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Biomedical subjects

R G Berlin

Publications and source records attributed to R G Berlin.

18 recordsLinked to original sources
PubMed1997

Leukotrienes in ulcerative colitis: results of a multicenter trial of a leukotriene biosynthesis inhibitor, MK-591.

BACKGROUND & AIMS: Leukotrienes (LTs) are believed to be important in the pathogenesis of ulcerative colitis (UC). The aim of this study was to determine whether inhibition of LT biosynthesis with a 5-lipoxygenase inhibitor (MK-591) induces remission in patients with mild to moderate UC. METHODS: One hundred eighty-three patients with mild to moderately active UC enrolled in this randomized parallel group, double-blind study. Patients received placebo or MK-591 at a dose of 12.5, 50, or 100 mg twice daily for 8 weeks. A subset of patients underwent rectal dialysis to determine LTB4 concentration. RESULTS: MK-591 reduced LTB4 concentrations in rectal dialysate at the final determination. The median percent of baseline LTB4 concentration for 100 mg taken twice daily was 1.4% (n = 4); for 50 mg taken twice daily, 16.5% (n = 6); for 12.5 mg taken twice daily, 12% (n = 6); and for placebo, 78% (n = 6). There was no correlation between reduction of LTB4 and remission. Patients in remission at week 8 were as follows: placebo, 9 of 44 (20.5%); 100 mg taken twice daily, 11 of 43 (25.6%); 50 mg taken twice daily, 8 of 49 (16.3%); and 12.5 mg taken twice daily, 4 of 47 (8.5%) (P > 0.10). CONCLUSIONS: MK-591 markedly inhibited LT biosynthesis, but it did not differ significantly from placebo in clinical efficacy. Inhibition of LT biosynthesis was not effective as a single therapeutic modality in active UC.

Adolescent↗
PubMed1995

Safety of acid-suppressing drugs.

There is an extensive literature on the adverse effects of drugs that inhibit gastric acid secretion. This study presents a critical examination of interactions between antisecretory drugs and other compounds, the frequency of serious adverse effects relating to various body systems, the safety of antisecretory drugs in pregnancy, and longer-term safety data from postmarketing surveillance studies. While interactions with some other drugs, alcohol, and certain carcinogens are of potential concern, in practice clinically significant reactions appear to be rare if they occur at all. A small number of major side-effects have been documented, but they occur rarely, and postmarketing surveillance has not detected other longer-term sequelae. Safety of these drugs in pregnancy is not established, as data are so few. It is concluded that antisecretory agents, by comparison with most other classes of drugs, are remarkably well tolerated.

Female↗
PubMed1994

Randomized, placebo-controlled comparison of famotidine 20 mg b.d. or 40 mg b.d. in patients with erosive oesophagitis.

METHODS: This US multicentre, randomized, double-blind, placebo-controlled, parallel group study determined the effects of two twice daily oral famotidine regimens on symptom relief and healing of erosive oesophagitis in patients with gastro-oesophageal reflux disease. Three hundred and eighteen patients were enrolled: 66 received placebo, 125 received famotidine 20 mg b.d., and 127 received famotidine 40 mg b.d. Patients maintained diaries of their symptoms. Endoscopy was performed at weeks 0 and 6, and again at week 12 if healing had not occurred. RESULTS: Healing at 6 and 12 weeks was (respectively) 48% (P < or = 0.01 vs. placebo) and 69% (P < or = 0.01 vs. placebo) for famotidine 40 mg b.d.; 32% and 54% (P < or = 0.01 vs. placebo) for famotidine 20 mg b.d., and 18% and 29% for placebo. At both 6 and 12 weeks the healing rates of famotidine 40 mg b.d. were significantly greater than placebo and famotidine 20 mg b.d. Compared to placebo, famotidine produced more frequent global symptom improvement and more rapid heartburn relief. There were no significant differences among treatment groups in the incidence of clinical or laboratory adverse events. CONCLUSIONS: Famotidine 40 mg b.d. was a better regimen than famotidine 20 mg b.d. or placebo. The clinical efficacy paralleled the previously documented effect of the famotidine regimens on decrease of oesophageal acid exposure.

Administration, Oral↗
PubMed1993

Efficacy of twice daily doses of 40 or 20 milligrams famotidine or 150 milligrams ranitidine for treatment of patients with moderate to severe erosive esophagitis. Famotidine Erosive Esophagitis Study Group.

The comparative efficacy of twice daily regimens of 40 mg famotidine (group 1), 20 mg famotidine (group 2), and 150 mg ranitidine (group 3) was investigated in a double-blind randomized study of parallel groups of patients with endoscopically documented erosive esophagitis. Patients were enrolled at 29 centers in 19 countries and treated for 6 to 12 weeks until healing, defined as complete resolution of visible ulceration or erosion of the esophageal mucosa, demonstrated by repeat endoscopy. Healing occurred in 71% of 175 group-1 patients, 68% of 93 group-2 patients, and 60% of 172 group-3 patients; the difference between groups 1 and 3 was significant (P < or = 0.05). The three treatments produced similar levels of global symptomatic improvement and relief of daytime and nighttime heartburn. All treatments were well tolerated. These results support the hypothesis that reduction of esophageal acid exposure by 40 mg famotidine twice daily produces healing of lesions in patients with erosive esophagitis and is more effective than regimens that provide lesser reductions in esophageal acid exposure time.

Double-Blind Method↗
PubMed1991

Omeprazole. Gastrin and gastric endocrine cell data from clinical studies.

Gastric enterochromaffin-like cell carcinoids have been detected in rats exposed lifelong to omeprazole. By inhibiting acid secretion, omeprazole causes hypergastrinemia which, with prolonged exposure, exerts a trophic effect on enterochromaffin-like cells with eventual enterochromaffin-like cell carcinoid formation in some animals. This mechanism seems to explain the appearance of enterochromaffin-like cell carcinoids in human hypergastrinemic states, whether associated with hyperchlorhydria, eg, Zollinger-Ellison syndrome, or with hypochlorhydria, eg, pernicious anemia (nonantral atrophic gastritis). Omeprazole produces modest serum gastrin elevations in humans when monitored over a 24-hr period. Gastrin levels are markedly lower and less sustained than in the above hypergastrinemic states. Extensive gastric biopsy data from patients enrolled in long-term studies indicate that omeprazole administration is not associated with clinically significant changes in the human oxyntic endocrine cell population. Man and rat differ markedly both in their gastrin response to a given level of acid inhibition and in their response to the trophic influence of gastrin on enterochromaffin-like cells. The rat model is a false indicator of risk in man.

Cell Count↗
PubMed1991

U.S. experience with omeprazole in duodenal ulcer. Multicenter double-blind comparative study with ranitidine. The Omeprazole DU Comparative Study Group.

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.

Double-Blind Method↗
PubMed1991

Nocturnal therapy with famotidine for 1 year is effective in preventing relapse of gastric ulcer.

A multicentre, double-blind, randomized, placebo-controlled trial was undertaken to investigate the therapeutic efficacy of a nocturnal dose of famotidine 20 mg to reduce the 1 year relapse rate of recently healed gastric ulcers. Twenty investigators in eight countries randomized 202 patients with endoscopically confirmed healed gastric ulcers. Repeat endoscopies were performed at 6 and 12 months or for symptoms compatible with ulcer relapse. A per protocol analysis of cumulative life table relapse at 12 months showed that famotidine 20 mg was superior to placebo in reducing gastric ulcer relapse, 24 versus 50%, respectively (P less than 0.01). Both placebo and famotidine were well tolerated. Since nocturnal dosing with famotidine 20 mg is effective in preventing gastric ulcer relapse over a 1-year period and is well tolerated, it offers a therapeutic option for the long-term treatment of patients with gastric ulcer.

Adult↗
PubMed1991

Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Results of a multicenter, placebo-controlled, dose-ranging study. USA Merck Gastroesophageal Reflux Disease Study Group.

We conducted a double-blind, placebo-controlled, multicenter trial comparing the efficacy of famotidine 40 mg administered at bedtime (HS), 20 mg given twice daily (BID), and placebo to relieve heartburn and to heal endoscopically documented esophageal erosions or ulcerations. A total of 338 patients were randomized: 135 to receive famotidine 40 mg HS, 137 to receive famotidine 20 mg BID, and 66 to receive placebo. In the group given famotidine 20 mg BID, there was a significantly greater proportion of patients with complete relief of daytime heartburn, and both famotidine groups demonstrated statistically significant advantages over placebo in global scores or by successful outcome. Antacid consumption was significantly reduced in the group given famotidine 20 mg BID as compared with placebo. Both famotidine regimens resulted in a significantly greater proportion of patients with complete endoscopic healing than placebo, with the BID dosing being numerically superior to the 40-mg HS dose.

Adult↗
PubMed1991

P450/losec.

Explore the source record for details and available documents.

Acetaminophen↗
PubMed1990

Prolonged inhibition of acid secretion causes hypergastrinaemia without altering pH inhibition of gastrin release in humans.

Hypergastrinaemia induced by potent inhibitors of acid secretion is thought to occur as a result of the elimination of the inhibitory effects of intragastric acid on gastrin release. The present study was designed to determine if the mechanisms responsible for feedback inhibition of gastrin release and acid secretion by intragastric acid are preserved during four weeks of varying degrees of drug-induced acid inhibition. Forty-eight healthy male volunteers were randomly assigned to one of four treatments for four weeks: 10 mg omeprazole o.m., 20 mg omeprazole o.m., 40 mg omeprazole o.m. or 150 mg ranitidine b.d. Gastrin release and acid secretion in response to peptone meals maintained at pH 2.5 and pH 5.5 by intragastric titration, and 24-hour gastrin profiles in response to standard meals were determined before treatment, at the fourth week of treatment and two weeks after discontinuing treatment. As expected, omeprazole produced dose-related effects on acid secretion and gastrin concentrations that were largely reversed after treatment was discontinued. Gastrin release in response to pH 5.5 peptone meals remained significantly greater than gastrin release in response to pH 2.5 meals during treatment with all doses of omeprazole. The ratio of pH 5.5/pH 2.5 peptone meal-stimulated gastrin release was approximately 1.5, and remained constant for all treatment groups throughout the study period. These data indicate that four weeks of drug induced hypochlorhydria causes an apparent increase in overall G-cell function, but it does not interfere with normal feedback inhibition of gastrin release and acid secretion mediated by intragastric acidity.

Adolescent↗
PubMed1989

Disulfiram hepatotoxicity: a consideration of its mechanism and clinical spectrum.

Disulfiram-induced hepatotoxicity is a recognised entity despite the difficulty in determining its contribution to the damage when alcoholism itself is a frequent cause of liver disease. Less well characterised is the mechanism of disulfiram-induced hepatotoxicity and the high fatality rate associated with this entity. The clinical spectrum of the disease is reviewed and experimental data suggesting the mechanism of toxicity are presented. Failure to recognise this problem and to terminate therapy as soon as possible may result in death due to massive hepatic necrosis.

Alcoholism↗
PubMed1986

Famotidine: an appraisal of its mode of action and safety.

Famotidine is a potent histamine (H2)-receptor antagonist that binds to the H2 receptor in a competitive reversible manner as shown by in vivo, in vitro, and clinical studies. Famotidine has shown no evidence of carcinogenicity, mutagenicity, or teratogenicity in extensive and adequately designed safety assessment studies. The drug produces neither prolonged anacidity nor doses its use result in significant elevations of serum gastrin levels beyond those seen with other available H2-receptor antagonists when used as recommended for the treatment of ulcer disease. Taken together, these data demonstrate no undue or disproportionate risk to the use of famotidine.

Animals↗
PubMedDate not supplied

Acid suppression by famotidine 20 mg twice daily or 40 mg twice daily in preventing relapse of endoscopic recurrence of erosive esophagitis.

Control of esophageal acid exposure is important in treating patients with gastroesophageal reflux disease (GERD). After complete healing of esophagitis, most patients will relapse within 6 months if left untreated. This multicenter, randomized, double-masked, placebo-controlled trial, conducted in the United States, examined whether two famotidine dosing regimens are effective in extending the time in remission for patients with moderate-to-severe erosive esophagitis. Of 172 patients enrolled, 31 received placebo, 69 received famotidine 20 mg twice daily (BID) , and 72 received famotidine 40 mg BID. Endoscopy was scheduled at baseline and at months 3 and 6. Patients assessed global heartburn and symptom relief at months 3 and 6 relative to the start of the study. Life table (Kaplan-Meier) relapse rates at 6 months were 22% (P < 0.001 vs placebo) for famotidine 20 mg BID, 11% (P < 0.001 vs placebo) for famotidine 40 mg BID, and 62% for placebo. Compared with placebo, patients in the famotidine groups were significantly less likely to note global symptomatic deterioration, as measured by the distribution of global assessment responses. The incidence of clinical and laboratory adverse experiences was similar among treatment groups. For maintenance treatment of GERD, famotidine 20 mg BID and 40 mg BID are more effective than placebo in extending the time in remission.

Adolescent↗