misoprostol and Chronic-Disease

Non-steroidal anti-inflammatory drugs (NSAIDs) are important agents in the management of arthritic and inflammatory conditions, and are among the most frequently prescribed medications in North America and Europe. However, there is overwhelming evidence linking these agents to a variety of gastrointestinal (GI) toxicities.. To review the effectiveness of common interventions for the prevention of NSAID induced upper GI toxicity.. A literature search was conducted, according to the Cochrane methodology for identification of randomized controlled trials in electronic databases, including MEDLINE from 1966 to June 2002, Current Contents for 6 months prior to June 2002, EMBASE to February 2002, and a search of the Cochrane Controlled Trials Register from 1973 to 2002. Biosis Previews(R), ADIS LMS Drug Alerts, Pharmaceutical News Index (PNI)(R) were searched to June 2002. New articles since the last search update were evaluated. Recent conference proceedings were reviewed and content experts and companies were contacted.. Randomized controlled clinical trials (RCTs) of prostaglandin analogues (PA), H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI) for the prevention of chronic NSAID induced upper GI toxicity were included.. Two independent reviewers extracted data regarding population characteristics, study design, methodological quality and number of patients with endoscopic ulcers, ulcer complications, symptoms, overall drop-outs, drop outs due to symptoms. Dichotomous data was pooled using RevMan V4.1. Heterogeneity was evaluated using a chi square test.. Forty RCTs met the inclusion criteria. All doses of misoprostol significantly reduced the risk of endoscopic ulcers. Misoprostol 800 ug/day was superior to 400 ug/day for the prevention of endoscopic gastric ulcers (RR=0.17, and RR=0.39 respectively, p=0.0055). A dose response relationship was not seen with duodenal ulcers. Misoprostol caused diarrhea at all doses, although significantly more at 800 ug/day than 400 ug/day (p=0.0012). Misoprostol was the only prophylactic agent documented to reduce ulcer complications. Standard doses of H2RAs were effective at reducing the risk of endoscopic duodenal (RR=0.36; 95% CI: 0.18-0.74) but not gastric ulcers(RR=0.73; 95% CI:0.50-1.09). Both double dose H2RAs and PPIs were effective at reducing the risk of endoscopic duodenal and gastric ulcers (RR=0.44; 95% CI:0.26-0.74 and RR=0.40;95% CI;0.32-0.51 respectively for gastric ulcer), and were better tolerated than misoprostol.. Misoprostol, PPIs, and double dose H2RAs are effective at preventing chronic NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol are less effective and are still associated with diarrhea. Only Misoprostol 800ug/day has been directly shown to reduce the risk of ulcer complications such as perforation hemorrhage or obstruction.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Chronic Disease; Duodenal Ulcer; Histamine H2 Antagonists; Humans; Misoprostol; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Stomach Ulcer

Non-steroidal anti-inflammatory drugs (NSAIDs) are important agents in the management of arthritic and inflammatory conditions, and are among the most frequently prescribed medications in North America and Europe. However, there is overwhelming evidence linking these agents to a variety of gastrointestinal (GI) toxicities.. To review the effectiveness of common interventions for the prevention of NSAID induced upper GI toxicity.. A literature search was conducted, according to the Cochrane methodology for identification of randomized controlled trials in electronic databases, including MEDLINE from 1966 to January 2000, Current Contents for 6 months prior to January 2000, Embase to Febuary 1999, and a search of the Cochrane Controlled Trials Register from 1973 to 1999. Recent conference proceedings were reviewed and content experts and companies were contacted.. Randomized controlled clinical trials (RCTs) of prostaglandin analogues (PA), H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI) for the prevention of chronic NSAID induced upper GI toxicity were included.. Two independent reviewers extracted data regarding population characteristics, study design, methodological quality and number of patients with endoscopic ulcers, ulcer complications, symptoms, overall drop-outs, drop outs due to symptoms. Dichotomous data was pooled using Revman V3.1. Heterogeneity was evaluated using a chi square test.. Thirty-three RCTs met the inclusion criteria. All doses of misoprostol significantly reduced the risk of endoscopic ulcers. Misoprostol 800 ug/day was superior to 400 ug/day for the prevention of endoscopic gastric ulcers (RR=0.18, and RR=0. 38 respectively, p=0.0055). A dose response relationship was not seen with duodenal ulcers. Misoprostol caused diarrhea at all doses, although significantly more at 800ug/day than 400ug/day (p=0.0012). Misoprostol was the only prophylactic agent documented to reduce ulcer complications. Standard doses of H2RAs were effective at reducing the risk of endoscopic duodenal (RR=0.24; 95% CI: 0.10-0. 57) but not gastric ulcers(RR=0.73; 95% CI:0.50-1.09). Both double dose H2RAs and PPIs were effective at reducing the risk of endoscopic duodenal and gastric ulcers (RR=0.44; 95% CI:0.26-0.74 and RR=0.37;95% CI;0.27-0.51 respectively for gastric ulcer), and were better tolerated than misoprostol.. Misoprostol, PPIs, and double dose H2RAs are effective at preventing chronic NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol are less effective and are still associated with diarrhea. Only Misoprostol 800ug/day has been directly shown to reduce the risk of ulcer complications.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Chronic Disease; Duodenal Ulcer; Histamine H2 Antagonists; Humans; Misoprostol; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Stomach Ulcer

Non-steroidal anti-inflammatory drugs (NSAIDs) are important agents in the management of arthritic and inflammatory conditions, and are among the most frequently prescribed medications in North America and Europe. However, there is overwhelming evidence linking these agents to a variety of gastrointestinal (GI) toxicities.. To review the effectiveness of common interventions for the prevention of NSAID induced upper GI toxicity.. A literature search was conducted, according to the Cochrane methodology for identification of randomized controlled trials in electronic databases, including MEDLINE from 1966 to January 2000, Current Contents for 6 months prior to January 2000, Embase to Febuary 1999, and a search of the Cochrane Controlled Trials Register from 1973 to 1999. Recent conference proceedings were reviewed and content experts and companies were contacted.. Randomized controlled clinical trials (RCTs) of prostaglandin analogues (PA), H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI) for the prevention of chronic NSAID induced upper GI toxicity were included.. Two independent reviewers extracted data regarding population characteristics, study design, methodological quality and number of patients with endoscopic ulcers, ulcer complications, symptoms, overall drop-outs, drop outs due to symptoms. Dichotomous data was pooled using Revman V3.1. Heterogeneity was evaluated using a chi square test.. Thirty-three RCTs met the inclusion criteria. All doses of misoprostol significantly reduced the risk of endoscopic ulcers. Misoprostol 800 ug/day was superior to 400 ug/day for the prevention of endoscopic gastric ulcers (RR=0.18, and RR=0.38 respectively, p=0.0055). A dose response relationship was not seen with duodenal ulcers. Misoprostol caused diarrhea at all doses, although significantly more at 800ug/day than 400ug/day (p=0.0012). Misoprostol was the only prophylactic agent documented to reduce ulcer complications. Standard doses of H2RAs were effective at reducing the risk of endoscopic duodenal (RR=0.24; 95% CI: 0.10-0.57) but not gastric ulcers(RR=0.73; 95% CI:0.50-1.09). Both double dose H2RAs and PPIs were effective at reducing the risk of endoscopic duodenal and gastric ulcers (RR=0.44; 95% CI:0.26-0.74 and RR=0.37;95% CI;0.27-0.51 respectively for gastric ulcer), and were better tolerated than misoprostol.. Misoprostol, PPIs, and double dose H2RAs are effective at preventing chronic NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol are less effective and are still associated with diarrhea. Only Misoprostol 800ug/day has been directly shown to reduce the risk of ulcer complications.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Chronic Disease; Duodenal Ulcer; Histamine H2 Antagonists; Humans; Misoprostol; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Stomach Ulcer

Misoprostol, a synthetic methyl ester analogue of prostaglandin E1 (PGE1) is both a powerful inhibitor of gastric secretion and is able to protect the gastroduodenal mucosa from damage produced by alcohol, aspirin, naproxen and tolmetin. The results of 12 double-blind, randomized, placebo- and cimetidine-controlled trials involving 4000 patients have been reviewed here and show that misoprostol, given in a dosage of 800 micrograms daily in two or four divided doses, is able to produce rates of complete ulcer healing and pain relief in both gastric and duodenal ulcer which are significantly superior to placebo therapy and comparable to those achieved with high or conventional doses of cimetidine. One further large trial has shown that misoprostol is able to heal a significant proportion of duodenal ulcers refractory to treatment with H2 receptor antagonists. In the compromised patient, two trials have suggested that misoprostol is able to abolish the adverse effects of smoking on duodenal ulcer, although this effect was not apparent in the gastric ulcer trials or in other duodenal ulcer trials. Similarly, while in volunteers pretreatment with misoprostol is able to protect the gastric mucosa from alcohol damage, there is little clinical evidence to support improved ulcer healing in the patient who abuses alcohol. Further studies in these areas should be conducted. Misoprostol could well have an important role to play in the protection of the gastroduodenal mucosa from damage produced by non-steroidal anti-inflammatory drugs (NSAIDs) in arthritic patients compelled to take these drugs for long periods. A series of double-blind placebo-controlled trials in healthy volunteers have shown that pretreatment with, or simultaneous administration of, 800 micrograms daily of misoprostol, reduces significantly mucosal damage produced by aspirin, tolmetin and naproxen. Two controlled clinical trials in a large number of arthritic patients have shown firstly, that misoprostol 800 micrograms daily is able to reduce significantly aspirin-induced mucosal bleeding as compared with placebo and secondly, in an endoscopically, placebo-controlled trial that it reduced significantly the frequency and severity of aspirin-induced mucosal lesions, accelerated the healing of erosions and ulcers and in other patients was able to protect the undamaged mucosa from injury. Misoprostol is well tolerated--a dose related, usually self limiting, diarrhoea occurred in a small proportion of

Topics: Alprostadil; Anti-Ulcer Agents; Chronic Disease; Clinical Trials as Topic; Duodenal Ulcer; Female; Humans; Male; Misoprostol; Stomach Ulcer

Radiation proctitis is a known complication of radiation therapy for prostate cancer. Available medical treatment is usually ineffective and has focused on relieving symptoms after damage has occurred. Our study aimed at evaluating the use of misoprostol rectal suppositories in the prevention of acute as well as chronic radiation proctitis symptoms.. A prospective, randomized, placebo-controlled, double-blinded trial was conducted in patients with recently diagnosed stages B and C prostate cancer who underwent external beam irradiation. Patients received either a misoprostol or a placebo suppository 1 h before each radiation session. Misoprostol suppositories were made from two 200-microg tablets (Cytotec, Searle Pharmaceuticals, Skokie, IL), whereas the placebo was made from cocoa butter. A 12-point radiation proctitis symptom score was obtained from each patient at 4, 8, 12, and 36 wk after radiation therapy.. A total of 16 patients were enrolled. Seven patients received placebo, and nine patients received misoprostol. Mean radiation proctitis symptom scores in the placebo group were 4.86, 5.86, 5.71, and 3.83 at 4, 8, 12, and 36 wk, respectively. The mean scores in the misoprostol group were 0.78, 0.67, 0.33, and 0.37 at 4, 8, 12, and 36 wk, respectively. The difference between the two groups was statistically significant (p < 0.05) at 4, 8, 12, and 36 wk.. Misoprostol rectal suppositories significantly reduce acute and chronic radiation proctitis symptoms in patients receiving radiation therapy for prostate cancer.

Topics: Acute Disease; Aged; Chronic Disease; Double-Blind Method; Humans; Male; Middle Aged; Misoprostol; Placebos; Proctitis; Prospective Studies; Prostatic Neoplasms; Radiation Injuries; Rectum; Suppositories

Prostaglandin E analogs have been shown to be effective in the treatment of refractory trigeminal neuralgia in patients with multiple sclerosis. Prostaglandin E inhibits the functions of T lymphocytes which are involved in the pathophysiology of cluster headache. Therefore, a double-blind, placebo-controlled, crossover study on the efficacy of misoprostol in chronic refractory cluster headache was performed. Eight patients were treated with 600 micrograms misoprostol and with placebo for a 2-week period. No differences in attack frequency, intensity, global impression, and side effects could be detected, suggesting that prostaglandin E analogs are not effective in the treatment of chronic cluster headache.

Topics: Adult; Chronic Disease; Cluster Headache; Cross-Over Studies; Double-Blind Method; Humans; Male; Middle Aged; Misoprostol; Pain, Intractable

Misoprostol is known to be effective in stimulating intestinal transit both in healthy individuals and in patients with chronic constipation when evaluated in short-term trials. The aim of this study was to determine the utility of misoprostol in the long-term management of patients with chronic refractory constipation.. Eighteen patients were offered misoprostol (600-2400 microg/day) as adjunctive therapy in an open-ended, non-blinded trial. All patients were encouraged to continue the drug for a minimum of 4 weeks, after which time the effect on bowel movement patterns was evaluated and continued use of misoprostol was offered to those patients who demonstrated a clinical benefit.. Six patients withdrew prior to 4 weeks because of side-effects. In the 12 patients who continued the treatment and were evaluated at 4 weeks, the mean interval between bowel movement frequency had decreased from a baseline of 11.25 to 4.8 days (P = 0.0004). Eight patients continued the long-term treatment, with sustained response seen in six. In a subset of patients (n = 4) the effect of single-dose misoprostol (400 microg) was evaluated compared to healthy controls (n = 5) on post-prandial segmental colonic motility. Misoprostol augmented the colonic motility response to a meal throughout the colon, and this was significantly greater in the left versus right colonic segments (P < 0.05).. Misoprostol can be effective as part of the long-term medical treatment of patients with chronic refractory constipation, but side-effects are observed at higher doses and can be a limiting factor. Part of misoprostol's action may be mediated through the augmentation of colonic motility, particularly of the left colon.

Topics: Adult; Aged; Cathartics; Chronic Disease; Constipation; Female; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Male; Middle Aged; Misoprostol; Postprandial Period; Time Factors

Chronic vascular rejection is a major cause of long-term graft failure after renal transplantation. We investigated the effect of the addition of misoprostol (200 micrograms four times daily) to standard immunosuppressive therapy on the outcome of chronic rejection in a double-blind, placebo-controlled trial. Patients had to fulfill predefined histological and clinical criteria. After an entry of 40 patients into the study (22 misoprostol, 18 placebo), the inclusion of additional patients was terminated because of a high incidence of withdrawal due to adverse effects. Of the patients who used their study medication for at least 3 months (16 misoprostol, 15 placebo), graft function deteriorated in all but 5 misoprostol-treated and all but 2 placebo-treated patients. There was no difference in dialysis-free survival. Withdrawal because of adverse effects (mainly gastrointestinal complaints) occurred in 3 cases in the placebo group and in 11 cases in the misoprostol group (P < 0.05). In conclusion, we found no evidence for a beneficial effect of misoprostol on the course of chronic renal allograft rejection, while use of the drug was accompanied by a high incidence of side effects.

Topics: Adult; Chronic Disease; Double-Blind Method; Female; Graft Rejection; Humans; Immunosuppressive Agents; Male; Middle Aged; Misoprostol

An endoscopic screening was carried out during the period between July 1989 and December 1991 in the Municipality of Roccagorga (LT) in order to: a) evaluate the presence of various forms of gastritis and pre-cancerous lesions; 2) verify the effect of the administration of prostaglandins (Misoprostol) on the evolution of superficial chronic gastritis (CG). A total of 468 endoscopy were performed (17% of the population aged between 20 and 75 years old). 22% of the subjects examined were found to be endoscopically normal; 34% presented symptoms of mild esophagitis and 4% of moderate esophagitis. The prevalence of duodenal ulcer was 10.6% and gastric ulcer 3.4%. Gastric carcinoma was diagnosed in 6 patients (1.2%). 8.5% of patients were found to have atrophic CG and 15.3% superficial CG. Thirty-six patients with superficial CG were randomly divided into two groups: A) treated with Misoprostol 600 mg/day for 6 months; B) controls (placebo). The administration of Misoprostol did not influence the evolution of CG, whereas it caused a reduction in the incidence of type 1 intestinal metaplasia. Misoprostol also led to an improvement in dyspeptic symptoms. The results of the present study do not suggest a role of prostaglandins in the natural evolution of CG.

Topics: Adult; Aged; Chronic Disease; Diagnosis, Differential; Duodenal Ulcer; Female; Gastritis; Gastroscopy; Humans; Male; Middle Aged; Misoprostol; Stomach Neoplasms; Stomach Ulcer

To assess the efficacy of misoprostol for the treatment of chronic erosive gastritis and associated symptoms.. We performed a double-blind controlled trial, administering 200-micrograms misoprostol tablets or placebo twice daily for 2 months to 48 patients with symptomatic chronic erosive gastritis. Symptomatology was assessed by means of a standard questionnaire at the beginning and at the end of the study, as well as endoscopic and histologic changes of the gastric mucosa.. At the end of the treatment period, a significant reduction in symptom score was observed in misoprostol-treated (from 86.6 +/- 66.2 to 17.6 +/- 18.2, p < 0.001) but not in placebo-treated patients. Endoscopic score was significantly reduced at the end of the treatment period in the misoprostol group, compared with that of the placebo group (p < 0.05). A significant reduction in the activity of histologic gastritis was observed only in patients on misoprostol. The prevalence of gastric colonization by Helicobacter pylori was rather low (30%), and no effect of treatment was observed.. Patients with symptomatic chronic erosive gastritis seem to profit from treatment with misoprostol: the treatment with misoprostol, but not with placebo, was effective in significantly reducing the extent of symptoms. Such an improvement was associated with a substantial improvement in the endoscopic and histologic appearance of the gastric mucosa.

Topics: Chronic Disease; Double-Blind Method; Female; Gastric Mucosa; Gastritis; Gastroscopy; Helicobacter pylori; Humans; Male; Middle Aged; Misoprostol

To assess the efficacy of misoprostol in the treatment of patients with severe chronic constipation, nine such patients were enrolled in a double-blind, randomized, crossover study of misoprostol (1200 micrograms/day) or placebo, that lasted three weeks. During this period each patient received the drug for one week and placebo for another with a week washout period in between. A colonic transit study, using radiopaque markers, was performed during each of the treatment weeks, while the number of stools and their total weight was recorded by each patient for the appropriate periods. Colonic transit time was significantly and consistently decreased by misoprostol compared to placebo [66 hr +/- 10.2 vs 109.4 hr +/- 8.1 (P = 0.0005)]. Misoprostol significantly increased the total stool weight per week [976.5 g +/- 288.8 vs 434.6 g +/- 190.5 (P = 0.001)] and also significantly increased the number of stools per week compared to placebo [6.5 +/- 1.3 vs 2.5 +/- 0.11 (P = 0.01)]. The incidence of abdominal pain was similar in both groups. We concluded that misoprostol, during a short trial period, proved effective in increasing the frequency and weight of bowel movements and decreasing colonic transit time in patients with severe chronic constipation. It may be used as a therapeutic measure to treat such patients.

Topics: Adult; Aged; Chronic Disease; Colon; Constipation; Double-Blind Method; Female; Gastrointestinal Transit; Humans; Middle Aged; Misoprostol

A pilot study to determine if the synthetic prostaglandin E1 misoprostol is effective in treating severe tinnitus, to test the hypothesis that tinnitus production is related to prostaglandin metabolism.. Blinded, placebo controlled, hemicrossover.. House Ear Clinic, Los Angeles, Calif.. A volunteer and convenience sample of 24 subjects complaining of severe tinnitus was recruited from mailings, telephone calls, and the clinic population. The patients were not preselected except to be in otherwise good health.. Subjects were started on a regimen of placebo or 200 micrograms/d of misoprostol. The dosage was increased every 5 days by 200 micrograms until a total of 800 micrograms/d was achieved. After 1 month of drug administration, the placebo group was crossed over to the active drug phase.. Outcome was measured in terms of subjective reports of tinnitus severity, sleep patterns, and ability to concentrate.. Eight (33%) of the 24 patients reported improvement during the active drug phase. There were no placebo responders. Responders reported improvement in tinnitus severity, sleep, and concentration.. Findings support the contention that prostaglandins may be useful in the treatment of tinnitus. Further studies with larger samples are needed before widespread use of this intervention can be recommended.

Topics: Adult; Aged; Audiometry; Capsules; Chronic Disease; Female; Humans; Male; Middle Aged; Misoprostol; Placebos; Remission Induction; Tinnitus

Misoprostol, a synthetic methyl ester analogue of prostaglandin E1 (PGE1) is both a powerful inhibitor of gastric secretion and is able to protect the gastroduodenal mucosa from damage produced by alcohol, aspirin, naproxen and tolmetin. The results of 12 double-blind, randomized, placebo- and cimetidine-controlled trials involving 4000 patients have been reviewed here and show that misoprostol, given in a dosage of 800 micrograms daily in two or four divided doses, is able to produce rates of complete ulcer healing and pain relief in both gastric and duodenal ulcer which are significantly superior to placebo therapy and comparable to those achieved with high or conventional doses of cimetidine. One further large trial has shown that misoprostol is able to heal a significant proportion of duodenal ulcers refractory to treatment with H2 receptor antagonists. In the compromised patient, two trials have suggested that misoprostol is able to abolish the adverse effects of smoking on duodenal ulcer, although this effect was not apparent in the gastric ulcer trials or in other duodenal ulcer trials. Similarly, while in volunteers pretreatment with misoprostol is able to protect the gastric mucosa from alcohol damage, there is little clinical evidence to support improved ulcer healing in the patient who abuses alcohol. Further studies in these areas should be conducted. Misoprostol could well have an important role to play in the protection of the gastroduodenal mucosa from damage produced by non-steroidal anti-inflammatory drugs (NSAIDs) in arthritic patients compelled to take these drugs for long periods. A series of double-blind placebo-controlled trials in healthy volunteers have shown that pretreatment with, or simultaneous administration of, 800 micrograms daily of misoprostol, reduces significantly mucosal damage produced by aspirin, tolmetin and naproxen. Two controlled clinical trials in a large number of arthritic patients have shown firstly, that misoprostol 800 micrograms daily is able to reduce significantly aspirin-induced mucosal bleeding as compared with placebo and secondly, in an endoscopically, placebo-controlled trial that it reduced significantly the frequency and severity of aspirin-induced mucosal lesions, accelerated the healing of erosions and ulcers and in other patients was able to protect the undamaged mucosa from injury. Misoprostol is well tolerated--a dose related, usually self limiting, diarrhoea occurred in a small proportion of

Topics: Alprostadil; Anti-Ulcer Agents; Chronic Disease; Clinical Trials as Topic; Duodenal Ulcer; Female; Humans; Male; Misoprostol; Stomach Ulcer

The natural history of chronic antral gastritis in relation to the healing of duodenal ulcer and its response to treatment, if any, are unknown. We performed a double-blind controlled trial using an oral prostaglandin E1, misoprostol, in 229 patients with active duodenal ulcer randomized to receive placebo (n = 76), misoprostol 200 micrograms (n = 77), or misoprostol 300 micrograms (n = 76), q.i.d. orally. Healing of duodenal ulcer was assessed biweekly up to 12 wk by endoscopy, during which procedures at least two antral and two fundal biopsy specimens were taken. The activity and the degree of chronic inflammation of gastritis, as assessed histologically by the infiltration of polymorphs and chronic inflammatory cells, respectively, was graded blindly by two pathologists as nil, mild, moderate, or severe. Before treatment, 99% of patients had chronic antral gastritis and 1.5% had chronic fundal gastritis. In the placebo group, healed duodenal ulcer was associated with significantly (p less than 0.01, life table analysis) higher incidence of improvement of the activity of the antral gastritis (nil or mild as endpoint) than unhealed ulcer (30% vs. 4% at week 8). Irrespective of whether duodenal ulcer was healed or unhealed, significantly (p less than 0.01) more patients on misoprostol (50% at week 8) showed improvement (nil or mild as endpoint) than the placebo group. The degree of chronic inflammation of the antral gastritis showed similar significant changes in favor of misoprostol. Smoking and alcohol intake had no significant effect on the improvement of chronic antral gastritis. In conclusion, healing of duodenal ulcer was associated with improvement of the activity of chronic antral gastritis, which, as shown for the first time, could be further enhanced by a therapeutic agent--prostaglandin E1.

Topics: Adult; Alprostadil; Chronic Disease; Double-Blind Method; Duodenal Ulcer; Female; Gastritis; Humans; Male; Misoprostol; Placebos; Prostaglandins E; Random Allocation

Prostaglandin, a key molecule that stimulates the complex array of ulcer healing mechanism, gets synthesized in the mucosal cells by cyclooxygenase (COX) enzymes: COX-1 and COX-2. High expression level of COX-2 protein at healing ulcer margins highlights its role in ulcer healing and hypothesized to be an important contributing factor in healing mechanism of anti-ulcer drugs. In the present study we have compared the expression profile of COX-2 protein, prostaglandin E2 (PGE2) levels and myeloperoxidase activity in acetic acid induced chronic gastric ulcer model in rats treated with omeprazole, misoprostol and COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) celecoxib. Both COX-2 expression and PGE2 level have shown differential pattern in different treated groups parallel to the differential effects of these drugs on ulcer healing. Omeprazole has significantly elevated the expression level of COX-2 protein, PGE2 level (19.37%), and decreased myeloperoxidase activity (81.92%), thereby causing the most effective ulcer healing (89.74%). Similar trend was observed with misoprostol, but with relatively less pronounced ulcer healing and COX-2 expression. Celecoxib has retarded COX-2 expression and delayed ulcer healing. Therefore, induction of COX-2 expression leading to higher level of prostaglandin appears to be an important contributing factor in drug mediated ulcer healing apart from the respective mechanisms of different drugs.

Topics: Animals; Anti-Ulcer Agents; Blotting, Western; Celecoxib; Chronic Disease; Cyclooxygenase 2; Dinoprostone; Female; Gastric Mucosa; Male; Misoprostol; Omeprazole; Peroxidase; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Sulfonamides; Wound Healing

To identify the unbiased differences in all cause mortality among populations using 4 non-steroidal antiinflammatory drugs (NSAID): nabumetone, Arthrotec, diclofenac plus a cytoprotective agent dispensed separately (diclofenac+), and naproxen.. We performed a population based historical cohort study using linked data from several provincial health care databases. Logistic regression was used to produce estimates of the mortality associated with the study drugs unbiased by known confounders. The entire population of the province of Saskatchewan, Canada entitled to drug plan benefits in 1995 was eligible (approximately 91% of 1 million people). Participants were identified if they filled a prescription for one of the 4 study NSAID (18,424 individuals). They were then followed forward in time for 6 months to determine all cause mortality.. Compared to nabumetone, the adjusted odds of death for participants taking Arthrotec was 1.4 (95% confidence interval, CI: 0.9-2.1), for diclofenac+ 2.0 (1.3-3.1), and naproxen 3.0 (1.9-4.6).. The multivariate analysis showed patients taking nabumetone and Arthrotec had significantly lower mortality than those taking other study drugs. Nabumetone had 1/3 to 1/5 the mortality associated with the diclofenac+ and naproxen groups. It appears that inherent gastroprotective strategies in the study NSAID may translate into decreased mortality at the population level.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Butanones; Cause of Death; Chronic Disease; Cohort Studies; Diclofenac; Drug Combinations; Female; Humans; Logistic Models; Male; Middle Aged; Misoprostol; Nabumetone; Naproxen; Risk; Saskatchewan; Survival Rate

Topics: Acute Disease; Anti-Anxiety Agents; Behavior Therapy; Benzodiazepines; Chronic Disease; Diclofenac; Disasters; Drug Combinations; Humans; Hypnotics and Sedatives; Life Change Events; Misoprostol; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Stress, Psychological; Terrorism; United States

We report a case where an acquired deficit in platelet aggregation was associated with the use of misoprostol and contributed to increased gastrointestinal blood loss. A 70-year-old man presented with chronic gastrointestinal blood loss secondary to widespread telangiectases. Investigations showed prolonged bleeding time and severely impaired platelet aggregation in vitro. Withdrawal of misoprostol resulted in resolution of the prolonged bleeding time and improvement in the platelet dysfunction. We conclude that misoprostol can lead to impaired platelet function and may exacerbate blood loss.

Topics: Aged; Anti-Ulcer Agents; Bleeding Time; Chronic Disease; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Misoprostol; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Telangiectasis

Twenty-five liver cirrhosis patients with endoscopically demonstrated gastro-duodenal mucosal damage (microhemorrhages, erosions, ulcers) were treated with misoprostol (prostaglandin E1) 400 mg/die. Eleven patients (44%) had abdominal pain and diarrhea and stopped treatment. Three months later, a new endoscopy was performed in the 11 patients that completed the study (3 patients were lost at follow up). Mucosal damage was stable in 5 patients (45%) and improved in 6 patients (55%), with complete absence of mucosal lesions in 2 patients (P = 0.027, Wilcoxon Ranks test). No case of worsening was observed and no patient had digestive bleeding during treatment. Digestive bleeding is a common complication of liver cirrhosis, originating in about 50% of cases from gastro-duodenal mucosal damage. Misoprostol suggests itself as a possible alternative therapy to the drugs usually utilized in these lesions (beta-blockers, H2-inhibitors), but individual intolerance is frequent and must be preliminary excluded.

Topics: Aged; Chronic Disease; Drug Evaluation; Duodenum; Endoscopy, Digestive System; Female; Gastric Mucosa; Humans; Intestinal Mucosa; Liver Cirrhosis; Male; Middle Aged; Misoprostol

Cyclosporin A has markedly improved graft survival in transplant patients but its side effects, such as renal toxicity and hypertension, pose management problems in transplant recipients. This toxicity has been attributed to prostaglandin inhibition. Concurrent administration of misoprostol (a prostaglandin E1 analog) prevents chronic cyclosporin A-induced nephrotoxicity but not hypertension in rats.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Creatinine; Cyclosporine; Drug Therapy, Combination; Electrolytes; Glomerular Filtration Rate; Heart Rate; Hypertension; Kidney Diseases; Misoprostol; Osmolar Concentration; Prostaglandins; Rats; Rats, Sprague-Dawley; Renal Circulation; Renin

A patient with rheumatoid arthritis, who also had documented achlorhydria, first had the diagnosis of an antral ulcer made by barium meal in 1980. She did well taking cimetidine intermittently after that, along with various nonsteroidal antiinflammatory drugs (NSAIDs). In 1988, a shallow antral ulcer was found, but the patient did not respond to H2 blockade or to sucralfate. At that time misoprostol therapy was prescribed. Despite the continued use of NSAIDs, the ulcer healed. It has remained healed for the past 3 years.

Topics: Achlorhydria; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Chronic Disease; Female; Gastric Acidity Determination; Humans; Misoprostol; Pentagastrin; Stomach Ulcer