Psychological processes underlying the association between childhood trauma and psychosis in daily life: an experience sampling study.

BACKGROUND: Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis. METHOD: We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire. RESULTS: Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all p FWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation. CONCLUSIONS: Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.

Randomized, double-blind, placebo-controlled, proof-of-concept study of the cortical spreading depression inhibiting agent tonabersat in migraine prophylaxis.

Tonabersat is a novel putative migraine prophylactic agent with an unique stereospecific binding site in the brain. Tonabersat has been shown, in animal models, to inhibit experimentally induced cortical spreading depression, the likely underlying mechanism for migraine aura, and cerebrovascular responses to trigeminal nerve stimulation. The aim was to study the potential for tonabersat as a migraine preventive. A randomized, double-blind, placebo-controlled, multicentre, parallel group study recruited patients with migraine with and without aura experiencing between two and six migraine attacks per month. After a 1-month baseline they received tonabersat 20 mg daily for 2 weeks and 40 mg daily for a further 10 weeks. The primary end-point was the change in mean number of migraine headache days between the third month and the baseline period in the intention-to-treat population comparing the placebo (n = 65) and tonabersat (n = 58) groups. At the primary end-point there was a 1.0-day (95% confidence interval -0.33, 2.39; P = 0.14) difference in reduction in migraine days between tonabersat and placebo. There were 10 secondary efficacy end-points, of which two were statistically significant. In month 3 of treatment, the responder rate, defined as a 50% reduction in migraine attacks, was 62% for tonabersat and 45% for placebo (P < 0.05), and the rescue medication use was reduced in the tonabersat group compared with placebo by 1.8 days (P = 0.02). Placebo responses were particularly high for all end-points. At least one treatment-emergent adverse event was reported in the tonabersat group in 61% of patients compared with 51% in the placebo group; none was worrisome. Placebo responses were unexpectedly high in this trial, complicating straightforward interpretation of the study results. The good tolerability and promising efficacy results support further exploration of higher doses of tonabersat in larger controlled trials.

A double-blind, randomized, placebo-controlled dose-ranging study to evaluate the efficacy of alosetron in the treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome is a common gastrointestinal disorder characterized by abdominal pain and discomfort and altered bowel habit. Antagonism at the 5-HT3 receptor may be of benefit in the treatment of irritable bowel syndrome. AIMS: To evaluate the effect of 12 weeks of treatment with alosetron, a 5-HT3 receptor antagonist at doses of 0.1 mg b.d., 0.5 mg b.d. and 2 mg b.d. in irritable bowel syndrome patients. METHODS: A double-blind, placebo-controlled, parallel-group study with a 2-week screening and a 12-week treatment period was conducted. A total of 462 patients (335 female) recorded details of the severity of their abdominal pain, and bowel function daily on a diary card throughout the study. At monthly clinic visits patients recorded the severity of their abdominal pain/discomfort and diarrhoea on a visual analogue scale. RESULTS: In the total population and in the female subpopulation (but not in males) alosetron 2 mg b.d. significantly increased the proportion of pain-free days and decreased the visual analogue scale score for diarrhoea compared with placebo. Alosetron at doses of 0.5 mg b.d. and 2 mg b.d. led to a significant hardening of stool, and a reduction in stool frequency in the total population. CONCLUSION: Alosetron at a dose of 2 mg b.d. is an effective treatment for female patients with irritable bowel syndrome.

Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients.

BACKGROUND: Irritable bowel syndrome is one of the most common gastrointestinal disorders, yet no therapy convincingly controls the multiple symptoms of this syndrome. AIM: To compare the efficacy and tolerability of the new 5-HT3-receptor antagonist alosetron and the smooth muscle relaxant mebeverine in a double-blind, multicentre, randomized trial. METHODS: Six hundred and twenty-three nonconstipated females with irritable bowel syndrome were randomized to receive alosetron 1 mg twice daily (n=319) or mebeverine 135 mg three times daily (n=304) for 12 weeks, followed by a 4-week post-treatment period. The primary efficacy end-point was monthly responders for adequate relief of irritable bowel syndrome related abdominal pain and discomfort (defined as patients reporting adequate relief on at least 2 out of 4 weeks). Secondary end-points included assessments of bowel function, including urgency, stool frequency and stool consistency. RESULTS: There were significantly more responders in the alosetron group compared with mebeverine at months 2 and 3 (P < 0.01). Compared with mebeverine, the alosetron group experienced significant decreases in proportion of days with urgency and mean stool frequency, and had firmer stools within 1 week of starting treatment. A similar proportion of patients reported adverse events in the two treatment groups. CONCLUSIONS: In nonconstipated female irritable bowel syndrome patients, alosetron is significantly more effective than mebeverine in improving symptoms.

Onset of action of antisecretory drugs: beneficial effects of a rapid increase in intragastric pH in acid reflux disease.

BACKGROUND: The majority of patients who have symptomatic acid reflux disease will have a normal oesophageal mucosa or will have only a mild degree of oesophagitis. Treatment to relieve symptoms as they occur may be the best way to manage these patients, to whom the speed of symptom relief is of primary importance. The effervescent complex used to formulate effervescent ranitidine contains sodium bicarbonate and monosodium citrate, and has, therefore, an intrinsic acid-neutralizing capacity in addition to the well-documented antisecretory activity. METHODS: The results of studies of the effects of effervescent ranitidine tablets on intragastric pH and on the relief of heartburn are reviewed. RESULTS AND CONCLUSIONS: When compared with the standard ranitidine tablet, the effervescent formulation results in a significantly greater and more rapid rise in intragastric pH in the hour immediately after dosing. Comparative studies show that intragastric pH is raised significantly faster after a single dose of effervescent ranitidine than after a famotidine rapid release tablet and after either an omeprazole or a lansoprazole capsule. In patients with acid reflux disease, effervescent ranitidine provides quicker relief of symptoms than a standard tablet and is preferred by most patients for this reason. The majority of patients (more than 80%) report symptom relief within 60 min of taking effervescent ranitidine.

Effect of hyperbaric oxygen on human skin cells in culture and in human dermal and skin equivalents.

A critical stage of cutaneous wound healing is the development and maturation of the epidermis. In the aged, and in certain pathologies, this repair process is compromised due to a variety of deficiencies, one of which is tissue oxygenation. Several phases of wound healing are dependent on adequate tissue oxygen levels, and hyperbaric oxygenation has been shown to transiently elevate these levels. The use of human cell monolayers, dermal equivalents and human skin equivalents provide excellent opportunities for studying wound healing using in vivo relevant models. The goal of this study was to examine the effect of hyperbaric oxygen on cell proliferation, differentiation, and matrix biosynthesis in monolayer cultures and epidermopoiesis in the developing skin equivalent. Normal human dermal fibroblasts, keratinocytes and melanocytes, dermal equivalents and skin equivalents were exposed to hyperbaric oxygen at pressures up to three atmospheres, for up to 10 consecutive daily treatments lasting 90 minutes each. Increase in fibroblast proliferation (cf., 30% at 1 atmosphere after 10 days treatment), was observed without a significant effect on proliferation of normal human melanocytes and glycosaminoglycan synthesis. Stimulation of collagen synthesis after two days of treatment was only significant at 1 atmosphere (about 20% increase) but this differential was not observed after 5 days of treatment. Hyperbaric oxygenation above 2 atmospheres, inhibited proliferation of fibroblasts and keratinocytes in cell monolayer cultures (e.g., a 10 day treatment at 3 atmospheres appeared cytostatic to keratinocytes). In contrast, hyperbaric treatment up to 3 atmospheres dramatically enhanced keratinocyte differentiation, and epidermopoiesis in the complete human skin equivalent. These results support the importance of hyperbaric oxygen therapy in wound healing, and should provide an insight into oxygen utilization during repair of peripheral human tissue. The results also show the utility of the human skin equivalent as a model for evaluation of parameters involved in wound healing.

A prospective randomised controlled study of the use of ranitidine in patients with gastric cancer. Yorkshire GI Tumour Group.

BACKGROUND: Does the use of the histamine H2 receptor antagonist ranitidine improve the outcome of patients with gastric cancer? PATIENTS: A total of 222 patients with gastric cancer who had received radical or palliative resection or who were deemed inoperable at presentation. SETTING: Hospitals within Yorkshire, the participating clinicians being members of the Yorkshire GI Tumour Group. METHODS: A multicentre prospective randomised double blind trial comparing ranitidine 150 mg twice daily with placebo twice daily was undertaken. The principal outcome measures were survival and survival excluding those who died within 30 days of operation. RESULTS: The median survival (95% confidence intervals) was 331 (232 to 393) days for patients in the ranitidine group compared with 187 (143 to 269) for those in the placebo group. The difference in survival was not statistically significant (p = 0.225). When patients who died within 30 days of operation were excluded (21 in the placebo group, 15 in the ranitidine group), the difference in survival remained not significant (p = 0.358). No subgroup could be identified who significantly benefited from treatment, but for patients with stage VIa cancer the median survival was 134 days with placebo compared with 313 days with ranitidine (p = 0.073). CONCLUSION: This study does not show significant benefit from the use of ranitidine for gastric cancer but further larger studies may be indicated.

Inhibition of intragastric acidity in healthy subjects dosed with ranitidine 75 mg: a comparative study with cimetidine and placebo.

BACKGROUND: Despite the widespread use of over-the-counter H2-receptor antagonists little is known about their duration of action on human gastric acid secretion. There are studies reporting inhibitory effects for up to 9 h post-dose but few data beyond this period. METHODS: Profiles of 20-h intragastric acidity were measured simultaneously in 24 healthy subjects who were dosed (at 12.30 h) with either ranitidine 75 mg, cimetidine 200 mg or placebo in a three-way crossover study, according to a standard protocol. Five-millilitre aliquots of gastric juice were aspirated half-hourly during the day (0-10 h post-dose) and hourly overnight (10-20 h post-dose). pH was measured to three decimal places with a glass electrode. Weighted intragastric acidity (AUC/time) was calculated for both day- and night-times using 2.5-h intervals during the day and 5-h intervals at night. Statistical analysis was by ANOVA. RESULTS: The results are expressed as mean weighted intragastric acidity (mmol/L). (i) Daytime (0-10 h post-dose): when dosed with placebo the weighted intragastric acidity was 31.03, decreasing to 10.37 (P < 0.001 vs. placebo) and 16.23 (P < 0.001 vs. placebo) when treated with ranitidine and cimetidine, respectively. Ranitidine inhibited weighted intragastric acidity to a greater degree than cimetidine (P < 0.001) during this period. (ii) Night-time (10-20 h post-dose): when dosed with placebo the weighted intragastric acidity was 21.36 decreasing to 16.65 (P < 0.001 vs. placebo) when dosed with ranitidine and remaining unchanged at 20.03 (P = 0.886 vs. placebo) when dosed with cimetidine. Ranitidine inhibited weighted intragastric acidity to a greater degree than cimetidine (P = 0.010) during this period. A sub-analysis of the two 5-h intervals showed that compared to placebo, ranitidine inhibited weighted intragastric acidity significantly in the 10-15 h period. However, its effect in the 15-20 h period did not differ from placebo. CONCLUSIONS: In healthy subjects, the inhibitory effect of ranitidine 75 mg on intragastric acidity can be detected 10-15 h after an oral dose. By contrast, the inhibitory effect of cimetidine 200 mg seems to be restricted to the first 10 h.

The safety of ranitidine in over a decade of use.

BACKGROUND: Ranitidine hydrochloride (Zantac) is one of the most extensively studied and widely used drugs of all time. This has provided an excellent opportunity to define its safety profile. METHODS: Data from 189 controlled clinical trials in which more than 26,000 patients received daily doses of ranitidine for 4 weeks or more were reviewed. More than 80% of patients were treated with up to 300 mg ranitidine daily; the remaining patients received doses of up to 1200 mg daily. Eighty-seven trials were placebo controlled. Analyses of post-marketing surveillance and a database of all spontaneously reported adverse events were also evaluated. RESULTS: Overall in the clinical trial programme adverse events were reported by 20% of those receiving ranitidine compared with 27% of those receiving placebo. The pattern of events was similar in all treatment groups with no evidence of dose-related toxicity in regimens encompassing an eightfold range of therapeutic doses. Similarly in a programme of studies designed to evaluate a dose of ranitidine of 75 mg for non-prescription (over-the-counter) use in the treatment of heartburn, ranitidine was not associated with an adverse event profile distinct from that of placebo. Analysis of spontaneously reported adverse event data allowed identification of rare idiosyncratic events. CONCLUSIONS: Review of data from a large population of controlled clinical trials with analyses of postmarketing surveillance studies and spontaneously reported adverse events confirmed the excellent safety profile of ranitidine.

Prevention of relapse in reflux esophagitis: a placebo controlled study of ranitidine 150 mg bid and 300 mg bid.

OBJECTIVE: To compare the efficacy and safety of long term use of ranitidine 150 mg bid, 300 mg bid and placebo in prevention of endoscopic and symptomatic relapse of reflux esophagitis in an international, double-blind, placebo controlled, parallel group study. PATIENTS AND METHODS: A total of 279 patients at least 18 years old from hospital out-patient departments with healed esophagitis (grade 0) with no or mild symptoms entered the study. Patients were randomly allocated to receive ranitidine 150 mg, 300 mg placebo twice daily for 48 weeks. Patients returned for symptom assessments at eight-week intervals and for re-endoscopy every 16 weeks. RESULTS: Both ranitidine regimens were significantly more effective than placebo in preventing endoscopic and symptomatic relapse of reflux esphagitis (p = 0.003 for ranitidine 150 mg bid; P < 0.001 for ranitidine 300 mg bid). No statistically significant differences were observed in relapse rates between the two ranitidine regiments. The percentage of patients with endoscopic relapse (grade 2) after 48 weeks were 60%, 37% and 27% for placebo, ranitidine 150 mg bid and ranitidine 300 mg bid, respectively (P = 0.002 for ranitidine 150 mg bid versus placebo; P < 0.001 for ranitidine 300 mg bid versus placebo). Ranitidine was well tolerated. CONCLUSIONS: Ranitidine 150 mg bid and 300 mg bid are safe and effective treatments in the prevention of reflux esophagitis relapse.

Ranitidine bismuth citrate plus clarithromycin for the eradication of H. pylori.

Reported observed intention-to-treat eradication rates for ranitidine bismuth citrate plus clarithromycin for 14 days range from 70-86% in studies from the USA and 82-96% in multinational studies carried out primarily in Europe. Two double-blind head-to-head comparisons with omeprazole plus clarithromycin or amoxycillin have shown that ranitidine bismuth citrate plus clarithromycin gives considerably higher eradication rates than the omeprazole based regimens. Ongoing studies will define the efficacy of shorter duration dual therapies and provide further data on two antibiotics with ranitidine bismuth citrate. The possibility that ranitidine bismuth citrate may help in the eradication of resistant organisms and even in the prevention of primary resistance requires further work to expand the preliminary in vitro observations. In the meantime, it can be concluded that ranitidine bismuth citrate, when used in conjunction with clarithromycin for 14 days, is an effective therapy for the eradication of H. pylori.

The safety of ranitidine bismuth citrate in controlled clinical studies.

Ranitidine bismuth citrate (Pylorid, Tritec) is a novel drug which heals peptic ulcers and when co-prescribed with either clarithromycin or amoxycillin eradicatesHelicobacter pylori. In controlled clinical studies it was well-tolerated when given alone or when co-prescribed with either antibiotic. Data from 20 clinical studies are reported in this analysis of safety with almost 5000 patients having received ranitidine bismuth citrate (200, 400, or 800 mg twice daily). The incidence of adverse events reported with this new drug, either alone or with an antibiotic, was not different from or lower than in patients given placebo and was independent of the dose of ranitidine bismuth citrate tested. Most commonly reported events (>1% of patients) were upper respiratory tract infection, constipation, diarrhoea, nausea and vomiting, dizziness, and headache, the latter being the only event reported by >2% of patients who received ranitidine bismuth citrate alone. Adverse events considered by the clinical investigator to be adverse reactions occurred with a similar frequency amongst patients given ranitidine bismuth citrate (8%), ranitidine hydrochloride (6%), or placebo (6%). The incidence of adverse reactions was greater when co-prescribed with amoxycillin (11%) or clarithromycin (20%) although it was not different from that noted with the antibiotics alone. Serious adverse events were reported in similar proportions of patients given placebo, ranitidine bismuth citrate alone or with an antibiotic, and ranitidine hydrochloride (range: <1-2%). The safety profile of ranitidine bismuth citrate was thus comparable to that of ranitidine hydrochloride (Zantac), a drug with a well-established record of safety in clinical use.

Combination of ranitidine and cisapride in the treatment of reflux oesophagitis.

OBJECTIVE: To compare the efficacy of treatment for 8 or 12 weeks with a combination of 150 mg ranitidine twice daily plus 20 mg cisapride twice daily with ranitidine 150 mg twice daily alone in patients with moderate-to-severe reflux oesophagitis. DESIGN: A double-blind, randomized, parallel-group clinical trial. SETTING: Forty-two out-patient centres in the UK, Germany, Ireland, Denmark and South Africa. PATIENTS: A total of 344 symptomatic patients with endoscopically confirmed reflux oesophagitis (Hetzel grade 3 or 4) were randomly assigned to receive the study medication. INTERVENTIONS: Patients underwent a follow-up endoscopy after 8 weeks' treatment. Healing was defined as Hetzel grade 0 or 1 upon endoscopy. Patients with unhealed oesophagitis continued their allocated treatment regimen for a further 4 weeks before undergoing a repeat endoscopy. MAIN OUTCOME MEASURES: The primary efficacy analysis was based on a comparison of 12-week cumulative healing rates between the two groups. RESULTS: A statistically significant difference (P = 0.015) in the cumulative healing rate was observed between patients given ranitidine plus cisapride (82%) and those given ranitidine alone (71%). Oesophagitis in patients who received the combination was twice as likely to heal as that in patients who received ranitidine alone. CONCLUSION: A combination of 150 mg ranitidine twice daily and 20 mg cisapride twice daily is a safe and effective treatment for moderate-to-severe reflux oesophagitis and offers increased efficacy over ranitidine alone.

Treatment of nonsteroidal anti-inflammatory drug-associated gastric and duodenal damage. Efficacy of antisecretory drugs and mucosal protective compounds.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment for rheumatic diseases. However, a significant number of patients receiving these drugs experience upper gastrointestinal side effects, including physical injury to the gastroduodenal mucosa. This may range from clinically insignificant bleeding and minor erosive changes to deeper ulceration, with attendant risk of haemorrhage or perforation. The majority of the published literature concerning healing of NSAID-associated peptic ulcer with antisecretory drugs involves studies of the use of the H2-receptor antagonists, ranitidine and cimetidine. Peptic ulcers associated with NSAID use can be healed with these H2-receptor antagonists using the same doses as those used for healing of idiopathic gastric or duodenal ulceration. Most ulcers heal within 4-8 weeks in those patients who are able to discontinue their anti-inflammatory therapy. If the NSAID is continued, healing may be slightly delayed. At present, limited data only are available with respect to the use of the proton pump inhibitor, omeprazole, and no firm conclusions can be drawn regarding the use of the prostaglandin analogue, misoprostol, for the healing of NSAID-associated peptic ulceration.

Does ranitidine affect blood alcohol concentrations?

No interaction occurs between ranitidine and alcohol when alcohol 0.3 g/kg or more is taken by either fed or fasted subjects. Ranitidine is associated with small increases (2-4 mg/dl) in blood alcohol concentrations in subjects given alcohol 0.15 g/kg under specific experimental conditions. Mean peak blood alcohol concentrations nevertheless remain low (< 20 mg/dl) after the amount, which is equivalent to about 3 oz of wine or 1 oz of 80-proof liquor. Such changes also occur when alcohol is ingested after different types of foods, and are smaller than the increases when it is drunk on an empty compared with a full stomach. The pharmacokinetic effect seen with ranitidine is without apparent clinical or social significance.

Association of age with the efficacy and safety of ranitidine and cimetidine in acute duodenal ulcer disease.

This multinational double-blind trial compared the efficacy and safety of ranitidine 300 mg nocte, 300 mg post-evening meal (pem) and cimetidine 800 mg nocte in patients with endoscopically verified duodenal ulcer disease aged < 60 years (n = 1318) and > or = 60 years (n = 354). The relative efficacy of the treatments was not dependent upon age after either 2 or 4 weeks of therapy. However, ulcer healing after 2 weeks of therapy was significantly higher in patients receiving ranitidine 300 mg pem than in those receiving cimetidine (p = 0.003) in the < 60-year group, but the difference was not significant in the > or = 60-year group. Fewer patients aged > or = 60 years on cimetidine (62%) became pain free compared with those on ranitidine (72% in both groups). Relief of epigastric pain and heartburn was related to pre-trial severity in both age groups. The incidence and type of adverse events were similar in the two age groups. It is concluded that ranitidine and cimetidine are as effective at healing duodenal ulcer and relieving ulcer symptoms in elderly as in younger patients.

Early evening dosing of ranitidine. Comparison with nighttime dosing of ranitidine or cimetidine in duodenal ulceration.

A double-blind multinational comparison of ranitidine 300 mg post evening meal (pem), ranitidine 300 mg nocte and cimetidine 800 mg nocte has been carried out in 1677 patients with endoscopically verified duodenal ulcer disease. Fifty-three percent of ulers healed by two weeks during treatment with ranitidine 300 mg pem and 88% by four weeks, while the results for ranitidine 300 mg nocte were 50% and 86%, respectively, and 44% and 84% for cimetidine. The difference between ranitidine 300 mg pem and cimetidine was significant at two weeks (P = 0.002, Mantel-Haenszel chi-squared test). The relative efficacy of the treatments was not dependent upon gender, smoking habit, alcohol intake, or ulcer frequency. However, the overall differences in healing between patients with small and large ulcers and patients with single and multiple ulcers were significantly different at weeks 2 and 4 (P < 0.001). Significantly more patients treated with ranitidine (60%) had complete relief of epigastric pain than those treated with cimetidine (54%) (P < 0.05). A meta-analysis of the four double-blind comparisons of ranitidine 300 mg pem (N = 841) and 300 mg nocte (N = 849), including the present study, failed to show the benefits of pem dosing, predicted from pharmacological studies.

Does co-prescription of sucralfate with ranitidine therapy enhance the healing of gastric ulcers?

It has been suggested that the co-administration of ranitidine and sucralfate may enhance peptic ulcer healing more than administration of either drug alone. This study compared the frequency of healing of gastric ulcers treated with either ranitidine 300 mg nocte plus sucralfate 1 g tds or with ranitidine 300 mg nocte plus placebo. Patients (n = 259) were treated initially for 4 wk, and this period was extended to 8 wk for those patients whose ulcers had not healed. Ulcer healing and patient symptom data were assessed at 4 and 8 wk, whereas patients recorded the presence of ulcer pain on a daily basis. Ulcer healing rates were 63% and 66% at 4 wk, and were 93% and 91% at 8 wk, in the ranitidine-plus-sucralfate group and the ranitidine-plus-placebo group, respectively. Both treatments were equally effective in relieving symptoms. Thus, combination therapy with sucralfate provided no additional benefit over treatment with ranitidine alone.

Ranitidine in the treatment of duodenal ulcer disease: relationship between antisecretory effect and ulcer healing rate.

The relationship between drug-induced suppression of intragastric acidity and the rate of duodenal ulcer healing was examined using data for a single drug, ranitidine, from 156 clinical trials involving 16,362 patients together with data on acid suppression from 37 studies of intragastric acidity in 630 subjects. In these studies ranitidine was given in doses ranging from 150 mg to 1200 mg per day administered in 9 different dosage regimens. The overall percentage of patients whose duodenal ulcers healed at 2 and 4 weeks on the different regimens was highly correlated with the percentage suppression of 24-hour intragastric acidity induced by different regimens. Thus the therapeutic benefit of a given ranitidine dosage regimen in healing duodenal ulcers relates directly to its antisecretory effect.