Misoprostol and ranitidine in the prevention of NSAID-induced ulcers: a prospective, double-blind, multicenter study.

OBJECTIVE: To compare ranitidine to misoprostol with respect to the prevention of gastric and duodenal ulcers in patients on chronic NSAID therapy. METHODS: A multi-center, 8-wk, randomized, double-blind study. Eligible patients were on chronic NSAID therapy and were experiencing NSAID-related upper gastrointestinal (UGI) pain without UGI endoscopic evidence of gastric or duodenal ulcers. Patients enrolled in the study were randomized to either misoprostol 200 micrograms q.i.d. or ranitidine 150 mg b.i.d.. Follow-up UGI endoscopy was performed after 4 and 8 wk of treatment. Therapeutic failure was considered the development of a gastric or duodenal ulcer > or = 0.3 cm in diameter with perceptible depth. RESULTS: Gastric ulcers were found in only 1/180 (0.56%) patient on misoprostol and in 11/194 (5.67%) patients on ranitidine, a difference that was statistically significant (p < 0.01). Duodenal ulcer rates were similar for the ranitidine (2/185 or 1.08%) and misoprostol (2/181 or 1.10%) groups. CONCLUSION: Misoprostol is significantly more effective than ranitidine in the prevention of NSAID-induced gastric ulcers. Ranitidine was as effective as misoprostol for the prevention of NSAID-induced duodenal ulcers. Misoprostol should be used for prophylaxis against both gastric and duodenal ulceration in patients on chronic NSAID therapy.

Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection.

BACKGROUND & AIMS: Multiple tests are available for determining Helicobacter pylori infection. Our aim was to compare the sensitivity, specificity, and negative and positive predictive value of the most widely available tests for diagnosis of H. pylori. METHODS: A total of 268 patients (mean age, 53.7 +/- 15.8 years; 142 male and 126 female; 125 white and 143 nonwhite) was tested for H. pylori infection by [13C]urea breath test (UBT), measurement of serum immunoglobulin (Ig) G and IgA antibody levels, and antral biopsy specimens for CLO test, histology, and Warthin-Starry stain. No patient received specific treatment for H. pylori before testing. The infection status for each patient was established by a concordance of test results. RESULTS: Warthin-Starry staining had the best sensitivity and specificity, although CLO test, UBT, and IgG levels were not statistically different in determining the correct diagnosis. The absence of chronic antral inflammation was the best method to exclude infection. Stratification of results by clinical characteristics showed that UBT and chronic inflammation were the best predictors of H. pylori status in patients older than 60 years of age. IgA was a better predictor in white patients. CONCLUSIONS: The noninvasive UBT and IgG serology test are as accurate in predicting H. pylori status in untreated patients as the invasive tests of CLO and Warthin-Starry.

Decrease in ornithine decarboxylase activity after eradication of Helicobacter pylori.

OBJECTIVE: Our aim was to determine whether gastric mucosal ODC activity is altered after successful eradication of HP. Recent reports have suggested that Helicobacter pylori (HP) infection of the stomach is associated with the development of gastric cancer. Gastrointestinal cancers usually do not arise de novo; a series of mucosal changes leading to neoplastic transformation and degrees of dysplasia are believed to precede the development of cancer. These conditions are associated with increased cellular proliferation. Ornithine decarboxylase (ODC) activity is induced by factors that stimulate cellular proliferation, and has been shown to be elevated in gastrointestinal neoplasia, including gastric cancer. METHODS: Gastric antral and body biopsies were obtained from 17 HP-positive patients at endoscopy, for ODC activity and histology (including Warthin Starry stain) before and 4-6 wk after successful triple therapy. RESULTS: Patients included 12 males and five females, with a mean age of 55 yr (27-73 yr). Mean ODC activity (in pmol CO2/mg protein/h) was significantly decreased after eradication of HP, compared with pretreatment levels in antral (147 +/- 26 vs. 80 +/- 15) and body mucosa (76 +/- 21 vs. 20 +/- 5) (p < 0.05). CONCLUSION: Successful eradication of HP decreases mucosal proliferative activity, as reflected by decreased ODC activity. We speculate that by decreasing mucosal proliferative activity, HP eradication may help decrease the subsequent risk of gastric cancer.

Long-term Helicobacter pylori recurrence after successful eradication with triple therapy.

To establish the rate of Helicobacter pylori recurrence after a standard triple-therapy regimen (bismuth subsalicylate, tetracycline, metronidazole) and determine which clinical factors affect reinfection, we prospectively followed 118 patients after successful H. pylori eradication. Elimination of H. pylori was confirmed by repeat endoscopy and urea breath test 4 wk after completion of therapy. Serial [13C]urea breath tests were performed at 3-month intervals; antral biopsies were used to verify reinfection. Recurrence of H. pylori infection occurred in 4/118 (3.4%) patients. Three of the four relapses occurred in the 1st yr after treatment. Gender, age, ethnic group, alcohol consumption, cigarette use, and gastrointestinal diagnosis do not predict H. pylori recurrence. We conclude that the rate of recurrence after successful H. pylori eradication is low, and that when reinfection takes place, it occurs most commonly within the 1st yr after treatment.

Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group.

OBJECTIVES: To determine the efficacy of misoprostol for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced duodenal and gastric ulcers in arthritis patients receiving NSAID therapy. DESIGN: A randomized, double-blind, multicenter, placebo-controlled trial. SETTING: Six hundred thirty-eight private, Veterans Affairs, health maintenance, and academic practices. PATIENTS: Six hundred thirty-eight patients with chronic inflammatory or noninflammatory arthritis who were taking an NSAID but who did not have a gastric or duodenal ulcer on screening endoscopy received treatment with ibuprofen, piroxicam, naproxen, sulindac, tolmetin, indomethacin, or diclofenac daily for 3 months. Four hundred fifty-five (71%) patients completed the trial. INTERVENTIONS: Patients meeting the entry criteria were randomized to receive either misoprostol, 200 micrograms, or placebo, four times a day for 12 weeks. MAIN OUTCOME MEASURES: The endoscopy was repeated at 4, 8, and 12 weeks. The development of a duodenal or gastric ulcer (defined as a circumscribed mucosal defect > or = 0.5 cm in diameter and with perceptible depth) was regarded as prophylactic failure. RESULTS: By 12 weeks, a duodenal ulcer developed in 2 of 320 (0.6%; 95% CI, 0.2% to 3.9%) patients randomized to receive misoprostol, compared with 15 of 323 (4.6%; CI, 2.8% to 8%) patients receiving placebo (P = 0.002). A gastric ulcer developed in 6 of 320 (1.9%; (CI, 0.8% to 4.4%) patients, compared with in 25 of 323 (7.7%; CI, 5.1% to 11.4%), respectively. CONCLUSION: Misoprostol significantly lowers the frequency of both duodenal and gastric ulcer development in patients who require long-term therapy with NSAIDS.

Patient factors affecting Helicobacter pylori eradication with triple therapy.

Duodenal ulcer recurrence and gastritis are reduced with successful Helicobacter pylori treatment. To identify the patient factor influencing H. pylori eradication, we prospectively evaluated 96 consecutive patients undergoing a single 2-wk course of bismuth, tetracycline, and metronidazole therapy. At the time of initial esophagogastroduodenoscopy with biopsies, each patient had a profile obtained which included demographic information, gastrointestinal pathology, and H. pylori status of the spouse. Elimination of H. pylori was confirmed by repeat esophagogastroduodenoscopy with biopsies 4 wk after the completion of therapy and serial urea breath tests. Eradication at 4 wk was successful in 80 of 96 (83%) patients. On multivariate analysis, H. pylori elimination was associated with advanced age (p = 0.002) and a greater amount of chronic inflammation on baseline antral biopsy (p = 0.024). Eradication was inversely associated with the presence of a gastric ulcer (p = 0.008) and lack of medication compliance (p = 0.030). Successful eradication reduced the severity of both acute and chronic antral mucosal inflammation. Household income, gender, ethnic group, smoking, alcohol intake, and H. pylori status of the spouse did not differ between the eradicated and noneradicated groups. We conclude that it will be important to control for influential patient factors in future studies of H. pylori treatment regimens.

Ulcer risk factors: interactions between Helicobacter pylori infection, nonsteroidal use, and age.

PURPOSE: To evaluate the influence of Helicobacter pylori, nonsteroidal anti-inflammatory drug (NSAID) use, tobacco and alcohol use, age, gender, ethnic group, and the indication for endoscopy on the frequency of gastric and duodenal ulcers in patients referred for upper endoscopy. PATIENTS AND METHODS: One thousand eighty-eight consecutive patients without prior antrectomy or active bleeding at endoscopy who were able to provide a history were interviewed prior to endoscopy, and antral biopsies were performed for H. pylori at endoscopy. Variables were tested for univariate association with duodenal or gastric ulcer and those variables with p < 0.25 were included in the logistic regression model building. RESULTS: One hundred seven patients had duodenal ulcer, 97 had gastric ulcers, and 5 had both. Significant risk factors in the final model for duodenal ulcer were H. pylori, history of previous ulcer, male gender, bleeding, and pain at presentation (p < 0.001), whereas alcohol was associated with a decreased risk (p = 0.026). H. pylori presence (p = 0.011), aspirin use (p = 0.009), and bleeding (p = 0.012) were associated with gastric ulcer in the final model; esophageal symptoms were associated with decreased risk of gastric ulcer (p = 0.003). NSAID use was associated with gastric ulcers only in those over 55 (p < 0.05), especially whites, and in nonwhites without prior ulcer. There was no interaction between H. pylori and NSAIDs. CONCLUSIONS: H. pylori was associated with an increased risk of duodenal and gastric ulcers. Aspirin increases the risk for gastric ulcer in patients of all ages, whereas nonaspirin, nonsteroidal use increases the risk for gastric ulcers to varying degrees in patients over age 55, depending on race and history of ulcer.

Helicobacter pylori seroprevalence in patients with rheumatoid arthritis: effect of nonsteroidal anti-inflammatory drugs and gold compounds.

PURPOSE: To investigate the relationship between Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) intolerance and the effect of gold use on the seroprevalence of H. pylori. PATIENTS AND METHODS: We examined the frequency of discontinuation of NSAIDs in 132 unselected patients with rheumatoid arthritis attending an outpatient subspecialty clinic, and the effect of gold compound use on the seroprevalence (by IgG enzyme-linked immunosorbent assay) of H. pylori infection in this population. Logistic and multivariate regression analysis was performed adjusting for age, gender, ethnic origin, history of ulcer, and duration of rheumatoid arthritis. RESULTS: Fifty-four patients had a positive serology for H. pylori (41%). Twenty-seven of the seropositive patients (50%), versus 45 of the seronegative patients (57.7%), had to discontinue NSAIDs (aspirin and/or nonaspirin) at least once since their diagnosis of rheumatoid arthritis because of gastrointestinal side effects (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.63 to 1.38). Forty-one of the seropositive patients (76%) had received gold compounds as compared with 62 of the seronegative patients (79.5%) (OR: 0.96; 95% CI: 0.61 to 1.50). CONCLUSION: We did not find any relationship between H. pylori seropositivity and NSAID intolerance in patients with rheumatoid arthritis. In addition, our results do not demonstrate a reduction in H. pylori seroprevalence in rheumatoid arthritis patients treated with gold compounds.

Symptoms, gastritis, and Helicobacter pylori in patients referred for endoscopy.

Acute Helicobacter pylori infection is associated with dyspeptic symptoms but chronic infection has not clearly been shown to cause symptoms. To define further the role of H. pylori infection and gastritis in dyspepsia, we interviewed all patients about to undergo upper endoscopy, recorded the primary indication for endoscopy, noted the endoscopic findings, and obtained antral biopsies. Among non-ulcer patients there was a strong correlation of acute gastritis with H. pylori. Gastritis and H. pylori increased with age, and non-steroidal anti-inflammatory drug use correlated with normal histology. Neither H. pylori concentration nor gastritis grade correlated with gender, use of alcohol and tobacco, indication for endoscopy, or symptoms (epigastric pain, nausea, vomiting, bloating, belching, heartburn, halitosis, and flatulence).

Increased density of Helicobacter pylori on antral biopsy is associated with severity of acute and chronic inflammation and likelihood of duodenal ulceration.

An increased risk of ulcers and severity of inflammation with increased degree of Helicobacter pylori (HP) infection (biological gradient) would support the hypothesis that HP causes ulcers. A blinded pathologist evaluated antral biopsies obtained at endoscopy in 903 patients. The level of HP infection was assessed on Warthin Starry stain, and the severity of acute and chronic inflammation on hematoxylin and eosin graded from 0 to 3. The presence of duodenal ulcers was associated with increasing HP density (grade 0, 6%; grade 1, 16%; grade 2, 19%; and grade 3, 27%) (p less than 0.0001, Wilcoxon rank sum test). Only a weak association between HP and gastric ulcers was detected (p = 0.06, Wilcoxon rank sum test), and this association diminished after adjusting for other risk factors. An increased acute and chronic inflammatory response correlated with increasing HP concentration (p less than 0.0001, Cochran-Mantel-Haenszel correlation statistic. The presence of this biologic gradient supports the hypothesis that HP is pathogenic in duodenal ulcers and in acute and chronic gastritis.

Myxedema ascites. Report of two cases and review of the literature.

Ascites is a well-known but uncommon occurrence in hypothyroid patients. We describe two patients with clinical ascites that resolved completely on thyroid replacement therapy. Our review of the literature found 21 well-documented cases of myxedema ascites. Prominent features of this condition include a high protein content of the ascitic fluid (greater than 2.5 g/dl), a high albumin serum-ascites gradient, a long duration of the ascites, and its resolution on thyroid replacement. We also found a slight female predominance. The exact mechanisms responsible for ascites accumulation are unknown and some of the hypotheses are discussed. We conclude that ascites associated with hypothyroidism is rare but must be recognized early since thyroid replacement is definitive therapy.

Helicobacter pylori-negative duodenal ulcer.

UNLABELLED: PURPOSE PATIENTS AND METHODS: Helicobacter pylori (HP) is present in more than 90% of duodenal ulcers (DUs). To investigate the pathophysiology in those patients with DU who are HP-negative compared with those who are HP-positive, we interviewed consecutive patients prior to endoscopy regarding factors often associated with ulcer disease. At esophagogastroduodenoscopy, antral biopsy specimens were obtained for urease test, culture, and Warthin Starry staining for HP in all patients with DU who did not have active bleeding. RESULTS: Compared with HP-positive patients who had DU, HP-negative patients with DU were more likely to be aspirin users and less likely to have had prior ulcers. HP-positive patients with DU had more severe antral inflammation than HP-negative patients. Whites were more likely to be HP-negative than blacks. HP-negative patients with DU most commonly presented with bleeding, whereas HP-positive patients with DU presented with pain. CONCLUSIONS: Our findings suggest a different mechanism for DUs in patients who are HP-positive versus those who are HP-negative, and this difference might have a bearing on treatment. The absence of HP should lead to a more thorough search for nonsteroidal anti-inflammatory drug/aspirin use, Zollinger-Ellison syndrome, and other potential causes of DUs.

Gastrocolic fistula with pyloric stenosis and benign gastric ulcer.

We have reported a case of gastrocolic fistula with gastric outlet obstruction as a complication of benign gastric ulcer. The single-stage surgical procedure described resulted in a successful outcome. Benign gastric ulcer currently appears to be the most prevalent cause of gastrocolic fistula.

Esophageal involvement in secondary amyloidosis mimicking achalasia.

Amyloidosis is usually considered as a cause of motor disorders of the esophagus, including achalasia. However, most patients with amyloid in the esophagus are AL-type amyloid. We report what we believe is the fourth case of secondary amyloidosis (AA-type) resulting from rheumatoid arthritis. Clinically and radiologically the picture was that of achalasia.

Barogenic perforation of the esophagus distal to a stricture after endoscopy.

Instrumentation is the most common cause of esophageal perforation, usually at or above a stricture. We report an unusual case in which the perforation occurred distal to a proximal esophageal stricture during diagnostic endoscopy. The perforation occurred close to the gastroesophageal junction involving an apparently normal esophagus, in a manner similar to that of "spontaneous," barogenic esophageal rupture (Boerhaave's syndrome). We postulate that the abrupt rise in pressure in the intraluminal esophagus, the inlet of which was obstructed by a tightly fitting instrument, was responsible for the rupture.

Secondary bacterial peritonitis due to Listeria monocytogenes after paracentesis.

Although it is a relatively rare cause of peritonitis, Listeria monocytogenes must be considered in cirrhotic patients with ascites and a suggestive clinical presentation. We believe this is the first report of a case of peritonitis due to L monocytogenes in a patient without sepsis, and the sixth reported case of bacterial peritonitis in a patient with cirrhosis.