were diagnosed with either pyrosis alone (N = 98), erosive esophagitis with or without pyrosis (N = 87), or Barrett's esophagus (N = 43). Mean basal acid output for the 228 patients with gastroesophageal reflux disease was 6.5 +/- 5.6 meq/hr, which was significantly different from 65 normal subjects with a mean basal acid output of 3.0 +/- 2.7 meq/hr (P < 0.0001). Compared to normal subjects, mean basal acid outputs significantly differed for patients with pyrosis (P < 0.05), esophagitis (P < 0.01), and Barrett's esophagus (P < 0.01). There was also a significant difference in mean basal acid output between the patients with pyrosis and Barrett's esophagus (P < 0.01). Nineteen of the 98 patients with pyrosis (19%), 24 of the 87 patients with esophagitis (28%), and 15 of the 43 patients with Barrett's esophagus (35%) had gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr). One hundred forty-six patients with gastroesophageal reflux disease were treated with ranitidine in doses that resulted in complete healing of esophagitis and disappearance of pyrosis. Ninety-three patients responded to ranitidine 300 mg/day; however, 53 patients required increased dose of ranitidine (mean 1205 mg/day, range 600-3000 mg/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Parenteral control of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome is increasingly required; however, existing methods of determining the required dose are cumbersome and not applicable in all centers. A previous study suggested that the required parenteral dose of histamine H2-receptor antagonists correlated with the previous oral dose. In the present study, in 31 patients with Zollinger-Ellison syndrome we evaluated the hypothesis that an effective parenteral histamine H2-receptor antagonist dose could be predicted from the previous oral dose. Twenty-three patients were taking oral ranitidine (mean 1.3 g/day), six patients famotidine (152 mg/day), and two patients cimetidine (1.8 g/day). Each patient was treated with a continuous intravenous infusion of the equivalent dose of ranitidine (mean dose 1 mg/kg/hr with 35% requiring 0.5 mg/kg/hr, 49% 1 mg/kg/hr, 3% 1.5 mg/kg/hr, 10% 2 mg/kg/hr, and 3% 2.5 mg/kg/hr. This dose of ranitidine acutely controlled acid secretion (< 10 meq/hr) in all patients. To evaluate long-term efficacy and safety, 20 patients were maintained on this dose through the peri- and postoperative periods. Mean duration was 7.1 days with 25% treated 3-5 days, 40% 6-8 days, 30% 8-10 days, and 5% > 10 days. The predicted dose continued to control acid secretion in 95% of patients with one patient requiring one dose adjustment. No biochemical, clinical, or hematological toxicity was seen, although ranitidine was stopped in one patient because of skin rash. These results demonstrate that the parenteral dose of ranitidine required to control acid secretion in patients with Zollinger-Ellison syndrome can be predicted from the oral dose.(ABSTRACT TRUNCATED AT 250 WORDS)

The charts of 54 children diagnosed with antral H. pylori were reviewed, to establish the incidence of gastroduodenal inflammation and compare therapeutic efficacies of antisecretory vs. antibacterial therapy. Histology demonstrated normal mucosa in three cases (6%) and gastric/duodenal inflammation (> or = Whitehead grade 3) in 51 biopsies (94%). 23/43 children (53%) initially responded to H2-blockers; however, by 10 mo, 13 had relapsed clinically. All of these patients subsequently responded to amoxicillin plus bismuth subsalicylate. Of the 20 children who failed to enter remission after an initial course of H2-blockers, all became symptom-free after treatment with amoxicillin/bismuth. Compared to antisecretory agents, antibacterial treatment induced clinical remission in 11/11 patients (p < 0.001), who remained symptom-free for 10 +/- 0.2 mo. Clinical remissions were maintained in significantly more patients following amoxicillin/bismuth vs. H2-blockers (44/54 vs. 10/43 courses, p < 0.001); and, the cumulative probability of remaining asymptomatic was significantly greater in the antibiotic group (p < 0.001). These data suggest that gastric colonization by H. pylori is highly predictive of mucosal pathology in children. Initial therapy should be directed toward achieving bacterial eradication, as opposed to gastric acid suppression.

Thirty critically ill patients with mixed diagnoses underwent continuous intragastric pH monitoring for 72 hr while confined to a shock/trauma intensive care unit. The first 24 hr were monitored under no specific acid-suppressing therapy (placebo control). During the second and third consecutive 24-hr periods, patients received continuous infusion of intravenous ranitidine in the dose of 6.25 mg/hr and 12.5 mg/hr, respectively. Results of the placebo-control 24-hr study revealed that one third (N = 10) of the patients were gastric acid hyposecretors (24-hr median intragastric pH values above pH 4.0). In the normosecreting group (N = 20), both ranitidine schedules significantly elevated 24-hr median pH values, when compared to placebo (placebo 24-hr median intragastric pH 1.75; ranitidine 6.25 mg/hr 24-hr median intragastric pH 4.625, P < 0.0001; ranitidine 12.5 mg/hr 24-hr median intragastric pH 6.29, P = 0.0099). Five patients (18%) failed to adequately respond to the ranitidine 12.5 mg/hr dose (24-hr median intragastric pH < 4.0). These findings suggest that a significant percentage of intensive care unit patients are not in need of acid-suppressing therapy as prophylaxis against stress-induced ulceration. Conversely, other patients may require more intensive acid-suppressing regimens because of failure to respond to high dose H2-antagonist therapy.

Secretion of gastric acid and volume, serum gastrin concentration, and ambulatory 24-hr esophageal pH monitoring were evaluated prospectively in 12 patients with idiopathic gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr) undergoing treatment for refractory chronic long-standing pyrosis. Treatment lasted six months and consisted of three months of ranitidine (mean 2150 mg/day, range 1200-3000 mg/day), followed by three months of omeprazole (mean 33 mg/day, range 20-60 mg/day). Both ranitidine and omeprazole significantly reduced gastric acid output (P less than 0.001) and gastric volume output (P less than 0.001) compared to a basal evaluation and resulted in complete disappearance of pyrosis. Total reflux time (percent 24 hr intraesophageal pH less than 4) was significantly reduced by ranitidine (P less than 0.02) and omeprazole (P less than 0.001) compared to basal evaluation; however, the effects of omeprazole were significantly greater than ranitidine (P less than 0.05). Omeprazole caused a significant increase in serum gastrin concentration compared to both basal and ranitidine (P less than 0.05). Endoscopically documented erosive esophagitis was present in nine of the 12 patients, and seven of the 12 patients had Barrett's epithelium. All 12 patients had complete resolution of pyrosis and healed esophagitis by six months, but no significant endoscopic regression was observed in the extent of Barrett's epithelium. No side effects occurred with these high doses of ranitidine or omeprazole. These results indicate that high-dose ranitidine and omeprazole are effective therapy for refractory gastroesophageal reflux disease. However, with omeprazole, total reflux times are reduced more than with ranitidine, often into the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Tolerance to the antisecretory effects of H2-receptor antagonists develops consistently in healthy volunteers. The aim of this study was to determine whether tolerance occurs with repeated dosing of H2-receptor antagonists in patients with duodenal ulcer. Continuous intragastric 24-hr pH measurements were performed in 12 patients with duodenal ulcer in symptomatic remission before, on days 1 and 29, and two days after receiving ranitidine 300 mg four times a day for 34 days. The 24-hr median intragastric pH (interquartile range) was 5.4 (4.4-6.1) on day 1 and 4.6 (4.0-5.2) on day 29 of dosing with ranitidine (not significant). Median nighttime pH was 6.8 (6.3-7.0) on day 1 and 6.8 (6.6-7.1) on day 29 (not significant). During the daytime, the median pH decreased marginally from 4.7 (3.8-5.2) on day 1 to 3.8 (3.0-4.6) on day 29 (P less than 0.03). There was no difference in median intragastric pH during 24-hr, day and night periods before and two days after ranitidine dosing. No significant tolerance or rebound to H2-receptor antagonists was observed in patients with duodenal ulcer disease. This contrasts with data gathered in healthy volunteers and may be due to defects in the regulation of acid secretion in duodenal ulcer disease.

The study was a multicenter double-blind parallel-group comparison of omeprazole, a proton-pump inhibitor, with the H2-receptor antagonist, ranitidine, in 206 patients with duodenal ulcer. There were 145 men and 62 women of mixed racial origin with an average age of 40 years (range 19-76); 63 of them were white, 7 black, 135 coloured and 1 Asian. Each drug was given for four weeks and ulcer healing rate, symptom relief, and adverse events were recorded and compared between treatment groups. Patients received either 20 mg omeprazole once daily in the morning (N = 104) or ranitidine 300 mg once daily at night (N = 106). Healing rates were significantly higher in the omeprazole group than in the ranitidine group at both two weeks (80% vs 52%, P less than 0.001) and four weeks (95% vs 85%, P less than 0.05), using the "per protocol" approach, and these results were confirmed using the "intention to treat" approach. Omeprazole-treated patients reported significantly less daytime epigastric pain (P = 0.02) and heartburn (P = 0.04) after two weeks than ranitidine-treated patients. By four weeks, there were no significant differences in symptom reporting between groups. Both treatments were well tolerated, and there were no serious adverse events.

Zollinger-Ellison syndrome and other gastric acid hypersecretory states in which a specific etiology is identified are defined as a basal acid output of greater than 15.0 meq/hr. To determine the level of basal acid output that defines idiopathic gastric hypersecretion, basal acid outputs were investigated in normal subjects and patients with duodenal ulcers, and functional and statistical definitions for idiopathic gastric acid hypersecretion were developed. Sixty-five normal subjects were evaluated to define idiopathic gastric acid hypersecretion on a statistical basis, and 22 patients with refractory duodenal ulcers were evaluated to define idiopathic gastric acid hypersecretion on a functional basis. Mean basal acid output for the 65 normal subjects was 3.0 +/- 2.7 meq/hr. Even though the mean basal acid output for the group of 28 normal male subjects was slightly higher than for the group of 37 normal female subjects, the groups were not significantly different. The 95% confidence interval around the mean basal acid output for all normal subjects was 2.4-3.7 meq/hr, with little difference between the male and female groups. The mean basal acid output plus two standard deviations and the mean basal acid output plus three standard deviations for the 65 normal subjects were 8.4 meq/hr and 11.1 meq/hr, respectively. Of 109 patients with active duodenal ulcers treated for eight weeks with standard doses of antisecretory medication, 22 showed no healing as documented by endoscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of ranitidine 150 mg twice daily and Maalox TC three tablets four times daily were compared in patients with endoscopically confirmed duodenal ulcer. Seventy-nine patients were randomly allocated to double-blind, double-dummy treatment, stratified for smokers. Endoscopy was repeated after four weeks. Those unhealed continued treatment for a further two weeks before final endoscopy. Per protocol analysis in 53 patients showed ulcer healing rates at week 4 and at weeks 4 and 6 combined of 78 and 89% on Maalox TC, and of 81 and 91% on ranitidine, respectively. The same analysis gave overall healing rates of 81% in smokers and 100% in nonsmokers, irrespective of treatment. Both treatments provided early ulcer pain relief. Diarrhea was a commoner side effect in patients on Maalox TC. The study showed Maalox TC and ranitidine were equally effective in healing duodenal ulceration.

To assess the comparative efficacy of omeprazole 20 mg, a proton pump inhibitor, versus ranitidine 150 mg twice a day, an H2-receptor antagonist, in healing duodenal ulcers we performed a randomized, double-blind, multicenter trial in 309 patients with endoscopically diagnosed ulcers. Patients were treated for up to four weeks and were seen at week 2 and at week 4, if unhealed at week 2, for determination of ulcer status by endoscopy, review of daily self-assessment symptom diaries, and clinical laboratory including fasting serum gastrin. Gastrin levels were repeated two weeks after cessation of study medication. Evaluation of baseline demographic and laboratory parameters demonstrated no significant differences between the two groups at entry. At week 2, 42% of the omeprazole and 34% of the ranitidine-treated patients were healed (P = NS). At week 4, there was a 19% advantage in ulcer healing for the omeprazole-treated patients in comparison to those treated with ranitidine (82% vs 63%, respectively, P less than 0.05). Healing of ulcers greater than or equal to 1.0 cm occurred in 83% of those treated with omeprazole versus 37% treated with ranitidine (P less than 0.01). There were no significant differences in rate of pain relief or incidence of clinical laboratory abnormalities. Mean fasting serum gastrin value during treatment increased over the baseline in both groups, (P less than 0.05). The percent change was significantly greater with omeprazole but few patients had elevations above the upper limit of normal for the assay. Both drugs were well tolerated. Omeprazole 20 mg demonstrated superiority in healing duodenal ulcers at four weeks in comparison to ranitidine 150 mg twice daily and was more effective in healing ulcers greater than or equal to 1.0 cm.

This study set out to investigate the effects of omeprazole or ranitidine on the progression of antral gastritis and Helicobacter pylori in patients with active duodenal ulcer. A double-blind, double-dummy trial was performed in 270 patients, 241 of whom were studied histologically for the presence of H. pylori. Patients were randomized to receive omeprazole, 10 mg every morning, omeprazole, 20 mg every morning, or ranitidine, 150 mg twice a day, for four weeks. Endoscopy was performed on entry and at weekly intervals during the study; at least two antral biopsies were taken on each occasion to assess the activity and degree of chronic inflammation, as reflected by the degree of polymorphonuclear leukocyte infiltration and mononuclear cell infiltration, respectively. Biopsy specimens also were assessed histologically for H. pylori. The sex, age and maximal acid output were comparable in the three treatment groups. The percentages of patients showing an improvement in the activity of gastritis in the four consecutive weeks of treatment were 9%, 40%, 51%, and 53% for omeprazole, 10 mg (N = 78); 14%, 42%, 49%, and 53% for omeprazole, 20 mg (N = 81); and 2%, 23%, 30%, and 33% for ranitidine, 150 mg twice a day (N = 82) (life table analysis gave P less than 0.01 for both omeprazole regimens compared with ranitidine). The degree of chronic inflammation showed similar changes. The density of H. pylori decreased significantly after treatment with omeprazole, 10 mg or 20 mg, (both, P less than 0.00001) but not with ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of ranitidine administration upon the hepatotoxic effect produced by a multidose acetaminophen administration regimen was examined. Seventy-two dogs received three subcutaneous injections of acetaminophen (750, 200, 200 mg/kg body wt) in DMSO (600 mg/ml) at time zero, 9 hr later, and 24 hr after the first dose. Ten control animals (group I) were not given ranitidine, the remaining 62 dogs received an intramuscular injection of ranitidine 30 min before each acetaminophen dose. Three different doses of ranitidine were used (mg/kg body wt): 50 mg, group II (33 dogs); 75 mg, group III (14 dogs); 120 mg, group IV (15 dogs). Ranitidine reduced the expected acetaminophen-induced hepatoxicity in a dose-response manner. Moreover, a significant correlation was found between the ranitidine dose and the survival rate, as evidenced by transaminase levels in the serum and histology of the liver. This model of fulminant hepatic failure induced by acetaminophen and its modulation with ranitidine provides clinical investigators with a research tool that will be useful in the future investigation of putative medical and surgical therapies being investigated for use in the clinical management of fulminant hepatic failure. Because of the size of the animal used in this model, frequent and serial analyses of blood and liver were available for study to determine the effect of therapy within a given animal as opposed to within groups of animals.

Eleven patients presenting to an ear, nose, and throat specialist were diagnosed as having idiopathic hoarseness and prospectively evaluated for evidence of gastroesophageal reflux (GER) to determine if an association existed. Testing for GER included voice analysis, EGD, esophageal manometry, Bernstein test, and ambulatory 24-hr pH monitoring. Six of the 11 (55%) hoarse patients studied had GER by pH monitoring (mean score 105 +/- 23), and most reflux episodes were supine and prolonged (20.9 +/- 8.2% supine pH less than 4.0, longest 129 min). All patients with abnormal pH monitoring had endoscopic esophagitis (Barrett's esophagus in two, peptic stricture in one, and erosive esophagitis in three), while none of the patients with normal scores had esophagitis. Symptoms of throat pain or nocturnal heartburn were more common in the GER-positive patients (6 of 6 vs 1 of 5), and clinically helpful in discriminating which hoarse patients had pathologic GER. Treatment with ranitidine 150 mg per os twice a day for 12 weeks improved esophagitis in all patients, but the voice improved in only one of the two patients with completely healed esophagitis. This study suggests that (1) GER is frequently seen in patients with idiopathic hoarseness (55%), (2) hoarse patients with throat pain or nocturnal heartburn are likely to have severe esophagitis and should be evaluated by EGD, and (3) additional antireflux and voice therapy may be necessary to heal esophagitis and improve the voice.

The efficacy and safety of omeprazole, 40 mg once daily for four to eight weeks of treatment, were studied in 61 patients with ulcerative reflux esophagitis. A double-blind controlled study design was used, and the patients were randomly allocated to treatment with either omeprazole 40 mg once daily or ranitidine 150 mg twice daily. Endoscopy was performed prior to inclusion into the study, after four weeks and, if unhealed, again after eight weeks. Healing of esophagitis was defined as complete disappearance of all esophageal ulcerations. Symptoms were recorded before entry, after four weeks, and again after eight weeks in unhealed patients. Fifty-one patients were included in the per-protocol analysis at day 29, and 50 patients at day 57. The healing rate after four weeks of treatment was 22 of 26 patients (85%) treated with omeprazole and 10 of 25 patients (40%) treated with ranitidine (P less than 0.001). The corresponding figures after eight weeks were 24 of 25 (96%), and 13 of 25 (52%) (P less than 0.001). These results were confirmed in the intent-to-treat analysis. Patients treated with omeprazole showed a significantly faster and more profound relief in heartburn than patients treated with ranitidine: 85% had no heartburn after four weeks of treatment with omeprazole compared to 24% in patients treated with ranitidine (P = 0.00007). The percentage of patients who were free of all reflux symptoms was significantly greater in the omeprazole-treated group as compared to the ranitidine-treated group (62% and 12% respectively; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of the H2-receptor antagonists cimetidine and ranitidine on pentagastrin-stimulated gastric acid secretion in anesthetized rats, and gastric mucosal lesion formation and gastric motility in unanesthetized cold-restrained rats was studied. Both cimetidine and ranitidine suppressed pentagastrin-stimulated gastric secretion in a dose-dependent fashion. Cold restraint-induced lesion formation was not prevented with doses of both agents that inhibited acid secretion by 75%. Doses which suppressed pentagastrin-stimulated acid secretion more than 90% significantly prevented the development of gastric mucosal lesions produced by cold restraint. Doses of both H2 blockers which demonstrated significant suppression of lesion formation had no effect on cold restraint-stimulated gastric contractility. We conclude that cimetidine and ranitidine suppress cold restraint-induced lesion formation by suppressing acid secretion and not by suppressing gastric contractility.

The effect of the new synthetic prostaglandin E1 analog, misoprostol, on intragastric acidity was evaluated by means of 24-hr intraluminal pH monitoring of 16 duodenal ulcer patients. They were randomly allocated into two groups: eight received no medication and misoprostol 400 micrograms bid and eight received ranitidine 150 mg and misoprostol 400 micrograms bid not less than one week apart. The comparison of the 24-hr areas under the curve related to the median pH values showed that no difference existed between misoprostol and untreated patients in the first group, while ranitidine was significantly more effective (P = 0.00003) than misoprostol in the second group. The analysis of arithmetic differences between the 24-hr median pH values showed that misoprostol increased pH values by at least one unit compared to the untreated subgroup for about 3.5 hr, while the antisecretory action of ranitidine was far superior to that of misoprostol throughout the whole 24-hr period. It can be concluded that the effect of twice daily doses of misoprostol 400 micrograms on 24-hr intragastric pH is small and not at all comparable to that of the well-known potent H2 blocker ranitidine.

The inhibitory effect of omeprazole, a benzimidazole derivative, on gastric acid secretion was investigated in seven patients with Zollinger-Ellison syndrome resistant to treatment with large doses of histamine H2-receptor antagonists administered alone or in combination with pirenzepine. In two patients with an acute form of the syndrome, rapid control of acid overproduction was achieved with 180-mg intravenous and 120-mg oral daily doses, respectively. The other five patients, who were free of complication, initially received a standard regimen of omeprazole 60 mg orally once a day; dosage was subsequently adjusted until the basal acid output, measured 1 hr before the next dose of the drug, was less than 10 mmol/hr. The initial daily dose proved to be adequate in three patients and had to be increased to 80 mg and 60 mg bid, respectively in the remaining two patients. In all patients omeprazole therapy resulted in clinical recovery and rapid healing of mucosal lesions. The seven patients have now been followed up for 4-24 months (average 15 months). The adequacy of the daily dosage was periodically reassessed by measuring basal acid output in the hour preceding the morning dose. In one patient initially treated with 180 mg/day, dosage could be reduced to 60 mg/day. In three others, who were initially controlled with 60 mg/day, dosage had to be increased during follow-up. Despite adequate control of gastric acid secretion, one patient underwent total gastrectomy and tumor resection and another died of extensive liver metastases. The five patients still receiving omeprazole remain free of symptoms and mucosal lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate possible differences between patients with refractory duodenal ulcers and those with duodenal ulcers that respond to standard doses of antisecretory medications, we determined basal acid outputs by nasogastric suction and daily smoking histories in 75 patients with endoscopically documented active duodenal ulcers. Patients were treated for at least eight weeks with standard doses of antisecretory medications and endoscopic healing or nonhealing was documented. Fifty-five patients that had complete healing of their duodenal ulcers had a mean basal acid output of 6.6 +/- 5.3 meq/hr, and 18/55 had daily cigarette smoking histories, whereas 20 patients that had nonhealing duodenal ulcers had a mean basal acid output of 20.0 +/- 9.6 meq/hr, and 8/20 had daily cigarette smoking histories. There were no significant differences between the two groups with regard to age, duodenal ulcer size, or cigarette smoking history. However, there were significant differences in male-female ratio (P less than 0.02) and in mean basal acid output (P less than 0.001), and all patients with nonhealing duodenal ulcers had basal acid outputs of greater than 10.0 meq/hr. Patients with nonhealing duodenal ulcers were treated with increased doses of ranitidine, mean 675 mg/day (range 600-1200 mg/day), and all had complete healing endoscopically documented. These results indicate that patients treated with standard doses of antisecretory medications with nonhealing duodenal ulcers have increased basal acid outputs of greater than 10.0 meq/hr, and the duodenal ulcers heal with increased doses of antisecretory medication.

This paper reports the results of a multicenter prospective study of 188 consecutive patients affected by gastric ulcer, verified by endoscopy, in whom the frequency of a mycotic infection of the lesion was evaluated as well as the eventual influence of such pathology on the efficiency of medical treatment, the healing rate, and the healing time. A mycotic infection, defined as penetration of the periulcerous mucosa by the fungi, was found in only 13 patients (6.9%). No significant differences were found in the healing rate and healing time among these patients treated with H2-receptor antagonists and a control group of 43 matched gastric ulcer patients treated in the same period with the same therapy. It would appear from the data that mycotic infections of the gastric ulcer do not modify the efficiency of medical treatment.

A multicenter, double-blind, randomized controlled trial comparing the efficacy and safety of famotidine with ranitidine in the treatment of acute, benign gastric ulcer disease was coupled with a community-based gastric ulcer disease registry. One hundred ninety-five patients with endoscopically documented gastric ulcer disease were enrolled in the trial and randomly allocated to treatment with either famotidine 40 mg at bedtime or ranitidine 150 mg twice a day. Healing rates were similar in both groups: at four weeks 49% vs 48%, at six weeks 71% vs 69%, and at eight weeks 83% vs 81% for famotidine and for ranitidine, respectively. Pain relief, antacid tablet use, and adverse experiences were also similar in the two groups. Only 25% of patients entered in the gastric ulcer registry were enrolled in the trial. Given that patients with more severe or complicated gastric ulcer disease should be excluded from controlled trials of new drugs, the screening criteria used in the present study be excluded from findings being representative of a quarter of the patients seen in these practices. Therefore, coupling a patient registry with a clinical trial helps determine the applicability of its results. Famotidine 40 mg at bedtime is an effective and well-tolerated treatment of acute, benign gastric ulcer disease and is comparable in efficacy and safety to ranitidine 150 mg twice a day.

The effect of ranitidine in preventing mucosal damage caused by nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated for eight weeks in a prospective study of 144 patients requiring NSAIDs. Patients with normal endoscopic findings were randomly assigned to receive either ranitidine 150 mg twice daily or placebo for eight weeks, along with either ibuprofen, indomethacin, naproxen, sulindac, or piroxicam. Duodenal damage was significantly less in the ranitidine group compared with the placebo group by weeks 4 and 8 (P less than or equal to 0.01). Duodenal ulcers did not develop in any patients on ranitidine (0/57) compared with 4/49 patients (8%) on placebo (P = 0.02). No significant difference was found between treatment groups with respect to gastric damage; 6/60 (10%) in the ranitidine group compared with 6/50 (12%) in the placebo group developed gastric ulcers. These findings suggest that acid suppression is of greater importance for mucosal protection in the duodenum than in the stomach, where other defense mechanisms may be operative. While ranitidine is an effective prophylaxis for NSAID-induced damage in the duodenum, further studies are needed to define specific risk groups and to assess the potential usefulness of more complete acid suppression in preventing gastric mucosal damage.