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Hypothesis: Small-bowel diaphragm disease is an important source of gastrointestinal tract bleeding and subacute intestinal obstruction that may require surgical intervention., Design: Case series., Setting: Tertiary-care academic medical center., Patients: Seven consecutive patients with histologically confirmed enteropathy induced by use of nonsteroidal anti-inflammatory drugs received treatment at our institution from February 2001 to February 2004., Interventions: Laparotomy with small-bowel resection., Main Outcome Measures: Initial symptoms and signs, findings at diagnostic workup, type of medication and duration of use, operation performed, and intraoperative findings were evaluated., Results: Patients were identified who had symptoms of subacute intestinal obstruction or signs of gastrointestinal tract bleeding and were determined to have used nonsteroidal anti-inflammatory drugs for differing periods. All 7 patients underwent extensive nondiagnostic radiologic and endoscopic examinations. The diagnosis of diaphragm disease was ultimately made at either video capsule endoscopy or laparotomy. Randomly distributed diaphragms throughout the jejunum and ileum necessitated resection in all cases. No patient has had a documented recurrence, although follow-up is short (range, 0-20 months)., Conclusions: Nonsteroidal anti-inflammatory drugs are clearly linked to pathologic findings of diaphragm disease in both the upper and lower gastrointestinal tracts. Although rarely reported in the surgical literature, small-bowel diaphragm disease may be more common than thought and can manifest as gastrointestinal tract bleeding or obstruction. Diagnosis is difficult and may require laparotomy and small-bowel resection.

Diaphragm disease of the small intestine is part of the spectrum of diseases associated with injury to the gastrointestinal tract induced by nonsteroidal anti-inflammatory drugs. Standard endoscopy or contrast studies of the small intestine rarely identify these lesions. The diagnosis usually is established at the time of surgery. We report the case of a 72-year-old woman with obscure gastrointestinal bleeding and intermittent obstruction of the small intestine who had had multiple hospitalizations and extensive testing. The patient had been treated with nonsteroidal anti-inflammatory drugs for osteoarthritis. A radiograph of the small intestine with barium contrast revealed no abnormalities, so capsule endoscopy was performed. Capsule endoscopy showed multiple small intestinal strictures beyond which the capsule could not pass. After the patient experienced continued symptoms suggestive of intermittent partial obstruction of the small intestine, computed tomography showed the capsule within a dilated loop of intestine adjacent to a stricture. After 9 days of conservative medical therapy and worsening symptoms, the patient required an exploratory laparotomy. The capsule was located in a 12-cm segment of intestine with 4 diaphragm-like lesions. Pathologic study found submucosal lesions with features identical to those of neuromuscular and vascular hamartoma (eg, mature, reactive tissue elements of smooth muscle, dense fibrous tissue, and nerve tissue bundles with scattered ganglion cells and vessels). No manifestations of Crohn disease were evident. This case represents the first diagnosis with capsule endoscopy of diaphragm disease of the small intestine with pathologic features of neuromuscular and vascular hamartoma.

Objective: Rapid urease tests (RUTs) are used commonly as a convenient method to detect Helicobacter pylori infection. New rapid tests have been commercially available with promotional literature suggesting enhanced utility. We compared CLOtest to a new reagent strip RUT, PyloriTek., Methods: Gastric antral mucosal biopsy specimens were obtained from 102 patients for comparison between CLOtest and PyloriTek (204 specimens). Biopsy specimens obtained from a nearby area were stained using the Genta stain for determination of H. pylori status. The RUT to be used first was selected randomly., Results: Sixty-five of the 102 patients had peptic ulcer disease, two had gastric cancer, and 35 had dyspepsia; 61 patients had active H. pylori infection. There were one false-negative and three false-positive CLOtest results, compared with one false-negative and 13 false-positive PyloriTek results (p < 0.02 for incorrect categorization with PyloriTek). Sensitivity and specificity were 98 and 92% compared with 98 and 68% for CLOtest and PyloriTek, respectively. An erroneous categorization of H. pylori status occurred in 3.9% (95% confidence interval [CI]: 1-9.7%) with CLOtest compared with 13.7% (95% CI: 7.7 -22%) with PyloriTek. When the PyloriTek was scored at 1 h (0-1 h) after obtaining the specimen, the accuracy improved; erroneous categorization of H. pylori status occurred in only 2.9% (95% CI: 0.6-8.3%)., Conclusion: Used according to manufacturer instructions, the new reagent strip RUT PyloriTek has too many false-positive results for use in a clinical situation. In contrast, when the test was interpreted within 1 h, accuracy was comparable to that of CLOtest.

Background: We studied the mRNA expressions of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and IL-12 in gastric biopsy and blood samples from patients with and without Helicobacter pylori infection, by reverse-transcription polymerase chain reaction (RT-PCR)., Methods: RT-PCR was performed on total RNA preparations, and the expressed mRNA were semiquantitated on the basis of band intensities on Southern blots., Results: In gastric mucosa the expression of IFN-gamma and IL-10 was found in most patients with and without H. pylori infection, whereas IL-12 was found in most of the infected ones. The level of IFN-gamma and IL-10 did not differ between groups, whereas the IL-12 level was significantly higher in those with H. pylori infection. In the blood IFN-gamma expression was found in most samples, with higher level in patients with gastritis than in normals. Few blood samples (33%) had IL-12, and none had IL-10., Conclusion: IFN-gamma and IL-10 expressions in healthy mucosa may indicate a biologic role in a healthy state. IL-12 expression in mucosa was related to the presence of bacterial stimulant and therefore resembles proinflammatory cytokines.

Background: Rapid ureas tests (RUTs) provide a simple, sensitive method of detecting Helicobacter pylori infection., Objectives: Our aim, therefore, was to determine whether the yield of detecting H. pylori infection by RUT varied depending on the site of gastric biopsy., Materials and Methods: Gastric biopsies were obtained from 50 patients for RUT by use of hpfast (GI Supply, Camp Hill, PA). Biopsies were taken from the prepyloric greater curve antrum, from the gastric angle, and from the greater curve in mid-corpus. One biopsy specimen was placed in the RUT gel, and the biopsy from the adjacent mucosa was placed in formalin for subsequent histological evaluation by using the Genta stain. RUTs were examined and scored at intervals of 5, 10, 15, 30, and 45 minutes and after 1, 2, 4, and 24 hours., Results: Fifty patients were entered in the rest (150 RUTs), 32 having H. pylori infection. There were no false-positive RUTs (specificity, 100%). The gastric angle site was positive in 100%. The prepyloric site was positive in 87%, and the corpus site was positive in 84.4% (p < .052 for angle or prepyloric antrum versus corpus). The most common pattern was for all to be positive (74%). The median time to positivity was similar with angle and prepyloric sites (37.5 and 60 minutes, respectively, p = not significant) and shorter than the corpus biopsy (180 minutes); (p < .05 for angle or prepyloric antrum versus corpus)., Conclusion: The maximum probability for detecting H. pylori infection using a RUT is to obtain a biopsy from the gastric angle. To prevent missing a positive result when intestinal metaplasia is present, we recommend that (at a minimum) biopsies be taken from both the angle and the corpus.

Background: Rapid urease tests are commonly used as a convenient method to detect Helicobacter pylori infection. Our previous experiments demonstrated enhanced efficacy of agar gel rapid urease test compared with reagent strip rapid urease tests. We evaluated the efficacy of PyloriTek, a new reagent strip rapid test for detecting H. pylori infection., Methods: Gastric antral mucosal biopsy specimens were obtained for comparison between agar gel rapid urease tests and PyloriTek (200 specimens). The rapid urease test to be used first was selected randomly. H. pylori status was determined using the Genta stain. Culture was performed to confirm H. pylori status when false rapid urease tests were suspected., Results: One hundred patients were studied; 68 had H. pylori infection. There were two false-negative and one false-positive PyloriTek when scored at 1 hour, compared with only one false-positive and no false-negative tests at 2 hours. With the agar gel rapid urease tests, there were no false-positive tests and 5 false-negative tests when scored at 1 hour, 2 false-negative tests at 12 hours and 1 at 24 hours; there were no false-positive tests. At 1 hour, 3% (95% CI = 1% to 9%) of PyloriTek tests had an erroneous categorization of H. pylori status compared with 5% for the agar gel rapid urease tests (95% CI = 1.6% to 11%) (p > 0.7)., Conclusion: The new reagent strip rapid urease test, PyloriTek, is rapid and comparable in accuracy to agar gel rapid urease tests for detecting H. pylori Infection.

Background: Multi-drug regimens are generally required to reliably cure H. pylori infection. We previously demonstrated that a 2-week three-times-a-day regimen of amoxycillin and clarithromycin was effective against H. pylori infection., Objectives: To evaluate the efficacy and side-effects of a 1-week twice-daily dosing schedule for the treatment of H. pylori infection., Methods: We studied the efficacy of 1-week of therapy with 20 mg of omeprazole, 1 g of amoxycillin and 250 mg of clarithromycin, all twice daily H. pylori status was determined at entry and 4 or more weeks after completing antimicrobial therapy using histology (Genta stain) and culture., Results: Thirty-one patients with documented peptic ulcer disease and H. pylori infection were treated. The H. pylori infection was cured in 24 (77%, 95% CI = 58-90%) (intention-to-treat). In a per protocol analysis the cure rate was 23 of 29 patients (79%, 95% CI = 60-92%). One patient took only 43% of the study drugs and another withdrew following development of an anaphylactic reaction to study medication. Mild side-effects were reported by 16% including diarrhoea, headache and altered taste. Compliance averaged 95%. Pretreatment clarithromycin resistance averaged 5% and had not been acquired by any strains post-therapy., Conclusion: This combination of omeprazole, amoxycillin and low-dose clarithromycin resulted in a relatively low cure rate even in patients with clarithromycin-sensitive isolates. Large comparative studies will be needed to define the optimal duration, dose and dosing interval if this combination of drugs is to become competitive.

Although there have been several reports of hyperplastic gastric polyps associated with persistent Helicobacter pylori gastritis, the association of H. pylori infection with metaplastic polyps in the duodenum has not hitherto been described. After a 52-year-old man had a single episode of hematemesis, endoscopy showed a smooth polyp 1 cm in greatest dimension formed by a proliferation of gastric epithelial cells of fundic and antral type found in the duodenal bulb. The outer surface was entirely covered with a single layer of hyperplastic columnar epithelium with many H. pylori organisms. After administration of metronidazole 500 mg, omeprazole 20 mg for 4 weeks, and clarithromycin 250 mg twice a day for 2 weeks, endoscopy showed a decrease in size of the duodenal polyp. At 12 weeks there was complete regression of the polyp. This report documents a new and unusual finding: resolution of a gastric metaplastic polyp in the duodenum associated with cure of H. pylori.

Background: Isolating Helicobacter pylori on culture media and performing antibiotic susceptibility testing is potentially the most useful tool for guiding antibiotic therapy, especially when antimicrobial resistance is suspected. The aim of this study was to determine whether the yield of H. pylori culture was related to the site from which the gastric specimen was obtained either before or after therapy., Methods: Gastric mucosal biopsies from the antrum and the corpus of the stomach were cultured. H. pylori status was determined by histological assessment using the Genta stain., Results: Fifty-two patients with documented H. pylori infection were studied: Twenty-three were tested before antibiotic therapy and 29 after therapy had failed. In 47 patients (90%), both antral and corpus culture specimens were positive. In 5 patients (10%), only one site was positive, with three false-negative antral and two false negative corpus cultures. The overall sensitivity of culture in detecting H. pylori infection was 95% (95% confidence interval = 89-98%) and was not significantly different for the antrum or corpus, either before or after therapy., Conclusion: Culture of gastric biopsies from either the antrum or the corpus has an excellent diagnostic yield even in patients who failed antimicrobial therapy.

Background: The variables responsible for false-positive and false-negative rapid urease tests are largely unexplored., Objectives: We compared the results of rapid urease testing with jumbo cup forceps (3.3 mm diameter) and tiny cup forceps (1.8 mm diameter) with two rapid urease tests., Methods: Antral biopsies were obtained. The order of forceps and rapid urease tests was randomized. Biopsies were also taken for Genta staining., Results: One hundred and two patients were studied; 59 had Helicobacter pylori infection. There were 22 false-negative tests (8 CLOtest, 16 hpfast) and 5 false-positive tests (3 CLOtest, 2 hpfast). All 5 false-positive tests were among those positive only in the second 12 hours. There was no difference in results with the jumbo and tiny cup forceps. Five percent to nine percent (average, 6.6%; 95% confidence interval, 4.4% to 9.6%) of tests with any of the combinations gave an erroneous categorization of H. pylori status. There were no clinical or statistical differences in H. pylori categorizations by CLOtest or hpfast., Conclusion: The diagnostic yield for detecting H. pylori infection by rapid urease tests is not adversely affected by small biopsy size, possibly because tiny biopsies obtain superficial tissue where H. pylori reside.

Background: Treatment of antibiotic-resistant Helicobacter pylori should be based on bacterial sensitivity testing that requires the ability to isolate the bacterium from gastric mucosal biopsies. The aim of this study was to determine whether the yield for detecting H. pylori infection by culture is reduced by immersion of biopsy forceps in formalin prior to obtaining the specimen., Materials and Methods: Gastric antral mucosal biopsies (100 specimens) from 50 patients were obtained for culture of H. pylori. An antral biopsy was taken for culture, and with the same forceps a biopsy was taken for histological examination. The biopsy specimen was removed by shaking, whereas the forceps was immersed in 10% buffered formalin for the histological investigation. The forceps was then used without rinsing to obtain a second specimen for culture from an area adjacent to the first site. H. pylori status was determined by histological assessment with the Genta stain and a rapid urease test., Results: Fifty patients with H. pylori infection documented by histological inquiry and positive rapid urease testing entered the study; 29 had duodenal ulcers, 5 had gastric ulcers, 1 had mucosal associated lymphoid tissue (MALT) lymphoma, and 15 were without ulcer disease. The results of culture both before and after immersion in formalin were identical. One patient had both cultures negative; the sensitivity of culture for detection of H. pylori infection was 98% (95% confidence interval = 93%-100%)., Conclusion: Preimmersion of biopsy forceps in formalin does not adversely affect the ability to culture H. pylori.

Background: Multi-drug regimens are generally required to reliably cure Helicobacter pylori infection. Metronidazole, clarithromycin and omeprazole has proven to be an effective combination therapy with a cure rate of 90% or greater., Methods: We evaluated a 14-day combination regimen for H.pylori infection consisting of metronidazole 500 mg b.d., clarithromycin 250 mg b.d. and ranitidine 300 mg b.d. (MRC) instead of omeprazole. Ranitidine alone was continued for an additional 4 weeks. H. pylori status was determined by rapid urease testing, histopathology using the Genta stain, and by culture at entry and 4 weeks after completing antimicrobial therapy., Results: Twenty-seven patients with documented peptic ulcer disease and H. pylori infection were treated. Five had previously failed macrolide-based antimicrobial therapy; none had received metronidazole. All ulcers were healed at week 6 except one patient taking naproxen; his H. pylori infection was cured. Overall, H. pylori infection was cured in 78% (95% CI = 58-91%). In patients with clarithromycin-sensitive isolates, the cure rate was 20 of 23 (87%, 95% C.I. = 66-97%); only one of four patients (25%) with clarithromycin-resistant isolates was cured. In contrast, four of five patients with metronidazole-resistant isolates were cured (80%). In patients with isolates sensitive to both antibiotics, the cure rate was 16 of 18 (89%, 95% C.I. = 65-99%). Mild side effects were reported by 27%, including diarrhoea and altered taste. Compliance averaged 98%., Conclusion: These results suggest that the combination of metronidazole, ranitidine and clarithromycin results in high cure rates in patients with clarithromycin-sensitive isolates. Omeprazole may not be required for Bazzoli's triple therapy; and large multicentre comparative trials are indicated.

Objective: Although omeprazole co-therapy enhances the effectiveness of some antimicrobials for the treatment of Helicobacter pylori infection, results have not been uniform. A meta-analysis suggested that 20 mg of omeprazole b.i.d. and 2 g or more of amoxicillin would yield a > 80% success rate (Gastroenterology 1994; 106: 142A). Our objective in this study was to test that hypothesis., Methods: Volunteers with H. pylori infection were studied. Anti-H. pylori therapy was administered with meals for 14 days (omeprazole 20 mg b.i.d. plus amoxicillin 1 g t.i.d., or omeprazole 20 mg b.i.d. plus amoxicillin 0.5 g t.i.d.). Endoscopy was performed 4-6 wk after antimicrobial therapy ended, and the presence or absence of H. pylori was determined with biopsy specimens by Genta stain., Results: Fifty-nine volunteers completed the study; 30 were studied twice. The overall success for initial treatment with either combination of amoxicillin and omeprazole was 18 of 59 [30.5%; 95% confidence interval (CI) = 19-44%]. The success rate with 500 mg amoxicillin t.i.d. was 7 of 29 (24%; 95% CI = 10-43%). With 1 g t.i.d. amoxicillin, the cure rate was higher (36.6%) (11 of 30; 95% CI = 20-56%), or intention-to-treat result was 11 of 31 (35.4%), which includes the early dropout. Compliance was > 95% for both therapies. Side effects were experienced by eight patients, two receiving 1.5 g amoxicillin and six receiving 3 g amoxicillin (p > 0.2). German trials suggest that better results might be achieved when amoxicillin is given as suspension while fasting. Thirty treatment failures were re-treated with 1 g amoxicillin suspension t.i.d., given fasting, and omeprazole 20 mg b.i.d. The cure rate was 16.6% (95% CI = 6-35%)., Conclusion: Amoxicillin/omeprazole combinations for treatment of H. pylori infection do not yield consistent results. The reason is unknown, but the reported high rate of success with 40 mg of omeprazole and 750 mg t.i.d. suggests that almost complete inhibition of acid secretion is necessary to obtain consistent results with this combination.

Background: Successful treatment of Helicobacter pylori infection results in cure of peptic ulcer disease. Multi-drug regimens are needed to cure this infection. We studied the effectiveness and side effect profile of two antibiotics active against Helicobacter pylori, metronidazole and clarithromycin, combined with omeprazole., Methods: We evaluated a combination therapy for H. pylori infection consisting of metronidazole (500 mg b.d.), omeprazole (20 mg b.d.), and clarithromycin (250 mg b.d.) for 2 weeks, followed by ranitidine 300 mg daily for 4 weeks., Results: Thirty-three patients with documented H. pylori infection were studied. Twenty had previously failed antimicrobial therapy, including one with metronidazole-based triple therapy and eight with macrolide-based therapy (five with clarithromycin-based therapy), and 11 with amoxycillin, tetracycline, and bismuth. H. pylori status was determined by histopathology using the Genta stain and by culture. H. pylori status was determined at entry and 4 weeks after completing antimicrobial therapy. The H. pylori infection was cured in 88% (95% CI = 72%-96%) including 90% of those who had failed previous anti-H. pylori therapies. Mild side effects were reported by 18%., Conclusion: We conclude that the combination of metronidazole, omeprazole and clarithromycin is an effective treatment for H. pylori infection.