Timothy T. Schubert

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.

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.

Role ofHelicobacter pylori serology in evaluating treatment success

Duodenal ulcer recurrence and gastritis are reduced with successfulHelicobacter pylori treatment. Serology is accurate in the diagnosis ofH. pylori, but its value in determining eradication is unproved. To evaluate the usefulness of serology in monitoring treatment, we measured serial serum antibodies in three patient groups: eradication success (N=57), eradication failure (N=19), and untreated patients (N=24). Eradication was determined by Warthin Starry staining of antral biopsies and repeat13C breath tests at six weeks. Subsequent13C breath tests were then performed at three-month intervals to monitor eradication. IgG antibody concentrations toH. pylori were determined by a commercially available ELISA kit. Serology concentrations remained constant throughout the study period in the untreated patients. IgG concentrations decreased slightly in the treatment failure group at six weeks but thereafter remained at baseline values. In the eradicated group, serum IgG concentrations decreased 26% by three months, 43% by six months and 55% at nine and 12 months (P<0.001). A 20% reduction in IgG concentrations by six months was associated with successful treatment (sensitivity 86% and specificity 88%). We conclude that serology is a potentially useful way to monitorH. pylori treatment success.

Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea

BACKGROUND/AIMS Diarrhea is a significant problem in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to determine octreotide effectiveness in refractory AIDS-associated diarrhea. METHODS In a 3-week protocol, 129 patients with a stool weight of > 500 g/day despite standard antidiarrheal therapy were randomized to receive octreotide or placebo (3:2 ratio). Octreotide dose was increased 100 micrograms weekly to a maximum of 300 micrograms three times a day based on weekly 72-hour stool collections. Subsequently, patients received open-label octreotide at doses of up to 500 micrograms three times a day. RESULTS A 30% decrease in stool weight defined response. After 3 weeks, 48% of octreotide- and 39% of placebo-treated patients had responded (P = 0.43). At 300 micrograms three times a day, 50% of octreotide- and 30.1% of placebo-treated patients responded (P = 0.12). At a baseline stool weight of 1000-2000 g/day, 57% of octreotide- and 25% of placebo-treated patients responded (P = 0.06). Response rates based on CD4 counts, diarrhea duration, body weight, human immunodeficiency virus risk factor, and presence or absence of pathogens showed no benefit of octreotide. Adverse events were more frequent in the octreotide-treated group. CONCLUSION In the doses studied, octreotide was not more effective than placebo in patients with refractory AIDS-associated diarrhea. This lack of effectiveness may be attributable to inadequate sample size, doses, and duration of study treatment.

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).

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.

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 (> 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.

Surgical Therapy of Diabetic Gastroparesis

Diabetic gastroparesis is a complication of diabetes mellitus that usually responds to medical management. We report a patient in whom medical management failed, and a gastrostomy, pyloroplasty, and jejunostomy were done to insure nutrition and to decompress the stomach. We also review the surgical management of this condition.

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.

A US multicenter study of enprostil 35 μg twice daily for treatment of prepyloric, pyloric channel, and duodenal bulb ulcers

One hundred twenty-seven patients with endoscopically diagnosed active duodenal, pyloric, or prepyloric ulcers participated in this multicenter, double-blind, randomized, controlled trial comparing placebo with enprostil 35 μg twice daily for up to four weeks. Cumulative endoscopic healing for the enprostil and placebo treatment groups, respectively, was 25% (15 of 59) and 12% (7 of 60) at two weeks (P=0.060) and 59% (34 of 58) and 33% (19 of 57) at four weeks (P=0.005). Excluding prepyloric ulcers, cumulative healing for the enprostil and placebo groups, respectively, was 22% (9 of 41) and 7% (3 of 44) at two weeks (P=0.104) and 56% (23 of 41) and 24% (10 of 42) at four weeks (P= 0.002). A greater percentage of prepyloric ulcers healed on enprostil than placebo, but the difference was not significant. Mean antacid use in both groups was identical, averaging only two or less tablets per day in each group throughout the study. Daytime pain was relieved more quickly in the enprostil group, while median time to relief of nighttime pain was essentially identical in both groups. The most common side effect in the enprostil treatment group, diarrhea, was mostly mild to moderate in intensity and was generally self-limiting, requiring no specific therapy; no patient withdrew because of this complaint. Other symptoms and laboratory profiles were similar in the two groups. These results indicate that enprostil 35 μg taken twice daily for four weeks is effective and safe for the treatment of prepyloric, pyloric channel, and duodenal ulcers.