Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for patients with ulcerative proctitis in remission. METHODS: In this 24-month, multicenter, double-blind trial, 65 patients with ulcerative proctitis in clinical and endoscopic remission were randomized to receive either a single nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or increase in stool frequency for > or =1 wk and active inflammation upon endoscopy). RESULTS: Mean time to relapse was 453.4 days for mesalamine-treated patients and 158.0 days for placebo-treated patients. Survival analysis demonstrated that time to relapse was significantly greater for mesalamine-treated patients than for placebo-treated patients (p < 0.001). In addition, at both 12 and 24 months, the proportion of placebo-treated patients (86% at 12 months and 89% at 24 months) who relapsed was significantly (p < or = 0.001) greater than mesalamine-treated patients (32% and 46%, respectively). No statistically significant differences occurred between treatment groups in the reporting of any particular adverse event or the number of patients reporting adverse events. CONCLUSIONS: The results demonstrate that mesalamine suppositories are efficacious, well tolerated, and safe for the long-term maintenance of remission of ulcerative proctitis.

Effect of combined anticoagulation and low-dose aspirin treatment on upper gastrointestinal bleeding.

Multiple studies link the use of nonsteroidal antiinflammatory drugs (NSAIDs) with severe upper gastrointestinal bleeding (UGIB); the incidence of such bleeding is 2-4%. One common regimen to assure patency after intracoronary stent placement requires an anticoagulant (warfarin) combined with aspirin as an antiplatelet agent. However, a 13-fold increase in the risk of UGIB occurs with long-term use of oral anticoagulants and NSAIDs. We retrospectively assessed the rate of UGIB in 138 patients who had received coronary stents (group I, receiving heparin followed by warfarin in combination with aspirin) and 109 angioplasty patients without stents (group II, receiving aspirin alone) between 1990 and 1994. UGIB was identified by hematemesis or melena, which led to gastrointestinal consultation. Patients were analyzed for multiple risk factors. UGIB occurred in 28 of 138 group I patients (20%; 95% CI 13.3-26.7%) and 0 of 109 group II patients (P < 0.0001). Esophagogastroduodenoscopy (EGD) findings on the 28 patients with UGIB included 13 patients with esophagitis or gastritis, 7 patients with gastric or duodenal ulcers, and 8 patients with no identifiable source of bleeding. UGIB occurred within a mean of 2.5 days of initiation of combination therapy. Of patients with UGIB, 10 required blood transfusion (mean number of units = 5.3). Previous history of peptic ulcer disease, smoking, and use of antiulcer medication did not significantly differ between the two groups. The concurrent use of anticoagulant and aspirin in patients with coronary stents creates a significant potential for UGIB and should be used only with extreme caution.

Abstinence in alcoholic chronic pancreatitis. Effect on pain and outcome.

The role of alcohol in causing chronic pancreatitis is well-known, but the role of abstinence remains controversial and not well-understood. In this article, I examine the literature dealing with the effect of abstinence on chronic pain and the long-term outcome of chronic pancreatitis. A series of 50 patients with alcoholic chronic pancreatitis from my practice supplements the data. Alcohol consumption > 70 g/day for 7 or more years is characteristic. Moderate to severe abdominal pain is the dominant symptom. When patients stop drinking, abdominal pain disappears in the majority, pancreatic function deteriorates more slowly, the death rate diminishes, and a normal life is often possible. If abdominal pain continues after abstinence and the pancreatic duct remains dilated, a lateral pancreatojejunostomy helps most patients. In many patients not suitable for surgery, pain resolves with time.

Update on traveler's diarrhea.

Traveler's diarrhea affects a substantial number of travelers to high-risk areas of the world. The key to controlling this troublesome disease is prevention. The most important preventive measures depend on educating patients to consume only safe foods and pure water. Physicians cannot overemphasize the importance of avoiding high-risk foods and of boiling water if a safe water supply is not available. Prophylactic medications are a secondary consideration and should be prescribed with discretion. In most cases, diarrhea is mild and self-limited, requiring only fluid and electrolyte replacement and perhaps an antidiarrheal agent. In moderate to severe cases, the addition of an antimicrobial agent may be of benefit. Until an efficacious polyvalent vaccine is developed, caution and common sense, together with discretionary dietary and hygienic practices, are the best defenses against traveler's diarrhea. The ultimate solution is greatly improved sanitation and personal hygiene, especially in high-risk countries. However, only dreamers will consider waiting for this transformation to occur.

Prevention of duodenal ulcer recurrence.

Recurrent duodenal ulcers, treated with cimetidine, 400 mg, or ranitidine, 150 mg, once nightly, or with sucralfate, 1 g twice daily, can be prevented in approximately 75% of patients for up to 1 year. Because these drugs are generally of equal efficacy, the choice is based on the patient's previous drug experience and tolerance, potential side effects, risk of drug interaction, frequency of administration, and cost. These medications do not alter the natural history of duodenal ulcer disease, and therapy may need to continue for longer than 1 year if there are no long-term side effects. Extra efforts should be made to help cigarette smokers discontinue smoking. Patients who have recurrent duodenal ulcers during maintenance therapy can be retreated with full-dose therapy. If optimal drug therapy is unsuccessful in preventing frequent recurrences or complications, surgical treatment is indicated.

Effect of ethanol and other aliphatic alcohols on the intestinal transport of folates.

The effect of ethanol and other aliphatic alcohols on the intestinal transport of 5-methyltetrahydrofolate and folic acid was examined using everted sacs from rat jejunum. Ethanol added to the mucosal medium inhibited the transport of both folate compounds in a parallel manner, and the inhibition increased with increasing ethanol concentration (0.5-10% v/v). Ethanol at 3% v/v in the mucosal medium caused: depression in the pH dependency of the active transport of 5-methyltetrahydrofolate; higher inhibition in the transport of low concentration (0.1 microM) than high concentration (10 microM) of 5-methyltetrahydrofolate, and inhibition in the active accumulation against a concentration gradient of 5-methyltetrahydrofolate and L-leucine. Methanol, propanol and butanol also inhibited the transport of the folate compounds; and in general, the inhibitory effect increased with the increase in the number of carbon atoms in the hydrophobic chain. This study indicates that ethanol and other alcohols inhibit the intestinal transport of folates, that the degree of inhibition is related to the concentration and chain length of the alcohol, that the inhibition is not specific for folates and finally that the mechanism of inhibition is multifactorial.

Inhibitory effect of unconjugated bile acids on the enterohepatic circulation of methotrexate.

The effect of unconjugated cholic and deoxycholic acids on intestinal and hepatic transport and bile secretion of methotrexate was studied using everted sacs of rat proximal jejunum and isolated perfused rat liver. Cholic and deoxycholic acids competitively inhibit the mucosal-to-serosal transport of methotrexate (Ki, 0.08 and 0.06 mM, respectively). Cholic and deoxycholic acids also decrease intestinal tissue content of methotrexate in a concentration-dependent manner. Structural and functional damage to the intestinal mucosa does not occur in tissue treated with 0.1 mM and lower concentration of deoxycholic acid as assessed by histological studies, transmural potential difference measurements and the release of the cytoplasmic marker enzyme, lactate dehydrogenase. In the isolated liver, cholic and deoxycholic acids inhibit the uptake, retention and biliary secretion of methotrexate. At 1 mM cholic and deoxycholic acids, 72 and 80% inhibition in liver uptake and 93 and 99% inhibition in bile secretion of 1 microM methotrexate are observed, respectively. These studies demonstrate that unconjugated bile acids inhibit the enterohepatic circulation of methotrexate by impairing its intestinal transport and hepatic uptake and retention and biliary secretion.

Inhibitory effect of unconjugated bile acids on the intestinal transport of 5-methyltetrahydrofolate in rat jejunum in vitro.

The effect of the unconjugated bile acids, cholic, deoxycholic, chenodeoxycholic, and ursodeoxycholic acids, and of the conjugated bile acid taurocholic acid on the mucosal-to-serosal transport and tissue uptake of the naturally occurring folate derivative, 5-methyltetrahydrofolate (5-CH3H4PteGlu) was examined in everted sacs of rat jejunum. Each of the unconjugated bile acids examined inhibited the transport and tissue uptake of 5-CH3H4PteGlu in a concentration dependent manner. At low concentrations (0.01-0.1 mM) of cholic and deoxycholic acids, no structural or functional damage to the intestinal mucosa occurred and the transport of 5-CH3H4PteGlu was inhibited competitively with Ki values of 0.114 mM and 0.055 mM for cholic and deoxycholic acids, respectively. The greater inhibition of 5-CH3H4PteGlu transport by unconjugated bile acids at 1 mM can be attributed to observed structural and functional damage to the intestinal mucosa. The addition of 2 mM lecithin to the mucosal medium failed to prevent the inhibitory effect of 0.1 mM deoxycholic acid on the transport of 0.5 microM 5-CH3H4PteGlu. Compared with the effect of unconjugated bile acids, the conjugated bile acid taurocholic acid (0.01-5 mM) showed no effect on the transport and tissue uptake of 5-CH3H4PteGlu. The results of this study show that intestinal transport and tissue uptake of 5-CH3H4PteGlu are inhibited by unconjugated bile acids in a dose-dependent fashion. The clinical and physiological implications of these observations are discussed.